• Basil Lythgoe. 18 August 1913—18 April 2009

      Jones, J. C. (The Royal Society, 2021-03-03)
      Basil Lythgoe was distinguished as an organic chemist. He began his career at the University of Manchester, where he had studied for his undergraduate and PhD degrees, before moving to University of Cambridge. During this period he collaborated with Alexander Todd on the structural elucidation and total synthesis of the natural nucleosides, and was also noted for his investigation of the structure of the natural substance macrozamin. In 1953 he moved to the chair of organic chemistry at the University of Leeds, running a research group from which several graduate students went on to academic careers of the highest distinction. At Leeds he worked on the structure of the alkaloid taxine 1 and calciferol, among other natural substances. Lythgoe's work was characterized by a combination of insight and high experimental skill.
    • Basil Lythgoe. 18 August 1913—18 April 2009

      Jones, J. C. (The Royal Society, 2021-03-03)
      Basil Lythgoe was distinguished as an organic chemist. He began his career at the University of Manchester, where he had studied for his undergraduate and PhD degrees, before moving to University of Cambridge. During this period he collaborated with Alexander Todd on the structural elucidation and total synthesis of the natural nucleosides, and was also noted for his investigation of the structure of the natural substance macrozamin. In 1953 he moved to the chair of organic chemistry at the University of Leeds, running a research group from which several graduate students went on to academic careers of the highest distinction. At Leeds he worked on the structure of the alkaloid taxine 1 and calciferol, among other natural substances. Lythgoe's work was characterized by a combination of insight and high experimental skill.
    • Convex hull estimation of mammalian body segment parameters

      Coatham, Samuel J.; orcid: 0000-0003-4597-6210; email: sam.coatham@postgrad.manchester.ac.uk; Sellers, William I.; orcid: 0000-0002-2913-5406; Püschel, Thomas A.; orcid: 0000-0002-2231-2297 (The Royal Society, 2021-06-30)
      Obtaining accurate values for body segment parameters (BSPs) is fundamental in many biomechanical studies, particularly for gait analysis. Convex hulling, where the smallest-possible convex object that surrounds a set of points is calculated, has been suggested as an effective and time-efficient method to estimate these parameters in extinct animals, where soft tissues are rarely preserved. We investigated the effectiveness of convex hull BSP estimation in a range of extant mammals, to inform the potential future usage of this technique with extinct taxa. Computed tomography scans of both the skeleton and skin of every species investigated were virtually segmented. BSPs (the mass, position of the centre of mass and inertial tensors of each segment) were calculated from the resultant soft tissue segments, while the bone segments were used as the basis for convex hull reconstructions. We performed phylogenetic generalized least squares and ordinary least squares regressions to compare the BSPs calculated from soft tissue segments with those estimated using convex hulls, finding consistent predictive relationships for each body segment. The resultant regression equations can, therefore, be used with confidence in future volumetric reconstruction and biomechanical analyses of mammals, in both extinct and extant species where such data may not be available.
    • Inferring kinetic parameters of oscillatory gene regulation from single cell time-series data

      Burton, Joshua; orcid: 0000-0001-8530-0464; Manning, Cerys S.; orcid: 0000-0001-8656-5878; Rattray, Magnus; orcid: 0000-0001-8196-5565; Papalopulu, Nancy; orcid: 0000-0001-6992-6870; email: Nancy.Papalopulu@manchester.ac.uk; Kursawe, Jochen; orcid: 0000-0002-0314-9623; email: jochen.kursawe@st-andrews.ac.uk (The Royal Society, 2021-09-29)
      Gene expression dynamics, such as stochastic oscillations and aperiodic fluctuations, have been associated with cell fate changes in multiple contexts, including development and cancer. Single cell live imaging of protein expression with endogenous reporters is widely used to observe such gene expression dynamics. However, the experimental investigation of regulatory mechanisms underlying the observed dynamics is challenging, since these mechanisms include complex interactions of multiple processes, including transcription, translation and protein degradation. Here, we present a Bayesian method to infer kinetic parameters of oscillatory gene expression regulation using an auto-negative feedback motif with delay. Specifically, we use a delay-adapted nonlinear Kalman filter within a Metropolis-adjusted Langevin algorithm to identify posterior probability distributions. Our method can be applied to time-series data on gene expression from single cells and is able to infer multiple parameters simultaneously. We apply it to published data on murine neural progenitor cells and show that it outperforms alternative methods. We further analyse how parameter uncertainty depends on the duration and time resolution of an imaging experiment, to make experimental design recommendations. This work demonstrates the utility of parameter inference on time course data from single cells and enables new studies on cell fate changes and population heterogeneity.
    • Making the most of potential: potential games and genotypic convergence

      Edhan, Omer; orcid: 0000-0002-4441-3304; email: omeredhan.idan@manchester.ac.uk; Hellman, Ziv; orcid: 0000-0002-2624-0577; Nehama, Ilan; orcid: 0000-0002-4152-4113 (The Royal Society, 2021-08-25)
      We consider genotypic convergence of populations and show that under fixed fitness asexual and haploid sexual populations attain monomorphic convergence (even under genetic linkage between loci) to basins of attraction with locally exponential convergence rates; the same convergence obtains in single locus diploid sexual reproduction but to polymorphic populations. Furthermore, we show that there is a unified theory underlying these convergences: all of them can be interpreted as instantiations of players in a potential game implementing a multiplicative weights updating algorithm to converge to equilibrium, making use of the Baum–Eagon Theorem. To analyse varying environments, we introduce the concept of ‘virtual convergence’, under which, even if fixation is not attained, the population nevertheless achieves the fitness growth rate it would have had under convergence to an optimal genotype. Virtual convergence is attained by asexual, haploid sexual and multi-locus diploid reproducing populations, even if environments vary arbitrarily. We also study conditions for true monomorphic convergence in asexually reproducing populations in varying environments.
    • Making the most of potential: potential games and genotypic convergence

      Edhan, Omer; orcid: 0000-0002-4441-3304; email: omeredhan.idan@manchester.ac.uk; Hellman, Ziv; orcid: 0000-0002-2624-0577; Nehama, Ilan; orcid: 0000-0002-4152-4113 (The Royal Society, 2021-08-25)
      We consider genotypic convergence of populations and show that under fixed fitness asexual and haploid sexual populations attain monomorphic convergence (even under genetic linkage between loci) to basins of attraction with locally exponential convergence rates; the same convergence obtains in single locus diploid sexual reproduction but to polymorphic populations. Furthermore, we show that there is a unified theory underlying these convergences: all of them can be interpreted as instantiations of players in a potential game implementing a multiplicative weights updating algorithm to converge to equilibrium, making use of the Baum–Eagon Theorem. To analyse varying environments, we introduce the concept of ‘virtual convergence’, under which, even if fixation is not attained, the population nevertheless achieves the fitness growth rate it would have had under convergence to an optimal genotype. Virtual convergence is attained by asexual, haploid sexual and multi-locus diploid reproducing populations, even if environments vary arbitrarily. We also study conditions for true monomorphic convergence in asexually reproducing populations in varying environments.
    • Outbreaks in care homes may lead to substantial disease burden if not mitigated

      Hall, Ian; orcid: 0000-0002-3033-2335; email: ian.hall@manchester.ac.uk; Lewkowicz, Hugo; orcid: 0000-0002-8944-0365; Webb, Luke; orcid: 0000-0001-6263-0575; House, Thomas; orcid: 0000-0001-5835-8062; Pellis, Lorenzo; orcid: 0000-0002-3436-6487; Sedgwick, James; orcid: 0000-0002-7200-4559; Gent, Nick; orcid: 0000-0002-2605-7369; on behalf of the University of Manchester COVID-19 Modelling Group and the Public Health England Modelling Team (The Royal Society, 2021-05-31)
      The number of COVID-19 outbreaks reported in UK care homes rose rapidly in early March of 2020. Owing to the increased co-morbidities and therefore worse COVID-19 outcomes for care home residents, it is important that we understand this increase and its future implications. We demonstrate the use of an SIS model where each nursing home is an infective unit capable of either being susceptible to an outbreak (S) or in an active outbreak (I). We use a generalized additive model to approximate the trend in growth rate of outbreaks in care homes and find the fit to be improved in a model where the growth rate is proportional to the number of current care home outbreaks compared with a model with a constant growth rate. Using parameters found from the outbreak-dependent growth rate, we predict a 73% prevalence of outbreaks in UK care homes without intervention as a reasonable worst-case planning assumption. This article is part of the theme issue ‘Modelling that shaped the early COVID-19 pandemic response in the UK’.
    • Outbreaks in care homes may lead to substantial disease burden if not mitigated

      Hall, Ian; orcid: 0000-0002-3033-2335; email: ian.hall@manchester.ac.uk; Lewkowicz, Hugo; orcid: 0000-0002-8944-0365; Webb, Luke; orcid: 0000-0001-6263-0575; House, Thomas; orcid: 0000-0001-5835-8062; Pellis, Lorenzo; orcid: 0000-0002-3436-6487; Sedgwick, James; orcid: 0000-0002-7200-4559; Gent, Nick; orcid: 0000-0002-2605-7369; on behalf of the University of Manchester COVID-19 Modelling Group and the Public Health England Modelling Team (The Royal Society, 2021-05-31)
      The number of COVID-19 outbreaks reported in UK care homes rose rapidly in early March of 2020. Owing to the increased co-morbidities and therefore worse COVID-19 outcomes for care home residents, it is important that we understand this increase and its future implications. We demonstrate the use of an SIS model where each nursing home is an infective unit capable of either being susceptible to an outbreak (S) or in an active outbreak (I). We use a generalized additive model to approximate the trend in growth rate of outbreaks in care homes and find the fit to be improved in a model where the growth rate is proportional to the number of current care home outbreaks compared with a model with a constant growth rate. Using parameters found from the outbreak-dependent growth rate, we predict a 73% prevalence of outbreaks in UK care homes without intervention as a reasonable worst-case planning assumption. This article is part of the theme issue ‘Modelling that shaped the early COVID-19 pandemic response in the UK’.
    • Palladium-doped hierarchical ZSM-5 for catalytic selective oxidation of allylic and benzylic alcohols

      Ding, Shengzhe; orcid: 0000-0003-2822-3882; Ganesh, Muhammad; Jiao, Yilai; Ou, Xiaoxia; Isaacs, Mark A.; orcid: 0000-0002-0335-4272; S'ari, Mark; Torres Lopez, Antonio; orcid: 0000-0001-7378-1811; Fan, Xiaolei; orcid: 0000-0002-9039-6736; email: xiaolei.fan@manchester.ac.uk; Parlett, Christopher M. A.; orcid: 0000-0002-3651-7314; email: christopher.parlett@manchester.ac.uk (The Royal Society, 2021-10-20)
      Hierarchical zeolites have the potential to provide a breakthrough in transport limitation, which hinders pristine microporous zeolites and thus may broaden their range of applications. We have explored the use of Pd-doped hierarchical ZSM-5 zeolites for aerobic selective oxidation (selox) of cinnamyl alcohol and benzyl alcohol to their corresponding aldehydes. Hierarchical ZSM-5 with differing acidity (H-form and Na-form) were employed and compared with two microporous ZSM-5 equivalents. Characterization of the four catalysts by X-ray diffraction, nitrogen porosimetry, NH3 temperature-programmed desorption, CO chemisorption, high-resolution scanning transmission electron microscopy, X-ray photoelectron spectroscopy and X-ray absorption spectroscopy allowed investigation of their porosity, acidity, as well as Pd active sites. The incorporation of complementary mesoporosity, within the hierarchical zeolites, enhances both active site dispersion and PdO active site generation. Likewise, alcohol conversion was also improved with the presence of secondary mesoporosity, while strong Brønsted acidity, present solely within the H-form systems, negatively impacted overall selectivity through undesirable self-etherification. Therefore, tuning support porosity and acidity alongside active site dispersion is paramount for optimal aldehyde production.
    • Scalability of resonant motor-driven flapping wing propulsion systems

      Nabawy, Mostafa R. A.; orcid: 0000-0002-4252-1635; email: mostafa.ahmednabawy@manchester.ac.uk; Marcinkeviciute, Ruta (The Royal Society, 2021-09-22)
      This work aims to develop an integrated conceptual design process to assess the scalability and performance of propulsion systems of resonant motor-driven flapping wing vehicles. The developed process allows designers to explore the interaction between electrical, mechanical and aerodynamic domains in a single transparent design environment. Wings are modelled based on a quasi-steady treatment that evaluates aerodynamics from geometry and kinematic information. System mechanics is modelled as a damped second-order dynamic system operating at resonance with nonlinear aerodynamic damping. Motors are modelled using standard equations that relate operational parameters and AC voltage input. Design scaling laws are developed using available data based on current levels of technology. The design method provides insights into the effects of changing core design variables such as the actuator size, actuator mass fraction and pitching kinematics on the overall design solution. It is shown that system efficiency achieves peak values of 30–36% at motor masses of 0.5–1 g when a constant angle of attack kinematics is employed. While sinusoidal angle of attack kinematics demands more aerodynamic and electric powers compared with the constant angle of attack case, sinusoidal angle of attack kinematics can lead to a maximum difference of around 15% in peak system efficiency.