Dispersion of 0.5- to 2-micron aerosol in microG and hypergravity as a probe of convective inhomogeneity in the lung.

We used aerosol boluses to study convective gas mixing in the lung of four healthy subjects on the ground (1 G) and during short periods of microgravity (microG) and hypergravity ( approximately 1. 6 G). Boluses of 0.5-, 1-, and 2-micron-diameter particles were inhaled at different points in an inspiration from residual volume to 1 liter above functional residual capacity. The volume of air inhaled after the bolus [the penetration volume (Vp)] ranged from 150 to 1,500 ml. Aerosol concentration and flow rate were continuously measured at the mouth. The dispersion, deposition, and position of the bolus in the expired gas were calculated from these data. For each particle size, both bolus dispersion and deposition increased with Vp and were gravity dependent, with the largest dispersion and deposition occurring for the largest G level. Whereas intrinsic particle motions (diffusion, sedimentation, inertia) did not influence dispersion at shallow depths, we found that sedimentation significantly affected dispersion in the distal part of the lung (Vp >500 ml). For 0.5-micron-diameter particles for which sedimentation velocity is low, the differences between dispersion in microG and 1 G likely reflect the differences in gravitational convective inhomogeneity of ventilation between microG and 1 G.     

Quantitative deposition of ultrafine stable particles in the human respiratory tract

Theoretical models of particle deposition in the respiratory tract predict high fractional deposition for particles of less than 0.1 micron, but there are few confirming experimental data for those predictions. We have measured the deposition fraction of a nonhygroscopic aerosol in the human respiratory tract. The aerosol had a count mean diameter of 0.044 micron SD of 1.93, as measured with an electrical aerosol analyzer, and was produced from a 0.01% solution of bis(2-ethylhexyl) sebacate using a condensation generator. Subjects inhaled the aerosol using a controlled respiratory pattern of 1 liter tidal volume, 12/min. Deposition was calculated as the difference in concentration between inhaled and exhaled aerosol of five size fractions corrected for system deposition and dead-space constants. Three deposition studies were done on each of five normal male volunteers. Means (+/- SE) for the five size fractions were 0.024 micron, 0.71 +/- 0.06; 0.043 micron, 0.62 +/- 0.06; 0.075 micron, 0.53 +/- 0.05; 0.13 micron, 0.44 +/- 0.04; and 0.24 micron, 0.37 +/- 0.06. These data demonstrate that deposition of inhaled particles in the 0.024- to 0.24-micron size range is high and increases with decreasing size. These observations agree with and validate predictions of mathematical models.     

Modified Spinning Top Homogeneous Spray Apparatus for Use in Experimental Respiratory Disease Studies

The May spinning top generator was adapted to a modified Henderson tube for producing large aerosol particles (>4 mum) to obtain almost exclusive upper respiratory tract deposition of infectious aerosols in exposed mice. The system was installed in a biological safety cabinet to permit experimentation with pathogens. A novel mechanism utilizing parts from a machinists micrometer and the mechanical stage from a light microscope was developed for the spinning top generator as a means for precisely positioning the liquid feed needle. Aerosol light-scatter properties were continuously analyzed to provide relative measures of particle size distribution and aerosol concentration. When mice were exposed to influenza virus aerosols in which none of the virus was contained in particles with aerodynamic diameters <4 mum, essentially all of the virus was deposited in the upper respiratory tract tissues.     

Effect of gravity on aerosol dispersion and deposition in the human lung after periods of breath holding.

To determine the extent of the role that gravity plays in dispersion and deposition during breath holds, we performed aerosol bolus inhalations of 1-microm-diameter particles followed by breath holds of various lengths on four subjects on the ground (1G) and during short periods of microgravity (microG). Boluses of approximately 70 ml were inhaled to penetration volumes (V(p)) of 150 and 500 ml, at a constant flow rate of approximately 0.45 l/s. Aerosol concentration and flow rate were continuously measured at the mouth. Aerosol deposition and dispersion were calculated from these data. Deposition was independent of breath-hold time at both V(p) in microG, whereas, in 1G, deposition increased with increasing breath hold time. At V(p) = 150 ml, dispersion was similar at both gravity levels and increased with breath hold time. At V(p) = 500 ml, dispersion in 1G was always significantly higher than in microG. The data provide direct evidence that gravitational sedimentation is the main mechanism of deposition and dispersion during breath holds. The data also suggest that cardiogenic mixing and turbulent mixing contribute to deposition and dispersion at shallow V(p).     

Retention and clearance of 0.9-micron particles inhaled by hamsters during rest or exercise

We assessed the retention and clearance of inhaled particles in six anatomic compartments of the respiratory tract. Hamsters were exposed for 45 min to 0.9-micron fluorescent latex particles either at rest (n = 9) or while running on a laddermill (n = 9). Oxygen consumption, which was used to estimate minute ventilation, was continuously monitored. Three animals from each group, rest and exercise, were killed at 10 min, 24 h, or 7 days after the exposure. Morphometric techniques were used to determine the number of particles retained in nose and oropharynx (NOSE), trachea and extrapulmonary airways, intrapulmonary conducting airways, respiratory bronchioles, alveolar ducts (AD), and alveoli (ALV). At 10 min, total particle retention increased linearly as a function of O2 consumption (slope = 1.4 +/- 0.3 x 10(6) particles.ml-1.g-1.h-1, P less than 0.015). Exercised hamsters retained 4.4 times more total particles in their NOSE than rested hamsters, but parenchymal retention (AD + ALV) was unaffected. After 7 days, 95% of the particles were cleared from the NOSE, 80% from the trachea and extrapulmonary airways, 44% from intrapulmonary conducting airways and respiratory bronchioles, and 16% from AD and ALV. There was evidence of particle redistribution from AD to ALV during the 1st day. We conclude that exercise enhances the deposition of 0.9-micron particles in the upper respiratory tract but not in the parenchyma. Subsequently, the deposited particles are cleared at varying rates depending on the lung compartment.     

Sub-micron particle behaviour and capture at an immuno-sensor surface in an ultrasonic standing wave

The capture of 200 nm biotinylated latex beads from suspensions of concentration 10(7) to 2.5 x 10(8) particle/ml on an immuno-coated surface of the acoustic reflector in an ultrasound standing wave (USW) resonator has been studied while the acoustic pathlength was less than one half wavelength (lambda/2). The particles were delivered to the reflector's surface by acoustically induced flow. The capture dependencies on suspension concentration, duration of experiments and acoustic pressure have been established at 1.09, 1.46 and 1.75 MHz. Five-fold capture increase has been obtained at 1.75 MHz in comparison to the control (no ultrasound) situation. The contrasting behaviours of 1, 0.5 and 0.2 mum fluorescent latex beads in a lambda/4 USW resonator at 1.46 MHz have been characterized. The particle movements were observed with an epi-fluorescent microscope and the velocities of the particles were measured by particle image velocimetry (PIV). The experiments showed that whereas the trajectories of 1 mum particles were mainly affected by the direct radiation force, 0.5 mum particles were influenced both by the radiation force and acoustic streaming. The 0.2 mum latex beads followed acoustic streaming in the chamber and were not detectably affected by the radiation force. The streaming-associated behaviour of the 200 nm particles has implications for enhanced immunocapture of viruses and macromolecules (both of which are also too small to experience significant acoustic radiation force).     

Particle Deposition in a Child Respiratory Tract Model: In Vivo Regional Deposition of Fine and Ultrafine Aerosols in Baboons

To relate exposure to adverse health effects, it is necessary to know where particles in the submicron range deposit in the respiratory tract. The possibly higher vulnerability of children requires specific inhalation studies. However, radio-aerosol deposition experiments involving children are rare because of ethical restrictions related to radiation exposure. Thus, an in vivo study was conducted using three baboons as a child respiratory tract model to assess regional deposition patterns (thoracic region vs. extrathoracic region) of radioactive polydisperse aerosols ([d16–d84], equal to [0.15 µm–0.5 µm], [0.25 µm–1 µm], or [1 µm–9 µm]). Results clearly demonstrated that aerosol deposition within the thoracic region and the extrathoraic region varied substantially according to particle size. High deposition in the extrathoracic region was observed for the [1 µm–9 µm] aerosol (72%±17%). The [0.15 µm–0.5 µm] aerosol was associated almost exclusively with thoracic region deposition (84%±4%). Airborne particles in the range of [0.25 µm–1 µm] showed an intermediate deposition pattern, with 49%±8% in the extrathoracic region and 51%±8% in the thoracic region. Finally, comparison of baboon and human inhalation experiments for the [1 µm–9 µm] aerosol showed similar regional deposition, leading to the conclusion that regional deposition is species-independent for this airborne particle sizes.     

Crossflow filtration of yeast broth cultivated in molasses

A broth of yeast cells cultivated in molasses was crossfiltered with a thin-channel module. The permeation flux gradually decreased at a constant cell concentration. The flux was much lower than that obtained for yeast broth cultivated in yeast extract, polypeptone, and dextrose (YPD) medium during the filtration. The flux did not depend on the membrane pore size (0.45 to 5 mum). The steady-state flux was one-twentieth that calculated for a cake filtration mode from the amount of cake per unit filtration area and the specific resistance of the cake measured in a dead-end filtration apparatus. The lower flux was due to small particles (most of which were less than 1 mum in diameter) in the molasses. The mehanism of crossflow filtration of broths of yeast cells cultivated in molasses was clarified by analysis of the change in flux with time and observations with scanning electron microscopy. At the initial stage of crossflow filtration the yeast cells and particles from the molasses were deposited on the membrane to form the molasses were deposited on the membrane to form a cake in a similar way to dead-end filtration. After the deposition of cells onto the membrane ceased, the fine particles from molasses formed a thin layer, which had higher resistance than the cake formed next to the membrane. The backwashing method was effective to increase the flux. The flux increased low when the pore size was 0.45 to 0.08 mum, but using larger pores of 3 to 5 mum it returned almost to the bases line. (c) 1994 John Wiley & Sons, Inc.     

Effects of oral airway geometry characteristics on the diffusional deposition of inhaled nanoparticles

The deposition of ultrafine aerosols in the respiratory tract presents a significant health risk due to the increased cellular-level response that these particles may invoke. However, the effects of geometric simplifications on local and regional nanoparticle depositions remain unknown for the oral airway and throughout the respiratory tract. The objective of this study is to assess the effects of geometric simplifications on diffusional transport and deposition characteristics of inhaled ultrafine aerosols in models of the extrathoracic oral airway. A realistic model of the oral airway with the nasopharynx (NP) included has been constructed based on computed tomography scans of a healthy adult in conjunction with measurements reported in the literature. Three other geometries with descending degrees of physical realism were then constructed with successive geometric simplifications of the realistic model. A validated low Reynolds number k-omega turbulence model was employed to simulate laminar, transitional, and fully turbulent flow regimes for the transport of 1-200 nm particles. Results of this study indicate that the geometric simplifications considered did not significantly affect the total deposition efficiency or maximum local deposition enhancement of nanoparticles. However, particle transport dynamics and the underlying flow characteristics such as separation, turbulence intensity, and secondary motions did show an observable sensitivity to the geometric complexity. The orientation of the upper trachea was shown to be a major factor determining local deposition downstream of the glottis and should be retained in future models of the respiratory tract. In contrast, retaining the NP produced negligible variations in airway dynamics and could be excluded for predominantly oral breathing conditions. Results of this study corroborate the use of existing diffusion correlations based on a circular oral airway model. In comparison to previous studies, an improved correlation for the deposition of nanoparticles was developed based on a wider range of particle sizes and flow rates, which captures the dependence of the Sherwood number on both Reynolds and Schmidt numbers.     

Characterization and Deposition of Respirable Large- and Small-Particle Bioaerosols

The deposition patterns of large-particle microbiological aerosols within the respiratory tract are not well characterized. A novel system (the flow-focusing aerosol generator [FFAG]) which enables the generation of large (>10-μm) aerosol particles containing microorganisms under laboratory conditions was characterized to permit determination of deposition profiles within the murine respiratory tract. Unlike other systems for generating large aerosol particles, the FFAG is compatible with microbiological containment and the inhalational challenge of animals. By use of entrapped Escherichia coli cells, Bacillus atrophaeus spores, or FluoSphere beads, the properties of aerosols generated by the FFAG were compared with the properties of aerosols generated using the commonly available Collison nebulizer, which preferentially generates small (1- to 3-μm) aerosol particles. More entrapped particulates (15.9- to 19.2-fold) were incorporated into 9- to 17-μm particles generated by the FFAG than by the Collison nebulizer. The 1- to 3-μm particles generated by the Collison nebulizer were more likely to contain a particulate than those generated by the FFAG. E. coli cells aerosolized using the FFAG survived better than those aerosolized using the Collison nebulizer. Aerosols generated by the Collison nebulizer and the FFAG preferentially deposited in the lungs and nasal passages of the murine respiratory tract, respectively. However, significant deposition of material also occurred in the gastrointestinal tract after inhalation of both the small (89.7%)- and large (61.5%)-particle aerosols. The aerosols generated by the Collison nebulizer and the FFAG differ with respect to mass distribution, distribution of the entrapped particulates, bacterial survival, and deposition within the murine respiratory tract.     

Physical characteristics of mouse sperm nuclei.

The nuclei of epididymal sperm, isolated from C57BL/6J and CBA/J inbred mice by their resistance to trypsin digestion, retain the shape differences of the intact sperm head. Various physical characteristics of these nuclei were measured and compared. The measurement of the projected dimensions of nuclei showed that the CBA nuclei are 13.5% longer than C57BL/6 nuclei (8.64 +/- 0.02 mum compared with 7.61 +/- 0.02 mum), 0.8% narrower (3.51 +/- 0.01 vs. 3.54 +/-0.01 mum) with 6.8% more area (22.34 +/- 0.10 vs. 20.91 +/- 0.09 mum2). However, the volumes of the nuclei as based on reconstructing calibrated electronmicrographs of serial sections of the nuclei indicated that CBA are about 7% smaller than C57BL/6 nuclei (3.72 +/- 0.08 vs. 4.01 +/- 0.03 mum3). The buoyant density of the CBA nuclei is 1.435 +/- 0.002 g/cm3 compared with 1.433 +/- 0.002 g/cm3 for the C57BL/6 nuclei as determined on linear CsCl and Renografin-76 density gradients and confirmed by a technique utilizing physiological tonicities. Therefore, the average mass of the CBA nuclei is less than that of the C57BL/6 nuclei (5.34 +/- 0.12 vs. 5.75 +/- 0.05 pg). The sedimentation velocities at unit gravity of nuclei from 11 inbred strains differ over a range of more than 6% with CBA nuclei sedimenting about 2.0% more slowly than C57BL/6 nuclei. We show that for these nuclei the sedimentation velocity can be related to their buoyant density, volume and a sedimentation shape factor. Within the errors of our measurements of these various characteristics, it was found that C57BL/6 and CBA nuclei have similar sedimentation shape factors. Therefore, the difference in sedimentation velocity between these nuclei appears to be primarily a result of differences in volume. The possible applications of these techniques to the physical separation of sperm are evaluated in the discussion.     

The density of protein precipitates and its effect on centrifugal sedimentation

Isoelectric soya-protein precipitate densities were measured for mean particle sizes ranging from 3.4-65 mum by gradient centrifugation, centrifugation in water-immiscible solvents, tracerdilution, gravity sedimentation of isolated particles. Coulter counter volume determination, and a comparison of Coulter counter and centrifugal sedimentation size distributions. The immiscible system and tracer dilution methods were both found to be unreliable due to experimental uncertainties. The Coulter counter volume measurement indicated the existence of a density-size relationship with the aggregate density decreasing as the size increased. Comparison with sedimentation measurements showed that the Coulter counter measures 80% of the total aggregate volume for 6-mum particles. The relation between aggregate density (rho(a), kg m (-3)) and size (d, mum) was measured for isoelectric soya protein and casein precipitated by ammonium sulfate, using a comparison of the Coulter counter size distribution and centrifugal sedimentation. The functions were described for soya by \documentclass{article}\pagestyle{empty}\begin{document}$$ \rho _a - 1004 = 246d;{ - 0.408} $$\end{document} and for casein by \documentclass{article}\pagestyle{empty}\begin{document}$$ \rho _a - 1136 = 31d;{ - 0.441} $$\end{document} The gradient centrifugation method measured the buoyant density of hydrated protein precipitate which was independent of size, and is consistent with an aggregate structure consisting of primary particles. However, the aggregate structure was not described for all sizes by the theoretical cubic packing of hard-sphere primary particles, nor by the successive random addition of primary particles. The density-size functions indicated up to a fivefold difference in Stokes settling velocities compared to those calculated assuming a constant density difference.     

Calculation of regional deposition of aerosol in the respiratory tract

The removal of air-borne particles in the respiratory tract is treated to enable regional deposition to be inferred from measurement of expired aerosol as well as predicted from theory of the primary removal processes. The analysis uses the analogy of a continuous tubular filter-bed and includes consideration of respiratory pauses and the mechanical mixing of gas flow. Derived equations relate regional deposition, distribution of aerosol in the expired air, and efficiency of removal at different depths in the respiratory tract.     

Effect of microgravity and hypergravity on deposition of 0.5-to 3-m-diameter aerosol in the human lung

Darquenne, Chantal, Manuel Paiva, John B. West, and G. KimPrisk. Effect of microgravity and hypergravity on deposition of0.5- to 3-µm-diameter aerosol in the human lung. J. Appl. Physiol. 83(6): 2029-2036, 1997.Wemeasured intrapulmonary deposition of 0.5-, 1-, 2-, and 3-µm-diameterparticles in four subjects on the ground (1 G) and during parabolicflights both in microgravity (µG) and at ~1.6 G. Subjects breathed aerosols at a constant flow rate (0.4 l/s) and tidalvolume (0.75 liter). At 1 G and ~1.6 G, deposition increased withincreasing particle size. In µG, differences in deposition as afunction of particle size were almost abolished. Deposition was anearly linear function of the G level for 2- and 3-µm-diameterparticles, whereas for 0.5- and 1.0-µm-diameter particles, depositionincreased less between µG and 1 G than between 1 G and ~1.6 G. Comparison with numerical predictions showed good agreement for 1-, 2-, and 3-µm-diameter particles at 1 and ~1.6 G, whereas the modelconsistently underestimated deposition in µG. The higher depositionobserved in µG compared with model predictions might be explained bya larger deposition by diffusion because of a higher alveolarconcentration of aerosol in µG and to the nonreversibility of theflow, causing additional mixing of the aerosols.

     

Role of Relative Humidity in the Survival of Airborne Mycoplasma pneumoniae

Aerosols of Mycoplasma pneumoniae were studied at several relative humidities at a controlled temperature of 27 C. Production of an experimentally reproducible aerosol required preatomization of the organism in its suspending fluid and was dependent on the type of fluid used in atomization as well as on the procedures used to produce an aerosol. The airborne particles studied were within the range of epidemiological significance, with most being 2 mum or less in diameter. Survival of the airborne mycoplasma in these particles was found to be best at very low and at very high humidities. The most lethal relative humidity levels were at 60 and 80%, at which levels fewer than 1% of the organisms survived over a 4-hr observation period. However, survival of the organism at most relative humidity levels was such that long-term infectivity could be expected from aerosols of M. pneumoniae. Because of the extreme sensitivity of M. pneumoniae at critical humidity levels, control of the airborne transmission of these organisms may be possible in selected spaces.     

Determining the basic characteristics of aerosols suitable for studies of deposition in the respiratory tract

Studies of aerosol particle deposition in the respiratory tract requires experimental inhalation of artificial model aerosols. The paper formulates some of the most important requirements for the properties of such aerosols. Several suitable fractions were prepared as part of a research project dealing with the use of microporous polymers for diagnostic purposes. 5 fractions of the polymer designated G-gel 60 with the particle size as stated by the manufacturer, ranging from 3 to 7 micron were evaluated using a 16-channel particle dispersity analyzer HIAC/ROYCO MT 3210 with the sensor 1200 and operated by a microprocessor, the equipment being coupled to an APPLE IIe computer. G-gel 60 particles introduced into the aerosol were characterized by the parameters CMAD, MMAD and sg both numerically and graphically. The measurement procedure was found to be very sensitive with respect to all fractions in evaluating the subtile differences between different lot numbers of the aerosol. G-gel 60 fractions characterized both numerically and graphically were compared with the known aerosols from paraffin oil and atmospheric air. The equipment MT 3210 enables prompt determination of the percentages of aerosol particles distribution by size class. The authors conclude that the procedure, both in its numerical and graphical versions, is particularly suitable for the diagnosis of aerosol particles deposition in the respiratory tract, offering a new application for HIAC/ROYCO in the field of medicine. In evaluating atmospheric aerosol in exhaled air, the number of particles was found to be below that in inhaled air, the difference being dependent on the choice of investigation methods. Percentual distribution of deposited particles following one minute ventilation proved to be at its maximum, as regards atmospheric aerosol, in the 0.30-0.50 micron range. The deposition curve was similar to already published curves, being characterized by an S-shaped pattern with maximum deposition in the greater size classes. An analysis of inhaled, exhaled and deposited aerosol suggested that deposited aerosol is more polydisperse and has particles of greater sizes than inhaled aerosol. Investigation of the effect of apnoe on deposition indicated that deposition increased as a function of apnoeic pause.     

Aerosol deposition characteristics in distal acinar airways under cyclic breathing conditions

Although the major mechanisms of aerosol deposition in the lung are known, detailed quantitative data in anatomically realistic models are still lacking, especially in the acinar airways. In this study, an algorithm was developed to build multigenerational three-dimensional models of alveolated airways with arbitrary bifurcation angles and spherical alveolar shape. Using computational fluid dynamics, the deposition of 1- and 3-μm aerosol particles was predicted in models of human alveolar sac and terminal acinar bifurcation under rhythmic wall motion for two breathing conditions (functional residual capacity = 3 liter, tidal volume = 0.5 and 0.9 liter, breathing period = 4 s). Particles entering the model during one inspiration period were tracked for multiple breathing cycles until all particles deposited or escaped from the model. Flow recirculation inside alveoli occurred only during transition between inspiration and expiration and accounted for no more than 1% of the whole cycle. Weak flow irreversibility and convective transport were observed in both models. The average deposition efficiency was similar for both breathing conditions and for both models. Under normal gravity, total deposition was ~33 and 75%, of which ~67 and 96% occurred during the first cycle, for 1- and 3-μm particles, respectively. Under zero gravity, total deposition was ~2-5% for both particle sizes. These results support previous findings that gravitational sedimentation is the dominant deposition mechanism for micrometer-sized aerosols in acinar airways. The results also showed that moving walls and multiple breathing cycles are needed for accurate estimation of aerosol deposition in acinar airways.     

Serum penicillin G levels are lower than expected in adults within two weeks of administration of 1.2 million units

When introduced in the 1950s, benzathine penicillin G (BPG) was shown to be effective in eradicating group A beta-hemolytic streptococcus (GAS) for at least 3 weeks after administration. Several studies since the 1990s suggest that at 3–4 weeks serum penicillin G levels are less than adequate (below MIC⁹⁰ of 0.016 µg/ml). We studied these levels for 4 weeks after the recommended dose of BPG in military recruits, for whom it is used as prophylaxis against GAS. The 329 subjects (mean age 20 years) each received 1.2 million units BPG IM and gave sera 1 day post injection and twice more at staggered time points over 4 weeks. Serum penicillin G levels were measured by liquid chromatography/tandem mass spectometry. The half-life of serum penicillin G was 4.1 days. By day 11, mean levels were <0.02 µg/ml, and by day 15<0.01 µg/ml. Levels in more than 50% of the subjects were below 0.02 µg/ml on day 9, and <.01 µg/ml on day 16. There was no demonstrable effect of subject body-surface area nor of the four different lots of BPG used. These data indicate that in healthy young adults serum penicillin G levels become less than protective <2½ weeks after injection of 1.2 million units of BPG. The findings require serious consideration in future medical and public health recommendations for treatment and prophylaxis of GAS upper respiratory tract infections.     

Validating CFD predictions of respiratory aerosol deposition: effects of upstream transition and turbulence

A number of computational fluid dynamics (CFD) studies have explored local deposition patterns of inhaled aerosols in the respiratory tract. These studies have highlighted the effects of multiple physiologic, geometric, and particle characteristics on deposition. However, very few studies have reported local or sub-branch quantitative comparisons to in vitro particle deposition data. The objective of this study is to numerically investigate the effects of transition and turbulence on highly localized particle deposition in a respiratory double bifurcation model in order to quantitatively validate CFD results. To perform the validations, local comparisons have been made to a specific in vitro case study of 10 microm particles depositing in a model of respiratory generations G3-G5. To achieve this objective, two geometric cases have been considered. The first case includes only the double bifurcation model. The second case includes a portion of the experimental particle delivery geometry, where transitional flow is expected. To evaluate the effectiveness of two-equation turbulence models in this system, the flow field solutions have been computed using laminar, standard k-omega, and low Reynolds number (LRN) k-omega approximations. Results indicate that even though the Reynolds number remained below the critical limit required for full turbulence, transition and turbulence have a significant impact on the flow field and local particle deposition patterns. For the experimental case considered, turbulence impacted the local deposition of 10 microm particles primarily by influencing the initial velocity and particle profiles. As such, both the laminar and LRN k-omega flow models provided good local quantitative matches to the in vitro deposition data, provided that the correct initial particle profile was specified. Implications of this study include the need for local quantitative validations of particle deposition results, the importance of correct inlet conditions, and the need to consider upstream effects in experimental and computational studies of the respiratory tract. Applications of these results to realistic respiratory geometries will require consideration on upstream flow conditions in the lung, transient flow, and intermittent turbulent structures.     

DNA of a Human Hepatitis B Virus Candidate

Particles containing DNA polymerase (Dane particles) were purified from the plasma of chronic carriers of hepatitis B antigen. After a DNA polymerase reaction with purified Dane particle preparations treated with Nonidet P-40 detergent, Dane particle core structures containing radioactive DNA product were isolated by sedimentation in a sucrose density gradient. The radioactive DNA was extracted with sodium dodecyl sulfate and isolated by band sedimentation in a preformed CsCl gradient. Examination of the radioactive DNA band by electron microscopy revealed exclusively circular double-stranded DNA molecules approximately 0.78 mum in length. Identical circular molecules were observed when DNA was isolated by a similar procedure from particles that had not undergone a DNA polymerase reaction. The molecules were completely degraded by DNase 1. When Dane particle core structures were treated with DNase 1 before DNA extraction, only 0.78-mum circular DNA molecules were detected. Without DNase treatment of core structures, linear molecules with lengths between 0.5 and 12 mum, in addition to the 0.78-mum circles were found. These results suggest that the 0.78-mum circular molecules were in a protected position within Dane particle cores and the linear molecules were not within core structures. Length measurements on 225 circular molecules revealed a mean length of 0.78 +/- 0.09 mum which would correspond to a molecular weight of around 1.6 x 10(6). The circular molecules probably serve as primer-template for the DNA polymerase reaction carried out by Dane particle cores. Thermal denaturation and buoyant density measurements on the Dane particle DNA polymerase reaction product revealed a guanosine plus cytosine content of 48 to 49%.