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Drag reduction in the turbulent Kolmogorov flow.

We investigate the phenomenon of drag reduction in a viscoelastic fluid model of dilute polymer solutions. By means of direct numerical simulations of the three-dimensional turbulent Kolmogorov flow we show that drag reduction takes place above a critical Reynolds number Re(c). An explicit expression for the dependence of Re(c) on polymer elasticity and diffusivity is derived. The values of the drag coefficient obtained for different fluid parameters collapse onto a universal curve when plotted as a function of the rescaled Reynolds number Re/ Re(c). The analysis of the momentum budget allows us to gain some insight on the physics of drag reduction, and suggests the existence of a Re-independent value of the drag cofficient--lower than the Newtonian one--for large Reynolds numbers.

Journal Article↗

Influence of hydrodynamic coupling on pair diffusion in a quasi-one-dimensional colloid system.

The effect of hydrodynamic interaction on the separation dependence of the center of mass and relative pair diffusion coefficients of colloid particles in a quasi-one-dimensional system, including the influence of proximate walls, is calculated using the method of reflections. There is excellent agreement between the theoretical predictions and the experimental data. We show that the separation dependence of the relative pair diffusion coefficient has an oscillatory structure on the scale length of the correlation length in the system, and we directly relate that oscillatory structure to the pair correlation function of the system.

Biopolymers↗

Myosin 5a controls insulin granule recruitment during late-phase secretion.

We have examined the importance of the actin-based molecular motor myosin 5a for insulin granule transport and insulin secretion. Expression of myosin 5a was downregulated in clonal INS-1E cells using RNAinterference. Stimulated hormone secretion was reduced by 46% and single-cell exocytosis, measured by capacitance recordings, was inhibited by 42% after silencing. Silencing of Slac-2c/MYRIP, which links insulin granules to myosin 5a, resulted in similar inhibition of single-cell exocytosis. Antibody inhibition of the myosin 5a-Slac-2c/MYRIP interaction significantly reduced the recruitment of insulin granules for release. The pool of releasable granules independent of myosin 5a activity was estimated to approximately 550 granules. Total internal reflection microscopy was then applied to directly investigate granule recruitment to the plasma membrane. Silencing of myosin 5a inhibited granule recruitment during late phase of insulin secretion. In conclusion, we propose a model where insulin granules are transported through the actin network via both myosin 5a-mediated transport and via passive diffusion, with the former playing the major role during stimulatory conditions.

Actins↗

Energy and angular distributions of photons from medical linear accelerators.

For accurate three-dimensional treatment planning, new models of dose calculations are being developed which require the knowledge of the energy spectra and angular distributions of the photons incident on the surface of the patient. Knowledge of the spectra is also useful in other applications, including the design of filters and beam modifying devices and determination of factors to convert ionization chamber measurements to dose. We have used Monte Carlo code (EGS) to compute photon spectra for a number of different linear accelerators. Both the target and the flattening filter have been accurately modeled. We find the mean photon energy to have a value lower than the generally perceived value of one-third the maximum energy. As expected, the spectra become softer as the distance from the central axis increases. Verification of the spectra is performed by computing dose distributions and half-value layers in water using the calculated spectra and comparing the results with measured data. We also examined the angular distributions of photons incident on the surface of the phantom. In currently used models of dose computations, it is assumed that the angular distribution of photons with respect to fan lines emanating from the source is negligible. Although the angular spread of photons with respect to the incident direction has been found to be small, its contribution to the diffuseness of the beam boundaries is significant.

Energy Transfer↗

Modeling [15O]oxygen tracer data for estimating oxygen consumption.

The most direct measure of oxidative tissue metabolism is the conversion rate of oxygen to water via mitochondrial respiration. To calculate oxygen consumption from the analysis of tissue residue curves or outflow dilution curves after injection of labeled oxygen one needs realistic mathematical models that account for convection, diffusion, and transformation in the tissue. A linear, three-region, axially distributed model accounts for intravascular convection, penetration of capillary and parenchymal cell barriers (with the use of appropriate binding spaces to account for oxygen binding to hemoglobin and myoglobin), the metabolism to [15O]water in parenchymal cells, and [15O]water transport into the venous effluent. Model solutions fit residue and outflow dilution data obtained in an isolated, red blood cell-perfused rabbit heart preparation and give estimates of the rate of oxygen consumption similar to those obtained experimentally from the flow times the arteriovenous differences in oxygen contents. The proposed application is for the assessment of regional oxidative metabolism in vivo from tissue 15O-residue curves obtained by positron emission tomography.

Animals↗

A tiered risk-based approach for predicting diffuse and point source phosphorus losses in agricultural areas.

Implementation of the European Union Water Framework Directive requires an assessment of the pressures from human activity, which, combined with information on the sensitivity of the receiving waterbody to the pressures, will identify those water bodies at risk of failing to meet the Directive's environmental objectives. Part of the process of undertaking the risk assessment for lakes is an assessment of diffuse agricultural phosphorus (P) pressures. Three approaches of increasing sophistication were developed for this purpose: a basic 'risk screening' approach (tier 1) applicable to all lakes in Great Britain (GB) and based on export coefficients for different land cover classes and animal types; the Pressure Delivery Risk Screening Matrix approach (tier 2) that differentiated between pressures in surface water and groundwater river basins; and the Phosphorus Indicators Tool (PIT), a simple model of locational risk and P delivery potential (tier 3). Application of the three approaches to a range of lake catchments in England demonstrated that a tiered risk assessment approach was appropriate which was tailored to the quality of the available data. A step-wise procedure was developed whereby if the tier 1 and 2 approaches showed a catchment to be at high risk of failing to meet the Directive's environmental objectives with regard to P, it was justifiable to undertake a more detailed assessment using the tier 3 approach. The tier 1 approach was applied to all lakes in GB greater than 1 ha in size on the assumption that the boundary between the good/moderate status classes under the Water Framework Directive guidelines represented a doubling of the total P (TP) reference conditions. The initial outputs suggested that 51% of lakes in GB are predicted to not meet the TP targets identified for high or good status and must, therefore, be considered at risk. There were regional differences in numbers of lakes at risk. Scotland appeared to have the fewest sites at risk (18%); England the most (88%), with Wales having an intermediate percentage (56%). A comparison of P pressures on freshwaters using the tier 2 approach with other pressures on waterbodies (e.g. nitrate, sediment) in GB is shown as risk maps on the Environment Agency website at: . The tier 3 approach was applied to data-rich catchments and identified at the 1 km(2) areas of relatively high risk of P delivery to water.

Agriculture↗

Synthesis of voltage-sensitive optical signals: application to panoramic optical mapping.

Fluorescent photon scattering is known to distort optical recordings of cardiac transmembrane potentials; however, this process is not well quantified, hampering interpretation of experimental data. This study presents a novel model, which accurately synthesizes fluorescent recordings over the irregular geometry of the rabbit ventricles. Using the model, the study aims to provide quantification of fluorescent signal distortion for different optical characteristics of the preparation and of the surrounding medium. A bi-domain representation of electrical activity is combined with finite element solutions to the photon diffusion equation simulating both the excitation and emission processes, along with physically realistic boundary conditions at the epicardium, which allow simulation of different experimental setups. We demonstrate that distortion in the optical signal as a result of fluorescent photon scattering is truly a three-dimensional phenomenon and depends critically upon the geometry of the preparation, the scattering properties of the tissue, the direction of wavefront propagation, and the specifics of the experimental setup. Importantly, we show that in an anatomically accurate model of ventricular geometry and fiber orientation, the morphology of the optical signal does not provide reliable information regarding the intramural direction of wavefront propagation. These findings underscore the potential of the new model in interpreting experimental data.

Animals↗

Hydrogen bonding interactions between adsorbed polymer molecules and crystal surface of acetaminophen.

The objective of this work was to investigate whether or not the hydrogen bonding interaction between polymer and crystal surface can be detected by the etching pattern changes in the presence of polymers. The (010) face of acetaminophen single crystal was used as a model solid surface. The etching patterns on the (010) face of acetaminophen crystal by water are in the directions of a- and c-axes, which are the same as the directions of the dominant attachment energies on the (010) face. In the presence of polymer, the hydrogen bonding interactions between adsorbed polymer and crystal surface can affect surface diffusion of acetaminophen molecules and change the etching patterns in the direction of a-axis, i.e., the direction of one hydrogen bond chain. Studies with 2-hydroxyethyl cellulose (HEC), hydroxypropyl cellulose (HPC), hydroxypropyl methylcellulose (HPMC) and poly(vinyl alcohol) (PVA) showed that polymers, which can form hydrogen bonds with acetaminophen crystal surface, can change etching patterns in the direction of a-axis. Study with Dextran suggested that if a polymer cannot form hydrogen bonds with crystal surface due to steric repulsion, it will not change the etching pattern in the direction of a-axis. Studies with poly(ethylene glycol) (PEG) and poly(propylene glycol) (PPG) further confirmed that only if a polymer can form hydrogen bonds with acetaminophen on crystal surface, the etching patterns in the direction of a-axis will be affected. The study results suggest that in the presence of polymers, the etching pattern change in the direction of hydrogen bond chain, the a-axis of acetaminophen crystals, can be used to indicate the existence of the hydrogen bonding interactions between adsorbed polymers and acetaminophen crystal surface.

Acetaminophen↗

Microglial activation in Alzheimer disease: Association with APOE genotype.

Microglial cells are considered to play an important role in the pathogenesis of Alzheimer disease. Apart from producing the Alzheimer amyloid precursor (APP) as an acute phase protein, microglial cells seem to be involved in the deposition of its amyloidogenic cleavage product, the amyloid-beta peptide (Abeta). Abeta is bound by apolipoprotein E (APOE) in an isoform-specific manner, and it has been demonstrated that inheritance of the AD susceptibility allele, APOE epsilon4, is associated with increased deposition of Abeta in the cerebral cortex. However, the relationship between APOE epsilon4 gene dose and microglial activation is unknown. Using microglial expression of major histocompatibility complex class II molecules as a marker, we have performed a quantitative genotype-phenotype analysis on microglial activation in frontal and temporal cortices of 20 APOE genotyped AD brains. The number of activated microglia and the tissue area occupied by these cells increased significantly with APOE epsilon4 gene dose. When a model of multiple linear regression was used to compare the relative influence of APOE genotype, sex, disease duration, age at death, diffuse and neuritic plaques as well as neurofibrillary tangles on microglial activation, only APOE genotype was found to have a significant effect. Thus, the APOE gene product represents an important determinant of microglial activity in AD. Since microglial activation by APP has been shown to be modulated by apoE in vitro, a direct role of microglia in AD pathogenesis is conceivable.

Aged↗

Fluorescein transport properties across artificial lipid membranes, Caco-2 cell monolayers and rat jejunum.

Membrane transport characteristics of a paracellular permeability marker fluorescein were evaluated using artificial membrane, Caco-2 cell monolayers and rat jejunum, all mounted in side-by-side diffusion cells. Modified Ringer buffers with varied pH values were applied as incubation salines on both sides of artificial membrane, cell culture monolayers or rat jejunum. Passive transport according to pH partition theory was determined using all three permeability models. In addition to that, active transport of fluorescein in the M-S (mucosal-to-serosal) direction through rat jejunum was observed. The highest M-S P(app) values regarding the active transport through the rat jejunum were observed in incubation saline with pH 6.5. Fluorescein transport through the rat jejunum was inhibited by DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid) and alpha-CHC (alpha-cyano-4-hydroxycinnamic acid). Thus, we assume that two pH-dependent influx transporters could be involved in the fluorescein membrane transport through the intestinal (jejunal) epithelium. One is very likely an MCT (monocarboxylic acid cotransporter) isoform, inhibited by specific MCT inhibitor alpha-CHC, while the involvement of the second one with overlapping substrate/inhibitor specificities (most probably a member of the organic anion-transporting polypeptide family, inhibited at least partially by DIDS) could not be excluded.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Investigations of reaction kinetics for immobilized enzymes--identification of parameters in the presence of diffusion limitation.

A method is proposed for identification of kinetic parameters when diffusion of substrates is limiting in reactions catalyzed by immobilized enzymes. This method overcomes conventional sequential procedures, which assume immobilization does not affect the conformation of the enzyme and, thus, consider intrinsic and inherent kinetics to be the same. The coupled equations describing intraparticle mass transport are solved simultaneously using numerical methods and are used for direct estimation of kinetic parameters by fitting modeling results to time-course measurements in a stirred tank reactor. While most traditional procedures were based on Michaelis-Menten kinetics, the method presented here is applicable to more complex kinetic mechanisms involving multiple state variables, such as ping-pong bi-bi. The method is applied to the kinetic resolution of (R/S)-1-methoxy-2-propanol with vinyl acetate catalyzed by Candida antarctica lipase B. A mathematical model is developed consisting of irreversible ping-pong bi-bi kinetics, including competitive inhibition of both enantiomers. The kinetic model, which fits to experimental data over a wide range of both substrates (5-95%) and temperatures (5-56 degrees C), is used for simulations to study typical behavior of immobilized enzyme systems.

Biotechnology↗

Biodegradation of sorbed chemicals in soil.

Rates of biodegradation of sorbed chemicals are usually lower in soil than in aqueous systems, in part because sorption reduces the availability of the chemical to microorganisms. Biodegradation, sorption, and diffusion occur simultaneously and are tightly coupled. In soil, the rate of biodegradation is a function of a chemical's diffusion coefficient, sorption partition coefficient, the distance it must diffuse from the site of sorption to microbial populations that can degrade it, and its biodegradation rate constant. A model (DSB model) was developed that describes biodegradation of chemicals limited in the availability by sorption and diffusion. Different kinetics expressions describe biodegradation depending on whether the reaction is controlled by mass transfer (diffusion and sorption) or the intrinsic biodegradation rate, and whether biodegradation begins during or after the majority of sorption has occurred. We tested the hypothesis that there is a direct relationship between how strongly a chemical is sorbed and the chemical's biodegradation rate. In six soils with different organic carbon contents, there was no relationship between the extent or rate of biodegradation and the sorption partition coefficient for phenanthrene. Aging of phenanthrene residues in soil led to a substantial reduction in the rate of biodegradation compared to biodegradation rates of recently added phenanthrene. Considerable research has focused on identification and development of techniques for enhancing in situ biodegradation of sorbed chemicals. Development of such techniques, especially those involving inoculation with microbial strains, should consider physical mass transfer limitations and potential decreases in bioavailability over time.

Absorption↗

Myocardial capillaries and tissue oxygenation.

The classical tissue model of August Krogh remains the cornerstone in the modeling of tissue PO2. However, heterogeneities of O2 determinants can profoundly affect the calculated oxygen fields. One of them is the heterogeneity in capillary spacing. At the present time there are two methods available for the estimation of capillary spacing: the method of capillary domains and the closest-individual method. The former estimates the distribution of the surface areas surrounding each capillary while the latter derives the distribution of distances of tissue points to the nearest capillary. Both can be transformed into the distribution of the radii of tissue cylinders according to the model of Krogh. Their distribution is approximately lognormal and is characterized by the mean (or median) value and the logarithmic standard deviation (log SD), which serves as the heterogeneity index. When applied to the same photomicrographs, both methods give similar values of the mean but the domain method yields a smaller log SD than does the closest-individual method. Subsequently, the calculated tissue PO2 histograms are also more uniform with the domain method. This difference is caused by the asymmetry of the domains. The shape of the domains is not circular and the capillary is not situated in the center as suggested by the model of Krogh. The method of capillary domains, however, is more direct and less time-consuming and thus more suitable for routine work. Nevertheless, the goal of future research is to develop a method that would characterize not only the distribution of the surface area of the domains but also their asymmetry.

Animals↗

Chain condensation in protein folding.

Three reactions (relaxation times: tau 1 = 140 +/- 8 ms, tau 2 = 840 +/- 30 ms and tau 3 = 30 + 3 s, at pH 7.0 at 25 degrees C) have been resolved by the stopped-flow kinetic method for the folding of the acid denatured staphylococcal nuclease (Chen et al (1991) J Mol Biol 220, 771; Biochemistry (1992) 31, 1483). Of the three reactions only the tau 2 reaction was dependent on the viscosity of the solution in a manner consistent with the diffusion/collision/coalescence model. Experiments with site-directed mutagenesis suggest that the forming of local structures by the electrostatic interactions between Glu75 and His121 and Lys9 may induce the chain condensation.

Diffusion↗

Coronary 64-slice computed tomographic angiography models employing aortic root and selective catheter directed contrast enhancement in swine: technical feasibility and preliminary results using 3D and 4D reconstructions.

PURPOSE: The technical feasibility of combining catheter directed coronary enhancement and multidetector computed tomographic angiography (MD-CTA) is presented in a swine model at various cardiac and injection rates. MATERIALS/METHODS: A 64-slice CT scanner was used under animal IRB approval in four sedated swine. Common femoral venous/arterial access with a 5 Fr micropuncture kit was ultrasound guided. Investigational 5 Fr diffusion-tip pigtail [aortic root (AR)-MD-CTA] and conventional 5 Fr coronary [selective (S)-MD-CTA] catheters were positioned on the CT table with c-arm fluoroscopy. AR-MD-CTA commenced 1-2 s after injection of 50 cc Visipaque mixed with 50 cc NS at 6 cc/s (n=3), 8 cc/s (n=5) or 10 cc/s (n=7) (HR=120, 100, 90, 80 or 65 bpm). S-MD-CTA (right and left, n=4) (HR= 90, 80, or 65 bpm) commenced 1-2 s after injection of 5 cc Visipaque mixed with 5 cc NS (1 cc/s). IV-MD-CTA (n=4) (HR=80 bpm) commenced 5 or 10 s after aortic peak density with 100 cc Visipaque (5 cc/s) and 50 or 75 cc NS (5 cc/s) flush. Conventional angiography (n=2) used standard protocol. MD-CTA was performed with the following parameters: collimation 0.6 mm, tube rotation time 0.3 s, table feed/rotation 3.8 mm, scan time 10-12 s, tube voltage 120 kVp, effective mAs 850, pitch 0.2, FOV 109-123 mm, slice thickness/increment 0.6 mm/0.3 mm, kernel B25 f smooth. Ex vivo imaging (64-slice CT, n=3) was also performed. Post-processing consisted of coronary peak densities, 3D-MIP's and 4D projections. RESULTS: Catheter directed MD-CTA was feasible at all injection rates at and below 100 bpm and yielded higher peak coronary attenuation values than IV-enhanced studies. Definition and clarity of the tributary and distal anatomy was also higher than IV-enhanced CTA. CONCLUSIONS: Catheter directed MD-CTA can be performed by retrofitting the current CT scanner with a portable c-arm fluoroscopy unit. S and AR MD-CTA provide high coronary anatomy definition and luminal attenuation without obscuring cardiac chamber signal and with the least iodinated contrast volume.

Animals↗

The establishment of follicular dominance in co-cultured mouse ovarian follicles.

An in vitro model of dominant and subordinate ovarian follicles was developed to allow a closer investigation of the phenomenon of follicular dominance. Preantral mouse ovarian follicles were cultured either alone or in pairs. Pairs of follicles were either in direct contact or in shared medium, but without physical contact. The experiments showed that where contact was allowed to develop between follicles one follicle invariably became dominant, while the other would grow and develop little during the culture period. In contrast, there was no effect of co-culture on follicle development in the absence of contact between the follicles. There was, therefore, no evidence of secretion of a diffusible factor by a dominant follicle that could affect the development of neighbouring follicles. After 6 days of co-culture with contact, histological examination of the subordinate follicle showed that it was healthy, in spite of remarkably little growth during culture. In a further experiment, the subordinate follicle was separated from the dominant one after 2 days of co-culture (when a significant difference in size had already developed), and cultured alone. These 'released' follicles exhibited a spurt of growth during the remaining culture period, attaining a size and appearance indistinguishable from those of controls by the end of culture. This confirms that the dominant follicle, while depressing the growth of its neighbour, is not inducing irreversible atresia in the subordinate follicle in this model. The in vitro model will allow a more detailed study of direct influences of dominant-subordinate follicle interactions, and should increase our knowledge of a poorly understood phenomenon.

Animals↗

[Experimental in vitro model of an artificial kidney--measurement of trace element levels using the ICP method. Preliminary studies].

Trace elements in blood serum is significantly changed in hemodialysed patients. The result of our experiment showed the manner and directions of the evaluated trace elements -Sr, Zn, Ni, Ba, B, Si, Mn and Cu movements. It was confirmed that reverse osmosis is efficient in the most tracers elimination, except Si, B, and Cu. The trace elements being present in the whole arrangement diffuse easily through the dialysers membrane used in our experiment, except Ni. In the membrane of the new, non-rinsed dialyser we detected Pb, Fe, V, Be, Ti and Al. It could possibly be the source of their contamination into the human organism. ICP-AES method of trace elements analysis reveals the possibilities of precisely, fast and simultaneous evaluation of big number various trace elements.

Hemodialysis Solutions↗

Assessment of frequency-dependent alterations in the level of extracellular Ca2+ in the synaptic cleft.

The synaptic cleft may be represented as a very thin disk of extracellular fluid. It is possible that at high stimulation frequencies the interval between pulses would be insufficient for diffusion of Ca2+ from the periphery of the cleft to replace extracellular Ca2+ depleted at the center of the cleft as a result of activation of postsynaptic, Ca2(+)-permeable channels. Computer modeling was employed to assess the impact of activation of glutamate receptor channels (GRCs) in the postsynaptic membrane on the level of extracellular Ca2+ within the synaptic cleft. The model includes calcium influx from the synaptic cleft into the postsynaptic compartment through GRC and calcium efflux through calcium pumps and Na/Ca exchangers. Concentrations of extracellular Ca2+ inside the cleft are estimated by using a compartmental model incorporating flux across the postsynaptic membrane and radial diffusion from the edges of the cleft. The simulations suggest that substantial extracellular Ca2+ depletion can occur in the clefts during activation of GRCs, particularly at high stimulation frequencies used to induce long-term potentiation (LTP). Only minimal transitory changes in extracellular Ca2+ are observed at low frequencies. These frequency-dependent alterations in extracellular Ca2+ dynamics are a direct reflection of the activity of GRCs and could be involved in the modulation of presynaptic function via a retrograde messenger mechanism, if there are extracellular Ca2+ sensors on the presynaptic membranes. The recently cloned extracellular Ca2(+)-sensing receptors that are known to be present in nerve terminals in hippocampus and other areas of the brain could potentially play such a role.

Calcium↗