Simon D. Angus

Microgel stars viaReversible Addition Fragmentation Chain Transfer (RAFT) polymerisation — a facile route to macroporous membranes, honeycomb patterned thin films and inverse opal substrates

Arm first microgel polymers were successfully synthesised utilising Reversible Addition Fragmentation Chain Transfer (RAFT) polymerisation techniques. A functional prearm linear AB block copolymer intermediate, (polystyrene)-block-(polydivinylbenzene), was prepared via RAFT by simple one pot chain extension and arm coupling of a preprepared polystyrene macromer. The arms are coupled together via the residual unsaturation present in the polydivinylbenzene block by free radical means to form core-crosslinked microgels. It was found that the arm coupling process could be described by invoking a two-stage coupling system. The initial induction period consists of the formation of largely two-arm (on average) species. This is followed by a latter growth period, where true core-crosslinked microgels are formed consisting of polyarm clusters having 16 arms (on average) per cluster. These microgel materials were cast under specific conditions to form porous polymer films of varying quality. Image analysis of these films demonstrated the importance of the linear component : microgel component ratio in determining both a uniform pore size and the formation of a hexagonal close packed array of pores.

A quantitative cellular automaton model of in vitro multicellular spheroid tumour growth

We report numerical results from a 2D cellular automaton (CA) model describing the dynamics of the in vitro cultivated multicellular spheroid obtained from EMT6/Ro (mammary carcinoma) cell line. Significantly, the CA model relaxes the often assumed one-to-one correspondence between cells and CA sites so as to correctly model the peripheral mitotic boundary region, and to enable the study of necrosis in large avascular tumours. By full calibration and scaling to available experimental data, the model produces with good accuracy experimentally comparable data on a range of bulk tumour kinetics and necrosis measures. Our main finding is that the metabolic production of H(+) ions is not sufficient to cause central necrosis prior to the sub-viable nutrient-deficient stage of tumour development being reached. Thus, the model suggests that an additional process is required to explain the experimentally observable onset of necrosis prior to the non-viable nutrient-deficient point being reached.

Did recent world record marathon runners employ optimal pacing strategies

Abstract We apply statistical analysis of high frequency (1 km) split data for the most recent two world-record marathon runs: Run 1 (2:03:59, 28 September 2008) and Run 2 (2:03:38, 25 September 2011). Based on studies in the endurance cycling literature, we develop two principles to approximate ‘optimal’ pacing in the field marathon. By utilising GPS and weather data, we test, and then de-trend, for each athlete’s field response to gradient and headwind on course, recovering standardised proxies for power-based pacing traces. The resultant traces were analysed to ascertain if either runner followed optimal pacing principles; and characterise any deviations from optimality. Whereas gradient was insignificant, headwind was a significant factor in running speed variability for both runners, with Runner 2 targeting the (optimal) parallel variation principle, whilst Runner 1 did not. After adjusting for these responses, neither runner followed the (optimal) ‘even’ power pacing principle, with Runner 2’s macro-pacing strategy fitting a sinusoidal oscillator with exponentially expanding envelope whilst Runner 1 followed a U-shaped, quadratic form. The study suggests that: (a) better pacing strategy could provide elite marathon runners with an economical pathway to significant performance improvements at world-record level; and (b) the data and analysis herein is consistent with a complex-adaptive model of power regulation.

Coalitions, tipping points and the speed of evolution

This study considers waiting times for populations to achieve efficient social coordination. Belloc and Bowles [1] conjecture that coalitional behavior will hasten such coordination. This turns out to be true when every member of the population interacts with every other member, but does not extend to more complex networks of interaction. Although it is in the interest of every player to coordinate on a single globally efficient norm, coalitional behavior at a local level can greatly slow, as well as hasten, convergence to efficiency.

A Resource Efficient Big Data Analysis Method for the Social Sciences: The Case of Global IP Activity☆

Abstract This paper presents a novel and efficient way of analysing big datasets used in social science research. We provide and demonstrate a way to deal with such datasets without the need for high performance distributed computational facilities. Using an Internet census dataset and with the help of freely available tools and programming libraries, we visualize global IP activity in a spatial and time dimension. We observe a considerable reduction in storage size of our dataset coupled with a faster processing time.

Emergence of Shared Intentionality Is Coupled to the Advance of Cumulative Culture

It has been hypothesized that the evolution of modern human cognition was catalyzed by the development of jointly intentional modes of behaviour. From an early age (1-2 years), human infants outperform apes at tasks that involve collaborative activity. Specifically, human infants excel at joint action motivated by reasoning of the form “we will do X” (shared intentions), as opposed to reasoning of the form “I will do X [because he is doing X]” (individual intentions). The mechanism behind the evolution of shared intentionality is unknown. Here we formally model the evolution of jointly intentional action and show under what conditions it is likely to have emerged in humans. Modelling the interaction of huntergatherers as a coordination game, we find that when the benefits from adopting new technologies or norms are low but positive, the sharing of intentions does not evolve, despite being a mutualistic behaviour that directly benefits all participants. When the benefits from adopting new technologies or norms are high, such as may be the case during a period of rapid environmental change, shared intentionality evolves and rapidly becomes dominant in the population. OurThere is evidence that the sharing of intentions was an important factor in the evolution of humans’ unique cognitive abilities. Here, for the first time, we formally model the coevolution of jointly intentional behavior and cumulative culture, showing that rapid techno-cultural advance goes hand in hand with the emergence of the ability to participate in jointly intentional behavior. Conversely, in the absence of opportunities for significant techno-cultural improvement, the ability to undertake jointly intentional behavior is selected against. Thus, we provide a unified mechanism for the suppression or emergence of shared intentions and collaborative behavior in humans, as well as a potential cause of inter-species diversity in the prevalence of such behavior.

A Matter of Timing: Identifying Significant Multi-Dose Radiotherapy Improvements by Numerical Simulation and Genetic Algorithm Search

Multi-dose radiotherapy protocols (fraction dose and timing) currently used in the clinic are the product of human selection based on habit, received wisdom, physician experience and intra-day patient timetabling. However, due to combinatorial considerations, the potential treatment protocol space for a given total dose or treatment length is enormous, even for relatively coarse search; well beyond the capacity of traditional in-vitro methods. In constrast, high fidelity numerical simulation of tumor development is well suited to the challenge. Building on our previous single-dose numerical simulation model of EMT6/Ro spheroids, a multi-dose irradiation response module is added and calibrated to the effective dose arising from 18 independent multi-dose treatment programs available in the experimental literature. With the developed model a constrained, non-linear, search for better performing cadidate protocols is conducted within the vicinity of two benchmarks by genetic algorithm (GA) techniques. After evaluating less than 0.01% of the potential benchmark protocol space, candidate protocols were identified by the GA which conferred an average of 9.4% (max benefit 16.5%) and 7.1% (13.3%) improvement (reduction) on tumour cell count compared to the two benchmarks, respectively. Noticing that a convergent phenomenon of the top performing protocols was their temporal synchronicity, a further series of numerical experiments was conducted with periodic time-gap protocols (10 h to 23 h), leading to the discovery that the performance of the GA search candidates could be replicated by 17–18 h periodic candidates. Further dynamic irradiation-response cell-phase analysis revealed that such periodicity cohered with latent EMT6/Ro cell-phase temporal patterning. Taken together, this study provides powerful evidence towards the hypothesis that even simple inter-fraction timing variations for a given fractional dose program may present a facile, and highly cost-effecitive means of significantly improving clinical efficacy.

A numerical model of EMT6/Ro spheroid dynamics under irradiation: calibration and estimation of the underlying irradiation-induced cell survival probability.

We present extensions to our quasi-2D cellular automata spheroid model that add a cellular kinetics module together with an irradiation and repair module. Significantly, our approach is not based on the Linear Quadratic (LQ) model, instead, we propose a simple two-parameter, algorithmic model which captures the essential biological features of irradiation-induced cell death, repair and associated cell cycle delays. This approach allows us to estimate directly the underlying irradiation-induced cell survival probability. We present the calibration of this extended model both with and without the application of single irradiation doses to the commonly studied (in vitro) EMT6/Ro (mammary carcinoma) cell line. A comparison of the estimated underlying cell survival probability with the in vitro survival probability data confirms the expected differences in the measures.

Watercooler chat, organizational structure and corporate culture

Modeling firms as networks of employees, occasional collaborative decision making around the office watercooler changes long run employee behavior (corporate culture). The culture that emerges in a given team of employees depends on team size and on how the team is connected to the wider firm. The implications of the model for organizational design are explored and related to empirical research on communication, innovation, the size and decision making of teams and trends in the design of hierarchical structures.

The bit‐economy: An artificial model of open‐ended technology discovery

We describe and demonstrate an artificial model of technology discovery called the Bit-Economy. The model is built from a minimal set of fundamental hallmarks of technology and develops under an open-ended evolutionary operator which rewards new technology which is able to coordinate both spatially and temporally with the existing technology set. The Bit-Economy, is able to replicate several features of real technology development including nonmonotonic growth, bunching of creation and destruction events, qualitative topologies of patent networks, and efficiency and waste-management gains. In contrast to related works, we do not apply an exogenous fitness landscape and so are able to study the process of technology discovery as a self-guided search toward more complex outcomes.