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Comparison of the in vivo and in vitro mechanical properties of aortic valve leaflets.

The mechanical properties of aortic valve leaflets are responsible for the efficiency and longevity of the valve. These properties in the radial direction were investigated in vivo in dogs. During cardiopulmonary bypass, radiopaque markers were placed on the leaflets. Later, from a normally functioning valve, the marker positions were recorded on videotape during fluoroscopy, and the leaflet length was determined. Leaflet length in the radial direction increased 31% from systole to diastole. During diastole, leaflet length increased by 3.9% as the pressure gradient increased from 60 to 200 mm Hg. During systole, the leaflet had a low elastic modulus. In vitro, the stress-strain properties of the leaflets were studied. For an increase in stress in vitro that corresponded to an increase in pressure gradient from 60 to 200 mm Hg, the leaflet length increased 8.7%. This increase was more than twice that measured in vivo, which indicates that during diastole the leaflet is much stiffer in vivo than in vitro. This stiffening appears to be due to stress in the circumferentially oriented collagen fibers of the leaflet, which prevents stretching in the radial direction. In systole, the lower elastic modulus reduces the flexion stresses, and in diastole, stiffening prevents the leaflet from prolapsing under pressure.

Animals↗

Simultaneous assessment of diameter and pressure waveforms in the carotid artery.

Simultaneous assessment of diameter and pressure waveforms allows the calculation of the incremental compliance, distensibility, pulse wave velocity and elastic modulus as function of the distending pressure. However, the waveforms must be obtained at the same position and acquired and processed with the same filter characteristics to circumvent possible temporal and spatial changes in amplitude and phase. In this paper, arterial diameter waveforms are assessed by means of ultrasound (US) and converted to pressure using an empirically derived exponential relationship between pressure and arterial cross-section. The derived pressure waveform is calibrated to brachial end diastolic and mean arterial pressure by iteratively changing the wall rigidity coefficient (i.e., the exponential power). Because pressure is derived directly from arterial cross-section, no phase delay is introduced due to spatial separation or different filter characteristics. The method was evaluated for the left common carotid artery of 51 healthy subjects ranging in age from 22 to 75 years old. In healthy subjects, the carotid pulse pressure is 29% lower than the brachial pulse pressure. Continuous assessment of arterial properties confirms that pulse-wave velocity and incremental elastic modulus increase, whereas distensibility and compliance decrease, as function of increasing distending blood pressure.

Adult↗

Arterial mechanical changes in children with familial hypercholesterolemia.

Atherosclerosis is preceded by a phase of changes in the arterial wall that could have functional consequences even before the appearance of atheromatous changes. We hypothesized that early alterations of the mechanical properties of the arterial wall could precede clinical and echographic modifications. We used an automatic, computerized, ultrasonic procedure to evaluate geometric and mechanical characteristics of the common carotid artery (CCA) in normotensive children with primary familial class IIA hypercholesterolemia (FH; n=30; mean+/-SD age, 11+/-2 years old; mean+/-SD systolic/diastolic blood pressure, 109+/-9/55+/-7 mm Hg). These subjects were compared with age-matched, nonobese control subjects (n=27; 11+/-3 years old; 112+/-10/55+/-7 mm Hg). Noninvasive ultrasonic measurements were performed by the same investigator to measure the CCA luminal systolic and diastolic diameters and intima-media thickness (IMT). The cross-sectional compliance, cross-sectional distensibility, and the incremental elastic modulus of the CCA wall were then calculated. Finally, we assessed the degree of reactive hyperemia in the brachial artery produced after distal cuff occlusion and release. The changes in brachial arterial diameter in response to reactive hyperemia (endothelium-dependent dilation) and to glyceryltrinitrate (endothelium-independent dilation) were then measured. In patients with FH, we observed a significant reduction of systodiastolic variations in diameter (by 20%, P:<0.001) without a significant difference in IMT. Cross-sectional compliance and cross-sectional distensibility were significantly reduced in FH subjects (by 15%, P:<0.05 and 19%, P:<0.01, respectively). In parallel, the incremental elastic modulus was significantly increased (by 27%, P:<0.01) in children with FH. No correlation was evident between the carotid incremental modulus and either IMT or plasma low density lipoprotein cholesterol level. There was no difference in diameter of the brachial artery at rest in control and FH subjects (3.0+/-0.5 versus 3.0+/-0.4 mm). The reactive hyperemia and glyceryltrinitrate dilation were also similar in the 2 groups. However, the flow-mediated dilation of the brachial artery was smaller in the FH subjects (4.2+/-2.9%) than in controls (9.0+/-3.1%, P:<0.001). In FH, endothelium-dependent dilation was negatively correlated with the plasma low density lipoprotein cholesterol level (P:<0.04). These results indicate that increased stiffness of the CCA wall in children with FH is independent of blood pressure and could be related to endothelial dysfunction. Thus, alterations in CCA wall mechanics could be early and easily measurable markers of atheromatous changes in the arterial wall.

Biomechanical Phenomena↗

Effect of bone mineral content on the tensile properties of cortical bone: experiments and theory.

The effect of mineral volume fraction on the tensile mechanical properties of cortical bone tissue is investigated by theoretical and experimental means. The mineral content of plexiform, bovine bone was lowered by 18% and 29% by immersion in fluoride solutions for 3 days and 12 days, respectively. The elastic modulus, yield strength and ultimate strength of bone tissue decreased, while the ultimate strain increased with a decrease in mineral content. The mechanical behavior of bone tissue was modeled by using a micromechanical shear lag theory consisting of overlapped mineral platelets reinforcing the organic matrix. The decrease in yield stress, by the 0.002 offset method, of the fluoride treated bones were matched in the theoretical curves by lowering the shear yield stress of the organic matrix. The failure criterion used was based on failure stresses determined from a failure envelope (Mohr's circle), which was constructed using experimental data. It was found that the model predictions of elastic modulus got worse with a decrease in mineral content (being 7.9%, 17.2% and 33.0% higher for the control, 3-day and 12-day fluoride-treated bones). As a result, the developed theory could not fully predict the yield strain of bones with lowered mineral content, being 12.9% and 21.7% lower than the experimental values. The predicted ultimate stresses of the bone tissues with lower mineral contents were within +/- 10% of the experimental values while the ultimate strains were 12.7% and 26.3% lower than the experimental values. Although the model developed in this study did not take into account the presence of hierarchical structures, voids, orientation of collagen molecules and micro cracks, it still indicated that the mechanical properties of the organic matrix depend on bone mineral content.

Animals↗

The effects of androgens on the mechanical properties of primate bone.

Feral adult female cynomolgus monkeys were divided into three groups and treated for two years: (1) normal controls; (2) weak androgenic treatment (androstenedione+estrone); and (3) strong androgenic treatment (testosterone). The tibiae and the trabecular bone of femoral head from each group were tested mechanically. There were no significant changes in the elastic modulus and shear modulus of the tibiae, measured by three point bending and torsion tests, among the three groups. Significant increases in energy absorption capacity (+45% for testosterone) and maximum shear stress (+19.4% for androstenedione and +39% for testosterone) of the tibiae, measured by torsion tests, and the cortical bone density (+5.5% for androstenedione and +8.7% for testosterone), were observed. Testosterone treatment significantly increased torsional rigidity (+23%) and bending stiffness (+15%) of the tibiae while androstenedione did not change any of these structural properties. The results of compression tests of the trabecular bone samples indicated significant increases in their elastic modulus after androstenedione (+88%) or testosterone (+107%) treatment. The maximum compressive stress of the testosterone treated samples was significantly higher than those of both normal (+28%) and androstenedione treated groups (+26%). The trabecular bone density increased after both androgenic treatments. This increase was significant for the testosterone treated group (+8.6%). We conclude that in the young cynomolgus monkey, long-term androgenic treatment significantly improves some of the mechanical properties of both cortical and trabecular bones, increases bone density, and the stronger the androgen, likely, the more pronounced is the effect.

Androstenedione↗

Quantitation of intracranial aneurysm neck size from diagnostic angiograms based on a biomathematical model.

Accurate measurement of the aneurysm neck size from diagnostic angiograms is crucial in the consideration and implementation of interventional embolotherapeutic procedures. Due to inherent problems in angiography, aneurysm morphology and location, and obstruction by overlying structures, accurate measurement of the aneurysm neck size is difficult. We are proposing a method for the angiographic measurement of aneurysm neck size based on a biomathematical model of an aneurysm. A biomathematical model of an intracranial saccular aneurysm was developed based on Laplace's law for a spherical elastic object, given by: Stress = Pressure x Radius/2 x Wall thickness. In addition, another biomechanical parameter used to describe an elastic sphere is the strain: Strain = delta R/Ri = (R-Ri)/Ri where R is the current aneurysm radius and Ri is the initial radius prior to aneurysm development. The stress and strain of an elastic structure are used to describe the elastic modulus, E: E = stress/strain = [PR/2h]/[(R-Ri)/Ri] = [PRRi]/[2hR-2hri]. It is assumed at this point that no additional tissue growth occurs through the developmental course of the aneurysm. The expression for E is now solved for Ri which, in essence, represents the radius of the aneurysm neck: Ri = [2hER]/[PR + 2hE]. Thus, the diameter of the neck, Dn, is given by Dn = 2 + i = 2 ([2hER]/[PR + 2hE]). During diagnostic angiography, the radius, R, and pressure, P, are easily obtained during the examination procedure. However, it is not possible to angiographically determine the elastic modulus, E, and the wall thickness, h. In this case, the following average values are used: E = 1.0 MPa and h = 50 microns. From the diagnostic angiograms and hospital records of 23 patients, the aneurysm neck size was determined using the biomathematical model and compared to the results obtained from the correlative relationship between the measured and accepted ratios of neck size to diameter of parent artery. The neck diameter as measured from the accepted ratios of neck size to parent artery diameter for the 23 patients ranged from 1.5 mm to 8.7 mm. The angiographically measured neck sizes were in excellent agreement with those obtained from the biomathematical model, particularly for the wide-necked aneurysms, as evidenced by the fact that all but two chi 2 values were < 1.0. We have described a simple yet accurate method for obtaining aneurysm neck size measurements from diagnostic angiograms using a biomathematical model. The model requires knowledge of only the aneurysm radius and blood pressure and becomes particularly important in characterizing wide-necked aneurysms.

Adult↗

[Propagation rate of arterial pressure waves as a function of age and physical training].

The arterial pulse wave velocity is determined to a large extent by the arterial elastic modulus. We tried to assess the importance of this parameter in cardio-vascular adaptation to exercise by measuring pulse wave velocity (c) in 45 sedentary subjects and 28 competitive cyclists whose ages ranged from 14 to 47 years. The measurements were performed at rest and during the recovery phase after ergometric exercise. At constant diastolic pressure, a positive linear relationship was demonstrated between c and age in both the sedentary and trained subjects. The slope of this relation was significantly different in the two groups. During the recovery phase, at constant diastolic pressure, a linear relationship was also established between c and the relative increase in systolic pressure in the sedentary group classified into six age subgroups. The slope of this relation increased with age. The part taken by diastolic flow velocity during exercise in the increase in c was demonstrated in 8 subjects by simultaneous Doppler ultrasonic recording of contra-lateral femoral arterial velocity. Nevertheless diastolic flow in exercise could not explain entirely the observed increase in c. An increase in arterial elasticity modulus during exercise should be postulated in order to explain the concomitant increase in arterial pulse wave velocity.

Adolescent↗

Aortic pulsatile pressure and diameter response to intravenous perfusions of angiotensin, norepinephrine, and epinephrine in conscious dogs.

The aortic elastic behavior has been studied in conscious dogs chronically instrumented with a pressure microtransducer and two ultrasonic crystals. Pressure and diameter measurements were analyzed in terms of their mean values and systolic-diastolic variations, enabling calculation of Peterson elastic modulus, and were displayed in the x-y form to obtain pressure diameter hysteresis loops. After recovery from surgery and under autonomic blockade, intravenous perfusions of angiotensin, norepinephrine, and epinephrine were made at incremental steps of doses until steady-state pressure-diameter changes were achieved. The slopes of the positive pressure-diameter correlations obtained at each dose of the same vasoactive substance were higher for angiotensin than norepinephrine (p less than 0.01) and epinephrine (p less than 0.001) and were higher for norepinephrine than epinephrine (p less than 0.05). Similarly, the slopes of the elastic modulus to mean pressure relation were significantly lower for angiotensin than for norepinephrine (p less than 0.05) and epinephrine (p less than 0.001) and were significantly lower for norepinephrine than epinephrine (p less than 0.001). Thus, at the same transmural pressure, the distension and stiffness of the aorta were lower and higher with epinephrine than with norepinephrine, respectively, and with norepinephrine than with angiotensin suggesting different potencies of these drugs in terms of smooth muscle activation in the aorta.

Angiotensin II↗

Bending undulations and elasticity of the erythrocyte membrane: effects of cell shape and membrane organization.

The undulatory excitations (flickering) of human and camel erythrocytes were evaluated by employing the previously used flicker spectroscopy and by local measurements of the autocorrelation function K (t) of the cell thickness fluctuations using a dynamic image processing technique. By fitting theoretical and experimental flicker spectra relative values of the bending elastic modulus Kc of the membrane and of the cytoplasmic viscosity eta were obtained. The effects of shape changes were monitored by simultaneous measurement of the average light intensity I0 passing the cells and by phase contrast microscopic observation of the cells. Evaluation of the cellular excitations in terms of the quasi-spherical model yielded values of Kc/R3(0) and mu.R0 (R0 = equivalent sphere radius) and allowed us to account (1) for volume changes, (2) for effects of surface tension and spontaneous curvature and (3) for the non-exponential decay of K (t). From the long time decay of K (t) we obtained an upper limit of the bending elastic modulus of normal cells of Kc = 2-3 x 10(-19) Nm which is an order of magnitude larger than the value found by reflection interference contrast microscopy (RICT, Kc = 3.4 x 10(-20) Nm, Zilker et al. 1987) but considerably lower than expected for a bilayer containing 50% cholesterol (Kc = 5 x 10(-19) Nm, Duwe et al. 1989). The major part of the paper deals with long time measurements (order of hours) of variations of the apparent Kc and eta values of single cells (and their reversibility) caused (1) by osmotic volume changes, (2) by discocyte-stomatocyte transitions induced by albumin and triflouperazine, (3) by discocyte-echinocyte transitions induced by expansion of the lipid/protein bilayer (by incubation with lipid vesicles) and by ATP-depletion in physiological NaCl solution, (4), by coupling or decoupling of bilayer and cytoskeleton using wheat germ agglutinin or erythrocytes with elliptocytosis and (5) by cross-linking the cytoskeleton using diamide. These experiments showed: (1) Kc and eta are minimal at physiological osmolarity and temperature and well controlled over a large range of these parameters. (2) Echinocyte formation does not markedly alter the apparent membrane bending stiffness. (3) During swelling the cell may undergo a transient discocyte-stomatocyte transition. (4) Strong increases of the apparent Kc and eta after cup-formation or strong swelling and deflation are due to the effect of shear elasticity and surface tension. Our major conclusions are: (1) The erythrocyte membrane exhibits a shear free deformation regime which requires ATP for its maintenance.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Contribution of fibrin stabilization to clot strength. Supplementation of factor XIII-deficient plasma with the purified zymogen.

The contribution of fibrin stabilization to clot strength, measured as the static elastic modulus, was evaluated in human plasma by two independent procedures. In the first approach, amine inhibitors of fibrin stabilization were examined for their effects on the rigidity of normal plasma clots. It is a unique property of these inhibitors that they do not interfere with the reversible aggregation of fibrin molecules, i.e., do not delay clotting time, but selectively prevent only the formation of gamma-glutamyl-epsilon-lysine protein-to-protein linkages. Though the compounds tested were of different chemical structures and potencies, a fivefold reduction in clot strength was obtained in each instance. This value of 20% of normal seems to correspond to the rigidity of the Factor XIII-deficient plasma clot because, as demonstrated by the second approach, when a plasma specimen that genetically lacked the fibrin stabilizing factor was supplemented by the addition of measured amounts of the purified zymogen, a fivefold increase in clot strength could be achieved. The described procedure of evaluating Factor XIII in terms of correcting the elastic modulus of a deficient plasma clot is considered an important assay for the functional competence of purified preparations of the zymogen for the purpose of therapeutic application.

Aminoacetonitrile↗

Subject-specific finite element model of the pelvis: development, validation and sensitivity studies.

A better understanding of the three-dimensional mechanics of the pelvis, at the patient-specific level, may lead to improved treatment modalities. Although finite element (FE) models of the pelvis have been developed, validation by direct comparison with subject-specific strains has not been performed, and previous models used simplifying assumptions regarding geometry and material properties. The objectives of this study were to develop and validate a realistic FE model of the pelvis using subject-specific estimates of bone geometry, location-dependent cortical thickness and trabecular bone elastic modulus, and to assess the sensitivity of FE strain predictions to assumptions regarding cortical bone thickness as well as bone and cartilage material properties. A FE model of a cadaveric pelvis was created using subject-specific computed tomography image data. Acetabular loading was applied to the same pelvis using a prosthetic femoral stem in a fashion that could be easily duplicated in the computational model. Cortical bone strains were monitored with rosette strain gauges in ten locations on the left hemipelvis. FE strain predictions were compared directly with experimental results for validation. Overall, baseline FE predictions were strongly correlated with experimental results (r2=0.824), with a best-fit line that was not statistically different than the line y=x (experimental strains = FE predicted strains). Changes to cortical bone thickness and elastic modulus had the largest effect on cortical bone strains. The FE model was less sensitive to changes in all other parameters. The methods developed and validated in this study will be useful for creating and analyzing patient-specific FE models to better understand the biomechanics of the pelvis.

Aged↗

Effects of recombinant factor VIIa on platelet function and clot structure in blood with deficient prothrombin conversion.

While recombinant factor VIIa (rFVIIa) shows promise as a broad-spectrum hemostatic agent, questions remain regarding the most appropriate dose and the best way to monitor its effects. In this study we tested the sensitivity of a thrombin dependent platelet assay, platelet contractile force, to the effects of rFVIIa in normal, factor-deficient, and inhibitor-containing blood samples. Dose dependent effects of rFVIIa on platelet contractile force (PCF) and clot elastic modulus (CEM) were measured in all blood samples. rFVIIa minimally affected PCF and CEM in normal blood clotted with thrombin or batroxobin. While rFVIIa minimally altered PCF and CEM in factor VIII (FVIII) deficient blood clotted with thrombin, rFVIIa increased PCF and CEM and shortened the lag phase in a dose dependent manner in batroxobin-induced clots. The effects of rFVIIa in factor IX (FIX) deficient blood mirrored the effects seen in FVIII deficient samples. Whether clotted with thrombin or batroxobin, baseline PCF and CEM were abnormally low in FVIII deficient samples containing FVIII inhibitors. In such samples, rFVIIa caused dose dependent improvement of PCF, CEM, and lag phases. In one patient with a spontaneous inhibitor, rFVIIa caused dose dependent increases in PCF and CEM in blood clotted with either enzyme. rFVIIa corrects the deficient thrombin generation seen in FVIII and FIX deficiency, and in blood containing FVIII inhibitors. As a consequence, platelet function is improved and clot structure is enhanced. Platelet contractile force and clot elastic modulus measurements are sensitive to the dose dependent effects of rFVIIa.

Adult↗

The role of mucus gel viscosity, spinnability, and adhesive properties in clearance by simulated cough.

We investigated the role of the viscoelastic and adhesive properties of mucus gel simulants on the clearance of mucus by simulated cough. Mucus-like gels with widely varying viscoelastic properties were prepared from polysaccharides crosslinked with sodium borate. Cough was simulated by opening a solenoid valve connecting a model trachea to a pressurized tank. The clearance of gels lining the model trachea was quantified by observing marker particle transport. Viscosity elastic modulus, relaxation time and yield stress were measured with a steady-shear viscoelastometer. Spinnability (thread formation) was determined with a filancemeter. Adhesivity (surface tension) was measured by the platinum ring technique. The viscoelastic and adhesive properties of the mucus gel simulants spanned the ranges observed for bronchial secretions from patients with COPD. The relationship between simulated cough clearance and the viscoelastic and adhesive properties of the gels was analyzed by stepwise linear regression of the non-zero data matrix. The major independent variable relating to clearance was viscosity. Secondary, but highly significant dependences, were also found for spinnability and adhesivity. Elastic modulus, relaxation time and yield stress had no independent effect on cough clearance over the investigated range. The results indicate that, in the absence of airway surface liquid, cough-type clearance relates primarily with mucus gel viscosity. For a given viscosity, clearance is also impaired by spinnability, i.e. the capacity of the mucus to form threads. At constant viscosity and spinnability, clearance is further impaired by an increase in the adhesivity of the mucus. The negative dependence of each of these physical factors can be rationalized in terms of their inhibitory effect on wave formation in the mucus lining layer during high velocity airflow interaction.

Adhesiveness↗

Relationship between damage accumulation and mechanical property degradation in cortical bone: microcrack orientation is important.

The accumulation of damage and the associated degradation of the mechanical properties of cortical bone are postulated to contribute to age-, disease-, overuse-, and disuse-related skeletal fragilities. Therefore, gaining insight into the relationship between damage and degradation processes is essential in understanding the etiology of skeletal fractures. In investigating this relationship, the damage measure ideally needs to account for the size, the distribution density, and the orientation of microcracks. Existing measures of damage address the size and distribution density of microcracks; however, the orientation of cracks has not been well-investigated. Because the overall orientation of microcracks determines the material axis along which the greatest degradation will be experienced, we hypothesized that the incorporation of the relative orientation between microcracks and loading direction will improve the significance of the relationship between damage accumulation and material property degradation. A three-cycle damage protocol was used to induce tensile damage and to quantify the degradation of the elastic modulus of specimens from human donor femoral cortical bone (a 24-year-old and a 72-year-old man). Microcracks were evaluated by en bloc basic fuchsin staining of specimens after testing. The length (L(i)) and the orientation with respect to the loading direction (beta(i)) of each crack were quantified by a video microscopy system. Three damage measures were quantified for each specimen: the number of linear microcracks (Cr #), the sum of the crack lengths (SigmaL(i)) accounting for the microcrack size alone, and the sum of the projected crack length [SigmaL(Pi) = SigmaL(i)cos(beta(i))] accounting for both crack size and orientation. Inclusion of the orientation parameter improved the coefficient of determination between damage accumulation and the degradation of the elastic modulus: the coefficient of determination of the sum of the projected crack length (R(2) = 0.239) was 60% greater than that of the sum the projected crack length (R(2) = 0.149) and 33% greater than that of the number of linear microcracks (R(2) = 0.180). We conclude that microcrack orientation is an essential physical variable in the relationship between damage accumulation and degradation of mechanical properties of cortical bone tissue.

Adult↗

Root resorption and its association with alterations in physical properties, mineral contents and resorption craters in human premolars following application of light and heavy controlled orthodontic forces.

OBJECTIVES: To study the effect of different orthodontic force levels on cementum, investigating from the point of view of its physical properties, alterations in the mineral components, type and location of the resorption craters and the exploration in 3D of space. DESIGN: In vivo human premolars subjected to heavy and light forces were employed for this study. After a period of movement they were analyzed for hardness and elasticity. Also, the mineral composition measuring Ca, P and F of the cementum root surface was investigated. A new method for volumetric analysis of resorption craters was developed. RESULTS: There were no significant differences for hardness and elastic modulus between the light and heavy force groups and no significant effects for different tooth positions. Significant inter-individual variation in the Ca, P and F concentrations was noted. Force-related data showed that mean volume of the resorption crater in light-force group was 3.49-fold greater than the control group, and the heavy-force group 11.59-fold more than control group. The heavy force group had 3.31-fold greater total resorption volume then light force group. Buccal cervical and lingual apical regions demonstrated significantly more resorption craters than the other regions. The 2D measurements were strongly correlated to 3D measurements. CONCLUSION: The application of light and heavy forces did not show any statistically significant differences in hardness and elastic modulus when compared with untreated teeth. The inconsistent increase or decrease of Ca, P and F contents between control and experimental teeth at sites of compression and tension were difficult to explain. There was more resorption by volume in the heavy force group as compared with the light group and controls. Our data also suggested that the high-pressure zones might be more susceptible to resorption after 28 days of force application.

Adolescent↗

Equilibrium and transition between single- and double-headed binding of kinesin as revealed by single-molecule mechanics.

Kinesin is a processive motor protein that "walks" on a microtubule toward its plus end. We reported previously that the distribution of unbinding force and elastic modulus for a single kinesin-microtubule complex was either unimodal or bimodal depending on the nucleotide states of the kinesin heads, hence showing that the kinesin may bind the microtubule either with one head or with both heads at once. Here, we found that the shape of the unbinding-force distribution depends both on the loading rate and on the manner of loading not only in the presence of AMP-PNP but also in the absence of nucleotides. Irrespective of the nucleotide state and the loading conditions examined here, the unbinding force obtained by loading directed toward the minus end of microtubule was 45% greater than that for plus end-directed loading. These results could be explained by a model in which equilibrium exists between single- and double-headed binding and the load (F) dependence of lifetime, tau(F), of each binding is expressed by tau(F) = tau(0)exp(-Fd/k(B)T), where tau(0) is the lifetime without external load and d a characteristic distance, both of which depend on single- or double-headed binding, k(B), the Boltzmann constant and T, the absolute temperature. The model analysis showed that the forward and backward rates of transition from single- to double-headed binding are 2 and 0.2/s for the AMP-PNP state, and 70 and 7/s for the nucleotide-free state. Moreover, in the presence of AMP-PNP, we detected the moment of transition from single- to double-headed binding through an abrupt increase in the elastic modulus and estimated the transition rate to be approximately 1/s, which is consistent with the model analysis.

Adenylyl Imidodiphosphate↗

Strain softening, yielding, and shear thinning in glassy colloidal suspensions.

A microscopic theory for the dependence on external strain, stress, and shear rate of the transient localization length, elastic modulus, alpha relaxation time, shear viscosity, and other dynamic properties of glassy colloidal suspensions is formulated and numerically applied. The approach is built on entropic barrier hopping as the elementary physical process. The concept of an ideal glass transition plays no role, and dynamical slowing down is a continuous, albeit precipitous, process with increasing colloid volume fraction. The relative roles of mechanically driven motion versus thermally activated barrier hopping and transport have been studied. Various scaling behaviors are found for the relaxation time and shear viscosity in both the controlled stress and shear rate mode of rheological experiments. Apparent power law and/or exponential dependences of the elastic modulus and perturbative and absolute yield stresses on colloid volume fraction are predicted. A nonmonotonic dependence of the absolute yield strain on volume fraction is also found. Qualitative and quantitative comparisons of calculations with experiments on high volume fraction glassy colloidal suspensions show encouraging agreement, and multiple testable predictions are made. The theory is generalizable to treat nonlinear rheological phenomena in other soft glassy complex fluids including depletion gels.

Journal Article↗

The neurofibrovascular bundle of the inferior oblique muscle as its ancillary origin.

PURPOSE: To establish that the neurofibrovascular bundle (NFVB) of the inferior oblique muscle (IO) has ligamentous qualities that enable it to function as an ancillary origin to the muscle. Also, to show that the NFVB does function as the ancillary origin for the IO muscle, particularly when recessing and anteriorly transposing its insertion. METHODS: Fresh (no formaldehyde preservative) cadaver and patient eyes were studied anatomically, histologically, and physiologically. Eighteen orbits were dissected to isolate the IO, the inferior rectus (IR), and the NFVB to demonstrate the linear course of the NFVB and its adjacent fibrous bands. The shape of the muscle was documented. Coronal sections of the two whole, intact orbits were analyzed histologically. Light and electron microscopic sections of an autopsy specimen and a surgical specimen were used to evaluate the capsule of the NFVB and the adjacent fibrous bands near the anterior portion of the NFVB and their attachment to the IR and IO muscle capsules. The elastic modulus was measured in six in situ and six in vitro cadaver NFVB specimens and in six in vivo surgical cases at the time of denervation of the NFVB. For additional comparison, four in vitro cadaver superior oblique tendons were similarly tested. Six eyes that developed recurrent IO overaction following an anterior transposition procedure were surgically explored to determine what structure was serving as its ancillary origin. RESULTS: Gross anatomic and microscopic studies showed a linear orientation of the NFVB with adjacent fibrous bands anteriorly joining the IO and IR muscle capsules. The surgical specimens of the anterior portion of the NFVB show about 50% nerve and 50% fibrocollagenous capsule with the collagen fibers aligned parallel to the NFVB. The elastic modulus was highest (stiffest) in surgical specimens of the NFVB and in situ cadaver NFVB, followed by in vitro cadaver NFVB and, finally, in vitro cadaver superior oblique tendon. In patients who have undergone anterior transposition surgery, the NFVB served as the ancillary origin of the IO. CONCLUSIONS: The name of the neurovascular bundle should be changed to the NFVB, since it has a prominent fibrocollagenous capsule and it is encased in fibrous tissue bands anteriorly. The NFVB has a linear course in the orbit from the apex to the IO muscle and is relatively stiff. The associated fibrous band extends posteriorly from the IO muscle capsule, encasing the nerve anteriorly and attaching 3 to 7 mm posteriorly into the capsule of the IR. The NFVB binds the mid posterior portion of the IO posteriorly. Its ligamentous qualities enable the NFVB to function as an ancillary origin for the IO.

Elastic Tissue↗