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385 result(s) for "Irvine, Mark"
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Structural basis of subtype-selective competitive antagonism for GluN2C/2D-containing NMDA receptors
N -Methyl-D-aspartate receptors (NMDARs) play critical roles in the central nervous system. Their heterotetrameric composition generates subtypes with distinct functional properties and spatio-temporal distribution in the brain, raising the possibility for subtype-specific targeting by pharmacological means for treatment of neurological diseases. While specific compounds for GluN2A and GluN2B-containing NMDARs are well established, those that target GluN2C and GluN2D are currently underdeveloped with low potency and uncharacterized binding modes. Here, using electrophysiology and X-ray crystallography, we show that UBP791 ((2 S *,3 R *)-1-(7-(2-carboxyethyl)phenanthrene-2-carbonyl)piperazine-2,3-dicarboxylic acid) inhibits GluN2C/2D with 40-fold selectivity over GluN2A-containing receptors, and that a methionine and a lysine residue in the ligand binding pocket (GluN2D-Met763/Lys766, GluN2C-Met736/Lys739) are the critical molecular elements for the subtype-specific binding. These findings led to development of UBP1700 ((2 S *,3 R *)-1-(7-(2-carboxyvinyl)phenanthrene-2-carbonyl)piperazine-2,3-dicarboxylic acid) which shows over 50-fold GluN2C/2D-selectivity over GluN2A with potencies in the low nanomolar range. Our study shows that the l -glutamate binding site can be targeted for GluN2C/2D-specific inhibition. Selectively inhibiting N-Methyl-D-aspartate receptors (NMDARs) containing the GluN2C/2D subunits has been challenging. Here, using electrophysiology and X-ray crystallography, authors show that compounds UBP791 and UBP1700 show over 40- and 50-fold selectivity for GluN2C/2D compared to GluN2A.
Performance of a low-cost optical particle counter (Alphasense OPC-N3) in estimating size-resolved dust emission flux using eddy covariance
The recent development of low-cost optical particle counters (OPCs) presents new opportunities for improving spatial coverage of particle concentration in the atmosphere as they are more affordable, compact, and energy efficient than traditional OPCs. In particular, these OPCs could improve our ability to quantify dust emissions in complex environments during aeolian soil erosion. The highfrequency sampling capacity (1 Hz) of some sensors may make them suitable for estimating dust emissions using the eddy-covariance method. Here, the capability of the low-cost OPC-N3 from Alphasense to estimate size-resolved dust flux using the eddy-covariance method is evaluated. During the Jordan Wind erosion And Dust Investigation (J-WADI) experiment, we tested one OPC-N3 against two traditional reference OPCs, the Promo and Fidas, from Palas GmbH. The N3 and Promo OPCs were located in close proximity to a sonic anemometer, enabling the correlation of dust concentration and vertical velocity fluctuations for estimating dust fluxes. Despite the high-temperature and dusty wind conditions of the campaign, the N3 monitored the dynamics and magnitude of dust concentration with reasonable precision. The turbulence characteristics of the dust concentration fluctuations measured by the N3, including variance, skewness, kurtosis, and energy spectrum, were similar to those from the Promo. However, the N3 flow rate exhibited variations under these outdoor conditions that affected the concentration of fine dust particles, and certain particles around 1 µm appeared to be misclassified in the upper size bin. After correcting the N3 dust concentration to address these discrepancies and after calibrating it against a reference OPC, the N3 accurately estimated the dust emission flux, with differences of less than 30 % compared to the reference OPC. Our results confirm the potential of low-cost OPCs for dust erosion research. Nonetheless, further evaluation of low-cost OPCs is still needed across different environments and weather conditions.
Turbulent Structures in a Pine Forest with a Deep and Sparse Trunk Space: Stand and Edge Regions
Forested landscapes often exhibit large spatial variability in vertical and horizontal foliage distributions. This variability may affect canopy-atmosphere exchanges through its action on the development of turbulent structures. Here we investigate in neutral stratification the turbulent structures encountered in a maritime pine forest characterized by a high, dense foliated layer associated with a deep and sparse trunk space. Both stand and edge regions are considered. In situ measurements and the results of large-eddy simulations are used and analyzed together. In stand conditions, far from the edge, canopy-top structures appear strongly damped by the dense crown layer. Turbulent wind fluctuations within the trunk space, where the momentum flux vanishes, are closely related to these canopy-top structures through pressure diffusion. Consequently, autocorrelation and spectral analyses are not quite appropriate to characterize the vertical scale of coherent structures in this type of canopy, as pressure diffusion enhances the actual scale of structures. At frequencies higher than those associated with canopy-top structures, wind fluctuations related to wake structures developing behind tree stems are observed within the trunk space. They manifest themselves in wind velocity spectra as secondary peaks in the inertial subrange region, confirming the hypothesis of spectral short-cuts in vegetation canopies. In the edge region specific turbulent structures develop just below the crown layer, in addition to canopy-top structures. They are generated by the wind shear induced by the sub-canopy wind jet that forms at the edge. These structures provide a momentum exchange mechanism similar to that observed at the canopy top but in the opposite direction and with a lower magnitude. They may develop as in plane mixing-layer flows, with some perturbations induced by canopy-top structures. Wake structures are also observed within the trunk space in the edge region.
A single-channel mechanism for pharmacological potentiation of GluN1/GluN2A NMDA receptors
NMDA receptors (NMDARs) contribute to several neuropathological processes. Novel positive allosteric modulators (PAMs) of NMDARs have recently been identified but their effects on NMDAR gating remain largely unknown. To this end, we tested the effect of a newly developed molecule UBP684 on GluN1/GluN2A receptors. We found that UBP684 potentiated the whole-cell currents observed under perforated-patch conditions and slowed receptor deactivation. At the single channel level, UBP684 produced a dramatic reduction in long shut times and a robust increase in mean open time. These changes were similar to those produced by NMDAR mutants in which the ligand-binding domains (LBDs) are locked in the closed clamshell conformation by incorporating a disulfide bridge. Since the locked glutamate-binding clefts primarily contributes to receptor efficacy these results suggests that UBP684 binding may induce switch in conformation similar to glutamate LBD locked state. Consistent with this prediction UBP684 displayed greater potentiation of NMDARs with only the GluN1 LBD locked compared to NMDARs with only the GluN2 LBD locked. Docking studies suggest that UBP684 binds to the GluN1 and GluN2 LBD interface supporting its potential ability in stabilizing the LBD closed conformation. Together these studies identify a novel pharmacological mechanism of facilitating the function of NMDARs.
Directional anisotropy in thermal infrared measurements over Toulouse city centre during the CAPITOUL measurement campaigns: first results
The measurements of surface temperature are prone to important directional anisotropy related to the structure of the canopy and the radiative and energy exchanges inside of it. Directional effects must be taken into account for a number of practical applications such as the correction of large swath satellite data, the assimilation of thermal infrared (TIR) measurements in surface models, the design of future spatial missions[em leader] For urban canopies, experimental measurements of TIR directional anisotropy previously performed during summer days over Marseille in the framework of the ESCOMPTE campaign (2001) revealed significant angular surface temperature variations with noticeable hot spot effects whose intensity was related to the canopy structure. The CAPITOUL project (http://medias.cnrs.fr/capitoul/) provided the opportunity to extend these results to other seasons and to nighttime conditions. The experimental setup is based on the use of 2 airborne TIR cameras with different lenses, inclination and resolution, and installed aboard a small aircraft. The flight protocol allowed the retrieval of directional anisotropy in all azimutal directions and in a range of zenith viewing angles between nadir and 62°. Measurements were performed during several intensive operation periods (IOP) in summer (2004 july), autumn (2004 September and October) and winter (2005 February). Only the first results of the 2004 autumn and 2005 winter IOPs are presented in this paper. The results obtained in daytime conditions confirm the systematic hot spot effects observed in previous experiments over cities. The variations found seem to be particularly important in winter when sun elevation is low: for instance they range between -4 and 10 K between oblique and nadir viewing in February. During nighttime conditions, angular variations are much lower (always less than 2 K between nadir and 60° zenithal viewing angle), whichever the azimutal viewing direction.
Temperature–Humidity Dissimilarity and Heat-to-water-vapour Transport Efficiency Above and Within a Pine Forest Canopy: the Role of the Bowen Ratio
Over the past 15 years atmospheric surface-layer experiments over heterogeneous canopies have shown that the vertical transfer of sensible heat and water vapour exhibit a strong dissimilarity. In particular, the sensible-heat-to-water-vapour transport efficiencies generally exceed unity. One of the main consequences is that evaporation (latent heat flux) computed by the flux-variance method is overestimated, as persistently demonstrated by comparisons with evaporation obtained with the eddy-correlation method. Various authors proposed to take into account the temperature-humidity dissimilarity to extend the applicability of the flux-variance method in order to compute evaporation from non-uniform surfaces. They attempted to connect the sensible-heat-to-water-vapour transport efficiency (λ) to the correlation coefficient between temperature and humidity turbulent fluctuations (R ^sub Tq^). This approach was found to be successful over 'wet' surfaces for which λ can be approximated by R ^sub Tq^ and 'dry' surfaces for which λ can be approximated by 1/R ^sub Tq^. However, no solution has been proposed until now for intermediate hydrological conditions. We investigated this question using eddy-correlation measurements above and inside a pine forest canopy. For both levels, our data present a strong likeness with previously published results over heterogeneous surfaces. In particular, they confirm that λ is R ^sub Tq^ in wet conditions and 1/R ^sub Tq^ in dry conditions. Moreover, we defined the range of the Bowen ratio (Bo) values for which those two approximations are valid (below 0.1 and greater than 1, respectively) and established a relationship between λ, R ^sub Tq^ and Bo for the intermediate range of Bo. We are confident that this new parameterization will enlarge the applicability of the flux-variance method to all kinds of heterogeneous surfaces in various hydrological conditions[PUBLICATION ABSTRACT]
Turbulent structures in a pine forest with a deep and sparse trunk space: stand and edge regions
Forested landscapes often exhibit large spatial variability in vertical and horizontal foliage distributions. This variability may affect canopy-atmosphere exchanges through its action on the development of turbulent structures. Here we investigate in neutral stratification the turbulent structures encountered in a maritime pine forest characterized by a high, dense foliated layer associated with a deep and sparse trunk space. Both stand and edge regions are considered. In situ measurements and the results of large-eddy simulations are used and analyzed together. In stand conditions, far from the edge, canopy-top structures appear strongly damped by the dense crown layer. Turbulent wind fluctuations within the trunk space, where the momentum flux vanishes, are closely related to these canopy-top structures through pressure diffusion. Consequently, autocorrelation and spectral analyses are not quite appropriate to characterize the vertical scale of coherent structures in this type of canopy, as pressure diffusion enhances the actual scale of structures. At frequencies higher than those associated with canopy-top structures, wind fluctuations related to wake structures developing behind tree stems are observed within the trunk space. They manifest themselves in wind velocity spectra as secondary peaks in the inertial subrange region, confirming the hypothesis of spectral short-cuts in vegetation canopies. In the edge region specific turbulent structures develop just below the crown layer, in addition to canopy-top structures. They are generated by the wind shear induced by the sub-canopy wind jet that forms at the edge. These structures provide a momentum exchange mechanism similar to that observed at the canopy top but in the opposite direction and with a lower magnitude. They may develop as in plane mixing-layer flows, with some perturbations induced by canopy-top structures. Wake structures are also observed within the trunk space in the edge region. Keywords Coherent eddy structures * Forest canopy * Large-eddy simulation * Plane mixing-layer flow * Trunk space * Wind spectra
Monitoring the sensible heat flux over urban areas using large aperture scintillometry: case study of Marseille city during the ESCOMPTE experiment
Sensible heat flux estimated by Large Aperture Scintillometry (LAS) has been tested against the more traditional eddy covariance technique over Marseille city centre, a reasonably homogeneous surface. Over the 3 week test period fluxes were found to be similar, yet less noisy for the LAS due to the spatial integration. No systematic bias between the estimates was found as a function of wind direction, indicating the homogeneity of the site. Sensitivity analysis of the required aerodynamic parameters shows that careful attention must be paid to the displacement height along the measurement path. Spatial variability of surface sensible heat flux is studied via a second LAS measurement path over the city.
Experimental evidence of a phase transition in the multifractal spectra of turbulent temperature fluctuations at a forest canopy top
Ramp–cliff patterns visible in scalar turbulent time series have long been suspected to enhance the fine-scale intermittency of scalar fluctuations compared to longitudinal velocity fluctuations. Here, we use the wavelet transform modulus maxima method to perform a multifractal analysis of air temperature time series collected at a pine forest canopy top for different atmospheric stability regimes. We show that the multifractal spectra exhibit a phase transition as the signature of the presence of strong singularities corresponding to sharp temperature drops (respectively jumps) bordering the so-called ramp (respectively inverted ramp) cliff patterns commonly observed in unstable (respectively stable) atmospheric conditions and previously suspected to contaminate and possibly enhance the internal intermittency of (scalar) temperature fluctuations. Under unstable (respectively stable) atmospheric conditions, these ‘cliff’ singularities are indeed found to be hierarchically distributed on a ‘Cantor-like’ set surrounded by singularities of weaker strength typical of intermittent temperature fluctuations observed in homogeneous and isotropic turbulence. Under near-neutral conditions, no such a phase transition is observed in the temperature multifractal spectra, which is a strong indication that the statistical contribution of the ‘cliffs’ is not important enough to account for the stronger intermittency of temperature fluctuations when compared to corresponding longitudinal velocity fluctuations.
From fine to giant: multi-instrument assessment of the dust particle size distribution at an emission source during the J-WADI field campaign
Mineral dust particles emitted from dry, uncovered soil can be transported over vast distances, thereby influencing climate and environment. Its impacts are highly size-dependent, yet large particles with diameters dp>10 µm remain understudied due to their low number concentrations and instrumental limitations. Accurately characterizing the particle size distribution (PSD) at emission is crucial for understanding dust transport and climate interactions. Here we characterize the dust PSD at an emission source during the Jordan Wind Erosion and Dust Investigation (J-WADI) campaign, conducted in Wadi Rum, Jordan, in September 2022, focusing on super-coarse (1062.5 µm) particles. This study is the first to continuously cover the full range of diameters from dp=0.4 to 200 µm at an emission source by using a suite of aerosol spectrometers with overlapping size ranges. This overlap enabled a systematic intercomparison and validation across instruments, improving PSD reliability. Results show significant PSD variability over the course of the campaign. During periods with friction velocities (u*) above 0.22 m s−1 (or ∼ 3.3 m s−1 threshold 4 m wind speed), the approximate threshold for local dust emission by saltation, both dust concentrations and the contributions of super-coarse and giant particles typically increased with increasing u*, especially under neutral to unstable atmospheric stability conditions. These large particles accounted for about 90 % of the total mass concentration during the campaign. A prominent mass concentration peak was observed near dp=60 µm in geometric diameter. While particle concentrations for dp<10 µm showed good agreement among most instruments, discrepancies appeared for larger dp due to reduced instrument sensitivity at the size range boundaries and sampling inefficiencies. Despite these challenges, physical samples collected using a flat-plate sampler largely confirmed the PSDs derived from the aerosol spectrometers. These findings help to advance our understanding of the dust PSD and the abundance of super-coarse and giant particle at emission sources.