Manned Lunar Missions: An Exercise in Propulsion Trades and Sensitivities

A recent study performed for the In-Space Propulsion Technology Office at the Marshall Space Flight Center investigated the effects of using different propellant types on the different stages required to perform a manned lunar mission. The original study included investigations into propellant type, propellant storage technology options and sensitivities to specific impulse variations for a lunar orbit rendezvous mission. The initial mission characteristics were based on previous work led by Langley Research Center. Outlined in this paper are the results of that study and the work that followed. A lunar direct return architecture was added to the analysis. Since both architectures required assembly of the various propulsive stages in low Earth orbit and multiple launches to deliver those stages, investigations of launch sequence and scheduling sensitivities were also included. Results show that lunar direct return architectures require more mass to complete missions when compared to lunar orbit rendezvous missions. Within the given architectures, trends in the results tended to be very similar with the architectures indicating very little sensitivity to launch sequence and specific impulse variations and indicating more sensitivity to the propellant choice made for each stage and the time between launches. Even though this study investigates a small subset of the possible lunar architecture trade space, it does begin to outline some of the issues that must be investigated and the characteristics of the mission and the mission elements that are of most importance to a full architecture assessment

Vaccinia virus immune evasion: mechanisms, virulence and immunogenicity

Virus infection of mammalian cells is sensed by pattern recognition receptors and leads to an innate immune response that restricts virus replication and induces adaptive immunity. In response, viruses have evolved many countermeasures that enable them to replicate and be transmitted to new hosts, despite the host innate immune response. Poxviruses, such as vaccinia virus (VACV), have large DNA genomes and encode many proteins that are dedicated to host immune evasion. Some of these proteins are secreted from the infected cell, where they bind and neutralize complement factors, interferons, cytokines and chemokines. Other VACV proteins function inside cells to inhibit apoptosis or signalling pathways that lead to the production of interferons and pro-inflammatory cytokines and chemokines. In this review, these VACV immunomodulatory proteins are described and the potential to create more immunogenic VACV strains by manipulation of the gene encoding these proteins is discussed

Bat and pig IFN-induced transmembrane protein 3 restrict cell entry by influenza virus and lyssaviruses

IFN-induced transmembrane protein 3 (IFITM3) is a restriction factor that blocks cytosolic entry of numerous viruses that utilize acidic endosomal entry pathways. In humans and mice, IFITM3 limits influenza-induced morbidity and mortality. Although many IFITM3-sensitive viruses are zoonotic, whether IFITMs function as antiviral restriction factors in mammalian species other than humans and mice is unknown. Here, IFITM3 orthologues in the microbat (Myotis myotis) and pig (Sus scrofa domesticus) were identified using rapid amplification of cDNA ends. Amino acid residues known to be important for IFITM3 function were conserved in the pig and microbat orthologues. Ectopically expressed pig and microbat IFITM3 co-localized with transferrin (early endosomes) and CD63 (late endosomes/multivesicular bodies). Pig and microbat IFITM3 restricted cell entry mediated by multiple influenza haemagglutinin subtypes and lyssavirus glycoproteins. Expression of pig or microbat IFITM3 in A549 cells reduced influenza virus yields and nucleoprotein expression. Conversely, small interfering RNA knockdown of IFITM3 in pig NPTr cells and primary microbat cells enhanced virus replication, demonstrating that these genes are functional in their species of origin at endogenous levels. In summary, we showed that IFITMs function as potent broad-spectrum antiviral effectors in two mammals – pigs and bats – identified as major reservoirs for emerging viruses

ISWE: A Case Study of Technology Utilization

The International Space Welding Experiment is a joint project between the E.O. Paton Welding Institute of Kiev, Ukraine and the George C. Marshall Space Flight Center in Huntsville, Alabama. When an international partner is involved in a project, differences in design and testing philosophy can become a factor in the development of the hardware. This report addresses selected issues that arose during the ISWE hardware development as well as the solutions the ISWE team made

The Landscape of Videofluoroscopy in the UK: A Web-Based Survey

Videofluoroscopy (VFS) is considered one of the gold-standard assessments of swallowing. Whilst guidelines for the application and conduct of VFS exist, their translation into clinical practice remain challenging. To build a greater understanding on how VFS clinics operate in the UK. A web-based survey was shared with speech and language therapists (SLTs) working in VFS clinics via professional networks and social media from October 2018 to January 2019. 101 responses were received. Two thirds of clinics were SLT-led, with the majority of clinics being run by two SLTs (73.6%) and a radiographer (95.5%) also known as radiologic technologists, diagnostic radiographers and medical radiation technologists. Less than 50% of radiographers had received specialist training. Around half of the clinics used a standard assessment or analysis protocol and 88.1% a rating scale. Set recipes for a range of textures were used in 53.4% of VFS clinics. Barium and water soluble contrasts were used, but only 15.8% knew the concentration of contrast used. The most commonly reported VFS pulse and frame rate was 15 per second. There was evidence of a lack of SLT knowledge regarding technical operation of VFS. Screening times varied from 0.7–10 min (median 3 min, IQR 2.5–3.5). Around 50% of respondents reported quality issues affecting analysis. In a survey of UK SLTs, translation of VFS guidance into practice was found to be limited which may impact on the quality of assessment and analysis. Collaboration with radiology, strengthening of guidelines and greater uptake of specialist training is deemed essential

Improved parametrization of Antarctic krill target strength models

Author Posting. © Acoustical Society of America, 2006. This article is posted here by permission of Acoustical Society of America for personal use, not for redistribution. The definitive version was published in Journal of the Acoustical Society of America 119 (2006): 232-242, doi:10.1121/1.2141229.There are historical discrepancies between empirical observations of Antarctic krill target strength and predictions using theoretical scattering models. These differences are addressed through improved understanding of key model parameters. The scattering process was modeled using the distorted-wave Born approximation, representing the shape of the animal as a bent and tapered cylinder. Recently published length-based regressions were used to constrain the sound speed and density contrasts between the animal and the surrounding seawater, rather than the earlier approach of using single values for all lengths. To constrain the parameter governing the orientation of the animal relative to the incident acoustic wave, direct measurements of the orientation of krill in situ were made with a video plankton recorder. In contrast to previous indirect and aquarium-based observations, krill were observed to orient themselves mostly horizontally. Averaging predicted scattering over the measured distribution of orientations resulted in predictions of target strength consistent with in situ measurements of target strength of large krill (mean length 40–43 mm) at four frequencies (43–420 kHz), but smaller than expected under the semi-empirical model traditionally used to estimate krill target strength.This project was supported by NSF U.S. Antarctic Program Grant No. OPP-9910307. G. Lawson was supported by an Office of Naval Research Graduate Traineeship Award in Ocean Acoustics (Grant No. N000 14-03-1-0212), a Fulbright Scholarship, a Natural Sciences and Engineering Research Council of Canada Post-Graduate Scholarship, and the Woods Hole Oceanographic Institution Academic Programs Office

UK Waste Sector COVID-19 Response and Resilience Report

This is the final version. Available from the Covid-19 Waste Project website via the link in this recordFrom the beginning of March 2020, when COVID-19 was confirmed as a pandemic by World Health Organization, many sectors across the UK had to respond to an uncertain and rapidly evolving situation, including the introduction of a UK-wide lockdown on the 23rd March. The resources and waste sector, as a frontline service that protects both human health and the environment, had to maintain operations and this necessitated contingency planning on an unforeseen scale, with significant cross-sector engagement and collaboration, and new methods of working. To capture some of the learning from the first six months after the start of the UK-wide lockdown, the Chartered Institution of Wastes Management (CIWM) has been working in partnership with the University of Exeter to undertake a UK wide research exercise with multiple stakeholders across the resources and waste management sector. This forms part of a wider project led by the University of Exeter and funded by the Economic and Social Research Council, as part of UK Research and Innovation’s Rapid Response to COVID-19. The study used a qualitative social science methodology, undertaking a series of workshops and in-depth interviews with representatives from across the sector. Participants included national and local government officers, environmental regulators, and local authority and private sector waste professionals. Held in October 2020, this stakeholder engagement exercise explored immediate challenges, winter preparedness, and what is needed to support longer term sector resilience. It should be noted that this report is based on the discussions and feedback from sector representatives who generously took part. It is not designed to be a comprehensive assessment or account of the sector’s response but rather a snapshot in time during Autumn 2020 as the UK readied itself for the likelihood of a second wave of COVID-19 through the winter months. Much of the data and evidence that will be needed for a thorough assessment of the full impact of the pandemic on the sector is not yet available, but this report is designed to be a first step in the process to stimulate further reflection and learning.Economic and Social Research Council (ESRC

Bat IFITM3 restriction depends on S-palmitoylation and a polymorphic site within the CD225 domain

Host interferon-induced transmembrane proteins (IFITMs) are broad-spectrum antiviral restriction factors. Of these, IFITM3 potently inhibits viruses that enter cells through acidic endosomes, many of which are zoonotic and emerging viruses with bats (order Chiroptera) as their natural hosts. We previously demonstrated that microbat IFITM3 is antiviral. Here, we show that bat IFITMs are characterized by strong adaptive evolution and identify a highly variable and functionally important site-codon 70-within the conserved CD225 domain of IFITMs. Mutation of this residue in microbat IFITM3 impairs restriction of representatives of four different virus families that enter cells via endosomes. This mutant shows altered subcellular localization and reduced S-palmitoylation, a phenotype copied by mutation of conserved cysteine residues in microbat IFITM3. Furthermore, we show that microbat IFITM3 is S-palmitoylated on cysteine residues C71, C72, and C105, mutation of each cysteine individually impairs virus restriction, and a triple C71A-C72A-C105A mutant loses all restriction activity, concomitant with subcellular re-localization of microbat IFITM3 to Golgi-associated sites. Thus, we propose that S-palmitoylation is critical for Chiropteran IFITM3 function and identify a key molecular determinant of IFITM3 S-palmitoylation

Thymectomy in the treatment of ocular myasthenia gravis

AbstractBackground: Thymectomy is an effective and accepted treatment for myasthenia gravis, but thymectomy for ocular myasthenia gravis (Osserman stage I) is controversial. Objective: To assess the efficacy and propriety of thymectomy for the treatment of ocular myasthenia gravis. Methods: We conducted a review and follow-up of all patients who had thymectomy for the treatment of ocular myasthenia gravis between 1970 and 1998 at the University of California, Davis, Medical Center, and the University of Rome, “La Sapienza,” Rome, Italy. Patient response to thymectomy was categorized as follows: cured, patients who became symptom-free and required no further medication; improved, patients who required less medication and whose symptoms were less severe; unchanged, patients whose symptoms and medications were the same; worse, patients who had more severe symptoms, needed more medication, or died. Results: Sixty-one patients (mean age 37 years; range 14–73 years) were followed up for a mean duration of 9 years (range 0.5–29 years). Ocular myasthenia gravis with mixed and cortical thymomas, stages I to IV, occurred in 12 patients, and ocular myasthenia without thymomas occurred in 49 patients. Transsternal thymectomy (n = 55) and transcervical thymectomy (n = 6) resulted in cure in 31 (51%) patients, improvement in 12 (20%) patients, no change in 16 (26%) patients, and worsening of symptoms (including 1 postoperative death) in 2 patients. Patient outcomes were statistically independent of the duration of preoperative symptoms (mean 9.5 months), patient age, or the presence or absence of thymoma. In patients with ocular myasthenia, 70% were cured or improved after thymectomy; in the subgroup of patients with ocular myasthenia and thymoma, 67% were cured or improved. Conclusion: Thymectomy is an effective and safe treatment for patients with ocular myasthenia gravis