Este trabalho teve como objetivo o desenvolvimento de um método de reticulação mais homogênea no pericárdio bovino (PB), utilizado na confecção de válvulas cardíacas, seguindo um tratamento seqüencial e não seqüencial com concentrações crescentes de glutaraldeído (GA), no intervalo entre 0,0010/0e 0,5%, com tempos de reação entre 5 e 90min, e temperatura entre 5 e 45&#176C. Os resultados de temperatura de encolhimento (Is) mostraram que a reticulação do pericárdio bovino é heterogênea, principalmente para baixas concentrações de glutaraldeído (0,001%). Entretanto esta heterogeneidade é menos perceptível para concentrações superiores de GA, principalmente para o tratamento seqüencial, sugerindo uma melhor qualidade de reação de reticulação. Em todos os tratamentos realizados, os melhores resultados foram obtidos para o tratamento seqüencial a 45&#176C, para 90 minutos de reação e 0,10/0 de GA, onde os valores de Ts (&#8773 90&#176C) foram muito próximos daqueles para concentrações superiores de GA (0,5%). Encontrou-se também, nestas condições, os menores valores de hidrólise enzimática (colagenase = 3,80/0e tripsina =1,90/0 ). Estes comportamentos devem estar associados a uma maior concentração de GA monomérico e, portanto, maior eficácia das soluções de GA na promoção das ligações de reticulação e também à exposição de um maior número de sítios de reação da matriz de PB. Os resultados dos ensaios de hidrólise enzimática com colagenase e tripsina, confirmaram a maior eficácia do tratamento seqüencial, principalmente sabendo-se que: a) a reação de PB com GA envolve amino grupos de lisina; b) a tripsina só age sobre ligações peptídicas envolvendo lisina com &#949-amino grupo livre. A partir disto, é possível prever que um maior número de &#949-amino grupos estão bloqueados, não permitindo a ação enzimática nestes locais, mostrando que o material encontra se mais reticulado. Testes mecânicos realizados nos materiais tratados nas condições citadas acima mostraram valores dentro da faixa aceitável para a confecção de válvulas cardíacas para o tratamento seqüencial. / The object of this work was the development of a new procedure for homogeneous crosslinking of bovine pericardium (BP), to improve its properties when used for cardiac valves confection. A sequential treatment with increasing concentrations of glutaraldehyde (GA), from 0.0010/0to 0.5%, was used in temperatures ranging from 5°C to 45°C and reaction times ranging from 5 to 90 min. Shrinkage temperature (Ts) results showed that non-sequential and sequential treatments produced heterogeneous crosslinking of bovine pericardium, mainly for lower concentrations of glutaraldehyde (0.001%). The heterogeneity is less perceptible for greater concentrations of glutaraldehyde, specially in the sequential treatment, suggesting better quality of crosslinking reaction. Best results were obtained for the sequential treatment at 45&#176C, for 90 min and 0.1% of glutaraldehyde, with Ts values (&#8773 90&#176C) very similar to those found for higher glutaraldehyde concentration (0.5%). In these conditions, the smaller values of enzymatic hydrolysis were obtained (collagenase = 3.80/0and tripsin = 1.90/0).This behavior, at 45&#176C, may be associated to the presence of higher monomeric glutaraldehyde concentration, more efficient in the crosslinking promotion, and to the exposition of a great number of reaction sites in bovine pericardium matrix. The results of enzymatic hidrolysis with collagenase and tripsin, confirmed that sequential treatment is more efficient, specially knowing that: a) the GA for BP reaction involved e-amino groups of lisin: b) the tripsin alone act over peptides bonds involving lisin with free e-amino groups. Then, it is possible to predict that a great number of e-amino groups were blocked, not permitting enzimatic action, showing that the materials were more crosslinked. Mechanical tests for materials treated as above demonstrated that for sequential treatment the values are within the acceptable range for cardiac valves construction.

Para algumas categorias de produtos, insumos como embalagem podem ter um peso significativo na composição do custo do produto final. No caso de vários produtos embalados em frascos plásticos este é um cenário comum que tem como conseqüência uma exigência de aumento de desempenho das máquinas sopradoras que produzem tais frascos. Com o objetivo de cumprir tal exigência, este trabalho realiza uma análise do sistema hidráulico de uma sopradora para redução do tempo de posicionamento nos principais movimentos executados por alguns dispositivos vitais, os quais possuem comandos eletrohidráulicos de controle de posição e velocidade constituídos de válvulas hidráulicas de controle de vazão, válvulas direcionais proporcionais e atuadores lineares. A forma desta análise é conduzida inicialmente através da modelagem dos componentes hidráulicos envolvidos nos movimentos destes dispositivos e, posteriormente, de um ensaio através do registro das grandezas físicas de interesse como pressões e velocidades de posicionamento utilizando como bancada de testes uma sopradora existente. O desempenho atual do equipamento em questão, registrado através do ensaio, pode ser então comparado com os resultados obtidos na modelagem para uma análise final com o objetivo de tornar a sopradora mais rápida e produtiva além de validar o modelo estabelecido para a realização de projetos futuros. / Many times, for some products classes, inputs as packaging may have an expressive weight in the final product cost structure. In the case of products packaged into plastic containers, this is an usual scenario that has as result, the increase of performance requirements of the blow mold machines that produce such containers. A point to be studied in the blow mold machines to fulfill such requirement is an analysis of its hydraulic system in a way to reduce the positioning time in the most significant movements performed by its main devices. Such devices have electro-hydraulic position and speed controls composed by flow control and proportional valves and linear actuators. So, it is presented in this work the description of blow mold machine, modeling of hydraulic components involved with the main equipment\'s movements and an experience to record physical values as pressures and positioning speeds using an existent blow mold machine as testing bench. The tested registers can be confronted against the results obtained in the modeling analysis as a target to make the blow mold machine more productive besides of validate the model to the future projects.

According to statistics from the American Heart Association, valvular heart disease directly leads to about 20,000 deaths a year and contributes to an additional 50,000. While significant advancements have been made in the treatment options available for valvular heart disease, complications still occur. For this reason, the future of valvular heart disease treatment lies in understanding the physiology of the heart valve, and subsequently bioengineering a valve from one's own tissue to mimic native valve processes. Valvular interstitial cells (VICs) are the major cell type populating the valve matrix. In the inactive fibroblast-like state, these cells are responsible for extracellular matrix deposition. Activated VICs display a myofibroblast morphology characterized by the expression of alpha smooth muscle actin and are responsible for valve maintenance and repair. The activation of VICs is hypothesized to be stimulated by mechanical tension, which, in the presence of TGF-â1 allows the complete differentiation of VICs from the inactive to the active form. However, little is known about the potential for reversal or dedifferentiation from the active to inactive state. The purpose of this study was to determine whether substrate stiffness, the mechanical tension hypothesized to initiate VIC activation, modulates alpha smooth muscle actin expression in the presence and absence of TGF-â1. To mimic conditions found in vivo, substrates were varied from physiologic to pathological stiffness levels. Results showed that when freshly isolated VICs are cultured in the presence of serum, alpha smooth muscle actin expression increased on all substrate stiffnesses. In TGF-â-free medium, there was an apparent increase on all stiffness levels as well, but a statistical significance between groups could not be demonstrated. Immunoblots used to detect TGF-â1 showed that intracellular TGF-â1 was upregulated in VICs cultured in the presence of serum compared to those cultured in TGF-â-free medium. Taken together, these results suggest that freshly isolated VICs become activated, as indicated by increased expression of alpha smooth muscle actin, on all substrate levels in the presence of serum. It also appears as though unknown factors which are present in serum are required to stimulate significant autocrine production of TGF-â1. To determine whether VICs which had transitioned to the myofibroblast phenotype had the ability to dedifferentiate, cells were cultured on polystyrene for a minimum of four days then replated on substrates of varying stiffness. Analysis of alpha smooth muscle actin expression showed that, in the presence of serum and when replated on all of substrates used, alpha smooth muscle actin expression decreased, suggesting that these cells indeed have the potential to dedifferentiate. A change in cell morphology to a more rounded phenotype as well as the loss of visible stress fibers further supported this possibility. These studies represent a unique approach to studying phenotypic differentiation of valvular interstitial cells. Using acrylamide substrates of varying stiffness, and growth factor free media, we have shown that by altering substrate stiffness, changes in alpha smooth muscle actin expression consistent with differentiation and dedifferentiation can be induced. This potential for dedifferentiation suggests that in engineering the next generation of bioartificial valves, it may be possible to use the patient's own cells to seed the manufactured scaffold. This would avoid complications associated with current treatments, including immune rejections.

Thesis. 1975. M.S.--Massachusetts Institute of Technology. Dept. of Mechanical Engineering. / Includes bibliographical references. / M.S.

Thesis. 1976. Ph.D.--Massachusetts Institute of Technology. Dept. of Aeronautics and Astronautics. / Microfiche copy available in Archives and Aero. / Vita. / Includes bibliographical references. / Ph.D.

Cardiovascular disease is the number one reason for emergency room visits in the United States. Understanding the different pathologies of the cardiovascular system is crucial when trying to prescribe proper treatment or intervention. In order best understand these issues proper computer simulations would be necessary. Due to the fact that every patient is different. Being able to analysis and properly simulate each patients data individually to better understanding their specific case is necessary for patient specific interventions. In order to achieve such requirement we propose a new method of mesh generation to better map patient specific geometries. This new framework takes a set of points in a 3D space and generates a 2D NURBS mesh. Insuring a smooth and accurate representation of the patient specific geometry will allow for more specific incite to possible medical issues that may arise. This NURBS based mesh can be then used to run either finite element analysis, computational fluid dynamics, or even fluid solid interactions. Running these patient-specific valve simulations using isogementric modeling is what will allow us to have patient specific treatments and intervention.

Proper aeration of cavitating hydraulic equipment can greatly reduce cavitation intensity, noise, and damage. This thesis quantifies the benefit, in terms of damage and noise, from aerating six inch butterfly valve. The incipient damage level of cavitation was obtained for both aerated and non -ae ra ted conditions. The level is defined as one pit per square inch of a soft aluminum test specimen per one minute of operation. A description of the cavitation pits that occurred plus where they appeared is presented. A graph showing the aerated and non-aerated limits of incipient damage is given along with a table showing the percent reduct ion of damage from aeration. A graph and table are also given depicting the reduction in noise. The proper location of aeration ports to allow natural aeration is outlined .

A Computational Fluid Dynamics (CFD) simulation of the Bishop Rotary Valve (BRV) engine is developed. The simulation used an existing commercial CFD code, CFX 4.3, with a number of new routines written to allow it to simulate the conditions and motions involved in an internal combustion engine. The code is extensively validated using results from other researchers, and several new validations are performed to directly validate the code for simulating internal combustion engine flows. Firstly, tumble vortex breakdown during the compression stroke of a square piston model engine is modelled. The results of the simulation are validated against published high quality experimental data. Both two- and three-dimensional models are tested, using the k-e and Reynolds stress turbulence models. The Reynolds stress turbulence model simulations successfully predicted the tumble break down process during the compression stroke. A simple three-dimensional Large Eddy Simulation model is also presented. The numerical simulation is then applied to the BRV engine. An in-cylinder flow field not previously described is discovered, created by the unique combustion chamber shape of the BRV engine. The flow field is not adequately described by the traditional descriptions of engine flows, being squish, swirl and tumble. The new flow structure is named 'dual cross tumble', and is characterised by two counter-rotating vortices in the cross tumble plane on either side of the inlet air jet. Analysis of the dual tumble structure indicates that it is most beneficial in high bore to stroke ratio engines. This flow structure has been predicted or visualised by a small number of previous researchers, however no published research has recognised its significance or potential benefits. The validated code is then used to predict the effect of modifying the valve cross sectional area, the effect of the inlet manifold wave, the effect of heat transfer from the inlet manifold walls, the effect of bore to stroke ratio, and the effect of engine speed. This work presents a numerical simulation of a new rotary valve engine technology. This opens up a whole new area of engine aerodynamics research as no detailed examination of the flows in a rotary valve engine have been presented previously. In the process, it discovers a new compression stroke turbulence generation mechanism, 'dual cross tumble', which offers the potential of performance levels not possible using poppet valve engines.

Posterior urethral valves cause bladder outflow obstruction and damage to the developing fetal kidney. Posterior urethral valves affect 1 in 8000 new-born males. A third of these children develop end stage renal failure by adolescence, despite valve ablation in the early post-natal period, implying that majority of the damage to the kidneys occurs in utero. How does this damage occur, and should we intervene in utero? The answers to these questions require further research, and are the basis to this thesis. This thesis focused on the effect bladder outflow obstruction has on morphology and apoptosis in the fetal kidney in a fetal lamb model. It also looked at the effect of bladder outflow obstruction on fetal stress hormone levels. Bladder outflow obstruction was created surgically in fetal lambs at day 70 of gestation, and fetal kidneys were analysed at day 2, 5, 10, 20 and 30 after creation of obstruction. Controls undergoing sham surgery were used for comparison. Four aspects were investigated: - effects of bladder outflow obstruction on renal histology effects of bladder outflow obstruction on expression of pro-apoptosis gene Bax and anti-apoptosis gene Bcl-X - effects of bladder outflow obstruction on renal regional apoptosis effects of bladder outflow obstruction on serum fetal ACTH and cortisol levels. Bladder outflow obstruction resulted in sequential morphological change in the fetal kidney over time. By 2 days post-obstruction, cystic change was noted. In addition, patchy attenuation of the nephrogenic blastema was evident by 5 days post-obstruction, with more confluent blastemal attenuation as well as generalized renal architectural disorganization by 10 days post-obstruction. By 20 and 30 days post-obstruction, cystic renal dysplasia had developed. Bladder outflow obstruction resulted in an increase in the ratio of renal expression of pro-apoptosis gene Bax to anti-apoptosis gene Bcl-X. Regional apoptosis counts showed increased tubular apoptosis compared to controls at 2 days post-obstruction, and increased blastemal apoptosis compared to controls at 5 days post-obstruction. By 10 days post-obstruction, blastemal apoptosis counts were reduced compared to controls. There were no significant differences in fetal serum ACTH and cortisol levels between fetal lambs with bladder outflow obstruction and controls. In conclusion, the results of this thesis outline the spectrum of morphological change in the fetal kidney over 30 days of bladder outflow obstruction. They show that detectable changes in morphology occur within two days of bladder outflow obstruction. Likewise, detectable changes in gene expression occur within 2 days of bladder outflow obstruction. The increased ratio of expression of Bax to Bcl-X suggests a swing towards increased apoptosis in response to bladder outflow obstruction. Further research is required to ascertain if these changes are reversible. However, the early onset of these changes as shown in this thesis suggests that any fetal intervention to protect the fetal kidney from the effects of bladder outflow obstruction may need to be instituted very early in gestation

A Tissue Engineering (TE) approach to heart valve replacement has the aim of producing an implant that is identical to healthy tissue in morphology, function and immune recognition. The aim is to harvest tissue from a patient, establish cells in culture from this tissue and then use these cells to grow a new tissue in a desired shape for the implant. The scaffold material that supports the growth of cells into a desired shape may be composed of a biodegradable polymer that degrades over time, so that the final engineered implant is composed entirely of living tissue. The approach used at Swinburne University was to induce the desired mechanical and functional properties of tissue and is to be developed in an environment subjected to flow stresses that mimicked the haemodynamic forces that natural tissue experiences. The full attainment of natural biomechanical and morphological properties of a TE structure has not as yet been demonstrated. In this thesis a review of Tissue Engineering of Heart Valves (TEHVs) is presented followed by an assessment of biocompatible materials currently used for TEHVs. The thrust of the work was the design and development of a Bioreactor (BR) system, capable of simulating the corresponding haemodynamic forces in vitro so that long-term cultivation of TEHVs and/or other structures can be mimicked. A full description of the developed BR and the verification of its functionality under various physiological conditions using Laser Doppler Anemometry (LDA) are given. An analysis of the fluid flow and shear stress forces in and around a heart valve scaffold is also provided. Finally, preliminary results related to a fabricated aortic TEHV-scaffold and the developed cell culture systems are presented and discussed. Attempts to establish viable cell lines from ovine cardiac tissue are also reported.