Collecting microlymphatics play a vital role in promoting lymph flow from the initial lymphatics in the interstitial spaces to the large transport lymph ducts. In most tissues, the primary mechanism for producing this flow is the spontaneous contractions of the lymphatic wall. Individual units, known as lymphangion, are separated by valves that help prevent backflow when the vessel contracts, thus promoting flow through the lymphatic network. Lymphatic contractile activity is inhibited by flow in isolated lymphatics, however there are virtually no in situ measurements of lymph flow in these vessels. Initially, a high speed imaging system was set up to image in situ preparations at 500 fps. These images were then manually processed to extract information regarding lymphocyte velocity (-4 to 10 mm/sec), vessel diameter (25 to 165 um), and particle location. Fluid modeling was performed to obtain reasonable estimates of wall shear stress (-8 to 17 dynes/cm2). One of the difficulties encountered was the time consuming methods of manual particle tracking. Using previously captured images, an image correlation method was developed to automate lymphatic flow measurements and to track wall movements as the vessel contracts. Using this method the standard error of prediction for velocity measurements was 0.4 mm/sec and for diameter measurements it was 7.0 µm. It was found that the actual physical quantity being measured through this approach is somewhere between the spatially averaged velocity and the maximum velocity of a Poiseuille flow model.

This study was conducted to determine threshold levels for Warner-Bratzler shear (WBS) force of the beef value cuts. USDA Choice and USDA Select M. biceps femoris, M. gluteus medius, M. infraspinatus, M. longissimus lumborum, M. rectus femoris, M. triceps brachii, and M. vastus lateralis steaks were evaluated for palatability characteristics and tenderness acceptability by a consumer panel (n = 205). Steaks also were evaluated by WBS analysis. The relationship between consumer tenderness-like ratings and WBS was investigated through regression analysis. Threshold WBS levels could not be determined due to the low correlation between consumer tenderness ratings and WBS. Within a muscle, percent tenderness acceptability was determined for each of the tenderness-like ratings. After analyzing the consumer ratings, tenderness acceptability, and WBS values, it was apparent that there may not be a single WBS threshold value suitable for all muscles. Research indicates that there may be muscle-specific WBS threshold levels; these values were not established from this research.

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Accelerated bridge construction methods are being progressively used to construct and replace bridges in North America. Unlike traditional bridge construction methods, accelerated bridge construction methods allow bridges to be built in a shortened period of time on the construction site. These methods reduce the road closure time and the traffic disruption that are associated with bridge construction. One of these methods is carried out by prefabricating the bridge elements offsite and then assembling them onsite in a time-efficient way to build the bridge. This construction method can be used to build steel-precast composite bridges, where steel plate girders are connected to full-depth precast concrete deck panels. For the expeditious construction of composite bridges, a proper shear connection detail is needed to develop composite action between the steel plate girders and the precast concrete deck panels. This research project investigated two types of shear connection that would accelerate the construction of steel-precast composite bridges. First, finite element analysis was used to study the behaviour of composite bridge girders with panel end connections. The girders were analyzed for their load-displacement behaviour, cross-sectional stress and strain profile, and connection force distributions. Secondly, experimental push tests were conducted to study the load-slip behaviour of bolted connections. The effects of steel-concrete interface condition, bolt diameter and bolt tension on the shear capacity of bolted connections were analyzed. Based on the finite element analysis results, it is concluded that the panel end connected girder exhibited strong composite action at service and ultimate load. The level of composite action decreased slightly when the panel end connection stiffness was reduced by a factor of ten. Based on the experimental results, it is concluded that the total shear capacity of the bolted connection is the sum of the friction resistance and the bolt dowel action resistance. The friction resistance of the connection depends on the interface condition and the bolt clamping force. An analytical model that can predict the ultimate shear capacity of bolted connections has been developed and recommended. The proposed model is shown to give reliable predictions of the experimental results. It should be noted that bolted connections exhibit good structural redundancy because the bolt fracture failures do not happen simultaneously.

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.

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.

During inflammation, leukocytes modulate α4β1(VLA-4) integrin avidity in order to rapidly stabilize nascent adhesive contacts to VCAM-1-expressing endothelial cells and resist detachment forces imparted by the flowing blood. Linkage to the actin cytoskeleton is critical for integrin function, yet the exact role of the actin cytoskeleton in leukocyte adhesion stabilization under conditions of fluid flow remains poorly understood. We modeled leukocyte (U937 cell, mouse lymphocyte and human monocyte) arrest and adhesion stabilization through the use of a parallel plate flow chamber and visualized cells by phase contrast or fluorescent confocal microscopy. Live cell imaging with Lifeact-transfected U937 cells revealed that mechanical forces imparted by fluid flow induced formation of upstream tension-bearing anchors attached to the VCAM-1-coated surface. Scanning electron microscopy confirmed that flow-induced mechanical force culminates in the formation of structures that anchor monocyte adhesion. These structures are critical for adhesion stabilization, since disruption of actin polymerization dramatically inhibited VLA-4-dependent resistance to detachment, but did not affect VLA-4 expression, affinity modulation, and clustering or constitutive linkage to F-actin. Transfection of dominant-negative constructs and inhibition of kinase function or expression revealed key signaling steps required for upstream actin polymerization and adhesion stabilization. Rap1 was shown to be critical for resistance to flow-induced detachment and accumulated in its GTP form at the sites of anchor formation. A key mediator of force-induced Rac activation and actin polymerization is PI3K. Live cell imaging revealed accumulation of PIP3 within tension-bearing anchors and blockade of PI3K or deficiency of PI3Kγ isoform reproduced the adhesion defect produced by inhibition of actin polymerization. Thus, rapid signaling and structural adaptations enable leukocytes to stabilize adhesion and resist detachment forces; these included activation of Rap1, phosphoinositide 3-kinase γ-isoform and Rac, but not Cdc42.

Inverse spectral techniques are developed in this dissertation for recovering the shear modulus and residual stress of soft tissues. Shear modulus is one of several quantities for measuring the stiffness of a material, and hence estimating it accurately is an important factor in tissue characterization. Residual stress is a stress that can exist in a body in the absence of externally applied loads, and beneficial for biological growth and remodeling. It is a challenge to recover the two quantities in soft tissues both theoretically and experimentally. The current inverse spectral techniques recover the two unknowns invasively, and are theoretically based on a novel use of the intravascular ultrasound technology (IVUS) by obtaining several natural frequencies of the vessel wall material. As the IVUS is interrogating inside the artery, it produces small amplitude, high frequency time harmonic vibrations superimposed on the quasistatic deformation of the blood pressure pre-stressed and residually stressed artery. The arterial wall is idealized as a nonlinear isotropic cylindrical hyperelastic body for computational convenience. A boundary value problem is formulated for the response of the arterial wall within a specific class of quasistatic deformations reflexive of the response due to imposed blood pressures. Subsequently, a boundary value problem is developed from intravascular ultrasound interrogation generating small amplitude, high frequency time harmonic vibrations superimposed on the quasistatic finite deformations via an asymptotic construction of the solutions. This leads to a system of second order ordinary Sturm-Liouville problems (SLP) with the natural eigenfrequencies from IVUS implementation as eigenvalues of the SLP. They are then employed to reconstruct the shear modulus and residual stress in a nonlinear approach by inverse spectral techniques. The shear modulus is recovered by a multidimensional secant method (MSM). The MSM avoids computing the Jacobian matrix of the equations and is shown to be convenient for manipulation. Residual stress is recovered via an optimization approach (OA) instead of the traditional equation-solving method. The OA increases the robustness of the algorithms by overdetermination of the problem, and comprehensive tests are performed to guarantee the accuracy of the solution. Numerical examples are displayed to show the viability of these techniques.

The lymphatic system plays an important role in fluid and protein balance within the interstitial spaces. Its dysfunction could result in a number of debilitating diseases, namely lymphedema. Lymphatic vessels utilize both intrinsic and extrinsic mechanisms to pump lymph. Intrinsic pumping involves the active contraction of vessels, a phenomenon that is regulated in part by nitric oxide (NO) produced by lymphatic endothelial cells (LECs). NO production by arterial endothelial cells has been shown to be sensitive to both shear stress and stretch. Therefore, because of the unique mechanical environment of the LECs, we hypothesize that mechanical forces play an important role in regulation of the lymphatic pumping. Parallel-plate flow chambers and indenter-based cyclic stretch devices were constructed and used to apply mechanical loads to LECs. In addition, high-throughput micro-scale channels were developed and tested for shear experiments to address the need to increase the productivity and high- resolution imaging. Twenty-four hours treatment of LECs with different shear stress conditions showed a shear-dependent elevation in NO production. Moreover, 2.5 folds increase in cumulative NO was observed for stretched cells compared to the unstretched cells over six hours period. In conclusion, the upregulation observed in NO production under mechanical stimuli suggest new regulatory mechanisms that can be pharmaceutically targeted. These results provide an unprecedented insight into lymphatic pumping mechanism.