Non-Gaussian water diffusion in aging white matter

Age-associated white matter degeneration has been well documented and is likely an important mechanism contributing to cognitive decline in older adults. Recent work has explored a range of noninvasive neuroimaging procedures to differentially highlight alterations in the tissue microenvironment. Diffusional kurtosis imaging (DKI) is an extension of diffusion tensor imaging (DTI) that accounts for non-Gaussian water diffusion and can reflect alterations in the distribution and diffusion properties of tissue compartments. We used DKI to produce whole-brain voxel-based maps of mean, axial, and radial diffusional kurtoses, quantitative indices of the tissue microstructure's diffusional heterogeneity, in 111 participants ranging from the age of 33 to 91 years. As suggested from prior DTI studies, greater age was associated with alterations in white-matter tissue microstructure, which was reflected by a reduction in all 3 DKI metrics. Prominent effects were found in prefrontal and association white matter compared with relatively preserved primary motor and visual areas. Although DKI metrics co-varied with DTI metrics on a global level, DKI provided unique regional sensitivity to the effects of age not available with DTI. DKI metrics were additionally useful in combination with DTI metrics for the classification of regions according to their multivariate “diffusion footprint”, or pattern of relative age effect sizes. It is possible that the specific multivariate patterns of age-associated changes measured are representative of different types of microstructural pathology. These results suggest that DKI provides important complementary indices of brain microstructure for the study of brain aging and neurologic disease.     

Clustering to identify RNA conformations constrained by secondary structure

RNA often folds hierarchically, so that its sequence defines its secondary structure (helical base-paired regions connected by single-stranded junctions), which subsequently defines its tertiary fold. To preserve base-pairing and chain connectivity, the three-dimensional conformations that RNA can explore are strongly confined compared to when secondary structure constraints are not enforced. Using three examples, we studied how secondary structure confines and dictates an RNA's preferred conformations. We made use of Macromolecular Conformations by SYMbolic programming (MC-Sym) fragment assembly to generate RNA conformations constrained by secondary structure. Then, to understand the correlations between different helix placements and orientations, we robustly clustered all RNA conformations by employing unique methods to remove outliers and estimate the best number of conformational clusters. We observed that the preferred conformation (as judged by largest cluster size) for each type of RNA junction molecule tested is consistent with its biological function. Further, the improved quality of models in our pruned datasets facilitates subsequent discrimination using scoring functions based either on statistical analysis (knowledge based) or experimental data.     

Correlation between Defects and Electrical Performances of Ion-Irradiated 4H-SiC p–n Junctions

In this study, 4H-SiC p–n junctions were irradiated with 700 keV He⁺ ions in the fluence range 1.0 × 10¹² to 1.0 × 10¹⁵ ions/cm². The effects of irradiation were investigated by current–voltage (I–V) and capacitance–voltage (C–V) measurements, while deep-level transient spectroscopy (DLTS) was used to study the traps introduced by irradiation defects. Modifications of the device’s electrical performances were observed after irradiation, and two fluence regimes were identified. In the low fluence range (≤10¹³ ions/cm²), I–V characteristics evidenced an increase in series resistance, which can be associated with the decrease in the dopant concentration, as also denoted by C–V measurements. In addition, the pre-exponential parameter of junction generation current increased with fluence due to the increase in point defect concentration. The main produced defect states were the Z_1/2, RD_1/2, and EH_6/7 centers, whose concentrations increased with fluence. At high fluence (>10¹³ ions/cm²), I–V curves showed a strong decrease in the generation current, while DLTS evidenced a rearrangement of defects. The detailed electrical characterization of the p–n junction performed at different temperatures highlights the existence of conduction paths with peculiar electrical properties introduced by high fluence irradiation. The results suggest the formation of localized highly resistive regions (realized by agglomeration of point defects) in parallel with the main junction.     

Spatiotemporal Analysis of COVID-19 Incidence Data

(1) Background: A better understanding of COVID-19 dynamics in terms of interactions among individuals would be of paramount importance to increase the effectiveness of containment measures. Despite this, the research lacks spatiotemporal statistical and mathematical analysis based on large datasets. We describe a novel methodology to extract useful spatiotemporal information from COVID-19 pandemic data. (2) Methods: We perform specific analyses based on mathematical and statistical tools, like mathematical morphology, hierarchical clustering, parametric data modeling and non-parametric statistics. These analyses are here applied to the large dataset consisting of about 19,000 COVID-19 patients in the Veneto region (Italy) during the entire Italian national lockdown. (3) Results: We estimate the COVID-19 cumulative incidence spatial distribution, significantly reducing image noise. We identify four clusters of connected provinces based on the temporal evolution of the incidence. Surprisingly, while one cluster consists of three neighboring provinces, another one contains two provinces more than 210 km apart by highway. The survival function of the local spatial incidence values is modeled here by a tapered Pareto model, also used in other applied fields like seismology and economy in connection to networks. Model’s parameters could be relevant to describe quantitatively the epidemic. (4) Conclusion: The proposed methodology can be applied to a general situation, potentially helping to adopt strategic decisions such as the restriction of mobility and gatherings.     

静息态脑功能网络分析的假设驱动和数据驱动方法综述

基于功能磁共振成像的研究已发现在脑区之间存在低频波动一致的脑功能网络.脑功能网络有助于认识脑功能和诊断神经精神疾病,而脑功能网络分析方法在其中具有重要地位.本文首先综述了假设驱动和数据驱动进行脑功能网络分析的两类方法,接着对常用的基于感兴趣区、基于体素、基于独立成分分析、基于主成分分析和基于聚类方法的原理、优缺点做了详细介绍,并着重阐述了最近提出的组信息指导的独立成分分析方法,及基于半监督学习技术的感兴趣区选择方法,最后对改进方向进行了展望.     

Receptor architecture of human cingulate cortex: Evaluation of the four‐region neurobiological model

The structural and functional organization of the human cingulate cortex is an ongoing focus; however, human imaging studies continue to use the century‐old Brodmann concept of a two region cingulate cortex. Recently, a four‐region neurobiological model was proposed based on structural, circuitry, and functional imaging observations. It encompasses the anterior cingulate, midcingulate, posterior cingulate, and retrosplenial cortices (ACC, MCC, PCC, and RSC, respectively). For the first time, this study performs multireceptor autoradiography of 15 neurotransmitter receptor ligands and multivariate statistics on human whole brain postmortem samples covering the entire cingulate cortex. We evaluated the validity of Brodmann's duality concept and of the four‐region model using a hierarchical clustering analysis of receptor binding according to the degree of similarity of each area's receptor architecture. We could not find support for Brodmann's dual cingulate concept, because the anterior part of his area 24 has significantly higher AMPA, kainate, GABA_B, benzodiazepine, and M₃ but lower NMDA and GABA_A binding site densities than the posterior part. The hierarchical clustering analysis distinguished ACC, MCC, PCC, and RSC as independent regions. The ACC has highest AMPA, kainate, α₂, 5‐HT_1A, and D₁ but lowest GABA_A densities. The MCC has lowest AMPA, kainate, α₂, and D₁ densities. Area 25 in ACC is similar in receptor‐architecture to MCC, particularly the NMDA, GABA_A, GABA_B, and M₂ receptors. The PCC and RSC differ in the higher M₁ and α₁ but lower M₃ densities of PCC. Thus, multireceptor autoradiography supports the four‐region neurobiological model of the cingulate cortex. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.     

Distributed cell assemblies for general lexical and category‐specific semantic processing as revealed by fMRI cluster analysis

Here, we ask whether frontotemporal cortex is functionally dissociated into distributed lexical and category‐specific semantic networks. To this end, fMRI activation patterns elicited during the processing of words from different semantic categories were categorized using k‐means cluster algorithms. Results showed a distributed pattern of inferiorfrontal, superiortemporal, and fusiform activation shared by different word categories. This shared activation contrasted with patterns of category‐specific semantic activation in widely distributed neural systems. Clustering revealed congruent functional specificity of focal area activations in frontal and temporal cortex; thus suggesting a correspondence between functional partitionings of frontocentral mirror neuron systems and those of inferiortemporal lexical and semantic circuits. Action words related to the face, arms, and legs specifically activated the motor system in a somatotopic manner, whereas form‐related words activated prefrontal areas. Similar functional specificity was evident in temporal cortex, where a different semantic topography emerged for form‐ and action‐related words. Results were replicated in a separate data set, therefore recommending fMRI cluster analysis as a reliable method for scrutinizing the brain basis of lexical, semantic, and conceptual systems in humans. As focal modules do not explain the distributed character of functionally specific clusters and their distinct topographies are at variance with general distributed processing accounts, the functionally‐homogenous distributed clusters specific to semantic types are best explained by specifically‐distributed cortical circuits which, similar to Hebbian cell assemblies, represent functional units with specific roles in cognitive processing, especially in lexical and semantic access and memory. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

2008-2012年北京市昌平区手足口病时空聚集性分析

目的分析2008-2012年北京市昌平区手足口病流行特征,为防控工作提供依据。方法从"疾病监测信息报告管理系统"中获取以乡镇为单位的昌平区2008-2012年手足口病疫情资料,使用SaTScan 9.0软件进行乡镇为空间单位、月为时间单位的时空扫描分析,利用ArcGIS 9.1软件建立数据库并展示病例时空聚集区域。结果 2008-2012年昌平区累计报告手足口病18 227例,年均发病率为324.91/10万。发病的季节性明显,高峰出现于每年4-6月。0~5岁儿童占病例总数的92.93%,散居儿童占多数。全区各乡镇均有手足口病流行,高发乡镇集中于南部。时空扫描分析探测到时间维度为5-8月,空间维度覆盖7个乡镇的一级聚集区(平均RR=1.83,P0.001),此聚集区在4年中位置相对固定。结论北京市昌平区手足口病发病存在明显季节差异和高发区域。高发聚集区位于昌平区南部,具有城乡结合部特征。高发聚集区的手足口病防控工作尚待加强。     

超Poisson方差模型对人免疫缺陷病毒流行聚集性的研究

目的定量分析人免疫缺陷病毒（HIV）流行在空间和人群两个层面聚集性随时间变化的趋势。方法结合重庆市HIV疫情数据,分别拟合超Poisson方差模型和多水平超Poisson方差模型,计算不同年度超方差系数,绘制系数变化曲线。结果1994－2009年间,HIV人群聚集方差系数和空间聚集方差系数均随时间推移逐步增大。结论HIV流行的人口聚集性和空间聚集性在逐渐升高。     

Identification of distant co-evolving residues in antigen 85C from Mycobacterium tuberculosis using statistical coupling analysis of the esterase family proteins

A fundamental goal in cellular signaling is to understand allosteric communication, the process by which sig-nals originating at one site in a protein propagate reliably to affect distant functional sites. The general principles of protein structure that underlie this process remain unknown. Statistical coupling analysis (SCA) is a statistical technique that uses evolutionary data of a protein family to measure correlation between distant functional sites and suggests allosteric communication. In proteins, very distant and small interactions between collections of amino acids provide the communication which can be important for signaling process. In this paper, we present the SCA of protein alignment of the esterase family (pfam ID: PF00756) containing the sequence of antigen 85C secreted by Mycobacterium tuberculosis to identify a subset of interacting residues. Clustering analysis of the pairwise correlation highlighted seven important residue positions in the esterase family alignments. These resi-dues were then mapped on the crystal structure of antigen 85C (PDB ID: 1DQZ). The mapping revealed corre-lation between 3 distant residues (Asp38, Leu123 and Met125) and suggests allosteric communication between them. This information can be used for a new drug against this fatal disease.