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R W Lee

Publications and source records attributed to R W Lee.

At least 73 records · Page 4Linked to original sources

Sequence-specific 1H-NMR assignments for the aromatic region of several biologically active, monomeric insulins including native human insulin.

The aromatic region of the 1H-FT-NMR spectrum of the biologically fully-potent, monomeric human insulin mutant, B9 Ser----Asp, B27 Thr----Glu has been investigated in D2O. At 1 to 5 mM concentrations, this mutant insulin is monomeric above pH 7.5. Coupling and amino acid classification of all aromatic signals is established via a combination of homonuclear one- and two-dimensional methods, including COSY, multiple quantum filters, selective spin decoupling and pH titrations. By comparisons with other insulin mutants and with chemically modified native insulins, all resonances in the aromatic region are given sequence-specific assignments without any reliance on the various crystal structures reported for insulin. These comparisons also give the sequence-specific assignments of most of the aromatic resonances of the mutant insulins B16 Tyr----Glu, B27 Thr----Glu and B25 Phe----Asp and the chemically modified species des-(B23-B30) insulin and monoiodo-Tyr A14 insulin. Chemical dispersion of the assigned resonances, ring current perturbations and comparisons at high pH have made possible the assignment of the aromatic resonances of human insulin, and these studies indicate that the major structural features of the human insulin monomer (including those critical to biological function) are also present in the monomeric mutant.

Amino Acid Sequence↗

Analysis of the substrate specificity of tyrosylprotein sulfotransferase using synthetic peptides.

Tyrosylprotein sulfotransferase (TPST) catalyzes the sulfation of proteins at tyrosine residues. We have analyzed the substrate specificity of TPST from bovine adrenal medulla with a novel assay, using synthetic peptides as substrates. The peptides were modeled after the known, or putative, tyrosine sulfation sites of the cholecystokinin precursor, chromogranin B (secretogranin I) and vitronectin, as well as the tyrosine phosphorylation sites of alpha-tubulin and pp60src. Varying the sequence of these peptides, we found that (i) the apparent Km of peptides with multiple tyrosine sulfation sites decreased exponentially with the number of sites; (ii) acidic amino acids were the major determinant for tyrosine sulfation, acidic amino acids adjacent to the tyrosine being more important than distant ones; (iii) a carboxyl terminally located tyrosine residue may be sulfated. Moreover, TPST catalyzed the sulfation of a peptide corresponding to the tyrosine autophosphorylation site of pp60v-src (Tyr-416) but not of a peptide corresponding to the non-autophosphorylation site of pp60c-src (Tyr-527). These results experimentally define structural determinants for the substrate specificity of TPST and show that this enzyme and certain autophosphorylating tyrosine kinases have overlapping substrate specificities in vitro.

Adrenal Medulla↗

1H NMR spectrum of the native human insulin monomer. Evidence for conformational differences between the monomer and aggregated forms.

The effects of high dilution on the 1H Fourier transform NMR spectrum of native human insulin at pH* 8.0 and 9.3 have been examined at 500 MHz resolution. The dependence of the spectrum on concentration and comparison with the spectrum of a biologically highly potent monomeric insulin mutant (SerB9----Asp) establish that at 36 microM (pH* 9.3) or 18 microM (pH* 8) and no added buffer or salts, human insulin is monomeric. Under these conditions of dilution, ionic strength, and pH*, human insulin and the SerB9----Asp mutant exhibit nearly identical 1H NMR spectra. At higher concentrations (i.e. greater than 36 microM to 0.91 mM), native human insulin dimerizes, and this aggregation causes a change in insulin conformation. Although there are many changes in the spectrum, the TyrB26 ring H3,5 proton signals located at 6.63 ppm and the methyl signal located at 0.105 ppm (characteristics of monomeric insulin) are particularly distinct signatures of the conformation change that accompanies dimerization. Magnetization transfer experiments show that the 0.105 ppm methyl signal shifts downfield to a new position at 0.45 ppm. We conclude that the 0.105 ppm methyl signal is due to a conformation in which a Leu methyl group is centered over and in van der Waals contact with the ring of an aromatic side chain. Dimerization causes a conformation change that alters this interaction, thereby causing the downfield shift. Nuclear Overhauser studies indicate that the methyl group involved is located within a cluster of aromatic side chains and that the closest ring-methyl group interaction is with the ring of PheB24.

Aspartic Acid↗

In vivo flow 31P FT-NMR spectroscopy of a nematode parasite.

31P NMR spectroscopy of a parasitic nematode. Steinernema carpocapsae, is described. In vivo spectra were generated from nematode suspensions continuously circulating through the spectrometer. By flowing the organism, saturation effects were avoided and short interpulse delays significantly reduced spectral generation time. To maximize sensitivity, 90 degrees pulses were employed. Changes in energetic status in response to oxygen availability were easily and rapidly monitored in circulating nematodes.

Animals↗

A review of prehospital care litigation in a large metropolitan EMS system.

A retrospective review of all claims brought against a large, metropolitan emergency medical services (EMS) system related to paramedic-patient encounters during the 12-year period from 1976 through 1987 was undertaken to review and describe the incidence and types of malpractice claims. During this period, EMS units responded to approximately 2 million calls and transported more than 1 million patients. Sixty claims occurred during the incidence study period (1976 through 1985). The overall litigation rate was one lawsuit per 27,371 paramedic-patient encounters and one lawsuit per 17,995 patient transports. While the total number of runs and transports did not change significantly during the study period, the data indicate a trend of increasing claims filed against the prehospital care provider. To date, 26 cases (38%) have been settled with the majority involving either no monetary awards or nominal out-of-court settlements.

Adolescent↗

Spectroscopic signatures of the T to R conformational transition in the insulin hexamer.

The cobalt(II)-substituted human insulin hexamer has been shown to undergo the phenol-induced T6 to R6 structural transition in solution. The accompanying octahedral to tetrahedral change in ligand field geometry of the cobalt ions results in dramatic changes in the visible region of the electronic spectrum and thus represents a useful spectroscopic method for studying the T to R transition. Changes in the Co2+ spectral envelope show that the aqua ligand associated with each tetrahedral Co2+ center can be replaced by SCN-, CN-, OCN-, N3-, Cl-, and NO2-. 19F NMR experiments show that the binding of m-trifluorocresol stabilizes the R6 state of zinc insulin. The chemical shift and line broadening of the CF3 singlet, which occur due to binding, provide a useful probe of the T6 to R6 transition. Due to the appearance of new resonances in the aromatic region, the 500 MHz 1H NMR spectrum of the phenol-induced R6 hexamer is readily distinguishable from that of the T6 form. 1H NMR studies show that phenol induces the T6 to R6 transition, both in the (GlnB13)6(Zn2+)2 hexamer and in the metal-free GlnB13 species; we conclude that metal binding is not a prerequisite for formation of the R state in this mutant.

Insulin↗

Mechanism for decrease in cardiac output with atrial natriuretic peptide in dogs.

To examine the mechanism by which atrial natriuretic peptide (ANP) decreases cardiac output, we studied changes in the heart, peripheral circulation, and blood flow distribution in eight dogs. ANP was given as a bolus (3.0 micrograms/kg) followed by an infusion of 0.3 microgram.kg-1.min-1. ANP did not change heart rate, total peripheral vascular resistance, and the first derivative of left ventricular pressure but decreased mean aortic pressure from 91 +/- 4 to 76 +/- 3 mmHg (P less than 0.001) and cardiac output from 153 +/- 15 to 130 +/- 9 ml.kg-1.min-1 (P less than 0.02). Right atrial pressure and left ventricular end-diastolic pressure also decreased. Mean circulatory filling pressure decreased from 7.1 +/- 0.3 to 6.0 +/- 0.3 mmHg (P less than 0.001), but venous compliance and unstressed vascular volume did not change. Resistance to venous return increased from 0.056 +/- 0.008 to 0.063 +/- 0.010 mmHg.ml-1.kg.min (P less than 0.05). Arterial compliance increased from 0.060 +/- 0.003 to 0.072 +/- 0.004 ml.mmHg-1.kg-1 (P less than 0.02). Total blood volume and central blood volume decreased from 82.2 +/- 3.1 to 76.2 +/- 4.6 and from 19.8 +/- 0.8 to 17.6 +/- 0.6 ml/kg (P less than 0.02), respectively. Blood flow increased to the kidneys. We conclude that ANP decreases cardiac output by decreasing total blood volume. This results in a lower operating pressure and volume in the venous capacitance system with no significant venodilating effects. Cardiac factors and a redistribution of flow to the splanchnic organs are not important mechanisms to explain the decrease in cardiac output with ANP.

Animals↗

Atrial natriuretic peptide reverses angiotensin-induced venoconstriction in dogs.

To determine whether atrial natriuretic peptide (ANP) can reverse angiotensin (ANG II)-induced venoconstriction, ANP was infused (0.3 micrograms.kg-1.min-1) in the presence of ANG II-induced hypertension in six ganglion-blocked dogs. ANG II was initially administered to increase mean arterial blood pressure (MAP) 50% above control. ANG II did not change heart rate or left ventricular rate of pressure development (LV dP/dt) but increased total peripheral vascular resistance (TPVR) and left ventricular end-diastolic pressure (LVEDP). Mean circulatory filling pressure (MCFP) increased, whereas cardiac output and venous compliance decreased. Unstressed vascular volume did not change, but central blood volume increased. ANP infusion during ANG II-induced hypertension resulted in a decrease in MAP, but TPVR did not change. There were no changes in heart rate or LV dP/dt. ANP decreased cardiac output further. LVEDP returned to base line with ANP. ANP also decreased MCFP and normalized venous compliance. There was no significant change in total blood volume, but central blood volume decreased. In summary, ANP can reverse the venoconstriction but not the arterial vasoconstriction produced by ANG II. The decrease in MAP was due to a decrease in cardiac output that resulted from venodilatation and aggravation of the preload-afterload mismatch produced by ANG II alone. Because TPVR did not change when MAP fell, we conclude that the interaction between ANG II and ANP occurs primarily in the venous circulation.

Angiotensin II↗

Captopril restores hemodynamic responsiveness to atrial natriuretic peptide in rats with heart failure.

Atrial natriuretic peptide levels are elevated in heart failure. However, the hemodynamic responses to exogenous atrial natriuretic peptide infusion in heart failure are blunted. To determine if captopril can restore hemodynamic responsiveness to atrial natriuretic peptide infusion in rats with heart failure, studies were performed in a rat model of heart failure after coronary artery ligation. Rats with heart failure received either captopril (2 g/l drinking water) or placebo for 4 weeks and then were treated with an infusion of atrial natriuretic peptide (0.3 microgram/kg/min). Captopril treatment alone improved hemodynamics. Left ventricular end-diastolic pressure, mean aortic pressure, and mean circulatory filling pressure decreased from 22 +/- 2 to 14 +/- 1, from 106 +/- 4 to 76 +/- 3, and from 10.5 +/- 0.6 to 8.8 +/- 0.4 mm Hg, respectively. Heart rate, right atrial pressure, and hematocrit were unchanged. Total blood volume decreased from 66.0 +/- 1.0 to 60.0 +/- 1.0 ml/kg; venous compliance increased from 2.1 +/- 0.1 to 2.7 +/- 0.1 ml/kg/mm Hg. Atrial natriuretic peptide alone had minimal hemodynamic effects on rats with heart failure. There was no change in right atrial pressure, mean aortic pressure, left ventricular end-diastolic pressure, mean circulatory filling pressure, and total blood volume. However, atrial natriuretic peptide infusion increased venous compliance from 2.1 +/- 0.1 to 2.4 +/- 0.1 ml/kg/mm Hg. Heart rate and hematocrit increased from 323 +/- 5 to 359 +/- 8 beats/min and from 48 +/- 1% to 51 +/- 1%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

1H Fourier transform NMR studies of insulin: coordination of Ca2+ to the Glu(B13) site drives hexamer assembly and induces a conformation change.

1H Fourier transform NMR investigations of metal ion binding to insulin in 2H2O were undertaken as a function of pH* to determine the effects of metal ion coordination to the Glu(B13) site on the assembly and structure of the insulin hexamer. The C-2 histidyl regions of the 1H NMR spectra of insulin species containing respectively one Ca2+ and two Zn2+/hexamer and three Cd2+/hexamer have been assigned. Both the Cd2+ derivative (In)6(Cd2+)2Cd2+, where two of the Cd2+ ions are coordinated to the His(B10) sites and the remaining Cd2+ ion is coordinated to the Glu(B13) site [Sudmeier, J.L., Bell, S.J., Storm, M. C., & Dunn, M.F. (1981) Science (Washington, D.C.) 212, 560], and the Zn2+-Ca2+ derivative (In)6-(Zn2+)2Ca2+, where the two Zn2+ ions are coordinated to the His(B10) sites and Ca2+ ion is coordinated to the Glu(B13) site, give spectra in which the C-2 proton resonances of His(B10) are shifted upfield relative to metal-free insulin. Spectra of insulin solutions (3-20 mg/mL) containing a ratio of In:Zn2+ = 6:2 in the pH* region from 8.6 to 10 were found to contain signals both from metal-free insulin species and from the 2Zn-insulin hexamer, (In)6(Zn2+)2. The addition of either Ca2+ (in the ratio In:Zn2+:Ca2+ = 6:2:1) or 40 mM NaSCN was found to provide sufficient additional thermodynamic drive to bring about the nearly complete assembly of insulin hexamers. Cd2+ in the ratio In:Cd2+ = 6:3 also drives hexamer assembly to completion. We postulate that the additional thermodynamic drive provide by Ca2+ and CD2+ is due to coordination of these metal ions to the Glu(B13) carboxylates of the hexamer. At high pH*, this coordination neutralizes the repulsive Coulombic interactions between the six Glu(B13) carboxylates and forms metal ion "cross-links" across the dimer-dimer interfaces. Comparison of the aromatic regions of the 1H NMR spectra for (In)6(Zn2+)2 with (In)6(Zn2+)2Ca2+, (In)6(Cd2+)2Cd2+, and (In)6(Cd2+)2Ca2+ indicates that binding of either Ca2+ or Cd2+ to the Glu(B13) site induces a conformation change that perturbs the environments of the side chains of several of the aromatic residues in the insulin structure. Since these residues lie on the monomer-monomer and dimer-dimer subunit interfaces, we conclude that the conformation change includes small changes in the subunit interfaces that alter the microenvironments of the aromatic rings.

Animals↗

Mutagenic activities of selected nitrofluoranthene derivatives in Salmonella typhimurium strains TA98, TA98NR and TA98/1,8-DNP6.

The mutagenic activities of novel nitrofluoranthene derivatives in Salmonella strains TA98, TA98NR and TA98/1,8-DNP6 (with and without S9 addition) are given. These derivatives were produced from the reactions of fluoranthene (FL) and its directly mutagenic 2- and 3-nitro derivatives with covalent dinitrogen pentoxide (N2O5) in CCl4 solution at ambient temperature. The influence of the addition of a nitro group on the observed activity of the resulting di- and tri-nitrofluoranthenes is discussed.

Fluorenes↗

Cocaine and cardiovascular function in dogs: effects on heart and peripheral circulation.

The effects of cocaine on the heart and peripheral circulation were examined in seven mongrel dogs. Hemodynamic variables, in addition to data on ventricular relaxation, mean circulatory filling pressure and arterial compliance, were measured during an intravenous infusion (0.5 mg/kg per min) of cocaine. Holter monitor recordings (6 h) and coronary arteriograms were also obtained. Cocaine increased (p less than 0.01) mean aortic pressure from 72 +/- 5 to 92 +/- 5, left ventricular systolic pressure from 102 +/- 3 to 121 +/- 5, left ventricular end-diastolic pressure from 4.9 +/- 1.3 to 8.2 +/- 1.4 and mean circulatory filling pressure from 7.9 +/- 0.4 to 10.9 +/- 0.5 mm Hg. Cardiac index and stroke volume decreased (p less than 0.01) from 166 +/- 17 to 125 +/- 8 ml/min per kg and from 44 +/- 4 to 29 +/- 3 ml, respectively. Ejection fraction decreased (p less than 0.01) from 61 +/- 1 to 49 +/- 3%. Heart rate, first derivative of left ventricular pressure (dP/dt) and right atrial, mean pulmonary artery and pulmonary artery wedge pressures did not change. The result was a 58% increase in systemic vascular resistance and a 32% decrease in arterial compliance. The pressure gradient for venous return did not change, but resistance to venous return increased 42%. Cocaine prolonged (p less than 0.05) the half-time of left ventricular isovolumic relaxation from 13.4 +/- 0.8 to 16.4 +/- 0.8 ms and the time constant of left ventricular isovolumic relaxation from 19.3 +/- 1.2 to 23.6 +/- 1.1 ms.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Observations and comments on the mechanism of epoxidation of alkenes by manganese(III) porphyrins with hypochlorite.

The kinetics of olefin epoxidation in a methylene chloride/water biphase containing a phase-transfer agent with hypochlorite as oxygen transfer reagent and manganese(III) tetraphenylporphyrin catalysts has been reinvestigated. The results do not support the accumulation of an intermediate composed of an alkene and a hypervalent metaloxo porphyrin. Second-order rate constants for oxygen transfer from hypochlorite to the manganese porphyrin, comproprotionation of the hypervalent manganese-oxo porphyrin with manganese(III) porphyrin, and olefin epoxidation by the hypervalent manganese-oxo porphyrin were obtained from experiments in a wet organic monophase.

Alkenes↗

Use of acetylcholine to measure total vascular pressure-volume relationship in dogs.

To define total vascular capacitance, we used acetylcholine to arrest the heart and measured mean circulatory filling pressure (MCFP) during controlled hemorrhage and volume loading in 12 splenectomized dogs after ganglion blockade with hexamethonium. We also examined the gross pathological and histological changes in the lungs. Controlled hemorrhage (n = 12) of 5 and 10 ml/kg decreased MCFP from 6.8 +/- 0.1 to 4.9 +/- 0.3 and 3.6 +/- 0.2 mmHg, respectively. Volume loading of 5 (n = 8) and 10 ml/kg (n = 4) increased MCFP to 9.3 +/- 0.2 and 12.1 +/- 0.1 mmHg, respectively. At MCFPs below 5 mmHg, the pressure (P)-volume (V) relationship was not linear [(P = P0ekV, where k is slope of ln (MCFP) vs. V, k = 0.061, R2 = 0.998]. At MCFPs between 5 and 12 mmHg, the pressure-volume relationship was linear (slope = 0.479 mmHg.ml-1.kg-1, R2 = 0.992) and total vascular compliance was 2.09 ml.mmHg-1.kg-1. There were no changes in heart rate, cardiac output, right atrial, pulmonary artery, and pulmonary artery wedge pressures when values at base line were compared with those measured 15 min after each arrest. There were no changes in arterial gas measurements or acid-base balance, and there was no evidence of atelectasis or interstitial or intra-alveolar edema. We conclude that the total body pressure-volume relationship in the presence of ganglion blockade had a nonlinear configuration. The use of acetylcholine to arrest the heart, four times with hexamethonium in reflex-blocked animals, did not result in changes in hemodynamics or pulmonary function.

Acetylcholine↗

Effects of thyroid state on venous compliance and left ventricular performance in rats.

The cardiovascular system of hypothyroid, normal, and hyperthyroid rats was studied by evaluation of the peripheral venous circulation and left ventricular (LV) systolic and diastolic performance in rats. Cardiac index (CI) and CI during a volume load were measured in open-chest rats. When compared with control, hypothyroid rats showed a decrease in heart rate, aortic pressure, LV systolic pressure, first derivative for LV pressure (LV dP/dt), CI, and CI during a volume load. LV pressure-volume relation was shifted to the right, muscle stiffness was unchanged, and LV relaxation was prolonged. There was a decrease in mean circulatory filling pressure (MCFP) to 6.3 +/- 0.2 from 7.6 +/- 0.2 mmHg in control rats. This was associated with an 11% decrease in unstressed vascular volume and 12% decrease in total blood volume but no change in venous compliance. In hyperthyroid rats there was an increase in heart rate, LV systolic pressure, LV dP/dt, CI, and CI during a volume load. LV chamber stiffness was increased, but muscle stiffness and LV relaxation were unchanged. There was an increase in MCFP to 9.5 +/- 0.3 mmHg and a decrease in venous compliance to 2.65 +/- 0.12 compared with 3.20 +/- 0.09 ml.mmHg-1.kg-1 in control rats. Unstressed vascular volume and total blood volume were unchanged. In conclusion, hyperthyroid rats have augmented LV systolic function and altered diastolic function which, combined with changes in the venous circulation, result in increased venous return and thus cardiac output. In hypothyroid rats both LV systolic and diastolic function are altered. When combined with changes of the venous circulation the changes result in a decrease in cardiac output.

Algorithms↗

Cardiac and peripheral circulatory responses to angiotension and vasopressin in dogs.

To determine the cardiac and peripheral circulatory responses to changes in afterload with angiotension and vasopressin, we increased mean aortic pressure 25% and 50% above control in splenectomized and ganglion-blocked dogs. We compared these responses to similar mechanical increases in aortic pressure produced by partial balloon occlusion of the descending aorta. With 25% or 50% increases in aortic pressure, angiotensin, vasopressin, and balloon inflation produced no changes in heart rate, right atrial, and mean pulmonary artery pressures. At 25% increase in aortic pressure, cardiac output was maintained with angiotensin and balloon occlusion but decreased with vasopressin. At 50% increase in aortic pressure, cardiac output was maintained with only balloon occlusion and decreased with both angiotensin and vasopressin. Whenever cardiac output fell, central blood volume did not increase as after-load increased. These changes in preload can be explained by alterations in the venous circulation. Vasopressin did not alter venous compliance or unstressed vascular volume but increased resistance to venous return. Angiotensin also increased resistance to venous return but decreased venous compliance and did not change unstressed vascular volume. Balloon occlusion had no effects on these parameters. We conclude that: (a) angiotensin caused significant venoconstriction resulting in maintenance of cardiac output at 25% but not 50% increase in aortic pressure; (b) vasopressin increased the resistance to venous return without venoconstriction; this resulted in a fall in cardiac output even with a 25% increase in aortic pressure; and (c) the effects of the agents on the venous circulation were independent of the mechanical effects of a pressure increase in the arterial circulation.

Angiotensin II↗

Effect of sequential implanting with zeranol on steer lifetime performance.

Three trials involving 513 exotic crossbred steers were conducted to determine the effect of zeranol implanting in the suckling and growing phases on subsequent feedlot performance and carcass characteristics. Treatments were 1) unimplanted control, 0000; 2) implanted twice in the finishing phase, 00II; 3) implanted in the growing phase and twice in the finishing phase, 0III; 4) implanted in the suckling phase and twice in the finishing phase, I0II; 5) implanted in the suckling and growing phases with a single implant in the finishing phase, III0; and 6) implanted in the suckling and growing phases and twice in the finishing phase, IIII. Implanting in the suckling period did not significantly affect preweaning gain. Implanting in the growing period produced a treatment x trial interaction (P less than .05), but zeranol increased gains by an average of 8.4% over the three trials. Growing period gain was not influenced by implanting during suckling. Implanting twice during the finishing period increased gain (P less than .05) over unimplanted and III0 steers. Finishing gain was not influenced by previous suckling and(or) growing implant treatment. Lifetime ADG of steers was increased (P less than .05) by all implant treatments compared with unimplanted controls. Zeranol tended (P = .14) to improve feed conversion in the finishing phase. All implant treatments increased hot carcass weight (P less than .05), and all but III0 reduced fat deposition, as indicated by lower quality grade (P less than .05). Other carcass characteristics were not significantly affected by treatment. These trials demonstrated that implanting in the suckling and(or) growing phases of production did not reduce performance in the finishing phase.

Animals↗

The mechanical stability of various noncemented tibial components.

Four different porous-coated tibial prosthetic implants were tested for their mechanical stability following implantation into paired cadaver tibias: Porous Coated Anatomic (PCA), Miller-Galante, Whiteside, and Anatomic Modular Knee (AMK). Following implantation the test sample was loaded eccentrically over the medial tibial plateau at 40 cycles per minute for 300,000 cycles, using an MTS machine. This represents the number of steps taken by the average person in a six- to 12-month period. Load varied sinusoidally from 5 to 115 kg. Subsidence and lift-off of the tibial plate from its bony bed was recorded for each implant, using linear variable differential transformers. The greatest degree of mechanical stability was observed with the AMK design, which is secured to the bone bed using four peripherally placed 6.5-mm cancellous screws. No motion in excess of 100 micron was observed. The central-stemmed Whiteside design and the cortical screw fixated Miller-Galante designs provided slightly less stability, each demonstrating approximately 200 micron of lift-off on the unweighted side. The PCA design exhibited the greatest amount of micromotion with subsidence and lift-off displacements of 500 micron (0.5 mm).

Biomechanical Phenomena↗