No description available.

Thesis. 1976. Ph.D.--Massachusetts Institute of Technology. Dept of Physics. / Microfiche copy available in Archives and Science. / Includes bibliographical references. / Ph.D.

The infinite order perturbation theory of Prigogine and coworkers is used, with some modifications, to discuss the theories of classical irreversible processes due to Bogoliubov, Sandri & Frieman, and Mazur & Biel. The latter authors use the BBKGY hierarchy of equations as a starting point. Accordingly, to discuss these theories the infinite order perturbation theory is written out in such a way that it relates easily to the BBKGY hierarchy. The nature of the assumptions involved in the theories of Bogoliubov and Sandri & Frieman become particularly clear when compared with the infinite order perturbation expansion. The relation of the theory of Mazur & Biel with the cluster expansion of Green is also elucidated. / Science, Faculty of / Physics and Astronomy, Department of / Graduate

No description available.

The research presented in this dissertation is the result of our laboratory's effort to develop a microfluidic platform to interrogate, manipulate, isolate, and enrich rare mammalian cells dispersed within heterogeneous populations. Relevant examples of these target cells are stem cells within a differentiated population, circulating tumor cells (CTCs) in the blood stream, and tumor initiating cells (TICs) in a population of benign cancer cells. The ability to isolate any of these rare cells types with high efficiency will directly lead to advances in tissue engineering, cancer detection, and individualized medicine. This work lead directly to the development of a new cell manipulation technique, termed contactless dielectrophoresis (cDEP). In this technique, cells are isolated from direct contact with metal electrodes by employing fluid electrode channels filled with a highly conductive media. Thin insulating barriers, approximately 20 μ­m, serve to isolate the fluid electrode channels from the low conductivity sample buffer. The insulating barriers in a fluid-electrical system create a number of unique and interesting challenges from an electrical engineering standpoint. Primarily, they block the flow of DC currents and create a non-constant frequency response which can confound experimental results attempting to characterize the electrical characteristics of cells. Due to these, and other, considerations, the use of high-voltage high-frequency signals are necessary to successfully manipulate cells. The effect of these high frequency fields on cells are studied and applied to microfluidic and tissue level applications. In later chapters, theoretical and experimental results show how high frequency and pulsed electric fields can ablate cells and tissue. Understanding the parameters necessary to electroporate cells aids in the development of cDEP devices where this phenomenon is undesirable and gives insight towards the development of new cancer ablation therapies where targeted cell death is sought after. This work shows that there exists a finite frequency spectrum over which cDEP devices can operate in which cells are minimally affected by the induced electric fields. Finally, lessons learned in the course of the development of cDEP were adapted and applied towards cancer ablation therapies where electroporation are favorable. It was found that bursts of high frequency pulsed electric fields can successfully kill cells and ablate tissue volumes through a process termed High Frequency Irreversible Electroporation (H-FIRE). This technique is advantageous as these waveforms mitigate or eliminate muscle contractions associated with traditional IRE technologies. Similarly, the use of fluid electrodes in cDEP inspired the use of an organs vascular system as the conductive pathway to deliver pulses. This novel approach allows for the ablation of large volumes of tissue without the use of puncturing electrodes. These techniques are currently undergoing evaluation in tissue engineering applications and pre-clinical evaluation in veterinary patients. / Ph. D.

Irreversible electroporation (IRE) is an energy directed focal ablation technique. This procedure typically involves the placement of two or more electrodes into, or around, a region of interest within the tissue and administering a sequence of short, intense, pulsed electric fields (PEFs). The application of these PEFs results in an increase in the transmembrane potential of all cells within the electric field above a critical value, destabilizing the lipid bilayer of the cellular membrane and increasing the cell-tissue permeability. For years, many have used this phenomenon to assist the transport of macromolecules typically unable to penetrate the cell membrane with the intent of avoiding cell necrosis or irreversible electroporation. More recently, however, irreversible electroporation has proven to be a successful alternative for the treatment of cancer. Proper tuning of the pulse parameters has allowed for a targeted treatment of localized tumors, and has shown immense value in the treatment of surgically inoperable tumors located near major blood vessels and nerves. While it is critical to ensure sufficient treatment of the target tissue, it can be equally vital to the treatment and patients overall outcome that the pulsing conditions are set to moderate the associated thermal effects with the electroporation of biological tissue. The development of thermal mitigation strategies for IRE treatment is the focus of this dissertation. Herein, the underlying theory and thermal considerations of tissue electroporation in various scenarios are described. Additionally, new thermal mitigation approaches with the intention of maintaining tissue temperature below a thermally damaging threshold, while also preserving or improving IRE lesion volume are detailed. Further, numerical models were developed and ex vivo tissue experiments performed using a perfused organ model to examine three thermal mitigation strategies in their ability to moderate temperature. Tests conducted using thermally mitigating treatment delivery on live tissue confirm the capacity to deliver more energy to the tissue at a thermally acceptable temperature, and provide the potential for a replete IRE lesion. / Doctor of Philosophy / Irreversible electroporation (IRE) is a minimally invasive therapy utilized to treat a variety of cancers. This procedure involves the delivery energy in the form of pulsed electric fields (PEFs) through two or more needle electrodes. These PEFs destabilize the cell membrane, increase the cell-tissue permeability, and ultimately induce cell death for any given cell within the targeted treatment region. Over the years, this treatment modality has shown a great deal of promise in the treatment of unresectable tumors in which the tumor is positioned near or around sensitive regions making the surgical removal of the tumor impossible and thermal ablation techniques limited in their ability to treat without irrevocably damaging the underlying tissue architecture and other critical surrounding structures. Thus, it can be vital to the treatment and patients overall outcome that the IRE therapy is set to moderate any associated thermal effects with the electroporation of biological tissue. However, the design of an electric field that simultaneously maps the entire region of interest for a single treatment and avoids undesirable thermal effects can be challenging when treating larger or irregularly shaped volumes of tissue. Thus, in this dissertation, we demonstrate various treatment delivery methods/ enhancements to reduce temperature rise during IRE therapy. The underlying theory of tissue electroporation and associated thermal considerations are described to provide a foundation and general context. Additionally, novel approaches to tissue electroporation therapy with the intention of maintaining tissue temperature below a thermally damaging threshold throughout treatment are detailed.

Call number: LD2668 .T4 1963 C45 / Master of Science

No description available.

We investigate a new perturbation technique introduced by E. Frieman to derive a kinetic equation from the equations of the BBGKY hierarchy. The orders of magnitude of the terms in the latter equations are calculated and Frieman's estimate is found incorrect. His derivation of the Landau's equation for a weakly coupled gas actually depends on the existence of the relaxation time rather than the much shorter mean free time as he expected. A physical interpretation of the Grad's theorem and Grad's original proof is given to justify the choice of the molecular chaos, conditions at the initial time. Two examples are given to clarify the applicability of the perturbation method. / Science, Faculty of / Physics and Astronomy, Department of / Graduate

Hydroxymethylglutaryl-CoA synthase (HMG-CoA synthase) catalyzes the formation of HMG-CoA from acetyl-CoA and acetoacetyl-CoA. F-244 (1), a naturally occurring J3-lactone isolated from Fusarium sp. ATCC 20788 and other species, is known to be a potent and specific inhibitor ofHMG-CoA synthase isolated from rat liver. 1Ji,, HO,.,._.. .. , '• .. ,....13_.,., ;=( 0 14 0 0 (1) (2) This thesis describes the 48 fold purification of HMG-CoA synthase from bakers yeast in a three step procedure involving ethanol fractionation followed by ammonium sulfate precipitation and then hydroxylapatite chromatography. This procedure was found to be reproducible and yields a preparation of specific activity 0.14 units (j...tmolfmin)/mg in an overall yield of 8%. In our study, F-244 was found to be a potent irreversible inhibitor of HMGCoA synthase isolated from bakers yeast, with an IC50 value of 0.009 j...tM. This value is almost identical to the inhibitory activity of F-244 on rat liver HMG-CoA synthase that has been reported in the literature. Tritium labeled F-244 was prepared, for the first time, by feeding methyl-[3H]methionine to cultures of Fusarium sp. The [15, 16, 17, 18-3H] F-244 isolated had a specific activity of 1.3 x 106 DPM/mg. This tritiated F-244 was then used as an affinity.label for HMG-CoA synthase. Attempts to isolate the enzyme-inhibitor complex were unsuccessful due to the low level of radioactivity associated with the tritiated F-244. HMG-CoA synthase was also shown to be inhibited in a time-dependent irreversible manner by {±)-(3-butyrolactone (2). The rate of inactivation (~) was found to be 0.4697 s-1 and the inhibition constant (K1) was found to be 9 mM. The inactivation was found to be irreversible over several hours. / Thesis / Master of Science (MS)