Cryogenic Orbital Testbed (CRYOTE) Ground Test Article, Final Report

Liquid propulsion has been used since Robert Goddard started developing a liquid oxygen (LO2) and gasoline powered rocket and fired it in 1923 (Ref. 1). In the following decades engineers settled on the combination of liquid hydrogen (LH2) and LO2 as the most efficient propellant combination for in-space travel. Due to their low temperatures (LH2 at 20 K and LO2 at 90 K), they require special handling and procedures. General Dynamics began developing LO2 and LH2 upper stages in 1956 in the form of Centaur, these efforts were soon funded by the Department of Defense in conjunction with NASA (beginning in 1958) (Ref. 2). Meanwhile NASA also worked with McDonnell Douglas to develop the SIV-B stage for the Saturn V rocket. In the subsequent years, the engineers were able to push the Centaur to up to 9 hr of orbital lifetime and the SIV-B to up to 6 hr. Due to venting the resultant boil-off from the high heat loads through the foam insulation on the upper stages, both vehicles remained in a settled configuration throughout the flights, thus the two phases of propellant (liquid and vapor) were separated at a known location. The one exception to this were the Titan/Centaur missions, which thanks to the lower boil-off using three layers of multilayer insulation (MLI), were able to coast unsettled for up to 5.25 hr during direct geosynchronous orbit insertion missions. In the years since there has been a continuous effort to extend the life of these upper stages from hours to days or even months

ALKBH3 partner ASCC3 mediates P-body formation and selective clearance of MMS-induced 1-methyladenosine and 3-methylcytosine from mRNA

BACKGROUND: Reversible enzymatic methylation of mammalian mRNA is widespread and serves crucial regulatory functions, but little is known to what degree chemical alkylators mediate overlapping modifications and whether cells distinguish aberrant from canonical methylations. METHODS: Here we use quantitative mass spectrometry to determine the fate of chemically induced methylbases in the mRNA of human cells. Concomitant alteration in the mRNA binding proteome was analyzed by SILAC mass spectrometry. RESULTS: MMS induced prominent direct mRNA methylations that were chemically identical to endogenous methylbases. Transient loss of 40S ribosomal proteins from isolated mRNA suggests that aberrant methylbases mediate arrested translational initiation and potentially also no-go decay of the affected mRNA. Four proteins (ASCC3, YTHDC2, TRIM25 and GEMIN5) displayed increased mRNA binding after MMS treatment. ASCC3 is a binding partner of the DNA/RNA demethylase ALKBH3 and was recently shown to promote disassembly of collided ribosomes as part of the ribosome quality control (RQC) trigger complex. We find that ASCC3-deficient cells display delayed removal of MMS-induced 1-methyladenosine (m CONCLUSIONS: Our findings conform to a model in which ASCC3-mediated disassembly of collided ribosomes allows demethylation of aberrant

Muon Spin Relaxation Study of (La, Ca)MnO3

We report predominantly zero field muon spin relaxation measurements in a series of Ca-doped LaMnO_3 compounds which includes the colossal magnetoresistive manganites. Our principal result is a systematic study of the spin-lattice relaxation rates 1/T_1 and magnetic order parameters in the series La_{1-x}Ca_xMnO_3, x = 0.0, 0.06, 0.18, 0.33, 0.67 and 1.0. In LaMnO_3 and CaMnO_3 we find very narrow critical regions near the Neel temperatures T_N and temperature independent 1/T_1 values above T_N. From the 1/T_1 in LaMnO_3 we derive an exchange integral J = 0.83 meV which is consistent with the mean field expression for T_N. All of the doped manganites except CaMnO_3 display anomalously slow, spatially inhomogeneous spin-lattice relaxation below their ordering temperatures. In the ferromagnetic (FM) insulating La_{0.82}Ca_{0.18}MnO_3 and ferromagnetic conducting La_{0.67}Ca_{0.33}MnO_3 systems we show that there exists a bi-modal distribution of \muSR rates \lambda_f and \lambda_s associated with relatively 'fast' and 'slow' Mn fluctuation rates, respectively. A physical picture is hypothesized for these FM phases in which the fast Mn rates are due to overdamped spin waves characteristic of a disordered FM, and the slower Mn relaxation rates derive from distinct, relatively insulating regions in the sample. Finally, likely muon sites are identified, and evidence for muon diffusion in these materials is discussed.Comment: 21 pages, 17 figure

Private Narratives and Infant Views: Iconizing 1970s Militancy in Contemporary Argentine Cinema

This is the author's accepted manuscript, made available with the permission of the publisher.This article analyses the connections between the subjective turn in the representation of militancy, iconicity, and historical examination in Infancia clandestina, a recent Argentine film that portrays the 1970s armed struggle through a child’s lens. Breaking with the leading interpretation that praises the movie because of its original exposition of left-leaning violence, I contend that this coming-of-age story fits within a version of militancy that originated in the mid-1990s and that has become quite common since the advent of the Kirchner administration in 2003. This particular version relies on a privatized and archaic image of activism that is at the core of the global iconization of 1970s militancy. An analysis of the filmic use of an infant perspective and of anime-style cartoons illuminates how contemporary Argentine cinema both registers and participates in this iconizing process

A Novel Neurotrophic Drug for Cognitive Enhancement and Alzheimer's Disease

Currently, the major drug discovery paradigm for neurodegenerative diseases is based upon high affinity ligands for single disease-specific targets. For Alzheimer's disease (AD), the focus is the amyloid beta peptide (Aß) that mediates familial Alzheimer's disease pathology. However, given that age is the greatest risk factor for AD, we explored an alternative drug discovery scheme that is based upon efficacy in multiple cell culture models of age-associated pathologies rather than exclusively amyloid metabolism. Using this approach, we identified an exceptionally potent, orally active, neurotrophic molecule that facilitates memory in normal rodents, and prevents the loss of synaptic proteins and cognitive decline in a transgenic AD mouse model

What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer's disease, about the therapeutic strategies in Alzheimer's research

Experimental models that faithfully mimic the developmental pathology of sporadic Alzheimer's disease (sAD) in humans are important for testing the novel therapeutic approaches in sAD treatment. Widely used transgenic mice AD models have provided valuable insights into the molecular mechanisms underlying the memory decline but, due to the particular β-amyloid-related gene manipulation, they resemble the familial but not the sporadic AD form, and are, therefore, inappropriate for this purpose. In line with the recent findings of sAD being recognised as an insulin resistant brains state (IRBS), a new, non-transgenic, animal model has been proposed as a representative model of sAD, developed by intracerebroventricular application of the betacytotoxic drug streptozotocin (STZ-icv). The STZ-icv-treated animals (mostly rats and mice) develop IRBS associated with memory impairment and progressive cholinergic deficits, glucose hypometabolism, oxidative stress and neurodegeneration that share many features in common with sAD in humans. The therapeutic strategies (acetylcholinesterase inhibitors, antioxidants and many other drugs) that have been tested until now on the STZ-icv animal model have been reviewed and the comparability of the drugs' efficacy in this non-transgenic sAD model and the results from clinical trials on sAD patients, evaluated