A comparison of submicrometer particle dose between Australian and Italian people

Alveolar and tracheobronchial-deposited submicrometer particle number and surface area data received by different age groups in Australia are shown. Activity patterns were combined with microenvironmental data through a Monte-Carlo method. Particle number distributions for the most significant microenvironments were obtained from our measurement survey data and people activity pattern data from the Australian Human Activity Pattern Survey were used. Daily alveolar particle number (surface area) dose received by all age groups was equal to 3.0×1010 particles (4.5×102 mm2), varying slightly between males and females. In contrast to gender, the lifestyle was found to significantly affect the daily dose, with highest depositions characterizing adults. The main contribution was due to indoor microenvironments. Finally a comparison between Italian and Australian people in terms of received particle dose was reported; it shows that different cooking styles can affect dose levels: higher doses were received by Italians, mainly due to their particular cooking activity.

Differential expression and distribution of syndecan-1 and -2 in periodontal wound healing of the rat

Cell-surface proteoglycans participate in several biological functions including interactions with adhesion molecules, growth factors and a variety of other effector molecules. Accordingly, these molecules play a central role in various aspects of cell–cell and cell–matrix interactions. To investigate the expression and distribution of the cell surface proteoglycans, syndecan-1 and -2, during periodontal wound healing, immunohistochemical analyses were carried out using monoclonal antibodies against syndecan-1, or -2 core proteins. Both syndecan-1 and -2 were expressed and distributed differentially at various stages of early inflammatory cell infiltration, granulation tissue formation, and tissue remodeling in periodontal wound healing. Expression of syndecan-1 was noted in inflammatory cells within and around the fibrin clots during the earliest stages of inflammatory cell infiltration. During granulation tissue formation it was noted in fibroblast-like cells and newly formed blood vessels. Syndecan-1 was not seen in newly formed bone or cementum matrix at any of the time periods studied. Syndecan-1 expression was generally less during the late stages of wound healing but was markedly expressed in cells that were close to the repairing junctional epithelium. In contrast, syndecan-2 expression and distribution was not evident at the early stages of inflammatory cell infiltration. During the formation of granulation tissue and subsequent tissue remodeling, syndecan-2 was expressed extracellularly in the newly formed fibrils which were oriented toward the root surface. Syndecan-2 was found to be significantly expressed on cells that were close to the root surface and within the matrix of repaired cementum covering root dentin as well as at the alveolar bone edge. These findings indicate that syndecan-1 and -2 may have distinctive functions during wound healing of the periodontium. The appearance of syndecan-1 may involve both cell–cell and cell–matrix interactions, while syndecan-2 showed a predilection to associate with cell–matrix interactions during hard tissue formation.

Individual dose and exposure of Italian children to ultrafine particles

Time-activity patterns and the airborne pollutant concentrations encountered by children each day are an important determinant of individual exposure to airborne particles. This is demonstrated in this work by using hand-held devices to measure the real-time individual exposure of more than 100 children aged 8-11 years to particle number concentrations and average particle diameter, as well as alveolar and tracheobronchial deposited surface area concentration. A GPS-logger and activity diaries were also used to give explanation to the measurement results. Children were divided in three sample groups: two groups comprised of urban schools (school time from 8:30 am to 1:30 pm) with lunch and dinner at home, and the third group of a rural school with only dinner at home. The mean individual exposure to particle number concentration was found to differ between the three groups, ranging from 6.2×104 part. cm-3 for children attending one urban school to 1.6×104 part. cm-3 for the rural school. The corresponding daily alveolar deposited surface area dose varied from about 1.7×103 mm2 for urban schools to 6.0×102 mm2 for the rural school. For all of the children monitored, the lowest particle number concentrations are found during sleeping time and the highest were found during eating time. With regard to alveolar deposited surface area dose, a child's home was the major contributor (about 70%), with school contributing about 17% for urban schools and 27% for the rural school. An important contribution arises from the cooking/eating time spent at home, which accounted for approximately 20% of overall exposure, corresponding to more than 200 mm2. These activities represent the highest dose received per time unit, with very high values also encountered by children with a fireplace at home, as well as those that spend considerable time stuck in traffic jams.

Measurements of particle emissions from nanotechnology processes, with assessment of measuring techniques and workplace controls

The overall aim of this project was to contribute to existing knowledge regarding methods for measuring characteristics of airborne nanoparticles and controlling occupational exposure to airborne nanoparticles, and to gather data on nanoparticle emission and transport in various workplaces. The scope of this study involved investigating the characteristics and behaviour of particles arising from the operation of six nanotechnology processes, subdivided into nine processes for measurement purposes. It did not include the toxicological evaluation of the aerosol and therefore, no direct conclusion was made regarding the health effects of exposure to these particles. Our research included real-time measurement of sub, and supermicrometre particle number and mass concentration, count median diameter, and alveolar deposited surface area using condensation particle counters, an optical particle counter, DustTrak photometer, scanning mobility particle sizer, and nanoparticle surface area monitor, respectively. Off-line particle analysis included scanning and transmission electron microscopy, energy-dispersive x-ray spectrometry, and thermal optical analysis of elemental carbon. Sources of fibrous and non-fibrous particles were included.

Signal patterns of piston slap of a four-cylinder diesel engine

This paper presents an experimental study on the vibration signal patterns associated with a simulated piston slap test of a four-cylinder diesel engine. It is found that a simulated worn-off piston results in an increase in vibration RMS peak amplitudes associated with the major mechanical events of the corresponding cylinder (i.e., inlet and exhaust valve closing and combustion of Cylinder 1). This then led to an increase of overall vibration amplitude of the time domain statistical features such as RMS, Crest Factor, Skewness and Kurtosis in all loading conditions. The simulated worn-off piston not only increased the impact amplitude of piston slap during the engine combustion, it also produced a distinct impulse response during the air induction stroke of the cylinder attributing to an increase of lateral impact force as a result of piston reciprocating motion and the increased clearance between the worn-off piston and the cylinder. The unique signal patterns of piston slap disclosed in this paper can be utilized to assist in the development of condition monitoring tools for automated diagnosis of similar diesel engine faults in practical applications.

Effect of body position on measurements of diffusion capacity after exercise

Background--Pulmonary diffusing capacity for carbon monoxide (Dlco), alveolar capillary membrane diffusing capacity (Dm), and pulmonary capillary blood volume (Vc) are all significantly reduced after exercise. Objective--To investigate whether measurement position affects this impaired gas transfer. Methods--Before and one, two, and four hours after incremental cycle ergometer exercise to fatigue, single breath Dlco, Dm, and Vc measurements were obtained in 10 healthy men in a randomly assigned supine and upright seated position. Results--After exercise, Dlco, Dm, and Vc were significantly depressed compared with baseline in both positions. The supine position produced significantly higher values over time for Dlco (5.22 (0.13) v 4.66 (0.15) ml/min/mm Hg/l, p = 0.022) and Dm (6.78 (0.19) v 6.03 (0.19) ml/min/mm Hg/l, p = 0.016), but there was no significant position effect for Vc. There was a similar pattern of change over time for Dlco, Dm, and Vc in the two positions. Conclusions--The change in Dlco after exercise appears to be primarily due to a decrease in Vc. Although the mechanism for the reduction in Vc cannot be determined from these data, passive relocation of blood to the periphery as the result of gravity can be discounted, suggesting that active vasoconstriction of the pulmonary vasculature and/or peripheral vasodilatation is occurring after exercise.

Polycaprolactone-based scaffold plus recombinant human bone morphogenic protein rhBMP-2) in a sheep thoracic spine fusion model

Adolescent idiopathic scoliosis is a complex three dimensional deformity affecting 2-3% of the general population. The resulting spinal deformity consists of coronal curvature, hypokyphosis of the thoracic spine and vertebral rotation in the axial plane with posterior elements turned into the curve concavity. The potential for curve progression is heightened during the adolescent growth spurt. Success of scoliosis deformity correction depends on solid bony fusion between adjacent vertebrae after the intervertebral (IV) discs have been surgically cleared and the disc spaces filled with graft material. Recently a bioactive and resorbable scaffold fabricated from medical grade polycaprolactone has been developed for bone regeneration at load bearing sites. Combined with rhBMP-2, this has been shown to be successful in acting as a bone graft substitute in a porcine lumbar interbody fusion model when compared to autologous bone graft alone. The study aimed to establish a large animal thoracic spine interbody fusion model, develop spine biodegradable scaffolds (PCL) in combination with biologics (rhBMP-2) and to establish a platform for research into spine tissue engineering constructs. Preliminary results demonstrate higher grades of radiologically evident bony fusion across all levels when comparing fusion scores between the 3 and 6 month postop groups at the PCL CaP coated scaffold level, which is observed to be a similar grade to autograft, while no fusion is seen at the scaffold only level. Results to date suggest that the combination of rhBMP-2 and scaffold engineering actively promotes bone formation, laying the basis of a viable tissue engineered constructs.

Biomechanical performance of polycaprolactone (PCL)-based scaffold with rhBMP-2 in a sheep thoracic spine fusion model

Adolescent idiopathic scoliosis is a complex three dimensional deformity affecting 2-3% of the general population. Resulting spine deformities include progressive coronal curvature, hypokyphosis, or frank lordosis in the thoracic spine and vertebral rotation in the axial plane with posterior elements turned into the curve concavity. The potential for curve progression is heightened during the adolescent growth spurt. Success of scoliosis deformity correction depends on solid bony fusion between adjacent vertebrae after the intervertebral discs have been surgically cleared and the disc spaces filled with graft material. Problems with bone graft harvest site morbidity as well as limited bone availability have led to the search for bone graft substitutes. Recently, a bioactive and resorbable scaffold fabricated from medical grade polycaprolactone (PCL) has been developed for bone regeneration at load bearing sites. Combined with recombinant human bone morphogenic protein–2 (rhBMP-2), this has been shown to be successful in acting as a bone graft substitute in acting as a bone graft substitute in a porcine lumbar interbody fusion model when compared to autologous bone graft. This in vivo sheep study intends to evaluate the suitability of a custom designed medical grade PCL scaffold in combination with rhBMP-2 as a bone graft substitute in the setting of mini–thoracotomy surgery as a platform for ongoing research to benefit patients with adolescent idiopathic scoliosis.

The ionic products from bredigite bioceramics induced cementogenic differentiation of periodontal ligament cells via activation of the Wnt/β-catenin signalling pathway

Periodontitis results from the destructive inflammatory reaction of the host elicited by a bacterial biofilm adhering to the tooth surface and if left untreated, may lead to the loss of the teeth and the surrounding tissues, including the alveolar bone. Cementum is a specialized calcified tissue covering the tooth root and an essential part of the periodontium which enables the attachment of the periodontal ligament to the root and the surrounding alveolar bone. Periodontal ligament cells (PDLCs) represent a promising cell source for periodontal tissue engineering. Since cementogenesis is the critical event for the regeneration of periodontal tissues, this study examined whether inorganic stimuli derived from bioactive bredigite (Ca7MgSi4O16) bioceramics could stimulate the proliferation and cementogenic differentiation of PDLCs, and further investigated the involvement of the Wnt/β-catenin signalling pathway during this process via analysing gene/protein expression of PDLCs which interacted with bredigite extracts. Our results showed that the ionic products from bredigite powder extracts led to significantly enhanced proliferation and cementogenic differentiation, including mineralization–nodule formation, ALP activity and a series of bone/cementum-related gene/protein expression (ALP, OPN, OCN, BSP, CAP and CEMP1) of PDLCs in a concentration dependent manner. Furthermore, the addition of cardamonin, a Wnt/β-catenin signalling inhibitor, reduced the pro-cementogenesis effect of the bredigite extracts, indicating the involvement of the Wnt/β-catenin signalling pathway in the cementogenesis of PDLCs induced by bredigite extracts. The present study suggests that an entirely inorganic stimulus with a specific composition of bredigite bioceramics possesses the capacity to trigger the activation of the Wnt/β-catenin signalling pathway, leading to stimulated differentiation of PDLCs toward a cementogenic lineage. The results indicate the therapeutic potential of bredigite ceramics in periodontal tissue engineering application.

The use of electronic portal imaging to verify patient position during intensity-modulated radiotherapy delivered by the dynamic MLC technique

Purpose: The precise shape of the three-dimensional dose distributions created by intensity-modulated radiotherapy means that the verification of patient position and setup is crucial to the outcome of the treatment. In this paper, we investigate and compare the use of two different image calibration procedures that allow extraction of patient anatomy from measured electronic portal images of intensity-modulated treatment beams. Methods and Materials: Electronic portal images of the intensity-modulated treatment beam delivered using the dynamic multileaf collimator technique were acquired. The images were formed by measuring a series of frames or segments throughout the delivery of the beams. The frames were then summed to produce an integrated portal image of the delivered beam. Two different methods for calibrating the integrated image were investigated with the aim of removing the intensity modulations of the beam. The first involved a simple point-by-point division of the integrated image by a single calibration image of the intensity-modulated beam delivered to a homogeneous polymethyl methacrylate (PMMA) phantom. The second calibration method is known as the quadratic calibration method and required a series of calibration images of the intensity-modulated beam delivered to different thicknesses of homogeneous PMMA blocks. Measurements were made using two different detector systems: a Varian amorphous silicon flat-panel imager and a Theraview camera-based system. The methods were tested first using a contrast phantom before images were acquired of intensity-modulated radiotherapy treatment delivered to the prostate and pelvic nodes of cancer patients at the Royal Marsden Hospital. Results: The results indicate that the calibration methods can be used to remove the intensity modulations of the beam, making it possible to see the outlines of bony anatomy that could be used for patient position verification. This was shown for both posterior and lateral delivered fields. Conclusions: Very little difference between the two calibration methods was observed, so the simpler division method, requiring only the single extra calibration measurement and much simpler computation, was the favored method. This new method could provide a complementary tool to existing position verification methods, and it has the advantage that it is completely passive, requiring no further dose to the patient and using only the treatment fields.

Cell migration and proliferation on homogeneous and non-homogeneous domains : modelling on the scale of individuals and populations

Cell migration is a behaviour critical to many key biological effects, including wound healing, cancerous cell invasion and morphogenesis, the development of an organism from an embryo. However, given that each of these situations is distinctly different and cells are extremely complicated biological objects, interest lies in more basic experiments which seek to remove conflating factors and present a less complex environment within which cell migration can be experimentally examined. These include in vitro studies like the scratch assay or circle migration assay, and ex vivo studies like the colonisation of the hindgut by neural crest cells. The reduced complexity of these experiments also makes them much more enticing as problems to mathematically model, like done here. The primary goal of the mathematical models used in this thesis is to shed light on which cellular behaviours work to generate the travelling waves of invasion observed in these experiments, and to explore how variations in these behaviours can potentially predict differences in this invasive pattern which are experimentally observed when cell types or chemical environment are changed. Relevant literature has already identified the difficulty of distinguishing between these behaviours when using traditional mathematical biology techniques operating on a macroscopic scale, and so here a sophisticated individual-cell-level model, an extension of the Cellular Potts Model (CPM), is been constructed and used to model a scratch assay experiment. This model includes a novel mechanism for dealing with cell proliferations that allowed for the differing properties of quiescent and proliferative cells to be implemented into their behaviour. This model is considered both for its predictive power and used to make comparisons with the travelling waves which result in more traditional macroscopic simulations. These comparisons demonstrate a surprising amount of agreement between the two modelling frameworks, and suggest further novel modifications to the CPM that would allow it to better model cell migration. Considerations of the model’s behaviour are used to argue that the dominant effect governing cell migration (random motility or signal-driven taxis) likely depends on the sort of invasion demonstrated by cells, as easily seen by microscopic photography. Additionally, a scratch assay simulated on a non-homogeneous domain consisting of a ’fast’ and ’slow’ region is also used to further differentiate between these different potential cell motility behaviours. A heterogeneous domain is a novel situation which has not been considered mathematically in this context, nor has it been constructed experimentally to the best of the candidate’s knowledge. Thus this problem serves as a thought experiment used to test the conclusions arising from the simulations on homogeneous domains, and to suggest what might be observed should this non-homogeneous assay situation be experimentally realised. Non-intuitive cell invasion patterns are predicted for diffusely-invading cells which respond to a cell-consumed signal or nutrient, contrasted with rather expected behaviour in the case of random-motility-driven invasion. The potential experimental observation of these behaviours is demonstrated by the individual-cell-level model used in this thesis, which does agree with the PDE model in predicting these unexpected invasion patterns. In the interest of examining such a case of a non-homogeneous domain experimentally, some brief suggestion is made as to how this could be achieved.

Fractional models for the migration of biological cells in complex spatial domains

Travelling wave phenomena are observed in many biological applications. Mathematical theory of standard reaction-diffusion problems shows that simple partial differential equations exhibit travelling wave solutions with constant wavespeed and such models are used to describe, for example, waves of chemical concentrations, electrical signals, cell migration, waves of epidemics and population dynamics. However, as in the study of cell motion in complex spatial geometries, experimental data are often not consistent with constant wavespeed. Non-local spatial models have successfully been used to model anomalous diffusion and spatial heterogeneity in different physical contexts. In this paper, we develop a fractional model based on the Fisher-Kolmogoroff equation and analyse it for its wavespeed properties, attempting to relate the numerical results obtained from our simulations to experimental data describing enteric neural crest-derived cells migrating along the intact gut of mouse embryos. The model proposed essentially combines fractional and standard diffusion in different regions of the spatial domain and qualitatively reproduces the behaviour of neural crest-derived cells observed in the caecum and the hindgut of mouse embryos during in vivo experiments.

Health effects of daily airborne particle dose in children : direct association between personal dose and respiratory health effects

Air pollution is a widespread health problem associated with respiratory symptoms. Continuous exposure monitoring was performed to estimate alveolar and tracheobronchial dose, measured as deposited surface area, for 103 children and to evaluate the long-term effects of exposure to airborne particles through spirometry, skin prick tests and measurement of exhaled nitric oxide (eNO). The mean daily alveolar deposited surface area dose received by children was 1.35×103 mm2. The lowest and highest particle number concentrations were found during sleeping and eating time. A significant negative association was found between changes in pulmonary function tests and individual dose estimates. Significant differences were found for asthmatics, children with allergic rhinitis and sensitive to allergens compared to healthy subjects for eNO. Variation is a child’s activity over time appeared to have a strong impact on respiratory outcomes, which indicates that personal monitoring is vital for assessing the expected health effects of exposure to particles.

Repeated intrauterine exposures to inflammatory stimuli attenuated transforming growth factor-β signaling in the ovine fetal lung

Background: Bronchopulmonary dysplasia (BPD) is one of the most common complications after preterm birth and is associated with intrauterine exposure to bacteria. Transforming growth factor-β (TGFβ) is implicated in the development of BPD. Objectives: We hypothesized that different and/or multiple bacterial signals could elicit divergent TGFβ signaling responses in the developing lung. Methods: Time-mated pregnant Merino ewes received an intra-amniotic injection of lipopolysaccharide (LPS) and/or Ureaplasma parvum serovar 3 (UP) at 117 days' and/or 121/122 days' gestational age (GA). Controls received an equivalent injection of saline and or media. Lambs were euthanized at 124 days' GA (term = 150 days' GA). TGFβ1, TGFβ2, TGFβ3, TGFβ receptor (R)1 and TGFβR2 protein levels, Smad2 phosphorylation and elastin deposition were evaluated in lung tissue. Results: Total TGFβ1 and TGFβ2 decreased by 24 and 51% after combined UP+LPS exposure, whereas total TGFβ1 increased by 31% after 7 days' LPS exposure but not after double exposures. Alveolar expression of TGFβR2 decreased 75% after UP, but remained unaltered after double exposures. Decreased focal elastin deposition after single LPS exposure was prevented by double exposures. Conclusions: TGFβ signaling components and elastin responded differently to intrauterine LPS and UP exposure. Multiple bacterial exposures attenuated TGFβ signaling and normalized elastin deposition.

Association study of calcitonin gene-related polypeptide-alpha (CALCA) gene polymorphism with migraine

Migraine is a neurological disorder that is associated with increased levels of calcitonin gene-related peptide (CGRP) in plasma. CGRP, being one of the mediators of neurogenic inflammation and a phenomenon implicated in the pathogenesis of migraine headache, is thus suggested to have an important role in migraine pathophysiology. Polymorphisms of the CALCA gene have been linked to Parkinson's disease, ovarian cancer and essential hypertension, suggesting a functional role for these polymorphisms. Given the strong evidence linking CGRP and migraine, it is hypothesised that polymorphisms in the CALCA gene may play a role in migraine pathogenesis. Seemingly non functional intronic polymorphisms are capable of disrupting normal RNA processing or introducing a splice site in the transcript. A 16 bp deletion in the first intron of the CALCA gene has been reported to be a good match for the binding site for a transcription factor expressed strongly in neural crest derived cells, AP-2. This deletion also eliminates an intron splicing enhancer (ISE) that may potentially cause exon skipping. This study investigated the role of the 16 bp intronic deletion in the CALCA gene in migraineurs and matched control individuals. Six hundred individuals were genotyped for the deletion by polymerase chain reaction followed by fragment analysis on the 3130 Genetic Analyser. The results of this study showed no significant association between the intronic 16 bp deletion in the CALCA gene and migraine in the tested Australian Caucasian population. However, given the evidence linking CGRP and migraine, further investigation of variants with this gene may be warranted.