Magnetoplasmadynamic thruster flows: Problems and progress

The topics are presented in viewgraph form and include the following: overall strategy for magnetoplasmadynamic (MPD) thruster development; high power MPD flows; moderate power MPD thrusters and components; qualitative spectroscopic studies of magnetic nozzle flow; hollow cathode studies; and anode flow studies

The cathode region of a quasi-steady magnetoplasmadynamic arcjet, supplement 8

Electric and magnetic field measurements in cathode region of quasi-steady magnetoplasmadynamic arcje

The Effects of Magnetic Nozzle Configurations on Plasma Thrusters

Over the course of eight years, the Ohio State University has performed research in support of electric propulsion development efforts at the NASA Lewis Research Center, Cleveland, OH. This research has been largely devoted to plasma propulsion systems including MagnetoPlasmaDynamic (MPD) thrusters with externally-applied, solenoidal magnetic fields, hollow cathodes, and Pulsed Plasma Microthrusters (PPT's). Both experimental and theoretical work has been performed, as documented in four master's theses, two doctoral dissertations, and numerous technical papers. The present document is the final report for the grant period 5 December 1987 to 31 December 1995, and summarizes all activities. Detailed discussions of each area of activity are provided in appendices: Appendix 1 - Experimental studies of magnetic nozzle effects on plasma thrusters; Appendix 2 - Numerical modeling of applied-field MPD thrusters; Appendix 3 - Theoretical and experimental studies of hollow cathodes; and Appendix 4 -Theoretical, numerical and experimental studies of pulsed plasma thrusters. Especially notable results include the efficacy of using a solenoidal magnetic field downstream of a plasma thruster to collimate the exhaust flow, the development of a new understanding of applied-field MPD thrusters (based on experimentally-validated results from state-of-the art, numerical simulation) leading to predictions of improved performance, an experimentally-validated, first-principles model for orificed, hollow-cathode behavior, and the first time-dependent, two-dimensional calculations of ablation-fed, pulsed plasma thrusters

Chemical inhibitor targeting the replication protein A-DNA interaction increases the efficacy of Pt-based chemotherapy in lung and ovarian cancer

Platinum-based chemotherapeutics exert their therapeutic efficacy via the formation of DNA adducts which interfere with DNA replication, transcription and cell division and ultimately induce cell death. Repair and tolerance of these Pt-DNA lesions by nucleotide excision repair (NER) and homologous recombination (HR) can substantially reduce the effectiveness of therapy. Inhibition of these repair pathways, therefore, holds the potential to sensitize cancer cells to Pt treatment and increase clinical efficacy. Replication Protein A (RPA) plays essential roles in both NER and HR, along with its role in DNA replication and DNA damage checkpoint activation. Each of these functions is, in part, mediated by RPA binding to single-stranded DNA (ssDNA). Here we report the synthesis and characterization of novel derivatives of RPA small molecule inhibitors and their activity in models of epithelial ovarian cancer (EOC) and non-small cell lung cancer (NSCLC). We have synthesized analogs of our previously reported RPA inhibitor TDRL-505 and determined the structure-activity relationships. These data led us to the identification of TDRL-551, which exhibited a greater than 2-fold increase in in vitro activity. TDRL-551 showed synergy with Pt in tissue culture models of EOC and in vivo efficacy, as a single agent and in combination with platinum, in a NSCLC xenograft model. These data demonstrate the utility of RPA inhibition in EOC and NSCLC and the potential in developing novel anticancer therapeutics that target RPA-DNA interactions

Differential activation of DNA-PK based on DNA strand orientation and sequence bias

DNA-PKcs and Ku are essential components of the complex that catalyzes non-homologous end joining (NHEJ) of DNA double-strand breaks (DSBs). Ku, a heterodimeric protein, binds to DNA ends and facilitates recruitment of the catalytic subunit, DNA-PKcs. We have investigated the effect of DNA strand orientation and sequence bias on the activation of DNA-PK. In addition, we assessed the effect of the position and strand orientation of cisplatin adducts on kinase activation. A series of duplex DNA substrates with site-specific cisplatin–DNA adducts placed in three different orientations on the duplex DNA were prepared. Terminal biotin modification and streptavidin (SA) blocking was employed to direct DNA-PK binding to the unblocked termini with a specific DNA strand orientation and cisplatin–DNA adduct position. DNA-PK kinase activity was measured and the results reveal that DNA strand orientation and sequence bias dramatically influence kinase activation, only a portion of which could be attributed to Ku-DNA binding activity. In addition, cisplatin–DNA adduct position resulted in differing degrees of inhibition depending on distance from the terminus as well as strand orientation. These results highlight the importance of how local variations in DNA structure, chemistry and sequence influence DNA-PK activation and potentially NHEJ

Statistical theory of quasi stationary states beyond the single water-bag case study

An analytical solution for the out-of-equilibrium quasi-stationary states of the paradigmatic Hamiltonian Mean Field (HMF) model can be obtained from a maximum entropy principle. The theory has been so far tested with reference to a specific class of initial condition, the so called (single-level) water-bag type. In this paper a step forward is taken by considering an arbitrary number of overlapping water bags. The theory is benchmarked to direct microcanonical simulations performed for the case of a two-levels water-bag. The comparison is shown to return an excellent agreement

Report on Characterization of U-10 wt.% Zr Alloy

This report summarizes the chemical and structural characterization results for a U-10 wt.% Zr alloy to be used in an ultra-high burn-up nuclear fuel concept. The as-cast alloy material was received from Texas A and M University. Characterization and an initial heat treatment of the alloy material were conducted at Lawrence Livermore National Laboratory. The as-received ingot was sectioned for X-ray analysis, metallography, SEM, TEM, and heat treatments, as shown in Figure 1

An Assessment of the Net Value of CSP Systems Integrated with Thermal Energy Storage

AbstractWithin this study, we evaluate the operational and capacity value—or total system value—for multiple concentrating solar power (CSP)plant configurations under an assumed 33% renewable penetration scenario in California. We calculate the first-year bid price for two CSP plants, including a 2013 molten-salt tower integrated with a conventional Rankine cycle and a hypothetical 2020 molten-salt tower system integrated with an advanced supercritical carbon-dioxide power block. The overall benefit to the regional grid, defined in this study as the net value, is calculated by subtracting the first-year bid price from the total system value.Re--sults of this study indicate a positive net value for a variety of scenarios, depending on technology assumptions and assumed values for natural gas price and tax incentives. We provide results for the 2013 and 2020 CSP configurations as a function of thermal energy storage capacity and solar field size. We provide a sensitivity of these results to natural gas price, which influence the operation value and thus the total system value. We also investigate the sensitivity of the net value to current and anticipated tax incentives

Testing the metal of ERCC2 in predicting the response to platinum-based therapy

DNA repair has been shown to affect the cellular response to platinum-based therapy in a variety of cancers; however, translating this knowledge to the clinic has proven difficult and yielded mixed results. In this issue of Cancer Discovery, Van Allen and colleagues have analyzed responders and nonresponders to neoadjuvant platinum-based therapy with locally advanced urothelial cancer and identified a series of mutations in the nucleotide excision repair (NER) gene ERCC2 that correlate with the response to platinum-based therapy. This work provides evidence that defects in NER can be exploited to maximize the efficacy of conventional platinum-based chemotherapy

Recognition of DNA Termini by the C-Terminal Region of the Ku80 and the DNA-Dependent Protein Kinase Catalytic Subunit

DNA double strand breaks (DSBs) can be generated by endogenous cellular processes or exogenous agents in mammalian cells. These breaks are highly variable with respect to DNA sequence and structure and all are recognized in some context by the DNA-dependent protein kinase (DNA-PK). DNA-PK is a critical component necessary for the recognition and repair of DSBs via non-homologous end joining (NHEJ). Previously studies have shown that DNA-PK responds differentially to variations in DSB structure, but how DNA-PK senses differences in DNA substrate sequence and structure is unknown. Here we explore the enzymatic mechanisms by which DNA-PK is activated by various DNA substrates and provide evidence that the DNA-PK is differentially activated by DNA structural variations as a function of the C-terminal region of Ku80. Discrimination based on terminal DNA sequence variations, on the other hand, is independent of the Ku80 C-terminal interactions and likely results exclusively from DNA-dependent protein kinase catalytic subunit interactions with the DNA. We also show that sequence differences in DNA termini can drastically influence DNA repair through altered DNA-PK activation. These results indicate that even subtle differences in DNA substrates influence DNA-PK activation and ultimately the efficiency of DSB repair