Showing papers in "Journal of the Royal Society Interface in 2014"

Homological scaffolds of brain functional networks

Abstract: Networks, as efficient representations of complex systems, have appealed to scientists for a long time and now permeate many areas of science, including neuroimaging (Bullmore and Sporns 2009 Nat. ...

Natural polymers for the microencapsulation of cells

Abstract: The encapsulation of living mammalian cells within a semi-permeable hydrogel matrix is an attractive procedure for many biomedical and biotechnological applications, such as xenotransplantation, maintenance of stem cell phenotype and bioprinting of three-dimensional scaffolds for tissue engineering and regenerative medicine. In this review, we focus on naturally derived polymers that can form hydrogels under mild conditions and that are thus capable of entrapping cells within controlled volumes. Our emphasis will be on polysaccharides and proteins, including agarose, alginate, carrageenan, chitosan, gellan gum, hyaluronic acid, collagen, elastin, gelatin, fibrin and silk fibroin. We also discuss the technologies commonly employed to encapsulate cells in these hydrogels, with particular attention on microencapsulation.

Mapping the stereotyped behaviour of freely moving fruit flies

Abstract: A frequent assumption in behavioural science is that most of an animal's activities can be described in terms of a small set of stereotyped motifs. Here, we introduce a method for mapping an animal's actions, relying only upon the underlying structure of postural movement data to organize and classify behaviours. Applying this method to the ground-based behaviour of the fruit fly, Drosophila melanogaster, we find that flies perform stereotyped actions roughly 50% of the time, discovering over 100 distinguishable, stereotyped behavioural states. These include multiple modes of locomotion and grooming. We use the resulting measurements as the basis for identifying subtle sex-specific behavioural differences and revealing the low-dimensional nature of animal motions.

Co-culture systems and technologies: taking synthetic biology to the next level.

Abstract: Co-culture techniques find myriad applications in biology for studying natural or synthetic interactions between cell populations. Such techniques are of great importance in synthetic biology, as multi-species cell consortia and other natural or synthetic ecology systems are widely seen to hold enormous potential for foundational research as well as novel industrial, medical and environmental applications with many proof-of-principle studies in recent years. What is needed for co-cultures to fulfil their potential? Cell–cell interactions in co-cultures are strongly influenced by the extracellular environment, which is determined by the experimental set-up, which therefore needs to be given careful consideration. An overview of existing experimental and theoretical co-culture set-ups in synthetic biology and adjacent fields is given here, and challenges and opportunities involved in such experiments are discussed. Greater focus on foundational technology developments for co-cultures is needed for many synthetic biology systems to realize their potential in both applications and answering biological questions.

Global rise in human infectious disease outbreaks

Abstract: To characterize the change in frequency of infectious disease outbreaks over time worldwide, we encoded and analysed a novel 33-year dataset (1980–2013) of 12 102 outbreaks of 215 human infectious ...

The digital traces of bubbles: feedback cycles between socio-economic signals in the Bitcoin economy

Abstract: What is the role of social interactions in the creation of price bubbles? Answering this question requires obtaining collective behavioural traces generated by the activity of a large number of actors. Digital currencies offer a unique possibility to measure socio-economic signals from such digital traces. Here, we focus on Bitcoin, the most popular cryptocurrency. Bitcoin has experienced periods of rapid increase in exchange rates (price) followed by sharp decline; we hypothesize that these fluctuations are largely driven by the interplay between different social phenomena. We thus quantify four socio-economic signals about Bitcoin from large datasets: price on online exchanges, volume of word-of-mouth communication in online social media, volume of information search and user base growth. By using vector autoregression, we identify two positive feedback loops that lead to price bubbles in the absence of exogenous stimuli: one driven by word of mouth, and the other by new Bitcoin adopters. We also observe that spikes in information search, presumably linked to external events, precede drastic price declines. Understanding the interplay between the socio-economic signals we measured can lead to applications beyond cryptocurrencies to other phenomena that leave digital footprints, such as online social network usage.

Cyclic dominance in evolutionary games: A review

Abstract: Rock is wrapped by paper, paper is cut by scissors and scissors are crushed by rock. This simple game is popular among children and adults to decide on trivial disputes that have no obvious winner, but cyclic dominance is also at the heart of predator–prey interactions, the mating strategy of side-blotched lizards, the overgrowth of marine sessile organisms and competition in microbial populations. Cyclical interactions also emerge spontaneously in evolutionary games entailing volunteering, reward, punishment, and in fact are common when the competing strategies are three or more, regardless of the particularities of the game. Here, we review recent advances on the rock–paper–scissors (RPS) and related evolutionary games, focusing, in particular, on pattern formation, the impact of mobility and the spontaneous emergence of cyclic dominance. We also review mean-field and zero-dimensional RPS models and the application of the complex Ginzburg–Landau equation, and we highlight the importance and usefulness of statistical physics for the successful study of large-scale ecological systems. Directions for future research, related, for example, to dynamical effects of coevolutionary rules and invasion reversals owing to multi-point interactions, are also outlined.

Interaction of colloidal nanoparticles with their local environment: the (ionic) nanoenvironment around nanoparticles is different from bulk and determines the physico-chemical properties of the nanoparticles

Abstract: The physico-chemical properties of colloidal nanoparticles (NPs) are influenced by their local environment, as, in turn, the local environment influences the physico-chemical properties of the NPs. In other words, the local environment around NPs has a profound impact on the NPs, and it is different from bulk due to interaction with the NP surface. So far, this important effect has not been addressed in a comprehensive way in the literature. The vicinity of NPs can be sensitively influenced by local ions and ligands, with effects already occurring at extremely low concentrations. NPs in the Huckel regime are more sensitive to fluctuations in the ionic environment, because of a larger Debye length. The local ion concentration hereby affects the colloidal stability of the NPs, as it is different from bulk owing to Debye Huckel screening caused by the charge of the NPs. This can have subtle effects, now caused by the environment to the performance of the NP, such as for example a buffering effect caused by surface reaction on ultrapure ligand-free nanogold, a size quenching effect in the presence of specific ions and a significant impact on fluorophore-labelled NPs acting as ion sensors. Thus, the aim of this review is to clarify and give an unifying view of the complex interplay between the NP's surface with their nanoenvironment.

The Matthew effect in empirical data.

Abstract: The Matthew effect describes the phenomenon that in societies, the rich tend to get richer and the potent even more powerful. It is closely related to the concept of preferential attachment in network science, where the more connected nodes are destined to acquire many more links in the future than the auxiliary nodes. Cumulative advantage and success-breads-success also both describe the fact that advantage tends to beget further advantage. The concept is behind the many power laws and scaling behaviour in empirical data, and it is at the heart of self-organization across social and natural sciences. Here, we review the methodology for measuring preferential attachment in empirical data, as well as the observations of the Matthew effect in patterns of scientific collaboration, socio-technical and biological networks, the propagation of citations, the emergence of scientific progress and impact, career longevity, the evolution of common English words and phrases, as well as in education and brain development. We also discuss whether the Matthew effect is due to chance or optimization, for example related to homophily in social systems or efficacy in technological systems, and we outline possible directions for future research.

The scaling of human interactions with city size

Abstract: The size of cities is known to play a fundamental role in social and economic life. Yet, its relation to the structure of the underlying network of human interactions has not been investigated empirically in detail. In this paper, we map society-wide communication networks to the urban areas of two European countries. We show that both the total number of contacts and the total communication activity grow superlinearly with city population size, according to well-defined scaling relations and resulting from a multiplicative increase that affects most citizens. Perhaps surprisingly, however, the probability that an individual's contacts are also connected with each other remains largely unaffected. These empirical results predict a systematic and scale-invariant acceleration of interaction-based spreading phenomena as cities get bigger, which is numerically confirmed by applying epidemiological models to the studied networks. Our findings should provide a microscopic basis towards understanding the superlinear increase of different socioeconomic quantities with city size, that applies to almost all urban systems and includes, for instance, the creation of new inventions or the prevalence of certain contagious diseases.

Liposomes in tissue engineering and regenerative medicine

Abstract: Liposomes are vesicular structures made of lipids that are formed in aqueous solutions. Structurally, they resemble the lipid membrane of living cells. Therefore, they have been widely investigated, since the 1960s, as models to study the cell membrane, and as carriers for protection and/or delivery of bioactive agents. They have been used in different areas of research including vaccines, imaging, applications in cosmetics and tissue engineering. Tissue engineering is defined as a strategy for promoting the regeneration of tissues for the human body. This strategy may involve the coordinated application of defined cell types with structured biomaterial scaffolds to produce living structures. To create a new tissue, based on this strategy, a controlled stimulation of cultured cells is needed, through a systematic combination of bioactive agents and mechanical signals. In this review, we highlight the potential role of liposomes as a platform for the sustained and local delivery of bioactive agents for tissue engineering and regenerative medicine approaches.

Photosynthetic light harvesting: excitons and coherence

Abstract: Photosynthesis begins with light harvesting, where specialized pigment–protein complexes transform sunlight into electronic excitations delivered to reaction centres to initiate charge separation. There is evidence that quantum coherence between electronic excited states plays a role in energy transfer. In this review, we discuss how quantum coherence manifests in photosynthetic light harvesting and its implications. We begin by examining the concept of an exciton, an excited electronic state delocalized over several spatially separated molecules, which is the most widely available signature of quantum coherence in light harvesting. We then discuss recent results concerning the possibility that quantum coherence between electronically excited states of donors and acceptors may give rise to a quantum coherent evolution of excitations, modifying the traditional incoherent picture of energy transfer. Key to this (partially) coherent energy transfer appears to be the structure of the environment, in particular the participation of non-equilibrium vibrational modes. We discuss the open questions and controversies regarding quantum coherent energy transfer and how these can be addressed using new experimental techniques.

Design and control of compliant tensegrity robots through simulation and hardware validation.

Abstract: To better understand the role of tensegrity structures in biological systems and their application to robotics, the Dynamic Tensegrity Robotics Lab at NASA Ames Research Center, Moffett Field, CA, USA, has developed and validated two software environments for the analysis, simulation and design of tensegrity robots. These tools, along with new control methodologies and the modular hardware components developed to validate them, are presented as a system for the design of actuated tensegrity structures. As evidenced from their appearance in many biological systems, tensegrity (‘tensile–integrity’) structures have unique physical properties that make them ideal for interaction with uncertain environments. Yet, these characteristics make design and control of bioinspired tensegrity robots extremely challenging. This work presents the progress our tools have made in tackling the design and control challenges of spherical tensegrity structures. We focus on this shape since it lends itself to rolling locomotion. The results of our analyses include multiple novel control approaches for mobility and terrain interaction of spherical tensegrity structures that have been tested in simulation. A hardware prototype of a spherical six-bar tensegrity, the Reservoir Compliant Tensegrity Robot, is used to empirically validate the accuracy of simulation.

The structure and mechanics of Moso bamboo material

Abstract: Although bamboo has been used structurally for millennia, there is currently increasing interest in the development of renewable and sustainable structural bamboo products (SBPs). These SBPs are analogous to wood products such as plywood, oriented strand board and glue-laminated wood. In this study, the properties of natural Moso bamboo (Phyllostachys pubescens) are investigated to further enable the processing and design of SBPs. The radial and longitudinal density gradients in bamboo give rise to variations in the mechanical properties. Here, we measure the flexural properties of Moso bamboo in the axial direction, along with the compressive strengths in the axial and transverse directions. Based on the microstructural variations (observed with scanning electron microscopy) and extrapolated solid cell wall properties of bamboo, we develop models, which describe the experimental results well. Compared to common North American construction woods loaded along the axial direction, Moso bamboo is approximately as stiff and substantially stronger, in both flexure and compression but denser. This work contributes to critical knowledge surrounding the microstructure and mechanical properties of bamboo, which are vital to the engineering and design of sustainable SBPs.

A method for estimating the oxygen consumption rate in multicellular tumour spheroids

Abstract: Hypoxia occurs when oxygen levels within a tissue drop below normal physiological levels. In tumours, hypoxia is associated with poor prognosis, increased likelihood of metastasis and resistance to therapy. Imaging techniques, for example, positron emission tomography, are increasingly used in the monitoring of tumour hypoxia and have the potential to help in the planning of radiotherapy. For this application, improved understanding of the link between image contrast and quantitative underlying oxygen distribution would be very useful. Mathematical models of tissue hypoxia and image formation can help understand this. Hypoxia is caused by an imbalance between vascular supply and tissue demand. While much work has been dedicated to the quantitative description of tumour vascular networks, consideration of tumour oxygen consumption is largely neglected. Oxidative respiration in standard two-dimensional cell culture has been widely studied. However, two-dimensional culture fails to capture the complexities of growing three-dimensional tissue which could impact on the oxygen usage. In this study, we build on previous descriptions of oxygen consumption and diffusion in three-dimensional tumour spheroids and present a method for estimating rates of oxygen consumption from spheroids, validated using stained spheroid sections. Methods for estimating the local partial pressure of oxygen, the diffusion limit and the extents of the necrotic core, hypoxic region and proliferating rim are also derived. These are validated using experimental data from DLD1 spheroids at different stages of growth. A relatively constant experimentally derived diffusion limit of 232 ± 22 μm and an O2 consumption rate of 7.29 ± 1.4 × 10−7 m3 kg−1 s−1 for the spheroids studied was measured, in agreement with laboratory measurements.

On the reliability of seasonal climate forecasts

Abstract: Seasonal climate forecasts are being used increasingly across a range of application sectors. A recent UK governmental report asked: how good are seasonal forecasts on a scale of 1–5 (where 5 is very good), and how good can we expect them to be in 30 years time? Seasonal forecasts are made from ensembles of integrations of numerical models of climate. We argue that ‘goodness’ should be assessed first and foremost in terms of the probabilistic reliability of these ensemble-based forecasts; reliable inputs are essential for any forecast-based decision-making. We propose that a ‘5’ should be reserved for systems that are not only reliable overall, but where, in particular, small ensemble spread is a reliable indicator of low ensemble forecast error. We study the reliability of regional temperature and precipitation forecasts of the current operational seasonal forecast system of the European Centre for Medium-Range Weather Forecasts, universally regarded as one of the world-leading operational institutes producing seasonal climate forecasts. A wide range of ‘goodness’ rankings, depending on region and variable (with summer forecasts of rainfall over Northern Europe performing exceptionally poorly) is found. Finally, we discuss the prospects of reaching ‘5’ across all regions and variables in 30 years time.

Reverse engineering and identification in systems biology: strategies, perspectives and challenges

Abstract: The interplay of mathematical modelling with experiments is one of the central elements in systems biology. The aim of reverse engineering is to infer, analyse and understand, through this interplay, the functional and regulatory mechanisms of biological systems. Reverse engineering is not exclusive of systems biology and has been studied in different areas, such as inverse problem theory, machine learning, nonlinear physics, (bio)chemical kinetics, control theory and optimization, among others. However, it seems that many of these areas have been relatively closed to outsiders. In this contribution, we aim to compare and highlight the different perspectives and contributions from these fields, with emphasis on two key questions: (i) why are reverse engineering problems so hard to solve, and (ii) what methods are available for the particular problems arising from systems biology?

Intrinsic foot muscles have the capacity to control deformation of the longitudinal arch

Abstract: The human foot is characterized by a pronounced longitudinal arch (LA) that compresses and recoils in response to external load during locomotion, allowing for storage and return of elastic energy within the passive structures of the arch and contributing to metabolic energy savings. Here, we examine the potential for active muscular contribution to the biomechanics of arch deformation and recoil. We test the hypotheses that activation of the three largest plantar intrinsic foot muscles, abductor hallucis, flexor digitorum and quadratus plantae is associated with muscle stretch in response to external load on the foot and that activation of these muscles (via electrical stimulation) will generate sufficient force to counter the deformation of LA caused by the external load. We found that recruitment of the intrinsic foot muscles increased with increasing load, beyond specific load thresholds. Interestingly, LA deformation and muscle stretch plateaued towards the maximum load of 150% body weight, when muscle activity was greatest. Electrical stimulation of the plantar intrinsic muscles countered the deformation that occurred owing to the application of external load by reducing the length and increasing the height of the LA. These findings demonstrate that these muscles have the capacity to control foot posture and LA stiffness and may provide a buttressing effect during foot loading. This active arch stiffening mechanism may have important implications for how forces are transmitted during locomotion and postural activities as well as consequences for metabolic energy saving.

What makes an accurate and reliable subject-specific finite element model? A case study of an elephant femur (Retraction of vol 9, pg 351, 2012)

Abstract: Finite element modelling is well entrenched in comparative vertebrate biomechanics as a tool to assess the mechanical design of skeletal structures and to better comprehend the complex interaction of their form–function relationships. But what makes a reliable subject-specific finite element model? To approach this question, we here present a set of convergence and sensitivity analyses and a validation study as an example, for finite element analysis (FEA) in general, of ways to ensure a reliable model. We detail how choices of element size, type and material properties in FEA influence the results of simulations. We also present an empirical model for estimating heterogeneous material properties throughout an elephant femur (but of broad applicability to FEA). We then use an ex vivo experimental validation test of a cadaveric femur to check our FEA results and find that the heterogeneous model matches the experimental results extremely well, and far better than the homogeneous model. We emphasize how considering heterogeneous material properties in FEA may be critical, so this should become standard practice in comparative FEA studies along with convergence analyses, consideration of element size, type and experimental validation. These steps may be required to obtain accurate models and derive reliable conclusions from them.

Biophysics of protein evolution and evolutionary protein biophysics

Abstract: The study of molecular evolution at the level of protein-coding genes often entails comparing large datasets of sequences to infer their evolutionary relationships. Despite the importance of a protein's structure and conformational dynamics to its function and thus its fitness, common phylogenetic methods embody minimal biophysical knowledge of proteins. To underscore the biophysical constraints on natural selection, we survey effects of protein mutations, highlighting the physical basis for marginal stability of natural globular proteins and how requirement for kinetic stability and avoidance of misfolding and misinteractions might have affected protein evolution. The biophysical underpinnings of these effects have been addressed by models with an explicit coarse-grained spatial representation of the polypeptide chain. Sequence–structure mappings based on such models are powerful conceptual tools that rationalize mutational robustness, evolvability, epistasis, promiscuous function performed by ‘hidden’ conformational states, resolution of adaptive conflicts and conformational switches in the evolution from one protein fold to another. Recently, protein biophysics has been applied to derive more accurate evolutionary accounts of sequence data. Methods have also been developed to exploit sequence-based evolutionary information to predict biophysical behaviours of proteins. The success of these approaches demonstrates a deep synergy between the fields of protein biophysics and protein evolution.

Fractional diffusion models of cardiac electrical propagation: role of structural heterogeneity in dispersion of repolarization

Abstract: Impulse propagation in biological tissues is known to be modulated by structural heterogeneity. In cardiac muscle, improved understanding on how this heterogeneity influences electrical spread is key to advancing our interpretation of dispersion of repolarization. We propose fractional diffusion models as a novel mathematical description of structurally heterogeneous excitable media, as a means of representing the modulation of the total electric field by the secondary electrical sources associated with tissue inhomogeneities. Our results, analysed against in vivo human recordings and experimental data of different animal species, indicate that structural heterogeneity underlies relevant characteristics of cardiac electrical propagation at tissue level. These include conduction effects on action potential (AP) morphology, the shortening of AP duration along the activation pathway and the progressive modulation by premature beats of spatial patterns of dispersion of repolarization. The proposed approach may also have important implications in other research fields involving excitable complex media.

Solving the shepherding problem: heuristics for herding autonomous, interacting agents

Abstract: Herding of sheep by dogs is a powerful example of one individual causing many unwilling individuals to move in the same direction. Similar phenomena are central to crowd control, cleaning the environment and other engineering problems. Despite single dogs solving this ‘shepherding problem’ every day, it remains unknown which algorithm they employ or whether a general algorithm exists for shepherding. Here, we demonstrate such an algorithm, based on adaptive switching between collecting the agents when they are too dispersed and driving them once they are aggregated. Our algorithm reproduces key features of empirical data collected from sheep–dog interactions and suggests new ways in which robots can be designed to influence movements of living and artificial agents.

Towards elucidating the connection between epithelial-mesenchymal transitions and stemness.

Abstract: Epithelial cells undergoing epithelial-to-mesenchymal transitions have often been shown to behave as cancer stem cells, but the precise molecular connection remains elusive. At the genetic level, stemness is governed by LIN28/let-7 double inhibition switch, whereas EMT/MET is controlled by miR-200/ZEB double inhibition circuit and LIN28 is inhibited by miR-200, coupling the two modules. Here, using a specially devised theoretical framework to investigate the dynamics of the LIN28/let-7 system, we show that it can operate as a three-way switch (between low, high and intermediate LIN28 levels termed the D, U and hybrid D/U states) similar to the three-way operation of the miR-200/ZEB circuit that allows for the existence of a hybrid epithelial/mesenchymal (E/M) phenotype. We find significant correspondence between the existence of the three states of the two circuits: E-D, M-U and E/M-D/U. Incorporating the activation of OCT4 by LIN28, we find that the hybrid E/M phenotype has high likelihood (when compared with either the E or M states) to gain stemness. Combining the LIN28/let-7 regulation by NF-κB and c-MYC, we find that NF-κB, but not c-MYC, elevates the likelihood of E/M phenotype to gain stemness. Our results are consistent with emerging concept that partial EMT can lead to stemness.

Biomechanical regulation of vascular smooth muscle cell functions: from in vitro to in vivo understanding

Abstract: Vascular smooth muscle cells (VSMCs) have critical functions in vascular diseases. Haemodynamic factors are important regulators of VSMC functions in vascular pathophysiology. VSMCs are physiologically active in the threedimensional matrix and interact with the shear stress sensor of endothelial cells (ECs). The purpose of this review is to illustrate how haemodynamic factors regulate VSMC functions under two-dimensional conditions in vitro or three-dimensional co-culture conditions in vivo .R ecent advances show that high shear stress induces VSMC apoptosis through endothelial-released nitric oxide and low shear stress upregulates VSMC proliferation and migration through platelet-derived growth factor released by ECs. This differential regulation emphasizes the need to construct more actual environments for future research on vascular diseases (such as atherosclerosis and hypertension) and cardiovascular tissue engineering.

Universal predictability of mobility patterns in cities

Abstract: Despite the long history of modelling human mobility, we continue to lack a highly accurate approach with low data requirements for predicting mobility patterns in cities. Here, we present a population-weighted opportunities model without any adjustable parameters to capture the underlying driving force accounting for human mobility patterns at the city scale. We use various mobility data collected from a number of cities with different characteristics to demonstrate the predictive power of our model. We find that insofar as the spatial distribution of population is available, our model offers universal prediction of mobility patterns in good agreement with real observations, including distance distribution, destination travel constraints and flux. By contrast, the models that succeed in modelling mobility patterns in countries are not applicable in cities, which suggests that there is a diversity of human mobility at different spatial scales. Our model has potential applications in many fields relevant to mobility behaviour in cities, without relying on previous mobility measurements.

Proton transfer reactions and hydrogen- bond networks in protein environments

Abstract: In protein environments, proton transfer reactions occur along polar or charged residues and isolated water molecules. These species consist of H-bond networks that serve as proton transfer pathways; therefore, thorough understanding of H-bond energetics is essential when investigating proton transfer reactions in protein environments. When the pKa values (or proton affinity) of the H-bond donor and acceptor moieties are equal, significantly short, symmetric H-bonds can be formed between the two, and proton transfer reactions can occur in an efficient manner. However, such short, symmetric H-bonds are not necessarily stable when they are situated near the protein bulk surface, because the condition of matching pKa values is opposite to that required for the formation of strong salt bridges, which play a key role in protein-protein interactions. To satisfy the pKa matching condition and allow for proton transfer reactions, proteins often adjust the pKa via electron transfer reactions or H-bond pattern changes. In particular, when a symmetric H-bond is formed near the protein bulk surface as a result of one of these phenomena, its instability often results in breakage, leading to large changes in protein conformation.

A typology of street patterns

Abstract: We propose a quantitative method to classify cities according to their street pattern. We use the conditional probability distribution of shape factor of blocks with a given area and define what could constitute the 'fingerprint' of a city. Using a simple hierarchical clustering method, these fingerprints can then serve as a basis for a typology of cities. We apply this method to a set of 131 cities in the world, and at an intermediate level of the dendrogram, we observe four large families of cities characterized by different abundances of blocks of a certain area and shape. At a lower level of the classification, we find that most European cities and American cities in our sample fall in their own sub-category, highlighting quantitatively the differences between the typical layouts of cities in both regions. We also show with the example of New York and its different boroughs, that the fingerprint of a city can be seen as the sum of the ones characterizing the different neighbourhoods inside a city. This method provides a quantitative comparison of urban street patterns, which could be helpful for a better understanding of the causes and mechanisms behind their distinct shapes.

On the strength of β-sheet crystallites of Bombyx mori silk fibroin.

Abstract: Silk fibroin, a natural multi-domain protein, has attracted great attention due to its superior mechanical properties such as ultra-high strength and stretchability, biocompatibility, as well as its versatile biodegradability and processability. It is mainly composed of β-sheet crystallites and amorphous domains. Although its strength is well known to be controlled by the dissociation of protein chains from β-sheet crystallites, the way that water as the solvent affects its strength and the reason that its theoretically predicted strength is several times higher than experimental measurement remain unclear. We perform all-atom molecular dynamics simulations on a β-sheet crystallite of Bombyx mori silk. We find that water solvent reduces the number and strength of hydrogen bonds between β-chains, and thus greatly weakens the strength of silk fibroin. By dissociating protein chains at different locations from the crystallite, we also find that the pulling strength for the interior chains is several times higher than that for the surface/corner chains, with the former being consistent with the theoretically predicted value, while the latter on par with the experimental value. It is shown that the weakest rupture strength controls the failure strength of silk fibre. Hence, this work sheds light on the role of water in the strength of silk fibroin and also provides clues on the origin of the strength difference between theory and experiment.

Separate enrichment analysis of pathways for up- and downregulated genes.

Abstract: Two strategies are often adopted for enrichment analysis of pathways: the analysis of all differentially expressed (DE) genes together or the analysis of up- and downregulated genes separately. However, few studies have examined the rationales of these enrichment analysis strategies. Using both microarray and RNA-seq data, we show that gene pairs with functional links in pathways tended to have positively correlated expression levels, which could result in an imbalance between the up- and downregulated genes in particular pathways. We then show that the imbalance could greatly reduce the statistical power for finding disease-associated pathways through the analysis of all-DE genes. Further, using gene expression profiles from five types of tumours, we illustrate that the separate analysis of up- and downregulated genes could identify more pathways that are really pertinent to phenotypic difference. In conclusion, analysing up- and downregulated genes separately is more powerful than analysing all of the DE genes together.

Improving controllable adhesion on both rough and smooth surfaces with a hybrid electrostatic/gecko-like adhesive.

Abstract: This paper describes a novel, controllable adhesive that combines the benefits of electrostatic adhesives with gecko-like directional dry adhesives. When working in combination, the two technologies create a positive feedback cycle whose adhesion, depending on the surface type, is often greater than the sum of its parts. The directional dry adhesive brings the electrostatic adhesive closer to the surface, increasing its effect. Similarly, the electrostatic adhesion helps engage more of the directional dry adhesive fibrillar structures, particularly on rough surfaces. This paper presents the new hybrid adhesive's manufacturing process and compares its performance to three other adhesive technologies manufactured using a similar process: reinforced PDMS, electrostatic and directional dry adhesion. Tests were performed on a set of ceramic tiles with varying roughness to quantify its effect on shear adhesive force. The relative effectiveness of the hybrid adhesive increases as the surface roughness is increased. Experimental data are also presented for different substrate materials to demonstrate the enhanced performance achieved with the hybrid adhesive. Results show that the hybrid adhesive provides up to 5.1× greater adhesion than the electrostatic adhesive or directional dry adhesive technologies alone.