East Asian summer monsoon delivers large abundances of very-short-lived organic chlorine substances to the lower stratosphere.

Deep convection in the Asian summer monsoon is a significant transport process for lifting pollutants from the planetary boundary layer to the tropopause level. This process enables efficient injection into the stratosphere of reactive species such as chlorinated very-short-lived substances (Cl-VSLSs) that deplete ozone. Past studies of convective transport associated with the Asian summer monsoon have focused mostly on the south Asian summer monsoon. Airborne observations reported in this work identify the East Asian summer monsoon convection as an effective transport pathway that carried record-breaking levels of ozone-depleting Cl-VSLSs (mean organic chlorine from these VSLSs ~500 ppt) to the base of the stratosphere. These unique observations show total organic chlorine from VSLSs in the lower stratosphere over the Asian monsoon tropopause to be more than twice that previously reported over the tropical tropopause. Considering the recently observed increase in Cl-VSLS emissions and the ongoing strengthening of the East Asian summer monsoon under global warming, our results highlight that a reevaluation of the contribution of Cl-VSLS injection via the Asian monsoon to the total stratospheric chlorine budget is warranted.

Vertical transport velocity of fine particles of aluminum smelter emissions.

In this study, the average values of vertical velocity of particles emitted from an aluminum smelter in the surface layer of the atmosphere were estimated using a semi-empirical method. The method is based on regression analysis of the horizontal profile of pollutants measured along the selected direction using moss bioindicators. The selection of epiphytic mosses Sanionia uncinata was carried out in 2013 in the zone of influence of a metallurgical industry enterprise in the city of Kandalaksha, Murmansk region. The concentrations of As, Si, Ni, Zn, Ti, Cd, Na, Pb, Co, K, Ba, Ca, Mg, Mn, Sr, Fe, Al, V, Cr, Cu were determined using atomic emission spectrometry. The conducted assessments showed that the average particle velocity toward the Earth's surface, when considering large spatial and temporal scales, is tens of times higher than gravitational settling velocities.

Convective Solvent Transport Pathways for Absorption of Drugs from Topical Formulation.

Physicochemical and formulation factors influencing penetration of drugs from topical products into the skin and mechanisms of drug permeation are well investigated and reported in the literature. However, mechanisms of drug absorption during short-term exposure have not been given sufficient importance. In this project, the extent of absorption of drug molecules into the skin from aqueous and ethanolic solutions following a 5-min application period was investigated. The experiments demonstrated measurable magnitude of absorption into the skin for all the molecules tested despite the duration of exposure being only few minutes. Among the two solvents used, absorption was greater from aqueous than ethanolic solution. The results suggest that an alternative penetration pathway, herein referred to as the convective transport pathway, is likely responsible for the rapid, significant uptake of drug molecules during initial few minutes of exposure. Additionally, absorption through the convective transport pathways is a function of the physicochemical nature of the formulation vehicle rather than the API.

Efficient In-Cloud Removal of Aerosols by Deep Convection.

Convective systems dominate the vertical transport of aerosols and trace gases. The most recent in situ aerosol measurements presented here show that the concentrations of primary aerosols including sea salt and black carbon drop by factors of 10 to 10,000 from the surface to the upper troposphere. In this study we show that the default convective transport scheme in the National Science Foundation/Department of Energy Community Earth System Model results in a high bias of 10-1,000 times the measured aerosol mass for black carbon and sea salt in the middle and upper troposphere. A modified transport scheme, which considers aerosol activation from entrained air above the cloud base and aerosol-cloud interaction associated with convection, dramatically improves model agreement with in situ measurements suggesting that deep convection can efficiently remove primary aerosols. We suggest that models that fail to consider secondary activation may overestimate black carbon's radiative forcing by a factor of 2.

Thermal dependence of large-scale freckle defect formation.

The fundamental mechanisms governing macroscopic freckle defect formation during directional solidification are studied experimentally in a Hele-Shaw cell for a low-melting point Ga-25 wt.% In alloy and modelled numerically in three dimensions using a microscopic parallelized Cellular Automata Lattice Boltzmann Method. The size and distribution of freckles (long solute channels, or chimneys) are shown to be strongly dependent on the thermal profile of the casting, with flat, concave and convex isotherms being considered. For the flat isotherm case, no large-scale freckles form, while for concave or convex isotherms, large freckles appear but in different locations. The freckle formation mechanism is as expected buoyancy-driven, but the chimney stability, its long-term endurance and its location are shown to depend critically on the detailed convective transport through the inter-dendritic region. Flow is generated by curved isopleths of solute concentration. As solute density is different from that of the bulk fluid, gravity causes 'uphill' or 'downhill' lateral flow from the sample centre to the edges through the mush, feeding the freckle. An excellent agreement is obtained between the numerical model and real-time X-ray observations of a solidifying sample under strictly controlled temperature conditions. This article is part of the theme issue 'Heterogeneous materials: metastable and non-ergodic internal structures'.

Modification of a Pollen Trap Design To Capture Airborne Conidia of Entomophaga maimaiga and Detection of Conidia by Quantitative PCR.

The goal of this study was to develop effective and practical field sampling methods for quantification of aerial deposition of airborne conidia of Entomophaga maimaiga over space and time. This important fungal pathogen is a major cause of larval death in invasive gypsy moth (Lymantria dispar) populations in the United States. Airborne conidia of this pathogen are relatively large (similar in size to pollen), with unusual characteristics, and require specialized methods for collection and quantification. Initially, dry sampling (settling of spores from the air onto a dry surface) was used to confirm the detectability of E. maimaiga at field sites with L. dispar deaths caused by E. maimaiga, using quantitative PCR (qPCR) methods. We then measured the signal degradation of conidial DNA on dry surfaces under field conditions, ultimately rejecting dry sampling as a reliable method due to rapid DNA degradation. We modified a chamber-style trap commonly used in palynology to capture settling spores in buffer. We tested this wet-trapping method in a large-scale (137-km) spore-trapping survey across gypsy moth outbreak regions in Pennsylvania undergoing epizootics, in the summer of 2016. Using 4-day collection periods during the period of late instar and pupal development, we detected variable amounts of target DNA settling from the air. The amounts declined over the season and with distance from the nearest defoliated area, indicating airborne spore dispersal from outbreak areas.IMPORTANCE We report on a method for trapping and quantifying airborne spores of Entomophaga maimaiga, an important fungal pathogen affecting gypsy moth (Lymantria dispar) populations. This method can be used to track dispersal of E. maimaiga from epizootic areas and ultimately to provide critical understanding of the spatial dynamics of gypsy moth-pathogen interactions.

Solute and Water Transport in Peritoneal Dialysis: A Case-Based Primer.

Peritoneal dialysis (PD) is an effective therapy for patients with end-stage kidney disease. Dialysis solutions containing physiologic concentrations of electrolytes and base, as well as glucose often at supraphysiologic concentrations, are infused into the peritoneal cavity for solute and water exchange, and the patient's own peritoneal membrane is used for dialysis. The peritoneal membrane is dominated by small pores, which allow transport of water and small-molecular-size solutes, including electrolytes, by way of both diffusion and convection. Through small pores, diffusion allows the movement of solutes from the high-concentration compartment to a lower-concentration region. Also, through small pores, water and solutes move together by convection in response to an osmotic force. The glucose in the dialysis solution generates osmotic force to drive convection. In addition to small pores, the peritoneal membrane contains a specialized water channel, aquaporin 1, which is also present in capillaries of the peritoneal membrane. These specialized water channels, which are upregulated by glucose, allow water transport without solute (free water) in response to the osmotic force induced by glucose in the PD solution. During a PD exchange, net loss or gain of electrolytes and base is determined by both their gradient between capillary blood and dialysis solution and the net ultrafiltration volume. Developing a PD prescription, including the amount of glucose used, and changing the prescription in response to dietary changes and/or loss of residual kidney function requires a sound understanding of the peritoneal physiology. The case studies presented here help solidify the basic elements of PD prescription and how the PD prescription should be altered in response to changing clinical situations.

Physiologically Based Modeling to Predict Monoclonal Antibody Pharmacokinetics in Humans from in vitro Physiochemical Properties.

A model-based framework is presented to predict monoclonal antibody (mAb) pharmacokinetics (PK) in humans based on in vitro measures of antibody physiochemical properties. A physiologically based pharmacokinetic (PBPK) model is used to explore the predictive potential of 14 in vitro assays designed to measure various antibody physiochemical properties, including nonspecific cell-surface interactions, FcRn binding, thermal stability, hydrophobicity, and self-association. Based on the mean plasma PK time course data of 22 mAbs from humans reported in the literature, we found a significant positive correlation (R = 0.64, p = .0013) between the model parameter representing antibody-specific vascular to endothelial clearance and heparin relative retention time, an in vitro measure of nonspecific binding. We also found that antibody-specific differences in paracellular transport due to convection and diffusion could be partially explained by antibody heparin relative retention time (R = 0.52, p = .012). Other physiochemical properties, including antibody thermal stability, hydrophobicity, cross-interaction and self-association, in and of themselves were not predictive of model-based transport parameters. In contrast to other studies that have reported empirically derived expressions relating in vitro measures of antibody physiochemical properties directly to antibody clearance, the proposed PBPK model-based approach for predicting mAb PK incorporates fundamental mechanisms governing antibody transport and processing, informed by in vitro measures of antibody physiochemical properties, and can be expanded to include more descriptive representations of each of the antibody processing subsystems, as well as other antibody-specific information.

Mapping Bubble Formation and Coalescence in a Tubular Cross-Flow Membrane Foaming System.

Membrane foaming is a promising alternative to conventional foaming methods to produce uniform bubbles. In this study, we provide a fundamental study of a cross-flow membrane foaming (CFMF) system to understand and control bubble formation for various process conditions and fluid properties. Observations with high spatial and temporal resolution allowed us to study bubble formation and bubble coalescence processes simultaneously. Bubble formation time and the snap-off bubble size (D0) were primarily controlled by the continuous phase flow rate (Qc); they decreased as Qc increased, from 1.64 to 0.13 ms and from 125 to 49 µm. Coalescence resulted in an increase in bubble size (Dcoal>D0), which can be strongly reduced by increasing either continuous phase viscosity or protein concentration-factors that only slightly influence D0. Particularly, in a 2.5 wt % whey protein system, coalescence could be suppressed with a coefficient of variation below 20%. The stabilizing effect is ascribed to the convective transport of proteins and the intersection of timescales (i.e., µs to ms) of bubble formation and protein adsorption. Our study provides insights into the membrane foaming process at relevant (micro-) length and time scales and paves the way for its further development and application.

A Compartment-Based Mathematical Model for Studying Convective Aerosol Transport in Newborns Receiving Nebulized Drugs during Noninvasive Respiratory Support.

Nebulization could be a valuable solution to administer drugs to neonates receiving noninvasive respiratory support. Small and irregular tidal volumes and air leaks at the patient interface, which are specific characteristics of this patient population and are primarily responsible for the low doses delivered to the lung (DDL) found in this application, have not been thoroughly addressed in in vitro and in vivo studies for quantifying DDL. Therefore, we propose a compartment-based mathematical model able to describe convective aerosol transport mechanisms to complement the existing deposition models. Our model encompasses a mechanical ventilator, a nebulizer, and the patient; the model considers the gas flowing between compartments, including air leaks at the patient-ventilator interface. Aerosol particles are suspended in the gas flow and homogeneously distributed. The impact of breathing pattern variability, volume of the nebulizer, and leaks level on DDL is assessed in representative conditions. The main finding of this study is that convective mechanisms associated to air leaks and breathing patterns with tidal volumes smaller than the nebulizer dramatically reduce the DDL (up to 70%). This study provides a possible explanation to the inconsistent results of drug aerosolization in clinical studies and may provide guidance to improve nebulizer design and clinical procedures.

A protein diffusion model of the sealing effect.

Water transport across the arterial endothelium is believed primarily to occur through breaks in the tight junction strands at the cell periphery between neighboring cells. Additional proteins arriving at the tight junction can close these breaks, thereby attenuating this water flux. Motivated by evidence that the diffusion of presynthesized protein from the interior of the cell to and incorporation into the cell border is the mechanism of endothelial tight junctional sealing, we develop a diffusion-limited mathematical model of intercellular gap sealing. A single endothelial cell is represented as a thin, axisymmetric disk, initially containing a uniform distribution of junctional protein that does not interact with the apical or basal cell surfaces. Upon application of a transmural pressure gradient, water flows through the junctional cleft, and tight junction remodeling begins. We assume that proteins at the junction are instantaneously incorporated into its strand, dropping the free protein concentration at the cell periphery to zero. This sets the diffusion of intracellular proteins toward the junction in motion. The solution of this one-dimensional initial value problem provides excellent fits to current and previously published experimental data over a wide variety of conditions. It yields three physically meaningful parameters for each fit, including a protein diffusivity in the cytoplasm that varies little within experimental treatments. Statistical variation of these parameters allows rational comparison of experimental runs and identification of outlier runs.

Is High-Volume Online Hemodiafiltration Associated With Malnutrition?

Chronic malnutrition is a common problem in patients with end-stage renal disease on hemodialysis. Some studies have reported albumin loss into dialysis fluid during postdilution online hemodiafiltration (OL-HDF). The aim of the study was to assess the nutritional status of patients on high-volume OL-HDF and to demonstrate that higher convective clearances are not associated with malnutrition due to possible loss of nutrients with ultrafiltration. Demographic and clinical data, corporal composition with bioimpedance spectroscopy, dialysis features, albumin loss into dialysis fluid and laboratory parameters were collected in twenty-eight patients with ESRD undergoing postdilution OL-HDF with stable convective volumes over 28 L/session. Convective volume (CV) in the last six months was 32.51 ± 3.52 L per session. Cross-sectional analysis of dialysis features showed 32.7 ± 3.34 L of CV and high reduction rates of beta-2-microglobulin (84.2 ± 3.8%) and cystatin-C (81.6 ± 3.47%). Beta-2-microglobulin reduction showed a positive correlation with prealbumin levels (P = 0.048). CV was only correlated with cystatin-C reduction (P = 0.025). Estimated albumin loss into dialysis fluid (1.82 ± 1.05 g/session) was not related to laboratory or bioimpedance nutritional parameters, or to CV. Among patients with higher CV, serum albumin levels maintained more stability during the observational period. High volume OL-HDF results in better convective clearances and is not associated with malnutrition. Albumin and nutrients loss into dialysis fluid should not be a limiting factor of the substitution volume.

Importance of Body Water in the Efficacy of Convective Solute Transport in Online Hemodiafiltration.

High-volume online hemodiafiltration (OL-HDF) has been associated with improved patient survival compared to conventional hemodialysis in recent trials, where the importance of convective volume (CV) in this benefit is noted. The purpose of this study was to determine the corporal composition parameters influencing the efficacy of CV in the removal of different molecular weight (MW) molecules. Demographic data, corporal composition parameters with bioimpedance spectroscopy, dialysis features and the reduction rates of different MW molecules in a four-hour OL-HDF session were collected in 61 patients. We observed a significant negative correlation of ß2-microglobulin, cystatin-C, myoglobin and prolactin reduction rates with body surface area, weight, total body extracellular (ECW) and intracellular water (ICW), lean tissue mass and body cellular mass. The multivariable regression analysis identified ECW and ICW as the only corporal composition factors independently associated to the relative elimination of ß2-microglobulin (Beta: -0.801, P = 0.002 for ECW and Beta: -1.710, P = 0.001 for ICW), cystatin-C (Beta: -0.656, P = 0.010 for ECW and Beta: -1.511, P = 0.004 for ICW) and myoglobin (Beta: -0.745, P = 0.014 for ECW and Beta: -2.103, P = 0.001 for ICW), in addition to CV. Prolactin reduction was only associated with ICW (Beta: -1.540, P = 0.028). When adjusting CV with ECW and ICW, only the ratio CV/ECW was an independent predictor for higher elimination of ß2-microglobulin, cystatin-C and myoglobin. The corporal composition parameters independently associated to the reduction of medium-sized molecules are the extracellular and intracellular water. The ratio "convective volume/extracellular water" predicts higher efficacy of convective transport. Adjusting the convective volume to patient features could be useful to monitor the efficacy of OL-HDF and to prescribe individualized therapies.

Albumin leakage in online hemodiafiltration, more convective transport, more losses?

Online hemodiafiltration (OL-HDF) has now demonstrated some benefits in reducing mortality. It seems that rising convective volumes improve the outcomes, but the risks of it, such as albumin leakage, are not well defined yet. The aim of the present study was to evaluate the albumin leakage using two different filters with 20 and 30 L of post-dilution OL-HDF. In this cross-sectional study, 20 prevalent patients receiving post-dilution OL-HDL were included. We analyzed two dialyzers: FX1000, FMC and Polyflux 210H, Gambro. During four consecutive dialysis sessions, monitors were programmed using control-volume to obtain 20 or 30 L with both dialyzers. We collected albumin samples of the effluent at 5, 15, 30, 45 and 60 min and performed area under the curve (AUC) determinations for evaluating the losses. Mean patient age was 60 ± 9 years, and 70% were men. Albumin leakage was significant higher with Polyflux 210H when compared to FX 1000 FMC. A convective volume of 30 L produced greater albumin leakage than 20 L with both filters, though only with the FX 1000 FMC was it significant (minimum albumin leakage during first hour with FX 1000 FMC 20 L: 79.2 [0.0-175.7] mg; 30 liters: 403.3 [63.5-960.7] mg; with PF 210 Gambro 20 L: 869.1 [420.0-3214.7] mg; 30 L: 1841.7 [443.8-3417.5] mg). During OL-HDF, convective transport causes albumin leakage at least during the first hour. The albumin concentration in the effluent differs according to the type of filter used and the convective volume.