Macrophage inhibitory cytokine-1 (MIC-1/GDF15) slows cancer development but increases metastases in TRAMP prostate cancer prone mice

Macrophage inhibitory cytokine-1 (MIC-1/GDF15), a divergent member of the TGF-β superfamily, is over-expressed by many common cancers including those of the prostate (PCa) and its expression is linked to cancer outcome. We have evaluated the effect of MIC-1/GDF15 overexpression on PCa development and spread in the TRAMP transgenic model of spontaneous prostate cancer. TRAMP mice were crossed with MIC-1/GDF15 overexpressing mice (MIC-1fms) to produce syngeneic TRAMPfmsmic-1 mice. Survival rate, prostate tumor size, histopathological grades and extent of distant organ metastases were compared. Metastasis of TC1-T5, an androgen independent TRAMP cell line that lacks MIC-1/GDF15 expression, was compared by injecting intravenously into MIC-1fms and syngeneic C57BL/6 mice. Whilst TRAMPfmsmic-1 survived on average 7.4 weeks longer, had significantly smaller genitourinary (GU) tumors and lower PCa histopathological grades than TRAMP mice, more of these mice developed distant organ metastases. Additionally, a higher number of TC1-T5 lung tumor colonies were observed in MIC-1fms mice than syngeneic WT C57BL/6 mice. Our studies strongly suggest that MIC-1/GDF15 has complex actions on tumor behavior: it limits local tumor growth but may with advancing disease, promote metastases. As MIC-1/GDF15 is induced by all cancer treatments and metastasis is the major cause of cancer treatment failure and cancer deaths, these results, if applicable to humans, may have a direct impact on patient care.

The Multidimensional Loss Scale : validating a cross cultural instrument for measuring loss in Burmese refugees

The Multidimensional Loss Scale: Initial Development and Psychometric Evaluation The Multidimensional Loss Scale (MLS) represents the first instrument designed specifically to measure loss in refugee populations. Researchers developed initial items of the Multidimensional Loss Scale to assess Experience of Loss Events and Loss Distress in a culturally sensitive manner across multiple domains (social, material, intra-personal and cultural). A sample of 70 recently settled Burmese adult refugees completed a battery of questionnaires, including new scale items. Analyses explored the scale’s factor structure, internal consistency, convergent validity and divergent validity. Principal Axis Factoring supported a five-factor model: Loss of Symbolic Self, Loss of Interdependence, Loss of Home, Interpersonal Loss, and Loss of Intrapersonal Integrity. Chronbach’s Alphas indicated satisfactory internal consistency for Experience of Loss Events (.85) and Loss Distress (.92). Convergent and divergent validity of Loss Distress were supported by moderate correlations with interpersonal grief and trauma symptoms and weak correlations with depression and anxiety. The new scale was well received by people from refugee backgrounds and shows promise for application in future research and practice

An automated tool for assessing security-critical designs and programs

This paper describes in detail our Security-Critical Program Analyser (SCPA). SCPA is used to assess the security of a given program based on its design or source code with regard to data flow-based metrics. Furthermore, it allows software developers to generate a UML-like class diagram of their program and annotate its confidential classes, methods and attributes. SCPA is also capable of producing Java source code for the generated design of a given program. This source code can then be compiled and the resulting Java bytecode program can be used by the tool to assess the program's overall security based on our security metrics.

Improving ultrasound excitation systems using a flexible power supply with adjustable voltage and frequency to drive piezoelectric transducers

The ability of a piezoelectric transducer in energy conversion is rapidly expanding in several applications. Some of the industrial applications for which a high power ultrasound transducer can be used are surface cleaning, water treatment, plastic welding and food sterilization. Also, a high power ultrasound transducer plays a great role in biomedical applications such as diagnostic and therapeutic applications. An ultrasound transducer is usually applied to convert electrical energy to mechanical energy and vice versa. In some high power ultrasound system, ultrasound transducers are applied as a transmitter, as a receiver or both. As a transmitter, it converts electrical energy to mechanical energy while a receiver converts mechanical energy to electrical energy as a sensor for control system. Once a piezoelectric transducer is excited by electrical signal, piezoelectric material starts to vibrate and generates ultrasound waves. A portion of the ultrasound waves which passes through the medium will be sensed by the receiver and converted to electrical energy. To drive an ultrasound transducer, an excitation signal should be properly designed otherwise undesired signal (low quality) can deteriorate the performance of the transducer (energy conversion) and increase power consumption in the system. For instance, some portion of generated power may be delivered in unwanted frequency which is not acceptable for some applications especially for biomedical applications. To achieve better performance of the transducer, along with the quality of the excitation signal, the characteristics of the high power ultrasound transducer should be taken into consideration as well. In this regard, several simulation and experimental tests are carried out in this research to model high power ultrasound transducers and systems. During these experiments, high power ultrasound transducers are excited by several excitation signals with different amplitudes and frequencies, using a network analyser, a signal generator, a high power amplifier and a multilevel converter. Also, to analyse the behaviour of the ultrasound system, the voltage ratio of the system is measured in different tests. The voltage across transmitter is measured as an input voltage then divided by the output voltage which is measured across receiver. The results of the transducer characteristics and the ultrasound system behaviour are discussed in chapter 4 and 5 of this thesis. Each piezoelectric transducer has several resonance frequencies in which its impedance has lower magnitude as compared to non-resonance frequencies. Among these resonance frequencies, just at one of those frequencies, the magnitude of the impedance is minimum. This resonance frequency is known as the main resonance frequency of the transducer. To attain higher efficiency and deliver more power to the ultrasound system, the transducer is usually excited at the main resonance frequency. Therefore, it is important to find out this frequency and other resonance frequencies. Hereof, a frequency detection method is proposed in this research which is discussed in chapter 2. An extended electrical model of the ultrasound transducer with multiple resonance frequencies consists of several RLC legs in parallel with a capacitor. Each RLC leg represents one of the resonance frequencies of the ultrasound transducer. At resonance frequency the inductor reactance and capacitor reactance cancel out each other and the resistor of this leg represents power conversion of the system at that frequency. This concept is shown in simulation and test results presented in chapter 4. To excite a high power ultrasound transducer, a high power signal is required. Multilevel converters are usually applied to generate a high power signal but the drawback of this signal is low quality in comparison with a sinusoidal signal. In some applications like ultrasound, it is extensively important to generate a high quality signal. Several control and modulation techniques are introduced in different papers to control the output voltage of the multilevel converters. One of those techniques is harmonic elimination technique. In this technique, switching angles are chosen in such way to reduce harmonic contents in the output side. It is undeniable that increasing the number of the switching angles results in more harmonic reduction. But to have more switching angles, more output voltage levels are required which increase the number of components and cost of the converter. To improve the quality of the output voltage signal with no more components, a new harmonic elimination technique is proposed in this research. Based on this new technique, more variables (DC voltage levels and switching angles) are chosen to eliminate more low order harmonics compared to conventional harmonic elimination techniques. In conventional harmonic elimination method, DC voltage levels are same and only switching angles are calculated to eliminate harmonics. Therefore, the number of eliminated harmonic is limited by the number of switching cycles. In the proposed modulation technique, the switching angles and the DC voltage levels are calculated off-line to eliminate more harmonics. Therefore, the DC voltage levels are not equal and should be regulated. To achieve this aim, a DC/DC converter is applied to adjust the DC link voltages with several capacitors. The effect of the new harmonic elimination technique on the output quality of several single phase multilevel converters is explained in chapter 3 and 6 of this thesis. According to the electrical model of high power ultrasound transducer, this device can be modelled as parallel combinations of RLC legs with a main capacitor. The impedance diagram of the transducer in frequency domain shows it has capacitive characteristics in almost all frequencies. Therefore, using a voltage source converter to drive a high power ultrasound transducer can create significant leakage current through the transducer. It happens due to significant voltage stress (dv/dt) across the transducer. To remedy this problem, LC filters are applied in some applications. For some applications such as ultrasound, using a LC filter can deteriorate the performance of the transducer by changing its characteristics and displacing the resonance frequency of the transducer. For such a case a current source converter could be a suitable choice to overcome this problem. In this regard, a current source converter is implemented and applied to excite the high power ultrasound transducer. To control the output current and voltage, a hysteresis control and unipolar modulation are used respectively. The results of this test are explained in chapter 7.

Rapid aminoacidemia enhances myofibrillar protein synthesis and anabolic intramuscular signaling responses after resistance exercise

Background: Ingestion of whey or casein yields divergent patterns of aminoacidemia that influence whole-body and skeletal muscle myofibrillar protein synthesis (MPS) after exercise. Direct comparisons of the effects of contrasting absorption rates exhibited by these proteins are confounded by their differing amino acid contents. Objective: Our objective was to determine the effect of divergent aminoacidemia by manipulating ingestion patterns of whey protein alone on MPS and anabolic signaling after resistance exercise. Design: In separate trials, 8 healthy men consumed whey protein either as a single bolus (BOLUS; 25-g dose) or as repeated, small, "pulsed" drinks (PULSE; ten 2.5-g drinks every 20 min) to mimic a more slowly digested protein. MPS and phosphorylation of signaling proteins involved in protein synthesis were measured at rest and after resistance exercise. Results: BOLUS increased blood essential amino acid (EAA) concentrations above those of PULSE (162% compared with 53%, P < 0.001) 60 min after exercise, whereas PULSE resulted in a smaller but sustained increase in aminoacidemia that remained elevated above BOLUS amounts later (180-220 min after exercise, P < 0.05). Despite an identical net area under the EAA curve, MPS was elevated to a greater extent after BOLUS than after PULSE early (1-3 h: 95% compared with 42%) and later (3-5 h: 193% compared with 121%) (both P < 0.05). There were greater changes in the phosphorylation of the Akt-mammalian target of rapamycin pathway after BOLUS than after PULSE. Conclusions: Rapid aminoacidemia in the postexercise period enhances MPS and anabolic signaling to a greater extent than an identical amount of protein fed in small pulses that mimic a more slowly digested protein. A pronounced peak aminoacidemia after exercise enhances protein synthesis.

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.

Enhancing learning in large undergraduate classes using custom made audio-visual cases

This is an exploratory study into the effective use of embedding custom made audiovisual case studies (AVCS) in enhancing the student’s learning experience. This paper describes a project that used AVCS for a large divergent cohort of undergraduate students, enrolled in an International Business course. The study makes a number of key contributions to advancing learning and teaching within the discipline. AVCS provide first hand reporting of the case material, where the students have the ability to improve their understanding from both verbal and nonverbal cues. The paper demonstrates how AVCS can be embedded in a student-centred teaching approach to capture the students’ interest and to enhance a deep approach to learning by providing real-world authentic experience.

Deeply divergent mitochondrial lineages reveal patterns of local endemism in chironomids of the Australian Wet Tropics

The Wet Tropics bioregion of north-eastern Australia has been subject to extensive fluctuations in climate throughout the late Pliocene and Pleistocene. Cycles of rainforest contraction and expansion of dry sclerophyll forest associated with such climatic fluctuations are postulated to have played a major role in driving geographical endemism in terrestrial rainforest taxa. Consequences for the distributions of aquatic organisms, however, are poorly understood.The Australian non-biting midge species Echinocladius martini Cranston (Diptera: Chironomidae), although restricted to cool, well-forested freshwater streams, has been considered to be able to disperse among populations located in isolated rainforest pockets during periods of sclerophyllous forest expansion, potentially limiting the effect of climatic fluctuations on patterns of endemism. In this study, mitochondrial COI and 16S data were analysed for E. martini collected from eight sites spanning theWet Tropics bioregion to assess the scale and extent of phylogeographic structure. Analyses of genetic structure showed several highly divergent cryptic lineages with restricted geographical distributions. Within one of the identified lineages, strong genetic structure implied that dispersal among proximate (<1 km apart) streams was extremely restricted. The results suggest that vicariant processes, most likely due to the systemic drying of the Australian continent during the Plio-Pleistocene, might have fragmented historical E. martini populations and, hence, promoted divergence in allopatry.

Young children as regenerative tissue donors : considering the need for legal reform in light of divergent ethical approaches

In Australia, young children who lack decision-making capacity can have regenerative tissue removed to treat another person suffering from a severe or life-threatening disease. While great good can potentially result from this as the recipient’s life may be saved, ethical unease remains over the ‘use’ of young children in this way. This paper examines the ethical approaches that have featured in the debate over the acceptability and limits of this practice, and how these are reflected in Australia’s legal regime governing removal of tissue from young children. This analysis demonstrates a troubling dichotomy within the Australia’s laws that requires decision-makers to adopt inconsistent ethical approaches depending on where a donor child is situated. It is argued that this inconsistency in approach warrants legal reform of this ethically sensitive issue.

A highly divergent South African geminivirus species illuminates the ancient evolutionary history of this family

Background. We have characterised a new highly divergent geminivirus species, Eragrostis curvula streak virus (ECSV), found infecting a hardy perennial South African wild grass. ECSV represents a new genus-level geminivirus lineage, and has a mixture of features normally associated with other specific geminivirus genera. Results. Whereas the ECSV genome is predicted to express a replication associated protein (Rep) from an unspliced complementary strand transcript that is most similar to those of begomoviruses, curtoviruses and topocuviruses, its Rep also contains what is apparently a canonical retinoblastoma related protein interaction motif such as that found in mastreviruses. Similarly, while ECSV has the same unusual TAAGATTCC virion strand replication origin nonanucleotide found in another recently described divergent geminivirus, Beet curly top Iran virus (BCTIV), the rest of the transcription and replication origin is structurally more similar to those found in begomoviruses and curtoviruses than it is to those found in BCTIV and mastreviruses. ECSV also has what might be a homologue of the begomovirus transcription activator protein gene found in begomoviruses, a mastrevirus-like coat protein gene and two intergenic regions. Conclusion. Although it superficially resembles a chimaera of geminiviruses from different genera, the ECSV genome is not obviously recombinant, implying that the features it shares with other geminiviruses are those that were probably present within the last common ancestor of these viruses. In addition to inferring how the ancestral geminivirus genome may have looked, we use the discovery of ECSV to refine various hypotheses regarding the recombinant origins of the major geminivirus lineages. © 2009 Varsani et al; licensee BioMed Central Ltd.

Empirical evaluation of brisbane macroscopic fundamental diagram

The Macroscopic Fundamental Diagram (MFD) relates space-mean density and flow, and the existence with dynamic features was confirmed in congested urban network with real data set from loop detectors and taxi probes. Since the MFD represents the area-wide network traffic performances, it gives foundations for perimeter control strategies and an area traffic state estimation enabling area-based network control. However, limited works have been reported on real world example from signalised arterial network. This paper fuses data from multiple sources (Bluetooth, Loops and Signals) and develops a framework for the development of the MFD for Brisbane. Existence of the MFD in Brisbane network is confirmed. Different MFDs (from whole network and several sub regions) are evaluated to discover the spatial partitioning in network performance representation.

The impact of incidents on macroscopic fundamental diagram

Macroscopic Fundamental Diagram (MFD) has been proved to exist in large urban road and freeway networks by theoretic method and real data in cities. However hysteresis and scatters have also been found existed both on motorway network and urban road. This paper investigates how the incident variables affect the scatter and shape of the MFD using both the simulated data and the real data collected from the Pacific Motorway M3 in Brisbane, Australia. Three key components of incident are investigated based on the simulated data: incident location, incident duration time and traffic demand. Results based on the simulated data indicate that MFD shape is a property not only of the network itself but also of the incident characteristics variables. MFDs for three types of real incidents (crash, hazard and breakdown) are explored separately. The results based on the empirical data are consistent with the simulated results. The hysteresis phenomenon occurs on both the upstream and the downstream of the incident location, but for opposite hysteresis loops. Gradient of the MFD for the upstream is more than that for the downstream on the incident site, when traffic demand is off peak.

Divergent outcomes following transcytosis of IgG targeting intracellular and extracellular chlamydial antigens

Antibodies can play a protective but non-essential role in natural chlamydial infections dependent on antigen specificity and antibody isotype. IgG is the dominant antibody in both male and female reproductive tract mucosal secretions, and is bi-directionally trafficked across epithelia by the neonatal Fc receptor (FcRn). Using physiologically relevant pH-polarized epididymal epithelia grown on Transwells®, IgG specifically targeting an extracellular chlamydial antigen; the Major Outer Membrane Protein (MOMP), enhanced uptake and translocation of infection at pH 6-6.5 but not at neutral pH. This was dependent on FcRn expression. Conversely, FcRn-mediated transport of IgG targeting the intracellular chlamydial inclusion membrane protein A (IncA), induced aberrant inclusion morphology, recruited autophagic proteins independent of lysosomes, and significantly reduced infection. Challenge of female mice with MOMP-specific IgG-opsonized C. muridarum delayed infection clearance but exacerbated oviduct occlusion. In male mice, MOMP-IgG elicited by immunization afforded no protection against testicular chlamydial infection, whereas; the transcytosis of IncA-IgG significantly reduced testicular chlamydial burden. Together these data show that the protective and pathological effects of IgG are dependent on FcRn-mediated transport as well as the specificity of IgG for intracellular or extracellular antigens.

Exploring the properties of macroscopic fundamental diagram : analysing Brisbane urban network

This thesis explored traffic characteristics at the aggregate level for area-wide traffic monitoring of large urban area. It focused on three aspects: understanding a macroscopic network performance under real-time traffic information provision, measuring traffic performance of a signalised arterial network using available data sets, and discussing network zoning for monitoring purposes in the case of Brisbane, Australia. This work presented the use of probe vehicle data for estimating traffic state variables, and illustrated dynamic features of regional traffic performance of Brisbane. The results confirmed the viability and effectiveness of area-wide traffic monitoring.

The game of clones and the Australia tax : divergent views about copyright business models and the willingness of Australian consumers to infringe

It is often said that Australia is a world leader in rates of copyright infringement for entertainment goods. In 2012, the hit television show, Game of Thrones, was the most downloaded television show over bitorrent, and estimates suggest that Australians accounted for a plurality of nearly 10% of the 3-4 million downloads each week. The season finale of 2013 was downloaded over a million times within 24 hours of its release, and again Australians were the largest block of illicit downloaders over BitTorrent, despite our relatively small population. This trend has led the former US Ambassador to Australia to implore Australians to stop 'stealing' digital content, and rightsholders to push for increasing sanctions on copyright infringers. The Australian Government is looking to respond by requiring Internet Service Providers to issue warnings and potentially punish consumers who are alleged by industry groups to have infringed copyright. This is the logical next step in deterring infringement, given that the operators of infringing networks (like The Pirate Bay, for example) are out of regulatory reach. This steady ratcheting up of the strength of copyright, however, comes at a significant cost to user privacy and autonomy, and while the decentralisation of enforcement reduces costs, it also reduces the due process safeguards provided by the judicial process. This article presents qualitative evidence that substantiates a common intuition: one of the major reasons that Australians seek out illicit downloads of content like Game of Thrones in such numbers is that it is more difficult to access legitimately in Australia. The geographically segmented way in which copyright is exploited at an international level has given rise to a ‘tyranny of digital distance’, where Australians have less access to copyright goods than consumers in other countries. Compared to consumers in the US and the EU, Australians pay more for digital goods, have less choice in distribution channels, are exposed to substantial delays in access, and are sometimes denied access completely. In this article we focus our analysis on premium film and television offerings, like Game of Thrones, and through semi-structured interviews, explore how choices in distribution impact on the willingness of Australian consumers to seek out infringing copies of copyright material. Game of Thrones provides an excellent case study through which to frame this analysis: it is both one of the least legally accessible television offerings and one of the most downloaded through filesharing networks of recent times. Our analysis shows that at the same time as rightsholder groups, particularly in the film and television industries, are lobbying for stronger laws to counter illicit distribution, the business practices of their member organisations are counter-productively increasing incentives for consumers to infringe. The lack of accessibility and high prices of copyright goods in Australia leads to substantial economic waste. The unmet consumer demand means that Australian consumers are harmed by lower access to information and entertainment goods than consumers in other jurisdictions. The higher rates of infringement that fulfils some of this unmet demand increases enforcement costs for copyright owners and imposes burdens either on our judicial system or on private entities – like ISPs – who may be tasked with enforcing the rights of third parties. Most worryingly, the lack of convenient and cheap legitimate digital distribution channels risks undermining public support for copyright law. Our research shows that consumers blame rightsholders for failing to meet market demand, and this encourages a social norm that infringing copyright, while illegal, is not morally wrongful. The implications are as simple as they are profound: Australia should not take steps to increase the strength of copyright law at this time. The interests of the public and those of rightsholders align better when there is effective competition in distribution channels and consumers can legitimately get access to content. While foreign rightsholders are seeking enhanced protection for their interests, increasing enforcement is likely to increase their ability to engage in lucrative geographical price-discrimination, particularly for premium content. This is only likely to increase the degree to which Australian consumers feel that their interests are not being met and, consequently, to further undermine the legitimacy of copyright law. If consumers are to respect copyright law, increasing sanctions for infringement without enhancing access and competition in legitimate distribution channels could be dangerously counter-productive. We suggest that rightsholders’ best strategy for addressing infringement in Australia at this time is to ensure that Australians can access copyright goods in a timely, affordable, convenient, and fair lawful manner.