Capillary Barrier Research Articles

Utility trenches: sinks or barriers? Modeling the fate of leaked water in a crowded subsurface

High permeability sand/gravel trenches surrounding utility pipes are deemed to create preferential pathways for water in the subsurface of urban environments. Although this can be true when both trench filling material and surrounding soils are fully water saturated, the same is not obvious in the unsaturated zone. This study explores the behavior of these anthropogenic features in the unsaturated zone and their role in the formation of the urban karst with specific interest to the fate of water leaked from utility pipelines and its potential to affect urban aquifers. A series of 3D steady state numerical simulations was performed assuming two groups of nearby utility trenches hosting a water pipeline, up to 6 concurrent leaks, different leak rates, native soil properties, slopes of the utility trenches, and initial water saturation profiles. The analysis showed that utility trenches in the unsaturated zone are more likely an obstacle to water flow originated from leaking water utilities. Indeed, they served as capillary barriers rather than sinks in the simulations, although with a limited diversion capacity. Nevertheless, a pronounced lateral spreading of leaked water within the trenches was predicted in some scenarios, which suggests that there is still potential for the urban karst effect to occur when native soil properties are not that far from those of the trench filling material, although high initial effective water saturations would be required in this case.

Bioactive Cell-Derived ECM Scaffold Forms a Unique Cellular Microenvironment for Lung Tissue Engineering.

Chronic lung diseases are one of the leading causes of death worldwide. Lung transplantation is currently the only causal therapeutic for lung diseases, which is restricted to end-stage disease and limited by low access to donor lungs. Lung tissue engineering (LTE) is a promising approach to regenerating a replacement for at least a part of the damaged lung tissue. Currently, lung regeneration is limited to a simplified local level (e.g., alveolar–capillary barrier) due to the sophisticated and complex structure and physiology of the lung. Here, we introduce an extracellular matrix (ECM)-integrated scaffold using a cellularization–decellularization–recellularization technique. This ECM-integrated scaffold was developed on our artificial co-polymeric BETA (biphasic elastic thin for air–liquid interface cell culture conditions) scaffold, which were initially populated with human lung fibroblasts (IMR90 cell line), as the main generator of ECM proteins. Due to the interconnected porous structure of the thin (<5 µm) BETA scaffold, the cells can grow on and infiltrate into the scaffold and deposit their own ECM. After a mild decellularization procedure, the ECM proteins remained on the scaffold, which now closely mimicked the cellular microenvironment of pulmonary cells more realistically than the plain artificial scaffolds. We assessed several decellularization methods and found that 20 mM NH4OH and 0.1% Triton X100 with subsequent DNase treatment completely removed the fibroblasts (from the first cellularization) and maintains collagen I and IV as the key ECM proteins on the scaffold. We also showed the repopulation of the primary fibroblast from human (without chronic lung disease (non-CLD) donors) and human bronchial epithelial (16HBE14o−) cells on the ECM-integrated BETA scaffold. With this technique, we developed a biomimetic scaffold that can mimic both the physico-mechanical properties and the native microenvironment of the lung ECM. The results indicate the potential of the presented bioactive scaffold for LTE application.

The Effects of Airway Pressure Release Ventilation on Pulmonary Permeability in Severe Acute Respiratory Distress Syndrome Pig Models.

Objective: The aim of the study was to compare the effects of APRV and LTV ventilation on pulmonary permeability in severe ARDS. Methods: Mini Bama adult pigs were randomized into the APRV group (n = 5) and LTV group (n = 5). A severe ARDS animal model was induced by the whole lung saline lavage. Pigs were ventilated and monitored continuously for 48 h. Results: Compared with the LTV group, CStat was significantly better (p < 0.05), and the PaO2/FiO2 ratio showed a trend to be higher throughout the period of the experiment in the APRV group. The extravascular lung water index and pulmonary vascular permeability index showed a trend to be lower in the APRV group. APRV also significantly mitigates lung histopathologic injury determined by the lung histopathological injury score (p < 0.05) and gross pathological changes of lung tissues. The protein contents of occludin (p < 0.05), claudin-5 (p < 0.05), E-cadherin (p < 0.05), and VE-cadherin (p < 0.05) in the middle lobe of the right lung were higher in the APRV group than in the LTV group; among them, the contents of occludin (p < 0.05) and E-cadherin (p < 0.05) of the whole lung were higher in the APRV group. Transmission electron microscopy showed that alveolar–capillary barrier damage was more severe in the middle lobe of lungs in the LTV group. Conclusion: In comparison with LTV, APRV could preserve the alveolar–capillary barrier architecture, mitigate lung histopathologic injury, increase the expression of cell junction protein, improve respiratory system compliance, and showed a trend to reduce extravascular lung water and improve oxygenation. These findings indicated that APRV might lead to more profound beneficial effects on the integrity of the alveolar–capillary barrier architecture and on the expression of biomarkers related to pulmonary permeability.

Assessment and prediction of coastal saline soil improvement effects combining substrate amendments and salt barrier materials in typical region of the Yangtze River Delta

Coastal saline regions are characterized by high salinity, low permeability, organic matter deficiency, shallow groundwater depth, which limit leaching and lead to salt return. However, there remains a lack of targeted research on long-term coastal saline soil improvement by combining permeation promotion and salt return suppression. Based on a case study of the coastal saline area of Jiangsu Province, China, we used dynamic monitoring of soil water and salt transport, along with laboratory and field scale experiments to analyze the effect of combining substrate amendments and salt barrier materials on salt leaching and return. And numerical simulations were used to predicted the effects of the optimized combination improvement schemes under different climatic conditions in the future. The 2–4% (w/w) straw amended soil had a greater increase (＞90%) in desalinization ratio and a higher reduction (more than half) in desalination time due to changes in soil physical properties. The geocomposite isolated salt effectively due to the formation of capillary barrier compared with traditional straw burial. The results of field scale experiments and numerical simulations showed that geocomposite salt barrier material combined with straw substrate amendment scheme provides a cost-effective solution of soil salinization in coastal areas.

Field-scale compression of Sphagnum moss to improve water retention in a restored bog

The restoration and subsequent regeneration of Sphagnum moss on harvested peatlands can result in poor hydrological connectivity between the regenerated Sphagnum moss and the remnant cutover peat due to the formation of a capillary barrier that favours retention of water in the underlying cutover peat. In a restored cutover peatland in Québec, Canada, this resulted in a lower soil water content of the regenerated Sphagnum moss compared to a natural analogue, which may limit carbon sequestration potential. Previous work has shown it may take > 40 years for the regenerated moss layer to overcome this capillary barrier effect, however mechanical compression may provide a novel restoration technique to weaken the capillary barrier in restored peatlands. This study evaluated the effectiveness of field-based mechanical compression to ameliorate the capillary barrier effect and increase the moisture content in a restored cutover peatland. A section of restored Bois-des-Bel peatland was compressed using a John Deere 6430 series tractor in January 2016, followed by hydrological monitoring May-August. The Compressed site was compared to a nearby Uncompressed site, and a natural peatland ∼ 2 km away, to determine relative success of mechanical compression. The compression reduced moss height by 48%, increasing bulk density by 37% and reducing the proportion of macropores by 15% throughout the moss layer. Consequently, compression increased soil water retention and average soil moisture content at the Compressed site was consistently higher throughout the moss profile than in the Uncompressed site. This increased the resilience of the moss to drying, though the degree of increased resilience is unknown. Despite not having the same hydrophysical properties of the Natural site, the Compressed site was wetter than the Uncompressed site due to the lessening of the capillary barrier effect and moving the surface closer to the water table, thus decreasing the water stress of the regenerated Sphagnum carpet.

Enhanced solvent extraction in a serial converging-diverging microchannel at high injection ratio

A microchannel with serial converging–diverging geometries, inspired by porous structures of rock, was designed to enhance the cross-interfacial mass transfer of two-phase flow at a high phase injection ratio up to 200:1. It was experimentally demonstrated that the design enhanced mass transfer coefficient by approximately four times compared to classic microchannel design. The superior performance of the microchannel was attributed to the retention of dispersed fluid before the converging geometry due to the capillary pressure barrier that resulted in velocity contrast between the two fluids and reduced the effective mass-transfer distance in continuous phase. Additionally, the deformation and dispersal of droplets at the diverging geometry further increased the interfacial area. The flow patterns in this geometry were experimentally identified. The serial converging–diverging design can be used for high phase ratio extraction applications.

Investigation of the Effect of Capillary Barrier on Water–Oil Movement in Water Flooding

Water flooding technology is widely used to improve oil recovery efficiency in oilfields. The capillary barrier effect induced by the complex pore structures in the reservoir rocks is a crucial reason for the trapping of a great deal of residual oil in oil reservoirs after water flooding. However, the formation condition along with the effect on the recovery rate of the capillary barrier under different wettability conditions should be investigated further. To bridge the gap between the microscopic mechanism of the capillary barrier effect and the macroscopic mechanism of oil displacement efficiency, a simple conceptual capillary model is constructed to obtain the formation conditions of the capillary barrier using the analysis method, and its influence on macroscopic oil displacement efficiency in the porous media model with an opening angle of 45° is systematically investigated in this study using direct numerical simulations (DNS) coupled with the volume of fluid method. The results showed that the capillary barrier effect plays a significant role in the formation of the residual oil in the reservoir rock and the contact angle and the opening angle are the primary factors for the formation of the capillary barrier. The capillary force is the driving force when the oil–water interface advances in the throat channel under water-wet conditions, while the capillary force hinders the movement of oil–water movement when the liquid flows out of the throat channel and when θ + β &gt; 90o. Furthermore, the highest oil displacement efficiency is achieved at the intermediate capillary number and in the case that the minimum conditions of occurrence of the capillary barrier phenomenon are satisfied. This is of great significance for controlling the optimized contact angle to further enhance the oil recovery rate of current oil reservoirs using waterflooding technology.

The design criterion for capillary barrier cover in multi-climate regions

The service performance of capillary barrier cover (CBC) under continuous rainfall is unclear, leading to a lack of the design criterion for CBC in humid regions. This study proposed a design criterion for CBC in multi-climate regions. First, the influence of fine layer thickness, initial water content and rainfall intensity on the performance of CBC under continuous rainfall was clarified through a soil column test. Subsequently, calculation models of effective water storage capacity and breakthrough time were derived based on test results. Finally, a design criterion for CBC in multi-climatic regions was proposed and verified. The main findings were as follows: (1) As expected, increasing the fine layer thickness and decreasing the initial water content enhanced the water storage capacity. Within the test range, the breakthrough time has a linearly positive, linearly negative, and negative power function relationship with the fine layer thickness, initial water content, and rainfall intensity, respectively. (2) The infiltration rate of CBC is controlled by saturated hydraulic conductivity under extremely continuous rainfall, and can be described by the equivalent infiltration rate. (3) The calculation results of the proposed water storage capacity and breakthrough time models are consistent with the test results, and the proposed design criterion is robust against various climates from drought to humidity. The research results can provide a reference for the design of CBC in multi-climate regions.

Long-Term Performance of the Water Infiltration and Stability of Fill Side Slope against Wetting in Expressways

Different settlements and instabilities of unsaturated subgrade subjected to wetting have been paid increasing attention in the southeast coastal areas of China. However, the treatments are costly when they are used in engineering. In addition, the long-term performances of the treatments are unclear. Based on seepage theory for unsaturated soils, a novel subgrade using a capillary barrier was proposed in this study to reduce the different settlements and stabilities. Compared with previous studies, a capillary barrier was merely applied in the landfill. The long-term performance and feasibility of a capillary barrier applied in a tilted subgrade slope is worthy of study, particularly in humid climates. Using Geo-Studio, the feasibility was verified by comparing a conventional subgrade with a subgrade using a capillary barrier in southeast coastal areas in terms of pore-water pressure, water content, settlement, and the safety factor. The numerical results showed that the subgrade using a capillary barrier could provide significant improvements in the performance of reducing the impact of pore-water pressure distribution it suffered from, so as to lead to smaller different settlements. The vertical settlement of the pavement using a capillary barrier over a 1 year period was 1 cm. Compared with a conventional subgrade, the settlement fell by 94%, and the safely factor increased by 15% for the subgrade using the capillary barrier.

Exaggerated Ventilator-Induced Lung Injury in an Animal Model of Type 2 Diabetes Mellitus: A Randomized Experimental Study.

Although ventilator-induced lung injury (VILI) often develops after prolonged mechanical ventilation in normal lungs, pulmonary disorders may aggravate the development of adverse symptoms. VILI exaggeration can be anticipated in type 2 diabetes mellitus (T2DM) due to its adverse pulmonary consequences. Therefore, we determined whether T2DM modulates VILI and evaluated how T2DM therapy affects adverse pulmonary changes. Rats were randomly assigned into the untreated T2DM group receiving low-dose streptozotocin with high-fat diet (T2DM, n = 8), T2DM group supplemented with metformin therapy (MET, n = 8), and control group (CTRL, n = 8). In each animal, VILI was induced by mechanical ventilation for 4 h with high tidal volume (23 ml/kg) and low positive end-expiratory pressure (0 cmH2O). Arterial and venous blood samples were analyzed to measure the arterial partial pressure of oxygen (PaO2), oxygen saturation (SaO2), and the intrapulmonary shunt fraction (Qs/Qt). Airway and respiratory tissue mechanics were evaluated by forced oscillations. Lung histology samples were analyzed to determine injury level. Significant worsening of VILI, in terms of PaO2, SaO2, and Qs/Qt, was observed in the T2DM group, without differences in the respiratory mechanics. These functional changes were also reflected in lung injury score. The MET group showed no difference compared with the CTRL group. Gas exchange impairment without significant mechanical changes suggests that untreated diabetes exaggerates VILI by augmenting the damage of the alveolar–capillary barrier. Controlled hyperglycemia with metformin may reduce the manifestations of respiratory defects during prolonged mechanical ventilation.

Implications of Hyperoxia over the Tumor Microenvironment: An Overview Highlighting the Importance of the Immune System.

Simple SummaryThe local conditions of tumor cell growth, known as the tumor microenvironment (TME), are characterized by low oxygen supply (hypoxia) caused by insufficient blood delivery. Hypoxic cancers have a strong invasive potential, metastasis, resistance to therapy, and a poor clinical prognosis. The use of supplemental oxygen, known as hyperoxia, has been described to diminish the hypoxic state and to achieve a better response to different treatments. Here, we provide an overview of how hyperoxia interacts with other therapies decreasing tumor progression and the negative effects of the use of high oxygen levels. We also perform an analysis, showing the differences in the patterns of expression between a tumor-derived cell line and a nonmalignant cell line.Hyperoxia is used in order to counteract hypoxia effects in the TME (tumor microenvironment), which are described to boost the malignant tumor phenotype and poor prognosis. The reduction of tumor hypoxic state through the formation of a non-aberrant vasculature or an increase in the toxicity of the therapeutic agent improves the efficacy of therapies such as chemotherapy. Radiotherapy efficacy has also improved, where apoptotic mechanisms seem to be implicated. Moreover, hyperoxia increases the antitumor immunity through diverse pathways, leading to an immunopermissive TME. Although hyperoxia is an approved treatment for preventing and treating hypoxemia, it has harmful side-effects. Prolonged exposure to high oxygen levels may cause acute lung injury, characterized by an exacerbated immune response, and the destruction of the alveolar–capillary barrier. Furthermore, under this situation, the high concentration of ROS may cause toxicity that will lead not only to cell death but also to an increase in chemoattractant and proinflammatory cytokine secretion. This would end in a lung leukocyte recruitment and, therefore, lung damage. Moreover, unregulated inflammation causes different consequences promoting tumor development and metastasis. This process is known as protumor inflammation, where different cell types and molecules are implicated; for instance, IL-1β has been described as a key cytokine. Although current results show benefits over cancer therapies using hyperoxia, further studies need to be conducted, not only to improve tumor regression, but also to prevent its collateral damage.

Experimental study and numerical simulation on effectiveness of different capillary barriers in silt low subgrade

Experimental study and numerical simulation on effectiveness of different capillary barriers in silt low subgrade

Numerical modelling of the application of capillary barrier systems for prevention of rainfall-induced slope instability

Numerical modelling of the application of capillary barrier systems for prevention of rainfall-induced slope instability

Analyzing Human Periodontal Soft Tissue Inflammation and Drug Responses In Vitro Using Epithelium-Capillary Interface On-a-Chip.

The gingival epithelium–capillary interface is a unique feature of periodontal soft tissue, preserving periodontal tissue homeostasis and preventing microorganism and toxic substances from entering the subepithelial tissue. However, the function of the interface is disturbed in periodontitis, and mechanisms of the breakdown of the interface are incompletely understood. To address these limitations, we developed a microfluidic epithelium–capillary barrier with a thin culture membrane (10 μm) that closely mimics the in vivo gingival epithelial barrier with an immune micro-environment. To test the validity of the fabricated gingival epithelial barrier model, epithelium–capillary interface-on-a-chip was cultured with human gingival epithelial cells (HGECs) and human vascular endothelial cells (HUVEC). Their key properties were tested using optical microscope, transepithelial/transendothelial electrical resistance (TEER), and permeability assays. The clear expression of VE-cadherin revealed the tight junctions in endothelial cells. Live/dead assays indicated a high cell viability, and the astrocytic morphology of HGE cells was confirmed by F-actin immunostaining. By the third day of cell culture, TEER levels typically exceeded in co-cultures. The resultant permeability coefficients showed a significant difference between 70 kDa and 40 kDa FITC-dextran. The expression of protein intercellular cell adhesion molecule (ICAM-1) and human beta defensin-2 (HBD2) decreased when exposed to TNF-α and LPS, but recovered with the NF-κB inhibitor treatment- Pyrrolidinedithiocarbamic acid (PDTC), indicating the stability of the fabricated chip. These results demonstrate that the developed epithelium-capillary interface system is a valid model for studying periodontal soft tissue function and drug delivery.

Nasal administration of a non-viable Lactobacillus casei to infant mice modulates lung damage induced by Poly I:C and hyperreactivity in airways

Viral respiratory infections caused by RNA viruses are one of the most important diseases around the world. The aim of this work was to study whether the nasal administration of non-viable Lactobacillus casei (LcM) was able to enhance respiratory antiviral defenses in young mice challenged with Poly I:C. Three-week-old BALB/c mice were nasally challenged with Poly I:C, used to mimic the pro-inflammatory state of lung infections caused by RNA viruses. LcM was nasally administered 2 days before Poly I:C challenge. Lactate dehydrogenase (LDH) activity, albumin concentration in broncho-alveolar lavages (BAL), wet-to-dry lung weight ratio, and total and differential leukocytes counts in blood were evaluated. Also, α, λ, γ interferons, IL-10, TNF-α, IL-4 in BAL and nasal lavages and total IgE in BAL and serum, were evaluated by ELISA. Poly I:C induced pulmonary injuries while alteration of bronchoalveolar–capillary barrier was reduced by nasal administration of LcM. Moreover, alterations in leukocyte counts induced by Poly I:C were regulated. LcM favorably modulated the cytokines responses triggered by Poly I:C challenge in nasal and lung mucosal compartments. Also, LcM decreased IgE levels in BAL and plasma compared with the Poly I:C group. LcM nasally administered reduced the lung damage induced by Poly I:C and prevented airway hyperreactivity.

Gas Phase Diffusion Does Not Limit Lung Volatile Anesthetic Uptake Rate.

Inefficiency of lung gas exchange during general anesthesia is reflected in alveolar (end-tidal) to arterial (end-tidal-arterial) partial pressure gradients for inhaled gases, resulting in an increase in alveolar deadspace. Ventilation-perfusion mismatch is the main contributor to this, but it is unclear what contribution arises from diffusion limitation in the gas phase down the respiratory tree (longitudinal stratification) or at the alveolar-capillary barrier, especially for gases of high molecular weight such as volatile anesthetics. The contribution of longitudinal stratification was examined by comparison of end-tidal-arterial partial pressure gradients for two inhaled gases with similar blood solubility but different molecular weights: desflurane and nitrous oxide, administered together at 2 to 3% and 10 to 15% inspired concentration (FiG), respectively, in 17 anesthetized ventilated patients undergoing cardiac surgery before cardiopulmonary bypass. Simultaneous measurements were done of tidal gas concentrations, of arterial and mixed venous blood partial pressures by headspace equilibration, and of gas uptake rate calculated using the direct Fick method using thermodilution cardiac output measurement. Adjustment for differences between the two gases in FiG and in lung uptake rate (VG) was made on mass balance principles. A 20% larger end-tidal-arterial partial pressure gradient relative to inspired concentration (PetG - PaG)/FiG for desflurane than for N2O was hypothesized as physiologically significant. Mean (SD) measured (PetG - PaG)/FiG for desflurane was significantly smaller than that for N2O (0.86 [0.37] vs. 1.65 [0.58] mmHg; P < 0.0001), as was alveolar deadspace for desflurane. After adjustment for the different VG of the two gases, the adjusted (PetG - PaG)/FiG for desflurane remained less than the 20% threshold above that for N2O (1.62 [0.61] vs. 1.98 [0.69] mmHg; P = 0.028). No evidence was found in measured end-tidal to arterial partial pressure gradients and alveolar deadspace to support a clinically significant additional diffusion limitation to lung uptake of desflurane relative to nitrous oxide.

Cell‐Free Hemoglobin Increases Leukocyte Adhesion and Mitochondrial Oxidative Damage in the Pulmonary Microvascular Endothelium

Sepsis is a critical problem in intensive care units globally, and accounts for 20% of all annual deaths. During septic shock, the highly inflammatory state leads to the release of cell‐free hemoglobin (CFH) from lysed red blood cells. Once released into the vascular circulation, CFH can oxidize from the normal ferrous 2+ state to methemoglobin (3+, ferric). We have shown previously that CFH is a key driver of acute respiratory distress syndrome due to the breakdown of the alveolar capillary barrier. However, the underlying mechanism of how CFH disrupts the pulmonary endothelium remains unknown. Originally, it was believed hemoglobin acted only in an oxidative damage fashion. We hypothesized that oxidized CFH disrupts the pulmonary endothelium due to mitochondrial oxidative damage and leads to increased leukocyte adhesion. We utilized primary human lung microvascular endothelial cells (HLMVECs) to probe the mechanism underlying CFH‐induced barrier dysfunction. Endothelial barrier function was analyzed using electric cell‐substrate impedance sensing (ECIS) to quantify the transendothelial resistance changes in real‐time following treatment with CFH2+ and CFH3+ (1.0 and 0.5 mg/mL). Permeability was assessed using the SynVivo idealized network coculture system using HLMVECs and small airway epithelial cells and was quantified using fluorescent 60 kDa dextrans mixed with CFH2+,3+ (1.0 mg/mL) in media flowed through the channels while images were taken every 15 minutes for 4 h. Cytokines were measured via ELISA post CFH3+ treatment from conditioned culture media at 1, 3, 6, and 24 h. Adhesion of leukocytes was quantified using immunofluorescence by counting the number of fluorescent polymorphonuclear cells (PMNs) adhered to an endothelial monolayer following pretreatment with CFH3+ of the endothelial cells, the PMNs, or both. Mitochondrial superoxide production was quantified by MitoSOX staining followed by flow cytometry analysis of CFH‐treated HLMVECs. We saw a dose‐dependent decrease in transendothelial resistance following oxidized CFH3+ treatment but not with CFH2+ treatment (‐1270 vs 262 max TER drop, p&lt;0.0001). Real‐time permeability assays using the SynVivo system showed an increase in barrier permeability from CFH3+ treatment compared to CFH2+ (47 vs 6 relative permeability). Surface expression of E‐selectin (p=0.037) and ICAM‐1 (p=0.0497) was increased following oxidized CFH3+ treatment versus vehicle. In addition, pretreatment of HLMVECs with CFH3+ increased adhesion of polymorphonuclear cells (PMNs) to the endothelium (1.69 x 108 vs 7.81 x 109 GFP intensity, p=0.0014), while pretreatment of the PMNs did not increase adhesion. Treatment of HLMVECs with CFH3+ for 24 h increased secretion of IL‐1b, IL‐6, and IL‐8 (p&lt;0.05). HLMVECs exposed to CFH3+ for 6 h have significantly increased mitochondrial superoxide compared to vehicle treated cells (608 vs 283 adjusted MFI, p=0.0014). These data demonstrate that oxidized CFH decreases pulmonary endothelial function through both immune and oxidative damage pathways. We also show that CFH induces endothelial dysfunction in an oxidation‐state dependent manner. In summary, these studies provide new evidence to the potential mechanism in which CFH harms the endothelium during sepsis beyond the conventionally attributed oxidative cycling of the heme moiety.

Amyloid‐Beta Precursor Protein: Essential to Lung Capillary Barrier Defense During Acute Infection

RationalePneumonia is a leading cause of acute respiratory distress syndrome (ARDS) and sepsis. Despite resolution of active infection, pro‐inflammatory mediators and cytotoxins elicited during the acute phase promote secondary tissue injury, impede recovery, and contribute to poor patient prognoses. Lung infection with Pseudomonas aeruginosa, Klebsiella pneumoniae, and influenza elicit pathogenic amyloids that propagate injury and likely contribute to this inflammatory milieu. However, clinical trials targeting amyloid‐beta (Aβ) have consistently failed. Lung endothelial‐derived amyloids have been implicated as innate antimicrobial effectors yet the contribution of Aβ to host defense of the lung capillary barrier remains poorly resolved. We hypothesized that lung endothelial Aβ contributes to 1) the attenuation of active infection, and 2) endothelial barrier resilience to infection.MethodsTo test our hypotheses, CRISPR/Cas9 was targeted to Aβ precursor protein (APP) in rat pulmonary microvascular endothelial cells (PMVECs), and the deletion was confirmed via PCR, sequencing, and immunoblotting. The contribution of APP expression to cell proliferation, self‐replication, wound closure, angiogenesis, and barrier integrity (transwell permeability, bacterial dissemination, ECIS) both at baseline and during virulent infection was assessed in both WT and APP‐/‐ PMVECs. Amyloid content was monitored with immunoblotting and Thioflavin T staining. Antimicrobicity was measured with kinetic bactericidal assays, agglutination, plating, and SYTO 9/propidium iodide.ResultsAPP‐/‐ cells were ~49% less effective in reducing the bacterial load of an active infection as compared to APP expressing PMVECs. Immunodepletion of Aβ from WT endothelial cell supernatant reduced bactericidal efficacy in a comparable manner. APP‐/‐ cells also exhibited impaired proliferation (WT: 0.59 days, APP‐/‐ 0.91 days), a ~2.2‐fold reduction in replication capacity, poor wound closure and barrier formation, and little resilience to infection with loss of barrier integrity in roughly half the time of infected WT PMVECs. Moreover, conditioning of naïve cells with supernatant derived from WT but not APP‐/‐ PMVECs significantly increased proliferation and angiogenic capacity.ConclusionsLung endothelial APP is an important contributor to host defense. Both APP and its Aβ variant(s) appear to constrain infective bacterial burden whereas APP products appear to function as mitogens/morphogens within the microvascular milieu, likely contributing to tissue repair and recovery post‐insult.

Numerical analysis of cover systems for mining waste in tropical regions

ABSTRACT The flow of water in mining waste may cause serious environmental impacts associated with acid-rock drainage. In relatively dry climates, dry soil covers have been considered as feasible alternatives to minimise such effects. The objective of this paper is to evaluate the influence of the hydrological cycle and soil type on the performance of dry cover systems, considering the tropical conditions found in Brazil’s central-west region. Numerical analyzes of four different cover systems composed of tropical soils were performed using the Finite Element Method. Among the proposed arrangements, three use a soil that presents a bimodal soil-water characteristic curve and the fourth system employs a unimodal soil. The thicknesses of intermediate materials were varied and different representative precipitation parameters were considered for a period of one year. The results obtained were compared in terms of the internal flow and the capacity of the cover to store water. The results indicate that bimodal soils may not be ideal materials and require specific compaction conditions to reduce the volume of macropores. Unimodal tropical soils presented adequate response as store-and-release materials. The use of an intermediate layer acting as a capillary barrier did not offer significant improvement to the cover systems evaluated.

Time-lapse imaging of flow instability and rock heterogeneity impacts on CO2 plume migration in meter long sandstone cores

Our understanding and modelling of flow instabilities (e.g. viscous, gravitational) in the presence of geological heterogeneity is limited by a lack of experimental observations at relevant scales in consolidated media. Typically, small sample sizes (<50 mm diameter) restrict the scale of heterogeneity, and the development of unstable fingers may be damped by the sample boundaries. Furthermore, there is a lack of 3D dynamic data, resolved at a level to observe finger growth and interaction. To this end, we conduct a series of drainage & imbibition fluid-flow experiments with nitrogen and brine in meter-long, 100 mm-diameter Bentheimer and Boise sandstone samples using an advanced, high-pressure setup with medical X-Ray CT (XCT) imaging. Using novel beam-hardening and noise removal methods, we can resolve fluid distributions with a spatial resolution of 1.2 mm3 and temporal resolution of 90 s. The mobility (M) regime in each case is weakly unstable, M ≈ 0.5-5, with flow velocities equivalent to field scale injection rates. In the case of the weakly heterogeneous Bentheimer sample (porosity 0.26 ± 0.025), we find the plume migration is mainly controlled by buoyancy. On the other hand, the fluid distribution in the Boise sample is controlled by the strong unstructured heterogeneity (porosity 0.3 ± 0.1). The heterogeneity increases the gas trapping as less of the core is ultimately bypassed, and residual gas saturation increases behind local capillary barriers. We see little viscous instability in each experiment despite the unstable regime; structural heterogeneity and buoyancy largely control the flow under these field-relevant conditions. The meter scale 3D experimental dataset is provided open-access and represents an ideal benchmark to calibrate and improve multiphase flow models and upscaling methods.