• Torque Curve Optimization of Ankle Push-Off in Walking Bipedal Robots Using Genetic Algorithm

      Ji, Qiaoli; email: jiql17@mails.jlu.edu.cn; Qian, Zhihui; email: zhqian@jlu.edu.cn; Ren, Lei; email: lei.ren@manchester.ac.uk; Ren, Luquan; email: lqren@jlu.edu.cn (MDPI, 2021-05-14)
      Ankle push-off occurs when muscle–tendon units about the ankle joint generate a burst of positive power at the end of stance phase in human walking. Ankle push-off mainly contributes to both leg swing and center of mass (CoM) acceleration. Humans use the amount of ankle push-off to induce speed changes. Thus, this study focuses on determining the faster walking speed and the lowest energy efficiency of biped robots by using ankle push-off. The real-time-space trajectory method is used to provide reference positions for the hip and knee joints. The torque curve during ankle push-off, composed of three quintic polynomial curves, is applied to the ankle joint. With the walking distance and the mechanical cost of transport (MCOT) as the optimization goals, the genetic algorithm (GA) is used to obtain the optimal torque curve during ankle push-off. The results show that the biped robot achieved a maximum speed of 1.3 m/s, and the ankle push-off occurs at 41.27−48.34% of the gait cycle. The MCOT of the bipedal robot corresponding to the high economy gait is 0.70, and the walking speed is 0.54 m/s. This study may further prompt the design of the ankle joint and identify the important implications of ankle push-off for biped robots.
    • Toward scalable biocatalytic conversion of 5-hydroxymethylfurfural by galactose oxidase using coordinated reaction and enzyme engineering

      Birmingham, William R.; orcid: 0000-0002-8880-5502; Toftgaard Pedersen, Asbjørn; orcid: 0000-0002-5283-3210; Dias Gomes, Mafalda; Bøje Madsen, Mathias; Breuer, Michael; Woodley, John M.; orcid: 0000-0002-7976-2483; Turner, Nicholas J.; orcid: 0000-0002-8708-0781; email: nicholas.turner@manchester.ac.uk (Nature Publishing Group UK, 2021-08-16)
      Abstract: 5-Hydroxymethylfurfural (HMF) has emerged as a crucial bio-based chemical building block in the drive towards developing materials from renewable resources, due to its direct preparation from sugars and its readily diversifiable scaffold. A key obstacle in transitioning to bio-based plastic production lies in meeting the necessary industrial production efficiency, particularly in the cost-effective conversion of HMF to valuable intermediates. Toward addressing the challenge of developing scalable technology for oxidizing crude HMF to more valuable chemicals, here we report coordinated reaction and enzyme engineering to provide a galactose oxidase (GOase) variant with remarkably high activity toward HMF, improved O2 binding and excellent productivity (>1,000,000 TTN). The biocatalyst and reaction conditions presented here for GOase catalysed selective oxidation of HMF to 2,5-diformylfuran offers a productive blueprint for further development, giving hope for the creation of a biocatalytic route to scalable production of furan-based chemical building blocks from sustainable feedstocks.
    • Toward scalable biocatalytic conversion of 5-hydroxymethylfurfural by galactose oxidase using coordinated reaction and enzyme engineering.

      Birmingham, William R; orcid: 0000-0002-8880-5502; Toftgaard Pedersen, Asbjørn; orcid: 0000-0002-5283-3210; Dias Gomes, Mafalda; Bøje Madsen, Mathias; Breuer, Michael; Woodley, John M; orcid: 0000-0002-7976-2483; Turner, Nicholas J; orcid: 0000-0002-8708-0781; email: nicholas.turner@manchester.ac.uk (2021-08-16)
      5-Hydroxymethylfurfural (HMF) has emerged as a crucial bio-based chemical building block in the drive towards developing materials from renewable resources, due to its direct preparation from sugars and its readily diversifiable scaffold. A key obstacle in transitioning to bio-based plastic production lies in meeting the necessary industrial production efficiency, particularly in the cost-effective conversion of HMF to valuable intermediates. Toward addressing the challenge of developing scalable technology for oxidizing crude HMF to more valuable chemicals, here we report coordinated reaction and enzyme engineering to provide a galactose oxidase (GOase) variant with remarkably high activity toward HMF, improved O<sub>2</sub> binding and excellent productivity (>1,000,000 TTN). The biocatalyst and reaction conditions presented here for GOase catalysed selective oxidation of HMF to 2,5-diformylfuran offers a productive blueprint for further development, giving hope for the creation of a biocatalytic route to scalable production of furan-based chemical building blocks from sustainable feedstocks.
    • Toward ‘Vaccine Internationalism’: The Need for an Equitable and Coordinated Global Vaccination Approach to Effectively Combat COVID-19

      Wong, Brian L. H.; email: b.wong@ucl.ac.uk; Green, Manfred S.; reid, John; Martin-Moreno, Jose M.; Davidovitch, Nadav; Chambaud, Laurent; Leighton, Lore; Sheek-Hussein, Mohamud; Dhonkal, Ranjeet; Otok, Robert; et al. (Frontiers Media S.A., 2021-04-14)
    • Toward ‘Vaccine Internationalism’: The Need for an Equitable and Coordinated Global Vaccination Approach to Effectively Combat COVID-19

      Wong, Brian L. H.; email: b.wong@ucl.ac.uk; Green, Manfred S.; Reid, John; Martin-Moreno, Jose M.; Davidovitch, Nadav; Chambaud, Laurent; Leighton, Lore; Sheek-Hussein, Mohamud; Dhonkal, Ranjeet; Otok, Robert; et al. (Frontiers Media S.A., 2021-04-14)
    • Towards a Bio-Inspired Real-Time Neuromorphic Cerebellum

      Bogdan, Petruţ A.; email: petrut.bogdan@manchester.ac.uk; Marcinnò, Beatrice; Casellato, Claudia; Casali, Stefano; Rowley, Andrew G.D.; Hopkins, Michael; Leporati, Francesco; D'Angelo, Egidio; Rhodes, Oliver (Frontiers Media S.A., 2021-05-31)
      This work presents the first simulation of a large-scale, bio-physically constrained cerebellum model performed on neuromorphic hardware. A model containing 97,000 neurons and 4.2 million synapses is simulated on the SpiNNaker neuromorphic system. Results are validated against a baseline simulation of the same model executed with NEST, a popular spiking neural network simulator using generic computational resources and double precision floating point arithmetic. Individual cell and network-level spiking activity is validated in terms of average spike rates, relative lead or lag of spike times, and membrane potential dynamics of individual neurons, and SpiNNaker is shown to produce results in agreement with NEST. Once validated, the model is used to investigate how to accelerate the simulation speed of the network on the SpiNNaker system, with the future goal of creating a real-time neuromorphic cerebellum. Through detailed communication profiling, peak network activity is identified as one of the main challenges for simulation speed-up. Propagation of spiking activity through the network is measured, and will inform the future development of accelerated execution strategies for cerebellum models on neuromorphic hardware. The large ratio of granule cells to other cell types in the model results in high levels of activity converging onto few cells, with those cells having relatively larger time costs associated with the processing of communication. Organizing cells on SpiNNaker in accordance with their spatial position is shown to reduce the peak communication load by 41%. It is hoped that these insights, together with alternative parallelization strategies, will pave the way for real-time execution of large-scale, bio-physically constrained cerebellum models on SpiNNaker. This in turn will enable exploration of cerebellum-inspired controllers for neurorobotic applications, and execution of extended duration simulations over timescales that would currently be prohibitive using conventional computational platforms.
    • Towards an improved prediction of concentrated antibody solution viscosity using the Huggins coefficient.

      Roche, Aisling; Gentiluomo, Lorenzo; Sibanda, Nicole; Roessner, Dierk; Friess, Wolfgang; Trainoff, Steven P; Curtis, Robin; email: r.curtis@manchester.ac.uk (2021-09-04)
      The viscosity of a monoclonal antibody solution must be monitored and controlled as it can adversely affect product processing, packaging and administration. Engineering low viscosity mAb formulations is challenging as prohibitive amounts of material are required for concentrated solution analysis, and it is difficult to predict viscosity from parameters obtained through low-volume, high-throughput measurements such as the interaction parameter, k , and the second osmotic virial coefficient, B . As a measure encompassing the effect of intermolecular interactions on dilute solution viscosity, the Huggins coefficient, k , is a promising candidate as a parameter measureable at low concentrations, but indicative of concentrated solution viscosity. In this study, a differential viscometry technique is developed to measure the intrinsic viscosity, [η], and the Huggins coefficient, k , of protein solutions. To understand the effect of colloidal protein-protein interactions on the viscosity of concentrated protein formulations, the viscometric parameters are compared to k and B of two mAbs, tuning the contributions of repulsive and attractive forces to the net protein-protein interaction by adjusting solution pH and ionic strength. We find a strong correlation between the concentrated protein solution viscosity and the k but this was not observed for the k or the b , which have been previously used as indicators of high concentration viscosity. Trends observed in [η] and k values as a function of pH and ionic strength are rationalised in terms of protein-protein interactions. [Abstract copyright: Copyright © 2021. Published by Elsevier Inc.]
    • Towards flexible personalized learning and the future educational system in the fourth industrial revolution in the wake of Covid-19

      Whalley, Brian; France, Derek; Park, Julian; Mauchline, Alice; welsh, Katharine (Informa UK Limited, 2021-02-25)
    • Towards flexible personalized learning and the future educational system in the fourth industrial revolution in the wake of Covid-19

      Whalley, Brian; France, Derek; Park, Julian; Mauchline, Alice; welsh, Katharine (Informa UK Limited, 2021-02-25)
    • Towards flexible personalized learning and the future educational system in the fourth industrial revolution in the wake of Covid-19

      Whalley, Brian; France, Derek; Park, Julian; Mauchline, Alice; welsh, Katharine (Informa UK Limited, 2021-02-25)
    • Towards Personalising the Use of Biologics in Rheumatoid Arthritis: A Discrete Choice Experiment.

      Vass, Caroline M; Barton, Anne; Payne, Katherine; orcid: 0000-0002-3938-4350; email: katherine.payne@manchester.ac.uk (2021-06-18)
      There have been promising developments in technologies and associated algorithm-based prescribing ('stratified approach') to target biologics to sub-groups of people with rheumatoid arthritis (RA). The acceptability of using an algorithm-guided approach in practice is likely to depend on various factors. This study quantified preferences for an algorithm-guided approach to prescribing biologics (termed 'biologic calculator'). An online discrete choice experiment (DCE) was designed to elicit preferences from patients and the public for using a 'biologic calculator' compared with conventional prescribing. Treatment approaches were described by five attributes: delay to starting treatment; positive and negative predictive value (PPV/NPV); risk of infection; and cost saving to the UK national health service. Each survey contained six choice sets asking respondents to select their preferred option from two hypothetical biologic calculators or conventional prescribing. Background questions included sociodemographics, health status and healthcare experiences. DCE data were analysed using mixed logit models. Completed choice data were collected from 292 respondents (151 patients with RA and 142 members of the public). PPV, NPV and risk of infection were the most highly valued attributes to respondents deciding between prescribing strategies. Respondents were generally receptive to personalised medicine in RA, but researchers developing personalised approaches should pay close attention to generating evidence on both the PPV and the NPV of their technologies.
    • Towards safer healthcare: qualitative insights from a process view of organisational learning from failure.

      Monazam Tabrizi, Negar; orcid: 0000-0003-1300-5030; email: negar.monazamtabrizi@manchester.ac.uk; Masri, Firas (2021-08-10)
      This study adopted a process view of organisational learning to investigate the barriers to effective organisational learning from medical errors. Qualitative data were collected from 40 clinicians in high and low performing hospitals. The fit between the organisational learning process and socio-technical factors was investigated systematically from a pre-reporting stage to reporting and post-reporting stages. The analysis uncovered that the major stumbling blocks to active learning lie largely in the post-reporting stages and that they are rooted in social rather than technical issues. Although the experience of the higher-performing hospital provides valuable pointers in terms of creating more trusting environment and using the potential of small failures towards ways in which the organisational learning process in the lower hospital might be improved, due to lack of local mangers' proactive engagement in integrating changes into practice the active learning takes place in neither of the hospitals. To ensure that the change solutions are firmly incorporated into the culture and routine practice of the hospital, we need to focus on fostering an organisational culture that encourages positive cooperation and mutual interactions between local managers and frontline clinicians. This process will lead to double-loop learning and an increase in system safety. [Abstract copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.]
    • Towards the Determination of Safe Operating Envelopes for Autonomous UAS in Offshore Inspection Missions

      Page, Vincent; email: v.page@liverpool.ac.uk; Dadswell, Christopher; email: c.m.dadswell@liverpool.ac.uk; Webster, Matt; email: m.p.webster@ljmu.ac.uk; Jump, Mike; email: mjump1@liverpool.ac.uk; Fisher, Michael; orcid: 0000-0002-0875-3862; email: michael.fisher@manchester.ac.uk (MDPI, 2021-07-28)
      A drive to reduce costs, carbon emissions, and the number of required personnel in the offshore energy industry has led to proposals for the increased use of autonomous/robotic systems for many maintenance tasks. There are questions over how such missions can be shown to be safe. A corollary exists in the manned aviation world for helicopter–ship operations where a test pilot attempts to operate from a ship under a range of wind conditions and provides subjective feedback on the level of difficulty encountered. This defines the ship–helicopter operating limit envelope (SHOL). Due to the cost of creating a SHOL there has been considerable research activity to demonstrate that much of this process can be performed virtually. Unmanned vehicles, however, have no test pilot to provide feedback. This paper therefore explores the possibility of adapting manned simulation techniques to the unmanned world to demonstrate that a mission is safe. Through flight modelling and simulation techniques it is shown that operating envelopes can be created for an oil rig inspection task and that, by using variable performance specifications, these can be tailored to suit the level of acceptable risk. The operating envelopes produced provide condensed and intelligible information regarding the environmental conditions under which the UAS can perform the task.
    • Trabant: Go with the legend

      Lowe, Austen; Stone, Mark (Drystone Radio, 2018-11-18)
      "The car is that mediation between state and society. If you look at when they finally opened the borders for people to go West, the Trabis also went with them." Modern Languages undergraduate Austen Lowe was invited to Drystone Radio's Backseat Driver show to discuss his research on the Trabant with Mark Stone. This radio broadcast outlines the misunderstandings surrounding GDR mobility. The conversation focusses on how the wooden and plastic car personifies the state in which it was made. The broadcast aims to draw parallels between production techniques in the GDR and the FRG, relating these methods to cars produced more recently in Zwickau. What did quality actually mean in the GDR and is the Trabant really a motoring legend?
    • Tracheostomy for COVID-19: evolving best practice

      Williams, Thomas; McGrath, Brendan A.; orcid: 0000-0003-3048-3480; email: brendan.mcgrath@manchester.ac.uk (BioMed Central, 2021-08-31)
      Abstract: This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2021. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901.
    • Tracheostomy for COVID-19: evolving best practice.

      Williams, Thomas; McGrath, Brendan A; orcid: 0000-0003-3048-3480; email: brendan.mcgrath@manchester.ac.uk (2021-08-31)
      This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2021. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2021 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .
    • Trading Global Catastrophes: NATO’s Science Diplomacy and Nuclear Winter

      Turchetti, Simone; orcid: 0000-0003-1834-2503; email: simone.turchetti@manchester.ac.uk (SAGE Publications, 2021-04-23)
      This essay explores the reception of ‘nuclear winter’ at the North Atlantic Treaty Organization (NATO). This response is paradigmatic of how scientific predictions can work as stimuli for science diplomacy activities, and either inflate or deflate these forecasts’ public resonance. Those who elaborated the theory in the early 1980s predicted that the environmental consequences of a future nuclear conflict would have been catastrophic; possibly rendering the earth uninhabitable and leading to the extinction of humankind. This prospect was particularly problematic for the Western defence alliance, since it was difficult to reconcile with the tenets of its nuclear posture, especially after the 1979 Dual Track decision, engendering concerns about the environmental catastrophe that the scientists predicted. Thus, NATO officials refrained from commenting on nuclear winter and its implications for the alliance’s deterrence doctrine for some time in an effort to minimize public criticism. Meanwhile, they progressively removed research on nuclear winter from the set of studies and scientific debates sponsored by NATO in the context of its science initiatives. In essence, NATO officials ‘traded’ the promotion of these problematic studies with that of others more amenable to the alliance’s diplomacy ambitions.
    • Transactions between Big‐5 personality traits and job characteristics across 20 years

      Holman, David J.; email: david.holman@manchester.ac.uk; Hughes, David J. (2021-02-04)
      Although understanding the relationship between the individual and work environment is a core concern of organizational research, few studies have examined longitudinal transactions between Big‐5 personality traits and job characteristics. Building on research in personality and job design we develop hypotheses detailing transactions between Big‐5 personality traits (i.e., openness, conscientiousness, extraversion, agreeableness, neuroticism) and two key job characteristics (i.e., job discretion and workload). Specifically, we hypothesize and test transactions with regard to the effects of job characteristics on personality, the effects of personality on job characteristics, and the reciprocal effects between these constructs. Our findings, based on a latent change score analysis of data collected over three waves across 20 years, show strongest support for the effects of job characteristics on personality, particularly the effects of workload on personality change in openness, extraversion, and agreeableness. We found no effects of job discretion on personality, limited support for the effects of personality on job characteristics (except a positive effect of neuroticism on job discretion), and no evidence of reciprocal effects. Practitioner points: Job demands can alter employee personality. Employees who consistently experienced high workloads over a 20‐year period incurred developmental increases in three personality traits – extraversion, openness, and agreeableness – such that they became more outgoing and assertive, more curious, and broadminded, as well as more helpful and sympathetic. Employees who experienced high job discretion did not incur similar development changes in personality.
    • Transcription factors that shape the mammalian pancreas

      Jennings, Rachel E.; orcid: 0000-0003-1492-600X; email: rachel.jennings@manchester.ac.uk; Scharfmann, Raphael; orcid: 0000-0001-7619-337X; email: raphael.scharfmann@inserm.fr; Staels, Willem; orcid: 0000-0001-8259-3329; email: willem.staels@vub.be (Springer Berlin Heidelberg, 2020-09-07)
      Abstract: Improving our understanding of mammalian pancreas development is crucial for the development of more effective cellular therapies for diabetes. Most of what we know about mammalian pancreas development stems from mouse genetics. We have learnt that a unique set of transcription factors controls endocrine and exocrine cell differentiation. Transgenic mouse models have been instrumental in studying the function of these transcription factors. Mouse and human pancreas development are very similar in many respects, but the devil is in the detail. To unravel human pancreas development in greater detail, in vitro cellular models (including directed differentiation of stem cells, human beta cell lines and human pancreatic organoids) are used; however, in vivo validation of these results is still needed. The current best ‘model’ for studying human pancreas development are individuals with monogenic forms of diabetes. In this review, we discuss mammalian pancreas development, highlight some discrepancies between mouse and human, and discuss selected transcription factors that, when mutated, cause permanent neonatal diabetes. Graphical abstract
    • Transcriptome Analysis in a Primary Human Muscle Cell Differentiation Model for Myotonic Dystrophy Type 1

      Todorow, Vanessa; email: vanessa.todorow@med.uni-muenchen.de; Hintze, Stefan; email: stefan.hintze@med.uni-muenchen.de; Kerr, Alastair R. W.; orcid: 0000-0001-9207-6050; email: alastair.kerr@cruk.manchester.ac.uk; Hehr, Andreas; email: andreas.hehr@humangenetik-regensburg.de; Schoser, Benedikt; orcid: 0000-0002-2757-8131; email: benedikt.schoser@med.uni-muenchen.de; Meinke, Peter; email: peter.meinke@med.uni-muenchen.de (MDPI, 2021-08-10)
      Myotonic dystrophy type 1 (DM1) is caused by CTG-repeat expansions leading to a complex pathology with a multisystemic phenotype that primarily affects the muscles and brain. Despite a multitude of information, especially on the alternative splicing of several genes involved in the pathology, information about additional factors contributing to the disease development is still lacking. We performed RNAseq and gene expression analyses on proliferating primary human myoblasts and differentiated myotubes. GO-term analysis indicates that in myoblasts and myotubes, different molecular pathologies are involved in the development of the muscular phenotype. Gene set enrichment for splicing reveals the likelihood of whole, differentiation stage specific, splicing complexes that are misregulated in DM1. These data add complexity to the alternative splicing phenotype and we predict that it will be of high importance for therapeutic interventions to target not only mature muscle, but also satellite cells.