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Virus diffusion in isolation rooms.

In hospitals, the ventilation of isolation rooms operating under closed-door conditions is vital if the spread of viruses and infection is to be contained. Engineering simulation, which employs computational fluid dynamics, provides a convenient means of investigating airflow behaviour in isolation rooms for various ventilation arrangements. A cough model was constructed to permit the numerical simulation of virus diffusion inside an isolation room for different ventilation system configurations. An analysis of the region of droplet fallout and the dilution time of virus diffusion of coughed gas in the isolation room was also performed for each ventilation arrangement. The numerical results presented in this paper indicate that the parallel-directional airflow pattern is the most effective means of controlling flows containing virus droplets. Additionally, staggering the positions of the supply vents at the door end of the room relative to the exhaust vents on the wall behind the bed head provides effective infection control and containment. These results suggest that this particular ventilation arrangement enhances the safety of staff when performing medical treatments within isolation rooms.

Adult↗

Effects of unstirred layers or transport number discontinuities on the transient and steady-state current-voltage relationships of membranes.

The effects of current-induced electrolyte accumulation and depletion on the electrical properties of a two-layered membrane system have been examined. The membrane consisted of a charged, ion permselective layer and an uncharged, non-selective layer. The model was designed to reveal the properties of membranes possessing long pores with ionic charges at one end or of ion-selective membranes bounded by highly unstirred aqueous layers. Electrolyte concentration profiles in the inert layer and their time-dependent changes were obtained from solutions of the diffusion equation under the condition of constant current. The profiles were then used to calculate the voltage developed across the membrane at various times after the current is switched on. The theoretical results are presented in the form of i-V curves with reduced coordinates that can be used to obtain time-current-voltage relationships for membranes of the type considered having any thickness of the non-selective layer and bathed in any concentration of any 1:1 electrolyte. Experimental results on a model composite membrane were in good agreement with calculations that assume that ion transport occurs only under the influence of electrical potential and concentration gradients, suggesting that in such systems, the combined effects of convection, osmosis, electro-osmosis, and concentration-dependence of diffusion coefficients, activity coefficients, and transference numbers are small. Voltage fluctuations in the form of periodic spikes were observed experimentally at the limiting current density (the current density at which the electrolyte concentration at one surface of the selective layer goes to 0). These phenomena were not seen when the current was in the direction leading to accumulation of electrolyte in the non-selective (unstirred) layer. Such composite membranes can exhibit S-shaped and N-shaped i-V curves under ramp-voltage and ramp-current clamps, respectively.

Diffusion↗

DNA-protein interactions under random jump conditions.

We model the site-specific association of a protein molecule with DNA as a random walk with random jumps. Results show that the simultaneous occurrence of processes such as sliding, hopping, and intersegmental transfer can facilitate the diffusion-controlled site-specific association rate. We have also shown that sliding would dominate at lower DNA length, whereas at higher lengths hopping and intersegmental transfer would dominate. Apart from this, we predict that the association rate is directly proportional to the size of nonspecific DNA that flanks the specific site. These results are consistent with the experimental observations.

Binding Sites↗

A pharmacokinetic approach to the study of cell membrane lithium transport in vivo.

Although many previous investigations have focused on in vitro studies of lithium transport by erythrocytes (RBCs) of psychiatric patients, the extent to which such studies actually reflect the transport of this drug by other types of cells in vivo is unknown. To study lithium transport in vivo, pharmacokinetic analysis of plasma lithium concentration data was performed in four subjects who were given single oral doses of lithium carbonate (600 mg). The data were analyzed according to a two-compartment model, consisting of a central compartment (extracellular, including plasma) and a peripheral (intracellular) compartment. Rate constants for the transfer of lithium into (ki) and out of (ko) the intracellular compartment were calculated. In RBCs from the same subjects, lithium transport in vitro was also directly measured. Rate constants were determined for phloretin-sensitive transport (ks), which corresponds to Na+-Li+ countertransport activity, and residual passive "leak" diffusion (kr). In RBCs, these two pathways account for major components of lithium efflux and influx, respectively. To compare the in vivo and in vitro rate constant data, the ratios ko/ki and ks/kr were also calculated. There was a significant correlation between these two rate-constant ratios (r = 0.96, p less than 0.05), although the values observed in vitro were higher than those found in vivo. Because the in vivo rate constants reflect lithium transport by many types of cells in the peripheral compartment, this finding supports the idea that the RBC may provide a useful model for studying lithium transport processes that are also operative in other types of cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Membrane Permeability↗

MRI techniques and cognitive impairment in the early phase of relapsing-remitting multiple sclerosis.

Correlation studies between various conventional and non-conventional MRI parameters and cognitive impairment in the early stages of multiple sclerosis (MS) are lacking, although it is known that a number of patients with early MS have mild cognitive impairment. Our aim was to explore whether this cognitive impairment is dependent on the extent and severity of the burden of disease, diffuse microscopic brain damage or both. We studied 63 patients with clinically definite relapsing-remitting (RR) MS, duration of disease 1-10 years and Expanded disability status scale scores < or = 5.0. Mean age was 35.4 years, mean duration of disease 5.8 years and median EDSS score 1.5. Neuropsychological performance, psychological function, neurological impairment and disability were assessed. The patients also underwent MRI, including magnetisation-transfer (MT) studies. We quantified the lesion load on T2- and T1-weighted images, the magnetisation transfer ratio (MTR) of normal-appearing brain tissue (NABT) and the brain parenchymal fraction (BPF). No significant difference was found between lesion loads in patients with and without cognitive impairment. In 15 patients (23.8%) with overall cognitive impairment, median BPF and average NABT MTR were significantly lower than those in patients without cognitive impairment (0.868 vs 0.892, P = 0.02 and 28.3 vs 29.7 P = 0.046, respectively). Multiple regression analysis models demonstrated that the only variables independently correlated with cognitive impairment were: BPF (R = 0.89, P = 0.001) and average NABT MTR (R = 0.76, P = 0.012). Our findings support the hypothesis that, cognitive decline in patients with MS, a low disability score and short duration of disease is directly associated with the extent and severity of diffuse brain damage. The loss of brain parenchyma did not correlate with the severity of microscopic damage in the NABT, indicating that the two processes could be distinct in the early stages of the disease.

Adult↗

Membrane-cytoskeleton dynamics in rat parietal cells: mobilization of actin and spectrin upon stimulation of gastric acid secretion.

The gastric parietal (oxyntic) cell is presented as a model for studying the dynamic assembly of the skeletal infrastructure of cell membranes. A monoclonal antibody directed to a 95-kD antigen of acid-secreting membranes of rat parietal cells was characterized as a tracer of the membrane movement occurring under physiological stimuli. The membrane rearrangement was followed by immunocytochemistry both at the light and electron microscopic level on semithin and thin frozen sections from resting and stimulated rat gastric mucosa. Double labeling experiments demonstrated that a specific and massive mobilization of actin, and to a lesser extent of spectrin (fodrin), was involved in this process. In the resting state, actin and spectrin were mostly localized beneath the membranes of all cells of the gastric gland, whereas the bulk of acid-secreting membranes appeared diffusely distributed in the cytoplasmic space of parietal cells without any apparent connection with cytoskeletal proteins. In stimulated cells, both acid-secreting material and actin (or spectrin) extensively colocalized at the secretory apical surface of parietal cells, reflecting that acid-secreting membranes were now exposed at the lumen of the secretory canaliculus and that this insertion was stabilized by cortical proteins. The data are compatible with a model depicting the membrane movement occurring in parietal cells as an apically oriented insertion of activated secretory membranes from an intracellular storage pool. The observed redistribution of actin and spectrin argues for a direct control by gastric acid secretagogues of the dynamic equilibrium existing between nonassembled (or preassembled) and assembled forms of cytoskeletal proteins.

Actins↗

A subpopulation analysis of f-MLP stimulated granulocytes migrating in filters.

Leukocyte migration in vitro has been studied extensively during many years without providing satisfactory theoretical models for the different migratory behaviors (chemotaxis and chemokinesis) of leukocyte populations. The present study utilized the fluid gradient chamber, which is a new method to study leukocyte migration in filters. Human neutrophils were applied between two stacked filters and migrated in all directions under the influence of constant concentrations or chemotactic gradients of f-MLP, maintained in fluid phase density gradients. The distributions of the granulocytes over filter depth were fitted to theoretical functions composed by 1-3 Gaussian distributions, representing subpopulations. The results showed that the neutrophils migrated as two discrete subpopulations during chemokinetic stimulation (a constant concentration of f-MLP). One of the subpopulations showed less active and passive (slow sedimentation under the influence of gravity) translocation. The most mobile subpopulation was divided into two new subpopulations when exposed to chemotactic stimulation (concentration gradient of f-MLP), one of which responded chemotactically and one of which migrated in random directions. The properties of the different subpopulations where characterized in terms of diffusion coefficient (random migration), convection velocity (chemotactic migration) and sedimentation coefficient (passive translocation).

Cell Movement↗

Coumaphos distribution in the hive ecosystem: case study for modeling applications.

Pesticides are currently used inside hives, against the honeybee parasite Varroa destructor, producing unwanted contamination effects. To assess the distribution and fate of one of these pesticides (coumaphos), two experimental hives were treated with Perizin (the commercial product containing the active ingredient coumaphos). Samples of honey, wax, pollen, adult bees and larvae taken before treatment and up to 104 days afterwards, showed diffuse contamination. Wood hedges and wax bridges, where the pesticide solution was applied, were analysed as well. A mass balance was calculated, yielding a recovered amount of around 60% just after treatment and 38% 1 month later. Directly contaminated surfaces and wax contained the highest amount of residues. Wax and honey contained different amounts (10, and 0.1% respectively) but both retained residues for long time. Bees ingest most of the product just after treatment, then rapidly eliminate it by metabolism, advection and deposition processes. On the basis of analytical results, a simple model (level I of the fugacity model) was applied to the hive system for different pesticides (coumaphos, malathion, fluvalinate and bromopropylate). Predicted concentrations in wax and honey were compared with those measured, indicating the good predictive capability of this approach.

Animals↗

Epithelial growth by rat vibrissae follicles in vitro requires mesenchymal contact via native extracellular matrix.

An in vitro assay utilizing the rat vibrissa anagen follicle as a model for studying the epithelial-mesenchymal interactions (EMI) in hair growth is described. Through selective disruption of the epithelial-mesenchymal interface, we investigate whether the specialized extracellular matrix (ECM) of the dermal papilla and basement membrane zone (BMZ) serves a crucial function in hair follicle EMI. Epithelial bulbs incubated intact within their follicular sheaths incorporate thymidine primarily into cells of the hair matrix and outer root sheath, as shown by autoradiography. However, after removal of its mesenchymal associations (dermal papilla and extrabulbar connective tissue), the epithelial bulb showed no incorporation. Neither externally added collagen (type I or IV) nor the basement membrane components in Matrigel could substitute for the growth supporting influence of native surrounding stroma. Mechanical separation of the bulb from the dermal papilla in the basement membrane zone inhibited thymidine incorporation by the epithelium even though mesenchyme was still in close proximity. Enzymatic digestion of the dermal papilla ECM and the basal lamina by Dispase, a fibronectinase and type IV collagenase, also inhibited bulb growth without evidence of cytotoxicity. These experiments suggest that direct epithelial to mesenchymal contact is required for the support of follicular epithelial growth in vitro and that specific ECM components, possibly fibronectin and/or type IV collagen, rather than diffusable factors alone, play a crucial role in the mechanism of hair follicle EMI. The in vitro system described here provides an alternative to developmental EMI models and may serve as a valuable tool for studying EMI in the adult mammalian organism.

Animals↗

Transport coefficients and orientational distributions of spheroidal particles with magnetic moment normal to the particle axis (Analysis for an applied magnetic field normal to the shear plane).

We have investigated the influence of the magnetic field strength, shear rate, and rotational Brownian motion on transport coefficients such as viscosity and diffusion coefficient, and also on the orientational distributions of rodlike particles of a dilute colloidal dispersion. The rodlike particle is modeled as a magnetic spheroidal particle which has a magnetic moment normal to the particle axis; such a particle may typically be a hematite particle. In the present study, an external magnetic field is applied in the direction normal to the shear plane of a simple shear flow. The basic equation of the orientational distribution function has been derived from the balance of torques and solved numerically. The results obtained here are summarized as follows. Although the orientational distribution function shows a sharp peak in the shear flow direction for a very strong magnetic field, such a peak is not restricted to the field direction alone, but continues in every direction of the shear plane. This is due to the characteristic particle motion that the particle can rotate around the axis of the magnetic moment in the shear plane, although the magnetic moment nearly points to the magnetic field direction. This particle motion in the shear plane causes negative values of the viscosity due to the magnetic field. The viscosity decreases, attains a minimum value, and then converges to zero as the field strength increases. Additionally, the diffusion coefficient is significantly influenced by such characteristic particle motion in the shear plane for a strong magnetic field.

Journal Article↗

Human complement regulator expression by the normal female reproductive tract.

BACKGROUND: The membrane-associated proteins that regulate human complement activation are ubiquitously expressed and function cooperatively to protect cells from autologous complement damage. For classical and alternative pathways, the primary regulators at the stage of C3 proteolysis and deposition are membrane cofactor protein (MCP; CD46) and decay-accelerating factor (DAF;CD55), whereas protectin or CD59 regulates terminal component assembly. There is increasing awareness in reproductive, tumor, and transplantation immunology of the conventional and non-complement roles of these proteins. The human reproductive system may serve as a model of the non-complement functions. METHODS: We performed immunohistochemical analyses of multiple normal ovaries, fallopian tubes, cervices, and uterine corpi by using well-characterized monoclonal antibodies to provide a detailed, direct comparison of complement regulator expression. RESULTS: Membrane cofactor protein was diffusely and strongly expressed on all epithelia and vascular endothelium and was the predominant regulator on oocytes. In contrast, decay-accelerating factor had variable expression in intensity and distribution on epithelia and was notably absent on certain epithelia and oocytes. It was the only regulator present on the connective tissue between muscle bundles in the myometrium and the cervix and was found on most stroma. CD59, although staining intensity varied, was present on virtually all epithelia, vascular tissue, and stroma. CONCLUSIONS: Distinct reproducible patterns of complement regulator expression are found throughout the female reproductive tract. Differential expression on certain epithelia and oocytes may suggest non-complement activities. This comprehensive study should provide a basis for further characterization of pathological tissues and mechanisms of cellular localization.

Antigens, CD↗

Polystyrene latex adsorption at the gold/electrolyte interface.

Irreversible deposition of polystyrene latex particles (average diameter, 1.5 microm) on various solid/electrolyte interfaces was studied experimentally by using the direct microscope observation method. The substrate surfaces included bare mica (reference interface), gold covered mica (layer thickness of 50 nm), and solid gold plate. The morphology and thickness of the gold layer on mica was determined by atomic force microscopy. Well-defined transport conditions of particles were created by using the new impinging-jet cell. A characteristic feature of the cell was that the suspension stream was directed obliquely to the interface. This unique characteristic was advantageous allowing one for direct, in situ, observation of particle deposition at metals and other nontransparent interfaces. Experiments performed for various flow intensities indicated that the initial deposition kinetics at all interfaces was identical within the error bounds, in accordance with the model based on the convective-diffusion theory. It was concluded that the limiting flux was governed by the bulk transport rather than by the specific surface interactions.

Journal Article↗

Measurements of coronary plasma and pericardial infusate adenosine concentrations during exercise in conscious dog: relationship to myocardial oxygen consumption and coronary blood flow.

A conscious dog model was employed to evaluate the relationship among myocardial oxygen consumption (MVO2), myocardial adenosine release and coronary blood flow (CNF) during graded treadmill exercise. Two methods were utilized simultaneously as indexes of changes in interstitial adenosine concentrations, (1) a pericardial infusate technique and (2) to measurement of arterial-coronary sinus plasma adenosine concentration differences. Graded exercise was associated with graded increases in MVO2, CBF, pericardial infusate adenosine concentration (PI Ado) and adenosine washout in coronary plasma. Regression analysis demonstrated significant linear relationships for MVO2 v. CBF (r = 0.78, P less than 0.01), MVO2 v. PI Ado (r = 0.52, P less than 0.01), and PI Ado v. CBF (r = 0.76, P less than 0.01). Coronary plasma adenosine arterio-sinus differences, sinus plasma concentrations, and net washout of adenosine also increased with graded exercise, however, a significant inter-animal variance was noted. These data suggest that the plasma adenosine assay is capable of detecting directional (qualitative) changes associated with changes in cardiac metabolism, however, it may not be reliable as a quantitative indicator of interstitial adenosine concentrations due to multiple factors which may influence the plasma adenosine pool. The pericardial infusate technique, which presumably represents a model of diffusion, is relatively invariant by comparison. The results demonstrate a significant correlation among MVO2, PI Ado and CBF, and thereby provide support to the hypothesis that adenosine is a major factor in the coupling of myocardial oxygen demand to oxygen supply under physiological conditions.

Adenosine↗

The Washington Heights-Inwood Healthy Heart Program: a third generation community-based cardiovascular disease prevention program in a disadvantaged urban setting.

The Washington Heights-Inwood Healthy Heart Program (WHIHHP) is part of the New York State Healthy Heart Program, which comprises eight community-based programs in different areas of the state. WHIHHP is directed at a population of approximately 200,000 people, predominantly Hispanic and of low socioeconomic status, living in northern Manhattan in New York City. The initial 3 years of experience are presented. Six potential barriers to diffusion of the community-based disease prevention model in disadvantaged inner city communities are discussed: (a) issues of scale and complexity; (b) adaptation of this model to a "community" without geopolitical boundaries or infrastructure; (c) linguistic and cultural diversity; (d) competing problems; (e) the role of evaluation; and (f) sustainability of the program in a poor community. Strategies for addressing obstacles to model adoption are also described, including program legitimization, building program infrastructure, setting realistic expectations, focusing on one risk factor at a time, defining target population segments, and emphasizing a small number of communication channels. Finally, research issues related to the diffusion of the community-based model are discussed, specifically: (a) Does the model work in disadvantaged urban settings? (b) What are the program effects on social class gradients for risk factors? (c) What are the barriers to program adoption in such settings? (d) What changes in the model will facilitate adoption in such settings? (e) What are the best methods for conducting formative evaluation in such programs? (f) What is the best way to select communities that may be ready to adopt the model? Our initial experience implementing this model in a disadvantaged urban setting supports the feasibility of model adoption. Unanswered questions about efficacy in such settings and regarding research issues related to model diffusion will require additional research investment.

Adolescent↗

Computer simulation studies of Newton black films.

We study via molecular dynamics simulations thin films (Newton black films, NBF) consisting of water coated with sodium dodecyl sulfate (SDS) surfactants. We analyze in detail the film properties (distribution of particles, pair correlation functions, roughness of the film, tilt angle of the hydrocarbon chain, electron density profiles, and mobility of water molecules) as a function of water content in the film core (i.e., film thickness, H). Our simulations indicate that water is part of the bilayer structure as solvation water. We estimate that around 2.25 water molecules per surfactant are part of this solvation structure. The structural analysis of the NBF shows that the headgroups exhibit a high degree of in-plane ordering. We find evidence for the existence of cavities in the monolayer, where only water is present. The basic structure of the monolayer is conserved down to water contents of the order of 4 water molecules per surfactant (H approximately equal to 11 A). The computed monolayer roughness for the present model is 2.5 A, in good agreement with the experimental data. We find that the roughness is very sensitive to the details of the interatomic potentials. Water mobility calculations emphasize the sluggish dynamics of very thin NBF. Diffusion coefficients of water in the lateral direction strongly decrease with film thickness. We find that the typical mean squared displacement of water in the direction normal to the bilayer is between 9 and 80 A2. Overall, our results indicate that the equilibrium SDS Newton black films studied in the X-ray experiments contain from 2 to 4 water molecules per surfactant.

Journal Article↗

Dynamics of a poly(ethylene oxide) tracer in a poly(methyl methacrylate) matrix: remarkable decoupling of local and global motions.

The tracer diffusion coefficient of unentangled poly(ethylene oxide) (PEO, M=1000 gmol) in a matrix of poly(methyl methacrylate) (PMMA, M=10 000 gmol) has been measured over a temperature range from 125 to 220 degrees C with forced Rayleigh scattering. The dynamic viscosities of blends of two different high molecular weight PEO tracers (M=440 000 and 900 000 gmol) in the same PMMA matrix were also measured at temperatures ranging from 160 to 220 degrees C; failure of time-temperature superposition was observed for these systems. The monomeric friction factors for the PEO tracers were extracted from the diffusion coefficients and the rheological relaxation times using the Rouse model. The friction factors determined by diffusion and rheology were in good agreement, even though the molecular weights of the tracers differed by about three orders of magnitude. The PEO monomeric friction factors were compared with literature data for PEO segmental relaxation times measured directly with NMR. The monomeric friction factors of the PEO tracer in the PMMA matrix were found to be from two to six orders of magnitude greater than anticipated based on direct measurements of segmental dynamics. Additionally, the PEO tracer terminal dynamics are a much stronger function of temperature than the corresponding PEO segmental dynamics. These results indicate that the fastest PEO Rouse mode, inferred from diffusion and rheology, is completely separated from the bond reorientation of PEO detected by NMR. This result is unlike other blend systems in which global and local motions have been compared.

Journal Article↗

Is water diffusion restricted in human brain white matter? An echo-planar NMR imaging study.

Water diffusion is extremely anisotropic in brain white matter, depending on myelin fiber orientation. A suggested, but unproven cause of anisotropy is that, in the direction transverse to the myelin fibers, axonal water diffusion is prevented by the presence of the myelin sheath. We found, however, using an ultra-fast nuclear magnetic resonance imaging technique, that the dependence of the diffusion coefficient on the diffusion time does not support the model of water restriction by impenetrable barriers. These results, which were obtained non-invasively in vivo in the human brain, imply that water diffuses with a measurable rate across myelin fibers.

Body Water↗

Aggregation and sedimentation in gas-fluidized beds of cohesive powders.

We present measurements on the settling velocity of gas-fluidized beds of fine cohesive powders. In the solidlike regime (solid volume fraction straight phi>straight phi(c)) particles are static, sustained by enduring contacts. The settling is hindered by interparticle contacts and is a very slow process. In the fluidlike regime (straight phi<straight phi(c)) permanent contacts no longer exist, and the bed displays a diffusive dynamics. The interparticle adhesive force leads to the formation of particle aggregates, and for this reason the sedimentation velocity exceeds the predicted value by empirical or theoretical laws on the settling of individual particles. We use an extension of the Richardson-Zaki empirical law for the settling of aggregates in the fluidlike regime to fit the experimental data. Aggregates are characterized by the number of aggregated particles N and by an effective radius R. The trend followed by these parameters with particle size is confirmed by direct visualization of the aggregates, and shows that cohesive effects become important when the adhesion force between particles is above particle weight. Results show that aggregates form open structures with a fractal dimension close to the predicted one in the diffusion-limited-aggregation model (D=2.5).

Journal Article↗