No description available.

Flow-mediated dilation (FMD) refers to the relaxation of vascular smooth muscle and the subsequent dilation of the vessel in response to increases in shear stress on the endothelial lining accompanying increases in blood flow. The phenomenon has been shown to be endothelium dependent and as such is used clinically and experimentally as an index of endothelial health. FMD can be assessed by imaging a conduit artery with ultrasound during a period of reactive hyperaemia, typically following a period of prior blood flow occlusion achieved by the inflation of a pneumatic cuff around the limb distal to the imaging site. Previous studies have shown that the health of the endothelium is predictive of the health of the cardiovascular system as a whole. This thesis set out to scrutinize the FMD test as a marker for endothelial health by testing the following five hypotheses: 1. A short burst of high shear is not adequate to elicit the FMD response. 2. Brachial artery dilation following 15 minutes of occlusion is a clearer indicator of endothelium dependent FMD than 5 minutes of occlusion with exercise. 3. Oscillating the post occlusion shear stress will decrease FMD compared to unidirectional shear). 4. Heavy dynamic hand grip exercise 6 minutes before an occlusion-only FMD protocol will result in an enhanced FMD response. 5. Long term bed-rest inactivity will attenuate the FMD response and an exercise program will preserve endothelial function. The experiments documented in Chapter 2 found that a 20-s shear stress stimulus following 15 min of forearm circulatory occlusion was not adequate to induce an FMD response compared to longer durations of shear and there was a progressive reduction in FMD when the magnitude of the initial peak shear was reduced by limiting the duration of prior occlusion. Also, the FMD response was correlated with the total shear to time of peak diameter for all shear durations and peaks that were studied while the same was not true of peak shear. In Chapter 3 it was revealed that an uncoupling of the shear-to-dilation ratio occurred when dynamic exercise was added to the FMD test as both 15 min of occlusion (15OC) and 5 min of occlusion with 1 min of exercise (1EXin5OC) yielded similar FMD responses, even though the shear stimulus was increased with the addition of exercise. Increased plasma nitrite during hyperaemia was observed only in the 15OC protocol, suggesting that the exercise in the 1EXin5OC protocol initiates dilatory mechanisms that are not as heavily reliant on the shear sensitive nitric oxide pathway . In Chapter 4 it was shown that 5 min of intense dynamic hand grip exercise (5EX) produced a greater dilation than either continuous (15OC) or intermittent (IO) shear following 15OC. Total shear to the time of peak diameter (AUCshear) and peak shear were both correlated to %dilation following 15OC; however this relationship was lost during 5EX and IO. The results of this study echoed the suggestion in Chapter 3 that there was an uncoupling of the intensity of the shear stimulus and the magnitude of vasodilatation when exercise was introduced, and adds that it may be in part due to the oscillatory nature of the shear profile during exercise. The acute effects of local exercise on the FMD response following 15OC were examined in Chapter 5. FMD in the brachial artery was blunted following dynamic hand grip exercise, even though the shear stimulus was greater during PostEX. Nitrite was significantly elevated in CON at 15s while PostEX nitrite was significantly elevated at 30s post cuff release but not different from CON at 15s. The results of this study suggested that prior exercise had a negative effect on FMD which may be related to exercise blunting post occlusion endothelial N ̇O production. Chapter 6 examined the effect of 56 days of head-down tilt bed rest (HDBR) and an exercise countermeasure on conduit artery FMD following release of distal limb ischemia and NMD following sublingual administration of 0.3 mg of nitroglycerin. HDBR without EX decreased the resting diameter of the popliteal artery while EX increased the diameter. HDBR had no effect on the resting diameter of the brachial artery. FMD was elevated in all groups for the brachial but only in the non-exercisers for the popliteal. When change in resting diameter was taken into account the preserved FMD in EX was removed. NMD was not altered by HDBR in any group. There was enhanced endothelial function relative to intrinsic dilatory capacity in both the brachial and popliteal arteries post HDBR. The results from Chapter 2 support hypothesis 1, showing that a 20 second burst of high shear stimulus was not adequate to elicit the FMD response during reactive hyperaemia. It is not clear whether hypothesis 2 was supported or not given that the results from Chapter 3 showed on the one hand that the %FMD did not change with the addition of exercise in the occlusion but on the other hand the shear to dilation ratio was altered. The finding, in Chapter 4, that FMD was not reduced when the hyperaemia was intermittent does not support hypothesis 3. In opposition to hypothesis 4, Chapter 5 showed that %FMD was reduced following bouts of heavy hand grip exercise; however the absolute magnitude of vessel diameter was similar in both post exercise and control tests. Finally, hypothesis 5 was also contradicted, with Chapter 6 showing that long term bed-rest enhanced rather than attenuated the FMD response in both arm and leg arteries, while an exercise countermeasure preserved pre-bed-rest FMD in the legs only. In addition to the specific hypotheses tested, there was evidence that acute exercise evoked dilatory mechanisms in the conduit arteries that were not shear/endothelium dependent given that the shear to dilation relationship was uncoupled during, following, and in occlusion protocols that include exercise. The precise mechanisms by which this is achieved are still unknown, but it may be partially due to the oscillatory nature of the elevated blood flow during exercise. I conclude that inference of cardiovascular health from endothelial function by the evaluation of %FMD should be approached with caution, especially in the event that physical activity is involved.

This research study examined the effect of corrosion of web reinforcement (stirrups) on the shear behaviour of slender reinforced concrete (RC) beams. The experimental program consisted of seventeen slender shear-critical RC beams: five uncorroded and twelve corroded beams. The test variables included: 1) corrosion level (0%, 7.5% and 15%); 2) type of stirrups (smooth and deformed); 3) stirrup diameter (D6, D12 and 10M); 4) stirrups spacing (100mm and 200mm); and 5) the presence of CFRP repair. The corroded beams had their stirrups subjected to corrosion using an accelerated corrosion technique and the mass loss in the stirrups was estimated based on Faraday’s law. All of the beams were monotonically tested to failure in three point bending. The corrosion cracks formed were parallel to the locations of stirrups as evidence of the corrosion damage in the corroded beams. The maximum decrease in the ultimate shear strength ranged from 11% to 14.4% for beams with high corrosion level of 15.6% mass loss. At a low corrosion level (4.39% mass loss), the shear strength of beams with smooth stirrups increased up to 35% due to the enhancement of shear friction at the concrete-corroded stirrups interface. The stiffness of the corroded beams was enhanced in comparison to the control beams. The ultimate deflection of the corroded beams was decreased up to 25% in comparison to the control beams. The CFRP repair increased the shear strength by 36% and improved the overall stiffness by 39% in comparison to the corroded unrepaired beams. All of the unrepaired beams failed in diagonal tension splitting, while the CFRP repaired corroded beams failed in diagonal tension splitting in addition to debonding of the FRP or concrete cover delamination. The actual corrosion mass loss results were in good correlation with Faraday’s law for the D12 and 10M stirrups. Poor correlation between actual and estimated mass loss was obtained for D6 smooth stirrups, possibly due to errors in the impressed corrosion. iv The analytical model used the modified compression field theory (MCFT) to predict the shear strength of uncorroded and corroded slender RC beams. In the corroded beams, two reduction factors were added to the MCFT model including the mass loss factor and the effective web width. Predictions based on the model revealed that the control beams gave a very good correlation with the ratio of experimental to predicted values that ranged from 0.94 to 1.02. On other hand, the ratio of experimental to predicted strength in the corroded beams ranged between1.06 to 1.4. The poor correlations were obtained for the beams with the D6 smooth stirrups. This study demonstrates that corrosion of web reinforcement can have a detrimental effect on the shear strength and ductility of slender shear-critical RC beams. The experimental results and analytical approach will be very useful for practicing engineers and researchers dealing with corrosion damage in slender RC members.

Flow-mediated dilation (FMD) refers to the relaxation of vascular smooth muscle and the subsequent dilation of the vessel in response to increases in shear stress on the endothelial lining accompanying increases in blood flow. The phenomenon has been shown to be endothelium dependent and as such is used clinically and experimentally as an index of endothelial health. FMD can be assessed by imaging a conduit artery with ultrasound during a period of reactive hyperaemia, typically following a period of prior blood flow occlusion achieved by the inflation of a pneumatic cuff around the limb distal to the imaging site. Previous studies have shown that the health of the endothelium is predictive of the health of the cardiovascular system as a whole. This thesis set out to scrutinize the FMD test as a marker for endothelial health by testing the following five hypotheses: 1. A short burst of high shear is not adequate to elicit the FMD response. 2. Brachial artery dilation following 15 minutes of occlusion is a clearer indicator of endothelium dependent FMD than 5 minutes of occlusion with exercise. 3. Oscillating the post occlusion shear stress will decrease FMD compared to unidirectional shear). 4. Heavy dynamic hand grip exercise 6 minutes before an occlusion-only FMD protocol will result in an enhanced FMD response. 5. Long term bed-rest inactivity will attenuate the FMD response and an exercise program will preserve endothelial function. The experiments documented in Chapter 2 found that a 20-s shear stress stimulus following 15 min of forearm circulatory occlusion was not adequate to induce an FMD response compared to longer durations of shear and there was a progressive reduction in FMD when the magnitude of the initial peak shear was reduced by limiting the duration of prior occlusion. Also, the FMD response was correlated with the total shear to time of peak diameter for all shear durations and peaks that were studied while the same was not true of peak shear. In Chapter 3 it was revealed that an uncoupling of the shear-to-dilation ratio occurred when dynamic exercise was added to the FMD test as both 15 min of occlusion (15OC) and 5 min of occlusion with 1 min of exercise (1EXin5OC) yielded similar FMD responses, even though the shear stimulus was increased with the addition of exercise. Increased plasma nitrite during hyperaemia was observed only in the 15OC protocol, suggesting that the exercise in the 1EXin5OC protocol initiates dilatory mechanisms that are not as heavily reliant on the shear sensitive nitric oxide pathway . In Chapter 4 it was shown that 5 min of intense dynamic hand grip exercise (5EX) produced a greater dilation than either continuous (15OC) or intermittent (IO) shear following 15OC. Total shear to the time of peak diameter (AUCshear) and peak shear were both correlated to %dilation following 15OC; however this relationship was lost during 5EX and IO. The results of this study echoed the suggestion in Chapter 3 that there was an uncoupling of the intensity of the shear stimulus and the magnitude of vasodilatation when exercise was introduced, and adds that it may be in part due to the oscillatory nature of the shear profile during exercise. The acute effects of local exercise on the FMD response following 15OC were examined in Chapter 5. FMD in the brachial artery was blunted following dynamic hand grip exercise, even though the shear stimulus was greater during PostEX. Nitrite was significantly elevated in CON at 15s while PostEX nitrite was significantly elevated at 30s post cuff release but not different from CON at 15s. The results of this study suggested that prior exercise had a negative effect on FMD which may be related to exercise blunting post occlusion endothelial N ̇O production. Chapter 6 examined the effect of 56 days of head-down tilt bed rest (HDBR) and an exercise countermeasure on conduit artery FMD following release of distal limb ischemia and NMD following sublingual administration of 0.3 mg of nitroglycerin. HDBR without EX decreased the resting diameter of the popliteal artery while EX increased the diameter. HDBR had no effect on the resting diameter of the brachial artery. FMD was elevated in all groups for the brachial but only in the non-exercisers for the popliteal. When change in resting diameter was taken into account the preserved FMD in EX was removed. NMD was not altered by HDBR in any group. There was enhanced endothelial function relative to intrinsic dilatory capacity in both the brachial and popliteal arteries post HDBR. The results from Chapter 2 support hypothesis 1, showing that a 20 second burst of high shear stimulus was not adequate to elicit the FMD response during reactive hyperaemia. It is not clear whether hypothesis 2 was supported or not given that the results from Chapter 3 showed on the one hand that the %FMD did not change with the addition of exercise in the occlusion but on the other hand the shear to dilation ratio was altered. The finding, in Chapter 4, that FMD was not reduced when the hyperaemia was intermittent does not support hypothesis 3. In opposition to hypothesis 4, Chapter 5 showed that %FMD was reduced following bouts of heavy hand grip exercise; however the absolute magnitude of vessel diameter was similar in both post exercise and control tests. Finally, hypothesis 5 was also contradicted, with Chapter 6 showing that long term bed-rest enhanced rather than attenuated the FMD response in both arm and leg arteries, while an exercise countermeasure preserved pre-bed-rest FMD in the legs only. In addition to the specific hypotheses tested, there was evidence that acute exercise evoked dilatory mechanisms in the conduit arteries that were not shear/endothelium dependent given that the shear to dilation relationship was uncoupled during, following, and in occlusion protocols that include exercise. The precise mechanisms by which this is achieved are still unknown, but it may be partially due to the oscillatory nature of the elevated blood flow during exercise. I conclude that inference of cardiovascular health from endothelial function by the evaluation of %FMD should be approached with caution, especially in the event that physical activity is involved.

Approximately 80% of the population will experience low-back pain within their lifetime. Significant research efforts have focused on compressive loading as an injury mechanism that could lead to low-back pain and injury. However, the influence of shear loading, and its relationship to vertebral tissue tolerances as well as modulating factors for these tolerances have not been studied as extensively. The primary objective of this thesis was to produce a series of investigations that begin to determine the roles of different modulating factors such as posture, compression, bone density, bone morphology, and repetitive load magnitude on measured vertebral joint shear failure tolerances. The thesis comprises four independent studies using in vitro mechanical testing, imaging modalities, and finite element modeling. Each of the in vitro studies within this thesis used a validated porcine cervical model as a surrogate for the human lumbar spine. The first study employed in vitro mechanical testing to investigate the combined roles of flexion/extension postural deviation and compressive load on the measured ultimate shear failure tolerances. Peripheral quantitative computed tomography scans of the pars interarticularis and measurements of vertebral bone morphology were used in the second investigation along with in vitro mechanical testing to identify the morphological characteristics that can be used to predict ultimate shear failure tolerances. The influence of sub-maximal shear load magnitude on the cumulative shear load and number of loading cycles sustained prior to failure were investigated with in vitro mechanical testing in the third study. Finally, a finite element model of the porcine C3-C4 functional spinal unit was used to investigate the plausibility of hypotheses, developed from previous research and the findings of the first investigation for this thesis, surrounding alterations in measured ultimate shear failure tolerances as a function of changes in facet interaction. Results from the first investigation showed that there was no statistically significant interaction between postural deviation and compressive force on ultimate shear failure tolerance. However, ultimate shear failure tolerance was reduced (compared to neutral) by 13.2% with flexed postures, and increased (compared to neutral) by 12.8% with extended postures. Each 15% increment (up to a maximum of 60% of predicted compressive failure tolerance) in compressive force was met with an average 11.1% increase in ultimate shear failure tolerance. It was hypothesized that alterations in flexion/extension posture and/or compressive force altered the location for the force centroid of facet contact. These changes in the location of facet contact were hypothesized to produce subsequent changes in the bending moment at the pars interarticularis that altered the measured ultimate shear failure tolerance. The three leading factors for calculating of measured ultimate shear failure tolerance were the pars interarticularis length for the cranial vertebra, the average facet angle measured in the transverse plane, and cortical bone area through the pars interarticularis. A bi-variate linear regression model that used the cranial vertebra’s pars interarticularis length and average facet angle as inputs was developed to nondestructively calculate ultimate shear failure tolerances of the porcine cervical spine. Longer pars interarticularis lengths and facets oriented closer to the sagittal plane were associated with higher measured ultimate shear failure tolerances. Fractures observed in this investigation were similar to those reported for studies performed with human specimens and also similar to reported spondylolitic fractures associated with shear loading in humans. This provided additional evidence that the porcine cervical spine is a suitable surrogate in vitro model for studying human lumbar spine mechanics. Altered sub-maximal shear load magnitude create a non-linear decrease in both the number of cycles and the cumulative shear load sustained prior to failure. These findings suggested that estimates of cumulative shear load should assign greater importance to higher instantaneous shear loads. This was due to an increased injury potential at higher instantaneous shear loads. Cumulative load sustained prior to failure was used to develop a tissue-based weighting factor equation that would apply nonlinearly increased weight to higher shear load magnitudes in estimates of cumulative shear load. A finite element model of the porcine C3-C4 functional spinal unit was created, and simulations were performed using similar boundary conditions as the comparable in vitro tests, to assess the plausibility of the moment arm hypothesis offered within the first investigation of this thesis. Moment arm length between the force centroid of facet contact and the location of peak stress within the pars interarticularis was increased for flexed postures and decreased for extended postures. Alterations in moment arm length were larger for postural deviation than compressive force, suggesting a secondary mechanism to explain the observed increase in shear failure tolerance with higher compressive loads from the first investigation. One such possibility was the increase in the number of contacting nodes with higher compressive forces. Alterations in moment arm length were able to explain 50% of the variance in measured ultimate shear failure tolerances from the first study. Thus, the finite element model was successful in demonstrating the plausibility of moment arm length between the force centroid of facet contact and the pars interarticularis as a modulator of measured ultimate shear failure tolerance. This thesis has developed the basis for understanding how failure of the vertebral joint exposed to shear loading can be modulated. In particular, this thesis has developed novel equations to predict the ultimate shear failure tolerance measured during in vitro testing, and to determine appropriate weighting factors for sub-maximal shear forces in calculations of cumulative shear load. Evidence presented within this thesis also provides support for the long-standing moment arm hypothesis for modulation of shear injury potential.

This thesis summarizes the results of an experimental investigation involving the testing of push-out specimens with channel shear connectors. The test program involved the testing of 78 push-out specimens and was aimed at the development of new equations for channel shear connectors embedded in solid concrete slabs and slabs with wide ribbed metal deck oriented parallel to the beam. <p>The test specimens were designed to study the effect of a number of parameters on the shear capacity of channel shear connectors. Six series of push-out specimens were tested in two phases. The primary difference between the two phases was the height of the channel connector. Other test parameters included the compressive strength of concrete, the length and the web thickness of the channel. <p>Three different types of failure mechanisms were observed. In specimens with higher strength concrete, failure was caused by the fracture of the channel near the fillet with the channel web acting like a cantilever beam. Crushing-splitting of concrete was the observed mode of failure in specimens with solid slabs when lower strength concrete was used. In most of the specimens with metal deck slabs, a concrete shear plane type of failure was observed. In the specimens involving this type of failure, the channel connector remained intact and the concrete contained within the flute in front of channel web sheared off along the interface. <p>The load carrying capacity of a channel connector increased almost linearly with the increase in channel length. On average, the increase was about 39% when the channel length was increased from 50 mm to 100 mm. There was a further increase of 24% when the channel length was increased from 100 mm to 150 mm. The influence of web thickness of channel connector was significant when the failure occurred due to channel web fracture but was minimal for a concrete crushing-splitting type of failure. <p>The specimens with solid concrete slabs carried higher load compared to those with metal deck slabs. The increase in load capacity was 33% for specimens with 150 mm long channels but only 12% for those with 50 mm long channel connectors. <p>This investigation resulted in the development of a new equation for predicting the shear strength of channel connectors embedded in solid concrete slabs. The proposed equation provides much better correlation to test results than those obtained using the current CSA equation. <p>The results of specimens with metal deck slabs were used to develop a new equation for predicting the shear capacity of channel connectors embedded in slabs with metal deck oriented parallel to the beam. The values predicted by the proposed equation were in good agreement with the observed test values.

Approximately 80% of pharmaceutical products and the ingredients required for their manufacture are in powder form. The solid dosage form (tablets and capsules) is manufactured by either dry-blending of fine powder ingredients or combining the ingredients in a wet granulation step, followed by drying. Arching, ratholing, caking, segregation and flooding are some of the commonly encountered flow problems in the handling of fine powders. These problems lead to losses worth thousands of dollars at production scale. Poor powder flowability is a consequence of the combined effects of many variables, including improper equipment design, particle size, size distribution, shape, moisture content and surface texture. In the present work, a systematic study has been performed to determine the relationship between the flowability of fine powders and their physical properties of mean size and size distribution, density and shape.<p> Flowability studies were done on six different powders: the NutraSweet® Brand sweetener (aspartame), Respitose ML001, Alpha-D-Lactose monohydrate, the pharmaceutical binder Methocel (R) F50 Premium Hydroxypropyl methylcellulose- HPMC, a placebo pharmaceutical granulate, and common pastry flour. Scanning electron microscopy (SEM) and stereomicroscopy were used for particle shape and size analysis. Particle size distribution was determined using the laser light scattering technique. Powder flowability was measured using shear strength, angle of repose, and tapped-to-bulk density measurements. A novel method of measuring the dynamic angle of repose using electrical capacitance tomography (ECT) was developed. <p> Analysis of the images from microscopy revealed that the particles of aspartame and HPMC powders were elongated, the particles of ML001, pastry flour and lactose monohydrate powders were irregular, and the particles of placebo granulate were nearly spherical. Particle size was found to be the most reliable indicator of powder flowability, with decreasing particle size corresponding to lower flowability; however other parameters such as particle elongation and irregularity, were also found to have an influence on powder flowability. Although HPMC and pastry flour had similar particle sizes, they exhibited differences in flowability. This can be explained by the greater irregularity of the flour particles. Particle irregularity may cause mechanical interlocking between the particles, thus reducing powder flowability. ECT was found to be a promising non-intrusive tool for the measurement of the dynamic angle of repose. Unlike other methods for the measurement of dynamic angle of repose, the results obtained from ECT were not influenced by the effect of end caps. The present technique could be used by pharmaceutical industries in process analytical technology (PAT) for the detection and elimination of potential flow problems early in the manufacturing process.

Fifteen splice specimens reinforced with plain steel bars, including three specimens instrumented with both steel and concrete strain gauges, were tested under monotonically applied four-point loading to develop a database of reliable bond test results and contribute to the development of a reliability based bond provision for plain steel bars to evaluate historical concrete structures. The maximum applied load for the specimens and their observed failure behaviour are reported. In addition to that, a strain compatibility analysis, average bond stress distribution, and flexural section analysis within the lap splice length of the instrumented specimens are also reported.<p> All of the specimens failed in bond within the lap splice length. The load capacity of two specimens reinforced with plain steel bars was 60% of the reported load resistance of specimens with identical geometry and reinforced with deformed bars. The CEB-FIP Model Code provisions for average bond stress of plain steel bars underestimated the maximum applied load recorded for the tested specimens by 16% on average. An empirically derived equation to predict the bond capacity of plain steel bars was determined to be proportional to both the splice length and the nominal bar diameter. <p> Observed cracks in the shear spans remained vertical and suggest the development of arch action within this region. The formation of a large crack at one end of the lap splice length and a review of the load versus deflection behaviour indicated a sudden bond failure of the specimens. Removal of concrete cover at the ends of the lap splice length following testing of the specimens showed evidence of slip of the lapped bars.<p> Instrumented splice specimens provided evidence of bond loss within the lap splice region. As-measured steel strains were higher than those measured for the surrounding concrete due to a loss of strain compatibility. The average bond stress distribution within the lap splice length became more uniform as the applied load approached the maximum applied load. The flexural analysis calculated based on concrete strains above the neutral axis and steel strain provided a reasonable estimate of specimen capacity.

Aortic valve disease (AVD) affects millions of people of all ages around the world. Current treatment for AVD consists of valvular replacement with a non-living prosthetic valve, which is incapable of growth, self-repair, or remodeling. While tissue engineering has great promise to develop a living heart valve alternative, success in animal models has been limited. This may be attributed to the fact that understanding of valvular cell biology has not kept pace with advances in biomaterial development. Aortic valve leaflets are exposed to a complex and dynamic mechanical environment unlike any in the vasculature, and it is likely that native endothelial and interstitial cells respond to mechanical forces differently from other vascular cells. The objective of this thesis was to compare valvular cell phenotype to vascular cell phenotype, and assess the influence of steady shear stress on valvular cell biology. This thesis demonstrates that valvular endothelial cells respond differently to shear than vascular endothelial cells, by aligning perpendicular to the direction of steady shear stress, and by the differential regulation of hundreds of genes in both static and fluid flow environments. Valvular interstitial cells expressed a combination of contractile and synthetic phenotypes not mimicked by vascular smooth muscle cells. Two three-dimensional leaflet models were developed to assess cellular interactions and the influences of steady laminar shear stress. Valvular co-culture models exhibited a physiological response profile, while interstitial cell-only constructs behaved more pathologically. Steady shear stress enhanced physiological functions of valvular co-cultures, but increased pathological response of interstitial cell-only constructs. These results showed that valvular cells, whether cultured separately or together, behaved distinctly different from vascular cells. It was also determined that shear stress alone cannot induce tissue remodeling to more resemble native valve leaflets. The leaflet models developed in this thesis can be used in future experiments to explore valvular cell biology, assess the progression of certain forms AVD, and develop targeted diagnostic and therapeutic strategies to hopefully eliminate the need for valvular replacement entirely.

This research investigates effects of tensile stresses in liquids. Areas of application include bearing lubrication and polymer processing, in which liquids may be subjected to hydrostatic tension or large shear stresses. A primary thrust of this research is the development of a criterion for liquid failure, or cavitation, based upon the general state of stress in the liquid. A variable pressure, rotating inner cylinder, Couette viscometer has been designed and used to test a hypothesized cavitation criterion. The criterion, that cavitation will occur when a principal normal stress in a liquid becomes more tensile than some critical stress, is supported by the results of experiments with the viscometer for a Newtonian liquid. Based upon experimental observation of cavitation, a model for cavitation inception from crevice stabilized gas nuclei, and gaseous, as opposed to vaporous, cavitation is hypothesized. The cavitation inception model is investigated through numerical simulation, primarily using the boundary element method. Only Newtonian liquids are modeled, and, for simulation purposes, the model is reduced to two dimensions and the limit of negligible inertia is considered. The model includes contact line dynamics. Mass transport of dissolved gas through the liquid and in or out of the gas nucleus is considered. The numerical simulations provide important information about the probable nature of cavitation nucleation sites as well as conditions for cavitation inception. The cavitation criterion predicts cavitation in simple shear, which has implications for rheological measurements. It can cause apparent shear thinning and thixotropy. Additionally, there is evidence suggesting a possible link between shear cavitation and extrusion defects such as sharkskin. A variable pressure capillary tube viscometer was designed and constructed to investigate a hypothesized relationship between shear cavitation and extrusion defects. Results indicate that despite the occasional coincidence of occurrence of cavitation and sharkskin defects, cavitation cannot explain the onset of extrusion defects. If nuclei are removed, then liquids can withstand a negative hydrostatic pressure. A falling body viscometer has been constructed and used to investigate the effect of negative pressures on viscosity. It is found that current pressure viscosity models can be accurately extrapolated to experimentally achievable negative pressures.