Evaluation of fasteners and fastener materials for space vehicles

Testing of fasteners, bolts, rivets, and fastener materials - high temperature alloy

Beryllium fastener technology

Program was conducted to develop, produce, and test optimum-configuration, beryllium prestressed and blind fasteners. The program was carried out in four phases - phase 1, feasibility study, phase 2, development, phase 3, evaluation of beryllium alloys, and phase 4, fabrication and testing

Evaluation of fasteners and fastener materials for space vehicles Final report, Nov. 1963 - Nov. 1965

Evaluation of high strength alloys used as fasteners for space vehicle

Evaluation of fasteners and fastener materials for space vehicles annual report, nov. 1963 - nov. 1964

Tensile and double shear tests at cryogenic and room temperature after thermal cycling of high strength fasteners and materials used on space vehicle

Development of a New Tacaribe Arenavirus Infection Model and Its Use to Explore Antiviral Activity of a Novel Aristeromycin Analog

Background A growing number of arenaviruses can cause a devastating viral hemorrhagic fever (VHF) syndrome. They pose a public health threat as emerging viruses and because of their potential use as bioterror agents. All of the highly pathogenic New World arenaviruses (NWA) phylogenetically segregate into clade B and require maximum biosafety containment facilities for their study. Tacaribe virus (TCRV) is a nonpathogenic member of clade B that is closely related to the VHF arenaviruses at the amino acid level. Despite this relatedness, TCRV lacks the ability to antagonize the host interferon (IFN) response, which likely contributes to its inability to cause disease in animals other than newborn mice. Methodology/Principal Findings Here we describe a new mouse model based on TCRV challenge of AG129 IFN-α/β and -γ receptor-deficient mice. Titration of the virus by intraperitoneal (i.p.) challenge of AG129 mice resulted in an LD50 of ∼100 fifty percent cell culture infectious doses. Virus replication was evident in the serum, liver, lung, spleen, and brain 4–8 days after inoculation. MY-24, an aristeromycin derivative active against TCRV in cell culture at 0.9 µM, administered i.p. once daily for 7 days, offered highly significant (P\u3c0.001) protection against mortality in the AG129 mouse TCRV infection model, without appreciably reducing viral burden. In contrast, in a hamster model of arenaviral hemorrhagic fever based on challenge with clade A Pichinde arenavirus, MY-24 did not offer significant protection against mortality. Conclusions/Significance MY-24 is believed to act as an inhibitor of S-adenosyl-L-homocysteine hydrolase, but our findings suggest that it may ameliorate disease by blunting the effects of the host response that play a role in disease pathogenesis. The new AG129 mouse TCRV infection model provides a safe and cost-effective means to conduct early-stage pre-clinical evaluations of candidate antiviral therapies that target clade B arenaviruses

Effective Oral Favipiravir (T-705) Therapy Initiated after the Onset of ClinicalDisease in a Model of Arenavirus Hemorrhagic Fever

Background Lassa and Junín viruses are the most prominent members of the Arenaviridae family of viruses that cause viral hemorrhagic fever syndromes Lassa fever and Argentine hemorrhagic fever, respectively. At present, ribavirin is the only antiviral drug indicated for use in treatment of these diseases, but because of its limited efficacy in advanced cases of disease and its toxicity, safer and more effective antivirals are needed. Methodology/Principal Findings Here, we used a model of acute arenaviral infection in outbred guinea pigs based on challenge with an adapted strain of Pichindé virus (PICV) to further preclinical development of T-705 (Favipiravir), a promising broad-spectrum inhibitor of RNA virus infections. The guinea pig-adapted passage 19 PICV was uniformly lethal with an LD50 of ∼5 plaque-forming units and disease was associated with fever, weight loss, thrombocytopenia, coagulation defects, increases in serum aspartate aminotransferase (AST) concentrations, and pantropic viral infection. Favipiravir (300 mg/kg/day, twice daily orally for 14 days) was highly effective, as all animals recovered fully from PICV-induced disease even when therapy was initiated one week after virus challenge when animals were already significantly ill with marked fevers and thrombocytopenia. Antiviral activity and reduced disease severity was evidenced by dramatic reductions in peak serum virus titers and AST concentrations in favipiravir-treated animals. Moreover, a sharp decrease in body temperature was observed shortly after the start of treatment. Oral ribavirin was also evaluated, and although effective, the slower rate of recovery may be a sign of the drug\u27s known toxicity. Conclusions/Significance Our findings support further development of favipiravir for the treatment of severe arenaviral infections. The optimization of the experimental favipiravir treatment regimen in the PICV guinea pig model will inform critical future studies in the same species based on challenge with highly pathogenic arenaviruses such as Lassa and Junín. Author Summary Several viruses in the Arenaviridae family cause severe life-threatening hemorrhagic fever syndromes, which are considered neglected tropical diseases in endemic areas of Africa and South America. Ribavirin, the only licensed antiviral indicated for use has limited efficacy when treating advanced cases of disease and is associated with toxicity. In the present study, we use a model of acute arenaviral disease in guinea pigs based on infection with an adapted strain of the Pichindé arenavirus (PICV) to further preclinical development of a promising broad-spectrum antiviral drug candidate, favipiravir. Oral favipiravir was highly effective in the treatment of sick animals with marked fevers, as all recovered fully from lethal PICV infection even when therapy was initiated one week after virus challenge. Antiviral activity and reduced disease severity was evidenced by dramatic reductions in serum virus loads and serum aspartate aminotransferase, an enzyme released into the bloodstream following tissue damage and a marker for severe arenaviral infections. Moreover, a sharp decrease in fever was observed shortly after the onset of treatment. Our findings support further development of favipiravir for the treatment of severe arenaviral infections, for which there are presently no safe and effective therapies for treating advanced cases of disease