Intestinal absorption by carrier-mediated transports: two-dimensional laminar flow model

The two-dimensional laminar flow model was adapted to the intestinal absorption of drug and biological substances by carrier-mediated transports in the single perfusion experiments and we investigated the effects of the unstirred water layer on the Michaelis constant and the maximum transport velocity. According to the calculated values, the half saturation concentration at the inlet was larger than the true Michaelis constant at the intestinal wall. The apparent values of the Michaelis constant and the maximum transport velocity obtained by the Lineweaver-Burk plots were larger than the true ones, and the relations were not linear. These deviations increased as the ratio of the maximum transport velocity to the Michaelis constant increased and as the perfusion rate decreased. In the concurrent presence of a passive transport, underestimation of the carrier-mediated transport component of the absorption rate (at steady state) was predicted. It is considered to cause the underestimation of the maximum transport velocity. When water was absorbed (or secreted), the absorption rate increased (or decreased) and did not saturate. This two-dimensional laminar flow model would enable us to analyze the experimental data to determine the true values of the Michaelis constant and the maximum transport velocity.     

Stream channel experiments on downstream movement of recently emerged trout, Salmo trutta L., and salmon, S. salar L.—11. Effects of constant and changing velocities and of day and night upon dispersal rate

Four experimental stream channels were used to study instantaneous downstream dispersal rates of young trout and salmon relative to day and night, constant low and high water velocities and changes of velocity from high to low and vice versa.
At high and low velocity for trout and at high velocity for salmon, the dispersal rate was higher by night than by day. Changes of velocity during daytime from high to low or low to high for trout and from high to low for salmon, were associated with much higher dispersal rates than were constant velocities.     

Responses of Paramecium to Temperature Change

SYNOPSIS. The effect of temperature on the swimming velocity of Paramecium was investigated. When paramecia cultured at 25 C were transferred to various temperatures, their swimming velocity was increased immediately and then decreased exponentially with time to a new steady velocity. The relaxation time was about 1 min, independent of the new temperature. At a constant temperature the steady velocity was inversely proportional to viscosity. The velocity acceleration was observed when the sudden temperature change was larger than ± 1 C. Its magnitude became constant when the temperature change was greater than several degrees. The steady velocity as a function of temperature had a sharp maximum at the culture temperature and decreased on both sides of this temperature. Incubation of paramecia at 30 C for several hr after cultivation at 25 C shifted the maximum temperature of the steady velocity to 30 C. The temperature at which paramecia gathered in a temperature gradient cell correlated closely with the temperature of the maximum steady velocity.     

The sulphatase of ox liver. XXI: kinetic studies of the substrate-induced inactivation of sulphatase A.

The theoretical basis is given for methods of determining the apparent velocity constant, k*, for the substrate-induced inactivation of sulphatase A (aryl-sulphate sulphohydrolase, EC 3.1.6.1) and the initial velocity, vo, of the catalytic reaction. The expression is of the same form as the empirical relationships previously used but the significance of the various terms is clearly established. The method has been applied to the characterisation of the inactivation occurring during the hydrolysis of a number of substrates and it has been shown that k* varies with so in a hyperbolic relationship described by k, a velocity constant at infinite substrate concentrations and by K, a constant analogous to the Michaelis constant. Although K varies considerably for different substrates, and is consistently less than the corresponding Km, k is almost constant at 0.23 min-1. It is therefore suggested that the inactivation of the enzyme does not proceed through an enzyme . substrate complex but through the enzyme . SO2-4 complex produced during the catalytic reaction. The effects of several variables on these parameters are described.     

The influence of water velocity on the downstream movement of alevins and fry of brown trout, Salmo trutta L.

Trout eggs were planted in four experimental stream channels, each channel being run at a different but constant discharge. Survival of the eggs to hatching was low and apparently unrelated to surface water velocity. However, movement of young trout out of channels was affected by water velocity, the higher the velocity the greater the proportion of trout that were lost. Virtually all fry moved out of a channel with a mean surface water velocity of 0.73 m s⁻¹. The rate of loss was not constant over the experiment but increased as the young trout entered the free-feeding stage. At the end of the experiment loss of fry, after abrupt increases in discharge, was demonstrated in the lower velocity channels.     

Velocity field of pulsatile flow in a porous tube

This paper describes velocity fields for fully developed periodic laminar flow in a rigid tube with a porous wall. We obtained an analytical solution of the flow by the linear approximation of the Navier-Stokes equation. Unlike the previous works with a constant seepage rate along the axis, we used a wall velocity which contained hydraulic permeation constant Lp. The axial velocity profile shows a local maximum velocity near the wall at a large Womersley number alpha. This suggests that concentration polarization in porous tubular membrane may be reduced at high frequencies if a membrane device is operated under pulsatile flow conditions. The magnitude of wall permeation velocity decreases linearly along the tube axis because the damping of the pressure difference between the inside and the outside of the tube is very small.     

低Ca~(2 )对豚鼠心室乳头肌电缆特性的影响

应用常规细胞内微电极技术和一支细胞外玻璃吸引电极,观察低Ca~(2 )对豚鼠心室乳头肌电缆特性及动作电位传导速度的影响。实验结果表明,1/6正常Ca~(2 )浓度(0.3mmol/L)溶液灌流时,与正常对照相比,空间常数减小23.9％(p<0.01),细胞内纵向电阻增大37.1％(p<0.01),动作电位传导速度减小16.1％(p<0.01)。单纯缺氧时,与正常对照相比,空间常数减小29.4％(p<0.01),膜时间常数减小30.1％(p<0.01),细胞内纵向电阻增大100％(p<0.01),动作电位传导速度减小28％(p<0.01)。低Ca~(2 )(0.6mmol/L)加缺氧时,上述变化更加明显,与正常对照相比,空间常数减小39.4％(p<0.01),膜时间常数减小25.8％(p<0.05),细胞内纵向电阻增大140.9％(p<0.01),动作电位传导速度减小37.7％(p<0.01)。     

A random walk model of fast-phase timing during optokinetic nystagmus

 Most vertebrate animals produce optokinetic nystagmus in response to rotation of their visual surround. Nystagmus consists of an alternation of slow-phase eye rotations, which follow the surround, and fast-phase eye rotations, which quickly reset eye position. The time intervals between fast phases vary stochastically, even during optokinetic nystagmus produced by constant velocity rotation of a uniform surround. The inter-fast-phase interval distribution has a long tail, and intervals that are long relative to the mode become even more likely as constant surround velocity is decreased. This paper provides insight into fast-phase timing by showing that the process of fast-phase generation during constant velocity optokinetic nystagmus is analogous to a random walk with drift toward a threshold. Neurophysiologically, the output of vestibular nucleus neurons, which drive the slow phase, would approximate a random walk with drift because they integrate the noisy, constant surround velocity signal they receive from the visual system. Burst neurons, which fire a burst to drive the fast phase and reset the slow phase, are brought to threshold by the vestibular nucleus neurons. Such a nystagmic process produces stochastically varying inter-fast-phase intervals, and long intervals emerge naturally because, as drift rate (related to surround velocity) decreases, it becomes more likely that any random walk can meander for a long time before it crosses the threshold. The theoretical probability density function of the first threshold crossing times of random walks with drift is known to be that of an inverse Gaussian distribution. This probability density function describes well the distributions of the intervals between fast phases that were either determined experimentally, or simulated using a neurophysiologically plausible neural network model of fast-phase generation, during constant velocity optokinetic nystagmus. Received: 1 June 1995/Accepted in revised form: 15 February 1996     

Changing the Mechanical Unfolding Pathway of FnIII10 by Tuning the Pulling Strength

We investigate the mechanical unfolding of the tenth type III domain from fibronectin (FnIII₁₀) both at constant force and at constant pulling velocity, by all-atom Monte Carlo simulations. We observe both apparent two-state unfolding and several unfolding pathways involving one of three major, mutually exclusive intermediate states. All three major intermediates lack two of seven native β-strands, and share a quite similar extension. The unfolding behavior is found to depend strongly on the pulling conditions. In particular, we observe large variations in the relative frequencies of occurrence for the intermediates. At low constant force or low constant velocity, all three major intermediates occur with a significant frequency. At high constant force or high constant velocity, one of them, with the N- and C-terminal β-strands detached, dominates over the other two. Using the extended Jarzynski equality, we also estimate the equilibrium free-energy landscape, calculated as a function of chain extension. The application of a constant pulling force leads to a free-energy profile with three major local minima. Two of these correspond to the native and fully unfolded states, respectively, whereas the third one can be associated with the major unfolding intermediates.     

THE ANALYSIS OF BIOLUMINESCENCES OF SHORT DURATION,RECORDED WITH PHOTOELECTRIC CELL AND STRING GALVANOMETER

1. The rapid decay of luminescence in extracts of the ostracod crustacean Cypridina hilgendorfii, has been studied by means of a photoelectric-amplifier-string galvanometer recording system. 2. For rapid flashes of luminescence, the decay is logarithmic if ratio of luciferin to luciferase is small; logarithmic plus an initial flash, if ratio of luciferin to luciferase is greater than five. The logarithmic plot of luminescence intensity against time is concave to time axis if ratio of luciferin to luciferase is very large. 3. The velocity constant of rapid flashes of luminescence is approximately proportional to enzyme concentration, is independent of luciferin concentration, and varies approximately inversely as the square root of the total luciferin (luciferin + oxyluciferin) concentration. For large total luciferin concentrations, the velocity constant is almost independent of the total luciferin. 4. The variation of velocity constant with total luciferin concentration (luciferin + oxyluciferin) and its independence of luciferin concentration is explained by assuming that light intensity is a measure of the luciferin molecules which become activated to oxidize (accompanied with luminescence) by adsorption on luciferase. The adsorption equilibrium is the same for luciferin and oxyluciferin and determines the velocity constant.     

Studying molecular motor-based cargo transport: what is real and what is noise?

Noise is a major problem in analyzing tracking data of cargos moved by molecular motors. We use Bayesian statistics to incorporate what is known about the noise in parsing the trajectory of a cargo into a series of constant velocity segments. Tracks with just noise and no underlying motion are fit with constant velocity segments to produce a calibration curve of fit quality versus average segment duration. Fits to tracks of moving cargos are compared to the calibration curves with similar noise. The fit with the optimum number of constant velocity states has the least number of segments needed to match the fit quality of the calibration curve. We have tested this approach using tracks with known underlying motion generated by computer simulations and with a specially designed in vitro experiment. We present the results of using this parsing approach to analyze transport of lipid droplets in Drosophila embryos.     

Cyclic nucleotides and calcium: their role in the control of cell communication in the heart

The effects of theophylline and di-butyryl cyclic adenosine 3',5'-monophosphate (db-cAMP) on the electrical coupling of heart cells were investigated in rat trabeculae. Theophylline (4 X 10(-4) M) and db-cAMP (5 X 10(-5) M) increased both the space constant and conduction velocity. The time constant of the membrane was not changed by either drug. Measurements of the time constant of the foot of the action potential and conduction velocity were used to calculate the intracellular longitudinal resistance. Both theophylline and db-cAMP were found to enhance cell-to-cell communication in the heart by decreasing the intracellular longitudinal resistance.     

The deficit of the isometric tetanic tension redeveloped after a release of frog muscle at a constant velocity

Frog sartorius muscles tetanized isometrically were released at a constant velocity from lengths lL to lS (delta l = lL -lS; Ls greater than lO). The tension PS redeveloped after the release was lower than the isometric tension PS at LS, and higher than the isometric tension PL at lL. The tension deficit D is defined as the difference PS-PS. The timing of the release during the tetanus did not influence D. D/PO was proportional to delta l/lO. The proportionality constant k was equal to 1.35 +/- 0.19 (n = 8) when the velocity of release was 2.5 mm/s. When the muscles were released the same delta l, D was found to be an exponential decreasing function of the velocity. The tension deficit was also found in experiments performed in the region lS less than lO. The proportionality constant k was smaller, but the influence of the velocity of the release on D was not modified. When the velocity of the release was changed during the release, D changed accordingly, showing that the effects of delta l and V are multiplicative. These facts suggest a working hypothesis based on the concept that the actin filaments which enter the overlap region during a release are strained by the tetanic stress and therefore unable to make normal cross-bridges.     

Functional implications of cold-stable microtubules in kinetochore fibers of insect spermatocytes during anaphase

In normal anaphase of crane fly spermatocytes, the autosomes traverse most of the distance to the poles at a constant, temperature-dependent velocity. Concurrently, the birefringent kinetochore fibers shorten while retaining a constant birefringent retardation (BR) and width over most of the fiber length as the autosomes approach the centrosome region. To test the dynamic equilibrium model of chromosome poleward movement, we abruptly cooled or heated primary spermatocytes of the crane fly Nephrotoma ferruginea (and the grasshopper Trimerotropis maritima) during early anaphase. According to this model, abrupt cooling should induce transient depolymerization of the kinetochore fiber microtubules, thus producing a transient acceleration in the poleward movement of the autosomal chromosomes, provided the poles remain separated. Abrupt changes in temperature from 22 degrees C to as low as 4 degrees C or as high as 31 degrees C in fact produced immediate changes in chromosome velocity to new constant velocities. No transient changes in velocity were observed. At 4 degrees C (10 degrees C for grasshopper cells), chromosome movement ceased. Although no nonkinetochore fiber BR remained at these low temperatures, kinetochore fiber BR had changed very little. The cold stability of the kinetochore fiber microtubules, the constant velocity character of chromosome movement, and the observed Arrhenius relationship between temperature and chromosome velocity indicate that a rate-limiting catalyzed process is involved in the normal anaphase depolymerization of the spindle fiber microtubules. On the basis of our birefringence observations, the kinetochore fiber microtubules appear to exist in a steady-state balance between comparatively irreversible, and probably different, physiological pathways of polymerization and depolymerization.     

Study of hepatic binding protein activity in jejuno-ileal by-passed rat hepatocytes

The kinetic constants of internalization of asialoorosomucoid were determined for normal and jejuno-ileal by-passed rat hepatocytes. In by-passed rats the maximum velocity of asialoorosomucoid internalization is decreased 3-fold, without any modification of apparant constant of internalization. Moreover, the rate constant of internalization was the same in the two groups of rats. These data suggest that the process of asialoorosomucoid internalization is not altered in by-passed hepatocytes and that the decrease of maximal velocity is only due to a decrease of total uptake receptor number.     

Frame of reference transformations in motion perception during smooth pursuit eye movements

Smooth pursuit eye movements change the retinal image velocity of objects in the visual field. In order to change from a retinocentric frame of reference into a head-centric one, the visual system has to take the eye movements into account. Studies on motion perception during smooth pursuit eye movements have measured either perceived speed or perceived direction during smooth pursuit to investigate this frame of reference transformation, but never both at the same time. We devised a new velocity matching task, in which participants matched both perceived speed and direction during fixation to that during pursuit. In Experiment 1, the velocity matches were determined for a range of stimulus directions, with the head-centric stimulus speed kept constant. In Experiment 2, the retinal stimulus speed was kept approximately constant, with the same range of stimulus directions. In both experiments, the velocity matches for all directions were shifted against the pursuit direction, suggesting an incomplete transformation of the frame of reference. The degree of compensation was approximately constant across stimulus direction. We fitted the classical linear model, the model of Turano and Massof (2001) and that of Freeman (2001) to the velocity matches. The model of Turano and Massof fitted the velocity matches best, but the differences between de model fits were quite small. Evaluation of the models and comparison to a few alternatives suggests that further specification of the potential effect of retinal image characteristics on the eye movement signal is needed.     

Kinetic constanis of asialoorosomucoid endocytosis comparison between hepatocytes from normal and streptozotocin-diabetic rats

The initial velocity of asialoorosomucoid internalization is determined for normal and diabetic rat hepatocytes. The analysis of results according to Woolf-Hofstee's method, showed no modification of the endocytosis constant. In contrast, the maximum velocity of asialoorosomucoid internalization is decreased by threefold in diabetic rat hepatocytes as compared to normal rat hepatocytes. No modification of internalization constant is observed between the two groups of rats. This suggests that the decrease of asialoorosomucoid total uptake, previously reported for diabetic rat hepatocytes is directly related to a decrease of total surface receptor number.     

Active drag related to velocity in male and female swimmers

Propulsive arm forces of 32 male and 9 female swimmers were measured during front crawl swimming using arms only, in a velocity range between 1.0 m s-1 and 1.8 m s-1. At constant velocity, the measured mean propulsive force Fp equals the mean active drag force (Fd). It was found that Fd is related to the swimming velocity v raised to the power 2.12 +/- 0.20 (males) or 2.28 +/- 0.35 (females). Although many subjects showed rather constant values of Fd/v2, 12 subjects gave significantly (p less than 0.01) stronger or weaker quadratic relationships. Differences in drag force and coefficient of drag between males and females (drag: 28.9 +/- 5.1 N, 20.4 +/- 1.9 N, drag coefficient: 0.64 +/- 0.09, 0.54 +/- 0.07 respectively) are especially apparent at the lowest swimming velocity (1 m s-1), which become less at higher swimming velocities. Possible explanations for the deviation of the power of the velocity from the ideal quadratic dependency are discussed.     

Equilibrium muscle cross-bridge behavior. Theoretical considerations.

We have developed a model for the equilibrium attachment and detachment of myosin cross-bridges to actin that takes into account the possibility that a given cross-bridge can bind to one of a number of actin monomers, as seems likely, rather than to a site on only a single actin monomer, as is often assumed. The behavior of this multiple site model in response to constant velocity, as well as instantaneous stretches, was studied and the influence of system parameters on the force response explored. It was found that in the multiple site model the detachment rate constant has considerably greater influence on the mechanical response than the attachment rate constant. It is shown that one can obtain information about the detachment rate constants either by examining the relationship between the apparent stiffness and duration of stretch for constant velocity stretches or by examining the force-decay rate constants following an instantaneous stretch. The main effect of the attachment rate constant is to scale the mechanical response by influencing the number of attached cross-bridges. The significance of the modeling for the interpretation of experimental results is discussed.