Showing papers in "Journal of the Royal Society Interface in 2015"
TL;DR: It is found that most urban indicators scale linearly with city size, regardless of the definition of the urban boundaries, however, when nonlinear correlations are present, the exponent fluctuates considerably.
Abstract: Cities can be characterized and modelled through different urban measures. Consistency within these observables is crucial in order to advance towards a science of cities. Bettencourt et al. have proposed that many of these urban measures can be predicted through universal scaling laws. We develop a framework to consistently define cities, using commuting to work and population density thresholds, and construct thousands of realizations of systems of cities with different boundaries for England and Wales. These serve as a laboratory for the scaling analysis of a large set of urban indicators. The analysis shows that population size alone does not provide us enough information to describe or predict the state of a city as previously proposed, indicating that the expected scaling laws are not corroborated. We found that most urban indicators scale linearly with city size, regardless of the definition of the urban boundaries. However, when nonlinear correlations are present, the exponent fluctuates considerably.
309 citations
TL;DR: This review focuses on how inflammation has been associated with IVD degeneration by describing observational and in vitro studies as well as in vivo animal models and provides an overview of IVD regenerative therapies that target key inflammatory players.
Abstract: Intervertebral disc (IVD) degeneration is one of the major causes of low back pain, a problem with a heavy economic burden, which has been increasing in prevalence as populations age. Deeper knowledge of the complex spatial and temporal orchestration of cellular interactions and extracellular matrix remodelling is critical to improve current IVD therapies, which have so far proved unsatisfactory. Inflammation has been correlated with degenerative disc disease but its role in discogenic pain and hernia regression remains controversial. The inflammatory response may be involved in the onset of disease, but it is also crucial in maintaining tissue homeostasis. Furthermore, if properly balanced it may contribute to tissue repair/regeneration as has already been demonstrated in other tissues. In this review, we focus on how inflammation has been associated with IVD degeneration by describing observational and in vitro studies as well as in vivo animal models. Finally, we provide an overview of IVD regenerative therapies that target key inflammatory players.
308 citations
TL;DR: This review generally describes the mechanotransductive process through discussion of well-known mechanosensors, and focuses on discussion of recent examples where AFM is used to specifically probe the elastic and inelastic responses of single cells undergoing deformation.
Abstract: Transmission of mechanical force is crucial for normal cell development and functioning. However, the process of mechanotransduction cannot be studied in isolation from cell mechanics. Thus, in order to understand how cells ‘feel’, we must first understand how they deform and recover from physical perturbations. Owing to its versatility, atomic force microscopy (AFM) has become a popular tool to study intrinsic cellular mechanical properties. Used to directly manipulate and examine whole and subcellular reactions, AFM allows for top-down and reconstitutive approaches to mechanical characterization. These studies show that the responses of cells and their components are complex, and largely depend on the magnitude and time scale of loading. In this review, we generally describe the mechanotransductive process through discussion of well-known mechanosensors. We then focus on discussion of recent examples where AFM is used to specifically probe the elastic and inelastic responses of single cells undergoing deformation. We present a brief overview of classical and current models often used to characterize observed cellular phenomena in response to force. Both simple mechanistic models and complex nonlinear models have been used to describe the observed cellular behaviours, however a unifying description of cell mechanics has not yet been resolved.
300 citations
TL;DR: Recent studies reported in the literature to functionalize scaffolds in the context of CTE, are discussed and the results of novel promising strategies and techniques are discussed.
Abstract: The development of biomaterials for cardiac tissue engineering (CTE) is challenging, primarily owing to the requirement of achieving a surface with favourable characteristics that enhances cell attachment and maturation. The biomaterial surface plays a crucial role as it forms the interface between the scaffold (or cardiac patch) and the cells. In the field of CTE, synthetic polymers (polyglycerol sebacate, polyethylene glycol, polyglycolic acid, poly-l-lactide, polyvinyl alcohol, polycaprolactone, polyurethanes and poly(N-isopropylacrylamide)) have been proven to exhibit suitable biodegradable and mechanical properties. Despite the fact that they show the required biocompatible behaviour, most synthetic polymers exhibit poor cell attachment capability. These synthetic polymers are mostly hydrophobic and lack cell recognition sites, limiting their application. Therefore, biofunctionalization of these biomaterials to enhance cell attachment and cell material interaction is being widely investigated. There are numerous approaches for functionalizing a material, which can be classified as mechanical, physical, chemical and biological. In this review, recent studies reported in the literature to functionalize scaffolds in the context of CTE, are discussed. Surface, morphological, chemical and biological modifications are introduced and the results of novel promising strategies and techniques are discussed.
267 citations
TL;DR: It is found that the combinatorial inventive process exhibits an invariant rate of ‘exploitation’ (refinements of existing combinations of technologies) and “exploration” (the development of new technological combinations) and the generation of novel technological combinations engenders a practically infinite space of technological configurations.
Abstract: Invention has been commonly conceptualized as a search over a space of combinatorial possibilities. Despite the existence of a rich literature, spanning a variety of disciplines, elaborating on the recombinant nature of invention, we lack a formal and quantitative characterization of the combinatorial process underpinning inventive activity. Here, we use US patent records dating from 1790 to 2010 to formally characterize invention as a combinatorial process. To do this, we treat patented inventions as carriers of technologies and avail ourselves of the elaborate system of technology codes used by the United States Patent and Trademark Office to classify the technologies responsible for an invention's novelty. We find that the combinatorial inventive process exhibits an invariant rate of ‘exploitation’ (refinements of existing combinations of technologies) and ‘exploration’ (the development of new technological combinations). This combinatorial dynamic contrasts sharply with the creation of new technological capabilities—the building blocks to be combined—that has significantly slowed down. We also find that, notwithstanding the very reduced rate at which new technologies are introduced, the generation of novel technological combinations engenders a practically infinite space of technological configurations.
218 citations
TL;DR: It is shown that such a strategy focusing on feed components which do not compete with direct human food consumption offers a viable complement to strategies focusing on increased efficiency in production or reduced shares of animal products in consumption.
Abstract: Increasing efficiency in livestock production and reducing the share of animal products in human consumption are two strategies to curb the adverse environmental impacts of the livestock sector. Here, we explore the room for sustainable livestock production by modelling the impacts and constraints of a third strategy in which livestock feed components that compete with direct human food crop production are reduced. Thus, in the outmost scenario, animals are fed only from grassland and by-products from food production. We show that this strategy could provide sufficient food (equal amounts of human-digestible energy and a similar protein/calorie ratio as in the reference scenario for 2050) and reduce environmental impacts compared with the reference scenario (in the most extreme case of zero human-edible concentrate feed: greenhouse gas emissions -18%; arable land occupation -26%, N-surplus -46%; P-surplus -40%; non-renewable energy use -36%, pesticide use intensity -22%, freshwater use -21%, soil erosion potential -12%). These results occur despite the fact that environmental efficiency of livestock production is reduced compared with the reference scenario, which is the consequence of the grassland-based feed for ruminants and the less optimal feeding rations based on by-products for non-ruminants. This apparent contradiction results from considerable reductions of animal products in human diets (protein intake per capita from livestock products reduced by 71%). We show that such a strategy focusing on feed components which do not compete with direct human food consumption offers a viable complement to strategies focusing on increased efficiency in production or reduced shares of animal products in consumption.
214 citations
TL;DR: It is argued that the evidence supports both a level of redundancy and a degree of selectivity in the structure–activity relationship between HS and heparin.
Abstract: Heparan sulfate (HS) polysaccharides are ubiquitous components of the cell surface and extracellular matrix of all multicellular animals, whereas heparin is present within mast cells and can be vie...
211 citations
TL;DR: This work surveys recent methods for collective mining (integration) of various types of networked biological data and proposes that recent non-negative matrix factorization-based approaches may become the integration methodology of choice, as they are well suited and accurate in dealing with heterogeneous data and have many opportunities for further development.
Abstract: Rapid technological advances have led to the production of different types of biological data and enabled construction of complex networks with various types of interactions between diverse biological entities. Standard network data analysis methods were shown to be limited in dealing with such heterogeneous networked data and consequently, new methods for integrative data analyses have been proposed. The integrative methods can collectively mine multiple types of biological data and produce more holistic, systems-level biological insights. We survey recent methods for collective mining (integration) of various types of networked biological data. We compare different state-of-the-art methods for data integration and highlight their advantages and disadvantages in addressing important biological problems. We identify the important computational challenges of these methods and provide a general guideline for which methods are suited for specific biological problems, or specific data types. Moreover, we propose that recent non-negative matrix factorization-based approaches may become the integration methodology of choice, as they are well suited and accurate in dealing with heterogeneous data and have many opportunities for further development.
204 citations
TL;DR: A new non-symmetric dispersion model is introduced, based on the bivariate von Mises distribution, which is used to construct a new structure tensor and provides specific ranges for the dispersion parameters and shows how previous models can be deduced as special cases.
Abstract: New experimental results on collagen fibre dispersion in human arterial layers have shown that the dispersion in the tangential plane is more significant than that out of plane. A rotationally symmetric dispersion model is not able to capture this distinction. For this reason, we introduce a new non-symmetric dispersion model, based on the bivariate von Mises distribution, which is used to construct a new structure tensor. The latter is incorporated in a strain-energy function that accommodates both the mechanical and structural features of the material, extending our rotationally symmetric dispersion model (Gasser et al. 2006 J. R. Soc. Interface 3, 15–35. (doi:10.1098/rsif.2005.0073)). We provide specific ranges for the dispersion parameters and show how previous models can be deduced as special cases. We also provide explicit expressions for the stress and elasticity tensors in the Lagrangian description that are needed for a finite-element implementation. Material and structural parameters were obtained by fitting predictions of the model to experimental data obtained from human abdominal aortic adventitia. In a finite-element example, we analyse the influence of the fibre dispersion on the homogeneous biaxial mechanical response of aortic strips, and in a final example the non-homogeneous stress distribution is obtained for circumferential and axial strips under fixed extension. It has recently become apparent that this more general model is needed for describing the mechanical behaviour of a variety of fibrous tissues.
198 citations
TL;DR: The nanobiocatalyst (NBC) is an emerging innovation that synergistically integrates advanced nanotechnology with biotechnology and promises exciting advantages for improving enzyme activity, stability, capability and engineering performances in bioprocessing applications.
Abstract: The nanobiocatalyst (NBC) is an emerging innovation that synergistically integrates advanced nanotechnology with biotechnology and promises exciting advantages for improving enzyme activity, stability, capability and engineering performances in bioprocessing applications. NBCs are fabricated by immobilizing enzymes with functional nanomaterials as enzyme carriers or containers. In this paper, we review the recent developments of novel nanocarriers/nanocontainers with advanced hierarchical porous structures for retaining enzymes, such as nanofibres (NFs), mesoporous nanocarriers and nanocages. Strategies for immobilizing enzymes onto nanocarriers made from polymers, silicas, carbons and metals by physical adsorption, covalent binding, cross-linking or specific ligand spacers are discussed. The resulting NBCs are critically evaluated in terms of their bioprocessing performances. Excellent performances are demonstrated through enhanced NBC catalytic activity and stability due to conformational changes upon immobilization and localized nanoenvironments, and NBC reutilization by assembling magnetic nanoparticles into NBCs to defray the high operational costs associated with enzyme production and nanocarrier synthesis. We also highlight several challenges associated with the NBC-driven bioprocess applications, including the maturation of large-scale nanocarrier synthesis, design and development of bioreactors to accommodate NBCs, and long-term operations of NBCs. We suggest these challenges are to be addressed through joint collaboration of chemists, engineers and material scientists. Finally, we have demonstrated the great potential of NBCs in manufacturing bioprocesses in the near future through successful laboratory trials of NBCs in carbohydrate hydrolysis, biofuel production and biotransformation.
191 citations
TL;DR: It is shown how this synergy has contributed to the understanding of multi-haem cytochromes and can be expected to continue to do so for greater insight into natural processes and their informed exploitation in biotechnologies.
Abstract: Multi-haem cytochromes are employed by a range of microorganisms to transport electrons over distances of up to tens of nanometres. Perhaps the most spectacular utilization of these proteins is in the reduction of extracellular solid substrates, including electrodes and insoluble mineral oxides of Fe(III) and Mn(III/IV), by species of Shewanella and Geobacter. However, multi-haem cytochromes are found in numerous and phylogenetically diverse prokaryotes where they participate in electron transfer and redox catalysis that contributes to biogeochemical cycling of N, S and Fe on the global scale. These properties of multi-haem cytochromes have attracted much interest and contributed to advances in bioenergy applications and bioremediation of contaminated soils. Looking forward, there are opportunities to engage multi-haem cytochromes for biological photovoltaic cells, microbial electrosynthesis and developing bespoke molecular devices. As a consequence, it is timely to review our present understanding of these proteins and we do this here with a focus on the multitude of functionally diverse multi-haem cytochromes in Shewanella oneidensis MR-1. We draw on findings from experimental and computational approaches which ideally complement each other in the study of these systems: computational methods can interpret experimentally determined properties in terms of molecular structure to cast light on the relation between structure and function. We show how this synergy has contributed to our understanding of multi-haem cytochromes and can be expected to continue to do so for greater insight into natural processes and their informed exploitation in biotechnologies.
TL;DR: The analysis reveals that the Fung and Gent models are inadequate for the modelling of brain or fat under combined stretch and shear, and so are the classical neo-Hookean and Mooney–Rivlin models used for elastomers, but a subclass of Ogden hyperelastic models are found to be in excellent agreement with the experiments.
Abstract: In some soft biological structures such as brain and fat tissues, strong experimental evidence suggests that the shear modulus increases significantly under increasing compressive strain, but not under tensile strain, whereas the apparent Young's elastic modulus increases or remains almost constant when compressive strain increases. These tissues also exhibit a predominantly isotropic, incompressible behaviour. Our aim is to capture these seemingly contradictory mechanical behaviours, both qualitatively and quantitatively, within the framework of finite elasticity, by modelling a soft tissue as a homogeneous, isotropic, incompressible, hyperelastic material and comparing our results with available experimental data. Our analysis reveals that the Fung and Gent models, which are typically used to model soft tissues, are inadequate for the modelling of brain or fat under combined stretch and shear, and so are the classical neo-Hookean and Mooney–Rivlin models used for elastomers. However, a subclass of Ogden hyperelastic models are found to be in excellent agreement with the experiments. Our findings provide explicit models suitable for integration in large-scale finite-element computations.
TL;DR: This work offers a proof of principle that self-assembly is an emergent property of cells that share a common (genetic and epigenetic) model of organismal form and suggests an interpretation of genetic codes as parametrizing a generative model—predicting the signals sensed by cells in the target morphology—and epigenetic processes as the subsequent inversion of that model.
Abstract: Understanding how organisms establish their form during embryogenesis and regeneration represents a major knowledge gap in biological pattern formation. It has been recently suggested that morphogenesis could be understood in terms of cellular information processing and the ability of cell groups to model shape. Here, we offer a proof of principle that self-assembly is an emergent property of cells that share a common (genetic and epigenetic) model of organismal form. This behaviour is formulated in terms of variational free-energy minimization—of the sort that has been used to explain action and perception in neuroscience. In brief, casting the minimization of thermodynamic free energy in terms of variational free energy allows one to interpret (the dynamics of) a system as inferring the causes of its inputs—and acting to resolve uncertainty about those causes. This novel perspective on the coordination of migration and differentiation of cells suggests an interpretation of genetic codes as parametrizing a generative model—predicting the signals sensed by cells in the target morphology—and epigenetic processes as the subsequent inversion of that model. This theoretical formulation may complement bottom-up strategies—that currently focus on molecular pathways—with (constructivist) top-down approaches that have proved themselves in neuroscience and cybernetics.
TL;DR: It is shown that this phenomenon is based on geometric principles, namely on a periodic pattern of interconnected half-open capillary channels that narrow and widen, and derived a theoretical model for the local behaviour of the liquid in such capillaries.
Abstract: Moisture-harvesting lizards such as the Texas horned lizard (Iguanidae: Phrynosoma cornutum) live in arid regions. Special skin adaptations enable them to access water sources such as moist sand and dew: their skin is capable of collecting and transporting water directionally by means of a capillary system between the scales. This fluid transport is passive, i.e. requires no external energy, and directs water preferentially towards the lizard's snout. We show that this phenomenon is based on geometric principles, namely on a periodic pattern of interconnected half-open capillary channels that narrow and widen. Following a biomimetic approach, we used these principles to develop a technical prototype design. Building upon the Young-Laplace equation, we derived a theoretical model for the local behaviour of the liquid in such capillaries. We present a global model for the penetration velocity validated by experimental data. Artificial surfaces designed in accordance with this model prevent liquid flow in one direction while sustaining it in the other. Such passive directional liquid transport could lead to process improvements and reduction of resources in many technical applications.
TL;DR: This work tests the hypothesis that intrinsic foot muscles, abductor hallucis, flexor digitorum brevis, FDB and quadratus plantae, actively lengthen and shorten during the stance phase of gait in response to loading of the foot, and provides the first in vivo evidence that the plantar intrinsicFoot muscles function in parallel to the plantAR aponeurosis.
Abstract: The longitudinal arch (LA) of the human foot compresses and recoils in response to being cyclically loaded. This has typically been considered a passive process, however, it has recently been shown that the plantar intrinsic foot muscles have the capacity to actively assist in controlling LA motion. Here we tested the hypothesis that intrinsic foot muscles, abductor hallucis (AH), flexor digitorum brevis (FDB) and quadratus plantae (QP), actively lengthen and shorten during the stance phase of gait in response to loading of the foot. Nine participants walked at 1.25 m s−1 and ran at 2.78 and 3.89 m s−1 on a force-instrumented treadmill while foot and ankle kinematics were recorded according to a multisegment foot model. Muscle–tendon unit (MTU) lengths, determined from the foot kinematics, and intramuscular electromyography (EMG) signals were recorded from AH, FDB and QP. Peak EMG amplitude was determined during the stance phase for each participant at each gait velocity. All muscles underwent a process of slow active lengthening during LA compression, followed by a rapid shortening as the arch recoiled during the propulsive phase. Changes in MTU length and peak EMG increased significantly with increasing gait velocity for all muscles. This is the first in vivo evidence that the plantar intrinsic foot muscles function in parallel to the plantar aponeurosis, actively regulating the stiffness of the foot in response to the magnitude of forces encountered during locomotion. These muscles may therefore contribute to power absorption and generation at the foot, limit strain on the plantar aponeurosis and facilitate efficient foot ground force transmission.
TL;DR: It is shown that whole-muscle force is dependent on its base-material properties and changes to the base material due to fatty inclusions result in reductions to force and muscle quality.
Abstract: Skeletal muscle accumulates intramuscular fat through age and obesity. Muscle quality, a measure of muscle strength per unit size, decreases in these conditions. It is not clear how fat influences this loss in performance. Changes to structural parameters (e.g. fibre pennation and connective tissue properties) affect the muscle quality. This study investigated the mechanisms that lead to deterioration in muscle performance due to changes in intramuscular fat, pennation and aponeurosis stiffness. A finite-element model of the human gastrocnemius was developed as a fibre-reinforced composite biomaterial containing contractile fibres within the base material. The base-material properties were modified to include intramuscular fat in five different ways. All these models with fat generated lower fibre stress and muscle quality than their lean counterparts. This effect is due to the higher stiffness of the tissue in the fatty models. The fibre deformations influence their interactions with the aponeuroses, and these change with fatty inclusions. Muscles with more compliant aponeuroses generated lower forces. The muscle quality was further reduced for muscles with lower pennation. This study shows that whole-muscle force is dependent on its base-material properties and changes to the base material due to fatty inclusions result in reductions to force and muscle quality.
TL;DR: Here, it is demonstrated that an institutional sanctioning policy called ‘first carrot, then stick’ is unexpectedly successful in promoting cooperation, and the adaptive hybridization of incentives offers the ‘best of both worlds’ by combining the effectiveness of rewarding in establishing cooperation with the effective of punishing in recovering it.
Abstract: Social institutions often use rewards and penalties to promote cooperation. Providing incentives tends to be costly, so it is important to find effective and efficient policies for the combined use of rewards and penalties. Most studies of cooperation, however, have addressed rewarding and punishing in isolation and have focused on peer-to-peer sanctioning as opposed to institutional sanctioning. Here, we demonstrate that an institutional sanctioning policy we call ‘first carrot, then stick’ is unexpectedly successful in promoting cooperation. The policy switches the incentive from rewarding to punishing when the frequency of cooperators exceeds a threshold. We find that this policy establishes and recovers full cooperation at lower cost and under a wider range of conditions than either rewards or penalties alone, in both well-mixed and spatial populations. In particular, the spatial dynamics of cooperation make it evident how punishment acts as a ‘booster stage’ that capitalizes on and amplifies the pro-social effects of rewarding. Together, our results show that the adaptive hybridization of incentives offers the ‘best of both worlds’ by combining the effectiveness of rewarding in establishing cooperation with the effectiveness of punishing in recovering it, thereby providing a surprisingly inexpensive and widely applicable method of promoting cooperation.
TL;DR: It is found that the composition of a user's ego network in terms of the type of contacts they keep is correlated with mobility behaviour, and a popular mobility model is extended to include movement choices based on social contacts and compared with two additional models of mobility.
Abstract: Studies using massive, passively collected data from communication technologies have revealed many ubiquitous aspects of social networks, helping us understand and model social media, information diffusion and organizational dynamics. More recently, these data have come tagged with geographical information, enabling studies of human mobility patterns and the science of cities. We combine these two pursuits and uncover reproducible mobility patterns among social contacts. First, we introduce measures of mobility similarity and predictability and measure them for populations of users in three large urban areas. We find individuals' visitations patterns are far more similar to and predictable by social contacts than strangers and that these measures are positively correlated with tie strength. Unsupervised clustering of hourly variations in mobility similarity identifies three categories of social ties and suggests geography is an important feature to contextualize social relationships. We find that the composition of a user's ego network in terms of the type of contacts they keep is correlated with mobility behaviour. Finally, we extend a popular mobility model to include movement choices based on social contacts and compare its ability to reproduce empirical measurements with two additional models of mobility.
TL;DR: It is shown that an appropriate fraction of conformists within the population introduces an effective surface tension around cooperative clusters and ensures smooth interfaces between different strategy domains and this mechanism works even under the most testing conditions and is robust against variations of the interaction network.
Abstract: The pursuit of highest payoffs in evolutionary social dilemmas is risky and sometimes inferior to conformity. Choosing the most common strategy within the interaction range is safer because it ensures that the payoff of an individual will not be much lower than average. Herding instincts and crowd behaviour in humans and social animals also compel to conformity in their own right. Motivated by these facts, we here study the impact of conformity on the evolution of cooperation in social dilemmas. We show that an appropriate fraction of conformists within the population introduces an effective surface tension around cooperative clusters and ensures smooth interfaces between different strategy domains. Payoff-driven players brake the symmetry in favour of cooperation and enable an expansion of clusters past the boundaries imposed by traditional network reciprocity. This mechanism works even under the most testing conditions, and it is robust against variations of the interaction network as long as degree-normalized payoffs are applied. Conformity may thus be beneficial for the resolution of social dilemmas.
TL;DR: It is shown that the amount of NSS-induced rupture of S. cerevisiae is dependent on both the adhesive qualities of the yeast cell and the nanostructure geometry of the NSS, the first empirical evidence that these parameters play a direct role in the rupturing of microbes on NSS.
Abstract: Recent studies have shown that some nanostructured surfaces (NSS), many of which are derived from surfaces found on insect cuticles, rupture and kill adhered prokaryotic microbes. Most important, the nanoscale topography is directly responsible for this effect. Although parameters such as cell adhesion and cell wall rigidity have been suggested to play significant roles in this process, there is little experimental evidence regarding the underlying mechanisms involving NSS-induced microbial rupture. In this work, we report the NSS-induced rupturing of a eukaryotic microorganism, Saccharomyces cerevisiae. We show that the amount of NSS-induced rupture of S. cerevisiae is dependent on both the adhesive qualities of the yeast cell and the nanostructure geometry of the NSS. Thus, we are providing the first empirical evidence that these parameters play a direct role in the rupturing of microbes on NSS. Our observations of this phenomenon with S. cerevisiae, particularly the morphological changes, are strikingly similar to that reported for bacteria despite the differences in the yeast cell wall structure. Consequently, NSS provide a novel approach for the control of microbial growth and development of broad-spectrum microbicidal surfaces.
TL;DR: The results provide a glimpse of the intriguing potential of ‘space synthetic biology’, and help focus related efforts for immediate, near-term impact.
Abstract: This paper demonstrates the significant utility of deploying non-traditional biological techniques to harness available volatiles and waste resources on manned missions to explore the Moon and Mars. Compared with anticipated non-biological approaches, it is determined that for 916 day Martian missions: 205 days of high-quality methane and oxygen Mars bioproduction with Methanobacterium thermoautotrophicum can reduce the mass of a Martian fuel-manufacture plant by 56%; 496 days of biomass generation with Arthrospira platensis and Arthrospira maxima on Mars can decrease the shipped wet-food mixed-menu mass for a Mars stay and a one-way voyage by 38%; 202 days of Mars polyhydroxybutyrate synthesis with Cupriavidus necator can lower the shipped mass to three-dimensional print a 120 m(3) six-person habitat by 85% and a few days of acetaminophen production with engineered Synechocystis sp. PCC 6803 can completely replenish expired or irradiated stocks of the pharmaceutical, thereby providing independence from unmanned resupply spacecraft that take up to 210 days to arrive. Analogous outcomes are included for lunar missions. Because of the benign assumptions involved, the results provide a glimpse of the intriguing potential of 'space synthetic biology', and help focus related efforts for immediate, near-term impact.
TL;DR: It is shown that the roughness induced interactions between the organic matrix and aragonite platelet, represented in the model by asperity elements, play a key role in strength and toughness of abalone nacre.
Abstract: Outstanding mechanical properties of biological multilayered materials are strongly influenced by nanoscale features in their structure. In this study, mechanical behaviour and toughening mechanisms of abalone nacre-inspired multilayered materials are explored. In nacre's structure, the organic matrix, pillars and the roughness of the aragonite platelets play important roles in its overall mechanical performance. A micromechanical model for multilayered biological materials is proposed to simulate their mechanical deformation and toughening mechanisms. The fundamental hypothesis of the model is the inclusion of nanoscale pillars with near theoretical strength (σth ~ E/30). It is also assumed that pillars and asperities confine the organic matrix to the proximity of the platelets, and, hence, increase their stiffness, since it has been previously shown that the organic matrix behaves more stiffly in the proximity of mineral platelets. The modelling results are in excellent agreement with the available experimental data for abalone nacre. The results demonstrate that the aragonite platelets, pillars and organic matrix synergistically affect the stiffness of nacre, and the pillars significantly contribute to the mechanical performance of nacre. It is also shown that the roughness induced interactions between the organic matrix and aragonite platelet, represented in the model by asperity elements, play a key role in strength and toughness of abalone nacre. The highly nonlinear behaviour of the proposed multilayered material is the result of distributed deformation in the nacre-like structure due to the existence of nano-asperities and nanopillars with near theoretical strength. Finally, tensile toughness is studied as a function of the components in the microstructure of nacre.
TL;DR: The development of the MEMS artificial versions of superficial and canal neuromasts and experimental characterization of their unique flow-sensing roles are reported and flexible and surface-mountable arrays of micro-electromechanical systems (MEMS) artificial hair cell flow sensors are developed.
Abstract: Using biological sensors, aquatic animals like fishes are capable of performing impressive behaviours such as super-manoeuvrability, hydrodynamic flow ‘vision’ and object localization with a success unmatched by human-engineered technologies. Inspired by the multiple functionalities of the ubiquitous lateral-line sensors of fishes, we developed flexible and surface-mountable arrays of micro-electromechanical systems (MEMS) artificial hair cell flow sensors. This paper reports the development of the MEMS artificial versions of superficial and canal neuromasts and experimental characterization of their unique flow-sensing roles. Our MEMS flow sensors feature a stereolithographically fabricated polymer hair cell mounted on Pb(Zr0.52Ti0.48)O3 micro-diaphragm with floating bottom electrode. Canal-inspired versions are developed by mounting a polymer canal with pores that guide external flows to the hair cells embedded in the canal. Experimental results conducted employing our MEMS artificial superficial neuromasts (SNs) demonstrated a high sensitivity and very low threshold detection limit of 22 mV/(mm s−1) and 8.2 µm s−1, respectively, for an oscillating dipole stimulus vibrating at 35 Hz. Flexible arrays of such superficial sensors were demonstrated to localize an underwater dipole stimulus. Comparative experimental studies revealed a high-pass filtering nature of the canal encapsulated sensors with a cut-off frequency of 10 Hz and a flat frequency response of artificial SNs. Flexible arrays of self-powered, miniaturized, light-weight, low-cost and robust artificial lateral-line systems could enhance the capabilities of underwater vehicles.
TL;DR: An absolute material tensile strength that is the highest recorded for a biological material is highlighted, outperforming the high strength of spider silk currently considered to be the strongest natural material, and approaching values comparable to those of the strongest man-made fibres.
Abstract: The teeth of limpets exploit distinctive composite nanostructures consisting of high volume fractions of reinforcing goethite nanofibres within a softer protein phase to provide mechanical integrity when rasping over rock surfaces during feeding. The tensile strength of discrete volumes of limpet tooth material measured using in situ atomic force microscopy was found to range from 3.0 to 6.5 GPa and was independent of sample size. These observations highlight an absolute material tensile strength that is the highest recorded for a biological material, outperforming the high strength of spider silk currently considered to be the strongest natural material, and approaching values comparable to those of the strongest man-made fibres. This considerable tensile strength of limpet teeth is attributed to a high mineral volume fraction of reinforcing goethite nanofibres with diameters below a defect-controlled critical size, suggesting that natural design in limpet teeth is optimized towards theoretical strength limits.
TL;DR: This review discusses how bacteria sense and overcome environmental challenges as a group using collective mechanisms of sensing, known as ‘quorum sensing’ (QS), and discusses the claim that such a strategy could overcome the evolution of resistance.
Abstract: Bacteria often face fluctuating environments, and in response many species have evolved complex decision-making mechanisms to match their behaviour to the prevailing conditions. Some environmental cues provide direct and reliable information (such as nutrient concentrations) and can be responded to individually. Other environmental parameters are harder to infer and require a collective mechanism of sensing. In addition, some environmental challenges are best faced by a group of cells rather than an individual. In this review, we discuss how bacteria sense and overcome environmental challenges as a group using collective mechanisms of sensing, known as ‘quorum sensing’ (QS). QS is characterized by the release and detection of small molecules, potentially allowing individuals to infer environmental parameters such as density and mass transfer. While a great deal of the molecular mechanisms of QS have been described, there is still controversy over its functional role. We discuss what QS senses and how, what it controls and why, and how social dilemmas shape its evolution. Finally, there is a growing focus on the use of QS inhibitors as antibacterial chemotherapy. We discuss the claim that such a strategy could overcome the evolution of resistance. By linking existing theoretical approaches to data, we hope this review will spur greater collaboration between experimental and theoretical researchers.
TL;DR: A mechanical concept is presented which improves upon the gecko's non-uniform load-sharing and results in a nearly even load distribution over multiple patches of gecko-inspired adhesive, yielding an improved scaling power law: σmax ∝ A−1/50.
Abstract: Since the discovery of the mechanism of adhesion in geckos, many synthetic dry adhesives have been developed with desirable gecko-like properties such as reusability, directionality, self-cleaning ability, rough surface adhesion and high adhesive stress. However, fully exploiting these adhesives in practical applications at different length scales requires efficient scaling (i.e. with little loss in adhesion as area grows). Just as natural gecko adhesives have been used as a benchmark for synthetic materials, so can gecko adhesion systems provide a baseline for scaling efficiency. In the tokay gecko ( Gekko gecko ), a scaling power law has been reported relating the maximum shear stress σ max to the area A : σ max ∝ A −1/4 . We present a mechanical concept which improves upon the gecko9s non-uniform load-sharing and results in a nearly even load distribution over multiple patches of gecko-inspired adhesive. We created a synthetic adhesion system incorporating this concept which shows efficient scaling across four orders of magnitude of area, yielding an improved scaling power law: σ max ∝ A −1/50 . Furthermore, we found that the synthetic adhesion system does not fail catastrophically when a simulated failure is induced on a portion of the adhesive. In a practical demonstration, the synthetic adhesion system enabled a 70 kg human to climb vertical glass with 140 cm 2 of adhesive per hand.
TL;DR: The Robot Scientist ‘Eve’ designed to make drug discovery more economical is reported, demonstrating that the use of AI to select compounds economically outperforms standard drug screening.
Abstract: There is an urgent need to make drug discovery cheaper and faster. This will enable the development of treatments for diseases currently neglected for economic reasons, such as tropical and orphan diseases, and generally increase the supply of new drugs. Here, we report the Robot Scientist 'Eve' designed to make drug discovery more economical. A Robot Scientist is a laboratory automation system that uses artificial intelligence (AI) techniques to discover scientific knowledge through cycles of experimentation. Eve integrates and automates library-screening, hit-confirmation, and lead generation through cycles of quantitative structure activity relationship learning and testing. Using econometric modelling we demonstrate that the use of AI to select compounds economically outperforms standard drug screening. For further efficiency Eve uses a standardized form of assay to compute Boolean functions of compound properties. These assays can be quickly and cheaply engineered using synthetic biology, enabling more targets to be assayed for a given budget. Eve has repositioned several drugs against specific targets in parasites that cause tropical diseases. One validated discovery is that the anti-cancer compound TNP-470 is a potent inhibitor of dihydrofolate reductase from the malaria-causing parasite Plasmodium vivax.
TL;DR: It is found that random variations in the intrinsic rotor frequencies increase the robustness of the average properties of the emergent metachronal waves, and that defects result from sufficiently steep local biases in the oscillators' intrinsic frequencies.
Abstract: Groups of eukaryotic cilia and flagella are capable of coordinating their beat- ing over large scales, routinely exhibiting collective dynamics in the form of metachronal waves. The origin of this behaviour—possibly influenced by both mechanical interactions and direct biological regulation—is poorly understood, in large part due to a lack of quantitative experimental studies. Here we characterize in detail flagellar coordination on the surface of the multicellular alga Volvox carteri, an emerging model organism for flagellar dynamics. Our studies reveal for the first time that the average metachronal coordination observed is punctuated by periodic phase defects during which synchrony is partial and limited to specific groups of cells. A minimal model of hydrodynamically coupled oscillators can reproduce semi-quantitatively the characteristics of the average metachronal dynamics, and the emergence of defects. We systematically study the model’s behaviour by assessing the effect of changing intrinsic rotor characteristics, including oscillator stiffness and the nature of their internal driving force, as well as their geometric properties and spatial arrangement. Our results suggest that metachronal coordination follows from deformations in the oscillators’ limit cycles induced by hydrodynamic stresses, and that defects result from sufficiently steep local biases in the oscillators’ intrinsic frequencies. Additionally, we find that random variations in the intrinsic rotor frequencies increase the robustness of the average properties of the emergent metachronal waves.
TL;DR: This work demonstrates a useful application of patient-specific modelling in personalized medicine and how mathematical modelling has the potential to unify multi-modality imaging and radiation treatment planning.
Abstract: Glioblastoma multiforme (GBM) is a highly invasive primary brain tumour that has poor prognosis despite aggressive treatment. A hallmark of these tumours is diffuse invasion into the surrounding brain, necessitating a multi-modal treatment approach, including surgery, radiation and chemotherapy. We have previously demonstrated the ability of our model to predict radiographic response immediately following radiation therapy in individual GBM patients using a simplified geometry of the brain and theoretical radiation dose. Using only two pre-treatment magnetic resonance imaging scans, we calculate net rates of proliferation and invasion as well as radiation sensitivity for a patient's disease. Here, we present the application of our clinically targeted modelling approach to a single glioblastoma patient as a demonstration of our method. We apply our model in the full three-dimensional architecture of the brain to quantify the effects of regional resistance to radiation owing to hypoxia in vivo determined by [18F]-fluoromisonidazole positron emission tomography (FMISO-PET) and the patient-specific three-dimensional radiation treatment plan. Incorporation of hypoxia into our model with FMISO-PET increases the model–data agreement by an order of magnitude. This improvement was robust to our definition of hypoxia or the degree of radiation resistance quantified with the FMISO-PET image and our computational model, respectively. This work demonstrates a useful application of patient-specific modelling in personalized medicine and how mathematical modelling has the potential to unify multi-modality imaging and radiation treatment planning.
TL;DR: This work shows for a suite of aspect ratios, which represent both animal and aircraft wings, that the attachment of the leading edge vortex on a revolving wing is determined by wing aspect ratio, defined with respect to the centre of revolution.
Abstract: Airplanes and helicopters use high aspect ratio wings to reduce the power required to fly, but must operate at low angle of attack to prevent flow separation and stall. Animals capable of slow sust...