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Earth system models (ESMs) typically represent surface heterogeneity on scales smaller than the atmospheric grid, while land–atmosphere coupling is based on grid mean values. Here we present a general approach allowing subgrid surface heterogeneity to influence the updraft thermodynamic properties in a multi-plume mass flux parameterization. The approach is demonstrated in single column experiments with an eddy diffusivity–mass flux (EDMF) boundary layer scheme. Instead of triggering based on grid mean surface values, updrafts are explicitly assigned to individual surface tiles with positive buoyancy flux. Joint distributions of near-surface vertical velocities and thermodynamic variables are defined over individual surface tiles, and updraft properties are drawn from the positive tails of the distributions. The approach allows updraft properties to covary with surface heterogeneity, and updrafts from different tiles maintain distinct properties to heights of several hundred meters. Mass flux contributions to subgrid variances are increased near the surface, but impacts on mean state variables are relatively small. We suggest that larger impacts might be obtained by adding a specialized plume to represent the effects of secondary circulations. [ABSTRACT FROM AUTHOR]

Earth system models currently struggle to account for the complex effects that land surface heterogeneity can have on land‐atmosphere interactions. There have been attempts to include the impact of this heterogeneity on the atmosphere, but they ignore the development of coherent circulations that can be driven by spatial differential surface heating. A wealth of literature, particularly large‐eddy simulation (LES) based studies, shows that these circulations have significant impacts on the development and organization of clouds. In this work, we describe a two‐column model with a parameterized circulation driven by atmospheric virtual potential temperature profiles, differences in near surface temperature between the two columns, patterns of surface heterogeneity, and the mean background wind. Key aspects of the proposed model structure are compared with LES output, and the model is then implemented between two otherwise independent single column models. While some avenues for improvement exist, when the circulations are parameterized, we see increased cloud development and realistic changes to the mean profiles of temperature and moisture. The proposed model qualitatively matches expectations from the literature and LES, and points to the potential success of its future implementation in coarse grid models. Plain Language Summary: This work addresses the challenge of incorporating land surface heterogeneity into earth system models to better understand land‐atmosphere interactions. Current models struggle to account for the complex effects of subgrid land surface heterogeneity on these interactions, especially when a warmer region near a cooler region can cause a circulation to occur. The study proposes a two‐column model that includes a parameterized circulation driven by vertical temperature profiles, surface temperature differences, surface heterogeneity patterns, and the background wind. The model is compared to high resolution large‐eddy simulation (LES) output for 3 days in the Southern Great Plains. The results show that the model qualitatively reproduces patterns observed in LES and the existing literature, primarily that cloud production increases and concentrates over warmer surface areas. The model's success suggests its potential implementation in coarse grid models to explore regional and global atmospheric impacts of subgrid land surface heterogeneity. Additionally, the similarities between land surface heterogeneity circulations and other thermally driven circulations indicate potential applicability in subgrid‐scale parameterization of sea and lake breezes. While limitations and opportunities for improvement exist, overall this work represents a promising step toward understanding the impacts of subgrid heterogeneity on cloud production and atmospheric processes in earth system models. Key Points: A parameterized circulation between two otherwise independent columns is described and evaluated for three simulation daysLarge‐eddy simulations (LES) show substantial agreement with the overall circulation model structure proposedWhen implemented, the parameterized circulation yields similar changes in the atmospheric profiles and cloud production to LES [ABSTRACT FROM AUTHOR]

Parameterized boundary layer turbulence and moist convection remain some of the largest sources of uncertainty in general circulation models. High-resolution climate modeling aims to reduce that uncertainty by explicitly attempting to resolve deep moist convective motions. An example of such a model is the Simple Cloud-Resolving E3SM Atmosphere Model (SCREAM) with a target global resolution of 3.25 km, allowing for a more accurate representation of complex mesoscale deep convective dynamics. Yet, small-scale planetary boundary layer turbulence and shallow convection still need to be parameterized, which in SCREAM is accomplished through the turbulent-kinetic-energy-based (TKE-based) simplified higher-order closure (SHOC) – a simplified version of the assumed-double-Gaussian-PDF (probability density function) higher-order-closure method. In this paper, we implement a stochastic-multiplume mass-flux (MF) parameterization of dry and shallow convection in SCREAM to go beyond the limitations of double-Gaussian-PDF closures and couple it to SHOC (SHOC + MF). The new parameterization implemented in a single-column model type version of SCREAM produces results for two shallow cumulus convection cases (marine and continental shallow convection) that agree well with the reference data from large-eddy simulations, thus improving the general representation of the thermodynamic quantities and their turbulent fluxes as well as cloud macrophysics in the model. Furthermore, SHOC + MF parameterization shows weak sensitivity to the vertical grid resolution and model time step. [ABSTRACT FROM AUTHOR]

Cloud Layers Unified By Binormals (CLUBB) adopts the joint probability density function (PDF) to close higher‐order turbulence and diagnose the cloud fraction. CLUBB assumes the equal PDF width of vertical velocity (w $w$) as the default closure scheme, called Analytic Double Gaussian 1 (ADG1). In this study, a new unequal width PDF closure scheme is adopted in CLUBB, in which the PDF width of w $w$ is assumed to be associated with skewness and kurtosis of vertical velocity. Offline calculation shows that the updated closure scheme improves the tail in the joint PDF and produces the saturation area from the joint PDF of the total water and liquid water potential temperature closer to that derived from large‐eddy simulations than ADG1. The new PDF scheme implemented in Community Atmosphere Model Version 6 is shown to increase low cloud fraction by 20%–30% in most stratocumulus‐to‐cumulus transition regions. The updated closure scheme is found to improve the low cloud simulation by simulating more symmetric turbulence in stratocumulus and stronger turbulent transport in shallow cumulus. Furthermore, the updated closure scheme enhances the cloud fraction near the cloud base by interacting with the microphysical scheme. Our work indicates the importance of continuous improvement in the PDF closures for higher‐order turbulence schemes. Plain Language Summary: Low clouds play an important role in global energy and water cycles, and their simulations in global climate models remain challenging. Here we improved the turbulence parameterization scheme in a climate model. The new scheme updates the width assumption of vertical velocity, temperature and moisture distribution, which improves the representation of extreme skewed turbulence and makes the turbulence parameterization closer to physical reality. The updated scheme is shown to improve the distribution of moisture and temperature in better agreement with high‐resolution simulation results, and increase low cloud fraction by 20%–30% in most low cloud regions compare with observations. Key Points: An updated unequal width probability density function (PDF) closure scheme is implemented in Community Atmosphere Model Version 6The new PDF closure scheme produces the joint PDF of vertical velocity, total water and liquid water potential temperature closer to large‐eddy simulation resultsThe new PDF closure scheme improves low cloud fraction simulations by 20%–30% in most stratocumulus‐to‐cumulus transition regions [ABSTRACT FROM AUTHOR]

Background and Purpose: Paclitaxel produces a chemotherapy‐induced peripheral neuropathy that persists in 50–60% of cancer patients upon treatment. Evidence from animal models suggests an axonopathy of peripheral A‐ and C‐type fibres that affects their excitability. However, direct effects of paclitaxel on sensory neuron excitability and sexual dimorphism remain poorly understood. Experimental Approach We used a long‐lasting (10 days in vitro) primary culture of rat dorsal root ganglion (DRG) neurons to investigate the time course effect of paclitaxel on the electrical activity of IB4(−) and IB4(+) sensory neurons of female and male adult Wistar rats. Key Results: Paclitaxel strongly and reversibly stimulated spontaneous activity and augmented action potential tonic firing in IB4(−) and IB4(+) neurons in both sexes, peaking at 48 h post‐treatment and virtually disappearing at 96 h. Paclitaxel decreased the current rheobase for action potential firing by reducing and accelerating the after‐hyperpolarization phase. Molecularly, paclitaxel modulated Na+ and K+ ion currents. Particularly, the drug significantly augmented the function of Nav1.8, TRPV1 and TRPM8 channels. Furthermore, paclitaxel increased Nav1.8 and TRPV1 expression at 48 h post‐treatment. Notably, we observed that female DRG neurons appear more sensitive to paclitaxel sensitization than their male counterparts. Conclusions and Implications: Our data indicate that paclitaxel similarly potentiated IB4(−) and IB4(+) electrogenicity and uncover a potential sex dimorphism in paclitaxel‐induced chemotherapy‐induced peripheral neuropathy. Our in vitro, pre‐clinical, chemotherapy‐induced peripheral neuropathy paradigm provides a tool for studying the dynamics and underlying molecular mechanisms contributing to nociceptor sensitization in peripheral neuropathies and for testing desensitizing compounds. [ABSTRACT FROM AUTHOR]

Many potential causes for painful diabetic neuropathy have been proposed including actions of cytokines and growth factors. High mobility group protein B1 (HMGB1) is a RAGE agonist, increased in diabetes, that contributes to pain by modulating peripheral inflammatory responses. HMGB1 enhances nociceptive behaviour in naïve animals through an unknown mechanism. We tested the hypothesis that HMGB1 causes pain through direct neuronal activation of RAGE and alteration of nociceptive neuronal responsiveness. HMGB1 and RAGE expression were increased in skin and primary sensory (DRG) neurons of diabetic rats at times when pain behaviour was enhanced. Agonist-evoked TRPV1-mediated calcium responses increased in cultured DRG neurons from diabetic rats and in neurons from naïve rats exposed to high glucose concentrations. HMGB1-mediated increases in TRPV1-evoked calcium responses in DRG neurons were RAGE and PKC-dependent, and this was blocked by co-administration of the growth factor splice variant, VEGF-A165b. Pain behaviour and DRG RAGE expression increases were blocked by VEGF-A165b treatment of diabetic rats in vivo. [ABSTRACT FROM AUTHOR]

Aim It has been demonstrated that brief episodes of mental stress can cause transient endothelial dysfunction, which is an important early event in atherogenesis. The purpose of this study is to examine the independent effect of hostility trait on resting endothelial function. Objective A total of 89 healthy adults were recruited. Hostility was measured by the Buss-Durkee Hostility Inventory- Chinese Version- Short Form. Vascular dilatory functions were measured by using ultrasound imaging of the brachial artery before and after cuff occlusion, before and after sublingual nitroglycerin. Conclusion Multiple regression analyses revealed the independent negative effect of hostility on flow-mediated dilation (FMD). And this association is independent from biomedical risk factors and other psychological factors, specifically anxiety and depression. With respect to Nitroglycerin-induced dilation, none of the psychological risk factors were found to have statistically significant contribution. [ABSTRACT FROM AUTHOR]

Details a study on whether islet amyloid polypeptide (IAPP) produces satiety by an endocrine mechanism. Theoretical background; Materials and methods; Results.

Although duodenogastric reflux is a physiological event, excessive reflux may be a pathogenetic factor in several diseases of the foregut, including cancer. Long term profound duodenogastric reflux produces pancreatic and gastric tumours in rats. The trophic effect of surgically induced duodenogastric reflux on the pancreas was investigated and the mechanisms involved were examined. Rats with profound reflux from a split gastroenterostomy were compared with sham operated and unoperated controls after two and six weeks. In the six week experiment, one reflux and one sham group were given the cholecystokinin (CCK) receptor antagonist devazepide (25 nmol/kg/h). Duodenogastric reflux caused a significant increase in pancreatic weight, DNA, and plasma CCK and gastrin concentrations at both two and six weeks. Devazepide substantially reduced the pancreatic weight increase after six weeks but did not abolish it completely. CCK and gastrin were not affected by devazepide. These results suggest that CCK is largely responsible for the pancreatic growth induced by reflux but another factor may also be involved. The trophic effect of duodenogastric reflux may contribute to the increased incidence of pancreatic cancer reported after gastric surgery. [ABSTRACT FROM PUBLISHER]

Mental stress has been shown to induce cardiovascular events, likely due to its negative impact on vascular function. Flavanols, plant-derived polyphenolic compounds, improve endothelial function and blood pressure (BP) in humans, however their effects during stress are not known. This study examined the effects of acute intake of cocoa flavanols on stress-induced changes on vascular function. In a randomised, controlled, double-blind, cross-over intervention study, 30 healthy men ingested a cocoa flavanol beverage (high-flavanol: 150 mg vs. low-flavanol < 4 mg (−)-epicatechin) 1.5 h before an 8-min mental stress task). Forearm blood flow (FBF), BP, and cardiovascular activity were assessed pre- and post-intervention, both at rest and during stress. Endothelial function (brachial flow-mediated dilatation, FMD) and brachial BP were measured before the intervention and 30 and 90 min post-stress. FMD was impaired 30 min post-stress, yet high-flavanol cocoa attenuated this decline and remained significantly higher compared to low-flavanol cocoa at 90 min post-stress. High-flavanol cocoa increased FBF at rest and during stress. Stress-induced cardiovascular and BP responses were similar in both conditions. Flavanols are effective at counteracting mental stress-induced endothelial dysfunction and improving peripheral blood flow during stress. These findings suggest the use of flavanol-rich dietary strategies to protect vascular health during stress. [ABSTRACT FROM AUTHOR]