Combining ganglion cell topology and data of patients with glaucoma to determine a structure-function map

PURPOSE: To introduce techniques for deriving a map that relates visual field locations to optic nerve head (ONH) sectors and to use the techniques to derive a map relating Medmont perimetric data to data from the Heidelberg Retinal Tomograph. METHODS: Spearman correlation coefficients were calculated relating each visual field location (Medmont M700) to rim area and volume measures for 10 degrees ONH sectors (HRT III software) for 57 participants: 34 with glaucoma, 18 with suspected glaucoma, and 5 with ocular hypertension. Correlations were constrained to be anatomically plausible with a computational model of the axon growth of retinal ganglion cells (Algorithm GROW). GROW generated a map relating field locations to sectors of the ONH. The sector with the maximum statistically significant (P < 0.05) correlation coefficient within 40 degrees of the angle predicted by GROW for each location was computed. Before correlation, both functional and structural data were normalized by either normative data or the fellow eye in each participant. RESULTS: The model of axon growth produced a 24-2 map that is qualitatively similar to existing maps derived from empiric data. When GROW was used in conjunction with normative data, 31% of field locations exhibited a statistically significant relationship. This significance increased to 67% (z-test, z = 4.84; P < 0.001) when both field and rim area data were normalized with the fellow eye. CONCLUSIONS: A computational model of axon growth and normalizing data by the fellow eye can assist in constructing an anatomically plausible map connecting visual field data and sectoral ONH data.

From mass communication to mass conversation : why 1984 wasn't like 1984

Marketers and commercial media alike are confronted by shifts in the social relations of media production and consumption in the global services economy, including the challenge of capturing, managing and commercialising media-user productivity. This trajectory of change in media cultures and economies is described here as ‘mass conversation’. Two media texts and a new media object provide a starting point for charting the ascendance and social impact of mass conversation. Apple’s 1984 television commercial, which launched the Macintosh computer, inverted George Orwell’s dystopian vision of the social consequences of panoptic communications systems. It invoked a revolutionary rhetoric to anticipate the social consequences of a new type of interactivity since theorised as ‘intercreativity’. This television commercial is contrasted with another used in Nike’s 2006 launch of its Nike+ (Apple iPod) system. The Nike+ online brand community is also used to consider how a multiplatform brand channel is seeking to manage the changing norms and practices of consumption and end-user agency. This analysis shows that intercreativity modifies the operations of ‘Big Brother’ but serves the more mundane than revolutionary purpose of generating commercial value from the affective labour of end-users.

Regulation of human stem cell research in Australia

Australia is currently well placed to contribute to the global growth of human stem cell research. However, as the science has progressed, authorities have had to deal with the ongoing challenges of regulating such a fast moving field of scientific endeavour. Australia’s past and current approach to regulating the use of embryos in human embryonic stem cell research provides an insight into how Australia may continue to adapt to future regulatory challenges presented by human stem cell research. In the broader context, a number of issues have been identified that may impact upon the success of future human stem cell research in Australia.

Stem cell technologies : regulation, patents and problems

Human embryonic stem cell research promises to deliver in the future a whole range of therapeutic treatments, but currently governments in different jurisdictions must try to regulate this burgeoning area. Part of the problem has been, and continues to be, polarised community opinion on the use of human embryonic stem cells for research. This article compares the approaches of the Australian, United Kingdom and United States governments in regulating human embryonic stem cell research. To date, these governments have approached the issue through implementing legislation or policy to control research. Similarly, the three jurisdictions have viewed the patentability of human embryonic stem cell technologies in their own ways with different policies being adopted by the three patent offices. This article examines these different approaches and discusses the inevitable concerns that have been raised due to the lack of a universal approach in relation to the regulation of research; the patenting of stem cell technologies; and the effects patents granted are having on further human embryonic stem cell research.

Development of a biaxial compression device for biological samples : preliminary experimental results for a closed cell foam

Biological tissues are subjected to complex loading states in vivo and in order to define constitutive equations that effectively simulate their mechanical behaviour under these loads, it is necessary to obtain data on the tissue's response to multiaxial loading. Single axis and shear testing of biological tissues is often carried out, but biaxial testing is less common. We sought to design and commission a biaxial compression testing device, capable of obtaining repeatable data for biological samples. The apparatus comprised a sealed stainless steel pressure vessel specifically designed such that a state of hydrostatic compression could be created on the test specimen while simultaneously unloading the sample along one axis with an equilibrating tensile pressure. Thus a state of equibiaxial compression was created perpendicular to the long axis of a rectangular sample. For the purpose of calibration and commissioning of the vessel, rectangular samples of closed cell ethylene vinyl acetate (EVA) foam were tested. Each sample was subjected to repeated loading, and nine separate biaxial experiments were carried out to a maximum pressure of 204 kPa (30 psi), with a relaxation time of two hours between them. Calibration testing demonstrated the force applied to the samples had a maximum error of 0.026 N (0.423% of maximum applied force). Under repeated loading, the foam sample demonstrated lower stiffness during the first load cycle. Following this cycle, an increased stiffness, repeatable response was observed with successive loading. While the experimental protocol was developed for EVA foam, preliminary results on this material suggest that this device may be capable of providing test data for biological tissue samples. The load response of the foam was characteristic of closed cell foams, with consolidation during the early loading cycles, then a repeatable load-displacement response upon repeated loading. The repeatability of the test results demonstrated the ability of the test device to provide reproducible test data and the low experimental error in the force demonstrated the reliability of the test data.

Development of a particle number and particle mass vehicle emissions inventory for an urban fleet

Motor vehicles are major emitters of gaseous and particulate pollution in urban areas, and exposure to particulate pollution can have serious health effects, ranging from respiratory and cardiovascular disease to mortality. Motor vehicle tailpipe particle emissions span a broad size range from 0.003-10µm, and are measured as different subsets of particle mass concentrations or particle number count. However, no comprehensive inventories currently exist in the international published literature covering this wide size range. This paper presents the first published comprehensive inventory of motor vehicle tailpipe particle emissions covering the full size range of particles emitted. The inventory was developed for urban South-East Queensland by combining two techniques from distinctly different disciplines, from aerosol science and transport modelling. A comprehensive set of particle emission factors were combined with traffic modelling, and tailpipe particle emissions were quantified for particle number (ultrafine particles), PM1, PM2.5 and PM10 for light and heavy duty vehicles and buses. A second aim of the paper involved using the data derived in this inventory for scenario analyses, to model the particle emission implications of different proportions of passengers travelling in light duty vehicles and buses in the study region, and to derive an estimate of fleet particle emissions in 2026. It was found that heavy duty vehicles (HDVs) in the study region were major emitters of particulate matter pollution, and although they contributed only around 6% of total regional vehicle kilometres travelled, they contributed more than 50% of the region’s particle number (ultrafine particles) and PM1 emissions. With the freight task in the region predicted to double over the next 20 years, this suggests that HDVs need to be a major focus of mitigation efforts. HDVs dominated particle number (ultrafine particles) and PM1 emissions; and LDV PM2.5 and PM10 emissions. Buses contributed approximately 1-2% of regional particle emissions.

Validation of 3D models of the outer and inner surfaces of an ovine femur

The validation of Computed Tomography (CT) based 3D models takes an integral part in studies involving 3D models of bones. This is of particular importance when such models are used for Finite Element studies. The validation of 3D models typically involves the generation of a reference model representing the bones outer surface. Several different devices have been utilised for digitising a bone’s outer surface such as mechanical 3D digitising arms, mechanical 3D contact scanners, electro-magnetic tracking devices and 3D laser scanners. However, none of these devices is capable of digitising a bone’s internal surfaces, such as the medullary canal of a long bone. Therefore, this study investigated the use of a 3D contact scanner, in conjunction with a microCT scanner, for generating a reference standard for validating the internal and external surfaces of a CT based 3D model of an ovine femur. One fresh ovine limb was scanned using a clinical CT scanner (Phillips, Brilliance 64) with a pixel size of 0.4 mm2 and slice spacing of 0.5 mm. Then the limb was dissected to obtain the soft tissue free bone while care was taken to protect the bone’s surface. A desktop mechanical 3D contact scanner (Roland DG Corporation, MDX 20, Japan) was used to digitise the surface of the denuded bone. The scanner was used with the resolution of 0.3 × 0.3 × 0.025 mm. The digitised surfaces were reconstructed into a 3D model using reverse engineering techniques in Rapidform (Inus Technology, Korea). After digitisation, the distal and proximal parts of the bone were removed such that the shaft could be scanned with a microCT (µCT40, Scanco Medical, Switzerland) scanner. The shaft, with the bone marrow removed, was immersed in water and scanned with a voxel size of 0.03 mm3. The bone contours were extracted from the image data utilising the Canny edge filter in Matlab (The Mathswork).. The extracted bone contours were reconstructed into 3D models using Amira 5.1 (Visage Imaging, Germany). The 3D models of the bone’s outer surface reconstructed from CT and microCT data were compared against the 3D model generated using the contact scanner. The 3D model of the inner canal reconstructed from the microCT data was compared against the 3D models reconstructed from the clinical CT scanner data. The disparity between the surface geometries of two models was calculated in Rapidform and recorded as average distance with standard deviation. The comparison of the 3D model of the whole bone generated from the clinical CT data with the reference model generated a mean error of 0.19±0.16 mm while the shaft was more accurate(0.08±0.06 mm) than the proximal (0.26±0.18 mm) and distal (0.22±0.16 mm) parts. The comparison between the outer 3D model generated from the microCT data and the contact scanner model generated a mean error of 0.10±0.03 mm indicating that the microCT generated models are sufficiently accurate for validation of 3D models generated from other methods. The comparison of the inner models generated from microCT data with that of clinical CT data generated an error of 0.09±0.07 mm Utilising a mechanical contact scanner in conjunction with a microCT scanner enabled to validate the outer surface of a CT based 3D model of an ovine femur as well as the surface of the model’s medullary canal.

Stem cell regulatory gene expression in human adult dental pulp and periodontal ligament cells undergoing odontogenic/osteogenic differentiation

Introduction During development and regeneration, odontogenesis and osteogenesis are initiated by a cascade of signals driven by several master regulatory genes. Methods In this study, we investigated the differential expression of 84 stem cell–related genes in dental pulp cells (DPCs) and periodontal ligament cells (PDLCs) undergoing odontogenic/osteogenic differentiation. Results Our results showed that, although there was considerable overlap, certain genes had more differential expression in PDLCs than in DPCs. CCND2, DLL1, and MME were the major upregulated genes in both PDLCs and DPCs, whereas KRT15 was the only gene significantly downregulated in PDLCs and DPCs in both odontogenic and osteogenic differentiation. Interestingly, a large number of regulatory genes in odontogenic and osteogenic differentiation interact or crosstalk via Notch, Wnt, transforming growth factor β (TGF-β)/bone morphogenic protein (BMP), and cadherin signaling pathways, such as the regulation of APC, DLL1, CCND2, BMP2, and CDH1. Using a rat dental pulp and periodontal defect model, the expression and distribution of both BMP2 and CDH1 have been verified for their spatial localization in dental pulp and periodontal tissue regeneration. Conclusions This study has generated an overview of stem cell–related gene expression in DPCs and PDLCs during odontogenic/osteogenic differentiation and revealed that these genes may interact through the Notch, Wnt, TGF-β/BMP, and cadherin signalling pathways to play a crucial role in determining the fate of dental derived cell and dental tissue regeneration. These findings provided a new insight into the molecular mechanisms of the dental tissue mineralization and regeneration

Beyond the inner city : real and imagined places in creative place policy and practice

As the economic and social benefits of creative industries development become increasingly visible, policymakers worldwide are working to create policy drivers to ensure that certain places become or remain ‘creative places’. Richard Florida’s work has become particularly influential among policymakers, as has Landry’s. But as the first wave of creative industrial policy development and implementation wanes, important questions are emerging. It is by now clear that an ‘ideal creative place’ has arisen from creative industries policy and planning literature, and that this ideal place is located in inner cities. This article shifts its focus away from the inner city to where most Australians live: the outer suburbs. It reports on a qualitative research study into the practices of outer-suburban creative industries workers in Redcliffe, Australia. It argues that the accepted geography of creative places requires some recalibration once the material and experiential aspects of creative places are taken into account.

Enhanced human bone marrow stromal cell affinity for modified poly(L-lactide) surfaces by the upregulation of adhesion molecular genes

To enhance and regulate cell affinity for poly (l-lactic acid) (PLLA) based materials, two hydrophilic ligands, poly (ethylene glycol) (PEG) and poly (l-lysine) (PLL), were used to develop triblock copolymers: methoxy-terminated poly (ethylene glycol)-block-poly (l-lactide)-block-poly (l-lysine) (MPEG-b-PLLA-b-PLL) in order to regulate protein absorption and cell adhesion. Bone marrow stromal cells (BMSCs) were cultured on different composition of MPEG-b-PLLA-b-PLL copolymer films to determine the effect of modified polymer surfaces on BMSC attachment. To understand the molecular mechanism governing the initial cell adhesion on difference polymer surfaces, the mRNA expression of 84 human extracellular matrix (ECM) and adhesion molecules was analysed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). It was found that down regulation of adhesion molecules was responsible for the impaired BMSC attachment on PLLA surface. MPEG-b-PLLA-b-PLL copolymer films improved significantly the cell adhesion and cytoskeleton expression by upregulation of relevant molecule genes significantly. Six adhesion genes (CDH1, ITGL, NCAM1, SGCE, COL16A1, and LAMA3) were most significantly influenced by the modified PLLA surfaces. In summary, polymer surfaces altered adhesion molecule gene expression of BMSCs, which consequently regulated cell initial attachment on modified PLLA surfaces.

Modulation of the SHBG signalling axis

Sex hormone-binding globulin (SHBG) is a homodimeric plasma glycoprotein that is the major sex steroid carrier-protein in the bloodstream and functions also as a key regulator of steroid bioavailability within target tissues, such as the prostate. Additionally, SHBG binds to prostatic cell membranes via the putative and unidentified SHBG receptor (RSHBG), activating a signal transduction pathway implicated in stimulating both proliferation and expression of prostate specific antigen (PSA) in prostate cell lines in vitro. A yeast-two hybrid assay suggested an interaction between SHBG and kallikrein-related protease (KLK) 4, which is a serine protease implicated in the progression of prostate cancer. The potential interaction between these two proteins was investigated in this PhD thesis to determine whether SHBG is a proteolytic substrate of KLK4 and other members of the KLK family including KLK3/PSA, KLK7 and KLK14. Furthermore, the effects from SHBG proteolytic degradation on SHBG-regulated steroid bioavailability and the activation of the putative RSHBG signal transduction pathway were examined in the LNCaP prostate cancer cell line. SHBG was found to be a proteolytic substrate of the trypsin-like KLK4 and KLK14 in vitro, yielding several proteolysis fragments. Both chymotrypsin-like PSA and KLK7 displayed insignificant proteolytic activity against SHBG. The kinetic parameters of SHBG proteolysis by KLK4 and KLK14 demonstrate a strong enzyme-substrate binding capacity, possessing a Km of 1.2 ± 0.7 µM and 2.1 ± 0.6 µM respectively. The catalytic efficiencies (kcat/Km) of KLK4 and KLK14 proteolysis of SHBG were 1.6 x 104 M-1s-1 and 3.8 x 104 M-1s-1 respectively, which were comparable to parameters previously reported for peptide substrates. N-terminal sequencing of the fragments revealed cleavage near the junction of the N- and C-terminal laminin globulin-like (G-like) domains of SHBG, resulting in the division of the two globulins and ultimately the full degradation of these fragments by KLK4 and KLK14 over time. Proteolytic fragments that may retain steroid binding were rapidly degraded by both proteases, while fragments containing residues beyond the steroid binding pocket were less degraded over the same period of time. Degradation of SHBG was inhibited by the divalent metal cations calcium and zinc for KLK4, and calcium, zinc and magnesium for KLK14. The human secreted serine protease inhibitors (serpins), α1-antitrypsin and α2-antiplasmin, inhibited KLK4 and KLK14 proteolysis of SHBG; α1-antichymotrypsin inhibited KLK4 but not KLK14 activity. The inhibition by these serpins was comparable and in some cases more effective than general trypsin protease inhibitors such as aprotinin and phenylmethanesulfonyl fluoride (PMSF). The binding of 5α-dihydrotestosterone (DHT) to SHBG modulated interactions with KLK4 and KLK14. Steroid-free SHBG was more readily digested by both enzymes than DHT-bound SHBG. Moreover, a binding interaction exists between SHBG and pro-KLK4 and pro-KLK14, with DHT strengthening the binding to pro-KLK4 only. The inhibition of androgen uptake by cultured prostate cancer cells, mediated by SHBG steroid-binding, was examined to assess whether SHBG proteolysis by KLK4 and KLK14 modulated this process. Proteolytic digestion eliminated the ability of SHBG to inhibit the uptake of DHT from conditioned media into LNCaP cells. Therefore, the proteolysis of SHBG by KLK4 and KLK14 increased steroid bioavailability in vitro, leading to an increased uptake of androgens by prostate cancer cells. Interestingly, different transcriptional responses of PSA and KLK2, which are androgen-regulated genes, to DHT-bounsd SHBG treatment were observed between low and high passage number LNCaP cells (lpLNCaP and hpLNCaP respectively). HpLNCaP cells treated with DHT-bound SHBG demonstrated a significant synergistic upregulation of PSA and KLK2 above DHT or SHBG treatment alone, which is similar to previously reported downstream responses from RSHBG-mediated signaling activation. As this result was not seen in lpLNCaP cells, only hpLNCaP cells were further investigated to examine the modulation of potential RSHBG activity by KLK4 and KLK14 proteolysis of SHBG. Contrary to reported results, no increase in intracellular cAMP was observed in hpLNCaP cells when treated with SHBG in the presence and absence of either DHT or estradiol. As a result, the modulation of RSHBG-mediated signaling activation could not be determined. Finally, the identification of the RSHBG from both breast (MCF-7) and prostate cancer (LNCaP) cell lines was attempted. Fluorescently labeled peptides corresponding to the putative receptor binding domain (RBD) of SHBG were shown to be internalized by MCF-7 cells. Crosslinking of the RBD peptide to the cell surfaces of both MCF-7 and LNCaP cells, demonstrated the interaction of the peptide with several targets. These targets were then captured using RBD peptides synthesized onto a hydrophilic scaffold and analysed by mass spectrometry. The samples captured by the RBD peptide returned statistically significantly matches for cytokeratin 8, 18 and 19 as well as microtubule-actin crosslinking factor 1, which may indicate a novel interaction between SHBG and these proteins, but ultimately failed to detect a membrane receptor potentially responsible for the putative RSHBG-mediated signaling. This PhD project has reported the proteolytic processing of SHBG by two members of the kallikrein family, KLK4 and KLK14. The effect of SHBG proteolysis by KLK4 and KLK14 on RSHBG-mediated signaling activation was unable to be determined as the reported signal transduction pathway was not activated after treatment with SHBG, in combination with either DHT or estradiol. However, the digestion of SHBG by these two proteases positively regulated androgen bioavailability to prostate cancer cells in vitro. The increased uptake of androgens is deleterious in prostate cancer due to the promotion of proliferation, metastasis, invasion and the inhibition of apoptosis. The increased bioavailability of androgens, from SHBG proteolysis by KLK4 and KLK14, may therefore promote both carcinogenesis and progression of prostate cancer. Finally, this information may contribute to the development of therapeutic treatment strategies for prostate cancer by inhibiting the proteolysis of SHBG, by KLK4 and KLK14, to prevent the increased uptake of androgens by hormone-dependent cancerous tissues.

Increase in Body Mass Index decreases body satisfaction of their abdominal, arm and thigh regions in young Japanese women [in Japanese]

The aim of the present study was to examine body concern and satisfactions in 191 female university students and their relationships with measured body composition and circumferences of selected body parts. Body composition and circumference measurements of participants were conducted after obtaining their consent. Body concern and satisfaction were determined using the Body Shape Questionnaire (BSQ) and the Body parts and General subscales from the Body Satisfaction Scales (BSS). Increase in body composition and circumferences were associated with decrease in body concern and satisfaction. Increase in body size, including circumferences did not decrease whole body satisfaction but increased dissatisfaction at the abdominal, arm and thigh regions.

Age-related development of a refractive index plateau in the human lens : evidence for a distinct nucleus

The human lens comprises two distinct regions in which the refractive index changes at different rates. The periphery contains a rapidly increasing refractive index gradient, which becomes steeper with age. The inner region contains a shallow gradient, which flattens with age, due to formation of a central plateau, of RI = 1.418, which reaches a maximum size of 7.0 × 3.05 mm around age 60 years. Formation of the plateau can be attributed to compression of fibre cells generated in prenatal life. Present in prenatal but not in postnatal fibre cells, γ-crystallin may play a role in limiting nuclear cell compression.

Uncertainty budget in the measurement of typical airborne number, surface area and mass particle distributions

The effects of particulate matter on environment and public health have been widely studied in recent years. A number of studies in the medical field have tried to identify the specific effect on human health of particulate exposure, but agreement amongst these studies on the relative importance of the particles’ size and its origin with respect to health effects is still lacking. Nevertheless, air quality standards are moving, as the epidemiological attention, towards greater focus on the smaller particles. Current air quality standards only regulate the mass of particulate matter less than 10 μm in aerodynamic diameter (PM10) and less than 2.5 μm (PM2.5). The most reliable method used in measuring Total Suspended Particles (TSP), PM10, PM2.5 and PM1 is the gravimetric method since it directly measures PM concentration, guaranteeing an effective traceability to international standards. This technique however, neglects the possibility to correlate short term intra-day variations of atmospheric parameters that can influence ambient particle concentration and size distribution (emission strengths of particle sources, temperature, relative humidity, wind direction and speed and mixing height) as well as human activity patterns that may also vary over time periods considerably shorter than 24 hours. A continuous method to measure the number size distribution and total number concentration in the range 0.014 – 20 μm is the tandem system constituted by a Scanning Mobility Particle Sizer (SMPS) and an Aerodynamic Particle Sizer (APS). In this paper, an uncertainty budget model of the measurement of airborne particle number, surface area and mass size distributions is proposed and applied for several typical aerosol size distributions. The estimation of such an uncertainty budget presents several difficulties due to i) the complexity of the measurement chain, ii) the fact that SMPS and APS can properly guarantee the traceability to the International System of Measurements only in terms of number concentration. In fact, the surface area and mass concentration must be estimated on the basis of separately determined average density and particle morphology. Keywords: SMPS-APS tandem system, gravimetric reference method, uncertainty budget, ultrafine particles.