This thesis highlights a comprehensive research for the cell nucleation, growth and coarsening mechanisms during plastic foaming processes. Enforced environmental regulations have forced the plastic foam industry to adopt alternative blowing agents (e.g., carbon dioxide, nitrogen, argon and helium). Nevertheless, the low solubilities and high diffusivities of these viable alternatives have made the production of foamed plastics to be non-trivial. Since the controls of the cell nucleation, growth and coarsening phenomena, and ultimately the cellular morphology, involve delicate thermodynamic, kinetic, and rheological mechanisms, the production of plastics foams with customized cell morphology have been challenging. In light of this, the aforementioned phenomena were investigated through a series of theoretical studies, computer simulations, and experimental investigations. Firstly, the effects of processing conditions on the cell nucleation phenomena were studied through the in-situ visualization of various batch foaming experiments. Most importantly, these investigations have led to the identification of a new heterogeneous nucleation mechanism to explain the inorganic fillers-enhanced nucleation dynamics. Secondly, a simulation scheme to precisely simulate the bubble growth behaviors, a modified heterogeneous nucleation theory to estimate the cell nucleation rate, and an integrated model to simultaneously simulate cell nucleation and growth processes were developed. Consequently, through the simulations of the cell nucleation, growth, and coarsening dynamics, this research has advanced the understanding of the underlying sciences that govern these different physical phenomena during plastic foaming. Furthermore, the impacts of various commonly adopted approximations or assumptions were studied. The end results have provided useful guidelines to conduct computer simulation on plastic foaming processes. Finally, an experimental research on foaming with blowing agent blends served as a case example to demonstrate how the elucidation of the mechanisms of various foaming phenomena would aid in the development of novel processing strategies to enhance the control of cellular structures in plastic foams.

This thesis highlights a comprehensive research for the cell nucleation, growth and coarsening mechanisms during plastic foaming processes. Enforced environmental regulations have forced the plastic foam industry to adopt alternative blowing agents (e.g., carbon dioxide, nitrogen, argon and helium). Nevertheless, the low solubilities and high diffusivities of these viable alternatives have made the production of foamed plastics to be non-trivial. Since the controls of the cell nucleation, growth and coarsening phenomena, and ultimately the cellular morphology, involve delicate thermodynamic, kinetic, and rheological mechanisms, the production of plastics foams with customized cell morphology have been challenging. In light of this, the aforementioned phenomena were investigated through a series of theoretical studies, computer simulations, and experimental investigations. Firstly, the effects of processing conditions on the cell nucleation phenomena were studied through the in-situ visualization of various batch foaming experiments. Most importantly, these investigations have led to the identification of a new heterogeneous nucleation mechanism to explain the inorganic fillers-enhanced nucleation dynamics. Secondly, a simulation scheme to precisely simulate the bubble growth behaviors, a modified heterogeneous nucleation theory to estimate the cell nucleation rate, and an integrated model to simultaneously simulate cell nucleation and growth processes were developed. Consequently, through the simulations of the cell nucleation, growth, and coarsening dynamics, this research has advanced the understanding of the underlying sciences that govern these different physical phenomena during plastic foaming. Furthermore, the impacts of various commonly adopted approximations or assumptions were studied. The end results have provided useful guidelines to conduct computer simulation on plastic foaming processes. Finally, an experimental research on foaming with blowing agent blends served as a case example to demonstrate how the elucidation of the mechanisms of various foaming phenomena would aid in the development of novel processing strategies to enhance the control of cellular structures in plastic foams.

Thesis (Ph.D.)--University of Tennessee Health Science Center, 2009. / Title from title page screen (viewed on February 4, 2010). Research advisor: John M. Cunningham, M.D. Document formatted into pages (xiv, 115 p. : ill.). Vita. Abstract. Includes bibliographical references (p. 89-103).

To develop or engineer artificial tissues in tissue engineering, a detailed knowledge of the in vitro culture process including cell and tissue growth inside porous scaffolds, nutrient transport, and the shear stress acting on the cells is of great advantage. It has been shown that obtaining such information by means of experimental techniques is exceedingly difficult and in some ways impossible. Mathematical modelling and computational simulation based on computational fluid dynamics (CFD) has emerged recently to be a promising tool to characterize the culture process. However, due to the complicated structure of porous scaffolds, modelling and simulation of the in vitro cell culture process has been shown to be a challenging task. Furthermore, due to the cell growth during the culture process, the geometry of the scaffold structure is not constant, but changes with time, which makes the task even more challenging. To overcome these challenges, the research presented in this thesis is aimed at developing a CFD-based mathematical model and multi-time scale computational framework for culturing cell-scaffold constructs placed in perfusion bioreactors. To predict the three-dimensional (3D) cell growth in a porous tissue scaffold placed inside a perfusion bioreactor, a model is developed based on the continuity and momentum equations, a convection-diffusion equation and a suitable cell growth equation, which characterize the fluid flow, nutrient transport and cell growth, respectively. To solve these equations in a coupled fashion, an in-house FORTRAN code is developed based on the multiple relaxation time lattice Boltzmann method (MRT LBM), where the D3Q19 MRT LBM and D3Q7 MRT LBM models have been used for the fluid flow and mass transfer simulation, respectively. In the model cell growth equation, the transport of nutrients, i.e. oxygen and glucose, as well as the shear stress induced on the cells are considered for predicting the cell growth rate. In the developed model and computational framework, the influence of the dynamic strand surface on the local flow and nutrient concentration has been addressed by using a two-way coupling between the cell growth and local flow field and nutrient concentration, where a control-volume method within the LBM framework is applied. The simulation results provide quantification of the biomechanical environment, i.e. fluid velocity, shear stress and nutrient concentration inside the bioreactor. The final simulation applied the cell growth model to the culture of a three-zone tissue scaffold where the scaffold strands were initially seeded with cells. The prediction for the 3D cell growth rate indicates that the increase in the cell volume fraction is much higher in the front region of the scaffold due to the higher nutrient supply. The higher cell growth in the front zone reduces the permeability of the porous scaffold and significantly reduces the nutrient supply to the middle and rear regions of the scaffold, which in turn limit the cell growth in those regions. However, implementation of a bi-directional perfusion approach, which reverses the flow direction for second half of the culture period, is shown to significantly improve the nutrient transport inside the scaffold and increase the cell growth in the rear zone of the scaffold. The results in this study also demonstrate that the developed mathematical model and computational framework are capable of realistically simulating the 3D cell growth over extended culture periods. As such, they represent a promising tool for enhancing the growth of tissues in perfusion bioreactors.

<p>Cell division and growth are complex processes fundamental to all living organisms. In the budding yeast, <italic>Saccharomyces cerevisiae</italic>, these two processes are known to be coordinated with one another as a cell's mass must roughly double before division. Moreover, cell-cycle progression is dependent on cell size with smaller cells at birth generally taking more time in the cell cycle. This dependence is a signature of size control. Systems biology is an emerging field that emphasizes connections or dependencies between biological entities and processes over the characteristics of individual entities. Statistical models provide a quantitative framework for describing and analyzing these dependencies. In this dissertation, I take a statistical systems biology approach to study cell division and growth and the dependencies within and between these two processes, drawing on observations from richly informative microscope images and time-lapse movies. I review the current state of knowledge on these processes, highlighting key results and open questions from the biological literature. I then discuss my development of machine learning and statistical approaches to extract cell-cycle information from microscope images and to better characterize the cell-cycle progression of populations of cells. In addition, I analyze single cells to uncover correlation in cell-cycle progression, evaluate potential models of dependence between growth and division, and revisit classical assertions about budding yeast size control. This dissertation presents a unique perspective and approach towards comprehensive characterization of the coordination between growth and division.</p> / Dissertation

In any population of cells, individual cells grow for some period of time and then divide into two or more parts, called daughters. To describe this process mathematically, we need to specify functions describing the growth rate, size at division, and proportions into which each cell divides. In this thesis, it is assumed that the growth rate of a cell can be determined precisely from its size, but that both its size at division and the proportions into which it divides may be described stochastically, by probability density functions whose parameters are dependent on cell size and age (or birth-size). Special cases are also considered where all cells with the same birth-size divide at the same size, or where all cells divide exactly in half. We consider a population of cells growing and dividing steadily, such that the total cell population is increasing, but the proportion of cells in any size class remains constant. In Chapter 1, equations are derived which need to be solved in order to deduce the shape of the steady size distribution (or steady size/age or size/birth-size distributions) from any given growth rate and probability distributions describing the division rate and division proportions. In the general case, a Fredholm-type integral equation is obtained, but if the probability of cell division depends on cell size only (i.e. not age or birth-size), and all cells divide into equal-sized daughters, then we obtain a functional differential equation. In two special cases, the resulting equations simplify considerably, and it is these cases which are explored further in this thesis. The first is where the probability of a cell dividing in any instant of time is a constant, independent of cell age or size. In Chapter 2, the functional differential equation resulting when cells divide into equal-sized daughters is solved for the special case where the growth rate is constant, and in an appendix the case where the growth rate is described by a power law is dealt with. The second case which simplifies is where the time-independent part of the growth rate of a cell is proportional to cell size. This case is particularly important, as it is a good first-order approximation to the real cell growth rate in some structured tissues, and in some bacteria. The special case in which this leads to a functional differential equation is discussed in Chapter 3, and the integral equation arising in the general case is dealt with in Chapter 4. Finally, the conditions under which the integral operator in Chapter 4 will be both square-integrable and non-factorable are discussed in Chapter 5. It is shown that if these conditions are satisfied then a unique, stable, steady size distribution will exist.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 3 uppsatser.

Thesis (Ph. D.)--University of Nevada, Reno, 1998. / Includes bibliographical references. Online version available on the World Wide Web.

A fototerapia com laser em baixa intensidade tem sido utilizada na odontologia em várias patologias bucais para o controle de dor e cicatrização. O objetivo do estudo foi comparar o efeito da fototerapia no crescimento de fibroblastos de polpa dentária humana usando irradiações com energia total aplicada de uma vez ou fracionada. Após a determinação da metodologia, a linhagem celular FP5 (1 x 103 células por poço) cresceu em placas de cultivo de 96 poços (1 para cada grupo experimental) em déficit nutricional (meio suplementado com 5 % de SFB). A irradiação laser foi realizada com laser de diodo InGaAlP (comprimento de onda 685 nm, 40mW, área do feixe 0,0028cm2) usando a técnica pontual, no modo contínuo e em contato. As energias totais foram aplicadas em irradiações únicas de 0,12 J (G1), 0,24J (G2), 0,36 J (G3). Essas energias totais foram fracionadas em múltiplas irradiações de 0,12 feitas com intervalos de 6 horas: duas para G4 e três para G5. Grupos não irradiados de células cultivadas em déficit nutricional (5 % SFB, G6) e em condições nutricionais regulares (10 % SFB, G7) foram usadas como controles negativo e positivo respectivamente. O número de células foi indiretamente obtido pela mensuração da atividade celular mitocondrial 24 horas após a primeira irradiação. Os dados em quadruplicata foram comparados pelo teste ANOVA complementado pelo teste de Tukey (p <= 0,05). Houve diferença significante entre os grupos. O controle positivo (G7) apresentou número de células significantemente maior quando comparado ao controle negativo (G6). Esse número foi similar aos dos grupos submetidos a irradiações múltiplas (G4 e G5). Os grupos irradiados uma única vez (G1 a G3) apresentaram número de células significantemente menores que aqueles do controle positivo e dos grupos com múltiplas irradiações. Com base na metodologia empregada concluiu-se que o fracionamento das energias de irradiação potencializa o efeito bioestimulador da fototerapia com laser em baixa intensidade no crescimento de fibroblastos de polpa dentária humana. / Phototherapy with low intensity lasers has been used in dentistry in several oral pathologies for pain and healing control. The aim of this study was to compare the effect of phototherapy on human dental pulp fibroblasts growth using irradiations with whole energy delivered at once or fractioned. After the determination of the methodology, the FP5 cell line (1x 103 cells per well) was grown in 96 wells-microtritation plates (one for each experimental group) in nutritional deficit (medium supplemented with 5% fetal bovine serum-fbs). Laser irradiation was carried out with an InGaAlP diode laser (?-685nm, 40 mW, spot size 0.028 cm2) using the punctual technique, at continuous mode and in contact. The whole energies were delivered in single irradiations of 0.12J (G1), 0.24J (G2), 0.36J (G3). These whole energies were fractioned in multiple irradiations of 0.12J done with 6h-intervals: two for G4 and three for G5. Non-irradiated groups of cell cultured in nutritional deficit (5% fbs; G6) and in nutritional regular condition (10 % fbs; G7) were used as negative and positive controls, respectively. The number of cells was indirectly assessed by measuring the cell mitochondrial activity 24 hours after the first irradiation. The data from four replicates were compared by the ANOVA complemented by the Tukey\'s test (p <= 0.05). There were significant differences amongst the groups. The positive control (G7) presented significantly higher number of cells when compared to the negative control (G6). This number was similar to those of multiple irradiation groups (G4 and G5). The single irradiated groups (G1 to G3) presented cell numbers significantly smaller than those of positive control and multiple irradiated groups. Under the conditions of this study it was concluded that multiple irradiations of fractioned energies improve the biostimulatory effect of the phototherapy with low intensity laser on the growth of dental pulp fibroblasts.

The multidisciplinary field of microfluidics has shown great promise for research at the interface of biology, chemistry, engineering, and physics. Laminar flow, versatile fabrication, and small length scales have made microfluidics especially well-suited for single-cell characterization. In particular, the evaluation of single-cell growth rates is of fundamental interest for studying the cell cycle and the effects of environmental factors, such as drugs, on cellular growth. This work presents aspects in the development of a microfluidic cell impedance sensor for measuring the volumetric growth rate of single cells and covers its application in the investigation of a new discovery relating to multidrug resistance in S. cerevisiae. While there are many avenues for the utilization and interpretation of growth rates, this application focused on the quantitative assessment of biological fitness—an important parameter in population genetics and mathematical biology. Through a combination of growth measurements and optics, this work concludes a novel case of bet-hedging in yeast, as well as the first ever case of bet-hedging in eukaryotic multidrug resistance.