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  • 1
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    Regulation of neuronal survival factor MEF2D by chaperone-mediated autophagy (2009)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2009-01-03
    Description: Chaperone-mediated autophagy controls the degradation of selective cytosolic proteins and may protect neurons against degeneration. In a neuronal cell line, we found that chaperone-mediated autophagy regulated the activity of myocyte enhancer factor 2D (MEF2D), a transcription factor required for neuronal survival. MEF2D was observed to continuously shuttle to the cytoplasm, interact with the chaperone Hsc70, and undergo degradation. Inhibition of chaperone-mediated autophagy caused accumulation of inactive MEF2D in the cytoplasm. MEF2D levels were increased in the brains of alpha-synuclein transgenic mice and patients with Parkinson's disease. Wild-type alpha-synuclein and a Parkinson's disease-associated mutant disrupted the MEF2D-Hsc70 binding and led to neuronal death. Thus, chaperone-mediated autophagy modulates the neuronal survival machinery, and dysregulation of this pathway is associated with Parkinson's disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2666000/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2666000/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Qian -- She, Hua -- Gearing, Marla -- Colla, Emanuela -- Lee, Michael -- Shacka, John J -- Mao, Zixu -- AG023695/AG/NIA NIH HHS/ -- NS038065/NS/NINDS NIH HHS/ -- NS048254/NS/NINDS NIH HHS/ -- NS055077/NS/NINDS NIH HHS/ -- NS47466/NS/NINDS NIH HHS/ -- NS57098/NS/NINDS NIH HHS/ -- P30 NS055077/NS/NINDS NIH HHS/ -- P30 NS055077-01A2/NS/NINDS NIH HHS/ -- P50 AG025688/AG/NIA NIH HHS/ -- P50 AG025688-03/AG/NIA NIH HHS/ -- R01 AG023695/AG/NIA NIH HHS/ -- R01 AG023695-02/AG/NIA NIH HHS/ -- R01 AG023695-03/AG/NIA NIH HHS/ -- R01 AG023695-04/AG/NIA NIH HHS/ -- R01 AG023695-05/AG/NIA NIH HHS/ -- R01 NS048254/NS/NINDS NIH HHS/ -- R01 NS048254-02/NS/NINDS NIH HHS/ -- R01 NS048254-03/NS/NINDS NIH HHS/ -- R01 NS048254-04/NS/NINDS NIH HHS/ -- R01 NS048254-05/NS/NINDS NIH HHS/ -- R01 NS048254-06/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2009 Jan 2;323(5910):124-7. doi: 10.1126/science.1166088.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19119233" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Ammonium Chloride/pharmacology ; Animals ; *Autophagy ; Brain/metabolism ; Cell Line ; Cell Nucleus/metabolism ; Cell Survival ; Cytoplasm/metabolism ; DNA/metabolism ; HSC70 Heat-Shock Proteins/metabolism ; Lysosomal-Associated Membrane Protein 2/metabolism ; Lysosomes/metabolism ; MADS Domain Proteins/*metabolism ; MEF2 Transcription Factors ; Mice ; Mice, Transgenic ; Molecular Chaperones/*metabolism ; Myogenic Regulatory Factors/chemistry/*metabolism ; Neurons/cytology/*metabolism ; Parkinson Disease/metabolism ; Protein Binding ; Protein Transport ; Rats ; Rats, Long-Evans ; alpha-Synuclein/genetics/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
    Electronic Resource
    Electronic Resource
    Downscaling of Pb(Zr,Ti)O3 film thickness for low-voltage ferroelectric capacitors: Effect of charge relaxation at the interfaces (2000)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 88 (2000), S. 2154-2156 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: In this communication we address two issues essential for low-voltage memory applications of ferroelectric thin films: the size effect on polarization switching, and polarization fatigue. According to the proposed concept, both of these phenomena are controlled by local injection of charge into the interfacial layers of the ferroelectric film. In the experimental part of this work, we show that the entrapped charge relaxation can be enhanced by introducing a thin RuO2 layer into the top interface of the Pt/PZT/Pt ferroelectric capacitor. Capacitors prepared in this way using PZT with a 45/55 Zr/Ti ratio show a substantial improvement of fatigue performance and withstand relatively well the thickness downscaling. As a result, these capacitors exhibited good ferroelectric properties for driving voltage amplitudes as low as 0.6–0.8 V. Our results suggest that control of charge relaxation at the interface is a key issue for development of low-voltage ferroelectric capacitors. © 2000 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.1305854
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  • 3
    Electronic Resource
    Electronic Resource
    Polarization fatigue in ferroelectric films: Basic experimental findings, phenomenological scenarios, and microscopic features (2001)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 90 (2001), S. 1387-1402 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The reduction in switchable polarization of ferroelectric thin films due to electrical stress (polarization fatigue) is a major problem in ferroelectric nonvolatile memories. There is a large body of available experimental data and a number of existing models which address this issue, however the origin of this phenomena is still not properly understood. This work synthesizes the current experimental data, models, and approaches in order to draw conclusions on the relative importance of different macro- and microscopic scenarios of fatigue. Special attention is paid to the role of oxygen vacancy migration and electron injection into the film and it is concluded that the latter plays the predominant role. Experiments and problems for theoretical investigations, which can contribute to the further elucidation of polarization fatigue mechanisms in ferroelectric thin films, are suggested. © 2001 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.1381542
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  • 4
    Electronic Resource
    Electronic Resource
    Identification of passive layer in ferroelectric thin films from their switching parameters (1995)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 78 (1995), S. 2623-2630 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The switching of the sandwich structure "ferroelectric+thin dielectric layer'' is theoretically studied. The behavior of the remanent polarization, Pr, coercive field, Ec, maximal polarization on the loop, Ps, and the slope of the hysteresis loop at Ec as a function of both, the relative thickness of the layer (the thickness of the dielectric divided by the thickness of the ferroelectric) and the amplitude of the measuring field, is analyzed. It is shown that the effect of the layer on Pr and the slope at Ec is qualitatively different from that on Ec and Ps. As the result of this analysis the set of characteristic features of the sandwich with the variable relative thickness of the dielectric layer have been have formulated. These characteristic features can be used for the identification of the presence of such a dielectric layer using the data on the switching parameters of the system. It is shown that the increase of the coercive field with increasing relative thickness of the dielectric layer, which was considered as an important sign of the presence of the dielectric layer, is not a real property of the sandwich structure but rather an artifact of the approximations which were used in the analysis performed by the previous workers. In fact, Ec is a decreasing function of the relative thickness of the dielectric layer. © 1995 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.360122
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  • 5
    Electronic Resource
    Electronic Resource
    Structure of Ba(Y+31/2Ta+51/2)O3 and its dielectric properties in the range 102–1014 Hz, 20–600 K (1994)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 76 (1994), S. 5864-5873 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The goal of this work was to understand the correlation between microscopic material parameters and the dielectric function of candidate materials for applications in the microwave frequency range. The structure and dielectric properties of Ba2+(Y3+1/2Ta5+1/2)O3 (BYT), a typical representative of the Ba(B3+1/2B5+1/2)O3 complex perovskite family, has been investigated from 102 to 1014 Hz and from 20 to 600 K. At Tc=253±1 K, BYT undergoes an equitranslational improper ferroelastic, second-order phase transition, characterized by the tilting of the oxygen octahedra. The space group symmetry changes from Fm3¯m, in the high temperature phase, to I4/m below Tc. The existence of an intermediate temperature region (Tc−40〈T〈Tc) has been observed, where the compound exhibits structural and dielectric properties different from those in the well-defined high (T(approximately-greater-than)Tc) and low (T〈Tc−40 K) temperature phases. Infrared reflectivity (1012–1014 Hz) and submillimeter transmission (1011–3×1012 Hz) measurements yield dielectric losses which are believed to be mainly of intrinsic origin (one- and two-phonon absorption). Comparing a theory of two-phonon difference absorption processes, due to thermally activated polar branches, with the loss measured at 400–1400 GHz, the intrinsic loss can be extrapolated to lower frequencies. At 10 GHz the extrapolated value is about 1/4 of the loss actually measured in a BYT resonator. Nonpolar phonons, including the soft branch, which have not been considered for the extrapolation procedure, are partially responsible. The temperature dependencies indicate the soft branch to be of considerable importance for intrinsic losses. Oxygen vacancies can be excluded as an extrinsic loss source, as sintering and annealing in N2, air, and O2 had no measurable influence on the loss at 10 GHz.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.358401
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  • 6
    Electronic Resource
    Electronic Resource
    Cold-field-emission test of the fatigued state of Pb(ZrxTi1−x)O3 films (1998)
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 73 (1998), S. 1361-1363 
    Details
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Fatigue phenomena occurring in Pb(ZrxTi1−x)O3 ferroelectric thin-film capacitors (FECAP) with Pt electrodes are studied by means of conduction measurements in the cold-field-emission (tunneling) regime. We have determined that conduction in virgin FECAPs is controlled by tunneling at temperatures 100–140 K and electric fields (2.3–3.0 MV/cm). The Fowler–Nordheim equation successfully describes observed current–voltage relations for reasonable values of the semiconductor parameters of the system. Fatigue of the switching polarization induced by bipolar voltage cycling provokes a substantial increase in tunneling conduction, shifting the I–V curve to lower fields by some 0.5 MV/cm. The partial restoration of the switching polarization produced by heating of the sample up to 490 K results in a complete restoration of the initial current–voltage characteristic. It is shown that the fatigue-induced increase in conduction can be modeled by the charging of an interfacial layer of a thickness comparable with the tunneling length. This interpretation is consistent with a fatigue scenario related to the space-charge-assisted blocking of near-by-electrode centers of domain nucleation. © 1998 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.122374
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  • 7
    Electronic Resource
    Electronic Resource
    Erratum: "Cold-field-emission test of the fatigued state of Pb(ZnxTi1−x)O3 films" [Appl. Phys. Lett. 73, 1361 (1998)] (1998)
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 73 (1998), S. 2221-2221 
    Details
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.122437
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  • 8
    Electronic Resource
    Electronic Resource
    Direct observation of region by region suppression of the switchable polarization (fatigue) in Pb(Zr,Ti)O3 thin film capacitors with Pt electrodes (1998)
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 72 (1998), S. 2763-2765 
    Details
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: The size, shape, and polarization orientation of fatigued areas formed during the suppression of the switchable polarization (Prs) (fatigue) in Pt–PZT–Pt ferroelectric capacitors (FECAPs), were observed by means of atomic force microscopy and by imaging the phase of the piezoelectric vibration induced by a low ac field applied between the top and bottom electrodes. In the virgin state (FECAP as prepared), the pattern of the polarization domains with opposite orientation was randomly distributed with typical sizes of 1–3 μm. The application of a dc field larger than the coercive field (Ec) enabled to fully orient the polarization of the regions in either directions. During the initial fatigue (〈35% of suppressed Prs), polarized regions with frozen orientation and size ranging between 100 nm and 1 μm became visible. In the fatigued state (〉65% of suppressed Prs), two main configurations of the frozen polarization domains were distinguished. One was characterized by a strong preferential direction (top to bottom electrode) and the other by randomly distributed regions of opposite oriented frozen polarization. The degrees of fatigue obtained by analyzing the vibration phase images are in good agreement with those obtained by standard polarization measurements. It is concluded that the Prs suppression (fatigue) is due to "region by region" or "grain by grain" freezing of Prs and that the frozen Prs can have a preferential orientation. © 1998 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.121083
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  • 9
    Electronic Resource
    Electronic Resource
    Fatigue of piezoelectric properties in Pb(Zr,Ti)O3 films (1996)
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 68 (1996), S. 2577-2579 
    Details
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Piezoelectric properties of Pb(Zr,Ti)O3 thin films are investigated as a function of the number of bipolar (switching) and unipolar (nonswitching) voltage pulses. The longitudinal piezoelectric coefficient d33 decreases with bipolar fatigue reflecting the decrease of switchable polarization. Simultaneously, a strong vertical shift of piezoelectric hysteresis loops is observed, which is considered as the buildup of fixed internal polarization due to the pinning of ferroelectric domains in a preferred orientation. Piezoelectric fatigue induced by unipolar (nonswitching) pulses is considerably smaller than the fatigue under bipolar conditions and can be described by the internal bias field which shifts piezoelectric hysteresis loops along the field axis. © 1996 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.116189
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  • 10
    Electronic Resource
    Electronic Resource
    Discrimination between bulk and interface scenarios for the suppression of the switchable polarization (fatigue) in Pb(Zr,Ti)O3 thin films capacitors with Pt electrodes (1998)
    Woodbury, NY : American Institute of Physics (AIP)
    Applied Physics Letters 72 (1998), S. 2478-2480 
    Details
    ISSN: 1077-3118
    Source: AIP Digital Archive
    Topics: Physics
    Notes: A simple and reliable method which allows one to distinguish between the two major microscopic scenarios for the suppression of the switching polarization (Prs), i.e., pinning of ferroelectric domain walls (DWs) through the Pb(Zr,Ti)O3 film (PZT) (bulk scenario) and inhibition of the growth of opposite domains due to the nucleus suppression at the electrode interfaces (interface scenario), is proposed. In addition, a new electric treatment able to significantly suppress Prs in Pt–PZT–Pt ferroelectric capacitors (FECAPs) of thicknesses above 1.4 μm, was discovered and studied. It consists of the application of an external alternating electric field (Ee) which cycles the polarization at very low frequency (1.7 mHz). After only 10–20 cycles, Prs can be suppressed by a factor of 10. The same FECAP, when subjected to Ee at higher frequency (30 kHz), endures at least 108 switches, before attaining an equivalent Prs suppression (hereafter called fatigue). The fatigued states obtained with the two different procedures appear to be different. In the first case (slow cycling) it is suggested that the suppression of Prs is related to the DW pinning scenario, whereas in the second case—which corresponds to the normal fatiguing procedure—it is related to the interface scenario. © 1998 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.121386
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