Polymorphisms in glutathione S-transferases and non-melanoma skin cancer risk in Australian renal transplant recipients

Caucasian renal transplant recipients from Queensland, Australia have the highest non-melanoma skin cancer (NMSC) risk worldwide. Although ultraviolet light (UVR) exposure is critical, genetic factors also appear important. We and others have shown that polymorphism in the glutathione S-transferases (GST) is associated with NMSC in UK recipients. However, the effect of high UVR exposure and differences in immunosuppressive regimen on these associations is unknown. In this study, we examined allelism in GSTM1, GSTM3, GSTT1 and GSTP1 in 361 Queensland renal transplant recipients. Data on squamous (SCC) and basal cell carcinoma (BCC), UVR/tobacco exposure and genotype were obtained. Associations with both NMSC risk and numbers were examined using logistic and negative binomial regression, respectively. In the total group, GSTM1 AB [P = 0.049, rate ratio (RR) = 0.23] and GSTM3 AA (P = 0.015, RR = 0.50) were associated with fewer SCC. Recipients were then stratified by prednisolone dose (less than or equal to7 versus >7 mg/day). In the low-dose group, GSTT1 null (P = 0.006, RR = 0.20) and GSTP1 Val/Val (P = 0.021, RR = 0.20) were associated with SCC numbers. In contrast, in the high-dose group, GSTM1 AB (P = 0.009, RR = 0.05), GSTM3 AB (P = 0.042, RR = 2.29) and BB (P = 0.014, RR = 5.31) and GSTP1 Val/Val (P = 0.036, RR = 2.98) were associated with SCC numbers. GSTM1 AB (P = 0.016) and GSTP1 Val/Val (P = 0.046) were also associated with fewer BCC in this group. GSTP1 associations were strongest in recipients with lower UVR/tobacco exposure. The data confirm our UK findings, suggesting that protection against UVR-induced oxidative stress is important in NMSC development in recipients, but that this effect depends on the immunosuppressant regimen.

Uncertainty reduction, self-enhancement, and ingroup identification

Two experiments tested the prediction that uncertainty reduction and self-enhancement motivations have an interactive effect on ingroup identification. In Experiment 1 (N = 64), uncertainty and group status were manipulated, and the effect on ingroup identification was measured. As predicted, low-uncertainty participants identified more strongly with a high- than low-status group, whereas high-uncertainty participants showed no preference; and low-status group members identified more strongly under high than low uncertainty, whereas high-status group members showed no preference. Experiment 2 (N = 210) replicated Experiment 1, but with a third independent variable that manipulated how prototypical participants were of their group. As predicted, the effects obtained in Experiment 1 only emerged where participants were highly prototypical. Low prototypicality depressed identification with a low-status group under high uncertainty. The implications of these results for intergroup relations and the role of prototypicality in social identity processes are discussed.

Reactions to positive deviance: Social identity and attribution dimensions

This research examines whether evaluations of positive deviates (i.e. high achieving group members) are influenced by the attributions they make for their performance. We argue that ingroup positive deviates who make group attributions help enhance the ingroup's image and thus attract favorable evaluations. In Experiment 1, ingroup positive deviates who made group attributions were generally evaluated more favorably than ingroup positive deviates who made individual attributions. There was also evidence that the positive deviates' attribution style influenced group and self-evaluations. Evaluations of outgroup positive deviates were not influenced by their attribution style. In Experiment 2, an ingroup positive deviate who was successful and attributed that success to the group was upgraded relative to an ingroup positive deviate who made individual attributions. Group evaluations were also higher when the positive deviate made group attributions. This pattern did not emerge when the positive deviate failed. The results are discussed from a social identity perspective.

Performance analysis of multi-radio AODV in hybrid wireless mesh networks

Wireless Mesh Networks (WMNs), based on commodity hardware, present a promising technology for a wide range of applications due to their self-configuring and self-healing capabilities, as well as their low equipment and deployment costs. One of the key challenges that WMN technology faces is the limited capacity and scalability due to co-channel interference, which is typical for multi-hop wireless networks. A simple and relatively low-cost approach to address this problem is the use of multiple wireless network interfaces (radios) per node. Operating the radios on distinct orthogonal channels permits effective use of the frequency spectrum, thereby, reducing interference and contention. In this paper, we evaluate the performance of the multi-radio Ad-hoc On-demand Distance Vector (AODV) routing protocol with a specific focus on hybrid WMNs. Our simulation results show that under high mobility and traffic load conditions, multi-radio AODV offers superior performance as compared to its single-radio counterpart. We believe that multi-radio AODV is a promising candidate for WMNs, which need to service a large number of mobile clients with low latency and high bandwidth requirements.

Developing a scalable model of recombinant protein yield from Pichia pastoris:the influence of culture conditions, biomass and induction regime

Background The optimisation and scale-up of process conditions leading to high yields of recombinant proteins is an enduring bottleneck in the post-genomic sciences. Typical experiments rely on varying selected parameters through repeated rounds of trial-and-error optimisation. To rationalise this, several groups have recently adopted the 'design of experiments' (DoE) approach frequently used in industry. Studies have focused on parameters such as medium composition, nutrient feed rates and induction of expression in shake flasks or bioreactors, as well as oxygen transfer rates in micro-well plates. In this study we wanted to generate a predictive model that described small-scale screens and to test its scalability to bioreactors. Results Here we demonstrate how the use of a DoE approach in a multi-well mini-bioreactor permitted the rapid establishment of high yielding production phase conditions that could be transferred to a 7 L bioreactor. Using green fluorescent protein secreted from Pichia pastoris, we derived a predictive model of protein yield as a function of the three most commonly-varied process parameters: temperature, pH and the percentage of dissolved oxygen in the culture medium. Importantly, when yield was normalised to culture volume and density, the model was scalable from mL to L working volumes. By increasing pre-induction biomass accumulation, model-predicted yields were further improved. Yield improvement was most significant, however, on varying the fed-batch induction regime to minimise methanol accumulation so that the productivity of the culture increased throughout the whole induction period. These findings suggest the importance of matching the rate of protein production with the host metabolism. Conclusion We demonstrate how a rational, stepwise approach to recombinant protein production screens can reduce process development time.

Altering the ribosomal subunit ratio in yeast maximizes recombinant protein yield

Background The production of high yields of recombinant proteins is an enduring bottleneck in the post-genomic sciences that has yet to be addressed in a truly rational manner. Typically eukaryotic protein production experiments have relied on varying expression construct cassettes such as promoters and tags, or culture process parameters such as pH, temperature and aeration to enhance yields. These approaches require repeated rounds of trial-and-error optimization and cannot provide a mechanistic insight into the biology of recombinant protein production. We published an early transcriptome analysis that identified genes implicated in successful membrane protein production experiments in yeast. While there has been a subsequent explosion in such analyses in a range of production organisms, no one has yet exploited the genes identified. The aim of this study was to use the results of our previous comparative transcriptome analysis to engineer improved yeast strains and thereby gain an understanding of the mechanisms involved in high-yielding protein production hosts. Results We show that tuning BMS1 transcript levels in a doxycycline-dependent manner resulted in optimized yields of functional membrane and soluble protein targets. Online flow microcalorimetry demonstrated that there had been a substantial metabolic change to cells cultured under high-yielding conditions, and in particular that high yielding cells were more metabolically efficient. Polysome profiling showed that the key molecular event contributing to this metabolically efficient, high-yielding phenotype is a perturbation of the ratio of 60S to 40S ribosomal subunits from approximately 1:1 to 2:1, and correspondingly of 25S:18S ratios from 2:1 to 3:1. This result is consistent with the role of the gene product of BMS1 in ribosome biogenesis. Conclusion This work demonstrates the power of a rational approach to recombinant protein production by using the results of transcriptome analysis to engineer improved strains, thereby revealing the underlying biological events involved.

The genetics of primary congenital glaucoma

One of the objectives of the molecular biological study of glaucoma is to establish how the disease develops as a result of the production of aberrant gene products. Many of the genes associated with glaucoma code for proteins which are likely to be directly or indirectly involved in the development and/or function of cells within the trabecular meshwork. The identification of specific defects in these genes is likely to lead to a better understanding of the mechanisms involved in PCG and glaucoma in general and to the development of alternative therapies to surgery. The CYP1B1 gene in particular, which is a linked to congenital glaucoma, and is expressed in the trabecular meshwork, codes for a member of the cytochrome P450 group of proteins. These iron binding proteins constitute a family of enzymes involved in the processes of xenobiotic metabolism, growth, and development. The discovery of the CYP1B1 gene in PCG emphases the importance of abnormalities in the molecular structure of proteins expressed in cells of the trabecular network as a cause of PCG. The identification of specific genetic defects leads to the possibility of more widespread screening for PCG especially in affected families and hence, the possibility of the identification of asymptomatic carriers of the disease. Early identification of 'at risk' parents may then enable earlier detection of PCG and intervention in the infant.

Representational modes of thinking employed by children aged thirteen and fourteen, and their relationship to performance in standardised tests of ability, measures of creativity and personality

This thesis proposes that despite many experimental studies of thinking, and the development of models of thinking, such as Bruner's (1966) enactive, iconic and symbolic developmental modes, the imagery and inner verbal strategies used by children need further investigation to establish a coherent, theoretical basis from which to create experimental curricula for direct improvement of those strategies. Five hundred and twenty-three first, second and third year comprehensive school children were tested on 'recall' imagery, using a modified Betts Imagery Test; and a test of dual-coding processes (Paivio, 1971, p.179), by the P/W Visual/Verbal Questionnaire, measuring 'applied imagery' and inner verbalising. Three lines of investigation were pursued: 1. An investigation a. of hypothetical representational strategy differences between boys and girls; and b. the extent to which strategies change with increasing age. 2. The second and third year children's use of representational processes, were taken separately and compared with performance measures of perception, field independence, creativity, self-sufficiency and self-concept. 3. The second and third year children were categorised into four dual-coding strategy groups: a. High Visual/High Verbal b. Low Visual/High Verbal c. High Visual/Low Verbal d. Low Visual/Low Verbal These groups were compared on the same performance measures. The main result indicates that: 1. A hierarchy of dual-coding strategy use can be identified that is significantly related (.01, Binomial Test) to success or failure in the performance measures: the High Visual/High Verbal group registering the highest scores, the Low Visual/High Verbal and High Visual/Low Verbal groups registering intermediate scores, and the Low Visual/Low Verbal group registering the lowest scores on the performance measures. Subsidiary results indicate that: 2. Boys' use of visual strategies declines, and of verbal strategies increases, with age; girls' recall imagery strategy increases with age. Educational implications from the main result are discussed, the establishment of experimental curricula proposed, and further research suggested.

Electronic properties of homoepitaxial (111) highly boron-doped diamond films

The use of diamond as a semiconductor for the realization of transistor structures, which can operate at high temperatures (>700 K), is of increasing interest. In terms of bipolar devices, the growth of n-type phosphorus doped diamond is more efficient on the (111) growth plane; p-type boron-doped diamond growth has been most usually grown in the (100) direction and, hence, this study into the electronic properties, at high temperatures, of boron-doped diamond (111) homoepitaxial layers. It is shown that highly doped layers (hole carrier concentrations as high as 2×1020 cm-3) can be produced without promoting the onset of (unwanted) hopping conduction. The persistence of valance-band conduction in these films enables relatively high mobility values to be measured ( ~ 20 cm2/V?s) and, intriguingly, these values are not significantly reduced at high temperatures. The layers also display very low compensation levels, a fact that may explain the high mobility values since compensation is required for hopping conduction. The results are discussed in terms of the potential of these types of layers for use with high temperature compatible diamond transistors.

Adaptive message rate control of infrastructured DSRC vehicle networks for coexisting road safety and non-safety applications

Intelligent transport system (ITS) has large potentials on road safety applications as well as nonsafety applications. One of the big challenges for ITS is on the reliable and cost-effective vehicle communications due to the large quantity of vehicles, high mobility, and bursty traffic from the safety and non-safety applications. In this paper, we investigate the use of dedicated short-range communications (DSRC) for coexisting safety and non-safety applications over infrastructured vehicle networks. The main objective of this work is to improve the scalability of communications for vehicles networks, ensure QoS for safety applications, and leave as much as possible bandwidth for non-safety applications. A two-level adaptive control scheme is proposed to find appropriate message rate and control channel interval for safety applications. Simulation results demonstrated that this adaptive method outperforms the fixed control method under varying number of vehicles. © 2012 Wenyang Guan et al.

Nucleoside diphosphate kinase--a component of the [Na+1]- and [Cl-]-sensitive phosphorylation cascade in human and murine airway epithelium

We have shown that proteins within apically enriched fractions of human nasal respiratory epithelium vary their phosphohistidine content with ambient [Cl-] and other anion concentrations. This membrane-delimited phosphorylation cascade includes a multifunctional protein histidine kinase - nucleoside diphosphate kinase (NDPK). NDPK is itself a cascade component in both human and ovine airway, the self-phosphorylation of which is inhibited selectively by [Na+] in the presence of ATP (but not GTP). These findings led us to propose the existence of a dual anion-/cation-controlled phosphorylation-based "sensor" bound to the apical membrane. The present study showed that this cascade uses ATP to phosphorylate a group of proteins above 45 kDa (p45-group, identities unknown). Additionally, the Cl- dependence of ATP (but not GTP) phosphorylation is conditional on phosphatase activity and that interactions exist between the ATP- and GTP-phosphorylated components of the cascade under Cl--free conditions. As a prelude to studies in cystic fibrosis (CF) mice, we showed in the present study that NDPK is present and functionally active in normal murine airway. Since NDPK is essential for UTP synthesis and regulates fetal gut development, G proteins, K+channels, neutrophil-mediated inflammation and pancreatic secretion, the presence of ion-regulated NDPK protein in mouse airway epithelium might aid understanding of the pathogenesis of CF.

ACARS:adaptive context - aware rate selection for DSRC in vehicular networks

Throughput plays a vital role for data transfer in Vehicular Networks which is useful for both safety and non-safety applications. An algorithm that adapts to mobile environment by using Context information has been proposed in this paper. Since one of the problems of existing rate adaptation algorithm is underutilization of link capacity in Vehicular environments, we have demonstrated that in wireless and mobile environments, vehicles can adapt to high mobility link condition and still perform better due to regular vehicles that will be out of communication range due to range checking and then de-congest the network thereby making the system perform better since fewer vehicles will contend for network resources. In this paper, we have design, implement and analyze ACARS, a more robust algorithm with significant increase in throughput performance and energy efficiency in the mist of high mobility of vehicles.

An artificial neural network stratifies the risks of reintervention and mortality after endovascular aneurysm repair:a retrospective observational study

Background Lifelong surveillance after endovascular repair (EVAR) of abdominal aortic aneurysms (AAA) is considered mandatory to detect potentially life-threatening endograft complications. A minority of patients require reintervention but cannot be predictively identified by existing methods. This study aimed to improve the prediction of endograft complications and mortality, through the application of machine-learning techniques. Methods Patients undergoing EVAR at 2 centres were studied from 2004-2010. Pre-operative aneurysm morphology was quantified and endograft complications were recorded up to 5 years following surgery. An artificial neural networks (ANN) approach was used to predict whether patients would be at low- or high-risk of endograft complications (aortic/limb) or mortality. Centre 1 data were used for training and centre 2 data for validation. ANN performance was assessed by Kaplan-Meier analysis to compare the incidence of aortic complications, limb complications, and mortality; in patients predicted to be low-risk, versus those predicted to be high-risk. Results 761 patients aged 75 +/- 7 years underwent EVAR. Mean follow-up was 36+/- 20 months. An ANN was created from morphological features including angulation/length/areas/diameters/ volume/tortuosity of the aneurysm neck/sac/iliac segments. ANN models predicted endograft complications and mortality with excellent discrimination between a low-risk and high-risk group. In external validation, the 5-year rates of freedom from aortic complications, limb complications and mortality were 95.9% vs 67.9%; 99.3% vs 92.0%; and 87.9% vs 79.3% respectively (p0.001) Conclusion This study presents ANN models that stratify the 5-year risk of endograft complications or mortality using routinely available pre-operative data.

Social support, risk, and adjustment of immigrant preadolescents

The current study was designed to explore the salience of social support, immigrant status, and risk in middle childhood and early adolescence across two time periods as indicated by measures of school adjustment and well-being. Participants included 691 children of public elementary schools in grades 4 and 6 who were interviewed in 1997 (Time 1) and reinterviewed two years later (Time 2); 539 were U.S.-born, and 152 were foreign-born. ^ Repeated measures multivariate analyses of variance (MANOVA's) were conducted to assess the effects of immigrant status and risk on total support, well-being, and school adjustment from Time 1 to Time 2. Follow-up analyses, including Student-Newman-Keuls post hoc tests, were used to test the significance of the differences among the means of support categories (low and high), immigrant status (U.S. born and non-U.S. born), risk (low and high) and time (time 1 and time 2). ^ Results showed that immigrant participants in the high risk group reported significantly lower levels of support than their peers. Further, children of low risk at Time 2 indicated the highest levels of support. Second, immigrant preadolescents, preadolescents who reported low levels of social support, and preadolescents of the high risk reported lower levels of emotional well-being. There was also an interaction of support by risk by time, indicating that children who are at risk and had low levels of social support reported more emotional problems at Time 1. Finally, preadolescents who are at risk and preadolescents who reported lower levels of support were more likely to show school adaptation problems. Findings from this study highlight the importance of a multivariable approach to the study of support, emotional adjustment, and academic adjustment of immigrant preadolescents. ^

Location management and routing in urban vehicular ad hoc networks

In recent years, urban vehicular ad hoc networks (VANETs) are gaining importance for inter-vehicle communication, because they allow for the local communication between vehicles without any infrastructure, configuration effort, and without expensive cellular networks. But such architecture may increase the complexity of routing since there is no central control system in urban VANETs. Therefore, a challenging research task is to improve urban VANETs' routing efficiency. ^ Hence, in this dissertation we propose two location-based routing protocols and a location management protocol to facilitate location-based routing in urban VANETs. The Multi-hop Routing Protocol (MURU) is proposed to make use of predicted mobility and geometry map in urban VANETs to estimate a path's life time and set up robust end-to-end routing paths. The Light-weight Routing Protocol (LIRU) is proposed to take advantage of the node diversity under dynamic channel condition to exploit opportunistic forwarding to achieve efficient data delivery. A scalable location management protocol (MALM) is also proposed to support location-based routing protocols in urban VANETs. MALM uses high mobility in VANETs to help disseminate vehicles' historical location information, and a vehicle is able to implement Kalman-filter based predicted to predict another vehicle's current location based on its historical location information. ^