Vascular endothelial growth factor (VEGF) is required for the development, growth and survival of blood vessels. Endothelial cell behavior is altered by cell substrate stiffness, suggesting that VEGF activity might also be influenced by cell-substrate mechanics. We studied VEGF binding, internalization, and signaling as a function of substrate stiffness using endothelial cells cultured on fibronectin (fn) linked polyacrylamide gels. Individual cell analysis of VEGF-induced calcium fluxes in endothelial cells on various stiffness extracellular matrices (ECM) revealed heterogeneity in our cell population that would have been lost using population based averaging. Cluster analysis of individual cells identified two key groups of reacting cells- a minor fraction of highly reactive cells and the bulk of the cells with minimal activation. At subsaturating VEGF doses, highly active cells were phenotypically smaller and thinner than the bulk population. Overall, cells on our softest substrates (4 kPa) were most sensitive to VEGF. To better understand the mechanisms underlying the changes in VEGF signaling due to stiffness, we explored how matrix binding of VEGF and tethering of cells to the matrix modulates VEGF processing. VEGF-ECM binding was enhanced with heparin pre-treatment, which exposed a cryptic VEGF binding site in the fn ECM. Cell produced ECM on the softest substrates were least responsive to heparin, but the cells internalized more VEGF and showed enhanced VEGF signaling compared to cells on all other substrates. Inhibiting VEGF-matrix binding with sucrose octasulfate decreased cell-internalization of VEGF in all conditions. β1 integrin, which connects cells to fn, modulated VEGF uptake in a stiffness dependent fashion. β1 protein levels were consistent with stiffness, yet cells on hard surfaces showed greater decreases in VEGF internalization than cells on softer matrices after β1 inhibition. Stiff matrices facilitate the unfolding of fn, which may reduce the binding capacity of β1 integrin. Thus a greater proportion of activated β1 integrin may be sensitive to inhibition in the stiff condition as compared to the soft. Ultimately, through analysis of individual and population-based VEGF-cell responses to stiffness, this study provides insight into how signaling dynamics, cell heterogeneity, and microenvironment influence tissue regeneration and response to injury and disease.

yes / This paper presents an experimental study on shear strength, stiffness and ductility of demountable shear connectors in metal decking composite slabs through push-off tests. Twelve full-scale push-off tests were carried out using different concrete strength, number of connectors and different connector diameter. The experimental results showed that the demountable shear connectors in metal decking composite slabs have similar shear capacity and behaviour as welded shear studs and fulfilled the minimum ductility requirement of 6mm required by Eurocode 4. The shear capacity was compared against the prediction methods used for the welded shear connections given in Eurocode 4, AISC 360-10, ACI 318-08 and method used for bolted connection in Eurocode 3. It was found that the AISC 360-10 method overestimated the shear capacity while the ACI 318-08 method underestimated the shear capacity of specimens with single shear connector per trough. The Eurocodes method was found to provide a safe prediction for specimens with single and pair demountable connectors per trough. In addition, prediction methods given in both AISC 360-10 and ACI 318-08 for welded shear studs overestimated the shear capacity of specimens with 22 mm diameter demountable connectors that failed in concrete crushing. / PhD work from EPSRC studentship

Yes / Extensive experimental and theoretical studies have been conducted on the compressive strength of concrete-filled steel tubular (CFST) columns, but little attention has been paid to their compressive stiffness and deformation capacity. Despite this, strength prediction approaches in existing design codes still have various limitations. A finite element model, which was previously proposed by the authors and verified using a large amount of experimental data, is used in this paper to generate simulation data covering a wide range of parameters for circular and rectangular CFST stub columns under axial compression. Regression analysis is conducted to propose simplified models to predict the compressive strength, the compressive stiffness, and the compressive strain corresponding to the compressive strength (ductility) for the composite columns. Based on the new strength prediction model, the capacity reduction factors for the steel and concrete materials are recalibrated to achieve a target reliability index of 3.04 when considering resistance effect only.

Cardiovascular diseases (CVDs) remain the leading cause of death worldwide. Patients at risk of evolving CVDs are assessed by evaluating a risk factor-based score that incorporates different bio-markers ranging from age and sex to arterial stiffness (AS). AS depicts the rigidity of the arterial vessels and leads to an increase in the arterial pulse pressure, affecting the heart and vascular physiology. These facts have encouraged researchers to propose surrogate markers of cardiovascular risks and develop simple and non-invasive models to better understand cardiovascular system operations. This work thus fundamentally capitalizes on developing a novel class of low-dimensional physics-based fractional-order models of systemic arteries and exploring the feasibility of fractional differentiation order to portray the vascular stiffness. Fractional-order modeling is a successful paradigm to integrate multiscale and interconnected mechanisms of the complex arterial system. However, this type of modeling alone often fails to efficiently integrate altered variabilities in vascular physiology from various sources of large datasets, multi-modalities, and levels. In this regard, combining fractional-order-based approaches with machine learning techniques presents a unique opportunity to develop a powerful prediction framework that reveals the correlation between intertwined vascular events. This work is divided into three parts. The first part contributes to developing the fractional-order lumped parametric model of the arterial system. First, we propose fractional-order representations to model and characterize the complex and frequency-dependent apparent arterial compliance. Second, we propose fractional-order arterial Windkessel modeling the aortic input impedance and hemodynamic. Subsequently, the proposed models have been applied and validated using both human in-silico healthy datasets and real vascular aging and hypertension. The second part addresses the non-zero initial value problem for fractional differential equations (FDEs) and proposes an estimation technique for joint estimation of the input, parameters, and fractional differentiation order of non-commensurate FDEs. The performance of the proposed estimation techniques is illustrated on arterial and neurovascular hemodynamic response models. The third part explores the feasibility of using machine learning algorithms to estimate the gold-standard measurement of AS, carotid-to-femoral pulse wave velocity. Different modalities have been investigated to generate informative input features and reduce the dimensionality of the time series pulse waves.

There has been a prevalence of long-distance running footwear incorporating carbon-fiber plates within their midsoles, effectively increasing their longitudinal bending stiffness (LBS). This modification of modern racing footwear has occurred concurrently with large improvements in running times (Bermon et al., 2021), putting into question how these footwear components affect performance (Muniz-Pardos et al., 2021). The current literature has investigated this at level running, but with the increasing popularity of trail running, it is of interest to investigate whether the benefits found during level running translate to graded running. Therefore, the overall aim of this study was to investigate the effects of increased footwear midsole longitudinal bending stiffness (i.e. carbon-fiber plates) on running energetics and biomechanics at various inclines. The effects of high LBS (Nike Vaporfly 4% with midsole intact) and low LBS (Nike Vaporfly 4% with mediolateral cuts made at the forefoot of the midsole through the carbon-fiber plate) footwear conditions were compared for running at 0°, 6°, and 12° inclines. Running energetics and biomechanics data were quantified by measuring metabolic rate and lower leg joint mechanics (from motion capture and ground reaction force measurements). Results from this study suggest that increasing longitudinal bending stiffness within the footwear midsoles has limited influence on running energetics (small non-significant improvements of metabolic power at all inclines), but has considerable effects on the biomechanics of the ankle and MTP joints. However, the most important between shoe differences were independent of grade, suggesting that the benefits of modern racing shoe observed for level running can be expected to translate to steep uphill running. Nevertheless, it should be noted that this study was only able to collect and use data for analysis from a limited number of participants (n=7), and therefore is underpowered, so there may be significant differences that go undetected

För att nå de Globala målen 2030 kommer vi som samhälle att behöva minska vårt globala ekologiska fotavtryck avsevärt. Textilbranschen står idag för en betydande del av detta ekologiska fotavtryck både genom markanvändning, klimatpåverkande utsläpp, förorening av mark och vatten med mera. Detta har lett till att man inom textilbranschen idag efterfrågar allt mera hållbara lösningar. Det finns ett antal sorters garn som bidrar med lägre miljöpåverkan på olika sätt, dock förekommer dessa idag mindre frekvent på marknaden. Dessa material skulle kunna vara en del av lösningen på textilindustrins stora miljöpåverkan idag. Ett av dessa material som vi valt att titta närmare på var pappersgarn, som vid framställning förbrukar betydligt mindre resurser som vatten, tillsatskemikalier och energi (Fakirov 2015). Pappersgarnets utveckling har dock än så länge begränsats av dess styvhet och dåliga stickbarhet. Detta projektetet har syftat till att försöka minska pappersgarnets styvhet och öka dess stickbarhet genom att tvinna det med olika antal garnsnodd av viskosgarn. Vi tvinnade ett entrådigt 17 tex hampaviskosgarn på 100, 300 och 500 garnsnodd/meter med kärnspunnen metoden. Sedan behandlades garnet med fettsyra för att motverka sprödheten och förbereda för stickning. Garnet stickades på en rundstickmaskin med bindningen slätstickning. Tester som gjordes på garn var dragprovning och friktion. På trikån utfördes också dragprovning(bristning) men även styvhetsprovning samt nötningsprovning. Trikå av blandgarn visades sig tillföra mjukare känsla på tyget jämfört med endast papper. Vid dragprovning av trikå framkom det att större andel av viskos tillför mer styrka i och med att det behövdes högre tryck samt tid för att uppnå brott på trikån. Tvinning med olika antal garnsnodd av viskosgarn har visat sig medföra små skillnader gällande stickbarhet då det tidvis uppstod hål på de fyra olika tyger som stickades under stickningsprocessen. Garner av 300- och 500 garnsnodd/meter hade dock flest svaga punkter (brott på pappersgarnet) utan att uppvisa synbara hål på tyget. Skillnader i styvhet av trikån var kännbara mellan alla tygen, dock gick det inte att få användbara resultat från styvhetsprovaren då denna testmetod var olämplig för den valda trikåbindningen eftersom tyget rullade sig. / To achieve the Global Goals 2030, we as a society will need to significantly reduce our global ecological footprint. The textile industry of today accounts for a significant part of this ecological footprint both through use of land, climate-affecting emissions, soil- and water pollution and more. This has led to an increasing demand for more sustainable solutions in the textile industry. There are a number of types of yarn that have a lower environmental impact. Many of them however have quite a lower market share today. One of these materials that we chose to take a closer look at was paper yarn, which in it’s production consumes significantly less resources than other usual yarns on the market (Fakirov 2015). However, the development of use of paper yarn has so far been limited by its rigidity and poor knitability. This project has aimed to try to reduce the stiffness of the paper yarn and increase its knitability. This was done by twisting different numbers of twist/meter of viscose yarn, around the paper yarn. We twisted a single-threaded 17 tex hemp viscose yarn around the paper yarn at 100, 300 and 500 twist/meter with the core-spun method. Then the yarn was treated with fatty acid to counteract the brittleness and prepare it for knitting. The yarn was knitted on a circular knitting machine with a single jersey stitch. Tests done on yarn were tensile testing and friction testing. The tricot also was subjected to tensile testing (rupture), stiffness testing and abrasion testing. Viscose mixed yarn knitwear was found to have a softer feeling of the fabric compared to just knitted paper yarn. During tensile testing of tricot, it was found that a larger proportion of viscose adds more strength as higher pressure was needed as well as time to achieve a stretch in the tricot. Twisting with different twists of viscose yarn has been shown to cause small differences in knitability as there were occasional holes in the paper yarn knit during the knitting process. Yarns of 300 and 500 twist/meter, however, had the most weak points without showing visible holes on the fabric. Differences in the stiffness of the tricot were noticeable between all the fabrics, however, it was not possible to obtain useful results from the stiffness tester as this test method was probably unsuitable for the selected tricot binding because the fabric rolled.

In order to remain competitive in the marketplace, all motor vehicle manufacturers face difficult decisions with regard to balancing cost vs. feature. That is to say that the manufacturer must balance the cost of the product to the customer to remain competitive whilst offering appropriate technology and standard features required by that customer. All motor manufacturers are therefore under pressure to keep costs of nonfeature items to a minimum. One of the cost reductions items prevalent on most vehicles is the deletion of the structural member that attaches the rear bumper, known as the bumper beam (RBB), which is researched in this Thesis. This generates average vehicle savings of $20 and, as this is invisible to the customer, should enable the manufacturers to realise a significant saving or allow this revenue to be spent on additional feature without loss of vehicle function. However, in nearly all cases, deletion of the rear bumper beam has the effect of degrading the steering responses of the vehicle by 1 to 1½ rating points (out of 10), which is contrary to the premise of cost reductions; which is to ensure that vehicle function is unaffected. Initial analysis of vehicles with deleted rear bumper beams cannot show an objective measurable difference in any vehicle behaviours with or without the beam fitted, and hence CAE studies using ADAMS models cannot verify the effects of the bumper beam. It was necessary to employ unconventional modelling and testing methods such as rigid body, flexible body model techniques as well as experimental studies included driving robots and expert driver appraisals. The research demonstrated that vehicle modelling methods currently used, cannot establish or predict the complete vehicle ride and handling status. A total vehicle model approach should be used without separating the body CAE model and vehicle dynamics ADAMS model into separate entities. Furthermore, it was concluded that the determination to the effects of body hysteresis rather than pure stiffness is of crucial importance and that the steering attribute could be maintained with the deletion of the RBB analytically.

Concrete-filled tubular (CFT) columns have been widely adopted in building structures owing to their superior structural performance, such as enhanced load bearing capacity, compared to hollow tubes. Circular, square and rectangular hollow sections are most commonly used in the past few decades. Elliptical hollow section (EHS) available recently is regarded as a new cross-section for the CFT columns due to its attractive appearance, optional orientation either on major axis or minor axis and improved structural efficiency. The state of the research in terms of elliptical columns, tubular joints between EHSs and connections with CFT columns, etc., are reviewed in this thesis, showing a lack of investigations on EHSs, especially on beam to elliptical column connections which are essential in framed structures. The structural behaviour of elliptical column to I-beam connections under bending is studied in this thesis to fill the research gap. Overall ten specimens with various joint assemblies were tested to failure to highlight the benefits of adopting concrete infill and stiffeners in the columns. A three-dimensional finite element model developed by using ABAQUS software is presented and verified against obtained experimental results, which shows acceptable accuracy and reliability in predicting failure modes of the connections and their moment capacities. Parametric studies were performed to access the main parameters that affecting the bending behaviour of the connections. A simple hand calculation method in terms of ultimate moment capacity is proposed according to experiments conducted for connections with concrete-filled columns.

Robotic surgery procedures may include long, thin flexible instruments that are inserted by the robot into the patient. As the robot inserts these devices, due to their geometry, they are prone to buckling failure. To mitigate buckling failure, a support system is needed on the robot. This system supports the device but also adapts to the varying ex vivo length of the device as it is inserted. This work presents four collapsible support systems designed to mitigate buckling failure of long, thin instruments while accounting for changing length. The Ori-Guide is an origami-inspired system that has enabled a part reduction from traditional rigid systems with over 70 parts to 3 parts. This system was enabled through the development of a novel origami pattern that integrates both actuation and support into the same pattern. This system was made from PET and performed as well as a rigid system. The PET used in the Ori-Guide was thermo-processed to hold a folded shape. The heat treatment put the Ori-Guide into tension and enabled a stiffer support system. Work was done to investigate the effect of thermo-processing on PET films used in origami-inspired engineering applications. It was discovered that there is a strong correlation between crystallization and the stiffness of a crease in the polymer film. The Zipper-Tube Reinforcement (ZTR) was developed to provide constant support along the entire length of the device, something that no other support device provides. This enables higher loads on the device and thinner and more flexible devices. It was developed as a tube that envelopes the device and zips to provide a tube to support the device then unzips to lay flat rolled about a mandrel for storage. The Wires in Tension concept was developed by focusing on adding tension to the support system. It provided support to the device but required high levels of force on the robot arm so the Orthogonal Beams was developed. The Orthogonal Beams employs geometry as the primary support rather than tension and therefore could provide higher support with less force on the robot. These systems all proved effective ways to support flexible devices. The concepts could also find application in other fields. The merits of each system are discussed in detail, including a discussion on other possible applications.

Perivascular adipose (PVAT) has been hypothesized to influence arterial health, where an excess can lead to pathogenesis of atherosclerosis and other arterial pathologies. A novel assessment of carotid PVAT is the use of carotid extra media thickness (EMT) ultrasonography. Currently, there is a lack of research to demonstrate the relationship between carotid EMT and existing measures of arterial health, notably, central pulse wave velocity, and carotid distensibility and intimal media thickness. In the current cross sectional study, 81 participants of younger recreationally active (ages 23.2 ± 2.5 years), younger sedentary (ages 26.4 ± 7.2 years), older healthy (ages 70.3 ± 5.4 years) and older adults with coronary artery disease (CAD) (ages 67.9 ± 8.7 years) were recruited. Resting measures of central arterial stiffness was examined through the assessment of aPWV, while measures of local carotid stiffness were examined through carotid distensibility. Aortic PWV was calculated using an accepted direct distance method (80% of carotid to femoral direct distance) and time difference between the feet of the carotid and femoral waveforms. Carotid intima-media thickness (IMT), a measure of the inner arterial walls, and carotid extra media thickness (EMT), a measure of carotid PVAT, were assessed through B-mode ultrasound images and a semi-automated edge tracking software. Carotid EMT, IMT, and aPWV were significantly greater in older adults than in younger adults (p < 0.05). No difference in carotid EMT was found between younger recreationally active (0.47 ± .08 mm) and sedentary adults (0.46 ± .06 mm). There were also no differences in carotid EMT between the older healthy (0.58 ± .06 mm) and older adults with CAD (0.54 ± 0.08 mm). Carotid EMT was also significantly correlated with age (r =0 .500), waist circumference (r = 0.521), aPWV (r =0.431), carotid distensibility (r = -0.364 and IMT (r = 0.404). Despite significant correlations, carotid EMT was not an independent predictor of aPWV, carotid distensibility and IMT. Because of the lack of predictive power in measures of arterial stiffness and carotid IMT, there is a potential that carotid EMT may be an independent vascular disease marker. Future investigations should involve carotid EMT in longitudinal studies to evaluate the potential marker for a more comprehensive cardiovascular risk assessment. / Thesis / Master of Science (MSc)