Scanning the genome for essential hypertension loci

1. Essential hypertension occurs in people with an underlying genetic predisposition who subject themselves to adverse environmental influences. The number of genes involved is unknown, as is the extent to which each contributes to final blood pressure and the severity of the disease. 2. In the past, studies of potential candidate genes have been performed by association (case-control) analysis of unrelated individuals or linkage (pedigree or sibpair) analysis of families. These studies have resulted in several positive findings but, as one may expect, also an enormous number of negative results. 3. In order to uncover the major genetic loci for essential hypertension, it is proposed that scanning the genome systematically in 100- 200 affected sibships should prove successful. 4. This involves genotyping sets of hypertensive sibships to determine their complement of several hundred microsatellite polymorphisms. Those that are highly informative, by having a high heterozygosity, are most suitable. Also, the markers need to be spaced sufficiently evenly across the genome so as to ensure adequate coverage. 5. Tests are performed to determine increased segregation of alleles of each marker with hypertension. The analytical tools involve specialized statistical programs that can detect such differences. Non- parametric multipoint analysis is an appropriate approach. 6. In this way, loci for essential hypertension are beginning to emerge.

Rank minimization across appearance and shape for AAM ensemble fitting

Active Appearance Models (AAMs) employ a paradigm of inverting a synthesis model of how an object can vary in terms of shape and appearance. As a result, the ability of AAMs to register an unseen object image is intrinsically linked to two factors. First, how well the synthesis model can reconstruct the object image. Second, the degrees of freedom in the model. Fewer degrees of freedom yield a higher likelihood of good fitting performance. In this paper we look at how these seemingly contrasting factors can complement one another for the problem of AAM fitting of an ensemble of images stemming from a constrained set (e.g. an ensemble of face images of the same person).

A parametric analysis technique for design of fuel cell and hybrid-electric vehicles

This paper presents a new simplified parametric analysis technique for the design of fuel cell and hybrid-electric vehicles. The technique utilizes a comprehensive set of ∼30 parameters to fully characterize the vehicle platform, powertrain components, vehicle performance requirements and driving conditions. It is best applied to the sizing of powertrain components and prediction of energy consumption in a vehicle. This new parametric technique makes a good complement to existing vehicle simulation software packages and therefore represents a potentially valuable tool for the hybrid vehicle designer.

Controlling whole blood activation and resultant clot properties on various material surfaces : a possible therapeutic approach for enhancing bone healing

Injured bone initiates the healing process by forming a blood clot at the damaged site. However, in severe damage, synthetic bone implants are used to provide structural integrity and restore the healing process. The implant unavoidably comes into direct contact with whole blood, leading to a blood clot formation on its surface. Despite this, most research in bone tissue engineering virtually ignores the important role of a blood clot in supporting healing. Surface chemistry of a biomaterial is a crucial property in mediating blood-biomaterials interactions, and hence the formation of the resultant blood clot. Surfaces presenting mixtures of functional groups carboxyl (–COOH) and methyl (–CH3) have been shown to enhance platelet response and coagulation activation, leading to the formation of fibrin fibres. In addition, it has been shown that varying the compositions of these functional groups and the length of alkyl groups further modulate the immune complement response. In this study, we hypothesised that a biomaterial surface with mixture of –COOH/–CH3(methyl), –CH2CH3 (ethyl) or –(CH2)3CH3 (butyl) groups at different ratios would modulate blood coagulation and complement activation, and eventually tailor the structural and functional properties of the blood clot formed on the surface, which subsequently impacts new bone formation. Firstly, we synthesised a series of materials composed of acrylic acid (AA), and methyl (MMA), ethyl (EMA) or butyl methacrylates (BMA) at different ratios and coated on the inner surfaces of incubation vials. Our surface analysis showed that the amount of –COOH groups on the surface coatings was lower than the ratios of AA prepared in the materials even though the surface content of –COOH groups increased with increasing in AA ratios. It was indicated that the surface hydrophobicity increased with increasing alkyl chain length: –CH 3 > –CH2CH3 > –(CH2)3CH3, and decreased with increasing –COOH groups. No significant differences in surface hydrophobicity was found on surfaces with –CH3 and –CH2CH3 groups in the presence of –COOH groups. The material coating was as smooth as uncoated glass and without any major flaws. The average roughness of material-coated surface (3.99 ± 0.54 nm) was slightly higher than that of uncoated glass surface (2.22 ± 0.29 nm). However, no significant differences in surface average roughness was found among surfaces with the same functionalities at different –COOH ratios nor among surfaces with different alkyl groups but the same –COOH ratios. These suggested that the surface functional groups and their compositions had a combined effect on modulating surface hydrophobicity but not surface roughness. The second part of our study was to investigate the effect of surface functional groups and their compositions on blood cascade activation and structural properties of the formed clots. It was found that surfaces with –COOH/–(CH2)3CH3 induced a faster coagulation activation than those with –COOH/–CH3 and –CH2CH3, regardless of the –COOH ratios. An increase in –COOH ratios on –COOH/–CH3 and –CH2CH3 surfaces decreased the rate of activation. Moreover, all material-coated surfaces markedly reduced the complement activation compared to uncoated glass surfaces, and the pattern of complement activation was entirely similar to that of surface-induced coagulation, suggesting there is an interaction between two cascades. The clots formed on material-coated surfaces had thicker fibrin with a tighter network at the exterior when compared to uncoated glass surfaces. Compared to the clot exteriors, thicker fibrins with a loose network were found in clot interiors. Coated surfaces resulted in more rigid clots with a significantly slower fibrinolysis after 1 h of lysis when compared to uncoated glass surfaces. Significant differences in fibrinolysis after 1 h of lysis among clots on material-coated surfaces correlated well with the differences in fibrin thickness and density at clot exterior. In addition, more growth factors were released during clot formation than during clot lysis. From an intact clot, there was a correlation between the amount of PDGF-AB release and fibrin density. Highest amount of PDGF-AB was released from clots formed on surfaces with 40% –COOH/60% –CH 3 (i.e. 65MMA). During clot lysis, the release of PDGF-AB also correlated with the fibrinolytic rate while the release of TGF-â1 was influenced by the fibrin thickness. This suggested that different clot structures led to different release profiles of growth factors in clot intact and degrading stages. We further validated whether the clots formed on material-coatings provide the microenvironment for improved bone healing by using a rabbit femoral defect model. In this pilot study, the implantation of clots formed on 65MMA coatings significantly increased new bone formation with enhanced chondrogenesis, osteoblasts activity and vascularisation, but decreased inflammatory macrophage number at the defects after 4 weeks when compared to commercial bone grafts ChronOSTM â-TCP granules. Empty defects were observed when blood clot formation was inhibited. In summary, our study demonstrated that surface functional groups and their relative ratios on material coatings synergistically modulate activation of blood cascades, resultant fibrin architecture, rigidity, susceptibility to fibrinolysis as well as growth factor release of the formed clots, which ultimately alter the healing microenvironment of injured bones.

Mainstreaming therapeutic jurisprudence and the adversarial paradigm—incommensurability and the possibility of a shared disciplinary matrix

Problem-solving courts appear to achieve outcomes that are not common in mainstream courts. There are increasing calls for the adoption of more therapeutic and problem-solving practices by mainstream judges in civil and criminal courts in a number of jurisdictions, most notably in the United States and Australia. Currently, a judge who sets out to exercise a significant therapeutic function is likely to be doing so in a specialist court or jurisdiction, outside the mainstream court system, and arguably, outside the adversarial paradigm itself. To some extent, this work is tolerated but marginalised. However, do therapeutic and problem-solving functions have the potential to help define, rather than simply complement, the role of judicial officers? The core question addressed in this thesis is whether the judicial role could evolve to be not just less adversarial, but fundamentally non-adversarial. In other words, could we see—or are we seeing—a juristic paradigm shift not just in the colloquial, casual sense of the word, but in the strong, worldview changing sense meant by Thomas Kuhn? This thesis examines the current relationship between adversarialism and therapeutic jurisprudence in the context of Kuhn’s conception of the transition from periods of ‘normal science’, through periods of anomaly and disciplinary crises to paradigm shifts. It considers whether therapeutic jurisprudence and adversarialism are incommensurable in the Kuhnian sense, and if so, what this means for the relationship between the two, and for the agenda to mainstream therapeutic jurisprudence. The thesis asserts that Kuhnian incommensurability is, in fact, a characteristic of the relationship between adversarialism and therapeutic jurisprudence, but that the possibility of a therapeutic paradigm shift in law can be reconciled with many adversarial and due process principles by relating this incommensurability to a broader disciplinary matrix.

'Sarcobesity' : a metabolic conundrum

Two independent but inter-related conditions that have a growing impact on healthy life expectancy and health care costs in developed nations are an age-related loss of muscle mass (i.e., sarcopenia) and obesity. Sarcopenia is commonly exacerbated in overweight and obese individuals. Progression towards obesity promotes an increase in fat mass and a concomitant decrease in muscle mass, producing an unfavourable ratio of fat to muscle. The coexistence of diminished muscle mass and increased fat mass (so-called 'sarcobesity') is ultimately manifested by impaired mobility and/or development of life-style-related diseases. Accordingly, the critical health issue for a large proportion of adults in developed nations is how to lose fat mass while preserving muscle mass. Lifestyle interventions to prevent or treat sarcobesity include energy-restricted diets and exercise. The optimal energy deficit to reduce body mass is controversial. While energy restriction in isolation is an effective short-term strategy for rapid and substantial weight loss, it results in a reduction of both fat and muscle mass and therefore ultimately predisposes one to an unfavourable body composition. Aerobic exercise promotes beneficial changes in whole-body metabolism and reduces fat mass, while resistance exercise preserves lean (muscle) mass. Current evidence strongly supports the inclusion of resistance and aerobic exercise to complement mild energy-restricted high-protein diets for healthy weight loss as a primary intervention for sarcobesity.

Analysis of acute-phase proteins, AHSG, C3, CLI, HP and SAA, reveals distinctive expression patterns associated with breast, colorectal and lung cancer

Early detection, clinical management and disease recurrence monitoring are critical areas in cancer treatment in which specific biomarker panels are likely to be very important in each of these key areas. We have previously demonstrated that levels of alpha-2-heremans-schmid-glycoprotein (AHSG), complement component C3 (C3), clusterin (CLI), haptoglobin (HP) and serum amyloid A (SAA) are significantly altered in serum from patients with squamous cell carcinoma of the lung. Here, we report the abundance levels for these proteins in serum samples from patients with advanced breast cancer, colorectal cancer (CRC) and lung cancer compared to healthy controls (age and gender matched) using commercially available enzyme-linked immunosorbent assay kits. Logistic regression (LR) models were fitted to the resulting data, and the classification ability of the proteins was evaluated using receiver-operating characteristic curve and leave-one-out cross-validation (LOOCV). The most accurate individual candidate biomarkers were C3 for breast cancer [area under the curve (AUC) = 0.89, LOOCV = 73%], CLI for CRC (AUC = 0.98, LOOCV = 90%), HP for small cell lung carcinoma (AUC = 0.97, LOOCV = 88%), C3 for lung adenocarcinoma (AUC = 0.94, LOOCV = 89%) and HP for squamous cell carcinoma of the lung (AUC = 0.94, LOOCV = 87%). The best dual combination of biomarkers using LR analysis were found to be AHSG + C3 (AUC = 0.91, LOOCV = 83%) for breast cancer, CLI + HP (AUC = 0.98, LOOCV = 92%) for CRC, C3 + SAA (AUC = 0.97, LOOCV = 91%) for small cell lung carcinoma and HP + SAA for both adenocarcinoma (AUC = 0.98, LOOCV = 96%) and squamous cell carcinoma of the lung (AUC = 0.98, LOOCV = 84%). The high AUC values reported here indicated that these candidate biomarkers have the potential to discriminate accurately between control and cancer groups both individually and in combination with other proteins. Copyright © 2011 UICC.

GOMA Birthday Song

This work was commissioned by the Queensland Art Gallery to mark the fifth birthday of the Gallery of Modern Art. The brief was quite open, with the only directive to make the work complement the major exhibition "we miss you magic land!" by Perth artists, Pip & Pop (Tanya Schultz and Nicole Andrijevic). This musical work draws on a similarly otherworldly, childlike theme, influenced in part by the cinematic world of Gene Wilder's Willy Wonka.

The Sessional Academic Success (SAS) project

The Sessional Academic Success (SAS) project is a sustainable, distributed model for supporting sessional staff at QUT. Developed by the Learning and Teaching Unit. SAS complements our Sessional Academic Program (SAP): a sequence of formal academic development workshops explained in complementary nomination. SAS recognises that while these programs are very well received and a crucial aspect of preparing and advancing sessional teachers, they are necessarily encapsulated in the moment of their delivery and are generic, as they address all faculties (with their varied cultures, processes and pedagogies). The SAS project extends this formal, centrally offered activity into local, ‘just in time’, ongoing support within schools. It takes a distributed leadership approach. Experienced sessional academics are recruited and employed as Sessional Academic Success Advisors (SASAs). They provide sessional staff in their schools with contextually specific, needs based, peer-to-peer development opportunities; one-on-one advice on classroom management and strategies for success; and help to trouble-shoot challenges. The SASAs are trained by the Learning and Teaching Unit co-ordinator, and ongoing support is provided centrally and by school-based co-ordinators. This team approach situates the SASAs at the centre of an organisation map (see diagram of support relationships below). The SAS project aims to support sessional staff in their professional development by: • Offering contextual, needs-based support at school level by harnessing local expertise; • Providing further development opportunities that are local and focal; SAS aims to retain Sessional Staff by: • Responding to self-nominated requests for support and ‘just in time’, safe and reliable advice in times of need; • Building sessional staff confidence through help with dealing with challenges from a trusted peer; • Building a supportive academic community for sessional staff, which helps them feel a part of faculty life, and a community of teaching practice. SAS aims to support sessional staff in the development of academic teaching careers by: • Recognising the capacity of experienced sessional staff to support their peers in ways that are unique, valuable and valued and providing the agency to do so; • Providing career advancement and leadership opportunities for sessional staff. SAS takes unique approaches within each school using strategies such as: • Welcomes and schools orientation by SASAs; • Regular check ins; face-to-face advice and online support; • Compiling local resources to complement university wide resources. • Sessional-to-sessional ‘just in time’ training (eg. assessment and marking when marking commences); • Peer feedback and mentoring (the opportunities to sit in more experiences sessionals’ classes; • Sessional staff awards (nominated by students); • Communities of practice to discuss topics and issues with a view to (and support for) publishing on learning and teaching. In these ways, SASAs complement support offered by unit coordinators, administrators, and the Learning and Teaching Unit. Pairing senior and ‘understudy’ advisors ensures a line of succession, sustainability and continuity. A pilot program commenced in 2012 involving three schools (Psychology and Social Work; Electrical Engineering and Computer Science; Media, Entertainment and Creative Arts). It will be expanded across schools in 2013.

Controlling whole blood activation and resultant clot properties by carboxyl and alkyl functional groups on material surfaces : a possible therapeutic approach for enhancing bone healing

Most research virtually ignores the important role of a blood clot in supporting bone healing. In this study, we investigated the effects of surface functional groups carboxyl and alkyl on whole blood coagulation, complement activation and blood clot formation. We synthesised and tested a series of materials with different ratios of carboxyl (–COOH) and alkyl (–CH3, –CH2CH3 and –(CH2)3CH3) groups. We found that surfaces with –COOH/–(CH2)3CH3 induced a faster coagulation activation than those with –COOH/– CH3 and –CH2CH3, regardless of the –COOH ratios. An increase in –COOH ratios on –COOH/–CH3 and –CH2CH3 surfaces decreased the rate of coagulation activation. The pattern of complement activation was entirely similar to that of surface-induced coagulation. All material coated surfaces resulted in clots with thicker fibrin in a denser network at the clot/material interface and a significantly slower initial fibrinolysis when compared to uncoated glass surfaces. The amounts of platelet-derived growth factor-AB (PDGF-AB) and transforming growth factor-b (TGF-b1) released from an intact clot were higher than a lysed clot. The release of PDGF-AB was found to be correlated with the fibrin density. This study demonstrated that surface chemistry can significantly influence the activation of blood coagulation and complement system, resultant clot structure, susceptibility to fibrinolysis as well as release of growth factors, which are important factors determining the bone healing process.

Development of an integrated GIS and land use planning course : impacts of hybrid instructional methods

This study reports an action research undertaken at Queensland University of Technology. It evaluates the effectiveness of the integration of GIS within the substantive domains of an existing land use planning course in 2011. Using student performance, learning experience survey, and questionnaire survey data, it also evaluates the impacts of incorporating hybrid instructional methods (e.g., in-class and online instructional videos) in 2012 and 2013. Results show that: students (re)iterated the importance of GIS in the course justifying the integration; the hybrid methods significantly increased student performance; and unlike replacement, the videos are more suitable as a complement to in-class activity.

DrsG from Streptococcus dysgalactiae subsp equisimilis inhibits the antimicrobial peptide LL- 37

SIC and DRS are related proteins present in only four of the more than 200 Streptococcus pyogenes emm-types. These proteins inhibit complement mediated lysis and/or the activity of certain antimicrobial peptides. A gene encoding a homologue of these proteins, herein called DrsG, has been identified in the related bacterium Streptococcus dysgalactiae subsp equisimilis (SDSE). Here we show that geographically dispersed isolates representing 14 of 50 emm-types examined possess variants of drsG. However not all isolates within the drsG-positive emm-types possess the gene. Sequence comparisons also reveal a high degree of conservation in different SDSE emm-types. To examine the biological activity of DrsG, recombinant versions of two major DrsG variants, DrsGS and DrsGL, were expressed and purified. Western blot analysis using antisera raised to these proteins demonstrated both variants to be expressed and secreted into culture supernatant. Unlike SIC, but similar to DRS, DrsG does not inhibit complement mediated lysis. However, like both SIC and DRS, DrsG is a ligand of the cathelcidin LL-37 and is inhibitory to its bactericidal activity in in vitro assays. The greatest similarity between DrsG and DRS/SIC is found in the signal sequence at the amino terminus and proline rich domains in the C-terminal half of the protein. Conservation of prolines in this latter region also suggests these residues are important in the biology of this family of proteins. This is the first report demonstrating the activity of an AMP inhibitory protein in SDSE. These results also suggest that inhibition of AMP activity is the primary function of this family of proteins. The acquisition of complement inhibitory activity of SIC may reflect its continuing evolution.

QUT Library advances the use of open public tools to navigate genetic inventions and builds research networks

Many emerging economies are dangling the patent system to stimulate bio-technological innovations with the ultimate premise that these will improve their economic and social growth. The patent system mandates full disclosure of the patented invention in exchange of a temporary exclusive patent right. Recently, however, patent offices have fallen short of complying with such a mandate, especially for genetic inventions. Most patent offices provide only static information about disclosed patent sequences and even some do not keep track of the sequence listing data in their own database. The successful partnership of QUT Library and Cambia exemplifies advocacy in Open Access, Open Innovation and User Participation. The library extends its services to various departments within the university, builds and encourages research networks to complement skills needed to make a contribution in the real world.

Whole-genome sequencing reveals untapped genetic potential in Africa’s indigenous cereal crop sorghum

Sorghum is a food and feed cereal crop adapted to heat and drought and a staple for 500 million of the world’s poorest people. Its small diploid genome and phenotypic diversity make it an ideal C4 grass model as a complement to C3 rice. Here we present high coverage (16–45 × ) resequenced genomes of 44 sorghum lines representing the primary gene pool and spanning dimensions of geographic origin, end-use and taxonomic group. We also report the first resequenced genome of S. propinquum, identifying 8 M high-quality SNPs, 1.9 M indels and specific gene loss and gain events in S. bicolor. We observe strong racial structure and a complex domestication history involving at least two distinct domestication events. These assembled genomes enable the leveraging of existing cereal functional genomics data against the novel diversity available in sorghum, providing an unmatched resource for the genetic improvement of sorghum and other grass species.

Paper-based mixed reality sketch augmentation as a conceptual design support tool

This undergraduate student paper explores usage of mixed reality techniques as support tools for conceptual design. A proof-of-concept was developed to illustrate this principle. Using this as an example, a small group of designers was interviewed to determine their views on the use of this technology. These interviews are the main contribution of this paper. Several interesting applications were determined, suggesting possible usage in a wide range of domains. Paper-based sketching, mixed reality and sketch augmentation techniques complement each other, and the combination results in a highly intuitive interface.