Concurrent engineering: Spacecraft and mission operations system design

Despite our awareness of the mission design process, spacecraft historically have been designed and developed by one team and then turned over as a system to the Mission Operations organization to operate on-orbit. By applying concurrent engineering techniques and envisioning operability as an essential characteristic of spacecraft design, tradeoffs can be made in the overall mission design to minimize mission lifetime cost. Lessons learned from previous spacecraft missions will be described, as well as the implementation of concurrent mission operations and spacecraft engineering for the Near Earth Asteroid Rendezvous (NEAR) program

Knee pain and related health in the community study (KPIC): a cohort study protocol

Background: The incidence, progression and related risk factors for recent-onset knee pain (KP) remain uncertain. This study aims to examine the natural history of KP including incidence and progression and to identify possible phenotypes and their associated risk factors. Methods: A prospective community-based cohort of men and women aged 40 years or over within the East Midlands region (UK) will be recruited via a postal questionnaire from their general practices. The questionnaire will enquire about: presence and onset of KP; pain severity (0–10 numerical rating scale (NRS)); pain catastrophizing and neuropathic-like pain (NP) using the painDETECT questionnaires (definite NP scores ≥19–38); risk factors for KP and/or osteoarthritis (OA) (age, body mass index, constitutional knee alignment, nodal OA, index: ring finger length (2D4D) ratio); quality of life (SF12); and mental health (Hospital Anxiety and Depression Scale). Clinical assessments will be undertaken in a sample of 400 participants comprising three groups: early KP (≤3 year’s duration), established KP (>3 years) and no KP. Assessments will include knee radiographs (standing semi-flexed and 300 skyline views); knee ultrasound (synovial effusion, hypertrophy, and Doppler activity); quantitative sensory testing; muscle strength (quadriceps, hip abductor, and hand-grip); balance; gait analysis (GAITrite); and biomarker sampling. A repeat questionnaire will be sent to responders at years 1 and 3. The baseline early KP group will undergo repeat assessments at year 1 (apart from radiographs) and year 3 (with radiographs). Any incident KP individuals identified at year 1 or 3 questionnaires will have clinical and radiographic assessments at the respective time points. Discussion: Baseline data will be used to examine risk factors for early onset KP and to identify KP phenotypes. Subsequent prospective data, at least to Year 3, will allow examination of the natural history of KP and risk factors for incidence and progression. Trial registration: The study was registered on the clinicaltrials.gov portal: NCT02098070) on the 14th of March 2014

The importance of quantum decoherence in brain processes

Based on a calculation of neural decoherence rates, we argue that that the degrees of freedom of the human brain that relate to cognitive processes should be thought of as a classical rather than quantum system, i.e., that there is nothing fundamentally wrong with the current classical approach to neural network simulations. We find that the decoherence timescales ~10^{-13}-10^{-20} seconds are typically much shorter than the relevant dynamical timescales (~0.001-0.1 seconds), both for regular neuron firing and for kink-like polarization excitations in microtubules. This conclusion disagrees with suggestions by Penrose and others that the brain acts as a quantum computer, and that quantum coherence is related to consciousness in a fundamental way.Comment: Minor changes to match accepted PRE version. 15 pages with 5 figs included. Color figures and links at http://www.physics.upenn.edu/~max/brain.html or from [email protected]. Physical Review E, in pres

H0LiCOW XI. A weak lensing measurement of the external convergence in the field of the lensed quasar B1608+656 using HST and Subaru deep imaging

We investigate the environment and line of sight of the H0LiCOW lens B1608+656 using Subaru Suprime-Cam and the Hubble Space Telescope (HST) to perform a weak lensing analysis. We compare three different methods to reconstruct the mass map of the field, i.e. the standard Kaiser-Squires inversion coupled with inpainting and Gaussian or wavelet filtering, and $\tt{Glimpse}$ a method based on sparse regularization of the shear field. We find no substantial difference between the 2D mass reconstructions, but we find that the ground-based data is less sensitive to small-scale structures than the space-based observations. Marginalising over the results obtained with all the reconstruction techniques applied to the two available HST filters F606W and F814W, we estimate the external convergence, $\kappa_{\rm ext}$ at the position of B1608+656 is $\kappa_{\rm ext} = 0.11^{+0.06}_{-0.04}$, where the error bars corresponds respectively to the 16th and 84th quartiles. This result is compatible with previous estimates using the number-counts technique, suggesting that B1608+656 resides in an over-dense line of sight, but with a completely different technique. Using our mass reconstructions, we also compare the convergence at the position of several groups of galaxies in the field of B1608+656 with the mass measurements using various analytical mass profiles, and find that the weak lensing results favor truncated halo models.Comment: Accepted MNRA

The writing on the wall: the concealed communities of the East Yorkshire horselads

This paper examines the graffiti found within late nineteenth and early-twentieth century farm buildings in the Wolds of East Yorkshire. It suggests that the graffiti were created by a group of young men at the bottom of the social hierarchy - the horselads – and was one of the ways in which they constructed a distinctive sense of communal identity, at a particular stage in their lives. Whilst it tells us much about changing agricultural regimes and social structures, it also informs us about experiences and attitudes often hidden from official histories and biographies. In this way, the graffiti are argued to inform our understanding, not only of a concealed community, but also about their hidden histor

Citizenship, Justice and the Right to the Smart City

This paper provides an introduction to the smart city and engages with its idea and ideals from a critical social science perspective. After setting out in brief the emergence of smart cities and current key debates, we note a number of practical, political and normative questions relating to citizenship, justice, and the public good that warrant examination. The remainder of the paper provides an initial framing for engaging with these questions. The first section details the dominant neoliberal conception and enactment of smart cities and how this works to promote the interests of capital and state power and reshape governmentality. We then detail some of the ethical issues associated with smart city technologies and initiatives. Having set out some of the more troubling aspects of how social relations are produced within smart cities, we then examine how citizens and citizenship have been conceived and operationalised in the smart city to date. We then follow this with a discussion of social justice and the smart city. In the final section, we explore the notion of the ‘right to the smart city’ and how this might be used to recast the smart city in emancipatory and empowering ways

Living for the weekend: youth identities in northeast England

Consumption and consumerism are now accepted as key contexts for the construction of youth identities in de-industrialized Britain. This article uses empirical evidence from interviews with young people to suggest that claims of `new community' are overstated, traditional forms of friendship are receding, and increasingly atomized and instrumental youth identities are now being culturally constituted and reproduced by the pressures and anxieties created by enforced adaptation to consumer capitalism. Analysis of the data opens up the possibility of a critical rather than a celebratory exploration of the wider theoretical implications of this process

Technical trading and cryptocurrencies

This paper carries out a comprehensive examination of technical trading rules in cryptocurrency markets, using data from two Bitcoin markets and three other popular cryptocurrencies. We employ almost 15,000 technical trading rules from the main five classes of technical trading rules and find significant predictability and profitability for each class of technical trading rule in each cryptocurrency. We find that the breakeven transaction costs are substantially higher than those typically found in cryptocurrency markets. To safeguard against data-snooping, we implement a number of multiple hypothesis procedures which confirms our findings that technical trading rules do offer significant predictive power and profitability to investors. We also show that the technical trading rules offer substantially higher risk-adjusted returns than the simple buy-and-hold strategy, showing protection against lengthy and severe drawdowns associated with cryptocurrency markets. However there is no predictability for Bitcoin in the out-of-sample period, although predictability remains in other cryptocurrency markets

Favourable antibody responses to human coronaviruses in children and adolescents with autoimmune rheumatic diseases

Background: Differences in humoral immunity to coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), between children and adults remain unexplained and the impact of underlying immune dysfunction or suppression unknown. Here, we sought to examine the antibody immune competence of children and adolescents with prevalent inflammatory rheumatic diseases, juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM) and juvenile systemic lupus erythematosus (JSLE), against the seasonal human coronavirus (HCoV)-OC43 that frequently infects this age group. // Methods: Sera were collected from JIA (n=118), JDM (n=49) and JSLE (n=30) patients, and from healthy control (n=54) children and adolescents, prior to the coronavirus disease-19 (COVID-19) pandemic. We employed sensitive flow cytometry-based assays to determine titres of antibodies that reacted with the spike and nucleoprotein of HCoV-OC43 and cross-reacted with the spike and nucleoprotein of SARS-CoV-2, and compared with respective titres in sera from patients with multisystem inflammatory syndrome in children and adolescents (MIS-C). // Findings: Despite immune dysfunction and immunosuppressive treatment, JIA, JDM and JSLE patients maintained comparable or stronger humoral responses than healthier peers, dominated by IgG antibodies to HCoV-OC43 spike, and harboured IgG antibodies that cross-reacted with SARS-CoV-2 spike. In contrast, responses to HCoV-OC43 and SARS-CoV-2 nucleoproteins exhibited delayed age-dependent class-switching and were not elevated in JIA, JDM and JSLE patients, arguing against increased exposure. // Conclusions: Consequently, autoimmune rheumatic diseases and their treatment were associated with a favourable ratio of spike to nucleoprotein antibodies

Unbiased metabolome screen leads to personalized medicine strategy for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is a rapidly progressive neurodegenerative disease that affects 1/350 individuals in the United Kingdom. The cause of amyotrophic lateral sclerosis is unknown in the majority of cases. Two-sample Mendelian randomization enables causal inference between an exposure, such as the serum concentration of a specific metabolite, and disease risk. We obtained genome-wide association study summary statistics for serum concentrations of 566 metabolites which were population matched with a genome-wide association study of amyotrophic lateral sclerosis. For each metabolite, we performed Mendelian randomization using an inverse variance weighted estimate for significance testing. After stringent Bonferroni multiple testing correction, our unbiased screen revealed three metabolites that were significantly linked to the risk of amyotrophic lateral sclerosis: Estrone-3-sulphate and bradykinin were protective, which is consistent with literature describing a male preponderance of amyotrophic lateral sclerosis and a preventive effect of angiotensin-converting enzyme inhibitors which inhibit the breakdown of bradykinin. Serum isoleucine was positively associated with amyotrophic lateral sclerosis risk. All three metabolites were supported by robust Mendelian randomization measures and sensitivity analyses; estrone-3-sulphate and isoleucine were confirmed in a validation amyotrophic lateral sclerosis genome-wide association study. Estrone-3-sulphate is metabolized to the more active estradiol by the enzyme 17β-hydroxysteroid dehydrogenase 1; further, Mendelian randomization demonstrated a protective effect of estradiol and rare variant analysis showed that missense variants within HSD17B1, the gene encoding 17β-hydroxysteroid dehydrogenase 1, modify risk for amyotrophic lateral sclerosis. Finally, in a zebrafish model of C9ORF72-amyotrophic lateral sclerosis, we present evidence that estradiol is neuroprotective. Isoleucine is metabolized via methylmalonyl-CoA mutase encoded by the gene MMUT in a reaction that consumes vitamin B12. Multivariable Mendelian randomization revealed that the toxic effect of isoleucine is dependent on the depletion of vitamin B12; consistent with this, rare variants which reduce the function of MMUT are protective against amyotrophic lateral sclerosis. We propose that amyotrophic lateral sclerosis patients and family members with high serum isoleucine levels should be offered supplementation with vitamin B12