The effect of unlocking RGD-motifs in collagen I on pre-osteoblast adhesion and differentiation

Denaturation of extracellular matrix proteins exposes cryptic binding sites. It is hypothesized that binding of cell adhesion receptors to these cryptic binding sites regulates cellular behaviour during tissue repair and regeneration. To test this hypothesis, we quantify the adhesion of pre-osteoblastic cells to native (Col) and partially-denatured (pdCol) collagen I using single-cell force spectroscopy. During early stages of cell attachment (≤180 s) pre-osteoblasts (MC3T3-E1) adhered significantly stronger to pdCol compared to Col. RGD (Arg-Gly-Asp)-containing peptides suppressed this elevated cell adhesion. We show that the RGD-binding α5β1- and αv-integrins mediated pre-osteoblast adhesion to pdCol, but not to Col. On pdCol pre-osteoblasts had a higher focal adhesion kinase tyrosine-phosphorylation level that correlated with enhanced spreading and motility. Moreover, pre-osteoblasts cultured on pdCol showed a pronounced matrix mineralization activity. Our data suggest that partially-denatured collagen exposes RGD-motifs that trigger binding of α5β1- and αv-integrins. These integrins initiate cellular processes that stimulate osteoblast adhesion, spreading, motility and differentiation. Taken together, these quantitative insights reveal an approach for the development of alternative collagen I- based surfaces for tissue engineering applications.

An empirical investigation of the level effect in Australian interest rates

An extensive literature examines the dynamics of interest rates, with particular attention given to the positive relationship between interest-rate volatility and the level of interest rates—the so-called level effect. This paper examines the interaction between the estimated level effect and competing parameterisations of interest-rate volatility for the Australian yield curve. We adopt a new methodology that estimates elasticity in a multivariate setting that explicitly accommodates the correlations that exist between various yield factors. Results show that significant correlations exist between the residuals of yield factors and that such correlations do indeed impact on model estimates. Within the multivariate setting, the level of the short rate is shown to be a crucial determinant of the conditional volatility of all three yield factors. Measures of model fit suggest that, in addition to the usual level effect, the incorporation of GARCH effects and possible regime shifts is important

Variation of the Stiles-Crawford effect with accommodation and myopia

Background: Mechanical forces either due to accommodation or myopia may stretch the retina and/or cause shear between the retina and choroid. This can be investigated by making use of the Stiles-Crawford effect (SCE), which is the phenomenon of light changing in apparent brightness as it enters through different positions in the pupil. The SCE can be measured by psychophysical and objective techniques, with the SCE parameters being directionality (rate of change across the pupil), and orientation (the location of peak sensitivity in the pupil). Aims: 1. To study the changes in foveal SCE with accommodation in emmetropes and myopes using a subjective (psychophysical) technique. 2. To develop and evaluate a quick objective technique of measuring the SCE using the multifocal electroretinogram. Methods: The SCE was measured in 6 young emmetropes and 6 young myopes for up to 8 D accommodation stimulus with a psychophysical technique and its variants. An objective technique using the multifocal electroretinogram was developed and evaluated with 5 emmetropes. Results: Using the psychophysical technique, the SCE directionality increased by similar amounts in both emmetropes and myopes as accommodation increased, with an increase of 15-20% with 6 D of accommodation. However, there were no significant orientation changes. Additional measurements showed that most of the change in the directionality was probably an artefact of optical factors such as higher-order aberrations and accommodative lag rather a true effect of accommodation. The multifocal technique demonstrated the presence of the SCE, but results were noisy and too variable to detect any changes in SCE directionality or orientation with accommodation. Conclusion: There is little true change in the SCE with accommodation responses up to 6 D in either emmetropes or myopes, although it is possible that substantial changes might occur at very high accommodation levels. The objective technique using the multifocal electroretinogram was quicker and less demanding for the subjects than the psychophysical technique, but as implemented in this thesis, it is not a reliable method of measuring the SCE.

Effect of optical aberrations on the colour appearance of small lights

Purpose: Small red lights (one minute of arc or less) change colour appearance with positive defocus. We investigated the influence of longitudinal chromatic aberration and monochromatic aberrations on the colour appearance of small narrow band lights. Methods: Seven cyclopleged, trichromatic observers viewed a small light (one minute of arc, λmax = 510, 532, 550, 589, 620, 628 nm, approximately 19 per cent Weber contrast) centred within a black annulus (4.5 minutes of arc) and surrounded by a uniform white field (2,170 cd/m2). Pupil size was four millimetres. An optical trombone varied focus. Longitudinal chromatic aberration was controlled with a two component Powell achromatising lens that neutralises the eye’s chromatic aberration; a doublet that doubles and a triplet that reverses the eye’s chromatic aberration. Astigmatism and higher order monochromatic aberrations were corrected using adaptive optics. Results: Observers reported a change in appearance of the small red light (628 nm) without the Powell lens at +0.49 ± 0.21 D defocus and with the doublet at +0.62 ± 0.16 D. Appearance did not alter with the Powell lens, and five of seven observers reported the phenomenon with the triplet for negative defocus (-0.80 ± 0.47 D). Correction of aberrations did not significantly affect the magnitude at which the appearance of the red light changed (+0.44 ± 0.18 D without correction; +0.46 ± 0.16 D with correction). The change in colour appearance with defocus extended to other wavelengths (λmax = 510 to 620 nm), with directions of effects being reversed for short wavelengths relative to long wavelengths. Conclusions: Longitudinal chromatic aberrations but not monochromatic aberrations are involved in changing the appearance of small lights with defocus.

Simulated cataracts and their effect on speech intelligibility

Purpose: The classic study of Sumby and Pollack (1954, JASA, 26(2), 212-215) demonstrated that visual information aided speech intelligibility under noisy auditory conditions. Their work showed that visual information is especially useful under low signal-to-noise conditions where the auditory signal leaves greater margins for improvement. We investigated whether simulated cataracts interfered with the ability of participants to use visual cues to help disambiguate the auditory signal in the presence of auditory noise. Methods: Participants in the study were screened to ensure normal visual acuity (mean of 20/20) and normal hearing (auditory threshold ≤ 20 dB HL). Speech intelligibility was tested under an auditory only condition and two visual conditions: normal vision and simulated cataracts. The light scattering effects of cataracts were imitated using cataract-simulating filters. Participants wore blacked-out glasses in the auditory only condition and lens-free frames in the normal auditory-visual condition. Individual sentences were spoken by a live speaker in the presence of prerecorded four-person background babble set to a speech-to-noise ratio (SNR) of -16 dB. The SNR was determined in a preliminary experiment to support 50% correct identification of sentence under the auditory only conditions. The speaker was trained to match the rate, intensity and inflections of a prerecorded audio track of everyday speech sentences. The speaker was blind to the visual conditions of the participant to control for bias.Participants’ speech intelligibility was measured by comparing the accuracy of their written account of what they believed the speaker to have said to the actual spoken sentence. Results: Relative to the normal vision condition, speech intelligibility was significantly poorer when participants wore simulated catarcts. Conclusions: The results suggest that cataracts may interfere with the acquisition of visual cues to speech perception.

The effect of monocular and binocular cataract blur on postural stability among older adults

Purpose: First-eye cataract surgery can reduce the rate of falls among older adults, yet the effect of second-eye surgery on the rate of falling remains unclear. The present study investigated the effect of monocular and binocular simulated cataract blur on postural stability among older adults. Methods: Postural stability was assessed on 34 healthy older adults (mean 68.2 years, SD 3.5) with normal vision, using a portable force platform (BT4, HUR Labs, Finland) which collected data on centre of pressure (COP) displacement. Stability was assessed on firm and foam surfaces under four binocular viewing conditions using Vistech filters to simulate cataract blur: [1] best-corrected vision both eyes; [2] blur over non-dominant eye, [3] blur over dominant eye and [4] blur over both eyes. Binocular logMAR visual acuity, Pelli-Robson contrast sensitivity and stereoacuity were also measured under these viewing conditions and ocular dominance measured using the hole-in-card test. Generalized estimating equations with an exchangeable correlation structure examined the effect of the surface and vision conditions on postural stability. Results: Visual acuity and contrast sensitivity were significantly reduced under monocular and binocular cataract blur compared to normal viewing. All blur conditions resulted in loss of stereoacuity. Binocular cataract blur significantly reduced postural stability compared to normal vision on the firm (COP path length; p=0.013) and foam surface (anterior-posterior COP RMS, COP path length and COP area; p<0.01). However, no significant differences in postural stability were found between the monocular blur conditions compared to normal vision, or between the dominant and non-dominant monocular blur conditions on either the firm or foam surfaces. Conclusions: Findings indicate that binocular blur significantly impairs postural stability, and suggests that improvements in postural stability may justify first-eye cataract surgery, particularly during somatosensory disruption. Postural stability was not significantly impaired in the monocular cataract blur conditions compared to the normal vision condition, nor was there any effect of ocular dominance on postural stability in the presence of monocular cataract blur.

The causal effect of income on health: Evidence from German reunification

We investigate whether therewas a causal effect of income changes on the health satisfaction of East and West Germans in the years following reunification. Our data source is the German Socio-Economic Panel (GSOEP) between 1984 and 2002, and we fit a recently proposed fixed-effects ordinal estimator to our health measures and use a causal decomposition technique to account for panel attrition.We find evidence of a significant positive effect of income changes on health satisfaction, but the quantitative size of this effect is small. This is the case with respect to current income and a measure of ‘permanent’ income.

The effect of prolonged reading on visual functions and reading performance in students with low vision

This study is the first to investigate the effect of prolonged reading on reading performance and visual functions in students with low vision. The study focuses on one of the most common modes of achieving adequate magnification for reading by students with low vision, their close reading distance (proximal or relative distance magnification). Close reading distances impose high demands on near visual functions, such as accommodation and convergence. Previous research on accommodation in children with low vision shows that their accommodative responses are reduced compared to normal vision. In addition, there is an increased lag of accommodation for higher stimulus levels as may occur at close reading distance. Reduced accommodative responses in low vision and higher lag of accommodation at close reading distances together could impact on reading performance of students with low vision especially during prolonged reading tasks. The presence of convergence anomalies could further affect reading performance. Therefore, the aims of the present study were 1) To investigate the effect of prolonged reading on reading performance in students with low vision 2) To investigate the effect of prolonged reading on visual functions in students with low vision. This study was conducted as cross-sectional research on 42 students with low vision and a comparison group of 20 students with normal vision, aged 7 to 20 years. The students with low vision had vision impairments arising from a range of causes and represented a typical group of students with low vision, with no significant developmental delays, attending school in Brisbane, Australia. All participants underwent a battery of clinical tests before and after a prolonged reading task. An initial reading-specific history and pre-task measurements that included Bailey-Lovie distance and near visual acuities, Pelli-Robson contrast sensitivity, ocular deviations, sensory fusion, ocular motility, near point of accommodation (pull-away method), accuracy of accommodation (Monocular Estimation Method (MEM)) retinoscopy and Near Point of Convergence (NPC) (push-up method) were recorded for all participants. Reading performance measures were Maximum Oral Reading Rates (MORR), Near Text Visual Acuity (NTVA) and acuity reserves using Bailey-Lovie text charts. Symptoms of visual fatigue were assessed using the Convergence Insufficiency Symptom Survey (CISS) for all participants. Pre-task measurements of reading performance and accuracy of accommodation and NPC were compared with post-task measurements, to test for any effects of prolonged reading. The prolonged reading task involved reading a storybook silently for at least 30 minutes. The task was controlled for print size, contrast, difficulty level and content of the reading material. Silent Reading Rate (SRR) was recorded every 2 minutes during prolonged reading. Symptom scores and visual fatigue scores were also obtained for all participants. A visual fatigue analogue scale (VAS) was used to assess visual fatigue during the task, once at the beginning, once at the middle and once at the end of the task. In addition to the subjective assessments of visual fatigue, tonic accommodation was monitored using a photorefractor (PlusoptiX CR03™) every 6 minutes during the task, as an objective assessment of visual fatigue. Reading measures were done at the habitual reading distance of students with low vision and at 25 cms for students with normal vision. The initial history showed that the students with low vision read for significantly shorter periods at home compared to the students with normal vision. The working distances of participants with low vision ranged from 3-25 cms and half of them were not using any optical devices for magnification. Nearly half of the participants with low vision were able to resolve 8-point print (1M) at 25 cms. Half of the participants in the low vision group had ocular deviations and suppression at near. Reading rates were significantly reduced in students with low vision compared to those of students with normal vision. In addition, there were a significantly larger number of participants in the low vision group who could not sustain the 30-minute task compared to the normal vision group. However, there were no significant changes in reading rates during or following prolonged reading in either the low vision or normal vision groups. Individual changes in reading rates were independent of their baseline reading rates, indicating that the changes in reading rates during prolonged reading cannot be predicted from a typical clinical assessment of reading using brief reading tasks. Contrary to previous reports the silent reading rates of the students with low vision were significantly lower than their oral reading rates, although oral and silent reading was assessed using different methods. Although the visual acuity, contrast sensitivity, near point of convergence and accuracy of accommodation were significantly poorer for the low vision group compared to those of the normal vision group, there were no significant changes in any of these visual functions following prolonged reading in either group. Interestingly, a few students with low vision (n =10) were found to be reading at a distance closer than their near point of accommodation. This suggests a decreased sensitivity to blur. Further evaluation revealed that the equivalent intrinsic refractive errors (an estimate of the spherical dioptirc defocus which would be expected to yield a patient’s visual acuity in normal subjects) were significantly larger for the low vision group compared to those of the normal vision group. As expected, accommodative responses were significantly reduced for the low vision group compared to the expected norms, which is consistent with their close reading distances, reduced visual acuity and contrast sensitivity. For those in the low vision group who had an accommodative error exceeding their equivalent intrinsic refractive errors, a significant decrease in MORR was found following prolonged reading. The silent reading rates however were not significantly affected by accommodative errors in the present study. Suppression also had a significant impact on the changes in reading rates during prolonged reading. The participants who did not have suppression at near showed significant decreases in silent reading rates during and following prolonged reading. This impact of binocular vision at near on prolonged reading was possibly due to the high demands on convergence. The significant predictors of MORR in the low vision group were age, NTVA, reading interest and reading comprehension, accounting for 61.7% of the variances in MORR. SRR was not significantly influenced by any factors, except for the duration of the reading task sustained; participants with higher reading rates were able to sustain a longer reading duration. In students with normal vision, age was the only predictor of MORR. Participants with low vision also reported significantly greater visual fatigue compared to the normal vision group. Measures of tonic accommodation however were little influenced by visual fatigue in the present study. Visual fatigue analogue scores were found to be significantly associated with reading rates in students with low vision and normal vision. However, the patterns of association between visual fatigue and reading rates were different for SRR and MORR. The participants with low vision with higher symptom scores had lower SRRs and participants with higher visual fatigue had lower MORRs. As hypothesized, visual functions such as accuracy of accommodation and convergence did have an impact on prolonged reading in students with low vision, for students whose accommodative errors were greater than their equivalent intrinsic refractive errors, and for those who did not suppress one eye. Those students with low vision who have accommodative errors higher than their equivalent intrinsic refractive errors might significantly benefit from reading glasses. Similarly, considering prisms or occlusion for those without suppression might reduce the convergence demands in these students while using their close reading distances. The impact of these prescriptions on reading rates, reading interest and visual fatigue is an area of promising future research. Most importantly, it is evident from the present study that a combination of factors such as accommodative errors, near point of convergence and suppression should be considered when prescribing reading devices for students with low vision. Considering these factors would also assist rehabilitation specialists in identifying those students who are likely to experience difficulty in prolonged reading, which is otherwise not reflected during typical clinical reading assessments.

Bioactive inorganic materials/alginate composite microspheres with controllable drug-delivery ability

Alginate microspheres are considered a promising material as a drug carrier in bone repair due to excellent biocompatibility, but their main disadvantage is low drug entrapment efficiency and non-controllable release. The aim of this study was to investigate the effect of incorporating mesoporous bioglass (MBG), non-mesoporous bioglass (BG) or hydroxyapatite (HAp) into alginate microspheres on their drug-loading and release properties. X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and atomic emission spectroscopy (AES) were used to analyse the composition, structure and dissolution of bioactive inorganic materials and their microspheres. Dexamethasone (DEX)-loading and release ability of four microspheres were tested in phosphate buffered saline with varying pHs. Results showed that the drug-loading capacity was enhanced with the incorporation of bioactive inorganic materials into alginate microspheres. The MBG/Alginate microspheres had the highest drug loading ability. DEX release from alginate microspheres correlated to the dissolution of MBG, BG and HAp in PBS, and that the pH was an efficient factor in controlling the DEX release; a high pH resulted in greater DEX release, whereas a low pH delayed DEX release. In addition, MBG/alginate, BG/alginate and HAp/alginate microspheres had varying apatite-formation and dissolution abilities, which indicate that the composites would behave differently with respect to bioactivity. The study suggests that microspheres made of a composite of bioactive inorganic materials and alginate have a bioactivity and degradation profile which greatly improves their drug delivery capacity, thus enhancing their potential applications as bioactive filler materials for bone tissue regeneration.

Influence of smectite suspension structure on sheet orientation in dry sediments : XRD and AFM applications

The structure-building phenomena within clay aggregates are governed by forces acting between clay particles. Measurements of such forces are important to understand in order to manipulate the aggregate structure for applications such as dewatering of mineral processing tailings. A parallel particle orientation is required when conducting XRD investigation on the oriented samples and conduct force measurements acting between basal planes of clay mineral platelets using at. force microscopy (AFM). To investigate how smectite clay platelets were oriented on silicon wafer substrate when dried from suspension range of methods like SEM, XRD and AFM were employed. From these investigations, we conclude that high clay concns. and larger particle diams. (up to 5 μm) in suspension result in random orientation of platelets in the substrate. The best possible laminar orientation in the clay dry film, represented in the XRD 0 0 1/0 2 0 intensity ratio of 47 was obtained by drying thin layers from 0.02 wt.% clay suspensions of the natural pH. Conducted AFM investigations show that smectite studied in water based electrolytes show very long-range repulsive forces lower in strength than electrostatic forces from double-layer repulsion. It was suggested that these forces may have structural nature. Smectite surface layers rehydrate in water environment forms surface gel with spongy and cellular texture which cushion approaching AFM probe. This structural effect can be measured in distances larger than 1000 nm from substrate surface and when probe penetrate this gel layer, structural linkages are forming between substrate and clay covered probe. These linkages prevent subsequently smooth detachments of AFM probe on way back when retrieval. This effect of tearing new formed structure apart involves larger adhesion-like forces measured in retrieval. It is also suggested that these effect may be enhanced by the nano-clay particles interaction.

Portfolio size effect in retirement accounts : what does it imply for lifecycle asset allocation funds?

Lifecycle funds offered by retirement plan providers allocate aggressively to risky asset classes when the employee participants are young, gradually switching to more conservative asset classes as they grow older and approach retirement. This approach focuses on maximizing growth of the accumulation fund in the initial years and preserving its value in the later years. The authors simulate terminal wealth outcomes based on conventional lifecycle asset allocation rules as well as on contrarian strategies that reverse the direction of asset switching. The evidence suggests that the growth in portfolio size over time significantly impacts the asset allocation decision. Due to the portfolio size effect that is observed by the authors, the terminal value of accumulation in retirement accounts is influenced more by the asset allocation strategy adopted in later years relative to that adopted in early years. By mechanistically switching to conservative assets in the later years of a plan, lifecycle strategies sacrifice significant growth opportunity and prove counterproductive to the participant's wealth accumulation objective. The authors' conclude that this sacrifice does not seem to be compensated adequately in terms of reducing the risk of potentially adverse outcomes.

Studying the effect of market orientation and organisational culture on a brand’s performance

It is now well accepted that effective implementation of market orientation leads to superior performance. This paper theorises that market orientation and an innovative culture enable organisations to achieve higher brand performance. To test this proposition data were gathered from a sample of firms across a range of industries. The results support the premise that market orientation and innovative cultures improve brand performance and that innovative culture influences market orientation. The results also indicate that innovative culture is the stronger driver of brand performance over market orientation.

Effect of representation size and visual ambiguity on RatSLAM system performance

RatSLAM is a vision-based SLAM system based on extended models of the rodent hippocampus. RatSLAM creates environment representations that can be processed by the experience mapping algorithm to produce maps suitable for goal recall. The experience mapping algorithm also allows RatSLAM to map environments many times larger than could be achieved with a one to one correspondence between the map and environment, by reusing the RatSLAM maps to represent multiple sections of the environment. This paper describes experiments investigating the effects of the environment-representation size ratio and visual ambiguity on mapping and goal navigation performance. The experiments demonstrate that system performance is weakly dependent on either parameter in isolation, but strongly dependent on their joint values.

Effects of starting strategy on 5-min cycling time-trial performance

The importance of pacing for middle-distance performance is well recognized, yet previous research has produced equivocal results. Twenty-six trained male cyclists (O2peak 62.8 ± 5.9 ml · kg-1 · min-1; maximal aerobic power output 340 ± 43 W; mean ± s) performed three cycling time-trials where the total external work (102.7 ± 13.7 kJ) for each trial was identical to the best of two 5-min habituation trials. Markers of aerobic and anaerobic metabolism were assessed in 12 participants. Power output during the first quarter of the time-trials was fixed to control external mechanical work done (25.7 ± 3.4 kJ) and induce fast-, even-, and slow-starting strategies (60, 75, and 90 s, respectively). Finishing times for the fast-start time-trial (4:53 ± 0:11 min:s) were shorter than for the even-start (5:04 ± 0:11 min:s; 95% CI = 5 to 18 s, effect size = 0.65, P < 0.001) and slow-start time-trial (5:09 ± 0:11 min:s; 95% CI = 7 to 24 s, effect size = 1.00, P < 0.001). Mean O2 during the fast-start trials (4.31 ± 0.51 litres · min-1) was 0.18 ± 0.19 litres · min-1 (95% CI = 0.07 to 0.30 litres · min-1, effect size = 0.94, P = 0.003) higher than the even- and 0.18 ± 0.20 litres · min-1 (95% CI = 0.5 to 0.30 litres · min-1, effect size = 0.86, P = 0.007) higher than the slow-start time-trial. Oxygen deficit was greatest during the first quarter of the fast-start trial but was lower than the even- and slow-start trials during the second quarter of the trial. Blood lactate and pH were similar between the three trials. In conclusion, performance during a 5-min cycling time-trial was improved with the adoption of a fast- rather than an even- or slow-starting strategy.