Shortly before the pandemic started to have an impact in the UK, I went to our local second-hand bookshop and bought a pile of old paperbacks to read. One of them was ‘Daisy Miller and Other Stories’ by Henry James (published in 1983 as Penguin Modern Classic). The title of this post is a quote from one of the ‘other stories’, ‘The Lesson of the Master’, which was first published in 1888. ‘Success is to have made people wriggle to another tune’ is said by the successful fictional novelist, Henry St George as words of encouragement to the young novelist Paul Ovett. It struck a chord with me because I think it sums up academic life. Success in teaching is to inspire a new level of insight and way of thinking amongst our students; while, success in research is to change the way in which society, or at least a section of it, thinks or operates, i.e. to have made people wriggle to another tune.
Along with many people, I have been working from home since mid-March and it seems likely that I will be doing so for the foreseeable future. Even if a vaccine is discovered for COVID-19, it will take many months to vaccinate the population. For the first few months of lockdown, I worked on an old workbench in the basement of our house; however, now I have an office set up in the attic and the picture above is the view from my desk. It certainly has eye-stretching potential but it is also frustrating because I can see the roof of the building in which my university office is located. However, the lockdown in the UK has been relaxed and so we are going on holiday to Cornwall where we will be walking sections of the South West Coastal Path and reading a pile of books. If you want experience the walking with us then I recommend reading ‘The Salt Path‘ by Raynor Winn [see ‘The Salt Path‘ on August 14th, 2019]. Although I will be indulging in a digital detox [see ‘Digital detox with a deep vacation‘ on August 10th, 2016] combined with some horizon therapy [see ‘Horizon therapy‘ on May 4th, 2016], the flow of posts to this blog will be uninterrupted because lock-down has allowed me write sufficient pieces in advance to maintain the publishing schedule.
I noticed that both of the posts cited above about the importance of relaxing were published in 2016, along with Steadiness and Placidity on July 171th, 2016. 2016 must have been a stressful year!
During the lock-down in the UK due to the coronavirus pandemic, I have been reading about viruses and the modelling of them. It is a multi-disciplinary and multi-scale problem; so, something that engineers should be well-equipped to tackle. It is a multi-scale because we need to understand the spread of the virus in the human population so that we can control it, we need to understand the process of infection in individuals so that we can protect them, and we need to understand the mechanisms of virus-cell interaction so that we can stop the replication of the virus. At each size scale, models capable of representing the real-world processes will help us explore different approaches to arresting the progress of the virus and will need to be calibrated and validated against measurements. This can be represented in the sort of model-test pyramid shown in the top graphic that has been used in the aerospace industry [1-2] for many years [see ‘Hierarchical modelling in engineering and biology’ on March 14th, 2018] and which we have recently introduced in the nuclear fission  and fusion  industries [see ‘Thought leadership in fusion engineering’ on October 9th, 2019]. At the top of the pyramid, the spread of the virus in the population is being modelled by epidemiologists, such as Professor Neil Ferguson , using statistical models based on infection data. However, I am more interested in the bottom of the pyramid because the particles of the coronavirus are about the same size as the nanoparticles that I have been studying for some years [see ‘Slow moving nanoparticles’ on December 13th, 2017] and their motion appears to be dominated by diffusion processes [see ‘Salt increases nanoparticle diffusion’ on April 22nd, 2020] [6-7]. The first step towards virus infection of a cell is diffusion of the virus towards the cell which is believed to be a relatively slow process and hence a good model of diffusion would assist in designing drugs that could arrest or decelerate infection of cells . Many types of virus on entering the cell make their way to the nucleus where they replicate causing the cell to die, afterwhich the virus progeny are dispersed to repeat the process. You can see part of this sequence for coronavirus (SARS-COV-2) in this sequence of images. The trafficking across the cytoplasm of the cell to the nucleus can occur in a number of ways including the formation of a capsule or endosome that moves across the cell towards the nuclear membrane where the virus particles leave the endosome and travel through microtubules into the nucleus. Holcman & Schuss  provide a good graphic illustrating these transport mechanisms. In 2019, Briane et al  reviewed models of diffusion of intracellular particles inside living eukaryotic cells, i.e. cells with a nuclear enclosed by a membrane as in all animals. Intracellular diffusion is believed to be driven by Brownian motion and by motor-proteins including dynein, kinesin and myosin that enable motion through microtubules. They observed that the density of the structure of cytoplasm, or cytoskeleton, can hinder the free displacement of a particle leading to subdiffusion; while, cytoskeleton elasticity and thermal bending can accelerate it leading to superdiffusion. These molecular and cellular interactions are happening at disparate spatial and temporal scales  which is one of the difficulties encountered in creating predictive simulations of virus-cell interactions. In other words, the bottom layers of the model-test pyramid appear to be constructed from many more strata when you start to look more closely. And, you need to add a time dimension to it. Prior to the coronavirus pandemic, more modelling efforts were perhaps focussed on understanding the process of infection by Human Immunodeficiency Virus (HIV), including by a multi-national group of scientists from Chile, France, Morocco, Russia and Spain [12-14]. However, the current coronavirus pandemic is galvanising researchers who are starting to think about novel ways of building multiscale models that encourage multidisciplinary collaboration by dispersed groups, [e.g. 15].
 Harris GL, Computer models, laboratory simulators, and test ranges: meeting the challenge of estimating tactical force effectiveness in the 1980’s, US Army Command and General Staff College, May 1979.
 Trevisani DA & Sisti AF, Air Force hierarchy of models: a look inside the great pyramid, Proc. SPIE 4026, Enabling Technology for Simulation Science IV, 23 June 2000.
 Patterson EA, Taylor RJ & Bankhead M, A framework for an integrated nuclear digital environment, Progress in Nuclear Energy, 87:97-103, 2016.
 Patterson EA, Purdie S, Taylor RJ & Waldon C, An integrated digital framework for the design, build and operation of fusion power plants, Royal Society Open Science, 6(10):181847, 2019.
 Verity R, Okell LC, Dorigatti I, Winskill P, Whittaker C, Imai N, Cuomo-Dannenburg G, Thompson H, Walker PGT, Fu H, Dighe A, Griffin JT, Baguelin M, Bhatia S, Boonyasiri A, Cori A, Cucunubá Z, FitzJohn R, Gaythorpe K, Green W, Hamlet A, Hinsley W, Laydon D, Nedjati-Gilani G, Riley S, van Elsland S, Volz E, Wang H, Wang Y, Xi X, Donnelly CA, Ghani AC, Ferguson NM, Estimates of the severity of coronavirus disease 2019: a model-based analysis., Lancet Infectious Diseases, 2020.
 Coglitore D, Edwardson SP, Macko P, Patterson EA, Whelan MP, Transition from fractional to classical Stokes-Einstein behaviour in simple fluids, Royal Society Open Science, 4:170507, 2017.
 Giorgi F, Coglitore D, Curran JM, Gilliland D, Macko P, Whelan M, Worth A & Patterson EA, The influence of inter-particle forces on diffusion at the nanoscale, Scientific Reports, 9:12689, 2019.
 Gilbert P-A, Kamen A, Bernier A & Garner A, A simple macroscopic model for the diffusion and adsorption kinetics of r-Adenovirus, Biotechnology & Bioengineering, 98(1):239-251,2007.
 Holcman D & Schuss Z, Modeling the early steps of viral infection in cells, Chapter 9 in Stochastic Narrow Escape in Molecular and Cellular Biology, New York: Springer Science+Business Media, 2015.
 Braine V, Vimond M & Kervrann C, An overview of diffusion models for intracellular dynamics analysis, Briefings in Bioinformatics, Oxford University Press, pp.1-15, 2019.
 Holcman D & Schuss Z, Time scale of diffusion in molecular and cellular biology, J. Physics A: Mathematical and Theoretical, 47:173001, 2014.
 Bocharov G, Chereshnev V, Gainov I, Bazhun S, Bachmetyev B, Argilaguet J, Martinez J & Meyerhans A, Human immunodeficiency virus infection: from biological observations to mechanistic mathematical modelling, Math. Model. Nat. Phenom., 7(5):78-104, 2012.
 Bocharov G, Meyerhans A, Bessonov N, Trofimchuk S & Volpert V, Spatiotemporal dynamics of virus infection spreading in tissues, PLOS One, 11(12):e)168576, 2016.
 Bouchnita A, Bocharov G, Meyerhans A & Volpert V, Towards a multiscale model of acute HIV infection, Computation, 5(6):5010006, 2017.
 Sego TJ, Aponte-Serrano JO, Ferrari-Gianlupi J, Heaps S, Quardokus EM & Glazier JA, A modular framework for multiscale spatial modeling of viral infection and immune respons in epithelial tissue, bioRxiv. 2020.
I am on vacation this week though, due to the restrictions on our movement imposed to prevent the spread of the coronavirus, it will a be staycation in our house. We usually go to the Lake District at this time of year to walk and read; so, I might make another virtual expedition [see: ‘Virtual ascent of Moel Famau’ on April 8th, 2020], perhaps to climb Stickle Pike and Great Stickle this time. I was asked recently about books I would recommend prospective science and engineering students to read in preparation for to going to university. It is not the first time that I have been asked the question. This time I thought I should respond via this blog since the disruption brought about by the pandemic probably means that many prospective students will have more time and less preparation prior to starting their university course. So, here are six books that are all available as ebooks, and might be of interest to anyone who is staying home to counter the spread of coronavirus and has time to fill:
 It is hard to find good novels either written by an engineer or about engineering [see ‘Engineering novelist‘ on August 5th, 2015]; however, Nevil Shute’s novel ‘Trustee from the toolroom‘ [Penguin Books, 1960] satisfies all of these criteria.
I have more than 40 years experience of engineering science so I am not the best person to ask about books that will appeal to young people just starting their journey in the field; however two books that have been popular recently are:  ‘Storm in a teacup: the physics of everyday life‘ by Helen Czerski [Penguin Books, 2016] and  ‘Think like an engineer‘ by Guru Madhavan [One World Publications, 2016]
Regular readers of this blog might have spotted some of my favourite science books in the lists of sources at the end of posts. Perhaps my top three at the moment are:
 Max Tegmark, Our Mathematical Universe, Penguin Books Ltd, 2014. [see: ‘Converting wealth into knowledge and back to wealth‘ on January 6th, 2016; ‘Trees are made of air‘ on April 1st, 2015; ‘Is the Earth a closed system? Does it matter?‘ on December 10th, 2014 & ‘Tidal energy‘ on September 17th, 2014]
 Susan Greenfield, A Day in the Life of the Brain, London: Allen Lane, 2016 [see: ‘Digital hive mind‘ on November 30th, 2016; ‘Gone walking‘ on April 19th, 2017 & ‘Walking through exams‘ on May 17th, 2017].
Of course, I should not omit the books that I ask students to read for my own first year module in thermodynamics:
Peter Atkins, A very short introduction to thermodynamics, Oxford: OUP, 2010.
Manuel Delanda ‘Philosophy and Simulation: The Emergence of Synthetic Reason‘, London: Continuum Int. Pub. Group, 2011 [see: ‘More violent storms‘ on March 1st, 2017; ‘Emergent properties‘ on September 16th, 2015 & ‘Emerging inequality‘ on March 5th, 2014].