Dots versus antidots : computational exploration of structure, magnetism, and half-metallicity in boron−nitride nanostructures

Triangle-shaped nanohole, nanodot, and lattice antidot structures in hexagonal boron-nitride (h-BN) monolayer sheets are characterized with density functional theory calculations utilizing the local spin density approximation. We find that such structures may exhibit very large magnetic moments and associated spin splitting. N-terminated nanodots and antidots show strong spin anisotropy around the Fermi level, that is, half-metallicity. While B-terminated nanodots are shown to lack magnetism due to edge reconstruction, B-terminated nanoholes can retain magnetic character due to the enhanced structural stability of the surrounding two-dimensional matrix. In spite of significant lattice contraction due to the presence of multiple holes, antidot super lattices are predicted to be stable, exhibiting amplified magnetism as well as greatly enhanced half-metallicity. Collectively, the results indicate new opportunities for designing h-BNbased nanoscale devices with potential applications in the areas of spintronics, light emission, and photocatalysis.

Characterization of inflammatory responses to eccentric exercise in humans

Eccentric exercise commonly results in muscle damage. The primary sequence of events leading to exercise-induced muscle damage is believed to involve initial mechanical disruption of sarcomeres, followed by impaired excitation-contraction coupling and calcium signaling, and finally, activation of calcium-sensitive degradation pathways. Muscle damage is characterized by ultrastructural changes to muscle architecture, increased muscle proteins and enzymes in the bloodstream, loss of muscular strength and range of motion and muscle soreness. The inflammatory response to exercise-induced muscle damage is characterized by leukocyte infiltration and production of pro-inflammatory cytokines within damaged muscle tissue, systemic release of leukocytes and cytokines, in addition to alterations in leukocyte receptor expression and functional activity. Current evidence suggests that inflammatory responses to muscle damage are dependent on the type of eccentric exercise, previous eccentric loading (repeated bouts), age and gender. Circulating neutrophil counts and systemic cytokine responses are greater after eccentric exercise using a large muscle mass (e.g. downhill running, eccentric cycling) than after other types of eccentric exercise involving a smaller muscle mass. After an initial bout of eccentric exercise, circulating leukocyte counts and cell surface receptor expression are attenuated. Leukocyte and cytokine responses to eccentric exercise are impaired in elderly individuals, while cellular infiltration into skeletal muscle is greater in human females than males after eccentric exercise. Whether alterations in intracellular calcium homeostasis influence inflammatory responses to muscle damage is uncertain. Furthermore, the effects of antioxidant supplements are variable, and the limited data available indicates that anti-inflammatory drugs largely have no influence on inflammatory responses to eccentric exercise. In this review, we compare local versus systemic inflammatory responses, and discuss some of the possible mechanisms regulating the inflammatory responses to exercise-induced muscle damage in humans.

Investigating epidermogenesis in a human skin equivalent model

Skin is the largest, and arguably, the most important organ of the body. It is a complex and multi-dimensional tissue, thus making it essentially impossible to fully model in vitro in conventional 2-dimensional culture systems. In view of this, rodents or pigs are utilised to study wound healing therapeutics or to investigate the biological effects of treatments on skin. However, there are many differences between the wound healing processes in rodents compared to humans (contraction vs. re-epithelialisation) and there are also ethical issues associated with animal testing for scientific research. Therefore, the development of skin equivalent (HSE) models from surgical discard human skin has become an important area of research. The studies in this thesis compare, for the first time, native human skin and the epidermogenesis process in a HSE model. The HSE was reported to be a comparable model for human skin in terms of expression and localisation of key epidermal cell markers. This validated HSE model was utilised to study the potential wound healing therapeutic, hyperbaric oxygen (HBO) therapy. There is a significant body of evidence suggesting that lack of cutaneous oxygen results in and potentiates the chronic, non-healing wound environment. Although the evidence is anecdotal, HBO therapy has displayed positive effects on re-oxygenation of chronic wounds and the clinical outcomes suggest that HBO treatment may be beneficial. Therefore, the HSE was subjected to a daily clinical HBO regime and assessed in terms of keratinocyte migration, proliferation, differentiation and epidermal thickening. HBO treatment was observed to increase epidermal thickness, in particular stratum corneum thickening, but it did not alter the expression or localisation of standard epidermal cell markers. In order to elucidate the mechanistic changes occurring in response to HBO treatment in the HSE model, gene microarrays were performed, followed by qRT-PCR of select genes which were differentially regulated in response to HBO treatment. The biological diversity of the HSEs created from individual skin donors, however, overrode the differences in gene expression between treatment groups. Network analysis of functional changes in the HSE model revealed general trends consistent with normal skin growth and maturation. As a more robust and longer term study of these molecular changes, protein localisation and expression was investigated in sections from the HSEs undergoing epidermogenesis in response to HBO treatment. These proteins were CDCP1, Metallothionein, Kallikrein (KLK) 1 and KLK7 and early growth response 1. While the protein expression within the HSE models exposed to HBO treatment were not consistent in all HSEs derived from all skin donors, this is the first study to detect and compare both KLK1 and CDCP1 protein expression in both a HSE model and native human skin. Furthermore, this is the first study to provide such an in depth analysis of the effect of HBO treatment on a HSE model. The data presented in this thesis, demonstrates high levels of variation between individuals and their response to HBO treatment, consistent with the clinical variation that is currently observed.

Relationship of moderate and low isometric lumbar extension through architectural and muscular activity variables: a cross sectional study

Background No study relating the changes obtained in the architecture of erector spinae (ES) muscle were registered with ultrasound and different intensities of muscle contraction recorded by surface EMG (electromyography) on the ES muscle was found. The aim of this study was analyse the relationship in the response of the ES muscle during isometric moderate and light lumbar isometric extension considering architecture and functional muscle variables. Methods Cross-sectional study. 46 subjects (52% men) with a group mean age of 30.4 (±7.78). The participants developed isometric lumbar extension while performing moderate and low isometric trunk and hip extension in a sitting position with hips flexed 90 degrees and the lumbar spine in neutral position. During these measurements, electromyography recordings and ultrasound images were taken bilaterally. Bilaterally pennation angle, muscle thickness, torque and muscle activation were measured. This study was developed at the human movement analysis laboratory of the Health Science Faculty of the University of Malaga (Spain). Results Strong and moderate correlations were found at moderate and low intensities contraction between the variable of the same intensity, with correlation values ranging from 0.726 (Torque Moderate – EMG Left Moderate) to 0.923 (Angle Left Light – Angle Right Light) (p < 0.001). This correlation is observed between the variables that describe the same intensity of contraction, showing a poor correlation between variables of different intensities. Conclusion There is a strong relationship between architecture and function variables of ES muscle when describe an isometric lumbar extension at light or moderate intensity. Keywords: Ultrasonography; Surface electromyography; Thickness; Pennation angle; Erector spinae

Low muscle glycogen concentration does not suppress the anabolic response to resistance exercise

We determined the effect of muscle glycogen concentration and postexercise nutrition on anabolic signaling and rates of myofibrillar protein synthesis after resistance exercise (REX). Sixteen young, healthy men matched for age, body mass, peak oxygen uptake (VO2peak) and strength (one repetition maximum; 1RM) were randomly assigned to either a nutrient or placebo group. After 48 h diet and exercise control, subjects undertook a glycogen-depletion protocol consisting of one-leg cycling to fatigue (LOW), whereas the other leg rested (NORM). The next morning following an overnight fast, a primed, constant infusion of L-[ring-13C6] phenylalanine was commenced and subjects completed 8 sets of 5 unilateral leg press repetitions at 80% 1RM. Immediately after REX and 2 h later, subjects consumed a 500 ml bolus of a protein/CHO (20 g whey + 40 g maltodextrin) or placebo beverage. Muscle biopsies from the vastus lateralis of both legs were taken at rest and 1 and 4 h after REX. Muscle glycogen concentration was higher in the NORM than LOW at all time points in both nutrient and placebo groups (P < 0.05). Postexercise Akt-p70S6K-rpS6 phosphorylation increased in both groups with no differences between legs (P < 0.05). mTORSer2448 phosphorylation in placebo increased 1 h after exercise in NORM (P < 0.05), whereas mTOR increased ?4-fold in LOW (P < 0.01) and ?11 fold in NORM with nutrient (P < 0.01; different between legs P < 0.05). Post-exercise rates of MPS were not different between NORM and LOW in nutrient (0.070 ± 0.022 vs. 0.068 ± 0.018 %/h) or placebo (0.045 ± 0.021 vs. 0.049 ± 0.017 %/h). We conclude that commencing high-intensity REX with low muscle glycogen availability does not compromise the anabolic signal and subsequent rates of MPS, at least during the early (4 h) postexercise recovery period.

Nutrient provision increases signalling and protein synthesis in human skeletal muscle after repeated sprints

The effect of nutrient availability on the acute molecular responses following repeated sprint exercise is unknown. The aim of this study was to determine skeletal muscle cellular and protein synthetic responses following repeated sprint exercise with nutrient provision. Eight healthy young male subjects undertook two sprint cycling sessions (10 × 6 s, 0.75 N m torque kg -1, 54 s recovery) with either pre-exercise nutrient (24 g whey, 4.8 g leucine, 50 g maltodextrin) or non-caloric placebo ingestion. Muscle biopsies were taken from vastus lateralis at rest, and after 15 and 240 min post-exercise recovery to determine muscle cell signalling responses and protein synthesis by primed constant infusion of L-[ring- 13C 6] phenylalanine. Peak and mean power outputs were similar between nutrient and placebo trials. Post-exercise myofibrillar protein synthetic rate was greater with nutrient ingestion compared with placebo ( ? 48%, P<0.05) but the rate of mitochondrial protein synthesis was similar between treatments. The increased myofibrillar protein synthesis following sprints with nutrient ingestion was associated with coordinated increases in Akt-mTOR-S6KrpS6 phosphorylation 15 min post-exercise (?200-600%, P<0.05), while there was no effect on these signalling molecules when exercise was undertaken in the fasted state. For the first time we report a beneficial effect of nutrient provision on anabolic signalling and muscle myofibrillar protein synthesis following repeated sprint exercise. Ingestion of protein/carbohydrate in close proximity to high-intensity sprint exercise provides an environment that increases cell signalling and protein synthesis.

Exercise-induced phosphorylation of the novel Akt substrates AS160 and filamin A in human skeletal muscle

Skeletal muscle contraction stimulates multiple signaling cascades that govern a variety of metabolic and transcriptional events. Akt/protein kinase B regulates metabolism and growth/muscle hypertrophy, but contraction effects on this target and its substrates are varied and may depend on the mode of the contractile stimulus. Accordingly, we determined the effects of endurance or resistance exercise on phosphorylation of Akt and downstream substrates in six trained cyclists who performed a single bout of endurance or resistance exercise separated by ?7 days. Muscle biopsies were taken from the vastus lateralis at rest and immediately after exercise. Akt Ser 473 phosphorylation was increased (1.8-fold; P = 0.011) after endurance but was unchanged after resistance exercise. Conversely, Akt Thr 308 phosphorylation was unaltered after either bout of exercise. Several exercise-responsive phosphoproteins were detected by immunoblot analysis with a phospho-Akt substrate antibody. pp160 and pp300 were identified as AS160 and filamin A, respectively, with increased phosphorylation (2.0- and 4.9-fold, respectively; P < 0.05) after endurance but not resistance exercise. In conclusion, AS160 and filamin A may provide an important link to mediate endurance exercise-induced bioeffects in skeletal muscle.

Prediction of muscular architecture of the rectus femoris and vastus lateralis from EMG during isometric contractions in soccer players

Objectives The purpose of the study was to establish regression equations that could be used to predict muscle thickness and pennation angle at different intensities from electromyography (EMG) based measures of muscle activation during isometric contractions. Design Cross-sectional study. Methods Simultaneous ultrasonography and EMG were used to measure pennation angle, muscle thickness and muscle activity of the rectus femoris and vastus lateralis muscles, respectively, during graded isometric knee extension contractions performed on a Cybex dynamometer. Data form fifteen male soccer players were collected in increments of approximately 25% intensity of the maximum voluntary contraction (MVC) ranging from rest to MVC. Results There was a significant correlation (P < 0.05) between ultrasound predictors and EMG measures for the muscle thickness of rectus femoris with an R2 value of 0.68. There was no significant correlation (P > 0.05) between ultrasound pennation angle for the vastus lateralis predictors for EMG muscle activity with an R2 value of 0.40. Conclusions The regression equations can be used to characterise muscle thickness more accurately and to determine how it changes with contraction intensity, this provides improved estimates of muscle force when using musculoskeletal models.

The evaluation of a clinical scar scale for porcine burn scars

This study describes the evaluation of a clinical scar scale for our porcine burn scars, which includes scar cosmetic outcome, colour, height and hair, supplemented with reference porcine scar photographs representing each scar outcome and scar colour scores. A total of 72 porcine burn scars at week 6 after burn were rated in vivo and/or on photographs. Good agreements were achieved for both intra-rater reliability (correlation is 0.86-0.98) and inter-rater reliability (ICC=80-85%). The results showed statistically significant correlations for each pair in this clinical scar scale (p<0.01), with the best correlation found between scar cosmetic outcome and scar colour. A multivariate principle components analysis revealed that this clinical scar assessment was highly correlated with scar histology, wound size, and re-epithelialisation data (p<0.001). More severe scars are clinically characterised by darker purple colouration, more elevation, no presence of hair, histologically by thicker scar tissue, thinner remaining normal dermis, are more likely to have worse contraction, and slower re-epithelialisation. This study demonstrates that our clinical scar scale is a reliable, independent and valuable tool for assessing porcine burn outcome and truthfully reflects scar appearance and function. To our knowledge, this is the first study demonstrating a high correlation between clinical scar assessment and scar histology, wound contraction and re-epithelialisation data on porcine burn scars. We believe that the successful use of porcine scar scales is invaluable for assessing potential human burn treatments.

Axial elongation associated with biomechanical factors during near work

Purpose: To investigate the changes occurring in the axial length, choroidal thickness and anterior biometrics of the eye during a 10 minute near task performed in downward gaze. Methods: Twenty young adult subjects (10 emmetropes and 10 myopes) participated in this study. To measure ocular biometrics in downward gaze, an optical biometer was inclined on a custom built, height and tilt adjustable table. Baseline measures were collected after each subject performed a distance primary gaze control task for 10 mins, to provide wash-out period for prior visual tasks before each of three different accommodation/gaze conditions. These other three conditions included a near task (2.5 D) in primary gaze, and a near (2.5 D) and a far (0 D) accommodative task in downward gaze (25°), all for 10 mins duration. Immediately after, and then 5 and 10 mins from the commencement of each trial, measurements of ocular biometrics (e.g. anterior biometrics, axial length, choroidal thickness and retinal thickness) were obtained. Results: Axial length increased with accommodation and was significantly greater for downward gaze with accommodation (mean change ± SD 23 ± 13 µm at 10 mins) compared to primary gaze with accommodation (mean change 8 ± 15 µm at 10 mins) (p < 0.05). A small amount of choroidal thinning was also found during accommodation that was statistically significant in downward gaze (13 ± 14 µm at 10 mins, p < 0.05). Accommodation in downward gaze also caused greater changes in anterior chamber depth and lens thickness compared to accommodation in primary gaze. Conclusion: Axial length, choroidal thickness and anterior eye biometrics change significantly during accommodation in downward gaze as a function of time. These changes appear to be due to the combined influence of biomechanical factors (i.e. extraocular muscle forces, ciliary muscle contraction) associated with near tasks in downward gaze.

Simulation of plant cell shrinkage during drying : A SPH–DEM approach

Plant based dried food products are popular commodities in global market where much research is focused to improve the products and processing techniques. In this regard, numerical modelling is highly applicable and in this work, a coupled meshfree particle-based two-dimensional (2-D) model was developed to simulate micro-scale deformations of plant cells during drying. Smoothed Particle Hydrodynamics (SPH) was used to model the viscous cell protoplasm (cell fluid) by approximating it to an incompressible Newtonian fluid. The visco-elastic characteristic of the cell wall was approximated to a Neo-Hookean solid material augmented with a viscous term and modelled with a Discrete Element Method (DEM). Compared to a previous work [H. C. P. Karunasena, W. Senadeera, Y. T. Gu and R. J. Brown, Appl. Math. Model., 2014], this study proposes three model improvements: linearly decreasing positive cell turgor pressure during drying, cell wall contraction forces and cell wall drying. The improvements made the model more comparable with experimental findings on dried cell morphology and geometric properties such as cell area, diameter, perimeter, roundness, elongation and compactness. This single cell model could be used as a building block for advanced tissue models which are highly applicable for product and process optimizations in Food Engineering.

Short-term changes in axial length during simulations of typical far, intermediate and near tasks

Purpose: To investigate the changes in axial length with the combined effect of accommodation and angle of gaze (convergence and downward gaze) over 5 minutes in groups of myopes and emmetropes. Methods: A total of 31 subjects (nine emmetropes, 10 low myopes, and 12 moderate to high myopes) aged from 18 to 31 years were recruited. To measure ocular biometrics in inferonasal gaze with accommodation, an optical biometer (Lenstar LS900) was inclined on a tilt and height adjustable stage, with the subject’s chinrest mounted on a rotary stage to induce various levels of convergence by rotation of the subject’s head in primary or downward gaze. Initially, the subjects performed a distance viewing task in primary gaze for 10 minutes to provide a ‘wash-out’ period for prior visual tasks, and then the subject’s axial length and ocular biometrics were measured in nine different combinations of gaze/accommodation over 5 minutes. These nine sessions for all gaze measurements (i.e. three levels of accommodation 9 three levels of convergence) were completed across 3 days of testing (one accommodation condition on each day).The nine combinations of gaze/accommodation were based on those required to view the centre, right and left edges of a distant TV at 6 m in primary gaze, an intermediate task (i.e. computer at 50 cm in 10° downward gaze) and a near task (i.e. reading A4 page at 20 cm in 20° downward gaze). Subjects were wearing a custom built three-axes head tracker throughout the experiment that monitored subjects’ relative head movements (roll, pitch and yaw) during measurements. Results: A significant increase in axial length occurred with the combined effect of accommodation, convergence and downward gaze (repeated measures ANOVA, p < 0.001), with the greatest axial elongation during the near task in downward gaze with convergence (i.e. downward 20°/inward 33°, with 5 D accommodation) (mean change 33 ± 13 lm, after 5 minutes task) followed by the intermediate task (i.e. downward 10°/inward 25°, with 2 D accommodation) (mean change 14 ± 11 lm, after 5 minutes task).Changes in axial length for the distance task (i.e. primary gaze/9° convergence, with 0.16 D accommodation) were not statistically significant (mean change 4 ± 8 lm, after 5 minutes task, p > 0.05). Moderate to high myopes had a greater change in the axial length (mean change 40 ± 11 lm after 5 minutes of near task) than that of emmetropes (mean change 29 ± 15 lm after 5 minutes of near task) and low myopes (mean change 29 ± 16 lm after 5 minutes of near task) associated with time (p = 0.02) and accommodation by time (p = 0.03). Conclusions: The combination of accommodation, convergence and downward angle has a significant short term effect on axial length over time. The near task in downward gaze with convergence caused a greater change in axial length than the intermediate and distant visual tasks. The greater axial elongation measured in the infero-nasal direction with accommodation is most likely associated with a combination of biomechanical factors such as, extraocular muscle forces and ciliary muscle contraction.

The type I collagen induction of MT1-MMP-mediated MMP-2 activation is repressed by αVβ3 integrin in human breast cancer cells

The influence of αVβ3 integrin on MT1-MMP functionality was studied in human breast cancer cells of differing β3 integrin status. Overexpression of β3 integrin caused increased cell surface expression of αV integrin and increased cellular adhesion to extracellular matrix (ECM) substrates in BT-549, MDA-MB-231 and MCF-7 cells. β3 integrin expression also enhanced the migration of breast cancer cells on ECM substrates and enhanced collagen gel contraction. In vivo, αVβ3 cooperated with MT1-MMP to increase the growth of MCF-7 cells after orthotopic inoculation in immunocompromised mice, but had no influence on in vitro proliferation. Despite these stimulatory effects, overexpression of β3 integrin suppressed the type I collagen (Col I) induced MMP-2 activation in all breast cancer cell lines analyzed. This was also evident in extracts from the MCF-7 tumors in vivo, where MMP-2 activation was stimulated by MT1-MMP transfection, but attenuated with β3 integrin expression. Although our studies confirm important biological effects of αVβ3 integrin on enhancing cell adhesion and migration, ECM remodeling and tumor growth, β3 integrin caused reduced MMP-2 activation in response to Col I in vitro, which appears to be physiologically relevant, as it was also seen in tumor xenografts in vivo. The reduction of MMP-2 activation (and thus MT1-MMP activity) by αVβ3 in response to Col I may be important in scenarios where cells which are activated for matrix degradation need to preserve some pericellular collagen, perhaps as a substrate for cell adhesion and migration, thus maintaining a balanced level of proteolysis required for efficient tumor growth.

Pleistocene climate fluctuations influence phylogeographical patterns in Melomys cervinipes across the mesic forests of eastern Australia

Aim Our aim was to clarify the lineage-level relationships for Melomys cervinipes and its close relatives and investigate whether the patterns of divergence observed for these wet-forest-restricted mammals may be associated with recognized biogeographical barriers. Location Mesic closed forest along the east coast of Australia, from north Queensland to mid-eastern New South Wales. Methods To enable rigorous phylogenetic reconstruction, divergence-date estimation and phylogeographical inference, we analysed DNA sequence and microsatellite data from 307 specimens across the complete distribution of M. cervinipes (45 localities). Results Three divergent genetic lineages were found within M. cervinipes, corresponding to geographically delineated northern, central and southern clades. Additionally, a fourth lineage, comprising M. rubicola and M. capensis, was identified and was most closely related to the northern M. cervinipes lineage. Secondary contact of the northern and central lineages was identified at one locality to the north of the Burdekin Gap. Main conclusions Contemporary processes of repeated habitat fragmentation and contraction, local extinction events and subsequent re-expansion across both small and large areas, coupled with the historical influence of the Brisbane Valley Barrier, the St Lawrence Gap and the Burdekin Gap, have contributed to the present phylogeographical structure within M. cervinipes. Our study highlights the need to sample close to the periphery of putative biogeographical barriers or risk missing vital phylogeographical information that may significantly alter the interpretation of biogeographical hypotheses.

A particle based model to simulate microscale morphological changes of plant tissues during drying

Fundamental understanding on microscopic physical changes of plant materials is vital to optimize product quality and processing techniques, particularly in food engineering. Although grid-based numerical modelling can assist in this regard, it becomes quite challenging to overcome the inherited complexities of these biological materials especially when such materials undergo critical processing conditions such as drying, where the cellular structure undergoes extreme deformations. In this context, a meshfree particle based model was developed which is fundamentally capable of handling extreme deformations of plant tissues during drying. The model is built by coupling a particle based meshfree technique: Smoothed Particle Hydrodynamics (SPH) and a Discrete Element Method (DEM). Plant cells were initiated as hexagons and aggregated to form a tissue which also accounts for the characteristics of the middle lamella. In each cell, SPH was used to model cell protoplasm and DEM was used to model the cell wall. Drying was incorporated by varying the moisture content, the turgor pressure, and cell wall contraction effects. Compared to the state of the art grid-based microscale plant tissue drying models, the proposed model can be used to simulate tissues under excessive moisture content reductions incorporating cell wall wrinkling. Also, compared to the state of the art SPH-DEM tissue models, the proposed model better replicates real tissues and the cell-cell interactions used ensure efficient computations. Model predictions showed good agreement both qualitatively and quantitatively with experimental findings on dried plant tissues. The proposed modelling approach is fundamentally flexible to study different cellular structures for their microscale morphological changes at dehydration.