4,507 research outputs found
TCN 201 selectively blocks GluN2A-containing NMDARs in a GluN1 co-agonist dependent but non-competitive manner
No full textAntagonists that are sufficiently selective to preferentially block GluN2A-containing N-methyl-d-aspartate receptors (NMDARs) over GluN2B-containing NMDARs are few in number. In this study we describe a pharmacological characterization of 3-chloro-4-fluoro-N-[4-[[2-(phenylcarbonyl)hydrazino]carbonyl]benzyl]benzenesulphonamide (TCN 201), a sulphonamide derivative, that was recently identified from a high-throughput screen as a potential GluN2A-selective antagonist. Using two-electrode voltage-clamp (TEVC) recordings of NMDAR currents from Xenopus laevis oocytes expressing either GluN1/GluN2A or GluN1/GluN2B NMDARs we demonstrate the selective antagonism by TCN 201 of GluN2A-containing NMDARs. The degree of inhibition produced by TCN 201 is dependent on the concentration of the GluN1-site co-agonist, glycine (or d-serine), and is independent of the glutamate concentration. This GluN1 agonist-dependency is similar to that observed for a related GluN2A-selective antagonist, N-(cyclohexylmethyl)-2-[{5-[(phenylmethyl)amino]-1,3,4-thiadiazol-2-yl}thio]acetamide (TCN 213). Schild analysis of TCN 201 antagonism indicates that it acts in a non-competitive manner but its equilibrium constant at GluN1/GluN2A NMDARs indicates TCN 201 is around 30-times more potent than TCN 213. In cortical neurones TCN 201 shows only modest antagonism of NMDAR-mediated currents recorded from young (DIV 9-10) neurones where GluN2B expression predominates. In older cultures (DIV 15-18) or in cultures where GluN2A subunits have been over-expressed TCN 201 gives a strong block that is negatively correlated with the degree of block produced by the GluN2B-selective antagonist, ifenprodil. Nevertheless, while TCN 201 is a potent antagonist it must be borne in mind that its ability to block GluN2A-containing NMDARs is dependent on the GluN1-agonist concentration and is limited by its low solubility
Investigation into the destructive and adaptive responses of neural cells to stress
No full textHomeostasis within the neuro-glial unit is essential to the longevity of neurons.
Conversely, loss of homeostasis, particularly of Ca2+ levels, of redox balance and of
ATP, contribute to neuronal loss and dysfunction in many neurodegenerative and
neurological disorders. This thesis is centred on better understanding the
vulnerability of neurons to stress, as well as adaptive responses to these stresses.
Since neurodegenerative conditions associated with Ca2+, redox and bioenergetic
dyshomeostasis are often characterised by early dendritic pathology, I first studied
dendritic vs. somatic responses of primary cortical neurons to these types of
challenges in real-time. Using a wide range of genetically-encoded probes to
measure Ca2+, ATP, NADH, glutathione and glutamate, I show that dendrites are
selectively vulnerable to oxidative stress, excitotoxicity as well as to metabolic
demand induced by action potential (AP) burst activity. However, I provide evidence
that neurons undergoing energetically demanding AP burst activity can adjust their
metabolic output by increasing mitochondrial NADH production in a manner
dependent on the mitochondrial calcium uniporter (MCU), as well as increase their
capacity to buffer their intracellular redox balance. Finally, I have studied
transcriptional programs in astrocytes triggered by neurons and neuronal activity to
better understand adaptive signaling between different cell types in the neuro-glial
unit. I developed a novel system combining neurons and astrocytes from closely-related
species, followed by RNA-seq and in silico read sorting. I uncovered a
program of neuron-induced astrocytic gene expression which drives and maintains
astrocytic maturity and neurotransmitter uptake function. In addition I identified a
novel form of synapse-to-nucleus signaling, mediated by glutamatergic activity and
acutely regulating diverse astrocytic genes involved in astrocyte-neuron metabolic
coupling. Of note, neuronal activity co-ordinately induced astrocytic genes involved
in astrocyte-to-neuron thyroid hormone signaling, extracellular antioxidant defences,
and the astrocyte-neuron lactate shuttle, suggesting that this non cell-autonomous
signaling may form part of the homeostatic machinery within the neuro-glial unit
Ge1-ySny (y=0.01-0.10) alloys on Ge-buffered Si: Synthesis, microstructure, and optical properties
No full textabstract: Novel hydride chemistries are employed to deposit light-emitting Ge [subscript 1- y] Sn [subscript y] alloys with y ≤ 0.1 by Ultra-High Vacuum Chemical Vapor Deposition (UHV-CVD) on Ge-buffered Si wafers. The properties of the resultant materials are systematically compared with similar alloys grown directly on Si wafers. The fundamental difference between the two systems is a fivefold (and higher) decrease in lattice mismatch between film and virtual substrate, allowing direct integration of bulk-like crystals with planar surfaces and relatively low dislocation densities. For y ≤ 0.06, the CVD precursors used were digermane Ge [subscript 2]H[subscript 6] and deuterated stannane SnD[subscript 4]. For y ≥ 0.06, the Ge precursor was changed to trigermane Ge [subscript 3]H[subscript 8], whose higher reactivity enabled the fabrication of supersaturated samples with the target film parameters. In all cases, the Ge wafers were produced using tetragermane Ge [subscript 4]H[subscript 10] as the Ge source. The photoluminescence intensity from Ge [subscript 1− y] Sn [subscript y] /Ge films is expected to increase relative to Ge [subscript 1− y] Sn [subscript y] /Si due to the less defected interface with the virtual substrate. However, while Ge [subscript 1− y] Sn [subscript y] /Si films are largely relaxed, a significant amount of compressive strain may be present in the Ge [subscript 1− y] Sn [subscript y] /Ge case. This compressive strain can reduce the emission intensity by increasing the separation between the direct and indirect edges. In this context, it is shown here that the proposed CVD approach to Ge [subscript 1− y] Sn [subscript y] /Ge makes it possible to approach film thicknesses of about 1 μm, for which the strain is mostly relaxed and the photoluminescence intensity increases by one order of magnitude relative to Ge [subscript 1− y] Sn [subscript y] /Si films. The observed strain relaxation is shown to be consistent with predictions from strain-relaxation models first developed for the Si[subscript 1− x] Ge [subscript x] /Si system. The defect structure and atomic distributions in the films are studied in detail using advanced electron-microscopy techniques, including aberration corrected STEM imaging and EELS mapping of the average diamond–cubic lattice.Copyright 2014 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. along with the following message: The following article appeared in 116, 13 (2014) and may be found at http://dx.doi.org/10.1063/1.489678
Atomic layer deposition of crystalline SrHfO3 directly on Ge (001) for high-k dielectric applications
No full textabstract: The current work explores the crystalline perovskite oxide, strontium hafnate, as a potential high-k gate dielectric for Ge-based transistors. SrHfO3 (SHO) is grown directly on Ge by atomic layer deposition and becomes crystalline with epitaxial registry after post-deposition vacuum annealing at ∼700 °C for 5 min. The 2 × 1 reconstructed, clean Ge (001) surface is a necessary template to achieve crystalline films upon annealing. The SHO films exhibit excellent crystallinity, as shown by x-ray diffraction and transmission electron microscopy. The SHO films have favorable electronic properties for consideration as a high-k gate dielectric on Ge, with satisfactory band offsets (>2 eV), low leakage current (<10[superscript −5] A/cm[superscript 2] at an applied field of 1 MV/cm) at an equivalent oxide thickness of 1 nm, and a reasonable dielectric constant (k ∼ 18). The interface trap density (Dit ) is estimated to be as low as ∼2 × 10[superscript 12] cm[superscript −2] eV[superscript −1] under the current growth and anneal conditions. Some interfacial reaction is observed between SHO and Ge at temperatures above ∼650 °C, which may contribute to increased Dit value. This study confirms the potential for crystalline oxides grown directly on Ge by atomic layer deposition for advanced electronic applications.Copyright 2015 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. along with the following message: The following article appeared in JOURNAL OF APPLIED PHYSICS 117, 5 (2015) and may be found at http://dx.doi.org/10.1063/1.490695
OB00040 - Damodarpur Copper Plate 1 (GE 163) of Budhagupta
No full textDamodarpur Copper Plate 1 (GE 163) of Budhagupt
[[alternative]]Raman Study of Folded Acoustic Phonons in Si/Ge Superlattice
No full text[[abstract]]This research presents three Raman Spectrums of Si/Ge superlattices growing on the substrate of Si by MBE. The period of superlattice samples N=5, the growing conditions of superlattice are: the Si-layer is 50nm；the Ge-layers are 2.2nm、3.8nm and 5.4nm. Measuring by TEM of samples firstly, the Si-layers are 50.18nm、48.65 nm and 48.89 nm；the Ge-layers are 2.46 nm、3.78 nm and 4.44 nm。
In the Spectrum, the peak of Si-Si mode is quite obvious；The peak of Ge-Ge mode is comparatively weak. In the room temperature, the peak of Si-Ge mode is quite unobvious due to the fewer periods.
Raman Spectrum of three superlattices shows many and obvious folded phonon signals in the low frequency (0 ~100 cm-1) area , so does the doublets of phonon are quite obvious. Fittting the frequency of folded phonons by Rytov’s theory finds that the Si-layers are 49.65nm、45.98 nm and 45.95 nm, the Ge-layers are 2.12 nm、3.78 nm and 5.01 nm. All the errors are within 6%, so Rytov’s theory is a good foundation to study Raman Spectrum of superlattice.
Fitting the intensity of folded spectrum of phonon with photoelastic mode , in the wavelength far away the energy of resonance ( As 476 nm) can get good result. Also getting the ratio of Si-layer thickness and the period of superlattice are 0.96（632 nm）、0.93（476 nm）and 0.93（476 nm）, compared with the result of fitting frequency of folded phonon by Rytov’s theory：0.96、0.92及0.90, matchs very well, except the 3% difference of sample-N107.
Besides, examining Ge-Ge mode in the spectrum with LCM, the roughness of Ge-layer can be examed, and the calculating layers are 2.22nm、3.83 nm and 5.37 nm, the difference is within 7% comparing with the result of fitting phonons.
In the various temperature (10 K~300 K) Raman Sprctrum, there are signals of continuous scattering of phonons around 200 cm-1 , and the lower the temperature, or the thinner the Ge-layer, the more obvious the continuous scattering of phonon is. We can find the phenomenon that E1 energy of Ge-layer is in the vicinity of 2.3 eV and distributed widely ,when we observe the folded phonon in low frequency, the resonance of Ge-Ge Mode, and the fluorescence in high frequency.
Neuronal activity-dependent protection against apoptotic and oxidative insults
No full textPatterns of physiological electrical activity in the central nervous system (CNS) cause longlasting
changes in gene expression that promote neuronal survival. These changes can be
mediated by signalling pathways activated by Ca2+ influx through synaptic N-methyl DAspartate
receptors (NMDARs). Identification and study of these, and other neuroprotective
signalling pathways of the CNS, is invaluable; as this may one day lead to therapeutic
strategies against the deleterious effects of CNS injury or degeneration. The data presented
in this thesis focuses on activity-dependent neuroprotection and how it interacts with other
signalling pathways to protect against apoptotic and oxidative insults.
A previously unobserved role of activity-dependent neuroprotection in mediating the effects
of the neuropeptide PACAP is demonstrated. By promoting cAMP/PKA signalling PACAP
triggers neuronal firing activity, which is essential for the neuroprotective effects mediated
by PACAP. This firing activity cooperates with direct signalling by PKA in promoting longlasting
CREB-mediated gene expression. The molecular events associated with PACAP
mediated stimulation of CRE-dependent gene expression are presented. Investigation of the
control of neuronal antioxidant defences by neuronal activity, both on its own and in
cooperation with astrocyte-derived support, was also investigated. Neuronal activity is
demonstrated to strongly increase the capacity of the antioxidant glutathione (GSH) system,
through a program of coordinated transcriptional events. The utilisation, biosynthesis and
recycling of GSH is enhanced in neurons, leading to increased resistance against oxidative
insults. Since several GSH pathway enzyme genes are regulated by the transcription factor
Nrf2, the ability of CDDO-F3, a small molecule activator of Nrf2, to mimic the effect of
firing activity on neuronal GSH levels was examined. CDDO-F3 sustains neuronal GSH
levels and confers neuroprotection against oxidative insult. These actions are dependent on
the presence of astrocytes; whereas Nrf2 mediated regulation of GSH pathway genes is
essentially inactive in neurons. Neuronal activity and activation of the astrocytic Nrf2
pathway can cooperate, maintaining neuronal GSH levels and protecting neurons against
strong oxidative insults. Collectively this work expands our knowledge as to the molecular
mechanisms of activity-dependent neuroprotection, and how such signals may synergise with
other protective pathways to promote neuronal health
The English Translation of the Epitaph of the Wu Kingdom Transcendent Duke Ge of the Left Palace of the Grand Bourne by Tao Hongjing
No full textabstract: This thesis is a translation and analysis of the “Epitaph of the Wu Kingdom
Transcendent Duke Ge of the Left Palace of the Grand Bourne” (Epitaph below). The author was Tao Hongjing (456 CE-536 CE). The subject of this Epitaph inscribed on a stele was Ge Xuan (trad. 164 CE-244 CE). Ge Xuan had two titles attributed to him by later Daoists. According to the Lingbao scriptures, Ge was appointed by the Perfected of Grand Bourne, a heavenly title. Later, in the Shangqing scriptures, Ge Xuan was said to be an earthly transcendent without any heavenly appointment. This debate occurred before Tao Hongjing began to write. This stele epitaph is essential, as it records sayings from both Lingbao and Shangqing scriptures. By reading this translated epitaph, scholars can know more about different versions of Ge Xuan's legend, as well as how Ge Xuan's legend was constantly rewritten by later Daoists.Dissertation/ThesisMasters Thesis Religious Studies 202
- …
