Experimental characterisation of walking locomotion on rigid level surfaces using motion capture system

This is the final version. Available on open access from Elsevier via the DOI in this recordLow-frequency structures, such as footbridges and long-span floors, are often sensitive to variations in dynamic loading induced by pedestrians. As a result, the design of these structures using traditional deterministic approaches is being replaced by stochastic load models that can accommodate different styles of walking. To inform development and facilitate wider implementation of the new stochastic approaches, a database of experimental data characterising both inter- and intra-subject variability of gait parameters is required. This study aims to contribute to the development of such a database by providing a set of data for walking over rigid level surfaces.The motion capture system Vicon was used for simultaneous monitoring of the kinematic and kinetic gait parameters. Ten test subjects walking at 13 different speeds participated in the experimental programme. Novel experimental data on pacing rate, step length, step width, angular positions of the legs and the trunk, and the force amplitude were collected and statistically characterised. The acquired data are suitable for calibration of the bipedal pedestrian models intended for civil engineering applications.Engineering and Physical Sciences Research Council (EPSRC)University of Warwic

Influence of Low-Frequency Vertical Vibration on Walking Locomotion

This is the final version. Available on open access license from American Society of Civil Engineers via the DOI in this recordData Availability: Electronic format of the data collected in this research can be downloaded freely from the University of Warwick webpages http://wrap.warwick.ac.uk/79038/.Walking locomotion has been a subject of studies in diverse research fields, such as computer, medical, and sport sciences, biomechanics, and robotics, resulting in improved understanding of underlying body motion and gait efficiency and pathology (when present). Only recently, a detailed understanding of kinematics and kinetics of the walking locomotion has become an important requirement in structural engineering applications due to an increasing sensitivity of modern, lightweight, low-frequency, and lightly damped footbridges to pedestrian-induced dynamic excitation. To facilitate development, calibration and verification of pedestrian models requires experimental characterization of walking gait parameters and understanding whether and how these parameters are influenced by the structural vibration. This study investigates whether low-frequency vibrations in the vertical direction affect seven walking locomotion parameters: pacing frequency, step length, step width, angle of attack, end-of-step angle, trunk angle, and amplitude of the first forcing harmonic. Three participants took part in a testing program consisting of walking on a treadmill placed on both stationary and vibrating supporting surfaces. The collected data suggest that an increasing level of vibration results in an increase in step-by-step variability for the majority of parameters. Furthermore, the existence of the self-excited force, previously observed only in numerical simulations of walking on pre-excited bridge decks, was confirmed. In addition, the deck vibration tended to have a beneficial effect of reducing the net force induced into the structure when walking at a pacing rate close to the vibration frequency. Finally, it was found that the vibration level perceptible by a pedestrian is one to two orders of magnitude larger than that typical of a standing person, and that the sensitivity to vibration decreases as the speed of walking increases.Engineering and Physical Sciences Research Council (EPSRC

Modelling pedestrian interaction with perceptibly vibrating footbridges

This is the final version. Available on open access from the publisher via the link in this recordTo evaluate the vibration serviceability of footbridge structures most structural engineers use pedestrian force models that are defined for walking on rigid surfaces. This approach is no longer applicable for slender, light-weight and low-frequency structures that are prone to perceptible vibrations under walking excitation. To overcome this issue, it is necessary to understand the pedestrian walking locomotion and how the locomotion process interacts with the vibrating structure. This paper compares three approaches for modelling pedestrian walking over lively structures, and it critically evaluates their suitability for modelling the feedback mechanism between the structure and the pedestrian. The models are evaluated with respect to their capability to reproduce human-like motion as well as to replicate the vibration patterns observed on lively bridges. It has been shown that models used in biomechanics are good candidates for applications in the structural engineering context. © Faculty of Mechanical Engineering, Belgrade.Engineering and Physical Sciences Research Council (EPSRC)University of Warwic

Evaluation of inverted-pendulum-with-rigid-legs walking locomotion models for civil engineering applications

This is the final version. Available from MDPI via the DOI in this record. Data Availability Statement: Data are contained within the article.Bipedal models for walkers, originally developed in the research field of biomechanics, have been identified as potential candidates for modelling pedestrians in structural engineering applications. These models provide insight into both the kinetics and kinematics of walking locomotion and are considered to have a significant potential to improve the vibration serviceability assessment of civil engineering structures. Despite this notion, the ability of the bipedal models to represent the key features of the walking gait and natural variability within the pedestrian population are still under-researched. This paper critically evaluates the performance of two bipedal models with rigid legs to realistically both reproduce key features of an individual pedestrian’s walking gait and represent a wide range of individuals. The evaluation is performed for walking on a rigid, rather than vibrating, structure due to the availability of experimental data and expectation that successful modelling on rigid surfaces is a necessary condition for progressing towards modelling on the vibrating structures. Ready-to-use equations are provided and the ability of the models to represent the kinematics and kinetics of individual pedestrians as well as the inter-subject variability typical of the human population is critically evaluated. It was found that the two models could generate realistic combinations of the gait parameters and their correlations, but are less successful in reproducing genuine kinetic and kinematics profiles.Engineering and Physical Sciences Research CouncilEngineering and Physical Sciences Research CouncilEuropean Union’s Horizon 2020China Scholarship Counci

Bringing the countryside to the city: practices and imaginations of the rural in Ho Chi Minh city, Vietnam

10.1177/0042098014563031Urban Studies532324-33

Characterising and Predicting Haploinsufficiency in the Human Genome

Haploinsufficiency, wherein a single functional copy of a gene is insufficient to maintain normal function, is a major cause of dominant disease. Human disease studies have identified several hundred haploinsufficient (HI) genes. We have compiled a map of 1,079 haplosufficient (HS) genes by systematic identification of genes unambiguously and repeatedly compromised by copy number variation among 8,458 apparently healthy individuals and contrasted the genomic, evolutionary, functional, and network properties between these HS genes and known HI genes. We found that HI genes are typically longer and have more conserved coding sequences and promoters than HS genes. HI genes exhibit higher levels of expression during early development and greater tissue specificity. Moreover, within a probabilistic human functional interaction network HI genes have more interaction partners and greater network proximity to other known HI genes. We built a predictive model on the basis of these differences and annotated 12,443 genes with their predicted probability of being haploinsufficient. We validated these predictions of haploinsufficiency by demonstrating that genes with a high predicted probability of exhibiting haploinsufficiency are enriched among genes implicated in human dominant diseases and among genes causing abnormal phenotypes in heterozygous knockout mice. We have transformed these gene-based haploinsufficiency predictions into haploinsufficiency scores for genic deletions, which we demonstrate to better discriminate between pathogenic and benign deletions than consideration of the deletion size or numbers of genes deleted. These robust predictions of haploinsufficiency support clinical interpretation of novel loss-of-function variants and prioritization of variants and genes for follow-up studies

Understanding the Warburg effect and the prognostic value of stromal caveolin-1 as a marker of a lethal tumor microenvironment

Cancer cells show a broad spectrum of bioenergetic states, with some cells using aerobic glycolysis while others rely on oxidative phosphorylation as their main source of energy. In addition, there is mounting evidence that metabolic coupling occurs in aggressive tumors, between epithelial cancer cells and the stromal compartment, and between well-oxygenated and hypoxic compartments. We recently showed that oxidative stress in the tumor stroma, due to aerobic glycolysis and mitochondrial dysfunction, is important for cancer cell mutagenesis and tumor progression. More specifically , increased autophagy/mitophagy in the tumor stroma drives a form of parasitic epithelial-stromal metabolic coupling. These findings explain why it is effective to treat tumors with either inducers or inhibitors of autophagy, as both would disrupt this energetic coupling. We also discuss evidence that glutamine addiction in cancer cells produces ammonia via oxidative mitochondrial metabolism. Ammonia production in cancer cells, in turn, could then help maintain autophagy in the tumor stromal compartment. In this vicious cycle, the initial glutamine provided to cancer cells would be produced by autophagy in the tumor stroma. Thus, we believe that parasitic epithelial-stromal metabolic coupling has important implications for cancer diagnosis and therapy, for example, in designing novel metabolic imaging techniques and establishing new targeted therapies. In direct support of this notion, we identified a loss of stromal caveolin-1 as a marker of oxidative stress, hypoxia, and autophagy in the tumor microenvironment, explaining its powerful predictive value. Loss of stromal caveolin-1 in breast cancers is associated with early tumor recurrence, metastasis, and drug resistance, leading to poor clinical outcome