Model development and prediction of anti-icing longevity of asphalt pavement with salt-storage additive

This study established a systematic simulation framework to predict the anti-icing longevity of a thin overlay of asphalt pavement with salt-storage additive (APSSA). The water and chloride transport in the overlay when subjected to varying precipitation, temperature, thermal cracking, and fatigue cracking over time were modeled using a Finite Element Method based software. The simulation included two parts: water transport followed by chloride transport. Water transport that obeys the law of conservation of mass was modeled using the phase transport in porous media (phtr) interface of COMSOL, while chloride transport based on Fick’s second law was modeled with the transport of diluted species (tds) interface. The simulation results show that the anti-icing function of a 16-mm thick overlay was fully effective in 2 years and 5 years for the minimum pavement temperature above -3.4 °C and -2.4 °C, respectively. These two pavement temperatures are equivalent to 97.4-percentile and 96.3-percentile of historical hourly pavement temperature near Pullman, Washington. Graphical abstract

Macrocycle-stabilization of its interaction with 14-3-3 increases plasma membrane localization and activity of CFTR

Impaired activity of the chloride channel CFTR is the cause of cystic fibrosis. 14-3-3 proteins have been shown to stabilize CFTR and increase its biogenesis and activity. Here, we report the identification and mechanism of action of a macrocycle stabilizing the 14-3-3/CFTR complex, a first-in-class molecular glue. This molecule rescues plasma membrane localization and chloride transport of F508del-CFTR and works additively with the CFTR pharmacological chaperone corrector lumacaftor (VX-809).

A personalizable autonomous neural mass model of epileptic seizures

The prospect of personalized computational modeling in neurological disorders, and in particular in epilepsy, is poised to revolutionize the field. Work in the last two decades has demonstrated that neural mass models (NMM) can realistically reproduce and explain epileptic seizure transitions as recorded by electrophysiological methods (EEG, SEEG). In previous work, advances were achieved by i) increasing excitation in NMM and ii) heuristically varying network inhibitory coupling parameters or, equivalently, inhibitory synaptic gains. Based on those studies, we provide here a laminar neural mass model capable of realistically reproducing the electrical activity recorded by SEEG in the epileptogenic zone during interictal to ictal states. With the exception of the external noise input onto the pyramidal cell population, the model dynamics are autonomous --- all model parameters are static. By setting the system at a point close to bifurcation, seizure-like transitions are generated, including pre-ictal spikes, low voltage fast activity, and ictal rhythmic activity. A novel element in the model is a physiologically plausible algorithm for chloride accumulation dynamics: the gain of GABAergic post-synaptic potentials is modulated by the pathological accumulation of Cl$^-$ in pyramidal cells, due to high inhibitory input and/or dysfunctional chloride transport. In addition, in order to simulate SEEG signals to compare with real recordings performed in epileptic patients, the NMM is embedded first in a layered model of the neocortex and then in a realistic physical model. We compare modeling results with data from four epilepsy patient cases. By including key pathophysiological mechanisms, the proposed framework captures succinctly the electrophysiological phenomenology observed in ictal states, paving the way for robust personalization methods using brain network models based on NMMs.

Effects of coupled heat and moisture and load damage on chloride transport in concrete

This paper presents a thoroughgoing research on chloride transport in damaged concrete. Effects of temperature and temperature gradient on chloride transport was investigated along with effects of relative humidity, humidity gradient, concrete damage and exposure time. The higher the temperature and the greater the humidity gradient were, the quicker chloride transport was. Moisture transport increased as concrete damage increased, while chloride transport decreased incrementally. Considering the effect of coupled heat and moisture on chloride transport in concrete, a chloride transport model was established and verified by experiments. Chloride profiles in damaged concrete were related to temperature, temperature gradient, relative humidity and humidity gradient. The chloride attack rate decreased with increasing concrete damage and exposure time. Hence, coupled heat and moisture as well as concrete damage had significant effects on chloride transport in damaged concrete, and effects of concrete damage on chloride transport should be considered when determining chloride profiles in damaged concrete.

SPAK Deficiency Attenuates Chemotherapy-Induced Intestinal Mucositis

IntroductionSte20-related protein proline/alanine-rich kinase (SPAK) affects cell proliferation, differentiation, and transformation, and sodium and chloride transport in the gut. However, its role in gut injury pathogenesis is unclear.ObjectiveWe determined the role of SPAK in chemotherapy-induced intestinal mucositis using in vivo and in vitro models.MethodsUsing SPAK-knockout (KO) mice, we evaluated the severity of intestinal mucositis induced by 5-fluorouracil (5-FU) by assessing body weight loss, histological changes in the intestinal mucosa, length of villi in the small intestine, pro-inflammatory cytokine levels, proliferative indices, and apoptotic indices. We also evaluated changes in gut permeability and tight junction-associated protein expression. Changes in cell permeability, proliferation, and apoptosis were assessed in SPAK siRNA-transfected 5FU-treated IEC-6 cells.Results5-FU-treated SPAK-KO mice exhibited milder intestinal mucositis, reduced pro-inflammatory cytokine expression, increased villus length, good maintenance of proliferative indices of villus cells, decreased apoptotic index of enterocytes, reduced gut permeability, and restoration of tight junction protein expression (vs. 5-FU-treated wild-type mice). Under in vitro conditions, siRNA-mediated SPAK-knockdown in IEC-6 cells decreased cell permeability and maintained homeostasis following 5-FU treatment.ConclusionSPAK deficiency attenuated chemotherapy-induced intestinal mucositis by modulating gut permeability and tight junction-associated protein expression and maintaining gut homeostasis in murine small intestinal tissues following gut injury. The expression of SPAK may influence the pathogenesis of chemotherapy-induced intestinal mucositis.

Modelling groundwater recharge, actual evaporation and transpiration in semi-arid sites of the Lake Chad Basin: The role of soil and vegetation on groundwater recharge

The Lake Chad Basin, located in the center of North Africa, is characterized by strong climate seasonality with a pronounced short annual precipitation period and high potential evapotranspiration. Groundwater is an essential source for drinking water supply as well as for agriculture and groundwater related ecosystems. Thus, assessment of groundwater recharge is very important although difficult, because of the strong effects of evaporation and transpiration as well as limited available data. A simple, generalized approach, which requires only a small number of field data, freely available remote sensing data as well as well-established concepts and models, is tested for assessing groundwater recharge in the southern part of the basin. This work uses the FAO-dual Kc concept to estimate E and T coefficients at six locations that differ in soil texture, climate, and vegetation conditions. Measured values of soil water content and chloride concentrations along vertical soil profiles together with different scenarios for E and T partitioning and a Bayesian calibration approach are used to numerically simulate water flow and chloride transport. Average groundwater recharge rates and the associated model uncertainty at the six locations are assessed for the 2003–2016 time-period. Model results show that interannual variability of groundwater recharge is generally greater than the uncertainty of the modelled groundwater recharge. Furthermore, the soil moisture dynamics at all locations are limited rather by water availability for evaporation in the uppermost part of the soil and by water uptake in the root zone than by the reference evapotranspiration.

Investigation on Numerical Simulation of Chloride Transport in Unsaturated Concrete

Marine atmosphere environment accelerates the process of chloride penetration into concrete under the coupling effect of ambient temperature and relative humidity, thereby reducing the durability and service life of concrete. This paper aims to investigate the change of water equilibrium saturation and the chloride transport properties of concrete materials in different environments. The water equilibrium saturation tests at three temperatures and five relative humidity (RH) and salt spray erosion tests at three temperatures were performed. The influence of RH and temperature on the equilibrium saturation of concrete and the influence of temperature and time on the chloride diffusion coefficient are investigated. The results show that, in the process of moisture absorption and desorption, the equilibrium saturation of concrete gradually decreases as temperature rises. At the same depth of concrete, the chloride content gradually increases with temperature increasing, as well as the chloride diffusion coefficient. However, as the corrosion time of salt spray increases, the altering of chloride diffusion coefficient becomes less. Based on the Kelvin equation, a relationship between capillary pressure and water saturation in concrete was established, and a moisture transfer model for concrete in the process of moisture absorption and desorption was derived. Further, based on the established chloride diffusion equation and heat balance equation, a model of temperature-wet-chloride coupling chloride transfer was derived. Theory model simulation results show the transfer speed of chloride under the coupling of diffusion and capillary is higher than pure diffusion in moisture in the absorption process. However, the opposite is true in the desorption process. Moreover, with the increment of saturation rate, the capillary effect on chloride transport is enhanced.

Chloride Transport Behaviour and Service Performance of Cracked Concrete Linings in Coastal Subway Tunnels

The concrete lining in subway tunnels often undergoes cracking damage in coastal cities. The combination of cracked tunnel lining structures and high concentrations of corrosive ions in the groundwater (e.g., chlorine) can accelerate concrete erosion, reduce the mechanical performance of the lining structures and shorten the tunnel service life. This paper investigates the chloride ion concentration in the groundwater of several subway tunnels in the coastal city of Qingdao, China. Indoor experiments and numerical simulations are conducted to investigate the chloride ion transport behaviour and service performance of cracked concrete linings. The results are applied to predict the service life of lining structures. The crack depth in concrete linings is found to have the most significant effect on the transport rate of chloride ions, followed by the crack width. The numerical simulations are carried out using COMSOL software to study the chloride transport behaviour in cracked specimens and predict the service lifetimes of lining structures of different thicknesses, and the results correspond well with the experimental data. The durability of a concrete lining can be enhanced by increasing the thickness of the protective concrete layer. Additional measures are proposed for treating cracked concrete linings to resist chloride ion attack in subway tunnels.

Analysis of multiple gene co-expression networks to discover interactions favoring CFTR biogenesis and ΔF508-CFTR rescue

Background We previously reported that expression of a miR-138 mimic or knockdown of SIN3A in primary cultures of cystic fibrosis (CF) airway epithelia increased ΔF508-CFTR mRNA and protein levels, and partially restored CFTR-dependent chloride transport. Global mRNA transcript profiling in ΔF508-CFBE cells treated with miR-138 mimic or SIN3A siRNA identified two genes, SYVN1 and NEDD8, whose inhibition significantly increased ΔF508-CFTR trafficking, maturation, and function. Little is known regarding the dynamic changes in the CFTR gene network during such rescue events. We hypothesized that analysis of condition-specific gene networks from transcriptomic data characterizing ΔF508-CFTR rescue could help identify dynamic gene modules associated with CFTR biogenesis. Methods We applied a computational method, termed M-module, to analyze multiple gene networks, each of which exhibited differential activity compared to a baseline condition. In doing so, we identified both unique and shared gene pathways across multiple differential networks. To construct differential networks, gene expression data from CFBE cells were divided into three groups: (1) siRNA inhibition of NEDD8 and SYVN1; (2) miR-138 mimic and SIN3A siRNA; and (3) temperature (27 °C for 24 h, 40 °C for 24 h, and 27 °C for 24 h followed by 40 °C for 24 h). Results Interrogation of individual networks (e.g., NEDD8/SYVN1 network), combinations of two networks (e.g., NEDD8/SYVN1 + temperature networks), and all three networks yielded sets of 1-modules, 2-modules, and 3-modules, respectively. Gene ontology analysis revealed significant enrichment of dynamic modules in pathways including translation, protein metabolic/catabolic processes, protein complex assembly, and endocytosis. Candidate CFTR effectors identified in the analysis included CHURC1, GZF1, and RPL15, and siRNA-mediated knockdown of these genes partially restored CFTR-dependent transepithelial chloride current to ΔF508-CFBE cells. Conclusions The ability of the M-module to identify dynamic modules involved in ΔF508 rescue provides a novel approach for studying CFTR biogenesis and identifying candidate suppressors of ΔF508.