908 research outputs found

    Robotics and AI-Enabled On-Orbit Operations With Future Generation of Small Satellites

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    The low-cost and short-lead time of small satellites has led to their use in science-based missions, earth observation, and interplanetary missions. Today, they are also key instruments in orchestrating technological demonstrations for On-Orbit Operations (O 3 ) such as inspection and spacecraft servicing with planned roles in active debris removal and on-orbit assembly. This paper provides an overview of the robotics and autonomous systems (RASs) technologies that enable robotic O 3 on smallsat platforms. Major RAS topics such as sensing & perception, guidance, navigation & control (GN&C) microgravity mobility and mobile manipulation, and autonomy are discussed from the perspective of relevant past and planned missions

    Distinct NAD(P)H binding configurations revealed by fluorescence lifetime, anisotropy and polarised two-photon absorption

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    NADH and NADPH play key roles in the regulation of metabolism. Their endogenous fluorescence is sensitive to enzyme binding, allowing changes in cellular metabolic state to be determined using fluorescence lifetime imaging microscopy (FLIM). However, to fully uncover the underlying biochemistry, the relationships between their fluorescence and binding dynamics require greater understanding. Here we accomplish this through time- and polarisation-resolved fluorescence and polarised two-photon absorption measurements. Two lifetimes result from binding of both NADH to lactate dehydrogenase and NADPH to isocitrate dehydrogenase. The composite fluorescence anisotropy indicates the shorter (1.3-1.6ns) decay component to be accompanied by local motion of the nicotinamide ring, pointing to attachment solely via the adenine moiety. For the longer lifetime (3.2-4.4ns), the nicotinamide conformational freedom is found to be fully restricted. As full and partial nicotinamide binding are recognised steps in dehydrogenase catalysis, our results unify photophysical, structural and functional aspects of NADH and NADPH binding and clarify the biochemical processes that underlie their contrasting intracellular lifetimes

    Improving engagement of stroke survivors using desktop virtual Reality-Based serious games for upper limb rehabilitation: A multiple case study

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    Engagement with upper limb rehabilitation post-stroke can improve rehabilitation outcomes. Virtual Reality can be used to make rehabilitation more engaging. In this paper, we propose a multiple case study to determine: (1) whether game design principles (identified in an earlier study as being likely to engage) actually do engage, in practice, a sample of stroke survivors with a Desktop Virtual Reality-based Serious Game designed for upper limb rehabilitation; and (2) what game design factors support the existence of these principles in the game. In this study, we considered 15 principles: awareness , feedback , interactivity , flow , challenge , attention , interest , involvement , psychological absorption , motivation , effort , clear instructions , usability , purpose , and a first-person view . Four stroke survivors used, for a period of 12 weeks, a Virtual Reality-based upper limb rehabilitation system called the Neuromender Rehabilitation System. The stroke survivors were then asked how well each of the 15 principles was supported by the Neuromender Rehabilitation System and how much they felt each principle supported their engagement with the system. All the 15 tested principles had good or reasonable support from the participants as being engaging. Use of feedback was emphasised as an important design factor for supporting the design principles, but there was otherwise little agreement in important design factors among the participants. This indicates that more personalised experiences may be necessary for optimised engagement. The insight gained can be used to inform the design of a larger scale statistical study into what engages stroke survivors with Desktop Virtual Reality-based upper limb rehabilitation

    Effect of New Zealand Blackcurrant Extract on Substrate Oxidation and Cycling Performance in Normobaric Hypoxia

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    Blackcurrant is high in anthocyanin content. We have shown enhanced whole-body fat oxidation and increased time trial performance during cycling, in addition to increased femoral artery diameter during a sustained submaximal isometric contraction of the m.quadriceps with intake of New Zealand blackcurrant (NZBC) extract in normobaric normoxia (Cook et al., 2015, 2017). The effect of blackcurrant on metabolic and physiological responses and performance during cycling in normobaric hypoxia are not known. PURPOSE: To examine the effect of NZBC extract on intensity-dependent physiological and metabolic responses and 16.1-km cycling time trial in trained cyclists in normobaric hypoxia. METHODS: The study used a double-blind randomized cross-over design. Eleven healthy men from cycling and triathlon clubs with at least 3 yrs experience and cycling 8-10 hr·wk−1 (age: 38±11 yrs, height: 179±4 cm, body mass: 76±8 kg, V̇O2max: 47±5 mL·kg−1·min−1, maximum power: 398±38 W, mean±SD) ingested NZBC extract (600 mg·day−1 containing 220 mg anthocyanins) or placebo (PL) for 7 days (washout 14 days). Participants performed bouts of 10 min at 45, 55 and 65% V̇O2max, using indirect calorimetry and blood sampling, followed by a 16.1 km timetrial on a SRM ergometer (SRM International, Germany). Participants were familiarized for the time-trial. All testing took place in a temperature controlled (15°C) normobaric hypoxic chamber set at an altitude of ~2500 m (15% FiO2) (TIS Services, Medstead, UK) in morning sessions. Data was analysed using paired t-tests. RESULTS: At each intensity, NZBC extract had no effect on metabolic and physiological responses (e.g. at 65% V̇O2max, heart rate - PL: 133±12, NZBC; 132±12 beats·min-1); fat oxidation - PL: 0.24±0.12, NZBC: 0.20±0.16 g·min-1; carbohydrate oxidation - PL: 2.34±0.42, NZBC: 2.48±0.35 g·min-1; lactate - PL: 1.37±0.45, NZBC: 1.56±0.57 mmol·L-1). No improvements in 16.1 km time-trial performance were observed (PL: 1685±92, NZBC: 1685±99 sec). CONCLUSION: Seven day intake of New Zealand blackcurrant extract does not change whole-body fat oxidation and 16.1 km time-trial performance during cycling in normobaric hypoxia

    Gradients of glucose metabolism regulate morphogen signalling required for specifying tonotopic organisation in the chicken cochlea

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    In vertebrates with elongated auditory organs, mechanosensory hair cells (HCs) are organised such that complex sounds are broken down into their component frequencies along a proximal-to-distal long (tonotopic) axis. Acquisition of unique morphologies at the appropriate position along the chick cochlea, the basilar papilla, requires that nascent HCs determine their tonotopic positions during development. The complex signalling within the auditory organ between a developing HC and its local niche along the cochlea is poorly understood. Using a combination of live imaging and NAD(P)H fluorescence lifetime imaging microscopy, we reveal that there is a gradient in the cellular balance between glycolysis and the pentose phosphate pathway in developing HCs along the tonotopic axis. Perturbing this balance by inhibiting different branches of cytosolic glucose catabolism disrupts developmental morphogen signalling and abolishes the normal tonotopic gradient in HC morphology. These findings highlight a causal link between graded morphogen signalling and metabolic reprogramming in specifying the tonotopic identity of developing HCs

    CHCHD4 regulates tumour proliferation and EMT-related phenotypes, through respiratory chain-mediated metabolism

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    Abstract: Background: Mitochondrial oxidative phosphorylation (OXPHOS) via the respiratory chain is required for the maintenance of tumour cell proliferation and regulation of epithelial to mesenchymal transition (EMT)-related phenotypes through mechanisms that are not fully understood. The essential mitochondrial import protein coiled-coil helix coiled-coil helix domain-containing protein 4 (CHCHD4) controls respiratory chain complex activity and oxygen consumption, and regulates the growth of tumours in vivo. In this study, we interrogate the importance of CHCHD4-regulated mitochondrial metabolism for tumour cell proliferation and EMT-related phenotypes, and elucidate key pathways involved. Results: Using in silico analyses of 967 tumour cell lines, and tumours from different cancer patient cohorts, we show that CHCHD4 expression positively correlates with OXPHOS and proliferative pathways including the mTORC1 signalling pathway. We show that CHCHD4 expression significantly correlates with the doubling time of a range of tumour cell lines, and that CHCHD4-mediated tumour cell growth and mTORC1 signalling is coupled to respiratory chain complex I (CI) activity. Using global metabolomics analysis, we show that CHCHD4 regulates amino acid metabolism, and that CHCHD4-mediated tumour cell growth is dependent on glutamine. We show that CHCHD4-mediated tumour cell growth is linked to CI-regulated mTORC1 signalling and amino acid metabolism. Finally, we show that CHCHD4 expression in tumours is inversely correlated with EMT-related gene expression, and that increased CHCHD4 expression in tumour cells modulates EMT-related phenotypes. Conclusions: CHCHD4 drives tumour cell growth and activates mTORC1 signalling through its control of respiratory chain mediated metabolism and complex I biology, and also regulates EMT-related phenotypes of tumour cells

    Cognitive and social activities and long-term dementia risk: the prospective UK Million Women Study

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    BACKGROUND: Although dementia is associated with non-participation in cognitive and social activities, this association might merely reflect the consequences of dementia, rather than any direct effect of non-participation on the subsequent incidence of dementia. Because of the slowness with which dementia can develop, unbiased assessment of any such direct effects must relate non-participation in such activities to dementia detection rates many years later. Prospective studies with long-term follow-up can help achieve this by analysing separately the first and second decade of follow-up. We report such analyses of a large, 20-year study. METHODS: The UK Million Women Study is a population-based prospective study of 1·3 million women invited for National Health Service (NHS) breast cancer screening in median year 1998 (IQR 1997-1999). In median year 2001 (IQR 2001-2003), women were asked about participation in adult education, groups for art, craft, or music, and voluntary work, and in median year 2006 (IQR 2006-2006), they were asked about reading. All participants were followed up through electronic linkage to NHS records of hospital admission with mention of dementia, the first mention of which was the main outcome. Comparing non-participation with participation in a particular activity, we used Cox regression to assess fully adjusted dementia risk ratios (RRs) during 0-4, 5-9, and 10 or more years, after information on that activity was obtained. FINDINGS: In 2001, 851 307 women with a mean age of 60 years (SD 5) provided information on participation in adult education, groups for art, craft, or music, and voluntary work. After 10 years, only 9591 (1%) had been lost to follow-up and 789 339 (93%) remained alive with no recorded dementia. Follow-up was for a mean of 16 years (SD 3), during which 31 187 (4%) had at least one hospital admission with mention of dementia, including 25 636 (3%) with a hospital admission with dementia mentioned for the first time 10 years or more after follow-up began. Non-participation in cognitive or social activities was associated with higher relative risks of dementia detection only during the first decade after participation was recorded. During the second decade, there was little association. This was true for non-participation in adult education (RR 1·04, 99% CI 0·98-1·09), in groups for art, craft, or music (RR 1·04, 0·99-1·09), in voluntary work (RR 0·96, 0·92-1·00), or in any of these three (RR 0·99, 0·95-1·03). In 2006, 655 118 women provided information on reading. For non-reading versus any reading, there were similar associations with dementia, again with strong attenuation over time since reading was recorded, but longer follow-up is needed to assess this reliably. INTERPRETATION: Life has to be lived forwards, but can be understood only backwards. Long before dementia is diagnosed, there is a progressive reduction in various mental and physical activities, but this is chiefly because its gradual onset causes inactivity and not because inactivity causes dementia. FUNDING: UK Medical Research Council, Cancer Research UK
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