High-Temperature Structures, Adhesives, and Advanced Thermal Protection Materials for Next-Generation Aeroshell Design

The next generation of planetary exploration vehicles will rely heavily on robust aero-assist technologies, especially those that include aerocapture. This paper provides an overview of an ongoing development program, led by NASA Langley Research Center (LaRC) and aimed at introducing high-temperature structures, adhesives, and advanced thermal protection system (TPS) materials into the aeroshell design process. The purpose of this work is to demonstrate TPS materials that can withstand the higher heating rates of NASA's next generation planetary missions, and to validate high-temperature structures and adhesives that can reduce required TPS thickness and total aeroshell mass, thus allowing for larger science payloads. The effort described consists of parallel work in several advanced aeroshell technology areas. The areas of work include high-temperature adhesives, high-temperature composite materials, advanced ablator (TPS) materials, sub-scale demonstration test articles, and aeroshell modeling and analysis. The status of screening test results for a broad selection of available higher-temperature adhesives is presented. It appears that at least one (and perhaps a few) adhesives have working temperatures ranging from 315-400 C (600-750 F), and are suitable for TPS-to-structure bondline temperatures that are significantly above the traditional allowable of 250 C (482 F). The status of mechanical testing of advanced high-temperature composite materials is also summarized. To date, these tests indicate the potential for good material performance at temperatures of at least 600 F. Application of these materials and adhesives to aeroshell systems that incorporate advanced TPS materials may reduce aeroshell TPS mass by 15% - 30%. A brief outline is given of work scheduled for completion in 2006 that will include fabrication and testing of large panels and subscale aeroshell test articles at the Solar-Tower Test Facility located at Kirtland AFB and operated by Sandia National Laboratories. These tests are designed to validate aeroshell manufacturability using advanced material systems, and to demonstrate the maintenance of bondline integrity at realistically high temperatures and heating rates. Finally, a status is given of ongoing aeroshell modeling and analysis efforts which will be used to correlate with experimental testing, and to provide a reliable means of extrapolating to performance under actual flight conditions. The modeling and analysis effort includes a parallel series of experimental tests to determine TSP thermal expansion and other mechanical properties which are required for input to the analysis models

The Impact of \u3ci\u3emsaABCR\u3c/i\u3e On \u3ci\u3esarA\u3c/i\u3e-Associated Phenotypes is Different in Divergent Clinical Isolates of \u3ci\u3eStaphylococcus aureus\u3c/i\u3e

The staphylococcal accessory regulator (sarA) plays an important role in Staphylococcus aureus infections including osteomyelitis, and the msaABCR operon has been implicated as an important factor in modulating expression of sarA. Thus, we investigated the contribution of msaABCR to sarA-associated phenotypes in the S. aureus clinical isolates LAC and UAMS-1. Mutation of msaABCR resulted in reduced production of SarA and a reduced capacity to form a biofilm in both strains. Biofilm formation was enhanced in a LAC msa mutant by restoring the production of SarA, but this was not true in a UAMS-1 msa mutant. Similarly, extracellular protease production was increased in a LAC msa mutant but not a UAMS-1 msa mutant. This difference was reflected in the accumulation and distribution of secreted virulence factors and in the impact of extracellular proteases on biofilm formation in a LAC msa mutant. Most importantly, it was reflected in the relative impact of mutating msa as assessed in a murine osteomyelitis model, which had a significant impact in LAC but not in UAMS-1. In contrast, mutation of sarA had a greater impact on all of these in vitro and in vivo phenotypes by comparison to mutation of msaABCR, and it did so in both LAC and UAMS-1. These results suggest that, at least in osteomyelitis, it would be therapeutically preferable to target sarA rather than msaABCR to achieve the desired clinical result, particularly in the context of divergent clinical isolates of S. aureus

Electrical design of TNS

The electrical design of the ORNL-Westinghouse next step (TNS) fusion reactor was begun in 1976, using a set of ground rules which were based on the overall program objectives. These objectives were to identify the design of reasonably-priced reactors, which would achieve ignition and be technology forcing. The term ''technology forcing'' was understood to mean the desirability of a large number of ignited D-T pulses and the incorporation of superconducting toroidal field (TF) coils, if at all possible. A trade study methodology was developed to compare different machine sizes and TF coil technologies and to aid in the selection of system and subsystem design approaches. The logic which led from the program objectives to the design ground rules and from the ground rules to the circuit selection is described below. The circuit design approaches were generalized and these models were incorporated into a computer program (COAST) which was used to examine the cost of overall tokamak systems as key design parameters were varied

From infancy to adolescence: fifteen years of continuous treatment with hydroxyurea in sickle cell anemia

Despite documented laboratory and clinical benefits of hydroxyurea for children with sickle cell anemia (SCA), the drug\u27s long-term safety and efficacy remains poorly defined. The HUSOFT trial and extension study examined feasibility, toxicity, and hematological efficacy of hydroxyurea in infants with SCA.This report describes HUSOFT participants who have continued hydroxyurea therapy for 15 years. With IRB approval, medical records were reviewed for clinical, laboratory, and growth parameters.Twenty-eight infants enrolled in the original 2-year HUSOFT study received open-label liquid hydroxyurea at 20 mg/kg/day; 17 completed the extension study with dose escalation to 30 mg/kg/day. Eight of these 17 (6 girls and 2 boys, all HbSS) have continued on daily hydroxyurea for at least 15 years (median age at last follow-up 17.6 years) without interruption. All hematologic indices (Hb concentration, mean corpuscular volume (MCV), fetal hemoglobin) showed sustained effect after 15 years. The median maximum tolerated dose of hydroxyurea has decreased from 30 to 26 mg/kg/day (range 19.5-31.2); neutropenia [absolute neutrophil count (ANC) \u3c 1.0 x 10/L] prompting temporary drug discontinuation occurred a total of 10 times in 4 subjects and there was no severe neutropenia (ANC \u3c 0.5 x 10/L). Growth rates over 15 years continued at the 50th percentile for both height and weight, and puberty occurred without delay (age range 10-14 years). There were 5.1 vaso-occlusive events (pain and acute chest syndrome)/100 patient years, 7.3 packed red blood cell transfusions/100 patient years. No malignancies, strokes, or deaths occurred. At last follow up, all subjects were at appropriate grade level (10-12 grade) with no history of repeated grades.A cohort of young teenagers with SCA who initiated treatment in infancy have had sustained and continued hematological benefits for a decade and a half. Growth and sexual development are normal and comparable to the general pediatric population. Continuous hydroxyurea therapy since infancy appears safe and efficacious in SCA

Nuclease Modulates Biofilm Formation in Community-Associated Methicillin-Resistant Staphylococcus aureus

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging contributor to biofilm-related infections. We recently reported that strains lacking sigma factor B (sigB) in the USA300 lineage of CA-MRSA are unable to develop a biofilm. Interestingly, when spent media from a USA300 sigB mutant was incubated with other S. aureus strains, biofilm formation was inhibited. Following fractionation and mass spectrometry analysis, the major anti-biofilm factor identified in the spent media was secreted thermonuclease (Nuc). Considering reports that extracellular DNA (eDNA) is an important component of the biofilm matrix, we investigated the regulation and role of Nuc in USA300. The expression of the nuc gene was increased in a sigB mutant, repressed by glucose supplementation, and was unaffected by the agr quorum-sensing system. A FRET assay for Nuc activity was developed and confirmed the regulatory results. A USA300 nuc mutant was constructed and displayed an enhanced biofilm-forming capacity, and the nuc mutant also accumulated more high molecular weight eDNA than the WT and regulatory mutant strains. Inactivation of nuc in the USA300 sigB mutant background partially repaired the sigB biofilm-negative phenotype, suggesting that nuc expression contributes to the inability of the mutant to form biofilm. To test the generality of the nuc mutant biofilm phenotypes, the mutation was introduced into other S. aureus genetic backgrounds and similar increases in biofilm formation were observed. Finally, using multiple S. aureus strains and regulatory mutants, an inverse correlation between Nuc activity and biofilm formation was demonstrated. Altogether, our findings confirm the important role for eDNA in the S. aureus biofilm matrix and indicates Nuc is a regulator of biofilm formation

Filter Component Assessment

Advanced particulate filtration systems are currently being developed at Westinghouse for use in both coal-fired Integrated Gasification Combined Cycle (IGCC) and Pressurized Fluidized Bed Combustion (PFBC) systems. To date, Westinghouse has demonstrated 5855 hours of successful operation of first generation monolithic filter elements in PFBC applications when ash bridging or process thermal transient excursions are avoided. Alternate advanced monolithic and second generation fiber reinforced, filament wound and vacuum infiltrated filters are also being developed which are considered to have enhanced high temperature creep resistance, improved fracture toughness, or enhanced thermal shock characteristics, respectively. Mechanical and component fabrication improvements, as well as degradation mechanisms for each filter element have been identified by Westinghouse during exposure to simulated PFBC operating conditions and alkali-containing steam/air environments. Additional effort is currently being focused on determining the stability of the advanced monolithic high temperature creep resistant clay bonded silicon carbide (SiC) materials, alumina/mullite, and chemically vapor infiltrated (CVI) SiC materials during operation in the Westinghouse Advanced Particulate Filtration (W-APF) system at Foster Wheeler`s pressurized circulating fluidized-bed combustion (PCFBC) test facility in Karhula, Finland. Select advanced filter materials are being defined for additional long-term exposure in integrated gasification combined cycle (IGCC) gas streams. The results of these efforts are summarized in this paper. 6 refs., 7 figs., 11 tabs

Decoherence-protected quantum gates for a hybrid solid-state spin register

Protecting the dynamics of coupled quantum systems from decoherence by the environment is a key challenge for solid-state quantum information processing. An idle qubit can be efficiently insulated from the outside world via dynamical decoupling, as has recently been demonstrated for individual solid-state qubits. However, protection of qubit coherence during a multi-qubit gate poses a non-trivial problem: in general the decoupling disrupts the inter-qubit dynamics, and hence conflicts with gate operation. This problem is particularly salient for hybrid systems, wherein different types of qubits evolve and decohere at vastly different rates. Here we present the integration of dynamical decoupling into quantum gates for a paradigmatic hybrid system, the electron-nuclear spin register. Our design harnesses the internal resonance in the coupled-spin system to resolve the conflict between gate operation and decoupling. We experimentally demonstrate these gates on a two-qubit register in diamond operating at room temperature. Quantum tomography reveals that the qubits involved in the gate operation are protected as accurately as idle qubits. We further illustrate the power of our design by executing Grover's quantum search algorithm, achieving fidelities above 90% even though the execution time exceeds the electron spin dephasing time by two orders of magnitude. Our results directly enable decoherence-protected interface gates between different types of promising solid-state qubits. Ultimately, quantum gates with integrated decoupling may enable reaching the accuracy threshold for fault-tolerant quantum information processing with solid-state devices.Comment: This is original submitted version of the paper. The revised and finalized version is in print, and is subjected to the embargo and other editorial restrictions of the Nature journa

Novel Bone-Targeting Agent for Enhanced Delivery of Vancomycin to Bone

We examined the pharmacokinetic properties of vancomycin conjugated to a bone-targeting agent (BT) with high affinity for hydroxyapatite after systemic intravenous administration. The results confirm enhanced persistence of BT-vancomycin in plasma and enhanced accumulation in bone relative to vancomycin. This suggests that BT-vancomycin may be a potential carrier for the systemic targeted delivery of vancomycin in the treatment of bone infections, potentially reducing the reliance on surgical debridement to achieve the desired therapeutic outcome

Small Molecule Inhibitors of Staphylococcus aureus RnpA Alter Cellular mRNA Turnover, Exhibit Antimicrobial Activity, and Attenuate Pathogenesis

Methicillin-resistant Staphylococcus aureus is estimated to cause more U.S. deaths annually than HIV/AIDS. The emergence of hypervirulent and multidrug-resistant strains has further amplified public health concern and accentuated the need for new classes of antibiotics. RNA degradation is a required cellular process that could be exploited for novel antimicrobial drug development. However, such discovery efforts have been hindered because components of the Gram-positive RNA turnover machinery are incompletely defined. In the current study we found that the essential S. aureus protein, RnpA, catalyzes rRNA and mRNA digestion in vitro. Exploiting this activity, high through-put and secondary screening assays identified a small molecule inhibitor of RnpA-mediated in vitro RNA degradation. This agent was shown to limit cellular mRNA degradation and exhibited antimicrobial activity against predominant methicillin-resistant S. aureus (MRSA) lineages circulating throughout the U.S., vancomycin intermediate susceptible S. aureus (VISA), vancomycin resistant S. aureus (VRSA) and other Gram-positive bacterial pathogens with high RnpA amino acid conservation. We also found that this RnpA-inhibitor ameliorates disease in a systemic mouse infection model and has antimicrobial activity against biofilm-associated S. aureus. Taken together, these findings indicate that RnpA, either alone, as a component of the RNase P holoenzyme, and/or as a member of a more elaborate complex, may play a role in S. aureus RNA degradation and provide proof of principle for RNA catabolism-based antimicrobial therapy