Lynx1 and the β2V287L mutation affect the stoichiometry of the α4β2 nicotinic acetylcholine receptor

GPI-anchored neurotoxin-like receptor binding proteins, such as lynx modulators, are topologically positioned to exert pharmacological effects by binding to the extracellular portion of nAChRs. These actions are generally thought to proceed when both lynx and the nAChRs are on the plasma membrane. Here, we demonstrate that lynx1 also exerts effects on α4β2 nAChRs within the endoplasmic reticulum. Lynx affects assembly of nascent α4 and β2 subunits, and alters the stoichiometry of the population that reaches the plasma membrane. Additionally, these data suggest that lynx1 alters nAChR stoichiometry primarily through this intracellular interaction, rather than via effects on plasma membrane nAChRs. To our knowledge, these data represent the first test of the hypothesis that a lynx family member, or indeed any GPI-anchored protein, could act within the cell to alter assembly of multi-subunit protein.

Binding Site Structure and Stoichiometry in Serotonin Type 3 Receptors

This dissertation primarily describes studies of serotonin type 3 (5-HT₃) receptors of the Cys-loop super-family of ligand gated ion channels. The first chapter provides a general introduction to these important proteins and the methods used to interrogate their structure and function. The second chapter details the delineation of a structural unit of the ligand binding site of homomeric 5-HT₃A receptors on which the ligands serotonin (5-HT) and m-chlorophenyl biguanide (mCPBG) are reliant for effective receptor activation. Unnatural amino acid mutagenesis results show that the details of each ligand’s interaction with this organizing feature of the binding site differ, providing insights into general principles of receptor activation.

The third chapter describes a study in which florescent protein fusions of the A and B subunits of the heteromeric 5-HT₃AB receptor are employed to determine the subunit stoichiometry and order within functional receptors. Strong evidence is found for an A₃B₂ stoichiometry with A-A-B-A-B order. The fourth chapter investigates the potential for ligand binding across heteromeric binding sites in the 5-HT₃AB receptor. Unlike serotonin, mCPBG is found to bind the receptor at heteromeric binding sites. Further mCPBG is capable of allosterically modulating the response of serotonin on the 5-HT₃AB receptor from these heteromeric sites.

Finally, the fifth chapter describes progress towards the application of unnatural amino acid mutagenesis to an important new class of proteins, transcription factors. Experiments optimizing novel methods for the detection of function are described, using RARα of the nuclear receptor family of transcription factors.

Efficiency, energy and stoichiometry in pelagic food webs; reciprocal roles of food quality and food quantity

In most lakes, zooplankton production is constrained by food quantity, but frequently high C:P poses an additional constraint on zooplankton production by reducing the carbon transfer efficiency from phytoplankton to zooplankton. This review addresses how the flux of matter and energy in pelagic food webs is regulated by food quantity in terms of C and its stoichiometric quality in terms of C:P. Increased levels of light, CO2 and phosphorus could each increase seston mass and, hence, food quantity for zooplankton, but while light and CO2 each cause increased C:P (i.e. reduced food quality for herbivores), increased P may increase seston mass and its stoichiometric quality by reducing C:P. Development of food quality and food quantity in response to C- or P-enrichments will differ between 'batch-type' lakes (dominated by one major, seasonal input of water and nutrients) and 'continuous-culture' types of lakes with a more steady flow-rate of water and nutrients. The reciprocal role of food quantity and stoichiometric quality will depend strongly on facilitation via grazing and recycling by the grazers, and this effect will be most important in systems with low renewal rates. At high food abundance but low quality, there will be a 'quality starvation' in zooplankton. From a management point of view, stoichiometric theory offers a general tool-kit for understanding the integrated role of C and P in food webs and how food quantity and stoichiometric quality (i.e. C:P) regulate energy flow and trophic efficiency from base to top in food webs.From a management point of view, stoichiometric theory offers a general tool-kit for understanding the integrated role of C and P in food webs and how food quantity and stoichiometric quality (i.e. C:P) regulate energy flow and trophic efficiency from base to top in food webs.

Effects of nonuniform reactant stoichiometry on thermoacoustic instability in a lean-premixed gas turbine combustor

Detailed experimental investigations of the amplitude dependence of flame describing functions (FDF) were performed using a stratified swirl-stabilized combustor, in order to understand the combustion-acoustic interactions of CH4/air flames propagating into nonhomogeneous reactant stoichiometry. Phase-synchronized OH planar laser induced fluorescence (OH PLIF) measurements were used to investigate local reaction zone structures of forced flames. To determine the amplitude-and frequency-dependent forced flame response, simultaneous measurements of inlet velocity and heat release rate oscillations were made using a constant temperature anemometer and photomultiplier tubes with narrow-band OH*/CH* interference filters. The measurements were made over a wide range of stratification ratios, including inner stream enrichment ( θ o>θ i) and outer stream enrichment ( θ o>θ i)) conditions, and compared to the baseline condition of spatially and temporally homogeneous cases ( θ o=θ i)). Results show that for the inlet conditions investigated, fuel stratification has a significant influence on local and global flame structures of unforced and forced flames. Under stratified conditions, length scales of local contours were found to be much larger than the homogeneous case due to high kinematic viscosities associated with high temperature. Stratification has a remarkable effect on flame-vortex interactions when the flame is subjected to high-amplitude acoustic forcing, leading to different evolution patterns of FDF (amplitude and disturbance convective time) in response to the amplitude of the imposed inlet velocity oscillation. The present experimental investigation reveals that intentional stratification has the potential to eliminate or suppress the occurrence of detrimental combustion instability problems in lean-premixed gas turbine combustion systems. © 2012 Copyright Taylor and Francis Group, LLC.

Effects of nonuniform reactant stoichiometry on combustion instability

This paper analyzes the forced response of swirl-stabilized lean-premixed flames to acoustic forcing in a laboratory-scale stratified burner. The double-swirler, double-channel annular burner was specially designed to generate acoustic velocity oscillations and radial fuel stratification at the inlet of the combustion chamber. Temporal oscillations of equivalence ratio along the axial direction are dissipated over a long distance, and therefore the effects of time-varying fuel/air ratio on the flame response are not considered. Simultaneous measurements of inlet velocity and heat release rate oscillations were made using a hot wire anemometer and photomultiplier tubes with narrowband OH*/CH* interference filters. Time-averaged CH* chemiluminescence intensities were measured using an intensified CCD camera. Results show that flame stabilization mechanisms vary depending on stratification ratio for a constant global equivalence ratio. For a uniformly premixed condition, an enveloped M-shaped flame is observed. For stratified conditions, however, a dihedral V-flame and a detached flame are developed for outer stream and inner stream fuel enrichment cases, respectively. Flame transfer function (FTF) measurement results indicate that a V-shaped flame tends to damp incident flow oscillations, while a detached flame acts as a strong amplifier relative to the uniformly premixed condition. The phase difference of FTF increases in the presence of stratification. More importantly, the dynamic characteristics obtained from the forced stratified flame measurements are well correlated with unsteady flame behavior under limit-cycle pressure oscillations. The results presented in this paper provide insight into the impact of nonuniform reactant stoichiometry on combustion instabilities, which has not been well explored to date. Copyright © 2011 by ASME.

The influence of stoichiometry on the structural stability and on the optical emission of erbium silicate thin films

We report the effects of thermal annealing performed in N2 or O2 ambient at 1200 °C on the structural and optical properties of Er silicate films having different compositions (Er2Si O 5,Er2 Si2 O7, and their mixture). We demonstrate that the chemical composition of the stoichiometric films is preserved after the thermal treatments. All different crystalline structures formed after the thermal annealing are identified. Thermal treatments in O 2 lead to a strong enhancement of the photoluminescence intensity, owing to the efficient reduction of defect density. In particular the highest optical efficiency is associated to Er ions in the α phase of Er 2 Si2 O7. © 2008 American Institute of Physics.

Relationship between deep-level centers and stoichiometry in semi-insulating gallium arsenide

Experimental results have shown the fact that the deep-level centers in semi-insulating GaAs decrease with the improvement in stoichiometry. The electrical resistivity doubles when the concentration of EL2 centers decreases to a half. The microgravity-growth experiments also show that improved crystal stoichiometry results in a decrease of deep-level centers. (C) 1998 American Institute of Physics. [S0021-8979(98)04921-4].

Improvement of stoichiometry in semi-insulating gallium arsenide grown under microgravity

A semi-insulating (SI) GaAs single crystal was recently grown in a retrievable satellite. The average etch pit density (EPD) of dislocations in the crystal revealed by molten KOH is 2.0 x 10(4) cm(-2), and the highest EPD is 3.1 x 10(4) cm(-2) This result indicates a quite good homogenity of the EPD which is much better than the ground-grown crystals. A similar better homogenity of the stoichiometry i.e., the [As]/([As] + [Ga]) ratio has been found in the space-grown SI-GaAs single crystal studied nondestructively using a new mapping method based upon X-ray Bond diffraction. The average stoichiometry in the space-grown crystal is 0.50007 with mean-square deviation of 6x10(-6), while the average stoichiometry in ground-grown SI-GaAs crystal is more than 0.50010. (C) 1998 Elsevier Science B.V. All rights reserved.

Nondestructive measurements of stoichiometry in undoped semi-insulating gallium arsenide by x-ray bond method

The influences of microdefects and dislocations on the lattice parameters of undoped semi-insulating GaAs single crystals were analyzed, and a novel nondestructive method for measuring stoichiometry in undoped semi-insulating GaAs was established in this letter. The comparison of this method with coulometric titration indicates that the method of nondestructive measurements is indeed convenient and reliable. (C) 1996 American Institute of Physics.

Non-stoichiometry Related Deep Level Defects in Semi-insulating InP

Semi-insulating (SI) InP materials have been prepared under different stoichiometric conditions, including Fe-doping in indium-rich melt and high temperature annealing undoped wafer in phosphorus and iron phosphide ambients. Deep level defects related with non-stoichiometry have been detected in the SI-InP samples. A close relationship between the material quality of electrical property and native deep defects has been revealed by a comprehensive study of defects in as-grown Fe-doped and annealed undoped SI-InP materials. Fe-doped SI-InP material with low carrier mobility and poor thermal stability contains a high concentration of deep defects with energy levels in the range of 0.1-0.4eV. The suppression of the defects by high temperature annealing undoped InP leads to the manufacture of high quality SI-InP with high mobility and good electrical uniformity. A technology for the growth of high quality SI-InP through stoichiometry control has been proposed based on the results.

Stoichiometry in GaAs grown in outer space measured nondestructively

A semi-insulating (SI) GaAs single crystal ingot was successfully grown in a recoverable satellite. The two-dimensional distribution of stoichiometry in space-grown SI-GaAs single crystal wafer was studied nondestructively based upon x-ray Band diffraction. The avenge stoichiometry in the space-grown crystal is 0.50007 with mean square deviation of 6 x 10(-6), and shows a better stoichiametric property than the ground-grown SI-GaAs. The average etch pit density (EPD) of dislocations in the crystal revealed by molten KOH is 2.0 x 10(4) cm(-2), and the highest EPD is 3.1 x 10(4) cm(-2). This result indicates that the structural properly of the crystal is quite good.

The effect of stoichiometry on nonlinear optical properties of LiNbO3

From the chemical bond viewpoint, second-order nonlinear optical (NLO) tensor coefficients of LiNbO3 have been investigated. The single-bond contributions to the second-order NLO susceptibility and the linear susceptibility were determined. The tensor values thus calculated are in good agreement with experimental data. Based on theoretical results of LiNbO3 with Li/Nb = 1, we also have calculated linear and nonlinear optical properties of nonstoichiometric samples with Li/Nb < 1. In the calculation, we find that the Li-O bond is an important type of chemical bond in these LiNbO3 samples, which have large NLO contributions to the total nonlinearities. The refractive indices and second-order NLO tensor coefficients have been determined as a function of the stoichiometry.