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http://hdl.handle.net/2005/5
2016-04-14T02:45:16ZModeling Lysis Dynamcis Of Pore Forming Toxins And Determination Of Mechanical Properties Of Soft Materials
http://hdl.handle.net/2005/2466
Title: Modeling Lysis Dynamcis Of Pore Forming Toxins And Determination Of Mechanical Properties Of Soft Materials
Authors: Vaidyanathan, M S
Abstract: Pore forming toxins are known for their ability to efficiently form transmembrane pores which eventually leads to cell lysis. PFTs have potential applications in devel-oping novel drug and gene delivery strategies. Although structural aspects of many pore forming toxins have been studied, very little is known about the dynamics and subsequent rupture mechanisms. In the first part of the thesis, a combined experimental and modeling study to understand the lytic action of Cytolysin A (ClyA) toxins on red blood cells (RBCs) has been presented. Lysis experiments are carried out on a 1% suspension of RBCs for different initial toxin concentrations ranging from 100 – 500 ng/ml and the extent of lysis is monitored spectrophotometrically. Using a mean field approach, we propose a non – equilibrium adsorption-reaction model to quantify the rate of pore formation on the cell surface. By analysing the model in a pre-lysis regime, the number of pores per RBC to initiate rupture was found to lie between 400 and 800. The time constants for pore formation are estimated to lie between 1-25 s and monomer conformation time scales were found to be 2-4 times greater than the oligomerization times. Using this model, we are able to predict the extent of cell lysis as a function of the initial toxin concentration. Various kinetic models for oligomerization mechanism have been explored. Irreversible sequential kinetic model has the best agreement with the available experimental data. Subsequent to the mean field approach, a population balance model was also formulated.
The mechanics of cell rupture due to pore formation is poorly understood. Efforts to address this issue are concerned with understanding the changes in the membrane mechanical properties such as the modulus and tension in the presence of pores. The second part of the thesis is concerned with using atomic force microscopy to measure the mechanical properties of cells. We explore the possibility of employing tapping mode AFM (TM-AFM) to obtain the elastic modulus of soft samples. The dynamics of TM-AFM is modelled to predict the elastic modulus of soft samples, and predict optimal cantilever stiffness for soft biological samples. From experiments using TM-AFM on Nylon-6,6 the elastic modulus is predicted to lie between 2 and 5 GPa. For materials having elastic moduli in the range of 1– 20 GPa, the cantilever stiffness from simulations is found to lie in the range of 1 – 50 N/m. For soft biological samples, whose elastic moduli are in the range of 10-1000 kPa, a narrower range of cantilever stiffness (0.1 – 0.6 N/m), should be used.2015-08-06T18:30:00ZExperimental Determination And New Correlations For Multi-Component Solid Solubilities In Supercritical Carbon Dioxide
http://hdl.handle.net/2005/2509
Title: Experimental Determination And New Correlations For Multi-Component Solid Solubilities In Supercritical Carbon Dioxide
Authors: Reddy, N Siva Mohan
Abstract: The fluids that are operated above their critical temperature and pressure are
known as supercritical fluids (SCFs). SCFs replaces the conventional organic solvents
in the chemical processes due to their attractive properties such as liquid like
densities, gas like diffusivities, negligible surface tension, lower viscosity and high compressibility. Carbon dioxide, being non-toxic, non-flammable with ambient
critical temperature and moderate critical pressure, is the most widely used SCF in
many chemical processes. Supercritical carbon dioxide (SCCO2) finds applications in
industrial processes such as extraction and separation processes. The feasibility of a
supercritical process can be determined from the solubility of solute in SCF. For the
efficient design of a SCF process, the effects of temperature and pressure on the
solubility of a solid should be examined thoroughly. In general, the solute of interest is not present alone; it is present along with many other components in the compound. The solute has to be extracted or separated from matrix of components. Therefore, it is important to determine the mixture solubilities in SCCO2.
The mixture solubility of a solute is not same as that of pure component solubility. The presence of the other component alters the solubility of the solute to a greater extent; hence the effects of the other components present along with the solute, temperature and pressure need to be known to understand the mixture behavior of the solute in SCCO2. The solubilities of solid isomers (ortho-, meta-, para-) in SCCO2 vary to a greater extent. This huge difference in the solubilities of isomers is due to interactions between the molecules. The high solubility of an isomer in SCCO2 might be due to the solute-solvent interactions. The interactions between the molecules are significant in the solid mixtures solubilities in SCCO2. This research
work focuses on experimental determination and modeling of mixture solubilities of
solids in SCCO2.
The solubilities of several pairs of isomers have been experimentally determined at different temperatures and pressures. These include the ternary solubilities of ntrophenols, nitrobenzoic acids and dihydroxy benzene isomers mixtures in SCCO2. The experimental solubilities of nitrophenol (meta- and para-) isomers mixture have been determined. This study includes the effect of temperature, pressure and each isomer on the ternary mixture solubilities of nitrophenol mixtures. The enhancements in the ternary solubilities of nitrophenols over their binary solubilities and the selectivity of SCCO2 for the nitrophenol mixture have been discussed in detail. The solubilities of dihydroxy benzene (ortho-: pyrocatechol, meta- : resorcinol and para-: hydroquinone) isomers in SCCO2 have been determined at various temperatures and pressures. The ternary solubilities of pyrocatechol and resorcinol and quaternary solubilities of pyrocatechol, resorcinol and hydroquinone mixtures in SCCO2 have been investigated. The effect of each isomer on the mixture solubilities of other isomers has been included in this work. Selectivity for dihydroxy benzene isomers and variation of solubilities enhancements with temperature and pressure has been presented in this study. The equilibrium mixture solubilities of nitrobenzoic acid isomers (meta- and para) mixture have been studied. The variation of mixture solubilities and their enhancements with temperature and pressure has been thoroughly analyzed. Selectivity of SCCO2 for this nitrobenzoic acid mixture has been studied in detail.
The increase or decrease in the ternary solubilities of the solid mixtures that
have been considered in this study is due to the interactions between the molecules.
The ternary solubilities of m-nitrophenol increase whereas they decrease for pnitrophenol for the nitrophenol solid mixture. Quaternary solubilities of dihydroxy
benzene isomers (pyrocatechol + resorcinol + hydroquinone) increases compared to
their pure component solubilities. The ternary solubilities of pyrocatechol increases while resorcinol decreases over the pressure range at different temperatures (except 338 K) considered in this study. The mixture solubilities of p-nitrobenzoic acid of nitrobenzoic acid isomers increase to a greater extent. An average of separation
efficiency of 70%, 85% and 90% has been observed for ternary solid mixtures of
nitrophenol, nitrobenzoic acid and dihydroxy benzene isomers respectively.
Modeling of high pressure multi-component systems is useful to understand the behavior of the mixtures. Moreover, the experimental determination of multicomponent solubilities of solids in SCCO2 is tedious and time consuming; hence the modeling of mixture solubilities is essential. The interactions between the molecules have been incorporated in the association theory and a five parameter equation with two constraints has been derived for binary systems. The new equation correlates the solubilities of m-dinitrobenzene in this study along with 72 other systems available in literature.
Seven new model equations have been developed to correlate ternary (2 for
cosolvent (solid + cosolvent + SCCO2) systems; 5 for solid mixtures in SCCO2)
solubilities of solids in SCCO2. A new model equation for cosolvent ternary systems
has been derived by using the concepts of association of molecules. The model equation contains seven adjustable parameters with three constraints and correlates mixture solubilities in terms of temperature, pressure, density and cosolvent composition. The interactions between the molecules have been included in the association theory then the number of parameters decreased to five with two constraints. The performance of the newly developed equations has been evaluated for 32 ternary systems with various cosolvents along with experimental data of mdinitrobenzene in methanol cosolvent of this study.
The same association theory has been extended to ternary (solid mixtures +
SCCO2) solubilities of solids in SCCO2 and two new equations have been derived with and without incorporating interactions between the molecules. Both the equations have five adjustable parameters with three constraints for the equation which has been derived from association theory alone and two constraints for the equation which has been derived by considering the interactions between the
molecules in the association theory. A new model equation has been derived by combining solution model with Wilson activity coefficient model to account for nonidealities of the solute. This equation has four adjustable parameters and no
constraints on the parameters. The non-idealities of both solutes in the solution model have been included and two more equations with no constraints on the parameters have been developed. One equation uses NRTL activity coefficient model which
results in three adjustable parameters while the other equation with five parameters
has been obtained from Wilson activity coefficient model for solid mixtures
solubilities in SCCO2. The performance of the newly developed equations has been
evaluated for the solid mixtures (ternary systems) in SCCO2. The equations with
constraints make them limited for few systems and the equations with no constraints
are able to correlate the solubilities of solids of all the ternary systems that are
available in literature along with the generated ternary experimental data of this study.
The quaternary solubilities of solids have been correlated by using a five parameter model equation which has been derived by combining solution and Wilson activity coefficient models. The equation for the quaternary systems does not have constraints on the parameters; hence can be applied for quaternary systems. The equation correlates the quaternary solubilities of solids in terms of temperature, pressure, density and cosolute compositions.
Chapter 1 gives a brief introduction on the solubilities of solid mixtures and their behavior in SCCO2. Chapter 2 presents the experimental setup and the solubility
data of binary, ternary and quaternary systems determined in this study. Chapter 3
focuses on the models that have been derived to correlate the solubilities of solids in
SCCO2. Chapter 4 discusses in detail about the results obtained in this research work.
Chapter 5 briefly summarizes the work and presents major conclusions. The new equations that have been developed here are first of its kind for the ternary and quaternary systems. These equations give information about the nonidealities of the systems. The nature of the interactions between the molecules can be determined from the parameters of the equations which incorporate interactions between the molecules. The multi-component solubilities of the solids can be correlated by using the semi-empirical equations that have been derived in this research.2016-03-01T18:30:00ZClosed-form Solutions For Rotating And Non-rotating Beams : An Inverse Problem Approach
http://hdl.handle.net/2005/1832
Title: Closed-form Solutions For Rotating And Non-rotating Beams : An Inverse Problem Approach
Authors: Sarkar, Korak
Abstract: Rotating Euler-Bernoulli beams and non-homogeneous Timoshenko beams are widely used to model important engineering structures. Hence the vibration analyses of these beams are an important problem from a structural dynamics point of view. The governing differential equations of both these type of beams do not yield any simple closed form solutions, hence we look for the inverse problem approach in determining the beam property variations given certain solutions.
Firstly, we look for a rotating beam, with pinned-free boundary conditions, whose eigenpair (frequency and mode-shape) is same as that of a uniform non-rotating beam for a particular mode. It is seen that for any given mode, there exists a flexural stiffness function (FSF) for which the ith mode eigenpair of a rotating beam with uniform mass distribution, is identical to that of a corresponding non-rotating beam with same length and mass distribution. Inserting these derived FSF's in a finite element code for a rotating pinned-free beam, the frequencies and mode shapes of a non-rotating pinned-free beam are obtained. For the first mode, a physically realistic equivalent rotating beam is possible, but for higher modes, the FSF has internal singularities. Strategies for addressing these singularities in the FSF for finite element analysis are provided. The proposed functions can be used as test functions for rotating beam codes and also for targeted destiffening of rotating beams.
Secondly, we study the free vibration of rotating Euler-Bernoulli beams, under cantilever boundary condition. For certain polynomial variations of the mass per unit length and the flexural stiffness, there exists a fundamental closed form solution to the fourth order governing differential equation. It is found that there are an infinite number of rotating beams, with various mass per unit length variations and flexural stiffness distributions, which share the same fundamental frequency and mode shape. The derived flexural stiffness polynomial functions are used as test functions for rotating beam numerical codes. They are also used to design rotating cantilever beams which may be required to vibrate with a particular frequency.
Thirdly, we study the free vibration of non-homogeneous Timoshenko beams, under fixed-fixed and fixed-hinged boundary conditions. For certain polynomial variations of the material mass density, elastic modulus and shear modulus, there exists a fundamental closed form solution to the coupled second order governing differential equations. It is found that there are an infinite number of non-homogeneous Timoshenko beams, with various material mass density, elastic modulus and shear modulus distributions, which share the same fundamental frequency and mode shape. They can be used to design non-homogeneous Timoshenko beams which may be required for certain engineering applications.2012-12-03T18:30:00ZIntegrating Product Model With Assembly Process Model Using Liaisons
http://hdl.handle.net/2005/2293
Title: Integrating Product Model With Assembly Process Model Using Liaisons
Authors: Swain, Abinash Kumar
Abstract: This thesis addresses the problem of achieving better convergence between different phases (here design and manufacturing) of the product development cycle. The use of liaison has been proposed to better integrate the product and assembly process. Two facets of integration have been addressed in this thesis. One is concurrent evolution of the process model with the product model and the second is associativity between product model and process model. A liaison data structure has been proposed, which is set of geometric entities, associated with one or more assembly process that acts as an interface between the product model and process model. As the liaison data is not available explicitly in the product model, a set of algorithms have been developed and implemented to identify and extract the geometric entities defined in the liaison data structure from assembly model. The proposed algorithms can identify and extract liaisons for riveting, welding, bolt fastening, screw fastening, adhesive bonding (gluing) and blind fastening. The developed algorithms have been implemented and tested.
The process model needs to evolve with the product model concurrently so that any mistakes or infeasibility in the process model can be flagged right away. The use of liaison enables the construction of process model as the product model is fleshed out. A framework based on liaison has been proposed and implemented to demonstrate the concurrent evolution of product and process model.
Linking the changes in the product model to flag the changes (or at least identify the need for changes) in the process model forms the associativity problem. The liaison has been used for maintaining associativity between the product and process model. A framework has been proposed for maintaining associativity between product model and process model that makes use of expert knowledge or tribal knowledge to track impact of changes in product model or process model. An aircraft wing box has been used as an example to illustrate and validate the proposed approaches.
Finally the thesis concludes by summarizing contributions of the research and outlining future work.2014-04-08T18:30:00Z