White Papers for the Next Decadal Survey: Thermal Protection Systems and Instrumentation

NASA is anticipated to commission the next Planetary Science Decadal Survey (PSDS) with preparation expected in early calendar year 2020. The new PSDS will outline the priorities of science missions for the decade spanning 2023-2032. For the previous PSDS, the science and technology communities have been invited to submit white papers to the PSDS sub-panels as background information to guide the PSDS recommendations. The National Research Council has previously stated that white papers that represent the opinion of many authors from different institutions carried more significant and weight, and the recommendations from the previous PSDS attempted to reflect more of a consensus opinion.In 2009, a total of 4 white papers were submitted to the PSDS panels regarding thermal protection system (TPS) readiness for missions, as well as one on TPS instrumentation. The TPS readiness papers were co-authored by 90 individuals from many institutions. These white papers surveyed the TPS materials for both forebody and afterbody of a probe and analyzed the suitability of materials for missions to each destination. In addition, each paper outlined the ground testing required and ongoing technology development. Recommendations were provided for further technology development and ground test capability in order to fulfill future missions. Planning for the next PSDS: Many improvements and changes have occurred in the past 10 years with regard to TPS materials and instrumentation. New materials have been developed and tested, such as the high density material Heatshield for Extreme Entry Environment Technology (HEEET), and new capabilities for ground testing for high heating and high pressures have been added such as the 3 nozzle at the Ames arc jet. NASA has also flown several TPS instrumentation suites, such as MEDLI and EFT-1.In order to provide the PSDS sub-panels with the most current information about the state-of-the-art suit-ability for TPS materials for entry missions, we are be-ginning to update and draft new white papers. We will present the outline for material to be covered in the white papers, and we invite all IPPW attendees to parti-ciate in co-authoring these papers

Short and canonical GRBs

Within the "fireshell" model for the Gamma-Ray Bursts (GRBs) we define a "canonical GRB" light curve with two sharply different components: the Proper-GRB (P-GRB), emitted when the optically thick fireshell of electron-positron plasma originating the phenomenon reaches transparency, and the afterglow, emitted due to the collision between the remaining optically thin fireshell and the CircumBurst Medium (CBM). We outline our "canonical GRB" scenario, with a special emphasis on the discrimination between "genuine" and "fake" short GRBs.Comment: 4 pages, 3 figures, in the Proceedings of the "Gamma Ray Bursts 2007" meeting, November 5-9, 2007, Santa Fe, New Mexico, US

Near-Infrared Spectroscopic Measurement of the Effect of Leg Dominance on Muscle Oxygen Saturation During Cycling

The effect of leg dominance on the symmetry of the biomechanics during cycling remains uncertain -- asymmetries have been observed in kinematics and kinetics, while symmetries were found in muscle activation. No studies have yet investigated the symmetry of muscle metabolism during cycling. Near-infrared spectroscopy (NIRS) provides a non-invasive method to investigate the metabolic responses of specific muscles during cycling. PURPOSE: To determine whether there was an effect of leg dominance on thigh muscle oxygen saturation (SmO2) during incrementally loaded submaximal cycling using NIRS. METHODS: Eight right leg dominant, untrained subjects (5 men, 3 women; 31+/-2 yrs; 168.6+/-1.0 cm; 67.2+/-1.8 kg, mean +/- SE) volunteered to participate. Spectra were collected bilaterally from the vastus lateralis (VL) during supine rest and cycling. SmO2 was calculated using previously published methods. Subjects pedaled at 65 rpm while resistance to pedaling was increased in 0.5 kp increments from 0.5 kp every 3 min until the subject reached 80% of age-predicted maximal heart rate. SmO2 was averaged over 3 min for each completed stage. A two-way ANOVA was performed to test for leg differences. A priori contrasts were used to compare work levels to rest. RESULTS: VL SmO2 was not different between the dominant and non-dominant legs at rest and during exercise (p=0.57). How SmO2 changed with workload was also not different between legs (p=0.32). SmO2 at 0.5 kp (60.3+/-4.0, p=0.12) and 1.0 kp (59.5+/-4.0, p=0.10) was not different from rest (69.1+/-4.0). SmO2 at 1.5 kp (55.4 4.0, p=0.02), 2.0 kp (55.7+/-5.0, p=0.04), and 2.5 kp (43.4+/-7.9, p=0.01) was significantly lower than rest. CONCLUSION: VL SmO2 during cycling is not different between dominant and non-dominant legs and decreases with moderate workload in untrained cyclists. Assuming blood flow is directed equally to both legs, similar levels of oxygen extraction (as indicated by SmO2) suggests the metabolic load of cycling is not different between legs. This is in agreement with a recent study demonstrating symmetrical increase of muscle activation of the VL during cycling. Leg dominance did not influence VL SmO2 during submaximal cycling, but may have an effect at higher loads or during other forms of exercise, such as walking and running

Heatshield for Extreme Entry Environment Technology (HEEET) for Missions to Saturn and Beyond

This poster provides an overview of the requirements, design, development and testing of the 3D Woven TPS being developed under NASAs Heatshield for Extreme Entry Environment Technology (HEEET) project. Under this current program, NASA is working to develop a Thermal Protection System (TPS) capable of surviving entry into Saturn. A primary goal of the project is to build and test an Engineering Test Unit (ETU) to establish a Technical Readiness Level (TRL) of 6 for this technology by 2017

Inhibiting caspase cleavage of huntingtin reduces toxicity and aggregate formation in neuronal and nonneuronal cells.

Huntington's disease is a neurodegenerative disorder caused by CAG expansion that results in expansion of a polyglutamine tract at the extreme N terminus of huntingtin (htt). htt with polyglutamine expansion is proapoptotic in different cell types. Here, we show that caspase inhibitors diminish the toxicity of htt. Additionally, we define htt itself as an important caspase substrate by generating a site-directed htt mutant that is resistant to caspase-3 cleavage at positions 513 and 530 and to caspase-6 cleavage at position 586. In contrast to cleavable htt, caspase-resistant htt with an expanded polyglutamine tract has reduced toxicity in apoptotically stressed neuronal and nonneuronal cells and forms aggregates at a much reduced frequency. These results suggest that inhibiting caspase cleavage of htt may therefore be of potential therapeutic benefit in Huntington's disease

Heatshield for Extreme Entry Environment Technology (HEEET) - Enabling Missions Beyond Heritage Carbon Phenolic

This poster provides an overview of the requirements, design, development and testing of the 3D Woven TPS being developed under NASA's Heatshield for Extreme Entry Environment Technology (HEEET) project. Under this current program, NASA is working to develop a Thermal Protection System (TPS) capable of surviving entry into Venus or Saturn. A primary goal of the project is to build and test an Engineering Test Unit (ETU) to establish a Technical Readiness Level (TRL) of 6 for this technology by 2017

Heatshield for Extreme Entry Environment Technology (HEEET) Enabling Missions Beyond Heritage Carbon Phenolic

This poster provides an overview of the requirements, design, development and testing of the 3D Woven TPS being developed under NASAs Heatshield for Extreme Entry Environment Technology (HEEET) project. Under this current program, NASA is working to develop a Thermal Protection System (TPS) capable of surviving entry into Venus or Saturn. A primary goal of the project is to build and test an Engineering Test Unit (ETU) to establish a Technical Readiness Level (TRL) of 6 for this technology by 2017

Huntingtin Interacting Proteins Are Genetic Modifiers of Neurodegeneration

Huntington's disease (HD) is a fatal neurodegenerative condition caused by expansion of the polyglutamine tract in the huntingtin (Htt) protein. Neuronal toxicity in HD is thought to be, at least in part, a consequence of protein interactions involving mutant Htt. We therefore hypothesized that genetic modifiers of HD neurodegeneration should be enriched among Htt protein interactors. To test this idea, we identified a comprehensive set of Htt interactors using two complementary approaches: high-throughput yeast two-hybrid screening and affinity pull down followed by mass spectrometry. This effort led to the identification of 234 high-confidence Htt-associated proteins, 104 of which were found with the yeast method and 130 with the pull downs. We then tested an arbitrary set of 60 genes encoding interacting proteins for their ability to behave as genetic modifiers of neurodegeneration in a Drosophila model of HD. This high-content validation assay showed that 27 of 60 orthologs tested were high-confidence genetic modifiers, as modification was observed with more than one allele. The 45% hit rate for genetic modifiers seen among the interactors is an order of magnitude higher than the 1%–4% typically observed in unbiased genetic screens. Genetic modifiers were similarly represented among proteins discovered using yeast two-hybrid and pull-down/mass spectrometry methods, supporting the notion that these complementary technologies are equally useful in identifying biologically relevant proteins. Interacting proteins confirmed as modifiers of the neurodegeneration phenotype represent a diverse array of biological functions, including synaptic transmission, cytoskeletal organization, signal transduction, and transcription. Among the modifiers were 17 loss-of-function suppressors of neurodegeneration, which can be considered potential targets for therapeutic intervention. Finally, we show that seven interacting proteins from among 11 tested were able to co-immunoprecipitate with full-length Htt from mouse brain. These studies demonstrate that high-throughput screening for protein interactions combined with genetic validation in a model organism is a powerful approach for identifying novel candidate modifiers of polyglutamine toxicity

Superconductivity in the Intercalated Graphite Compounds C6Yb and C6Ca

In this letter we report the discovery of superconductivity in the isostructural graphite intercalation compounds C6Yb and C6Ca, with transition temperatures of 6.5K and 11.5K respectively. A structural characterisation of these compounds shows them to be hexagonal layered systems in the same class as other graphite intercalates. If we assume that all the outer s-electrons are transferred from the intercalant to the graphite sheets, then the charge transfer in these compounds is comparable to other superconducting graphite intercalants such as C8K 1,2 . However, the superconducting transition temperatures of C6Yb and C6Ca are up to two orders of magnitude greater. Interestingly, superconducting upper critical field studies and resistivity measurements suggest that these compounds are significantly more isotropic than pure graphite. This is unexpected as the effect of introducing the intercalant is to move the graphite layer further apart.Comment: 2 Figures. Please see accompanying theoretical manuscript, "Electronic Structure of the Superconducting Graphite Intercalates" by Csanyi et al., cond-mat/050356

Insulin-like growth factor 2 (IGF2) protects against Huntington's disease through the extracellular disposal of protein aggregates

Impaired neuronal proteostasis is a salient feature of many neurodegenerative diseases, highlighting alterations in the function of the endoplasmic reticulum (ER). We previously reported that targeting the transcription factor XBP1, a key mediator of the ER stress response, delays disease progression and reduces protein aggregation in various models of neurodegeneration. To identify disease modifier genes that may explain the neuroprotective effects of XBP1 deficiency, we performed gene expression profiling of brain cortex and striatum of these animals and uncovered insulin-like growth factor 2 (Igf2) as the major upregulated gene. Here, we studied the impact of IGF2 signaling on protein aggregation in models of Huntington's disease (HD) as proof of concept. Cell culture studies revealed that IGF2 treatment decreases the load of intracellular aggregates of mutant huntingtin and a polyglutamine peptide. These results were validated using induced pluripotent stem cells (iPSC)-derived medium spiny neurons from HD patients and spinocerebellar ataxia cases. The reduction in the levels of mutant huntingtin was associated with a decrease in the half-life of the intracellular protein. The decrease in the levels of abnormal protein aggregation triggered by IGF2 was independent of the activity of autophagy and the proteasome pathways, the two main routes for mutant huntingtin clearance. Conversely, IGF2 signaling enhanced the secretion of soluble mutant huntingtin species through exosomes and microvesicles involving changes in actin dynamics. Administration of IGF2 into the brain of HD mice using gene therapy led to a significant decrease in the levels of mutant huntingtin in three different animal models. Moreover, analysis of human postmortem brain tissue and blood samples from HD patients showed a reduction in IGF2 level. This study identifies IGF2 as a relevant factor deregulated in HD, operating as a disease modifier that buffers the accumulation of abnormal protein species