Criticality and Characteristic Neutronic Analysis of a Transient-State Shockwave in a Pulsed Spherical Gaseous Uranium-Hexafluoride Reactor

The purpose of this study is to analyze the theoretical criticality of a spherical uranium-hexafluoride reactor with a transient, pulsed shockwave emanating from the center of the sphere in an outward-radial direction. This novel nuclear reactor design, based upon pulsed fission in a spherical enclosure is proposed for possible use in direct energy conversion, where the energy from fission products is captured through the use of electrostatic fields or through induction. An analysis of the dynamic behavior of the shockwave in this reactor is the subject of this thesis. As a shockwave travels through a fluid medium, the characteristics of the medium will change across the shockwave boundary. Pressure, temperature, and density are all affected by the shockwave. Changes in these parameters will affect the neutronic characteristics of a fissile medium. If the system is initially in a subcritical state, the increases in pressure, temperature, and density, all brought about by the introduction of the shockwave, will increase the reactivity of the nuclear system, creating a brief super critical state that will return to a subcritical state after the shockwave dissipates. Two major problems are required to be solved for this system. One is the effects of the shockwave on the gas, and the second is the resulting effects on system criticality. These problems are coupled due to the unique nature of the speed of the expanding shockwave in the uranium-hexafluoride medium and the energy imparted to the system by the shockwave with respect to the fissile uranium-hexafluoride. Using compressible flow and shockwave theories, this study determines the properties of the gaseous medium for reference points before, during, and behind the shockwave as it passes through the fissile medium. These properties include pressure changes, temperature changes, and density changes that occur to the system. Using the parameters calculated from the shockwave, the neutron transport equation is solved with the appropriate boundary conditions to identify system criticality, neutron flux, and the appropriate changes to system variables such as buckling, and migration length. The analytical solution is then verified using MCNPX, a Monte Carlo method for computational analysis of the neutron transport equation. Through manipulation of the initial pressure of the system, which is intrinsically linked to the density of the system by the ideal gas Equation of State, neutron and flux multiplication trends are corroborated. The results show that both compressible flow theory and shockwave theory are in relatively close agreement for parameter changes across, after, and along the shockwave expansion. The solution to the analytical transport equation is in good agreement with the results from MCNPX. The change in the effective multiplication factor is similar between both the analytical solution and the computational solution. Furthermore, a new method for determining the transient effective multiplication factor is devised. These results show the maximum criticality of the reactor is at the initiation of the shockwave. The shockwave creates a local supercriticality until the wave dissipates below Mach 1. Several tools and methods are employed in this study, including the use of Monte Carlo numerical methods, Euler method solutions, and computer programs, such as MCNP, MATLAB, and Mathcad, which provide necessary the necessary computational abilities to understand the mathematical model of the system

Role of Tissue Factor in Venous Thrombosis

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality worldwide. However, the mechanisms by which clots are formed in the deep veins have not been determined. Tissue factor (TF) is the primary initiator of the coagulation cascade and is essential for hemostasis. Under pathological conditions, TF is released into the circulation on small-membrane vesicles termed microparticles (MPs). Recent studies suggest that elevated levels of MPTF may trigger thrombosis. This review provides an overview of the role of TF in VTE

Tissue Factor and Tissue Factor Pathway Inhibitor as Key Regulators of Global Hemostasis: Measurement of Their Levels in Coagulation Assays

The tissue factor (TF)/factor (F)VIIa complex is the primary initiator of coagulation in vivo. Tissue factor pathway inhibitor (TFPI) is the physiological inhibitor of the TF/FVIIa complex. Deficiencies of either TF or TFPI have not been reported in humans, and a complete absence of either of these two proteins in mice is embryonically lethal. To maintain normal hemostasis, levels of TF and TFPI need to be balanced. Increased levels of TF can overwhelm the inhibitory capacity of TFPI, resulting in thrombosis. Decreased levels of TF are associated with bleeding. Global assays of coagulation are defined as tests capable of evaluating all components of the clotting cascade that are present in plasma. In these tests the thrombogenic surface is either provided by platelets or exogenous phospholipids. Clotting assays currently used in clinical practice are not designed to measure endogenous levels of TF and TFPI. Therefore, there is a need to develop sensitive and specific assays for measuring levels of functional TF and TFPI in whole blood and plasma. These assays could be useful in patient management in many scenarios

Anthracycline Treatment of the Human Monocytic Leukemia Cell Line THP-1 Increases Phosphatidylserine Exposure and Tissue Factor Activity

Introduction: Cancer associated thrombosis is a well-recognized phenomenon that results in considerable patient morbidity and mortality. Malignancy conveys an increased risk for thrombosis and chemotherapy further elevates this risk. The pathophysiological mechanisms underlying this process remain poorly defined. Materials and Methods: A human acute monocytic leukemia cell line (THP-1) was treated with commonly used anthracycline chemotherapeutics at concentrations similar to those found in the plasma of cancer patients. Cells were analyzed for tissue factor (TF) mRNA, protein, and activity. Microparticle (MP) TF activity was also measured. Phosphatidylserine (PS) exposure on cells and MPs was analyzed by flow cytometry. PS levels on MPs was also evaluated in an annexin V capture assay. Results: Anthracycline treatment of THP-1 cells resulted in a concentration-dependent increase in cellular TF activity without a change in TF protein, which was associated with increased PS exposure on the cell surface and apoptosis. The increase in TF activity was abolished by annexin V or lactadherin indicating that PS exposure was required. Anthracycline treatment of THP-1 cells also increased the number of TF-positive MPs. Conclusion: Treatment of THP-1 cells with anthracyclines induces apoptosis and increases cellular TF activity. The increased activity required an increase in exposure of PS. Additionally, anthracyclines increase the release of TF-positive MPs from THP-1 cells. We propose that the increase in cellular TF activity in circulating leukemic cells, combined with increased numbers of TF-positive MPs, may contribute to thrombosis in cancer patients receiving chemotherapy

Phase I/II trial of nano-camptothecin CRLX101 with capecitabine and radiotherapy as neoadjuvant treatment for locally advanced rectal cancer.

CRLX101 is a nanoparticle-drug conjugate with a camptothecin payload. We assessed the toxicity and pathologic complete response (pCR) rate of CRLX101 with standard neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer. A single-arm study was conducted with a 3 + 3 dose escalation phase Ib followed by phase II at the maximum tolerated dose (MTD). Thirty-two patients were enrolled with 29 (91%) patients having T3/4 and 26 (81%) N1/2 disease. In phase Ib, no patient experienced a dose limiting toxicity (DLT) with every other week dosing, while 1/9 patients experienced a DLT with weekly dosing. The weekly MTD was identified as 15 mg/