Flow field analysis in a compliant acinus replica model using particle image velocimetry (PIV)

Inhaled particles reaching the alveolar walls have the potential to cross the blood–gas barrier and enter the blood stream. Experimental evidence of pulmonary dosimetry, however, cannot be explained by current whole lung dosimetry models. Numerical and experimental studies shed some light on the mechanisms of particle transport, but realistic geometries have not been investigated. In this study, a three dimensional expanding model including two generations of respiratory bronchioles and five terminal alveolar sacs was created from a replica human lung cast. Flow visualization techniques were employed to quantify the fluid flow while utilizing streamlines to evaluate recirculation. Pathlines were plotted to track the fluid motion and estimate penetration depth of inhaled air. This study provides evidence that the two generations immediately proximal to the terminal alveolar sacs do not have recirculating eddies, even for intense breathing. Results of Peclet number calculations indicate that substantial convective motion is present in vivo for the case of deep breathing, which significantly increases particle penetration into the alveoli. However, particle diffusion remains the dominant mechanism of particle transport over convection, even for intense breathing because inhaled particles do not reach the alveolar wall in a single breath by convection alone. Examination of the velocity fields revealed significant uneven ventilation of the alveoli during a single breath, likely due to variations in size and location. This flow field data, obtained from replica model geometry with realistic breathing conditions, provides information to better understand fluid and particle behavior in the acinus region of the lung.     

Performance of a model for a local neuron population

A model of a local neuron population is considered that contains three subsets of neurons, one main excitatory subset, an auxiliary excitatory subset and an inhibitory subset. They are connected in one positive and one negative feedback loop, each containing linear dynamic and nonlinear static elements. The network also allows for a positive linear feedback loop. The behaviour of this network is studied for sinusoidal and white noise inputs. First steady state conditions are investigated and with this as starting point the linearized network is defined and conditions for stability is discovered. With white noise as input the stable network produces rhythmic activity whose spectral properties are investigated for various input levels. With a mean input of a certain level the network becomes unstable and the characteristics of these limit cycles are investigated in terms of occurence and amplitude. An electronic model has been built to study more closely the waveforms under both stable and unstable conditions. It is shown to produce signals that resemble EEG background activity and certain types of paroxysmal activity, in particular spikes.     

Performance characteristics of yeast growth in a modified airlift fermenter

Two types of airlift fermenters, conventional (UT-ALF) and modified (CDT-ALF) were investigated to evaluate their performance with respect to baker's yeast growth. The riser tube of conventional external loop airlift fermenter is replaced by a converging-diverging tube, which is named as modified airlift fermenter having downcomer to riser cross-sectional area ratio A _d /A _r =1.8.The results were compared for the two types of airlift fermenter. A modified growth kinetics model for baker's yeast with oxygen as limiting substrate, has been proposed. The values of K _s and K _d of the growth model were determined from experimental data. The proposed model represented better for CDT-ALF system compared to UT-ALF. Compared to UT-ALF, CDT-ALF always showed higher cell mass concentration and low residual sugar concentration irrespective of the operating conditions. At optimum operating condition (initial glucose concentration 30 g/l, air flow rate 0.5 vvm and fermentation time 8 hrs.) 16.7% higher cell mass was observed in CDT-ALF compared to that in UT-ALF and yield (Y _x/s ) was found to be 0.51 which was theoretically very near to maximum achievable value.Symbols ALF Airlift fermenter - UT Uniform tube - CDT Converging-diverging tube - A _r Cross sectional area of riser - A _d Cross sectional area of downcomer - C _s Glucose cone, at any time, g/l - C _l Dissolved oxygen conc, at any time, g/l - _max Max. sp. growth rate, hr^–1 - Sp. growth rate, hr^–1 - X ₀ Initial cell mass cone. (dry wt.), g/l - X Cell mass conc. at any time t, g/l - C _s0 Initial glucose conc., g/l - C _s Glucose conc. at any time t, g/l - C _l Equilibrium conc. of oxygen, 0.0076 g/l - y _x/s Yield coefficient (dimensionless) - y _x/s gm cell mass produced/gm glucose consumed - Y _O2 gm cell produced/gm oxygen consumed - k _d maintenance coefficient, hr^–1 - K _L a volumetric mass transfer coefficient, hr^–1 - k _s saturation constant for the substrate, g/l - K _O2 saturation constant for the substrate of dissolved oxygen, g/l. This work was supported by a research grant from the Department of Biotechnology Govt. of India.     

Distribution of alcohol dehydrogenase isoenzymes in the human liver acinus

 By the use of a newly developed technique of ultrathin-layer electrophoresis, class I and class II alcohol dehydrogenase activity could be demonstrated in microdissected samples of the periportal, intermediate, and perivenous zones of the liver acinus in men and women. It could be demonstrated that both classes exhibit low activity in the periportal zone. From there, a rising gradient in the direction of the perivenous end was apparent. This increase, however, was found to be significant only in women. The analysis of class I alcohol dehydrogenase isoenzymes showed that the expression of α-, β-, and γ-containing isoforms did not differ in relation to the intraacinar position. The constant proportions of the isoenzymes to the maxima and minima of the total alcohol dehydrogenase activity support the view that the adult liver-specific isoenzyme pattern is determined during postnatal development. Accepted: 1 February 1999     

Small Rho GTPases are important for acinus formation in a human salivary gland cell line

Rho GTPases participate in a wide variety of signal transduction pathways regulating the actin cytoskeleton, gene expression, cellular migration and proliferation. The aim of this study was to evaluate the role of Rho GTPases in signal transduction pathways during acinus formation in a human salivary gland (HSG) cell line initiated by extracellular matrix (ECM; Matrigel) alone or in combination with epidermal growth factor, basic fibroblast growth factor and lysophosphatidic acid (LPA). Immunohistochemical and Western blotting analyses showed that HSG cells contained RhoA, RhoB, Rac1 and Cdc42 proteins. All growth factors enhanced the effects of ECM on acinus formation, in a pathway dependent on PI3-kinase and Rho GTPases. The role of ROCK, a major RhoA effector, seemed limited to cortical actin polymerization. LPA stimulated cell migration and acinus formation in a PI3-kinase-independent pathway. The results suggest that Rho proteins are important for epithelial-mesenchymal interactions during salivary gland development.This work was supported by FAPESP (grant numbers: 97/09507-6, 01/09047-2).     

Mixing characteristics of sludge simulant in a model anaerobic digester

This study aims to investigate the mixing characteristics of a transparent sludge simulant in a mechanically agitated model digester using flow visualisation technique. Video images of the flow patterns were obtained by recording the progress of an acid–base reaction and analysed to determine the active and inactive volumes as a function of time. The doughnut-shaped inactive region formed above and below the impeller in low concentration simulant decreases in size with time and disappears finally. The ‘cavern’ shaped active mixing region formed around the impeller in simulant solutions with higher concentrations increases with increasing agitation time and reaches a steady state equilibrium size, which is a function of specific power input. These results indicate that the active volume is jointly determined by simulant rheology and specific power input. A mathematical correlation is proposed to estimate the active volume as a function of simulant concentration in terms of yield Reynolds number.     

Extended life span is associated with insulin resistance in a transgenic mouse model of insulinoma secreting human islet amyloid polypeptide

Pancreatic amyloid is found in patients with insulinomas and type 2 diabetes. To study mechanisms of islet amyloidogenesis, we produced transgenic mice expressing the unique component of human islet amyloid, human islet amyloid polypeptide (hIAPP). These mice develop islet amyloid after 12 mo of high-fat feeding. To determine whether we could accelerate the rate of islet amyloid formation, we crossbred our hIAPP transgenic animals with RIP-Tag mice that develop islet tumors and die at 12 wk of age from hypoglycemia. At 12 wk of age, this new line of hIAPPxRIP-Tag mice was heavier (29.7 +/- 1.0 vs. 25.0 +/- 1.3 g, P < 0.05) and had increased plasma glucose levels (4.6 +/- 0.4 vs. 2.9 +/- 0.6 mmol/l, P < 0.05) compared with littermate RIP-Tag mice. However, the hIAPPxRIP-Tag mice did not display islet amyloid or amyloid fibrils despite high circulating hIAPP levels (24.6 +/- 7.0 pmol/l). Interestingly, hIAPPxRIP-Tag mice had a longer life span than RIP-Tag mice (121 +/- 8 vs. 102 +/- 5 days, P < 0.05). This increase in life span in hIAPPxRIP-Tag was positively correlated with body weight (r = 0.48, P < 0.05) and was associated with decreased insulin sensitivity compared with RIP-Tag mice. hIAPPxRIP-Tag mice did not develop amyloid during their 4-mo life span, suggesting that increased hIAPP secretion is insufficient for islet amyloid formation within such a short time. However, hIAPPxRIP-Tag mice did have an increase in life span that was associated with insulin resistance, suggesting that hIAPP has extrapancreatic effects, possibly on peripheral glucose metabolism.     

Performance characteristics of a reversible immunosensor with a heterobifunctional enzyme conjugate as signal generator

Factors that control the performance of a reversible immunosensor with an analyte (progesterone)-enzyme (horseradish peroxidase) conjugate as signal generator have been investigated. The conjugate is used in conjunction with two antibodies, which are specific to progesterone and to horseradish peroxidase, immobilized on two spatially separated polypropylene mesh discs. The conjugate and two antibodies are confined to an internal compartment of a microdialyzer by a semipermeable membrane. The small analyte from an external medium permeates across the membrane into the internal compartment where the analyte concentration determines the relative amounts of the bound conjugate on the two solid surfaces. By measuring two signals from the conjugate bound at two separate sites, we experimentally obtained time-response curves to a concentration pulse of the external analyte. A mathematical (kinetic) model describing the sensor system was developed and used for the determination of rate-limiting factors. In semicontinuous monitoring of the analyte concentrations, operation of the immunosensor with the enzyme conjugate as signal generator required special attention to (a) enzyme stability, (b) analyte permeation (dependence on medium components), and (c) kinetics related to the different accessibility to the same antibody of the small analyte (to be measured) vs. the larger counterpart on the enzyme conjugate (for signal generation). (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 56: 221-231, 1997.     

Building a secreting nanomachine: a structural overview of the T3SS

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Effect of individual characteristics on a mathematical model of human thermoregulation

A multi-segmental mathematical model of human thermoregulation was tested for its capability to predict individualized physiological responses. We compared the model predictions obtained for an average person with measured individual responses of subjects exposed to mild cold. Secondly, body composition (BC) data, the resting metabolic rate (MR), and the actual measured MR during the test were used as input into the model.

The data was obtained from 20 subjects (age: 19–36 years; BMI: 17–32 kg/m²). BC, MR, rectal and skin temperatures were measured for 1 h at 22 °C, followed by 3 h at 15 °C.

A mean bias of 1.8 °C, with a standard error of 0.7 °C, resulted for the mean skin temperature of an average person at 15 °C. When subjective BC and measured MR were incorporated the bias was −0.2±0.9 °C. For the hand-back skin temperature the bias ± standard error fell from 5.3±2.8 °C for an average person to 2.0±2.5 °C, when using individualized characteristics. Trunk skin temperatures were not significantly affected by the adjustments.

In conclusion, this study shows that on a group level predictions of skin temperatures can be improved when adopting individualized body characteristics and measured MR, but the predictions on an individual level were not improved.     

Isolation of a human stromal cell strain secreting hemopoietic growth factors

A diploid fibroblastoid cell strain, termed "ST-1," has been established from a long-term liquid culture of human fetal liver cells. ST-1 cells are nonphagocytic, nonspecific esterase negative and do not possess factor VIII-related antigen but stain with antibodies specific for fibronectin and type I collagen. The ST-1 cells produce nondialyzable hemopoietic growth factors capable of stimulating the development of erythroid bursts, mixed granulocyte-macrophage colonies, pure granulocyte colonies, and pure macrophage colonies. These factors are active on both human fetal liver and human adult bone marrow progenitors. When liquid cultures of human fetal liver hemopoietic progenitors are established with a preformed monolayer of ST-1 cells, the yields of nonadherent cells, erythroid progenitors, and myeloid progenitors are greatly increased. These studies demonstrate that the fibroblastoid ST-1 cells support hemopoiesis in vitro and may be a critical element in the stromal microenviroment in vivo.     

Performance characteristics of a new photometer with a moving filter tape for luminescence assay.

The performance characteristics of a new photometer that incorporated a reaction system consisting of a movable filtration tape have been studied for use with the firefly luciferase assay for adenosine 5'-triphosphate. Precision, linearity, and sensitivity are given for measuring a graded series of constant-light emitters, concentrations of adenosine 5'-triphosphate, and washed bacterial cells. Precision ranged from 1 to 10% coefficient of variation. The coefficient of correlation was 0.9985 for 7 X 10(8) to 7 X 10(3) bacteria per ml; however, the accuracy decreased at the low levels. The sample processing time was 2 min for a 1-ml sample. This instrument shows potential for many applications in quantitating small numbers of organisms, e.g., pollution, water monitoring, and clinical infection detection.     

Alternative animal behavior: a model and its statistical characteristics

The rats' alternative behaviour in T-maze at simultaneous two-sided food refreshment in 13 trials a day during 6 days has been studied. It has been found that in the first testing days the indexes of alternative behaviour of animals correspond to the characteristics of the random alternation. However, on the 5-6th day of testing in the overwhelming majority of rats the true deviation of alternation index above or below than the theoretical values has been revealed. A question on the existence of two strategies of cognitive behaviour alteration and perseveration in rat population is under discussion.     

Performance characteristics of a new photometer with a moving filter tape for luminescence assay.

The performance characteristics of a new photometer that incorporated a reaction system consisting of a movable filtration tape have been studied for use with the firefly luciferase assay for adenosine 5'-triphosphate. Precision, linearity, and sensitivity are given for measuring a graded series of constant-light emitters, concentrations of adenosine 5'-triphosphate, and washed bacterial cells. Precision ranged from 1 to 10% coefficient of variation. The coefficient of correlation was 0.9985 for 7 X 10(8) to 7 X 10(3) bacteria per ml; however, the accuracy decreased at the low levels. The sample processing time was 2 min for a 1-ml sample. This instrument shows potential for many applications in quantitating small numbers of organisms, e.g., pollution, water monitoring, and clinical infection detection.