Sortase A : an ideal target for anti-virulence drug development

Sortase A is a membrane enzyme responsible for the anchoring of surface-exposed proteins to the cell wall envelope of Gram-positive bacteria. As a well-studied member of the sortase subfamily catalysing the cell wall anchoring of important virulence factors to the surface of staphylococci, enterococci and streptococci, sortase A plays a critical role in Gram-positive bacterial pathogenesis. It is thus considered a promising target for the development of new anti-infective drugs that aim to interfere with important Gram-positive virulence mechanisms, such as adhesion to host tissues, evasion of host defences, and biofilm formation. The additional properties of sortase A as an enzyme that is not required for Gram-positive bacterial growth or viability and is conveniently located on the cell membrane making it more accessible to inhibitor targeting, constitute additional reasons reinforcing the view that sortase A is an ideal target for anti-virulence drug development. Many inhibitors of sortase A have been identified to date using high-throughput or in silico screening of compound libraries (synthetic or natural), and while many have proved useful tools for probing the action model of the enzyme, several are also promising candidates for the development into potent inhibitors. This review is focused on the most promising sortase A inhibitor compounds that are currently in development as leads towards a new class of anti-infective drugs that are urgently needed to help combat the alarming increase in antimicrobial resistance.

Adaptive finite element analysis of elliptic problems based on bubble-type local mesh generation

A new mesh adaptivity algorithm that combines a posteriori error estimation with bubble-type local mesh generation (BLMG) strategy for elliptic differential equations is proposed. The size function used in the BLMG is defined on each vertex during the adaptive process based on the obtained error estimator. In order to avoid the excessive coarsening and refining in each iterative step, two factor thresholds are introduced in the size function. The advantages of the BLMG-based adaptive finite element method, compared with other known methods, are given as follows: the refining and coarsening are obtained fluently in the same framework; the local a posteriori error estimation is easy to implement through the adjacency list of the BLMG method; at all levels of refinement, the updated triangles remain very well shaped, even if the mesh size at any particular refinement level varies by several orders of magnitude. Several numerical examples with singularities for the elliptic problems, where the explicit error estimators are used, verify the efficiency of the algorithm. The analysis for the parameters introduced in the size function shows that the algorithm has good flexibility.

Student reporting abroad : a journalism project built on internationalisation

This article updates research by the writer on overseas reporting trips for Australian Journalism students, conducted since 2000. It describes changing educational contexts, with expanded internationalisation and work integrated learning. A precursor of both, the trips project provides a Faculty-level model for implementing such changes. Previous research, to 2008, recorded 60 students making nine field trips, to South-east Asia, China, Papua New Guinea or Europe. Participants working as foreign correspondents for campus-based media outlets, would apply that experience to theoretical work, e.g. on international journalism or inter-cultural issues. The research has supported arguments for internationalisation of the curriculum, positing that intensified experience will concentrate the mind, improve skills and stimulate reflection. The present work goes further, with more individual and detailed probing of student responses. As a case study, nine participants travelling to South-east Asia and Europe in 2012 documented their experience and their reflective work. The investigation concludes such travel programs can be highly effective in core learning.

Mapping Hydrophobicity on the Protein Molecular Surface at Atom-Level Resolution

A precise representation of the spatial distribution of hydrophobicity, hydrophilicity and charges on the molecular surface of proteins is critical for the understanding of the interaction with small molecules and larger systems. The representation of hydrophobicity is rarely done at atom-level, as this property is generally assigned to residues. A new methodology for the derivation of atomic hydrophobicity from any amino acid-based hydrophobicity scale was used to derive 8 sets of atomic hydrophobicities, one of which was used to generate the molecular surfaces for 35 proteins with convex structures, 5 of which, i.e., lysozyme, ribonuclease, hemoglobin, albumin and IgG, have been analyzed in more detail. Sets of the molecular surfaces of the model proteins have been constructed using spherical probes with increasingly large radii, from 1.4 to 20 A˚, followed by the quantification of (i) the surface hydrophobicity; (ii) their respective molecular surface areas, i.e., total, hydrophilic and hydrophobic area; and (iii) their relative densities, i.e., divided by the total molecular area; or specific densities, i.e., divided by property-specific area. Compared with the amino acid-based formalism, the atom-level description reveals molecular surfaces which (i) present an approximately two times more hydrophilic areas; with (ii) less extended, but between 2 to 5 times more intense hydrophilic patches; and (iii) 3 to 20 times more extended hydrophobic areas. The hydrophobic areas are also approximately 2 times more hydrophobicity-intense. This, more pronounced "leopard skin"-like, design of the protein molecular surface has been confirmed by comparing the results for a restricted set of homologous proteins, i.e., hemoglobins diverging by only one residue (Trp37). These results suggest that the representation of hydrophobicity on the protein molecular surfaces at atom-level resolution, coupled with the probing of the molecular surface at different geometric resolutions, can capture processes that are otherwise obscured to the amino acid-based formalism.

Moving forwards with the aim of going backwards fast : high performance rowing as a learning environment

Background and Purpose: - This paper focuses on the learning culture within the high performance levels of rowing. In doing so, we explore the case of an individual’s learning as he moves across athletic, coaching and administrative functions. This exploration draws on a cultural learning framework and complementary theorisings related to reflexivity. Method - This study makes use of an intellectually, morally and collaboratively challenging approach whereby one member of the research team was also the sole participant of this study. The participant’s careers as a high performance athlete, coach and administrator, coupled with his experience in conducting empirical research presented a rare opportunity to engage in collaborative research (involving degrees of insider and outsider status for each of the research team). We acknowledge that others have looked to combine roles of coach / athlete / administrator with that of researcher however few (if any) have attempted to combine them all in one project. Moreover, coupled with the approach to reflexivity adopted in this study and the authorship contributions we consider this scholarly direction uncommon. Data were comprised of recorded research conversations, a subsequently constructed learning narrative, reflections on the narrative, a stimulated reflective piece from the participant, and a final (re)construction of the participant’s story. Accordingly, data were integrated through an iterative process of thematic analysis. Results - The cultural (i.e., the ways things get done) and structural (e.g., the rules and regulations) properties of high performance rowing were found to shape both the opportunities to be present (e.g., secure a place in the crew) and to learn (e.g., learn the skills required to perform at an Olympic level). However, the individual’s personal properties were brought to bear on re-shaping the constraints such that many limitations could be overcome. In keeping with the theory of learning cultures, the culture of rowing was found to position individuals (a coxswain in this case) differentially. In a similar manner, a range of structural features was found to be important in shaping the cultural and personal elements in performance contexts. For example, the ‘field of play’ was found to be important as a structural feature (i.e., inability of coach to communicate with athletes) in shaping the cultural and personal elements of learning in competition (e.g., positioning the coxswain as an in-boat coach and trusted crewmate). Finally, the cultural and structural elements in rowing appeared to be activated by the participant’s personal elements, most notably his orientation towards quality performance. Conclusion - The participant in this study was found to be driven by the project that he cares about most and at each turn he has bent his understanding of his sport back on itself to see if he can find opportunities to learn and subsequently explore ways to improve performance. The story here emphasises the importance of learner agency, and this is an aspect that has often been missing in recent theorising about learning. In this study, we find an agent using his ‘personal emergent powers to activate the resources in the culture and structure of his sport in an attempt to improve performance. We conclude from this account that this particular high performance rowing culture is one that provided support but nonetheless encouraged those involved, to ‘figure things out’ for themselves – be it as athletes, coaches and/or administrators.

Effects of strain artefacts arising from a pre-defined callus domain in models of bone healing mechanobiology

Iterative computational models have been used to investigate the regulation of bone fracture healing by local mechanical conditions. Although their predictions replicate some mechanical responses and histological features, they do not typically reproduce the predominantly radial hard callus growth pattern observed in larger mammals. We hypothesised that this discrepancy results from an artefact of the models’ initial geometry. Using axisymmetric finite element models, we demonstrated that pre-defining a field of soft tissue in which callus may develop introduces high deviatoric strains in the periosteal region adjacent to the fracture. These bone-inhibiting strains are not present when the initial soft tissue is confined to a thin periosteal layer. As observed in previous healing models, tissue differentiation algorithms regulated by deviatoric strain predicted hard callus forming remotely and growing towards the fracture. While dilatational strain regulation allowed early bone formation closer to the fracture, hard callus still formed initially over a broad area, rather than expanding over time. Modelling callus growth from a thin periosteal layer successfully predicted the initiation of hard callus growth close to the fracture site. However, these models were still susceptible to elevated deviatoric strains in the soft tissues at the edge of the hard callus. Our study highlights the importance of the initial soft tissue geometry used for finite element models of fracture healing. If this cannot be defined accurately, alternative mechanisms for the prediction of early callus development should be investigated.

Aerothermal-strucutral analysis of a rocket launched Mach 8 scramjet experiment : ascent

This paper reports on the methodology and results of a weak-coupled aerothermalstructural analysis on the ascent phase of the SCRAMSPACE Mach 8 scramjet flight experiment. This vehicle was essentially un-shrouded during the flight trajectory, relying on the thin, 5mm thick aluminium external shell of the payload to maintain structural integrity and protect the flight experiment. As such, understanding the thermal-structural response of the vehicle was imperative to mission success. Using two- and three-dimensional models, an iterative procedure was employed to compute the flowfield, convective heating, wall temperatures and structural coupling at flight times covering both peak heating and peak surface temperature. Accounting for such coupling resulted in a 150K reduction in wall temperature compared to the more conservative cold wall assumption. Despite this, peak temperatures remained of the order of 550 K. Further, thermally induced stresses within these regions were in excess of four times the material failure limits. Irreversible material failure during ascent was therefore concluded likely to occur on the external shell. Two alternate materials, steel 1006 and copper, were therefore assessed with the results indicating that steel sections on the external shell resulted in the best thermal-structural response of the payload.

ICEPOLE: High-speed, hardware-oriented authenticated encryption

This paper introduces our dedicated authenticated encryption scheme ICEPOLE. ICEPOLE is a high-speed hardware-oriented scheme, suitable for high-throughput network nodes or generally any environment where specialized hardware (such as FPGAs or ASICs) can be used to provide high data processing rates. ICEPOLE-128 (the primary ICEPOLE variant) is very fast. On the modern FPGA device Virtex 6, a basic iterative architecture of ICEPOLE reaches 41 Gbits/s, which is over 10 times faster than the equivalent implementation of AES-128-GCM. The throughput-to-area ratio is also substantially better when compared to AES-128-GCM. We have carefully examined the security of the algorithm through a range of cryptanalytic techniques and our findings indicate that ICEPOLE offers high security level.

A fast semi-implicit difference method for a nonlinear two-sided space-fractional diffusion equation with variable diffusivity coefficients

In this paper, we derive a new nonlinear two-sided space-fractional diffusion equation with variable coefficients from the fractional Fick’s law. A semi-implicit difference method (SIDM) for this equation is proposed. The stability and convergence of the SIDM are discussed. For the implementation, we develop a fast accurate iterative method for the SIDM by decomposing the dense coefficient matrix into a combination of Toeplitz-like matrices. This fast iterative method significantly reduces the storage requirement of O(n2)O(n2) and computational cost of O(n3)O(n3) down to n and O(nlogn)O(nlogn), where n is the number of grid points. The method retains the same accuracy as the underlying SIDM solved with Gaussian elimination. Finally, some numerical results are shown to verify the accuracy and efficiency of the new method.

A method for optimal fit of patient-specific fracture fixation plates

Anatomically pre-contoured fracture fixation plates are a treatment option for bone fractures. A well-fitting plate can be used as a tool for anatomical reduction of the fractured bone. However, recent studies showed that some plates fit poorly for many patients due to considerable shape variations between bones of the same anatomical site. Therefore, the plates have to be manually fitted and deformed by surgeons to fit each patient optimally. The process is time-intensive and labor-intensive, and could lead to adverse clinical implications such as wound infection or plate failure. This paper proposes a new iterative method to simulate the patient-specific deformation of an optimally fitting plate for pre-operative planning purposes. We further demonstrate the validation of the method through a case study. The proposed method involves the integration of four commercially available software tools, Matlab, Rapidform2006, SolidWorks, and ANSYS, each performing specific tasks to obtain a plate shape that fits optimally for an individual tibia and is mechanically safe. A typical challenge when crossing multiple platforms is to ensure correct data transfer. We present an example of the implementation of the proposed method to demonstrate successful data transfer between the four platforms and the feasibility of the method.

Theorizing why in digital learning: Opening frontiers for inquiry and innovation with technology

Asking why is an important foundation of inquiry and fundamental to the development of reasoning skills and learning. Despite this, and despite the relentless and often disruptive nature of innovations in information and communications technology (ICT), sophisticated tools that directly support this basic act of learning appear to be undeveloped, not yet recognized, or in the very early stages of development. Why is this so? To this question, there is no single factual answer. In response, however, plausible explanations and further questions arise, and such responses are shown to be typical consequences of why-questioning. A range of contemporary scenarios are presented to highlight the problem. Consideration of the various inputs into the evolution of digital learning is introduced to provide historical context and this serves to situate further discussion regarding innovation that supports inquiry-based learning. This theme is further contextualized by narratives on openness in education, in which openness is also shown to be an evolving construct. Explanatory and descriptive contents are differentiated in order to scope out the kinds of digital tools that might support inquiry instigated by why-questioning and which move beyond the search paradigm. Probing why from a linguistic perspective reveals versatile and ambiguous semantics. The why dimension—asking, learning, knowing, understanding, and explaining why—is introduced as a construct that highlights challenges and opportunities for ICT innovation. By linking reflective practice and dialogue with cognitive engagement, this chapter points to specific frontiers for the design and development of digital learning tools, frontiers in which inquiry may find new openings for support.

Numerical modeling of railway track supporting system using finite–infinite and thin layer elements

The present contribution deals with the numerical modelling of railway track-supporting systems-using coupled finite-infinite elements-to represent the near and distant field stress distribution, and also employing a thin layer interface element to account for the interfacial behaviour between sleepers and ballast. To simulate the relative debonding, slipping and crushing at the contact area between sleepers and ballast, a modified Mohr-Coulomb criterion was adopted. Further more an attempt was made to consider the elasto plastic materials’ non-linearity of the railway track supporting media by employing different constitutive models to represent steel, concrete and other supporting materials. It is seen that during an incremental-iterative mode of load application, the yielding initially started from the edge of the sleepers and then flowed vertically downwards and spread towards the centre of the railway supporting system.

Achievement unlocked: Investigating the design of effective gamification experiences for mobile applications and devices

This thesis investigates the design of motivating and engaging software experiences. In particular it examines the use of video game elements in non-game contexts, known as gamification, and how to effectively design gamification experiences for smartphone applications. The original contribution of this thesis is a novel framework for designing gamification, derived from an iterative process of evaluating gamified prototypes. The outcomes of this research can help us to better understand the impact of gamification in today's society and how it can be used to design more effective software.

Centroid training to achieve effective text classification

Traditional text classification technology based on machine learning and data mining techniques has made a big progress. However, it is still a big problem on how to draw an exact decision boundary between relevant and irrelevant objects in binary classification due to much uncertainty produced in the process of the traditional algorithms. The proposed model CTTC (Centroid Training for Text Classification) aims to build an uncertainty boundary to absorb as many indeterminate objects as possible so as to elevate the certainty of the relevant and irrelevant groups through the centroid clustering and training process. The clustering starts from the two training subsets labelled as relevant or irrelevant respectively to create two principal centroid vectors by which all the training samples are further separated into three groups: POS, NEG and BND, with all the indeterminate objects absorbed into the uncertain decision boundary BND. Two pairs of centroid vectors are proposed to be trained and optimized through the subsequent iterative multi-learning process, all of which are proposed to collaboratively help predict the polarities of the incoming objects thereafter. For the assessment of the proposed model, F1 and Accuracy have been chosen as the key evaluation measures. We stress the F1 measure because it can display the overall performance improvement of the final classifier better than Accuracy. A large number of experiments have been completed using the proposed model on the Reuters Corpus Volume 1 (RCV1) which is important standard dataset in the field. The experiment results show that the proposed model has significantly improved the binary text classification performance in both F1 and Accuracy compared with three other influential baseline models.

Emergence in interactive artistic visualization

This research draws on theories of emergence to inform the creation of an artistic and direct visualization. This is an interactive artwork and drawing tool for creative participant experiences. Emergence is characteristically creative and many different models of emergence exist. It is therefore possible to effect creativity through the application of emergence mechanisms from these different disciplines. A review of theories of emergence and examples of visualization in the arts, is provided. An art project led by the author is then discussed in this context. This project, Iterative Intersections, is a collaboration with community artists from Cerebral Palsy League. It has resulted in a number of creative outcomes including the interactive art application, Of me with me. Analytical discussion of this work shows how its construction draws on aspects of experience design, fractal and emergent theory to effect perceptual emergence and creative experience as well as to facilitate self-efficacy.