Browsing by Author "Yang, Jin"

Now showing 1 - 3 of 3
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    A mechanistic model for the study of the arterial myogenic response
    (2002) Yang, Jin; Clark, John W., Jr.
    This study is concerned with the development of a multiple compartment model of the isolated cerebral artery in rat. The smooth muscle/arterial wall complex is an important component of the circulatory model and serves as a "vasomotor organ", which provides the myogenic mechanism that underlies the phenomenon of the autoregulation of blood flow. We have focused on this myogenic mechanism and have developed a model of the electrophysiological and contractile characteristics of the single smooth muscle cell of the posterior cerebral artery. This cell model is used to interrelate the topics of arterial wall stress, changes in transmembrane potential, intracellular Ca 2+ concentration and contraction. Moreover, the smooth muscle cell model is imbedded in a larger arterial wall model which converts contractile activity into changes in lumen diameter. The complete model consisting of component models of cell, wall, vessel and testing apparatus is used to provide biophysically based explanations of the myogenic mechanisms underlying the autoregulation of cerebral blood flow.
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    Modeling vascular smooth muscle contraction
    (2004) Yang, Jin; Clark, John W., Jr.
    This thesis work presents a multi-scale mathematical modeling framework to investigate issues regarding vascular smooth muscle contraction. The overall structure of this thesis consists of (1) a model of single vascular smooth muscle cell membrane electrophysiology, contractile system kinetics and cell mechanics; (2) a model of signal transduction of nitric-oxide induced vascular smooth muscle relaxation, and (3) a cellular-based model for myogenic responses of isolated arteries. These models present a general and comprehensive description of VSM contraction and its associated signal transduction, which integrates information from both microscopic (cellular and subcellular interactions) and macroscopic (isolated vessel) levels. These models were utilized to investigate many underlying principles of vascular smooth muscle contraction mediated by multiple signaling pathways and can be applied to study functions of vascular smooth muscle under a variety of physiological and pathological conditions.
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    A synthetic circuit for buffering gene dosage variation between individual mammalian cells
    (Springer Nature, 2021) Yang, Jin; Lee, Jihwan; Land, Michelle A.; Lai, Shujuan; Igoshin, Oleg A.; St-Pierre, François; Bioengineering; Biosciences; Chemistry; Systems, Synthetic, and Physical Biology
    Precise control of gene expression is critical for biological research and biotechnology. However, transient plasmid transfections in mammalian cells produce a wide distribution of copy numbers per cell, and consequently, high expression heterogeneity. Here, we report plasmid-based synthetic circuits – Equalizers – that buffer copy-number variation at the single-cell level. Equalizers couple a transcriptional negative feedback loop with post-transcriptional incoherent feedforward control. Computational modeling suggests that the combination of these two topologies enables Equalizers to operate over a wide range of plasmid copy numbers. We demonstrate experimentally that Equalizers outperform other gene dosage compensation topologies and produce as low cell-to-cell variation as chromosomally integrated genes. We also show that episome-encoded Equalizers enable the rapid generation of extrachromosomal cell lines with stable and uniform expression. Overall, Equalizers are simple and versatile devices for homogeneous gene expression and can facilitate the engineering of synthetic circuits that function reliably in every cell.