Rapid differentiation of isomeric lipids by photodissociation mass spectrometry of fatty acid derivatives

RATIONALE Both traditional electron ionization and electrospray ionization tandem mass spectrometry have demonstrated limitations in the unambiguous identification of fatty acids. In the former case, high electron energies lead to extensive dissociation of the radical cations from which little specific structural information can be obtained. In the latter, conventional collision-induced dissociation (CID) of even-electron ions provides little intra-chain fragmentation and thus few structural diagnostics. New approaches that harness the desirable features of both methods, namely radical-driven dissociation with discrete energy deposition, are thus required. METHODS Herein we describe the derivatization of a structurally diverse suite of fatty acids as 4-iodobenzyl esters (FAIBE). Electrospray ionization of these derivatives in the presence of sodium acetate yields abundant [M+Na]+ ions that can be mass-selected and subjected to laser irradiation (=266nm) on a modified linear ion-trap mass spectrometer. RESULTS Photodissociation (PD) of the FAIBE derivatives yields abundant radical cations by loss of atomic iodine and in several cases selective dissociation of activated carboncarbon bonds (e.g., at allylic positions) are also observed. Subsequent CID of the [M+NaI]center dot+ radical cations yields radical-directed dissociation (RDD) mass spectra that reveal extensive carboncarbon bond dissociation without scrambling of molecular information. CONCLUSIONS Both PD and RDD spectra obtained from derivatized fatty acids provide a wealth of structural information including the position(s) of unsaturation, chain-branching and hydroxylation. The structural information obtained by this approach, in particular the ability to rapidly differentiate isomeric lipids, represents a useful addition to the lipidomics tool box. Copyright (c) 2013 John Wiley & Sons, Ltd.

Clinician-driven automated classification of limb fractures from free-text radiology reports

The aim of this research is to report initial experimental results and evaluation of a clinician-driven automated method that can address the issue of misdiagnosis from unstructured radiology reports. Timely diagnosis and reporting of patient symptoms in hospital emergency departments (ED) is a critical component of health services delivery. However, due to disperse information resources and vast amounts of manual processing of unstructured information, a point-of-care accurate diagnosis is often difficult. A rule-based method that considers the occurrence of clinician specified keywords related to radiological findings was developed to identify limb abnormalities, such as fractures. A dataset containing 99 narrative reports of radiological findings was sourced from a tertiary hospital. The rule-based method achieved an F-measure of 0.80 and an accuracy of 0.80. While our method achieves promising performance, a number of avenues for improvement were identified using advanced natural language processing (NLP) techniques.

Stimulation of osteogenic and angiogenic ability of cells on polymers by pulsed laser deposition of uniform akermanite-glass nanolayer

Polymer biomaterials have been widely used for bone replacement/regeneration because of their unique mechanical properties and workability. Their inherent low bioactivity makes them lack osseointegration with host bone tissue. For this reason, bioactive inorganic particles have been always incorporated into the matrix of polymers to improve their bioactivity. However, mixing inorganic particles with polymers always results in inhomogeneity of particle distribution in polymer matrix with limited bioactivity. This study sets out to apply the pulsed laser deposition (PLD) technique to prepare uniform akermanite (Ca2MgSi2O7, AKT) glass nanocoatings on the surface of two polymers (non-degradable polysulfone (PSU) and degradable polylactic acid (PDLLA)) in order to improve their surface osteogenic and angiogenic activity. The results show that a uniform nanolayer composed of amorphous AKT particles (∼30nm) of thickness 130nm forms on the surface of both PSU and PDLLA films with the PLD technique. The prepared AKT-PSU and AKT-PDLLA films significantly improved the surface roughness, hydrophilicity, hardness and apatite mineralization, compared with pure PSU and PDLLA, respectively. The prepared AKT nanocoatings distinctively enhance the alkaline phosphate (ALP) activity and bone-related gene expression (ALP, OCN, OPN and Col I) of bone-forming cells on both PSU and PDLLA films. Furthermore, AKT nanocoatings on two polymers improve the attachment, proliferation, VEGF secretion and expression of proangiogenic factors and their receptors of human umbilical vein endothelial cells (HUVEC). The results suggest that PLD-prepared bioceramic nanocoatings are very useful for enhancing the physicochemical, osteogenic and angiogenic properties of both degradable and non-degradable polymers for application in bone replacement/regeneration.

A standing vehicle occupant is likely to sustain a more severe injury than one who has flexed knees in an under‐vehicle explosion : a cadaveric study

The lower limb of military vehicle occupants has been the most injured body part due to undervehicle explosions in recent conflicts. Understanding the injury mechanism and causality of injury severity could aid in developing better protection. Therefore, we tested 4 different occupant postures (seated, brace, standing, standing with knee locked in hyper‐extension) in a simulated under‐vehicle explosion (solid blast) using our traumatic injury simulator in the laboratory; we hypothesised that occupant posture would affect injury severity. No skeletal injury was observed in the specimens in seated and braced postures. Severe, impairing injuries were observed in the foot of standing and hyper‐extended specimens. These results demonstrate that a vehicle occupant whose posture at the time of the attack incorporates knee flexion is more likely to be protected against severe skeletal injury to the lower leg.

Evolving a design driven ‘hybrid’ research approach to inform and advance sustainable outcomes in the built environment sector

A significant reduction in global greenhouse gas (GHG) emissions is a priority, and the preservation of existing building stock presents a significant opportunity to reduce the carbon footprint of our built environment. Within this ‘wicked’ problem context, and moving beyond the ad hoc and incremental performance improvements that have been made to date, collaborative and multidisciplinary efforts are required to find rapid and transformational solutions. Design has emerged as a strategic and redirective practice, and lessons can therefore be learned about transformation and potentially applied in the built environment. The purpose of this paper is to discuss a pragmatic and novel research approach for undertaking such applied design driven research. This paper begins with a discussion of key contributions from design science (rational) and action research (reflective) philosophies in creating an emerging methodological ‘hybrid design approach’. This research approach is then discussed in relation to its application to specific research exploring the processes, methods and lessons from design in heritage building retrofit projects. Drawing on both industry and academic knowledge to ensure relevance and rigour, it is anticipated that the hybrid design approach will be useful for others tackling such complex wicked problems that require context-specific solutions.

Model-driven service engineering in home telecare

Health care systems are highly dynamic not just due to developments and innovations in diagnosis and treatments, but also by virtue of emerging management techniques supported by modern information and communication technology. A multitude of stakeholders such as patients, nurses, general practitioners or social carers can be integrated by modeling complex interactions necessary for managing the provision and consumption of health care services. Furthermore, it is the availability of Service-oriented Architecture (SOA) that supports those integration efforts by enabling the flexible and reusable composition of autonomous, loosely-coupled and web-enabled software components. However, there is still the gap between SOA and predominantly business-oriented perspectives (e.g. business process models). The alignment of both views is crucial not just for the guided development of SOA but also for the sustainable evolution of holistic enterprise architectures. In this paper, we combine the Semantic Object Model (SOM) and the Business Process Modelling Notation (BPMN) towards a model-driven approach to service engineering. By addressing a business system in Home Telecare and deriving a business process model, which can eventually be controlled and executed by machines; in particular by composed web services, the full potential of a process-centric SOA is exploited.

eHealth-as-a-Service (eHaaS) : a data-driven decision making approach in Australian context

A commitment in 2010 by the Australian Federal Government to spend $466.7 million dollars on the implementation of personally controlled electronic health records (PCEHR) heralded a shift to a more effective and safer patient centric eHealth system. However, deployment of the PCEHR has met with much criticism, emphasised by poor adoption rates over the first 12 months of operation. An indifferent response by the public and healthcare providers largely sceptical of its utility and safety speaks to the complex sociotechnical drivers and obstacles inherent in the embedding of large (national) scale eHealth projects. With government efforts to inflate consumer and practitioner engagement numbers giving rise to further consumer disillusionment, broader utilitarian opportunities available with the PCEHR are at risk. This paper discusses the implications of establishing the PCEHR as the cornerstone of a holistic eHealth strategy for the aggregation of longitudinal patient information. A viewpoint is offered that the real value in patient data lies not just in the collection of data but in the integration of this information into clinical processes within the framework of a commoditised data-driven approach. Consideration is given to the eHealth-as-a-Service (eHaaS) construct as a disruptive next step for co-ordinated individualised healthcare in the Australian context.

Nanoherding : plasma-chemical synthesis and electric-charge-driven self organization of SiO2 nanodots

We report on the chemical synthesis of the arrays of silicon oxide nanodots and their self-organization on the surface via physical processes triggered by surface charges. The method based on chemically active oxygen plasma leads to the rearrangement of nanostructures and eventually to the formation of groups of nanodots. This behavior is explained in terms of the effect of electric field on the kinetics of surface processes. The direct measurements of the electric charges on the surface demonstrate that the charge correlates with the density and arrangement of nanodots within the array. Extensive numerical simulations support the proposed mechanism and prove a critical role of the electric charges in the self-organization. This simple and environment-friendly self-guided process could be used in the chemical synthesis of large arrays of nanodots on semiconducting surfaces for a variety of applications in catalysis, energy conversion and storage, photochemistry, environmental and biosensing, and several others.

Solitary filamentary structures and nanosecond dynamics in atmospheric-pressure plasmas driven by tailored dc pulses

Nanosecond dynamics of two separated discharge cycles in an asymmetric dielectric barrier discharge is studied using time-resolved current and voltage measurements synchronized with high-speed (∼5 ns) optical imaging. Nanosecond dc pulses with tailored raise and fall times are used to generate solitary filamentary structures (SFSs) during the first cycle and a uniform glow during the second. The SFSs feature ∼1.5 mm thickness, ∼1.9 A peak current, and a lifetime of several hundred nanoseconds, at least an order of magnitude larger than in common microdischarges. This can be used in alternating localized and uniform high-current plasma treatments in various applications.

Effect of Coulomb blockade, gold resistance, and thermal expansion on the electrical resistance of ultrathin gold films

Controlling the electrical resistance of granular thin films is of great importance for many applications, yet a full understanding of electron transport in such films remains a major challenge. We have studied experimentally and by model calculations the temperature dependence of the electrical resistance of ultrathin gold films at temperatures between 2 K and 300 K. Using sputter deposition, the film morphology was varied from a discontinuous film of weakly coupled meandering islands to a continuous film of strongly coupled coalesced islands. In the weak-coupling regime, we compare the regular island array model, the cotunneling model, and the conduction percolation model with our experimental data. We show that the tunnel barriers and the Coulomb blockade energies are important at low temperatures and that the thermal expansion of the substrate and the island resistance affect the resistance at high temperatures. At low temperatures our experimental data show evidence for a transition from electron cotunneling to sequential tunneling but the data can also be interpreted in terms of conduction percolation. The resistivity and temperature coefficient of resistance of the meandering gold islands are found to resemble those of gold nanowires. We derive a simple expression for the temperature at which the resistance changes from non-metal-like behavior into metal-like behavior. In the case of strong island coupling, the total resistance is solely determined by the Ohmic island resistance.

Plasma-driven self-organization of Ni nanodot arrays on Si(100)

The results of the combined experimental and numerical study suggest that nonequilibrium plasma-driven self-organization leads to better size and positional uniformity of nickel nanodot arrays on a Si(100) surface compared with neutral gas-based processes under similar conditions. This phenomenon is explained by introducing the absorption zone patterns, whose areas relative to the small nanodot sizes become larger when the surface is charged. Our results suggest that strongly nonequilibrium and higher-complexity plasma systems can be used to improve ordering and size uniformity in nanodot arrays of various materials, a common and seemingly irresolvable problem in self-organized systems of small nanoparticles. © 2008 American Institute of Physics.

Investigation on bioactivity of titanium dioxide thin films fabricated by electron cyclotron resonance plasma aided pulsed laser deposition

Titanium dioxide thin films with a rutile crystallinite size around 20 nm were fabricated by pulsed laser deposition (PLD) aided with an electron cyclotron resonance (ECR) plasma. With annealing treatment, the crystal size of the rutile crystallinite increased to 100 nm. The apatite-forming ability of the films as deposited and after annealing was investigated in a kind of simulated body fluid with ion concentrations nearly equal to those of human blood plasma. The results indicate that ECR aided PLD is an effective way both to fabricate bioactive titanium dioxide thin films and to optimize the bioactivity of titanium dioxide, with both crystal size and defects of the film taken into account.

Thermodynamical and plasma-driven kinetic growth of high-aspect-ratio nanostructures : effect of hydrogen termination

The results of studies on the growth of high-aspect nanostructures in low-temperature non-equilibrium plasmas of reactive gas mixtures with or without hydrogen are presented. The results suggest that the hydrogen in the reactive plasma strongly affects the length of the nanostructures. This phenomenon is explained in terms of selective hydrogen passivation of the lateral and top surfaces of the surface-supported nanostructures. The theoretical model describes the effect of the atomic hydrogen passivation on the nanostructure shape and predicts the critical hydrogen coverage of the lateral surfaces necessary to achieve the nanostructure growth with the pre-determined shape. Our results demonstrate that the use of a strongly non-equilibrium plasma is very effective in significantly improving the shape control of quasi-one-dimensional single-crystalline nanostructures.

Development of reverse phase protein microarrays for clinical applications and patient-tailored therapy

While genomics provide important information about the somatic genetic changes, and RNA transcript profiling can reveal important expression changes that correlate with outcome and response to therapy, it is the proteins that do the work in the cell. At a functional level, derangements within the proteome, driven by post-translational and epigenetic modifications, such as phosphorylation, is the cause of a vast majority of human diseases. Cancer, for instance, is a manifestation of deranged cellular protein molecular networks and cell signaling pathways that are based on genetic changes at the DNA level. Importantly, the protein pathways contain the drug targets in signaling networks that govern overall cellular survival, proliferation, invasion and cell death. Consequently, the promise of proteomics resides in the ability to extend analysis beyond correlation to causality. A critical gap in the information knowledge base of molecular profiling is an understanding of the ongoing activity of protein signaling in human tissue: what is activated and “in use” within the human body at any given point in time. To address this gap, we have invented a new technology, called reverse phase protein microarrays, that can generate a functional read-out of cell signaling networks or pathways for an individual patient obtained directly from a biopsy specimen. This “wiring diagram” can serve as the basis for both, selection of a therapy and patient stratification.

Fusiform activation to animals is driven by the process, not the stimulus

Previous studies have found that the lateral posterior fusiform gyri respond more robustly to pictures of animals than pictures of manmade objects and suggested that these regions encode the visual properties characteristic of animals. We suggest that such effects actually reflect processing demands arising when items with similar representations must be finely discriminated. In a positron emission tomography (PET) study of category verification with colored photographs of animals and vehicles, there was robust animal-specific activation in the lateral posterior fusiform gyri when stimuli were categorized at an intermediate level of specificity (e.g., dog or car). However, when the same photographs were categorized at a more specific level (e.g., Labrador or BMW), these regions responded equally strongly to animals and vehicles. We conclude that the lateral posterior fusiform does not encode domain-specific representations of animals or visual properties characteristic of animals. Instead, these regions are strongly activated whenever an item must be discriminated from many close visual or semantic competitors. Apparent category effects arise because, at an intermediate level of specificity, animals have more visual and semantic competitors than do artifacts.