The phosphorylation of serine 10 in histone 3 (p-S10H3) has recently been demonstrated to participate in spinal nociceptive processing. However, superficial dorsal horn (SDH) neurons involved in p-S10H3-mediated nociception have not been fully characterized. In the present work, we combined immunohistochemistry, in situ hybridization with the retrograde labeling of projection neurons to reveal the subset of dorsal horn neurons presenting an elevated level of p-S10H3 in response to noxious heat (60 °C), causing burn injury. Projection neurons only represented a small percentage (5%) of p-S10H3-positive cells, while the greater part of them belonged to excitatory SDH interneurons. The combined immunolabeling of p-S10H3 with markers of already established interneuronal classes of the SDH revealed that the largest subset of neurons with burn injury-induced p-S10H3 expression was dynorphin immunopositive in mice. Furthermore, the majority of p-S10H3-expressing dynorphinergic neurons proved to be excitatory, as they lacked Pax-2 and showed Lmx1b-immunopositivity. Thus, we showed that neurochemically heterogeneous SDH neurons exhibit the upregulation of p-S10H3 shortly after noxious heat-induced burn injury and consequential tissue damage, and that a dedicated subset of excitatory dynorphinergic neurons is likely a key player in the development of central sensitization via the p-S10H3 mediated pathway. 相似文献
Chameleonic properties, i. e., the capacity of a molecule to hide polarity in non-polar environments and expose it in water, help achieving sufficient permeability and solubility for drug molecules with high MW. We present models of experimental measures of polarity for a set of 24 FDA approved drugs (MW 405-1113) and one PROTAC (MW 1034). Conformational ensembles in aqueous and non-polar environments were generated using molecular dynamics. A linear regression model that predicts chromatographic apparent polarity (EPSA) with a mean unsigned error of 10 Å2 was derived based on separate terms for donor, acceptor, and total molecular SASA. A good correlation (R2=0.92) with an experimental measure of hydrogen bond donor potential, Δlog Poct-tol, was found for the mean hydrogen bond donor SASA of the conformational ensemble scaled with Abraham's A hydrogen bond acidity. Two quantitative measures of chameleonic behaviour, the chameleonic efficiency indices, are introduced. We envision that the methods presented herein will be useful to triage designed molecules and prioritize those with the best chance of achieving acceptable permeability and solubility. 相似文献
Bioactive ceramic scaffolds for bone regeneration consisting of a three-dimensional mesh of interpenetrating struts with square section were fabricated via Digital Light Processing (DLP). The ability of the technique to manufacture 3D porous structures from β-tricalcium phosphate (β-TCP) powders with different dimensions of struts and pores was evaluated, identifying the possibilities and limitations of the manufacturing process. Small pore sizes were found to seriously complicate the elimination of excess slurry from the scaffold’s innermost pores. The effect of the strut/pore size on the mechanical performance of the scaffolds under compressive stresses was also evaluated, but no significant influence was found. Under compressive stresses, the structures resulted weaker when tested perpendicularly to the printing plane due to interlayer shear failure. Interlayer superficial grooves are proposed as potential failure-controlling defects, which could also explain the lack of a Weibull size effect on the mechanical strength of the fabricated DLP scaffolds. 相似文献
Chemical engineering systems often involve a functional porous medium, such as in catalyzed reactive flows, fluid purifiers, and chromatographic separations. Ideally, the flow rates throughout the porous medium are uniform, and all portions of the medium contribute efficiently to its function. The permeability is a property of a porous medium that depends on pore geometry and relates flow rate to pressure drop. Additive manufacturing techniques raise the possibilities that permeability can be arbitrarily specified in three dimensions, and that a broader range of permeabilities can be achieved than by traditional manufacturing methods. Using numerical optimization methods, we show that designs with spatially varying permeability can achieve greater flow uniformity than designs with uniform permeability. We consider geometries involving hemispherical regions that distribute flow, as in many glass chromatography columns. By several measures, significant improvements in flow uniformity can be obtained by modifying permeability only near the inlet and outlet. 相似文献
Scientometrics - Examining the relationships among scientific disciplines is important today, but existing methods are limited by the contents and structure of their bibliographic databases. We... 相似文献
A silica-based glass-ceramic, with Y2Ti2O7 as the major crystalline phase, is designed, characterised and tested as an oxidation-protective coating for a titanium suboxide (TiOx) thermoelectric material at temperatures of up to 600 °C. The optimised sinter-crystallisation treatment temperatures are found to be 1300 °C and 855 °C for a duration of 30 min, and this treatment leads to a glass-ceramic with cubic Y2Ti2O7 and CaAl2Si2O8 as crystalline phases. An increase of ~270 °C in the dilatometric softening temperature is observed after devitrification of the parent glass, thus further extending its working temperature range.Excellent adhesion of the glass-ceramic coating to the thermoelectric material is maintained after exposure to a temperature of 600 °C for 120 h under oxidising conditions, thus confirming the effectiveness of the T1 glass-ceramic in protecting the TiOx material. 相似文献
Journal of Signal Processing Systems - Convolutional Neural Networks (CNNs) have improved several computer vision applications, like object detection and classification, when compared to other... 相似文献
Osteosarcoma (OS) is a rare condition with very poor prognosis in a metastatic setting. Basic research has enabled a better understanding of OS pathogenesis and the discovery of new potential therapeutic targets. Phase I and II clinical trials are already ongoing, with some promising results for these patients. This article reviews OS pathogenesis and new potential therapeutic targets. 相似文献
Both water balance (WB) and rating curve (RC) are methods for estimating streamflow. The first is mostly used to estimate reservoir outflows, while the second is usually adopted in hydrometeorological network streamflow gauges. While WB uses hourly collected data, the RC estimates streamflow using current water level and extrapolation techniques. The objective of this study was to analyze variations in the reservoir’s hourly outflow at Queimado Hydroelectric Power Plant (HPP Queimado) and to propose a method to evaluate whether the estimate of the daily outflows, obtained by the WB method, is similar to the flow values obtained at a conventional station. The logistic regression (LR) model was used because it is a method that adopts binary, categorically dependent variables to identify the event of interest. The results showed that the values of streamflow, obtained from an average of two daily readings, were a good representation of the flows in the region. The LR was able to identify atypical data, especially in the rainy season. This means that data consistency analysis can be faster and safer, when adequately employed and considering the proposed conditions, contributing to both management policies and the management of water resources.