Browsing by Author "Tian, Lin"

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    Aberrant Calcium Signaling in Astrocytes Inhibits Neuronal Excitability in a Human Down Syndrome Stem Cell Model
    Mizuno, Grace O.; Wang, Yinxue; Shi, Guilai; Wang, Yizhi; Sun, Junqing; Papadopoulos, Stelios; Broussard, Gerard J.; Unger, Elizabeth K.; Deng, Wenbin; Weick, Jason; Bhattacharyya, Anita; Chen, Chao-Yin; Yu, Guoqiang; Looger, Loren L.; Tian, Lin (Elsevier, 2018-07-10)
    Down syndrome (DS) is a genetic disorder that causes cognitive impairment. The staggering effects associated with an extra copy of human chromosome 21 (HSA21) complicates mechanistic understanding of DS pathophysiology. We examined the neuronastrocyte interplay in a fully recapitulated HSA21 trisomy cellular model differentiated from DS-patientderived induced pluripotent stem cells (iPSCs). By combining calciumimaging with genetic approaches, we discovered the functional defects of DS astroglia and their effects on neuronal excitability. Compared with control isogenic astroglia, DS astroglia exhibited more-frequent spontaneous calcium fluctuations, which reduced the excitability of co-cultured neurons. Furthermore, suppressed neuronal activity could be rescued by abolishing astrocytic spontaneous calcium activity either chemically by blocking adenosine-mediated signaling or genetically by knockdown of inositol triphosphate (IP3) receptors or S100B, a calcium binding protein coded on HSA21. Our results suggest a mechanism by which DS alters the function of astrocytes, which subsequently disturbs neuronal excitability.
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    Analysis of Time-Varying Characteristics of Simulated Turbulence in Wind Tunnel
    Tian, Lin (Virginia Tech, 1999-05-28)
    Eight roughness configurations in Clemson boundary layer wind tunnel are presented. For these configurations, flow parameters such as turbulent intensities, integral length scales, large- and small- scale turbulence, and spectra of velocity components of the wind are obtained and studied to the simulated turbulence. At the same time, new analyzing tools, orthogonal wavelet techniques, are applied to provide additional information in time domain. This makes it possible to study the intermittency event, one important characteristic associated with pressure peak activities in turbulence. Three parameters, scale energy, intermittency factor and intermittency energy are defined. Variation of these quantities as a result of different configuration is discussed. Finally, the corresponding variations in measured pressure peaks in relation with the variations of configuration as well as with the intermittency parameters are investigated. The work here is of important significance for future wind tunnel and field data comparison, and this could help to find the best simulation among all configurations.
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    Automated Functional Analysis of Astrocytes from Chronic Time-Lapse Calcium Imaging Data
    Wang, Yinxue; Shi, Guilai; Miller, David J.; Wang, Yizhi; Wang, Congchao; Broussard, Gerard J.; Wang, Yue; Tian, Lin; Yu, Goquiang (Frontiers, 2017-07-14)
    Recent discoveries that astrocytes exert proactive regulatory effects on neural information processing and that they are deeply involved in normal brain development and disease pathology have stimulated broad interest in understanding astrocyte functional roles in brain circuit. Measuring astrocyte functional status is now technically feasible, due to recent advances in modern microscopy and ultrasensitive cell-type specific genetically encoded Ca²⁺ indicators for chronic imaging. However, there is a big gap between the capability of generating large dataset via calcium imaging and the availability of sophisticated analytical tools for decoding the astrocyte function. Current practice is essentially manual, which not only limits analysis throughput but also risks introducing bias and missing important information latent in complex, dynamic big data. Here, we report a suite of computational tools, called Functional AStrocyte Phenotyping (FASP), for automatically quantifying the functional status of astrocytes. Considering the complex nature of Ca²⁺ signaling in astrocytes and low signal to noise ratio, FASP is designed with data-driven and probabilistic principles, to flexibly account for various patterns and to perform robustly with noisy data. In particular, FASP explicitly models signal propagation, which rules out the applicability of tools designed for other types of data. We demonstrate the effectiveness of FASP using extensive synthetic and real data sets. The findings by FASP were verified by manual inspection. FASP also detected signals that were missed by purely manual analysis but could be confirmed by more careful manual examination under the guidance of automatic analysis. All algorithms and the analysis pipeline are packaged into a plugin for Fiji (ImageJ), with the source code freely available online at https://github.com/VTcbil/FASP.