Tag Archives: dynamics

Happy New Year!

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Decorative photograph of sculpture of a skeletal person leading a skeletal dinosaurThis year I have written about 20,000 words in 52 posts (including this one); and, since this is the last post of the year, I thought I would take a brief look back at what has preoccupied me in 2021.  Perhaps, not surprisingly the impact of the coronavirus on our lifestyle has featured regularly – almost every week for a month between mid-March and mid-April when we were in lockdown in the UK.  However, the other topics that I have written about frequently are my research on the dynamics of nanoparticles and, in the last six months, on dealing with uncertainty in digital engineering and decision making.  I have also returned several times to innovation processes and transitioning lab-based research into industry.  While following the COP26 in early November, I wrote a series of three posts focussed on energy consumption and the paradigm shifts required to slow down climate change.  There are some connections between these topics: viruses are nanoparticles whose transport and dynamics we do not fully understand; and, digital engineering tools are being used to explore zero-carbon approaches to, for example, energy generation and air transport.  The level of complexity, innovation and urgency associated with developing solutions to these challenges mean that there are always some unknowns and uncertainty when making associated decisions.

The links below are grouped by the topics mentioned above.  I expect there will be more on all of these topics in 2022; however, the topic of next week’s post is unknown because I have not written any posts in advance.  I hope that the uncertainty about the topic of the next post will keep you reading in 2022! 

Coronavirus pandemic: ‘Distancing ourselves from each other‘ on January 13th, 2021; ‘On the impact of writing on well-being‘ on March 3rd, 2021; ‘Collegiality as a defence against pandemic burnout‘ on March 24th, 2021; ‘It’s tiring looking at yourself‘ on March 31st, 2021; ‘Switching off and walking in circles‘ on April 7th, 2021; ‘An upside to lockdown‘ on April 14th, 2021; ‘A brief respite in a long campaign to overcome coronavirus‘ on June 23rd, 2021; and ‘It is hard to remain positive‘ November 3rd 2021.

Energy and climate change: ‘When you invent the ship, you invent the shipwreck‘ on August 25th, 2021; ‘It is hard to remain positive‘ November 3rd 2021; ‘Where we are and what we have‘ on November 24th, 2021; ‘Disruptive change required to avoid existential threats‘ on December 1st, 2021; and ‘Bringing an end to thermodynamic whoopee‘ on December 8th, 2021.

Innovation processes: ‘Slowly crossing the valley of death‘ on January 27th, 2021; ‘Out of the valley of death into a hype cycle?‘ on February 24th, 2021; ‘Innovative design too far ahead of the market?‘ on May 5th, 2021 and ‘Jigsaw puzzling without a picture‘ on October 27th, 2021.

Nanoparticles: ‘Going against the flow‘ on February 3rd, 2021; ‘Seeing things with nanoparticles‘ on March 10th, 2021; and ‘Nano biomechanical engineering of agent delivery to cells‘ on December 15th, 2021.

Uncertainty: ‘Certainty is unattainable and near-certainty is unaffordable‘ on May 12th, 2021; ‘Neat earth objects make tomorrow a little less than certain‘ on May 26th, 2021; ‘Negative capability and optimal ambiguity‘ on July 7th, 2021; ‘Deep uncertainty and meta ignorance‘ on July 21st, 2021; ‘Somethings will always be unknown‘ on August 18th, 2021; ‘Jigsaw puzzling without a picture‘ on October 27th, 2021; and, ‘Do you know RIO?‘ on November 17th, 2021.

Nano biomechanical engineering of agent delivery to cells

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figure 1 from [1] with text explanationWhile many of us are being jabbed in the arm to deliver an agent that stimulates our immune system to recognize the coronavirus SARS-CoV-2 as a threat and destroy it, my research group has been working, in collaboration with colleagues at the European Commission Joint Research Centre, on the dynamics of nanoparticles [1] [see ‘Size matters‘ on October 23rd, 2019] which could be used as carriers for the targeted delivery of therapeutic, diagnostic and imaging agents in the human body [2].  The use of nanoparticles to mechanically stimulate stem cells to activate signalling pathways and modulate their differentiation also has some potential [3]. In studies of the efficacy of nanoparticles in these biomedical applications, the concentration of nanoparticles interacting with the cell is a primary factor influencing both the positive and negative effects.  Such studies often involve exposing a monolayer of cultured cells adhered to the bottom of container to a dose of nanoparticles and monitoring the response over a period of time.  Often, the nominal concentration of the nanoparticles in biological medium supporting the cells is reported and used as the basis for determining the dose-response relationships.  However, we have shown that this approach is inaccurate and leads to misleading results because the nanoparticles in solution are subject to sedimentation due to gravity, Brownian motion [see ‘Slow moving nanoparticles‘ on December 13th, 2017] and inter-particle forces [see ‘ Going against the flow‘ on February 3rd, 2021] which affect their transport within the medium [see graphic] and the resultant concentration adjacent to the monolayer of cells.  Our experimental results using the optical method of caustics [see ‘Holes in fluids‘ on October 22nd, 2014] have shown that nanoparticle size, colloidal stability and solution temperature influence the distribution of nanoparticles in solution.  For particles larger than 60 nm in diameter (about one thousandth of the diameter of a human hair) the nominal dose differs significantly from the dose experienced by the cells.  We have developed and tested a theoretical model that accurately describes the settling dynamics and concentration profile of nanoparticles in solution which can be used to design in vitro experiments and compute dose-response relationships.

References

[1] Giorgi F, Macko P, Curran JM, Whelan M, Worth A & Patterson EA. 2021 Settling dynamics of nanoparticles in simple and biological media. Royal Society Open Science, 8:210068.

[2] Daraee H, Eatemadi A, Abbasi E, Aval SF, Kouhi M, & Akbarzadeh A. 2016 Application of gold nanoparticles in biomedical and drug delivery. Artif. Cells Nanomed. Biotechnol. 44, 410–422. (doi:10.3109/21691401.2014.955107)

[3] Wei M, Li S, & Le W. 2017 Nanomaterials modulate stem cell differentiation: biological
interaction and underlying mechanisms. J. Nanobiotechnol. 15, 75. (doi:10.1186/s12951-
017-0310-5)

From strain measurements to assessing El Niño events

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Figure 11 from RSOS 201086One of the exciting aspects of leading a university research group is that you can never be quite sure where the research is going next.  We published a nice example of this unpredictability last week in Royal Society Open Science in a paper called ‘Transformation of measurement uncertainties into low-dimensional feature space‘ [1].  While the title is an accurate description of the contents, it does not give much away and certainly does not reveal that we proposed a new method for assessing the occurrence of El Niño events.  For some time we have been working with massive datasets of measurements from arrays of sensors and representing them by fitting polynomials in a process known as image decomposition [see ‘Recognising strain‘ on October 28th, 2015]. The relatively small number of coefficients from these polynomials can be collated into a feature vector which facilitates comparison with other datasets [see for example, ‘Out of the valley of death into a hype cycle‘ on February 24th, 2021].  Our recent paper provides a solution to the issue of representing the measurement uncertainty in the same space as the feature vector which is roughly what we set out to do.  We demonstrated our new method for representing the measurement uncertainty by calibrating and validating a computational model of a simple beam in bending using data from an earlier study in a EU-funded project called VANESSA [2] — so no surprises there.  However, then my co-author and PhD student, Antonis Alexiadis went looking for other interesting datasets with which to demonstrate the new method.  He found a set of spatially-varying uncertainties associated with a metamodel of soil moisture in a river basin in China [3] and global oceanographic temperature fields collected monthly over 11 years from 2002 to 2012 [4].  We used the latter set of data to develop a new technique for assessing the occurrence of El-Niño events in the Pacific Ocean.  Our technique is based on global ocean dynamics rather than on the small region in the Pacific Ocean which is usually used and has the added advantages of providing a confidence level on the assessment as well as enabling straightforward comparisons of predictions and measurements.  The comparison of predictions and measurements is a recurring theme in our current research but I did not expect it to lead into ocean dynamics.

Image is Figure 11 from [1] showing convex hulls fitted to the cloud of points representing the uncertainty intervals for the ocean temperature measurements for each month in 2002 using only the three most significant principal components . The lack of overlap between hulls can be interpreted as implying a significant difference in the temperature between months.

References:

[1] Alexiadis, A. and Ferson, S. and  Patterson, E.A., , 2021. Transformation of measurement uncertainties into low-dimensional feature vector space. Royal Society Open Science, 8(3): 201086.

[2] Lampeas G, Pasialis V, Lin X, Patterson EA. 2015.  On the validation of solid mechanics models using optical measurements and data decomposition. Simulation Modelling Practice and Theory 52, 92-107.

[3] Kang J, Jin R, Li X, Zhang Y. 2017, Block Kriging with measurement errors: a case study of the spatial prediction of soil moisture in the middle reaches of Heihe River Basin. IEEE Geoscience and Remote Sensing Letters, 14, 87-91.

[4] Gaillard F, Reynaud T, Thierry V, Kolodziejczyk N, von Schuckmann K. 2016. In situ-based reanalysis of the global ocean temperature and salinity with ISAS: variability of the heat content and steric height. J. Climate. 29, 1305-1323.

Reduction in usefulness of reductionism

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decorative paintingA couple of months ago I wrote about a set of credibility factors for computational models [see ‘Credible predictions for regulatory decision-making‘ on December 9th, 2020] that we designed to inform interactions between researchers, model builders and decision-makers that will establish trust in the predictions from computational models [1].  This is important because computational modelling is becoming ubiquitous in the development of everything from automobiles and power stations to drugs and vaccines which inevitably leads to its use in supporting regulatory applications.  However, there is another motivation underpinning our work which is that the systems being modelled are becoming increasingly complex with the likelihood that they will exhibit emergent behaviour [see ‘Emergent properties‘ on September 16th, 2015] and this makes it increasingly unlikely that a reductionist approach to establishing model credibility will be successful [2].  The reductionist approach to science, which was pioneered by Descartes and Newton, has served science well for hundreds of years and is based on the concept that everything about a complex system can be understood by reducing it to the smallest constituent part.  It is the method of analysis that underpins almost everything you learn as an undergraduate engineer or physicist. However, reductionism loses its power when a system is more than the sum of its parts, i.e., when it exhibits emergent behaviour.  Our approach to establishing model credibility is more holistic than traditional methods.  This seems appropriate when modelling complex systems for which a complete knowledge of the relationships and patterns of behaviour may not be attainable, e.g., when unexpected or unexplainable emergent behaviour occurs [3].  The hegemony of reductionism in science made us nervous about writing about its short-comings four years ago when we first published our ideas about model credibility [2].  So, I was pleased to see a paper published last year [4] that identified five fundamental properties of biology that weaken the power of reductionism, namely (1) biological variation is widespread and persistent, (2) biological systems are relentlessly nonlinear, (3) biological systems contain redundancy, (4) biology consists of multiple systems interacting across different time and spatial scales, and (5) biological properties are emergent.  Many engineered systems possess all five of these fundamental properties – you just to need to look at them from the appropriate perspective, for example, through a microscope to see the variation in microstructure of a mass-produced part.  Hence, in the future, there will need to be an increasing emphasis on holistic approaches and systems thinking in both the education and practices of engineers as well as biologists.

For more on emergence in computational modelling see Manuel Delanda Philosophy and Simulation: The Emergence of Synthetic Reason, Continuum, London, 2011. And, for more systems thinking see Fritjof Capra and Luigi Luisi, The Systems View of Life: A Unifying Vision, Cambridge University Press, 2014.

References:

[1] Patterson EA, Whelan MP & Worth A, The role of validation in establishing the scientific credibility of predictive toxicology approaches intended for regulatory application, Computational Toxicology, 17: 100144, 2021.

[2] Patterson EA &Whelan MP, A framework to establish credibility of computational models in biology. Progress in biophysics and molecular biology, 129: 13-19, 2017.

[3] Patterson EA & Whelan MP, On the validation of variable fidelity multi-physics simulations, J. Sound & Vibration, 448:247-258, 2019.

[4] Pruett WA, Clemmer JS & Hester RL, Physiological Modeling and Simulation—Validation, Credibility, and Application. Annual Review of Biomedical Engineering, 22:185-206, 2020.