Activation of skeletal muscle is controlled by a dual-filament mechano-sensing mechanism

Contraction of skeletal muscle is triggered by a transient rise in intracellular calcium concentration leading to a structural change in the actin-containing thin filaments that allows binding of myosin motors from the thick filaments. Most myosin motors are unavailable for actin binding in resting muscle because they are folded back against the thick filament backbone. Release of the folded motors is triggered by thick filament stress, implying a positive feedback loop in the thick filaments. However, it was unclear how thin and thick filament activation mechanisms are coordinated, partly because most previous studies of the thin filament regulation were conducted at low temperatures where the thick filament mechanisms are inhibited. Here, we use probes on both troponin in the thin filaments and myosin in the thick filaments to monitor the activation states of both filaments in near-physiological conditions. We characterize those activation states both in the steady state, using conventional titrations with calcium buffers, and during activation on the physiological timescale, using calcium jumps produced by photolysis of caged calcium. The results reveal three activation states of the thin filament in the intact filament lattice of a muscle cell that are analogous to those proposed previously from studies on isolated proteins. We characterize the rates of the transitions between these states in relation to thick filament mechano-sensing and show how thin- and thick-filament-based mechanisms are coupled by two positive feedback loops that switch on both filaments to achieve rapid cooperative activation of skeletal muscle

Solar sail science mission applications and advancement : solar sailing: concepts, technology, missions

Solar sailing has long been envisaged as an enabling or disruptive technology. The promise of open-ended missions allows consideration of radically new trajectories and the delivery of spacecraft to previously unreachable or unsustainable observation outposts. A mission catalogue is presented of an extensive range of potential solar sail applications, allowing identification of the key features of missions which are enabled, or significantly enhance, through solar sail propulsion. Through these considerations a solar sail application-pull technology development roadmap is established, using each mission as a technology stepping-stone to the next. Having identified and developed a solar sail application-pull technology development roadmap, this is incorporated into a new vision for solar sailing. The development of new technologies, especially for space applications, is high-risk. The advancement difficulty of low technology readiness level research is typically underestimated due to a lack of recognition of the advancement degree of difficulty scale. Recognising the currently low technology readiness level of traditional solar sailing concepts, along with their high advancement degree of difficulty and a lack of near-term applications a new vision for solar sailing is presented which increases the technology readiness level and reduces the advancement degree of difficulty of solar sailing. Just as the basic principles of solar sailing are not new, they have also been long proven and utilised in spacecraft as a low-risk, high-return limited-capability propulsion system. It is therefore proposed that this significant heritage be used to enable rapid, near-term solar sail future advancement through coupling currently mature solar sail, and other, technologies with current solar sail technology developments. As such the near-term technology readiness level of traditional solar sailing is increased, while simultaneously reducing the advancement degree of difficulty along the solar sail application-pull technology development roadmap

Realistic Earth escape strategies for solar sailing

With growing interest in solar sailing comes the requirement to provide a basis for future detailed planetary escape mission analysis by drawing together prior work, clarifying and explaining previously anomalies. Previously unexplained seasonal variations in sail escape times from Earth orbit are explained analytically and corroborated within a numerical trajectory model. Blended-sail control algorithms, explicitly independent of time, which providenear-optimal escape trajectories and maintain a safe minimum altitude and which are suitable as a potential autonomous onboard controller, are then presented. These algorithms are investigated from a range of initial conditions and are shown to maintain the optimality previously demonstrated by the use of a single-energy gain control law but without the risk of planetary collision. Finally, it is shown that the minimum sail characteristic acceleration required for escape from a polar orbit without traversing the Earth shadow cone increases exponentially as initial altitude is decreased

Perceptions and Experiences of the University of Nottingham Pilot SARS-CoV-2 Asymptomatic Testing Service: A Mixed-Methods Study

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. We aimed to explore student and staff perceptions and experiences of a pilot SARS-CoV-2 asymptomatic testing service (P-ATS) in a UK university campus setting. This was a mixed-method study comprised of an online survey, and thematic analysis of qualitative data from interviews and focus groups conducted at the mid-point and end of the 12-week P-ATS programme. Ninety-nine students (84.8% female, 70% first year; 93.9% P-ATS participants) completed an online survey, 41 individuals attended interviews or focus groups, including 31 students (21 first year; 10 final year) and 10 staff. All types of testing and logistics were highly acceptable (virus: swab, saliva; antibody: finger prick) and 94.9% would participate again. Reported adherence to weekly virus testing was high (92.4% completed ≥6 tests; 70.8% submitted all 10 swabs; 89.2% completed ≥1 saliva sample) and 76.9% submitted ≥3 blood samples. Students tested to “keep campus safe”, “contribute to national efforts to control COVID-19”, and “protect others”. In total, 31.3% had high anxiety as measured by the Generalized Anxiety Disorder scale (GAD-7) (27.1% of first year). Students with lower levels of anxiety and greater satisfaction with university communications around P-ATS were more likely to adhere to virus and antibody tests. Increased adherence to testing was associated with higher perceived risk of COVID-19 to self and others. Qualitative findings revealed 5 themes and 13 sub-themes: “emotional responses to COVID-19”, “university life during COVID-19”, “influences on testing participation”, “testing physical and logistical factors” and “testing effects on mental wellbeing”. Asymptomatic COVID-19 testing (SARS-CoV-2 virus/antibodies) is highly acceptable to students and staff in a university campus setting. Clear communications and strategies to reduce anxiety are likely to be important for testing uptake and adherence. Strategies are needed to facilitate social connections and mitigate the mental health impacts of COVID-19 and self-isolation