Spacecraft Dynamics and Control Program at AFRPL

A number of future DOD and NASA spacecraft such as the space based radar will be not only an order of magnitude larger in dimension than the current spacecraft, but will exhibit extreme structural flexibility with very low structural vibration frequencies. Another class of spacecraft (such as the space defense platforms) will combine large physical size with extremely precise pointing requirement. Such problems require a total departure from the traditional methods of modeling and control system design of spacecraft where structural flexibility is treated as a secondary effect. With these problems in mind, the Air Force Rocket Propulsion Laboratory (AFRPL) initiated research to develop dynamics and control technology so as to enable the future large space structures (LSS). AFRPL's effort in this area can be subdivided into the following three overlapping areas: (1) ground experiments, (2) spacecraft modeling and control, and (3) sensors and actuators. Both the in-house and contractual efforts of the AFRPL in LSS are summarized

Peptide gels of fully-defined composition and mechanics for probing cell-cell and cell-matrix interactions in vitro

© 2019 Current materials used for in vitro 3D cell culture are often limited by their poor similarity to human tissue, batch-to-batch variability and complexity of composition and manufacture. Here, we present a “blank slate” culture environment based on a self-assembling peptide gel free from matrix motifs. The gel can be customised by incorporating matrix components selected to match the target tissue, with independent control of mechanical properties. Therefore the matrix components are restricted to those specifically added, or those synthesised by encapsulated cells. The flexible 3D culture platform provides full control over biochemical and physical properties, allowing the impact of biochemical composition and tissue mechanics to be separately evaluated in vitro. Here, we demonstrate that the peptide gels support the growth of a range of cells including human induced pluripotent stem cells and human cancer cell lines. Furthermore, we present proof-of-concept that the peptide gels can be used to build disease-relevant models. Controlling the peptide gelator concentration allows peptide gel stiffness to be matched to normal breast (1 kPa), with higher stiffness favouring the viability of breast cancer cells over normal breast cells. In parallel, the peptide gels may be modified with matrix components relevant to human breast, such as collagen I and hyaluronan. The choice and concentration of these additions affect the size, shape and organisation of breast epithelial cell structures formed in co-culture with fibroblasts. This system therefore provides a means of unravelling the individual influences of matrix, mechanical properties and cell-cell interactions in cancer and other diseases

Preparation of a User-Defined Peptide Gel for Controlled 3D Culture Models of Cancer and Disease

There is a growing awareness that cells grown in 3D better model in vivo behavior than those grown in 2D. In this protocol, we describe a simple and tunable 3D hydrogel, suitable for culturing cells and tissue in a setting that matches their native environment. This is particularly important for researchers investigating the initiation, growth, and treatment of cancer where the interaction between cells and their local extracellular matrix is a fundamental part of the model

Local is not always better: the impact of climate information on values, behavior and policy support

In the current research, we experimentally examined the effect of providing local or global information about the impacts of climate change on individuals’ perceived importance of climate change and on their willingness to take action to address it, including policy support. We examined these relationships in the context of individuals’ general value orientations. Our findings, from 99 US residents, suggest that different kinds of climate information (local, global, or none) interact with values vis-à-vis our dependent variables. Specifically, while self-transcendent values predict perceived importance and pro-environmental behavior across all three information conditions, the effect on policy support is less clear. Furthermore, we detected a “reactance effect” where individuals with self-enhancing values who read local information thought that climate change was less important and were less willing to engage in pro-environmental behavior and support policy than self-enhancing individuals in the other information conditions. These results suggest that policy makers and public communicators may want to be cognizant of their audience’s general value orientation. Local information may not only be ineffective but may also prove counterproductive with individuals whose value orientations are more self-enhancing than self-transcendent

Climate change and climate variability: personal motivation for adaptation and mitigation

BACKGROUND: Global climate change impacts on human and natural systems are predicted to be severe, far reaching, and to affect the most physically and economically vulnerable disproportionately. Society can respond to these threats through two strategies: mitigation and adaptation. Industry, commerce, and government play indispensable roles in these actions but so do individuals, if they are receptive to behavior change. We explored whether the health frame can be used as a context to motivate behavioral reductions of greenhouse gas emissions and adaptation measures. METHODS: In 2008, we conducted a cross-sectional survey in the United States using random digit dialing. Personal relevance of climate change from health threats was explored with the Health Belief Model (HBM) as a conceptual frame and analyzed through logistic regressions and path analysis. RESULTS: Of 771 individuals surveyed, 81% (n = 622) acknowledged that climate change was occurring, and were aware of the associated ecologic and human health risks. Respondents reported reduced energy consumption if they believed climate change could affect their way of life (perceived susceptibility), Odds Ratio (OR) = 2.4 (95% Confidence Interval (CI): 1.4-4.0), endanger their life (perceived severity), OR = 1.9 (95% CI: 1.1-3.1), or saw serious barriers to protecting themselves from climate change, OR = 2.1 (95% CI: 1.2-3.5). Perceived susceptibility had the strongest effect on reduced energy consumption, either directly or indirectly via perceived severity. Those that reported having the necessary information to prepare for climate change impacts were more likely to have an emergency kit OR = 2.1 (95% CI: 1.4-3.1) or plan, OR = 2.2 (95% CI: 1.5-3.2) for their household, but also saw serious barriers to protecting themselves from climate change or climate variability, either by having an emergency kit OR = 1.6 (95% CI: 1.1-2.4) or an emergency plan OR = 1.5 (95%CI: 1.0-2.2). CONCLUSIONS: Motivation for voluntary mitigation is mostly dependent on perceived susceptibility to threats and severity of climate change or climate variability impacts, whereas adaptation is largely dependent on the availability of information relevant to climate change. Thus, the climate change discourse could be framed from a health perspective to motivate behaviour change

OptoRheo: Simultaneous in situ micro-mechanical sensing and 3D imaging of live cell cultures

Biomechanical cues from the extracellular matrix (ECM) are essential for directing many cellular processes, from normal development and repair, to disease progression. To better understand cell-matrix interactions, we have developed a new instrument named ‘OptoRheo’ that combines light sheet fluorescence microscopy with particle tracking microrheology. OptoRheo lets us image cells in 3D as they proliferate over several days while simultaneously sensing the mechanical properties of the surrounding extracellular and pericellular matrix at a sub-cellular length scale. OptoRheo can be used in two operational modalities (with and without an optical trap) to extend the dynamic range of microrheology measurements. We corroborated this by characterising the ECM surrounding live breast cancer cells in two distinct culture systems, cell clusters in 3D hydrogels and spheroids in suspension culture. This cutting-edge instrument will transform the exploration of drug transport through complex cell culture matrices and optimise the design of the next-generation of disease models

The RESET project: constructing a European tephra lattice for refined synchronisation of environmental and archaeological events during the last c. 100 ka

This paper introduces the aims and scope of the RESET project (. RESponse of humans to abrupt Environmental Transitions), a programme of research funded by the Natural Environment Research Council (UK) between 2008 and 2013; it also provides the context and rationale for papers included in a special volume of Quaternary Science Reviews that report some of the project's findings. RESET examined the chronological and correlation methods employed to establish causal links between the timing of abrupt environmental transitions (AETs) on the one hand, and of human dispersal and development on the other, with a focus on the Middle and Upper Palaeolithic periods. The period of interest is the Last Glacial cycle and the early Holocene (c. 100-8 ka), during which time a number of pronounced AETs occurred. A long-running topic of debate is the degree to which human history in Europe and the Mediterranean region during the Palaeolithic was shaped by these AETs, but this has proved difficult to assess because of poor dating control. In an attempt to move the science forward, RESET examined the potential that tephra isochrons, and in particular non-visible ash layers (cryptotephras), might offer for synchronising palaeo-records with a greater degree of finesse. New tephrostratigraphical data generated by the project augment previously-established tephra frameworks for the region, and underpin a more evolved tephra 'lattice' that links palaeo-records between Greenland, the European mainland, sub-marine sequences in the Mediterranean and North Africa. The paper also outlines the significance of other contributions to this special volume: collectively, these illustrate how the lattice was constructed, how it links with cognate tephra research in Europe and elsewhere, and how the evidence of tephra isochrons is beginning to challenge long-held views about the impacts of environmental change on humans during the Palaeolithic. © 2015 Elsevier Ltd.RESET was funded through Consortium Grants awarded by the Natural Environment Research Council, UK, to a collaborating team drawn from four institutions: Royal Holloway University of London (grant reference NE/E015905/1), the Natural History Museum, London (NE/E015913/1), Oxford University (NE/E015670/1) and the University of Southampton, including the National Oceanography Centre (NE/01531X/1). The authors also wish to record their deep gratitude to four members of the scientific community who formed a consultative advisory panel during the lifetime of the RESET project: Professor Barbara Wohlfarth (Stockholm University), Professor Jørgen Peder Steffensen (Niels Bohr Institute, Copenhagen), Dr. Martin Street (Romisch-Germanisches Zentralmuseum, Neuwied) and Professor Clive Oppenheimer (Cambridge University). They provided excellent advice at key stages of the work, which we greatly valued. We also thank Jenny Kynaston (Geography Department, Royal Holloway) for construction of several of the figures in this paper, and Debbie Barrett (Elsevier) and Colin Murray Wallace (Editor-in-Chief, QSR) for their considerable assistance in the production of this special volume.Peer Reviewe

Performance evaluation of a non-invasive one-step multiplex RT-qPCR assay for detection of SARS-CoV-2 direct from saliva

Polymerase chain reaction (PCR) has proven to be the gold-standard for SARS-CoV-2 detection in clinical settings. The most common approaches rely on nasopharyngeal specimens obtained from swabs, followed by RNA extraction, reverse transcription and quantitative PCR. Although swab-based PCR is sensitive, swabbing is invasive and unpleasant to administer, reducing patient compliance for regular testing and resulting in an increased risk of improper sampling. To overcome these obstacles, we developed a non-invasive one-step RT-qPCR assay performed directly on saliva specimens. The University of Nottingham Asymptomatic Testing Service protocol simplifies sample collection and bypasses the need for RNA extraction, or additives, thus helping to encourage more regular testing and reducing processing time and costs. We have evaluated the assay against the performance criteria specified by the UK regulatory bodies and attained accreditation (BS EN ISO/IEC 17,025:2017) for SARS-CoV-2 diagnostic testing by the United Kingdom Accreditation Service. We observed a sensitivity of 1 viral copy per microlitre of saliva, and demonstrated a concordance of > 99.4% between our results and those of other accredited testing facilities. We concluded that saliva is a stable medium that allows for a highly precise, repeatable, and robust testing method

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.