Showing papers in "Journal of the Royal Society Interface in 2011"
TL;DR: A review of growth factor delivery in tissue engineering provides an overview of fundamental issues and design strategies relevant to the material carriers that are being actively pursued to address specific technical objectives.
Abstract: The identification and production of recombinant morphogens and growth factors that play key roles in tissue regeneration have generated much enthusiasm and numerous clinical trials, but the results of many of these trials have been largely disappointing. Interestingly, the trials that have shown benefit all contain a common denominator, the presence of a material carrier, suggesting strongly that spatio-temporal control over the location and bioactivity of factors after introduction into the body is crucial to achieve tangible therapeutic effect. Sophisticated materials systems that regulate the biological presentation of growth factors represent an attractive new generation of therapeutic agents for the treatment of a wide variety of diseases. This review provides an overview of growth factor delivery in tissue engineering. Certain fundamental issues and design strategies relevant to the material carriers that are being actively pursued to address specific technical objectives are discussed. Recent progress highlights the importance of materials science and engineering in growth factor delivery approaches to regenerative medicine.
1,214 citations
TL;DR: It is concluded that ultrasonic imaging of soft tissue strain and elasticity is now sufficiently well developed to have clinical utility and is anticipated that the technology will become a powerful mainstream investigative tool.
Abstract: After X-radiography, ultrasound is now the most common of all the medical imaging technologies. For millennia, manual palpation has been used to assist in diagnosis, but it is subjective and restricted to larger and more superficial structures. Following an introduction to the subject of elasticity, the elasticity of biological soft tissues is discussed and published data are presented. The basic physical principles of pulse-echo and Doppler ultrasonic techniques are explained. The history of ultrasonic imaging of soft tissue strain and elasticity is summarized, together with a brief critique of previously published reviews. The relevant techniques—low-frequency vibration, step, freehand and physiological displacement, and radiation force (displacement, impulse, shear wave and acoustic emission)—are described. Tissue-mimicking materials are indispensible for the assessment of these techniques and their characteristics are reported. Emerging clinical applications in breast disease, cardiology, dermatology, gastroenterology, gynaecology, minimally invasive surgery, musculoskeletal studies, radiotherapy, tissue engineering, urology and vascular disease are critically discussed. It is concluded that ultrasonic imaging of soft tissue strain and elasticity is now sufficiently well developed to have clinical utility. The potential for further research is examined and it is anticipated that the technology will become a powerful mainstream investigative tool.
460 citations
TL;DR: Biomechanical measurements offer promise for identifying individuals at risk of falling and can be obtained with relatively low-cost tools, and both linear and nonlinear measures of foot time series during gait seem to hold predictive ability in distinguishing healthy from fall-prone elderly adults.
Abstract: Falls not only present a considerable health threat, but the resulting treatment and loss of working days also place a heavy economic burden on society. Gait instability is a major fall risk factor, particularly in geriatric patients, and walking is one of the most frequent dynamic activities of daily living. To allow preventive strategies to become effective, it is therefore imperative to identify individuals with an unstable gait. Assessment of dynamic stability and gait variability via biomechanical measures of foot kinematics provides a viable option for quantitative evaluation of gait stability, but the ability of these methods to predict falls has generally not been assessed. Although various methods for assessing gait stability exist, their sensitivity and applicability in a clinical setting, as well as their cost-effectiveness, need verification. The objective of this systematic review was therefore to evaluate the sensitivity of biomechanical measures that quantify gait stability among elderly individuals and to evaluate the cost of measurement instrumentation required for application in a clinical setting. To assess gait stability, a comparative effect size (Cohen's d) analysis of variability and dynamic stability of foot trajectories during level walking was performed on 29 of an initial yield of 9889 articles from four electronic databases. The results of this survey demonstrate that linear variability of temporal measures of swing and stance was most capable of distinguishing between fallers and non-fallers, whereas step width and stride velocity prove more capable of discriminating between old versus young (OY) adults. In addition, while orbital stability measures (Floquet multipliers) applied to gait have been shown to distinguish between both elderly fallers and non-fallers as well as between young and old adults, local stability measures (λs) have been able to distinguish between young and old adults. Both linear and nonlinear measures of foot time series during gait seem to hold predictive ability in distinguishing healthy from fall-prone elderly adults. In conclusion, biomechanical measurements offer promise for identifying individuals at risk of falling and can be obtained with relatively low-cost tools. Incorporation of the most promising measures in combined retrospective and prospective studies for understanding fall risk and designing preventive strategies is warranted.
331 citations
TL;DR: This study supports the viability of frequent, remote, cost-effective, objective, accurate UPDRS telemonitoring based on self-administered speech tests, and proposes a number of novel, nonlinear signal processing algorithms which reveal pathological characteristics in PD more accurately than existing approaches.
Abstract: The standard reference clinical score quantifying average Parkinson's disease (PD) symptom severity is the Unified Parkinson's Disease Rating Scale (UPDRS). At present, UPDRS is determined by the subjective clinical evaluation of the patient's ability to adequately cope with a range of tasks. In this study, we extend recent findings that UPDRS can be objectively assessed to clinically useful accuracy using simple, self-administered speech tests, without requiring the patient's physical presence in the clinic. We apply a wide range of known speech signal processing algorithms to a large database (approx. 6000 recordings from 42 PD patients, recruited to a six-month, multi-centre trial) and propose a number of novel, nonlinear signal processing algorithms which reveal pathological characteristics in PD more accurately than existing approaches. Robust feature selection algorithms select the optimal subset of these algorithms, which is fed into non-parametric regression and classification algorithms, mapping the signal processing algorithm outputs to UPDRS. We demonstrate rapid, accurate replication of the UPDRS assessment with clinically useful accuracy (about 2 UPDRS points difference from the clinicians' estimates, p < 0.001). This study supports the viability of frequent, remote, cost-effective, objective, accurate UPDRS telemonitoring based on self-administered speech tests. This technology could facilitate large-scale clinical trials into novel PD treatments.
264 citations
TL;DR: The focus of this brief review is to point out some possible commonalities in the molecular pathways in response to endothelial shear stress and circumferential wall stretch.
Abstract: Blood vessels are under constant mechanical loading from blood pressure and flow which cause internal stresses (endothelial shear stress and circumferential wall stress, respectively). The mechanical forces not only cause morphological changes of endothelium and blood vessel wall, but also trigger biochemical and biological events. There is considerable evidence that physiologic stresses and strains (stretch) exert vasoprotective roles via nitric oxide and provide a homeostatic oxidative balance. A perturbation of tissue stresses and strains can disturb biochemical homeostasis and lead to vascular remodelling and possible dysfunction (e.g. altered vasorelaxation, tone, stiffness, etc.). These distinct biological endpoints are caused by some common biochemical pathways. The focus of this brief review is to point out some possible commonalities in the molecular pathways in response to endothelial shear stress and circumferential wall stretch.
258 citations
TL;DR: In this paper, the authors measured the size distribution of airborne influenza A viruses and found that 64% of the viral genome copies were associated with fine particles smaller than 2.5 µm, which can remain suspended for hours.
Abstract: The relative importance of the aerosol transmission route for influenza remains contentious. To determine the potential for influenza to spread via the aerosol route, we measured the size distribution of airborne influenza A viruses. We collected size-segregated aerosol samples during the 2009–2010 flu season in a health centre, a day-care facility and onboard aeroplanes. Filter extracts were analysed using quantitative reverse transcriptase polymerase chain reaction. Half of the 16 samples were positive, and their total virus concentrations ranged from 5800 to 37 000 genome copies m−3. On average, 64 per cent of the viral genome copies were associated with fine particles smaller than 2.5 µm, which can remain suspended for hours. Modelling of virus concentrations indoors suggested a source strength of 1.6 ± 1.2 × 105 genome copies m−3 air h−1 and a deposition flux onto surfaces of 13 ± 7 genome copies m−2 h−1 by Brownian motion. Over 1 hour, the inhalation dose was estimated to be 30 ± 18 median tissue culture infectious dose (TCID50), adequate to induce infection. These results provide quantitative support for the idea that the aerosol route could be an important mode of influenza transmission.
232 citations
TL;DR: A simple DNA gate architecture that appears suitable for practical synthesis of large-scale circuits involving possibly thousands of gates is proposed.
Abstract: The prospects of programming molecular systems to perform complex autonomous tasks have motivated research into the design of synthetic biochemical circuits. Of particular interest to us are cell-free nucleic acid systems that exploit non-covalent hybridization and strand displacement reactions to create cascades that implement digital and analogue circuits. To date, circuits involving at most tens of gates have been demonstrated experimentally. Here, we propose a simple DNA gate architecture that appears suitable for practical synthesis of large-scale circuits involving possibly thousands of gates.
209 citations
TL;DR: The study focuses on the synthesis of a novel polymeric scaffold having good porosity and mechanical characteristics synthesized by using natural polymers and their optimization for application in cartilage tissue engineering and suggests the potential of CAG cryogels as a good three-dimensional scaffold for cartilage tissues engineering.
Abstract: The study focuses on the synthesis of a novel polymeric scaffold having good porosity and mechanical characteristics synthesized by using natural polymers and their optimization for application in cartilage tissue engineering. The scaffolds were synthesized via cryogelation technology using an optimized ratio of the polymer solutions (chitosan, agarose and gelatin) and cross-linker followed by the incubation at sub-zero temperature (2128C). Microstructure examination of the chitosan – agarose – gelatine (CAG) cryogels was done using scanning electron microscopy (SEM) and fluorescent microscopy. Mechanical analysis, such as the unconfined compression test, demonstrated that cryogels with varying chitosan concentrations, i.e. 0.5 – 1% have a high compression modulus. In addition, fatigue tests revealed that scaffolds are suitable for bioreactor studies where gels are subjected to continuous cyclic strain. In order to confirm the stability, cryogels were subjected to high frequency (5 Hz) with 30 per cent compression of their original length up to 1 � 10 5 cycles, gels did not show any significant changes in their mass and dimensions during the experiment. These cryogels have exhibited degradation capacity under aseptic conditions. CAG cryogels showed good cell adhesion of primary goat chondrocytes examined by SEM. Cytotoxicity of the material was checked by MTT assay and results confirmed the biocompatibility of the material. In vivo biocompatibility of the scaffolds was checked by the implantation of the scaffolds in laboratory animals. These results suggest the potential of CAG cryogels as a good three-dimensional scaffold for cartilage tissue engineering.
204 citations
TL;DR: A system capable of tracking the three-dimensional position and body orientation of animals such as flies and birds that operates with less than 40 ms latency and can track multiple animals simultaneously is described.
Abstract: Automated tracking of animal movement allows analyses that would not otherwise be possible by providing great quantities of data. The additional capability of tracking in real time—with minimal latency—opens up the experimental possibility of manipulating sensory feedback, thus allowing detailed explorations of the neural basis for control of behaviour. Here, we describe a system capable of tracking the three-dimensional position and body orientation of animals such as flies and birds. The system operates with less than 40 ms latency and can track multiple animals simultaneously. To achieve these results, a multi-target tracking algorithm was developed based on the extended Kalman filter and the nearest neighbour standard filter data association algorithm. In one implementation, an 11-camera system is capable of tracking three flies simultaneously at 60 frames per second using a gigabit network of nine standard Intel Pentium 4 and Core 2 Duo computers. This manuscript presents the rationale and details of the algorithms employed and shows three implementations of the system. An experiment was performed using the tracking system to measure the effect of visual contrast on the flight speed of Drosophila melanogaster. At low contrasts, speed is more variable and faster on average than at high contrasts. Thus, the system is already a useful tool to study the neurobiology and behaviour of freely flying animals. If combined with other techniques, such as ‘virtual reality’-type computer graphics or genetic manipulation, the tracking system would offer a powerful new way to investigate the biology of flying animals.
198 citations
TL;DR: Formal mathematical links are demonstrated between several prima facie unrelated dynamical approximations and used to derive two novel dynamical models for network epidemiology, which are compared against explicit stochastic simulation.
Abstract: Networks are increasingly central to modern science owing to their ability to conceptualize multiple interacting components of a complex system. As a specific example of this, understanding the implications of contact network structure for the transmission of infectious diseases remains a key issue in epidemiology. Three broad approaches to this problem exist: explicit simulation; derivation of exact results for special networks; and dynamical approximations. This paper focuses on the last of these approaches, and makes two main contributions. Firstly, formal mathematical links are demonstrated between several prima facie unrelated dynamical approximations. And secondly, these links are used to derive two novel dynamical models for network epidemiology, which are compared against explicit stochastic simulation. The success of these new models provides improved understanding about the interaction of network structure and transmission dynamics.
197 citations
TL;DR: An overview of the solutions developed to enhance the sensitivity and specificity of the resistive-pulse technique based on biological and solid-state nanopores with emphasis on biosensing applications.
Abstract: Nanopores are emerging as powerful tools for the detection and identification of macromolecules in aqueous solution. In this review, we discuss the recent development of active and passive controls over molecular transport through nanopores with emphasis on biosensing applications. We give an overview of the solutions developed to enhance the sensitivity and specificity of the resistive-pulse technique based on biological and solid-state nanopores.
TL;DR: It is shown that weather radar can extract near real-time bird density altitude profiles that closely correspond to the density profiles measured by dedicated bird radar, and can be used as a reliable sensor for quantifying bird densities aloft in an operational setting, which enables the mapping and continuous monitoring of bird migration flyways.
Abstract: A fully automated method for the detection and quantification of bird migration was developed for operational C-band weather radar, measuring bird density, speed and direction as a function of altitude. These weather radar bird observations have been validated with data from a high-accuracy dedicated bird radar, which was stationed in the measurement volume of weather radar sites in The Netherlands, Belgium and France for a full migration season during autumn 2007 and spring 2008. We show that weather radar can extract near real-time bird density altitude profiles that closely correspond to the density profiles measured by dedicated bird radar. Doppler weather radar can thus be used as a reliable sensor for quantifying bird densities aloft in an operational setting, which—when extended to multiple radars—enables the mapping and continuous monitoring of bird migration flyways. By applying the automated method to a network of weather radars, we observed how mesoscale variability in weather conditions structured the timing and altitude profile of bird migration within single nights. Bird density altitude profiles were observed that consisted of multiple layers, which could be explained from the distinct wind conditions at different take-off sites. Consistently lower bird densities are recorded in The Netherlands compared with sites in France and eastern Belgium, which reveals some of the spatial extent of the dominant Scandinavian flyway over continental Europe.
TL;DR: An optimal condition for sand-swimming is demonstrated and the RFT, in agreement with the simulated and physical models, predicts that for a single-period sinusoidal wave, maximal speed occurs for A/λ ≈ 0.2, the same kinematics used by the sandfish.
Abstract: We integrate biological experiment, empirical theory, numerical simulation and a physical model to reveal principles of undulatory locomotion in granular media. High-speed X-ray imaging of the sandfish lizard, Scincus scincus, in 3 mm glass particles shows that it swims within the medium without using its limbs by propagating a single-period travelling sinusoidal wave down its body, resulting in a wave efficiency, η, the ratio of its average forward speed to the wave speed, of approximately 0.5. A resistive force theory (RFT) that balances granular thrust and drag forces along the body predicts η close to the observed value. We test this prediction against two other more detailed modelling approaches: a numerical model of the sandfish coupled to a discrete particle simulation of the granular medium, and an undulatory robot that swims within granular media. Using these models and analytical solutions of the RFT, we vary the ratio of undulation amplitude to wavelength (A/λ) and demonstrate an optimal condition for sand-swimming, which for a given A results from the competition between η and λ. The RFT, in agreement with the simulated and physical models, predicts that for a single-period sinusoidal wave, maximal speed occurs for A/λ ≈ 0.2, the same kinematics used by the sandfish.
TL;DR: A fluid-dynamics-motivated mechanism for platelet activation, convection and deposition in AAAs that has the potential of improving the current understanding of the pathophysiology of fluid-driven ILT growth.
Abstract: Abdominal aortic aneurysms (AAAs) are frequently characterized by the development of an intra-luminal thrombus (ILT), which is known to have multiple biochemical and biomechanical implications. Dev ...
TL;DR: This paper shows that a structurally motivated phenomenological ‘four-fibre family’ constitutive relation captures the biaxial mechanical behaviour of both the human AA, from ages less than 30 to over 60, and abdominal aortic aneurysms, and that it provides important insight needed to construct growth and remodelling models for aneurYSms, which in turn promise to improve the ability to predict disease progression.
Abstract: The abdominal aorta (AA) in older individuals can develop an aneurysm, which is of increasing concern in our ageing population. The structural integrity of the ageing aortic wall, and hence aneurysm, depends primarily on effective elastin and multiple families of oriented collagen fibres. In this paper, we show that a structurally motivated phenomenological ‘four-fibre family’ constitutive relation captures the biaxial mechanical behaviour of both the human AA, from ages less than 30 to over 60, and abdominal aortic aneurysms. Moreover, combining the statistical technique known as non-parametric bootstrap with a modal clustering method provides improved confidence intervals for estimated best-fit values of the eight associated constitutive parameters. It is suggested that this constitutive relation captures the well-known loss of structural integrity of elastic fibres owing to ageing and the development of abdominal aneurysms, and that it provides important insight needed to construct growth and remodelling models for aneurysms, which in turn promise to improve our ability to predict disease progression.
TL;DR: ‘Soil engineering in vivo’, wherein the natural capacity of soil as a living ecosystem is used to provide multiple solutions simultaneously, may provide new, innovative, sustainable solutions to some of these great challenges of the twenty-first century.
Abstract: Carbon sequestration, infrastructure rehabilitation, brownfields clean-up, hazardous waste disposal, water resources protection and global warming—these twenty-first century challenges can neither be solved by the high-energy consumptive practices that hallmark industry today, nor by minor tweaking or optimization of these processes. A more radical, holistic approach is required to develop the sustainable solutions society needs. Most of the above challenges occur within, are supported on, are enabled by or grown from soil. Soil, contrary to conventional civil engineering thought, is a living system host to multiple simultaneous processes. It is proposed herein that ‘soil engineering in vivo’, wherein the natural capacity of soil as a living ecosystem is used to provide multiple solutions simultaneously, may provide new, innovative, sustainable solutions to some of these great challenges of the twenty-first century. This requires a multi-disciplinary perspective that embraces the science of biology, chemistry and physics and applies this knowledge to provide multi-functional civil and environmental engineering designs for the soil environment. For example, can native soil bacterial species moderate the carbonate cycle in soils to simultaneously solidify liquefiable soil, immobilize reactive heavy metals and sequester carbon—effectively providing civil engineering functionality while clarifying the ground water and removing carbon from the atmosphere? Exploration of these ideas has begun in earnest in recent years. This paper explores the potential, challenges and opportunities of this new field, and highlights one biogeochemical function of soil that has shown promise and is developing rapidly as a new technology. The example is used to propose a generalized approach in which the potential of this new field can be fully realized.
TL;DR: It is concluded that LWs are neither a universal optimal search strategy, nor are they as widespread in nature as was once thought.
Abstract: The hypothesis that the optimal search strategy is a Levy walk (LW) or Levy flight, originally suggested in 1995, has generated an explosion of interest and controversy. Long-standing empirical evidence supporting the LW hypothesis has been overturned, while new models and data are constantly being published. Statistical methods have been criticized and new methods put forward. In parallel with the empirical studies, theoretical search models have been developed. Some theories have been disproved while others remain. Here, we gather together the current state of the art on the role of LWs in optimal foraging theory. We examine the body of theory underpinning the subject. Then we present new results showing that deviations from the idealized one-dimensional search model greatly reduce or remove the advantage of LWs. The search strategy of an LW with exponent μ = 2 is therefore not as robust as is widely thought. We also review the available techniques, and their potential pitfalls, for analysing field data. It is becoming increasingly recognized that there is a wide range of mechanisms that can lead to the apparent observation of power-law patterns. The consequence of this is that the detection of such patterns in field data implies neither that the foragers in question are performing an LW, nor that they have evolved to do so. We conclude that LWs are neither a universal optimal search strategy, nor are they as widespread in nature as was once thought.
TL;DR: Using long-term data from the Serengeti Lion Project, the contact network structure of a territorial wildlife population is characterized and the epidemiological impact of nomadic individuals is addressed.
Abstract: Territoriality in animal populations creates spatial structure that is thought to naturally buffer disease invasion. Often, however, territorial populations also include highly mobile, non-residential individuals that potentially serve as disease superspreaders. Using long-term data from the Serengeti Lion Project, we characterize the contact network structure of a territorial wildlife population and address the epidemiological impact of nomadic individuals. As expected, pride contacts are dominated by interactions with neighbouring prides and interspersed by encounters with nomads as they wander throughout the ecosystem. Yet the pride–pride network also includes occasional long-range contacts between prides, making it surprisingly small world and vulnerable to epidemics, even without nomads. While nomads increase both the local and global connectivity of the network, their epidemiological impact is marginal, particularly for diseases with short infectious periods like canine distemper virus. Thus, territoriality in Serengeti lions may be less protective and non-residents less important for disease transmission than previously considered.
TL;DR: A general overview of the potential of bioinspired textile structures is provided by highlighting a few specific examples of pertinent, inherently sustainable biological systems.
Abstract: The natural world around us provides excellent examples of functional systems built with a handful of materials. Throughout the millennia, nature has evolved to adapt and develop highly sophisticated methods to solve problems. There are numerous examples of functional surfaces, fibrous structures, structural colours, self-healing, thermal insulation, etc., which offer important lessons for the textile products of the future. This paper provides a general overview of the potential of bioinspired textile structures by highlighting a few specific examples of pertinent, inherently sustainable biological systems. Biomimetic research is a rapidly growing field and its true potential in the development of new and sustainable textiles can only be realized through interdisciplinary research rooted in a holistic understanding of nature.
TL;DR: The recorded stress–strain response of individual MCFs under tension shows an initial linear deformation region for all fibrils, followed by inhomogeneous deformation above a critical strain, indicative of fibrs exhibiting either yield or strain hardening and suggests possible mineral compositional changes within each fibril.
Abstract: Mineralized collagen fibrils (MCFs) are distinct building blocks for bone material and perform an important mechanical function. A novel experimental technique using combined atomic force microscopy and scanning electron microscopy is used to manipulate and measure the mechanical properties of individual MCFs from antler, which is a representative bone tissue. The recorded stress–strain response of individual MCFs under tension shows an initial linear deformation region for all fibrils, followed by inhomogeneous deformation above a critical strain. This inhomogeneous deformation is indicative of fibrils exhibiting either yield or strain hardening and suggests possible mineral compositional changes within each fibril. A phenomenological model is used to describe the fibril nano-mechanical behaviour.
TL;DR: Computer simulations demonstrate that variation among individuals in connectivity accelerates information flow to an extent equivalent to an increase in the total number of interactions in the entrance chamber.
Abstract: Social insects exhibit coordinated behaviour without central control. Local interactions among individuals determine their behaviour and regulate the activity of the colony. Harvester ants are recruited for outside work, using networks of brief antennal contacts, in the nest chamber closest to the nest exit: the entrance chamber. Here, we combine empirical observations, image analysis and computer simulations to investigate the structure and function of the interaction network in the entrance chamber. Ant interactions were distributed heterogeneously in the chamber, with an interaction hot-spot at the entrance leading further into the nest. The distribution of the total interactions per ant followed a right-skewed distribution, indicating the presence of highly connected individuals. Numbers of ant encounters observed positively correlated with the duration of observation. Individuals varied in interaction frequency, even after accounting for the duration of observation. An ant's interaction frequency was explained by its path shape and location within the entrance chamber. Computer simulations demonstrate that variation among individuals in connectivity accelerates information flow to an extent equivalent to an increase in the total number of interactions. Individual variation in connectivity, arising from variation among ants in location and spatial behaviour, creates interaction centres, which may expedite information flow.
TL;DR: The energy-minimizing gaits of many different simple biped models are obtained, indicating that a running animal's metabolic cost could be dominated by the cost of producing isometric force, even though performing muscle work is usually expensive.
Abstract: A popular hypothesis regarding legged locomotion is that humans and other large animals walk and run in a manner that minimizes the metabolic energy expenditure for locomotion. Here, using numerical optimization and supporting analytical arguments, I obtain the energy-minimizing gaits of many different simple biped models. I consider bipeds with point-mass bodies and massless legs, with or without a knee, with or without a springy tendon in series with the leg muscle and minimizing one of many different ‘metabolic cost’ models—correlated with muscle work, muscle force raised to some power, the Minetti–Alexander quasi-steady approximation to empirical muscle metabolic rate (from heat and ATPase activity), a new cost function called the ‘generalized work cost’ Cg having some positivity and convexity properties (and includes the Minetti–Alexander cost and the work cost as special cases), and generalizations thereof. For many of these models, walking-like gaits are optimal at low speeds and running-like gaits at higher speeds, so a gait transition is optimal. Minimizing the generalized work cost Cg appears mostly indistinguishable from minimizing muscle work for all the models. Inverted pendulum walking and impulsive running gaits minimize the work cost, generalized work costs Cg and a few other costs for the springless bipeds; in particular, a knee-torque-squared cost, appropriate as a simplified model for electric motor power for a kneed robot biped. Many optimal gaits had symmetry properties; for instance, the left stance phase was identical to the right stance phases. Muscle force–velocity relations and legs with masses have predictable qualitative effects, if any, on the optima. For bipeds with compliant tendons, the muscle work-minimizing strategies have close to zero muscle work (isometric muscles), with the springs performing all the leg work. These zero work gaits also minimize the generalized work costs Cg with substantial additive force or force rate costs, indicating that a running animal's metabolic cost could be dominated by the cost of producing isometric force, even though performing muscle work is usually expensive. I also catalogue the many differences between the optimal gaits of the various models. These differences contain information that might help us develop models that better predict locomotion data. In particular, for some biologically plausible cost functions, the presence or absence of springs in series with muscles has a large effect on both the coordination strategy and the absolute cost; the absence of springs results in more impulsive (collisional) optimal gaits and the presence of springs leads to more compliant optimal gaits. Most results are obtained for specific speed and stride length combinations close to preferred human behaviour, but limited numerical experiments show that some qualitative results extend to other speed-stride length combinations as well.
TL;DR: The uncovered dynamical self-similarity implies that the brain is spontaneously at a continuously changing intermediate state between two extremes, one of excessive cortical integration and the other of complete segregation, which may be seen as an important marker of brain well-being in both health and disease.
Abstract: Adaptive behaviour, cognition and emotion are the result of a bewildering variety of brain spatio-temporal activity patterns. An important problem in neuroscience is to understand the mechanism by which the human brain's 100 billion neurons and 100 trillion synapses manage to produce this large repertoire of cortical configurations in a flexible manner. In addition, it is recognized that temporal correlations across such configurations cannot be arbitrary, but they need to meet two conflicting demands: while diverse cortical areas should remain functionally segregated from each other, they must still perform as a collective, i.e. they are functionally integrated. Here, we investigate these large-scale dynamical properties by inspecting the character of the spatio-temporal correlations of brain resting-state activity. In physical systems, these correlations in space and time are captured by measuring the correlation coefficient between a signal recorded at two different points in space at two different times. We show that this two-point correlation function extracted from resting-state functional magnetic resonance imaging data exhibits self-similarity in space and time. In space, self-similarity is revealed by considering three successive spatial coarse-graining steps while in time it is revealed by the 1/f frequency behaviour of the power spectrum. The uncovered dynamical self-similarity implies that the brain is spontaneously at a continuously changing (in space and time) intermediate state between two extremes, one of excessive cortical integration and the other of complete segregation. This dynamical property may be seen as an important marker of brain well-being in both health and disease.
TL;DR: This work presents an original individual-based model of collective animal motion that reproduces the previous findings and bridges the current gap between previous model analysis and recent evidence, and presents a framework for further study.
Abstract: The mechanism of self-organization resulting in coordinated collective motion has received wide attention from a range of scientists interested in both its technical and biological relevance. Models have been highly influential in highlighting how collective motion can be produced from purely local interactions between individuals. Typical models in this field are termed ‘metric’ because each individual only reacts to conspecifics within a fixed distance. A recent large-scale study has, however, provided evidence that interactions ruling collective behaviour occur between a fixed number of nearest neighbours (‘topological’ framework). Despite their importance in clarifying the nature of the mechanism underlying animal interactions, these findings have yet to be produced by either metric or topological models. Here, we present an original individual-based model of collective animal motion that reproduces the previous findings. Our approach bridges the current gap between previous model analysis and recent evidence, and presents a framework for further study.
TL;DR: The results suggest that the nervous system responds to dry skin by exaggerated grip forces that cannot be simply explained by a change in the coefficient of friction.
Abstract: The dynamics of fingertip contact manifest themselves in the complex skin movements observed during the transition from a stuck state to a fully developed slip. While investigating this transition, we found that it depended on skin hydration. To quantify this dependency, we asked subjects to slide their index fingertip on a glass surface while keeping the normal component of the interaction force constant with the help of visual feedback. Skin deformation inside the contact region was imaged with an optical apparatus that allowed us to quantify the relative sizes of the slipping and sticking regions. The ratio of the stuck skin area to the total contact area decreased linearly from 1 to 0 when the tangential force component increased from 0 to a maximum. The slope of this relationship was inversely correlated to the normal force component. The skin hydration level dramatically affected the dynamics of the contact encapsulated in the course of evolution from sticking to slipping. The specific effect was to reduce the tendency of a contact to slip, regardless of the variations of the coefficient of friction. Since grips were more unstable under dry skin conditions, our results suggest that the nervous system responds to dry skin by exaggerated grip forces that cannot be simply explained by a change in the coefficient of friction.
TL;DR: The specific inhibition of the Rho-kinase activity causes cells to not only lose their stress fibres and focal adhesions, but also to appear to lose their cytoplasmic tension.
Abstract: Stress fibres and associated focal adhesions in cells constitute a contractile apparatus that regulates cell motility and contraction. Rho-kinase, an effector molecule of small GTPases, regulates non-muscle cell motility and contractility. Rho-kinase mediates the contraction of stress fibres in a Ca2+-independent manner, and is responsible for slower and more finely tuned contraction of stress fibres than that regulated by myosin light chain kinase activity in living cells. The specific inhibition of the Rho-kinase activity causes cells to not only lose their stress fibres and focal adhesions, but also to appear to lose their cytoplasmic tension. Activated Rho-kinase is also involved in the organization of newly formed stress fibres and focal adhesions in living cells.
TL;DR: A new optical system is prepared that can simultaneously measure both the spectrum and direction of the reflected light, which are expected to be closely related to each other in the Venetian blind model.
Abstract: The structural colour of the neon tetra is distinguishable from those of, e.g., butterfly wings and bird feathers, because it can change in response to the light intensity of the surrounding environment. This fact clearly indicates the variability of the colour-producing microstructures. It has been known that an iridophore of the neon tetra contains a few stacks of periodically arranged light-reflecting platelets, which can cause multilayer optical interference phenomena. As a mechanism of the colour variability, the Venetian blind model has been proposed, in which the light-reflecting platelets are assumed to be tilted during colour change, resulting in a variation in the spacing between the platelets. In order to quantitatively evaluate the validity of this model, we have performed a detailed optical study of a single stack of platelets inside an iridophore. In particular, we have prepared a new optical system that can simultaneously measure both the spectrum and direction of the reflected light, which are expected to be closely related to each other in the Venetian blind model. The experimental results and detailed analysis are found to quantitatively verify the model.
TL;DR: An overview of a series of recent theoretical studies aimed at probing the basic mechanical principles of focal contacts in cell–matrix adhesion via stochastic–elastic models, with results showing that intermediate adhesion size, stiff substrate, cytoskeleton stiffening, low-angle pulling and moderate cytoskeletal pretension are factors that contribute to stable FAs.
Abstract: Cell–matrix adhesion depends on the collective behaviours of clusters of receptor–ligand bonds called focal contacts between cell and extracellular matrix. While the behaviour of a single molecular bond is governed by statistical mechanics at the molecular scale, continuum mechanics should be valid at a larger scale. This paper presents an overview of a series of recent theoretical studies aimed at probing the basic mechanical principles of focal contacts in cell–matrix adhesion via stochastic–elastic models in which stochastic descriptions of molecular bonds and elastic descriptions of interfacial traction–separation are unified in a single modelling framework. The intention here is to illustrate these principles using simple analytical and numerical models. The aim of the discussions is to provide possible clues to the following questions: why does the size of focal adhesions (FAs) fall into a narrow range around the micrometre scale? How can cells sense and respond to substrates of varied stiffness via FAs? How do the magnitude and orientation of mechanical forces affect the binding dynamics of FAs? The effects of cluster size, cell–matrix elastic modulus, loading direction and cytoskeletal pretension on the lifetime of FA clusters have been investigated by theoretical arguments as well as Monte Carlo numerical simulations, with results showing that intermediate adhesion size, stiff substrate, cytoskeleton stiffening, low-angle pulling and moderate cytoskeletal pretension are factors that contribute to stable FAs. From a mechanistic point of view, these results provide possible explanations for a wide range of experimental observations and suggest multiple mechanisms by which cells can actively control adhesion and de-adhesion via cytoskeletal contractile machinery in response to mechanical properties of their surroundings.
TL;DR: It is suggested that osteogenic culture conditions amplify the stimulatory effect of vibration loading on differentiation of hASCs towards bone-forming cells and simultaneously inhibit differentiation towards fat tissue.
Abstract: Mechanical stimulation is an essential factor affecting the metabolism of bone cells and their precursors. We hypothesized that vibration loading would stimulate differentiation of human adipose stem cells (hASCs) towards bone-forming cells and simultaneously inhibit differentiation towards fat tissue. We developed a vibration-loading device that produces 3g peak acceleration at frequencies of 50 and 100 Hz to cells cultured on well plates. hASCs were cultured using either basal medium (BM), osteogenic medium (OM) or adipogenic medium (AM), and subjected to vibration loading for 3 h d(-1) for 1, 7 and 14 day. Osteogenesis, i.e. differentiation of hASCs towards bone-forming cells, was analysed using markers such as alkaline phosphatase (ALP) activity, collagen production and mineralization. Both 50 and 100 Hz vibration frequencies induced significantly increased ALP activity and collagen production of hASCs compared with the static control at 14 day in OM. A similar trend was detected for mineralization, but the increase was not statistically significant. Furthermore, vibration loading inhibited adipocyte differentiation of hASCs. Vibration did not affect cell number or viability. These findings suggest that osteogenic culture conditions amplify the stimulatory effect of vibration loading on differentiation of hASCs towards bone-forming cells.
TL;DR: To better characterize the spread of the 1918 major wave, a range of city-to-city transmission models are fitted to mortality data collected for 246 population centres in England and Wales and 47 cities in the US and it is found that parameters estimated from theEngland and Wales dataset can be applied to the US data with no likelihood penalty.
Abstract: There is still limited understanding of key determinants of spatial spread of influenza. The 1918 pandemic provides an opportunity to elucidate spatial determinants of spread on a large scale. To better characterize the spread of the 1918 major wave, we fitted a range of city-to-city transmission models to mortality data collected for 246 population centres in England and Wales and 47 cities in the US. Using a gravity model for city-to-city contacts, we explored the effect of population size and distance on the spread of disease and tested assumptions regarding density dependence in connectivity between cities. We employed Bayesian Markov Chain Monte Carlo methods to estimate parameters of the model for population, infectivity, distance and density dependence. We inferred the most likely transmission trees for both countries. For England and Wales, a model that estimated the degree of density dependence in connectivity between cities was preferable by deviance information criterion comparison. Early in the major wave, long distance infective interactions predominated, with local infection events more likely as the epidemic became widespread. For the US, with fewer more widely dispersed cities, statistical power was lacking to estimate population size dependence or the degree of density dependence, with the preferred model depending on distance only. We find that parameters estimated from the England and Wales dataset can be applied to the US data with no likelihood penalty.