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RISS 인기검색어
- 검색키워드
- 저자 : Himes, B. Timothy (검색결과 5 건)
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Park, Kook In,Himes, B. Timothy,Stieg, Philip E.,Tessler, Alan,Fischer, Itzhak,Snyder, Evan Y. Elsevier 2006 Experimental neurology Vol.199 No.1
<P><B>Abstract</B></P><P>Previously, we reported that, when clonal neural stem cells (NSCs) were transplanted into brains of postnatal mice subjected to unilateral hypoxic–ischemic (HI) injury (optimally 3–7 days following infarction), donor-derived cells homed preferentially (from even distant locations) to and integrated extensively within the large ischemic areas that spanned the hemisphere. A subpopulation of NSCs and host cells, particularly in the penumbra, “shifted” their differentiation towards neurons and oligodendrocytes, the cell types typically damaged following asphyxia and least likely to regenerate spontaneously and in sufficient quantity in the “post-developmental” CNS. That no neurons and few oligodendrocytes were generated from the NSCs in intact postnatal cortex suggested that novel signals are transiently elaborated following HI to which NSCs might respond. The proportion of “replacement” neurons was ∼5%. Neurotrophin-3 (NT-3) is known to play a role in inducing neuronal differentiation during development and perhaps following injury. We demonstrated that NSCs express functional TrkC receptors. Furthermore, the donor cells continued to express a foreign reporter transgene robustly within the damaged brain. Therefore, it appeared feasible that neuronal differentiation of exogenous NSCs (as well as endogenous progenitors) might be enhanced if donor NSCs were engineered prior to transplantation to (over)express a bioactive gene such as NT-3. A subclone of NSCs transduced with a retrovirus encoding NT-3 (yielding >90% neurons in vitro) was implanted into unilaterally asphyxiated postnatal day 7 mouse brain (emulating one of the common causes of cerebral palsy). The subclone expressed NT-3 efficiently in vivo. The proportion of NSC-derived neurons increased to ∼20% in the infarction cavity and >80% in the penumbra. The neurons variously differentiated further into cholinergic, GABAergic, or glutamatergic subtypes, appropriate to the cortex. Donor-derived glia were rare, and astroglial scarring was blunted. NT-3 likely functioned not only on donor cells in an autocrine/paracrine fashion but also on host cells to enhance neuronal differentiation of both. Taken together, these observations suggest (1) the feasibility of taking a fundamental biological response to injury and augmenting it for repair purposes and (2) the potential use of migratory NSCs in some degenerative conditions for simultaneous combined gene therapy and cell replacement during the same procedure in the same recipient using the same cell (a unique property of cells with stem-like attributes).</P>
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Di Maio, Alessandro,Skuba, Andrew,Himes, B Timothy,Bhagat, Srishiti L,Hyun, Jung Keun,Tessler, Alan,Bishop, Derron,Son, Young-Jin The Society 2011 The Journal of neuroscience Vol.31 No.12
<P>Dorsal root (DR) axons regenerate in the PNS but turn around or stop at the dorsal root entry zone (DREZ), the entrance into the CNS. Earlier studies that relied on conventional tracing techniques or postmortem analyses attributed the regeneration failure to growth inhibitors and lack of intrinsic growth potential. Here, we report the first in vivo imaging study of DR regeneration. Fluorescently labeled, large-diameter DR axons in thy1-YFPH mice elongated through a DR crush site, but not a transection site, and grew along the root at >1.5 mm/d with little variability. Surprisingly, they rarely turned around at the DREZ upon encountering astrocytes, but penetrated deeper into the CNS territory, where they rapidly stalled and then remained completely immobile or stable, even after conditioning lesions that enhanced growth along the root. Stalled axon tips and adjacent shafts were intensely immunolabeled with synapse markers. Ultrastructural analysis targeted to the DREZ enriched with recently arrived axons additionally revealed abundant axonal profiles exhibiting presynaptic features such as synaptic vesicles aggregated at active zones, but not postsynaptic features. These data suggest that axons are neither repelled nor continuously inhibited at the DREZ by growth-inhibitory molecules but are rapidly stabilized as they invade the CNS territory of the DREZ, forming presynaptic terminal endings on non-neuronal cells. Our work introduces a new experimental paradigm to the investigation of DR regeneration and may help to induce significant regeneration after spinal root injuries.</P>
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Himeli Chakrabarti,Reshmi Maity,Tijana Kevkić,Vladica Stojanović,N. P. Maity 한국전기전자재료학회 2021 Transactions on Electrical and Electronic Material Vol.22 No.4
This article is about an elaborative description of two dimensional investigative mathematical structure of fully depleted graded channel (GC) dual-material-double-gate (DMDG) silicon-on-insulator metal–oxide–semiconductor-fi eld-eff ecttransistor (SOI MOSFET). The surface potential contours in addition with electric field variation throughout the channel establish reduction of short-channel-effects (SCEs). To get better operational analysis, some new characteristics such as temperature effect and interface charge eff ects have been incorporated in the model. In this representation we also incorporate the consequences of high-k dielectric medium HfO2 instead of SiO2 and have made a comparison with the effect in various frameworks. In the GC DMDG composition, the surface potential as well as electric field throughout the channel shows close to step function variations which help to defeat the hot carrier along with drain-induced-barrier-lowering (DIBL) effects. As an outcome, the structure shows that the surface potential profi le increases by using GC DMDG structure over DMDG. All these outcomes of the proposed analytical representation have been compared by TCAD simulation consequence. Very good conformity is observed between them.
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