Stochastic simulation of chemical reactions in spatially complex media

Discrete stochastic simulations, via techniques such as the Stochastic Simulation Algorithm (SSA) are a powerful tool for understanding the dynamics of chemical kinetics when there are low numbers of certain molecular species. However, an important constraint is the assumption of well-mixedness and homogeneity. In this paper, we show how to use Monte Carlo simulations to estimate an anomalous diffusion parameter that encapsulates the crowdedness of the spatial environment. We then use this parameter to replace the rate constants of bimolecular reactions by a time-dependent power law to produce an SSA valid in cases where anomalous diffusion occurs or the system is not well-mixed (ASSA). Simulations then show that ASSA can successfully predict the temporal dynamics of chemical kinetics in a spatially constrained environment.

Stochastic modelling of T cell homeostasis for two competing clonotypes via the master equation

Stochastic models for competing clonotypes of T cells by multivariate, continuous-time, discrete state, Markov processes have been proposed in the literature by Stirk, Molina-París and van den Berg (2008). A stochastic modelling framework is important because of rare events associated with small populations of some critical cell types. Usually, computational methods for these problems employ a trajectory-based approach, based on Monte Carlo simulation. This is partly because the complementary, probability density function (PDF) approaches can be expensive but here we describe some efficient PDF approaches by directly solving the governing equations, known as the Master Equation. These computations are made very efficient through an approximation of the state space by the Finite State Projection and through the use of Krylov subspace methods when evolving the matrix exponential. These computational methods allow us to explore the evolution of the PDFs associated with these stochastic models, and bimodal distributions arise in some parameter regimes. Time-dependent propensities naturally arise in immunological processes due to, for example, age-dependent effects. Incorporating time-dependent propensities into the framework of the Master Equation significantly complicates the corresponding computational methods but here we describe an efficient approach via Magnus formulas. Although this contribution focuses on the example of competing clonotypes, the general principles are relevant to multivariate Markov processes and provide fundamental techniques for computational immunology.

N-Aryl stilbazolium dyes as sensitizers for solar cells

Eight new N-arylstilbazolium chromophores with electron donating –NR2 (R = Me or Ph) substituents have been synthesized via Knoevenagel condensations and isolated as their PF6− salts. These compounds have been characterized by using various techniques including 1H NMR and IR spectroscopies and electrospray mass spectrometry. UV–vis absorption spectra recorded in acetonitrile are dominated by intense, low energy π → π* intramolecular charge-transfer (ICT) bands, and replacing Me with Ph increases the ICT energies. Cyclic voltammetric studies show irreversible reduction processes, together with oxidation waves that are irreversible for R = Me, but reversible for R = Ph. Single crystal X-ray structures have been determined for three of the methyl ester-substituted stilbazolium salts and for the Cl− salts of their picolinium precursors. Time-dependent density functional theory calculations afford reasonable predictions of ICT energies, but greater rigour is necessary for –NPh2 derivatives. The four new acid-functionalized dyes give moderate sensitization efficiencies (ca. 0.2%) when using TiO2-based photoanodes, with relatively higher values for R = Ph vs Me, while larger efficiencies (up to 0.8%) are achieved with ZnO substrates.

The influence of ambient temperature on birth outcomes in Brisbane, Australia

Lately, there has been increasing interest in the association between temperature and adverse birth outcomes including preterm birth (PTB) and stillbirth. PTB is a major predictor of many diseases later in life, and stillbirth is a devastating event for parents and families. The aim of this study was to assess the seasonal pattern of adverse birth outcomes, and to examine possible associations of maternal exposure to temperature with PTB and stillbirth. We also aimed to identify if there were any periods of the pregnancy where exposure to temperature was particularly harmful. A retrospective cohort study design was used and we retrieved individual birth records from the Queensland Health Perinatal Data Collection Unit for all singleton births (excluding twins and triplets) delivered in Brisbane between 1 July 2005 and 30 June 2009. We obtained weather data (including hourly relative humidity, minimum and maximum temperature) and air-pollution data (including PM10, SO2 and O3) from the Queensland Department of Environment and Resource Management. We used survival analyses with the time-dependent variables of temperature, humidity and air pollution, and the competing risks of stillbirth and live birth. To assess the monthly pattern of the birth outcomes, we fitted month of pregnancy as a time-dependent variable. We examined the seasonal pattern of the birth outcomes and the relationship between exposure to high or low temperatures and birth outcomes over the four lag weeks before birth. We further stratified by categorisation of PTB: extreme PTB (< 28 weeks of gestation), PTB (28–36 weeks of gestation), and term birth (≥ 37 weeks of gestation). Lastly, we examined the effect of temperature variation in each week of the pregnancy on birth outcomes. There was a bimodal seasonal pattern in gestation length. After adjusting for temperature, the seasonal pattern changed from bimodal, to only one peak in winter. The risk of stillbirth was statistically significant lower in March compared with January. After adjusting for temperature, the March trough was still statistically significant and there was a peak in risk (not statistically significant) in winter. There was an acute effect of temperature on gestational age and stillbirth with a shortened gestation for increasing temperature from 15 °C to 25 °C over the last four weeks before birth. For stillbirth, we found an increasing risk with increasing temperatures from 12 °C to approximately 20 °C, and no change in risk at temperatures above 20 °C. Certain periods of the pregnancy were more vulnerable to temperature variation. The risk of PTB (28–36 weeks of gestation) increased as temperatures increased above 21 °C. For stillbirth, the fetus was most vulnerable at less than 28 weeks of gestation, but there were also effects in 28–36 weeks of gestation. For fetuses of more than 37 weeks of gestation, increasing temperatures did not increase the risk of stillbirth. We did not find any adverse affects of cold temperature on birth outcomes in this cohort. My findings contribute to knowledge of the relationship between temperature and birth outcomes. In the context of climate change, this is particularly important. The results may have implications for public health policy and planning, as they indicate that pregnant women would decrease their risk of adverse birth outcomes by avoiding exposure to high temperatures and seeking cool environments during hot days.

The acute adaptations of normal and pathological human Achilles tendons to eccentric and concentric exercise

Eccentric exercise is the conservative treatment of choice for mid-portion Achilles tendinopathy. While there is a growing body of evidence supporting the medium to long term efficacy of eccentric exercise in Achilles tendinopathy treatment, very few studies have investigated the short term response of the tendon to eccentric exercise. Moreover, the mechanisms through which tendinopathy symptom resolution occurs remain to be established. The primary purpose of this thesis was to investigate the acute adaptations of the Achilles tendon to, and the biomechanical characteristics of, the eccentric exercise protocol used for Achilles tendinopathy rehabilitation and a concentric equivalent. The research was conducted with an orientation towards exploring potential mechanisms through which eccentric exercise may bring about a resolution of tendinopathy symptoms. Specifically, the morphology of tendinopathic and normal Achilles tendons was monitored using high resolution sonography prior to and following eccentric and concentric exercise, to facilitate comparison between the treatment of choice and a similar alternative. To date, the only proposed mechanism through which eccentric exercise is thought to result in symptom resolution is the increased variability in motor output force observed during eccentric exercise. This thesis expanded upon prior work by investigating the variability in motor output force recorded during eccentric and concentric exercises, when performed at two different knee joint angles, by limbs with and without symptomatic tendinopathy. The methodological phase of the research focused on establishing the reliability of measures of tendon thickness, tendon echogenicity, electromyography (EMG) of the Triceps Surae and the standard deviation (SD) and power spectral density (PSD) of the vertical ground reaction force (VGRF). These analyses facilitated comparison between the error in the measurements and experimental differences identified as statistically significant, so that the importance and meaning of the experimental differences could be established. One potential limitation of monitoring the morphological response of the Achilles tendon to exercise loading is that the Achilles tendon is continually exposed to additional loading as participants complete the walking required to carry out their necessary daily tasks. The specific purpose of the last experiment in the methodological phase was to evaluate the effect of incidental walking activity on Achilles tendon morphology. The results of this study indicated that walking activity could decrease Achilles tendon thickness (negative diametral strain) and that the decrease in thickness was dependent on both the amount of walking completed and the proximity of walking activity to the sonographic examination. Thus, incidental walking activity was identified as a potentially confounding factor for future experiments which endeavoured to monitor changes in tendon thickness with exercise loading. In the experimental phase of this thesis the thickness of Achilles tendons was monitored prior to and following isolated eccentric and concentric exercise. The initial pilot study demonstrated that eccentric exercise resulted in a greater acute decrease in Achilles tendon thickness (greater diametral strain) compared to an equivalent concentric exercise, in participants with no history of Achilles tendon pain. This experiment was then expanded to incorporate participants with unilateral Achilles tendinopathy. The major finding of this experiment was that the acute decrease in Achilles tendon thickness observed following eccentric exercise was modified by the presence of tendinopathy, with a smaller decrease (less diametral strain) noted for tendinopathic compared to healthy control tendon. Based on in vitro evidence a decrease in tendon thickness is believed to reflect extrusion of fluid from the tendon with loading. This process would appear to be limited by the presence of pathology and is hypothesised to be a result of the changes in tendon structure associated with tendinopathy. Load induced fluid movement may be important to the maintenance of tendon homeostasis and structure as it has the potential to enhance molecular movement and stimulate tendon remodelling. On this basis eccentric exercise may be more beneficial to the tendon than concentric exercise. Finally, EMG and motor output force variability (SD and PSD of VGRF) were investigated while participants with and without tendinopathy performed the eccentric and concentric exercises. Although between condition differences were identified as statistically significant for a number of force variability parameters, the differences were not greater than the limits of agreement for repeated measures. Consequently the meaning and importance of these findings were questioned. Interestingly, the EMG amplitude of all three Triceps Surae muscles did not vary with knee joint angle during the performance of eccentric exercise. This raises questions pertaining to the functional importance of performing the eccentric exercise protocol at each of the two knee joint angles as it is currently prescribed. EMG amplitude was significantly greater during concentric compared to eccentric muscle actions. Differences in the muscle activation patterns may result in different stress distributions within the tendon and be related to the different diametral strain responses observed for eccentric and concentric muscle actions.

Free convection heat transfer through coupled thermal boundary layers in a partitioned triangular enclosure

A numerical investigation has been carried out for the coupled thermal boundary layers on both sides of a partition placed in an isosceles triangular enclosure along its middle symmetric line. The working fluid is considered as air which is initially quiescent. A sudden temperature difference between two zones of the enclosure has been imposed to trigger the natural convection. It is anticipated from the numerical simulations that the coupled thermal boundary layers development adjacent to the partition undergoes three distinct stages; namely an initial stage, a transitional stage and a steady state stage. Time dependent features of the coupled thermal boundary layers as well as the overall natural convection flow in the partitioned enclosure have been discussed and compared with the non-partitioned enclosure. Moreover, heat transfer as a form of local and overall average Nusselt number through the coupled thermal boundary layers and the inclined walls is also examined. The details results will be discussed in the full paper.

Interactive axial shortening of columns and walls in high rise buildings

Concrete is commonly used as a primary construction material for tall building construction. Load bearing components such as columns and walls in concrete buildings are subjected to instantaneous and long term axial shortening caused by the time dependent effects of "shrinkage", "creep" and "elastic" deformations. Reinforcing steel content, variable concrete modulus, volume to surface area ratio of the elements and environmental conditions govern axial shortening. The impact of differential axial shortening among columns and core shear walls escalate with increasing building height. Differential axial shortening of gravity loaded elements in geometrically complex and irregular buildings result in permanent distortion and deflection of the structural frame which have a significant impact on building envelopes, building services, secondary systems and the life time serviceability and performance of a building. Existing numerical methods commonly used in design to quantify axial shortening are mainly based on elastic analytical techniques and therefore unable to capture the complexity of non-linear time dependent effect. Ambient measurements of axial shortening using vibrating wire, external mechanical strain, and electronic strain gauges are methods that are available to verify pre-estimated values from the design stage. Installing these gauges permanently embedded in or on the surface of concrete components for continuous measurements during and after construction with adequate protection is uneconomical, inconvenient and unreliable. Therefore such methods are rarely if ever used in actual practice of building construction. This research project has developed a rigorous numerical procedure that encompasses linear and non-linear time dependent phenomena for prediction of axial shortening of reinforced concrete structural components at design stage. This procedure takes into consideration (i) construction sequence, (ii) time varying values of Young's Modulus of reinforced concrete and (iii) creep and shrinkage models that account for variability resulting from environmental effects. The capabilities of the procedure are illustrated through examples. In order to update previous predictions of axial shortening during the construction and service stages of the building, this research has also developed a vibration based procedure using ambient measurements. This procedure takes into consideration the changes in vibration characteristic of structure during and after construction. The application of this procedure is illustrated through numerical examples which also highlight the features. The vibration based procedure can also be used as a tool to assess structural health/performance of key structural components in the building during construction and service life.

Methodological challenges when estimating the effects of season and seasonal exposures on birth outcomes

Background Many previous studies have found seasonal patterns in birth outcomes, but with little agreement about which season poses the highest risk. Some of the heterogeneity between studies may be explained by a previously unknown bias. The bias occurs in retrospective cohorts which include all births occurring within a fixed start and end date, which means shorter pregnancies are missed at the start of the study, and longer pregnancies are missed at the end. Our objective was to show the potential size of this bias and how to avoid it. Methods To demonstrate the bias we simulated a retrospective birth cohort with no seasonal pattern in gestation and used a range of cohort end dates. As a real example, we used a cohort of 114,063 singleton births in Brisbane between 1 July 2005 and 30 June 2009 and examined the bias when estimating changes in gestation length associated with season (using month of conception) and a seasonal exposure (temperature). We used survival analyses with temperature as a time-dependent variable. Results We found strong artificial seasonal patterns in gestation length by month of conception, which depended on the end date of the study. The bias was avoided when the day and month of the start date was just before the day and month of the end date (regardless of year), so that the longer gestations at the start of the study were balanced by the shorter gestations at the end. After removing the fixed cohort bias there was a noticeable change in the effect of temperature on gestation length. The adjusted hazard ratios were flatter at the extremes of temperature but steeper between 15 and 25°C. Conclusions Studies using retrospective birth cohorts should account for the fixed cohort bias by removing selected births to get unbiased estimates of seasonal health effects.

Visualisation of complex flows using texture-based techniques

Complex flow datasets are often difficult to represent in detail using traditional vector visualisation techniques such as arrow plots and streamlines. This is particularly true when the flow regime changes in time. Texture-based techniques, which are based on the advection of dense textures, are novel techniques for visualising such flows (i.e., complex dynamics and time-dependent). In this paper, we review two popular texture-based techniques and their application to flow datasets sourced from real research projects. The texture-based techniques investigated were Line Integral Convolution (LIC), and Image-Based Flow Visualisation (IBFV). We evaluated these techniques and in this paper report on their visualisation effectiveness (when compared with traditional techniques), their ease of implementation, and their computational overhead.

Asset health prediction using the explicit hazard model

The ability to estimate the asset reliability and the probability of failure is critical to reducing maintenance costs, operation downtime, and safety hazards. Predicting the survival time and the probability of failure in future time is an indispensable requirement in prognostics and asset health management. In traditional reliability models, the lifetime of an asset is estimated using failure event data, alone; however, statistically sufficient failure event data are often difficult to attain in real-life situations due to poor data management, effective preventive maintenance, and the small population of identical assets in use. Condition indicators and operating environment indicators are two types of covariate data that are normally obtained in addition to failure event and suspended data. These data contain significant information about the state and health of an asset. Condition indicators reflect the level of degradation of assets while operating environment indicators accelerate or decelerate the lifetime of assets. When these data are available, an alternative approach to the traditional reliability analysis is the modelling of condition indicators and operating environment indicators and their failure-generating mechanisms using a covariate-based hazard model. The literature review indicates that a number of covariate-based hazard models have been developed. All of these existing covariate-based hazard models were developed based on the principle theory of the Proportional Hazard Model (PHM). However, most of these models have not attracted much attention in the field of machinery prognostics. Moreover, due to the prominence of PHM, attempts at developing alternative models, to some extent, have been stifled, although a number of alternative models to PHM have been suggested. The existing covariate-based hazard models neglect to fully utilise three types of asset health information (including failure event data (i.e. observed and/or suspended), condition data, and operating environment data) into a model to have more effective hazard and reliability predictions. In addition, current research shows that condition indicators and operating environment indicators have different characteristics and they are non-homogeneous covariate data. Condition indicators act as response variables (or dependent variables) whereas operating environment indicators act as explanatory variables (or independent variables). However, these non-homogenous covariate data were modelled in the same way for hazard prediction in the existing covariate-based hazard models. The related and yet more imperative question is how both of these indicators should be effectively modelled and integrated into the covariate-based hazard model. This work presents a new approach for addressing the aforementioned challenges. The new covariate-based hazard model, which termed as Explicit Hazard Model (EHM), explicitly and effectively incorporates all three available asset health information into the modelling of hazard and reliability predictions and also drives the relationship between actual asset health and condition measurements as well as operating environment measurements. The theoretical development of the model and its parameter estimation method are demonstrated in this work. EHM assumes that the baseline hazard is a function of the both time and condition indicators. Condition indicators provide information about the health condition of an asset; therefore they update and reform the baseline hazard of EHM according to the health state of asset at given time t. Some examples of condition indicators are the vibration of rotating machinery, the level of metal particles in engine oil analysis, and wear in a component, to name but a few. Operating environment indicators in this model are failure accelerators and/or decelerators that are included in the covariate function of EHM and may increase or decrease the value of the hazard from the baseline hazard. These indicators caused by the environment in which an asset operates, and that have not been explicitly identified by the condition indicators (e.g. Loads, environmental stresses, and other dynamically changing environment factors). While the effects of operating environment indicators could be nought in EHM; condition indicators could emerge because these indicators are observed and measured as long as an asset is operational and survived. EHM has several advantages over the existing covariate-based hazard models. One is this model utilises three different sources of asset health data (i.e. population characteristics, condition indicators, and operating environment indicators) to effectively predict hazard and reliability. Another is that EHM explicitly investigates the relationship between condition and operating environment indicators associated with the hazard of an asset. Furthermore, the proportionality assumption, which most of the covariate-based hazard models suffer from it, does not exist in EHM. According to the sample size of failure/suspension times, EHM is extended into two forms: semi-parametric and non-parametric. The semi-parametric EHM assumes a specified lifetime distribution (i.e. Weibull distribution) in the form of the baseline hazard. However, for more industry applications, due to sparse failure event data of assets, the analysis of such data often involves complex distributional shapes about which little is known. Therefore, to avoid the restrictive assumption of the semi-parametric EHM about assuming a specified lifetime distribution for failure event histories, the non-parametric EHM, which is a distribution free model, has been developed. The development of EHM into two forms is another merit of the model. A case study was conducted using laboratory experiment data to validate the practicality of the both semi-parametric and non-parametric EHMs. The performance of the newly-developed models is appraised using the comparison amongst the estimated results of these models and the other existing covariate-based hazard models. The comparison results demonstrated that both the semi-parametric and non-parametric EHMs outperform the existing covariate-based hazard models. Future research directions regarding to the new parameter estimation method in the case of time-dependent effects of covariates and missing data, application of EHM in both repairable and non-repairable systems using field data, and a decision support model in which linked to the estimated reliability results, are also identified.

The effects of acute exercise-induced cortisol on CCR2 expression on human monocytes

CC-chemokine receptor 2 (CCR2) and its ligand, monocyte chemotactic protein-1 (MCP-1, also known as CCL2), are crucial for the recruitment of monocytes/macrophages to sites of inflammation. We conducted a series of experiments to investigate the relationship between stress, monocyte CCR2 expression and migration activity. First, we collected peripheral blood mononuclear cells (PBMC) from untrained subjects (n=8) and measured CCR2 expression on CD14(+) monocytes cultured with cortisol, epinephrine and norepinephrine. Second, we collected PBMC from the subjects before and after they cycled for 60 min at 70% peak O(2) uptake (VO2(peak)), and measured alterations in CCR2 expression on monocytes following exercise. Third, we cultured PBMC with serum obtained before and after exercise and the glucocorticoid antagonist RU-486 to determine the effect of cortisol on CCR2 expression in vitro. Last, we measured the ability of PBMC treated with serum or cortisol to migrate through membrane filters in response to CCL2. Cortisol (but not epinephrine or norepinephrine) increased CCR2 expression on monocytes in a dose- and time-dependent manner. Exercise did not influence CCR2 expression on PBMC, whereas incubation of PBMC with post-exercise serum significantly increased CCR2 expression. Both cortisol and post-exercise serum increased the migration of PBMC toward CCL2. The increase in CCR2 expression on PBMC following stimulation with cortisol and serum was blocked by the glucocorticoid receptor antagonist RU-486. In conclusion, cortisol released during exercise increased monocyte CCR2 expression and migration activity in vitro. These alterations may influence inflammation and regeneration of damaged tissue after acute stress.

Ruthenium(II) dichloro or dithiocyanato complexes with 4,4′:2′,2″:4″,4‴-quaterpyridinium ligands : towards photosensitisers with enhanced low-energy absorption properties

Fourteen new complexes of the form cis-\[RuIIX2(R2qpy2+)2]4+ (R2qpy2+ = a 4,4′:2′,2″:4″,4‴-quaterpyridinium ligand, X = Cl− or NCS−) have been prepared and isolated as their PF6− salts. Characterisation involved various techniques including 1H NMR spectroscopy and +electrospray or MALDI mass spectrometry. The UV–Vis spectra display intense intraligand π → π∗ absorptions, and also metal-to-ligand charge-transfer (MLCT) bands with two resolved maxima in the visible region. Red-shifts in the MLCT bands occur as the electron-withdrawing strength of the pyridinium groups increases, while replacing Cl− with NCS− causes blue-shifts. Cyclic voltammograms show quasi-reversible or reversible RuIII/II oxidation waves, and several ligand-based reductions that are irreversible. The variations in the redox potentials correlate with changes in the MLCT energies. A single-crystal X-ray structure has been obtained for a protonated form of a proligand salt, \[(4-(CO2H)Ph)2qpyH3+]\[HSO4]3·3H2O. Time-dependent density functional theory calculations give adequate correlations with the experimental UV–Vis spectra for the two carboxylic acid-functionalised complexes in DMSO. Despite their attractive electronic absorption spectra, these dyes are relatively inefficient photosensitisers on electrodes coated with TiO2 or ZnO. These observations are attributed primarily to weak electronic coupling with the surfaces, since the DFT-derived LUMOs include no electron density near the carboxylic acid anchors.

Synthesis of an erodible biomimetic hydrogel for drug delivery using native chemical ligation

Hydrogels are hydrophilic, three dimensional polymers that imbibe large quantities of water while remaining insoluble in aqueous solutions due to chemical or physical cross-linking. The polymers swell in water or biological fluids, immobilizing the bioactive agent, leading to drug release in a well-defined specific manner. Thus the hydrogels’ elastic properties, swellability and biocompatibility make them excellent formulations for drug delivery. Currently, many drug potencies and therapeutic effects are limited or otherwise reduced because of the partial degradation that occurs before the administered drug reaches the desired site of action. On the other hand, sustained release medications release drugs continually, rather than providing relief of symptoms and protection solely when necessary. In fact, it would be much better if drugs could be administered in a manner that precisely matches physiological needs at desired times and at the desired site (site specific targeting). There is therefore an unmet need to develop controlled drug delivery systems especially for delivery of peptide and protein bound drugs. The purpose of this project is to produce hydrogels for structural drug delivery and time-dependent sustained release of drugs (bioactive agents). We use an innovative polymerisation strategy based on native chemical ligation (NCL) to covalently cross-link polymers to form hydrogels. When mixed in aqueous solution, four armed (polyethylene glycol) amine (PEG-4A) end functionalised with thioester and four branched Nterminal cysteine peptide dendrimers spontaneously conjugated to produce biomimetic hydrogels. These hydrogels showed superior resistance to shear stress compared to an equivalent PEG macromonomer system and were shown to be proteolytically degradable with concomitant release of a model payload molecule. This is the first report of a peptide dendrimers/PEG macromonomer approach to hydrogel production and opens up the prospect of facile hydrogel synthesis together with tailored payload release.

Measuring the mechanical properties of ground ophthalmic polymer surfaces using nanoindentation

This work is motivated by the need to efficiently machine the edges of ophthalmic polymer lenses for mounting in spectacle or instrument frames. The polymer materials used are required to have suitable optical characteristics such high refractive index and Abbe number, combined with low density and high scratch and impact resistance. Edge surface finish is an important aesthetic consideration; its quality is governed by the material removal operation and the physical properties of the material being processed. The wear behaviour of polymer materials is not as straightforward as for other materials due to their molecular and structural complexity, not to mention their time-dependent properties. Four commercial ophthalmic polymers have been studied in this work using nanoindentation techniques which are evaluated as tools for probing surface mechanical properties in order to better understand the grinding response of polymer materials.

The acute response of tendon to loading: implications for rehabilitation

Achilles tendinopathy is a common disorder involving physically active and sedentary individuals alike. Although the processes underlying its development are poorly understood, tendinopathy is widely regarded as an ‘overuse’ injury in which the tendon fails to adapt to prevalent loading conditions. Paradoxically, there is emerging evidence that heavy eccentric loading of the Achilles tendon may be an effective conservative approach for treatment of tendinopathy, with success rates of 60–80% reported. Interestingly, loading exercises involving other forms of muscle action, such as concentric activation, have been shown to be less effective treatment options. However, little is known about the acute response of tendon to exercise at present, and there are few plausible explanatory mechanisms for the observed beneficial effects of eccentric exercise, as opposed to other forms of strain stimuli. This paper presents the findings from a series of experiments undertaken to evaluate the effect of various strain stimuli on the time-dependent response of human Achilles tendon in vivo. It was shown for the first time, that heavy resistive ankle plantarflexion/ dorsiflexion exercises induced an immediate and significant decrease in Achilles tendon thickness (~15%). While thickness returned to pre-exercise levels within 24 hours, the recovery was exponential, with primary recovery occurring in less than 6 hours post-exercise. We proposed that such a diametral strain response with tensile loading reflects collagen realignment, Poison’s effects and radial extrusion of water from the tendon core. With unloading, the recovery of tendon dimensions likely reflects the re-diffusion of water via osmotic and/or inflammatory driven processes. Interestingly, prolonged walking was found to induce a similar diametral strain response. In subsequent studies, we demonstrated that eccentric exercise resulted in a greater reduction (-21%) in Achilles tendon thickness than isolated concentric exercise alone (-5%), despite a similar loading impulse. These novel findings, coupled with observations of a reduced diametral strain response with tendon pathology, highlight the importance of fluid movement to tendon function, nutrition and health. They also provide new insights into potential mechanisms underlying Achilles tendinopathy that impact rehabilitation strategies.