Strategies for co-targeting the PI3K/AKT/mTOR pathway in NSCLC

The PI3K/AKT/mTOR pathway regulates cell growth and proliferation and is often dysregulated in cancer due to mutation, amplification, deletion, methylation and post-translational modifications. We and others have shown that activation of this pathway in non-small cell lung cancer (NSCLC) leads to a more aggressive disease which correlates to poor prognosis for patients. A multitude of selective inhibitors are in development which target key regulators in this pathway, however the success of PI3K targeted inhibition has been hampered by a high rate of innate and acquired resistance. Response to PI3K inhibition may be improved by co-targeting potential mediators of resistance, such as related cell surface receptors or other intracellular signaling pathways which cross-talk with the PI3K pathway. Inhibition of the PI3K pathway may also overcome radioresistance, chemoresistance and immune evasion in NSCLC. The identification of appropriate patient cohorts who will benefit from PI3K co-targeted inhibition strategies will be key to the success of these inhibitors.

From single crystal surfaces to single atoms : investigating active sites in electrocatalysis

Electrocatalytic processes will undoubtedly be at the heart of energising future transportation and technology with the added importance of being able to create the necessary fuels required to do so in an environmentally friendly and cost effective manner. For this to be successful two almost mutually exclusive surface properties need to be reconciled, namely producing highly active/reactive surface sites that exhibit long term stability. This article reviews the various approaches which have been undertaken to study the elusive nature of these active sites on metal surfaces which are considered as adatoms or clusters of adatoms with low coordination number. This includes the pioneering studies at extended well defined stepped single crystal surfaces using cyclic voltammetry up to the highly sophisticated in situ electrochemical imaging techniques used to study chemically synthesised nanomaterials. By combining the information attained from single crystal surfaces, individual nanoparticles of defined size and shape, density functional theory calculations and new concepts such as mesoporous multimetallic thin films and single atom electrocatalysts new insights into the design and fabrication of materials with highly active but stable active sites can be achieved. The area of electrocatalysis is therefore not only a fascinating and exciting field in terms of realistic technological and economical benefits but also from the fundamental understanding that can be acquired by studying such an array of interesting materials.

Immunization with a MOMP-based vaccine protects mice against a Pulmonary Chlamydia challenge and identifies a disconnection between infection and pathology

Chlamydia pneumoniae is responsible for up to 20% of community acquired pneumonia and can exacerbate chronic inflammatory diseases. As the majority of infections are either mild or asymptomatic, a vaccine is recognized to have the greatest potential to reduce infection and disease prevalence. Using the C. muridarum mouse model of infection, we immunized animals via the intranasal (IN), sublingual (SL) or transcutaneous (TC) routes, with recombinant chlamydial major outer membrane protein (MOMP) combined with adjuvants CTA1-DD or a combination of cholera toxin/CpG-oligodeoxynucleotide (CT/CpG). Vaccinated animals were challenged IN with C. muridarum and protection against infection and pathology was assessed. SL and TC immunization with MOMP and CT/CpG was the most protective, significantly reducing chlamydial burden in the lungs and preventing weight loss, which was similar to the protection induced by a previous live infection. Unlike a previous infection however, these vaccinations also provided almost complete protection against fibrotic scarring in the lungs. Protection against infection was associated with antigen-specific production of IFNγ, TNFα and IL-17 by splenocytes, however, protection against both infection and pathology required the induction of a similar pro-inflammatory response in the respiratory tract draining lymph nodes. Interestingly, we also identified two contrasting vaccinations capable of preventing infection or pathology individually. Animals IN immunized with MOMP and either adjuvant were protected from infection, but not the pathology. Conversely, animals TC immunized with MOMP and CTA1-DD were protected from pathology, even though the chlamydial burden in this group was equivalent to the unimmunized controls. This suggests that the development of pathology following an IN infection of vaccinated animals was independent of bacterial load and may have been driven instead by the adaptive immune response generated following immunization. This identifies a disconnection between the control of infection and the development of pathology, which may influence the design of future vaccines.

Orienting preservice teachers towards gifted education : School university partnerships

Addressing the needs of gifted students is predicated on an understanding of many factors not least the nature of giftedness, appropriate curriculum design and specialist pedagogical practices. Knowledge needs to be acquired in context. Preservice teacher education programs tend to focus on pedagogical practices and present preservice teachers with content related to inclusive philosophies, strategies for teaching, and assessment techniques. Many preservice teachers do not have an awareness of the nature of giftedness or understandings around models of curriculum advocated for gifted education, despite practicum experiences and university education. This paper presents two case studies that describe interventions constructed through partnerships with schools to raise awareness of the nature of giftedness and provide concrete experiences for preservice teachers’ interactions with gifted students. It will report strategies through which preservice teachers become engaged with gifted students in regular classrooms. Qualitative and quantitative evidence will be presented on the effectiveness of these models.

Evaluation of MegaVoltage Cone Beam CT image quality with an unmodified Elekta Precise Linac and EPID : a feasibility study

In order to increase the accuracy of patient positioning for complex radiotherapy treatments various 3D imaging techniques have been developed. MegaVoltage Cone Beam CT (MVCBCT) can utilise existing hardware to implement a 3D imaging modality to aid patient positioning. MVCBCT has been investigated using an unmodified Elekta Precise linac and 15 iView amorphous silicon electronic portal imaging device (EPID). Two methods of delivery and acquisition have been investigated for imaging an anthropomorphic head phantom and quality assurance phantom. Phantom projections were successfully acquired and CT datasets reconstructed using both acquisition methods. Bone, tissue and air were 20 clearly resolvable in both phantoms even with low dose (22 MU) scans. The feasibility of MegaVoltage Cone beam CT was investigated using a standard linac, amorphous silicon EPID and a combination of a free open source reconstruction toolkit as well as custom in-house software written in Matlab. The resultant image quality has 25 been assessed and presented. Although bone, tissue and air were resolvable 2 in all scans, artifacts are present and scan doses are increased when compared with standard portal imaging. The feasibility of MVCBCT with unmodified Elekta Precise linac and EPID has been considered as well as the identification of possible areas for future development in artifact correction techniques to 30 further improve image quality.

Rapid quantification of free cholesterol in tears using direct insertion/electron ionization-Mass spectrometry

Purpose. To establish a simple and rapid analytical method, based on direct insertion/electron ionization-mass spectrometry (DI/EI-MS), for measuring free cholesterol in tears from humans and rabbits. Methods. A stable-isotope dilution protocol employing DI/EI-MS in selected ion monitoring mode was developed and validated. It was used to quantify the free cholesterol content in human and rabbit tear extracts. Tears were collected from adult humans (n = 15) and rabbits (n = 10) and lipids extracted. Results. Screening, full-scan (m/z 40-600) DI/EI-MS analysis of crude tear extracts showed that diagnostic ions located in the mass range m/z 350 to 400 were those derived from free cholesterol, with no contribution from cholesterol esters. DI/EI-MS data acquired using selected ion monitoring (SIM) were analyzed for the abundance ratios of diagnostic ions with their stable isotope-labeled analogues arising from the D6-cholesterol internal standard. Standard curves of good linearity were produced and an on-probe limit of detection of 3 ng (at 3:1 signal to noise) and limit of quantification of 8 ng (at 10:1 signal to noise). The concentration of free cholesterol in human tears was 15 ± 6 μg/g, which was higher than in rabbit tears (10 ± 5 μg/g). Conclusions. A stable-isotope dilution DI/EI-SIM method for free cholesterol quantification without prior chromatographic separation was established. Using this method demonstrated that humans have higher free cholesterol levels in their tears than rabbits. This is in agreement with previous reports. This paper provides a rapid and reliable method to measure free cholesterol in small-volume clinical samples. © 2013 The Association for Research in Vision and Ophthalmology, Inc.

Functional encryption for threshold functions (or fuzzy IBE) from lattices

Cryptosystems based on the hardness of lattice problems have recently acquired much importance due to their average-case to worst-case equivalence, their conjectured resistance to quantum cryptanalysis, their ease of implementation and increasing practicality, and, lately, their promising potential as a platform for constructing advanced functionalities. In this work, we construct “Fuzzy” Identity Based Encryption from the hardness of the Learning With Errors (LWE) problem. We note that for our parameters, the underlying lattice problems (such as gapSVP or SIVP) are assumed to be hard to approximate within supexponential factors for adversaries running in subexponential time. We give CPA and CCA secure variants of our construction, for small and large universes of attributes. All our constructions are secure against selective-identity attacks in the standard model. Our construction is made possible by observing certain special properties that secret sharing schemes need to satisfy in order to be useful for Fuzzy IBE. We also discuss some obstacles towards realizing lattice-based attribute-based encryption (ABE).

Automatic classification of free-text radiology reports to identify limb fractures using machine learning and the SNOMED CT ontology

Objective To develop and evaluate machine learning techniques that identify limb fractures and other abnormalities (e.g. dislocations) from radiology reports. Materials and Methods 99 free-text reports of limb radiology examinations were acquired from an Australian public hospital. Two clinicians were employed to identify fractures and abnormalities from the reports; a third senior clinician resolved disagreements. These assessors found that, of the 99 reports, 48 referred to fractures or abnormalities of limb structures. Automated methods were then used to extract features from these reports that could be useful for their automatic classification. The Naive Bayes classification algorithm and two implementations of the support vector machine algorithm were formally evaluated using cross-fold validation over the 99 reports. Result Results show that the Naive Bayes classifier accurately identifies fractures and other abnormalities from the radiology reports. These results were achieved when extracting stemmed token bigram and negation features, as well as using these features in combination with SNOMED CT concepts related to abnormalities and disorders. The latter feature has not been used in previous works that attempted classifying free-text radiology reports. Discussion Automated classification methods have proven effective at identifying fractures and other abnormalities from radiology reports (F-Measure up to 92.31%). Key to the success of these techniques are features such as stemmed token bigrams, negations, and SNOMED CT concepts associated with morphologic abnormalities and disorders. Conclusion This investigation shows early promising results and future work will further validate and strengthen the proposed approaches.

Learning and teaching epidemiology with audience response technology

Background The learning and teaching of epidemiology is core to many public health programs. Many students find the content of epidemiology, and specifically risk of bias assessment, challenging to learn. Howbeit, learning is enhanced when knowledge is able to be acquired from an active-learning, hands-on experience. Methods The innovative use of wireless audience response technology “clickers” was incorporated into the lectures of the university’s post-graduate epidemiology units and the tailored epidemiological modules delivered for professional disciplines (e.g. optometry). Clickers were used to apply several pedagogical approaches of active learning including peer-instruction and real-world simulation. Students were also assessed for their gain in knowledge within the lecture (pre-post) and their perceptions of how the use of clickers helped them learn. The routine university-wide end of semester Insight Survey provided further information of the student’s satisfaction with the approach. Results The technology was useful in identifying deficits of knowledge of key concepts either before or after instruction. Where key concepts were re-tested post-lecture, as expected, knowledge increased significantly and provided immediate feed-back to students. Across the lecture series, typically 85% of students identified the technology helped them learn, increased their opportunity to interact with the lecturer, and recommend their use for future classes. The Insight Survey report identified 93% of respondents identified the unit in which clickers were consistently used provided good learning opportunities. Numerous student comments supported the teaching method. Conclusions Epidemiological subject matter lends itself to incorporation of audience response technology. The use of the technology to facilitate interactive voting provides an instant response and participation of everyone to enhance the classroom experience. The pedagogical approach increases students’ knowledge and increases their satisfaction with the unit.

Living City 2013 Workshop

Living City 2013 Workshop, as part of a school term’s design-based curriculum connected to the KGSC/QUT Design Excellence Program and run from 11 February – 1 May, 2013, was essentially a three-day place-based urban design immersion workshop program for 25 Year 11 Visual Art and Design Students and 2 Teachers from Kelvin Grove State College (KGSC) held at both Queensland University of Technology (QUT) Gardens Point Campus and The Edge, State Library of Queensland. Mentored by 4 design professionals, 2 tertiary design academics, 2 public artists, and 12 QUT tertiary design students, the workshop explored youth-inspired public space design solutions for the active Brisbane City Council redevelopment site of Queens Wharf Road precinct. As well as the face-to-face workshops, for Living City 2013, an interactive web environment was introduced to enable students to connect with each other and program mentors throughout the course of the program. The workshop, framed within notions of ecological, economic, social and cultural sustainability, aimed to raise awareness of the layered complexity and perspectives involved in the design of shared city spaces and to encourage young people to voice their own concerns as future citizens about the shape and direction of their city. The program commenced with an introductory student briefing by stakeholders and mentors at KGSC on 11 February, an introduction to site appraisal and site visit held at QUT and Queens Wharf Road on 20 February, and a follow up site analysis session on 6 March. Day 1 Workshop on April 17 at the Edge, State Library of Queensland, as part of the Design Minds partnership (http://designminds.org.au/kelvin-grove-state-college-excellence-in-art-design/), focused on mentoring team development of a concept design for a range of selected sites. Two workshops on April 22 and 23 at QUT, to develop these designs and presentation schemes, followed this. The workshop program culminated in a visual presentation of concept design ideas and discussion with a public audience in the Ideas Gallery on The Deck, King George Square during the Brisbane City Council City Centre Master Plan Ideas Fiesta on 1 May, 2013, as referenced in the Ideas Fiesta Wrap-up Report (http://www.brisbane.qld.gov.au/planning-building/planning-guidelines-tools/city-centre-master-plan/city-centre-master-plan-ideas-fiesta). Students were introduced to design methodology, team thinking strategies, the scope of design practices and professions, presentation skills and post-secondary pathways, while participating teachers acquired content and design learning strategies transferable in many other contexts. The program was fully documented on the Living City website (http://www.livingcity.net.au/LC2013x/index.html) and has been recognised by the Brisbane City Council Youth Strategy 2014-2019 as a best practice model for making Brisbane a well-designed, subtropical city.

On managing information technology capabilities

Information technology (IT) plays a critical role of enabler of activities that improve the performance of business processes. This enabling role of IT resources means continuous investment in IT is a strategic necessity. It is established that organizations’ IT-related capabilities leverage the enabling potential of IT resources. Today’s turbulent and challenging business environment requires organizations to do more from their existing and newly acquired IT resources. To achieve this, organizations need to discover ways or establish environments to nourish their existing IT-related capabilities, and develop new IT-related capabilities. We suggest one such environment, a dynamic IT-learning environment that could contribute to nourishing existing IT-related capabilities, and developing new IT-related capabilities. This environment is a product of coordination of four organizational factors that relate to the ways in which IT-related knowledge is applied to business processes, the accompanying reward structures, and ways in which the IT-related learning and knowledge is shared within the organization. Using 216 field survey responses, this paper shows that two IT-related capabilities of top management commitment to IT initiatives, and shared organizational knowledge between the IT and business unit managers has a stronger positive influence on business process performance in the presence of this dynamic IT-learning environment. The study also shows that a marginal IT-related capability, technical IT skills, has a positive and significant influence on business process performance in the presence of this environment. These outcomes imply that organizations’ internal environments could contribute to the management of their IT-related capabilities.

Pore accessibility by methane and carbon dioxide in coal as determined by neutron scattering

Contrast-matching ultrasmall-angle neutron scattering (USANS) and small-angle neutron scattering (SANS) techniques were used for the first time to determine both the total pore volume and the fraction of the pore volume that is inaccessible to deuterated methane, CD4, in four bituminous coals in the range of pore sizes between ∼10 Å and ∼5 μm. Two samples originated from the Illinois Basin in the U.S.A., and the other two samples were commercial Australian bituminous coals from the Bowen Basin. The total and inaccessible porosity were determined in each coal using both Porod invariant and the polydisperse spherical particle (PDSP) model analysis of the scattering data acquired from coals both in vacuum and at the pressure of CD4, at which the scattering length density of the pore-saturating fluid is equal to that of the solid coal matrix (zero average contrast pressure). The total porosity of the coals studied ranged from 7 to 13%, and the volume of pores inaccessible to CD4 varied from ∼13 to ∼36% of the total pore volume. The volume fraction of inaccessible pores shows no correlation with the maceral composition; however, it increases with a decreasing total pore volume. In situ measurements of the structure of one coal saturated with CO2 and CD4 were conducted as a function of the pressure in the range of 1−400 bar. The neutron scattering intensity from small pores with radii less than 35 Å in this coal increased sharply immediately after the fluid injection for both gases, which demonstrates strong condensation and densification of the invading subcritical CO2 and supercritical methane in small pores.

Small angle X-ray scattering mapping and kinetics study of sub-critical CO2 sorption by two Australian coals

Time- and position-resolved synchrotron small angle X-ray scattering data were acquired from samples of two Australian coal seams: Bulli seam (Bulli 4, Ro=1.42%, Sydney Basin), which naturally contains CO2 and Baralaba seam (Ro=0.67%, Bowen Basin), a potential candidate for sequestering CO2. This experimental approach has provided unique, pore-size-specific insights into the kinetics of CO2 sorption in the micro- and small mesopores (diameter 5 to 175 Å) and the density of the sorbed CO2 at reservoir-like conditions of temperature and hydrostatic pressure. For both samples, at pressures above 5 bar, the density of CO2 confined in pores was found to be uniform, with no densification in near-wall regions. In the Bulli 4 sample, CO2 first flooded the slit pores between polyaromatic sheets. In the pore-size range analysed, the confined CO2 density was close to that of the free CO2. The kinetics data are too noisy for reliable quantitative analysis, but qualitatively indicate faster kinetics in mineral-matter-rich regions. In the Baralaba sample, CO2 preferentially invaded the smallest micropores and the confined CO2 density was up to five times that of the free CO2. Faster CO2 sorption kinetics was found to be correlated with higher mineral matter content but, the mineral-matter-rich regions had lower-density CO2 confined in their pores. Remarkably, the kinetics was pore-size dependent, being faster for smaller pores. These results suggest that injection into the permeable section of an interbedded coal-clastic sequence could provide a viable combination of reasonable injectivity and high sorption capacity.

Identifying factors that promote consumer behaviours causing expired domestic food waste

Many commentators argue that domestic food waste is strongly influenced by consumer behaviours. This article reports on a study using mixed-methods to identify key factors responsible for promoting consumer behaviours that lead to domestic food waste through the lens of the Value-Belief-Norm (VBN) theory. Based on the study’s findings, three factors are proposed that cause behaviours that lead to food waste: supply knowledge – does a consumer know what food they have available; location knowledge – does a consumer know where to locate food items, and; food literacy – to what degree do past experience and acquired knowledge impact on a consumer’s food consumption and wastage practices. We analyse the study’s findings in light of a review of literature about consumer food wastage behaviours and in turn, present new insights into consumer behaviour, food waste, and the use of technology to reduce food waste.

Location of hydrogen atoms in hydronium jarosite

Various models for the crystal structure of hydronium jarosite were determined from Rietveld refinements against neutron powder diffraction patterns collected at ambient temperature and also single-crystal X-ray diffraction data. The possibility of a lower symmetry space group for hydronium jarosite that has been suggested by the literature was investigated. It was found the space group is best described as R3¯m, the same for other jarosite minerals. The hydronium oxygen atom was found to occupy the 3¯m site (3a Wyckoff site). Inadequately refined hydronium bond angles and bond distances without the use of restraints are due to thermal motion and disorder of the hydronium hydrogen atoms across numerous orientations. However, the acquired data do not permit a precise determination of these orientations; the main feature up/down disorder of hydronium is clear. Thus, the highest symmetry model with the least disorder necessary to explain all data was chosen: The hydronium hydrogen atoms were modeled to occupy an m (18 h Wyckoff site) with 50 % fractional occupancy, leading to disorder across two orientations. A rigid body description of the hydronium ion rotated by 60° with H–O–H bond angles of 112° and O–H distances of 0.96 Å was optimal. This rigid body refinement suggests that hydrogen bonds between hydronium hydrogen atoms and basal sulfate oxygen atoms are not predominant. Instead, hydrogen bonds are formed between hydronium hydrogen atoms and hydroxyl oxygen atoms. The structure of hydronium alunite is expected to be similar given that alunite supergroup minerals are isostructural.