Visual analytics for large-scale bioinformatic data sets

Rapid advances in sequencing technologies (Next Generation Sequencing or NGS) have led to a vast increase in the quantity of bioinformatics data available, with this increasing scale presenting enormous challenges to researchers seeking to identify complex interactions. This paper is concerned with the domain of transcriptional regulation, and the use of visualisation to identify relationships between specific regulatory proteins (the transcription factors or TFs) and their associated target genes (TGs). We present preliminary work from an ongoing study which aims to determine the effectiveness of different visual representations and large scale displays in supporting discovery. Following an iterative process of implementation and evaluation, representations were tested by potential users in the bioinformatics domain to determine their efficacy, and to understand better the range of ad hoc practices among bioinformatics literate users. Results from two rounds of small scale user studies are considered with initial findings suggesting that bioinformaticians require richly detailed views of TF data, features to compare TF layouts between organisms quickly, and ways to keep track of interesting data points.

A large-scale analysis of genetic variants within putative miRNA binding sites in prostate cancer

Prostate cancer is the second most common malignancy among men worldwide. Genome-wide association studies have identified 100 risk variants for prostate cancer, which can explain approximately 33% of the familial risk of the disease. We hypothesized that a comprehensive analysis of genetic variations found within the 3' untranslated region of genes predicted to affect miRNA binding (miRSNP) can identify additional prostate cancer risk variants. We investigated the association between 2,169 miRSNPs and prostate cancer risk in a large-scale analysis of 22,301 cases and 22,320 controls of European ancestry from 23 participating studies. Twenty-two miRSNPs were associated (P<2.3×10(-5)) with risk of prostate cancer, 10 of which were within 7 genes previously not mapped by GWAS studies. Further, using miRNA mimics and reporter gene assays, we showed that miR-3162-5p has specific affinity for the KLK3 rs1058205 miRSNP T-allele, whereas miR-370 has greater affinity for the VAMP8 rs1010 miRSNP A-allele, validating their functional role. SIGNIFICANCE Findings from this large association study suggest that a focus on miRSNPs, including functional evaluation, can identify candidate risk loci below currently accepted statistical levels of genome-wide significance. Studies of miRNAs and their interactions with SNPs could provide further insights into the mechanisms of prostate cancer risk.

R1SVM: A randomised nonlinear approach to large-scale anomaly detection

The problem of unsupervised anomaly detection arises in a wide variety of practical applications. While one-class support vector machines have demonstrated their effectiveness as an anomaly detection technique, their ability to model large datasets is limited due to their memory and time complexity for training. To address this issue for supervised learning of kernel machines, there has been growing interest in random projection methods as an alternative to the computationally expensive problems of kernel matrix construction and sup-port vector optimisation. In this paper we leverage the theory of nonlinear random projections and propose the Randomised One-class SVM (R1SVM), which is an efficient and scalable anomaly detection technique that can be trained on large-scale datasets. Our empirical analysis on several real-life and synthetic datasets shows that our randomised 1SVM algorithm achieves comparable or better accuracy to deep auto encoder and traditional kernelised approaches for anomaly detection, while being approximately 100 times faster in training and testing.

Towards a typology of hashtag publics: A large-scale comparative study of user engagement across trending topics

Twitter’s hashtag functionality is now used for a very wide variety of purposes, from covering crises and other breaking news events through gathering an instant community around shared media texts (such as sporting events and TV broadcasts) to signalling emotive states from amusement to despair. These divergent uses of the hashtag are increasingly recognised in the literature, with attention paid especially to the ability for hashtags to facilitate the creation of ad hoc or hashtag publics. A more comprehensive understanding of these different uses of hashtags has yet to be developed, however. Previous research has explored the potential for a systematic analysis of the quantitative metrics that could be generated from processing a series of hashtag datasets. Such research found, for example, that crisis-related hashtags exhibited a significantly larger incidence of retweets and tweets containing URLs than hashtags relating to televised events, and on this basis hypothesised that the information-seeking and -sharing behaviours of Twitter users in such different contexts were substantially divergent. This article updates such study and their methodology by examining the communicative metrics of a considerably larger and more diverse number of hashtag datasets, compiled over the past five years. This provides an opportunity both to confirm earlier findings, as well as to explore whether hashtag use practices may have shifted subsequently as Twitter’s userbase has developed further; it also enables the identification of further hashtag types beyond the “crisis” and “mainstream media event” types outlined to date. The article also explores the presence of such patterns beyond recognised hashtags, by incorporating an analysis of a number of keyword-based datasets. This large-scale, comparative approach contributes towards the establishment of a more comprehensive typology of hashtags and their publics, and the metrics it describes will also be able to be used to classify new hashtags emerging in the future. In turn, this may enable researchers to develop systems for automatically distinguishing newly trending topics into a number of event types, which may be useful for example for the automatic detection of acute crises and other breaking news events.

Thermogravimetric analysis of selected layered double hydroxides

Thermogravimetric analysis (TG) and powder X-ray diffraction (PXRD) were used to study some selected Mg/Al and Zn/Al layered double hydroxides (LDHs) prepared by co-precipitation. A Mg/Al hydrotalcite was investigated before and after reformation in fluoride and nitrate solutions. Little change in the TG or PXRD patterns was observed. It was proposed that successful intercalation of nitrate anions has occurred. However, the absence of any change in the d(003) interlayer spacing suggests that fluoride anions were not intercalated between the LDH layers. Any fluoride anions that were removed from solution are most likely adsorbed onto the outer surfaces of the hydrotalcite. As fluoride removal was not quantified it is not possible to confirm that this has happened without further experimentation. Carbonate is probably intercalated into the interlayer of these hydrotalcites, as well as fluoride or nitrate. The carbonate most likely originates from either incomplete decarbonation during thermal activation or adsorption from the atmosphere or dissolved in the deionised water. Small and large scale co-precipitation syntheses of a Zn/Al LDH were also investigated to determine if there was any change in the product. While the small scale experiment produced a good quality LDH of reasonable purity; the large scale synthesis resulted in several additional phases. Imprecise measurement and difficulty in handling the large quantities of reagents appeared to be sufficient to alter the reaction conditions causing a mixture of phases to be formed.

Large-volume methacrylate monolith for plasmid purification : process engineering approach to synthesis and application

The extent of exothermicity associated with the construction of large-volume methacrylate monolithic columns has somewhat obstructed the realisation of large-scale rapid biomolecule purification especially for plasmid-based products which have proven to herald future trends in biotechnology. A novel synthesis technique via a heat expulsion mechanism was employed to prepare a 40 mL methacrylate monolith with a homogeneous radial pore structure along its thickness. Radial temperature gradient was recorded to be only 1.8 °C. Maximum radial temperature recorded at the centre of the monolith was 62.3 °C, which was only 2.3 °C higher than the actual polymerisation temperature. Pore characterisation of the monolithic polymer showed unimodal pore size distributions at different radial positions with an identical modal pore size of 400 nm. Chromatographic characterisation of the polymer after functionalisation with amino groups displayed a persistent dynamic binding capacity of 15.5 mg of plasmid DNA/mL. The maximum pressure drop recorded was only 0.12 MPa at a flow rate of 10 mL/min. The polymer demonstrated rapid separation ability by fractionating Escherichia coli DH5α-pUC19 clarified lysate in only 3 min after loading. The plasmid sample collected after the fast purification process was tested to be a homogeneous supercoiled plasmid with DNA electrophoresis and restriction analysis.

Climatic records over the past 30 ka from temperate Australia – a synthesis from the Oz-INTIMATE workgroup

Temperate Australia sits between the heat engine of the tropics and the cold Southern Ocean, encompassing a range of rainfall regimes and falling under the influence of different climatic drivers. Despite this heterogeneity, broad-scale trends in climatic and environmental change are evident over the past 30 ka. During the early glacial period (∼30–22 ka) and the Last Glacial Maximum (∼22–18 ka), climate was relatively cool across the entire temperate zone and there was an expansion of grasslands and increased fluvial activity in regionally important Murray–Darling Basin. The temperate region at this time appears to be dominated by expanded sea ice in the Southern Ocean forcing a northerly shift in the position of the oceanic fronts and a concomitant influx of cold water along the southeast (including Tasmania) and southwest Australian coasts. The deglacial period (∼18–12 ka) was characterised by glacial recession and eventual disappearance resulting from an increase in temperature deduced from terrestrial records, while there is some evidence for climatic reversals (e.g. the Antarctic Cold Reversal) in high resolution marine sediment cores through this period. The high spatial density of Holocene terrestrial records reveals an overall expansion of sclerophyll woodland and rainforest taxa across the temperate region after ∼12 ka, presumably in response to increasing temperature, while hydrological records reveal spatially heterogeneous hydro-climatic trends. Patterns after ∼6 ka suggest higher frequency climatic variability that possibly reflects the onset of large scale climate variability caused by the El Niño/Southern Oscillation.

Synthesis of novel inhibitors blocking Wnt signaling downstream of β-Catenin

Large scale screening of libraries consisting of natural and small molecules led to the identification of many small molecule inhibitors repressing Wnt/β-Catenin signaling. However, targeted synthesis of novel Wnt pathway inhibitors has been rarely described. We developed a modular and expedient way to create the aromatic ring system with an aliphatic ring in between. Our synthesis opens up the possibility, in principle, to substitute all positions at the ring system with any desired substituent. Here, we tested five different haloquinone analogs carrying methoxy- and hydroxy-groups at different positions. Bona fide Wnt activity assays in cell culture and in Xenopus embryos revealed that two of these compounds act as potent inhibitors of aberrant activated Wnt/β-Catenin signaling.

Chemo-enzymatic synthesis of unnatural amino acids

A general chemo-enzymatic process has been developed to prepare enantiomerically pure L- and D-amino acids in high yield by deracemisation of racemic starting materials. The method has been developed from initial academic studies to be a robust, scalable industrial process. Unnatural amino acids, in high optical purity, are a rapidly growing class of intermediates required for pharmaceuticals, agrochemicals and other fine chemical applications. However, no single method has proven sufficiently adaptable to prepare these compounds generally at large scale. Our approach uses an enantioselective oxidase biocatalyst and a non-selective chemical reducing agent to effect the stereoinversion of one enantiomer and can result in an enantiomeric excess of > 99 % from a starting racemate, and product yields over 90 %. The current approach compares very favourably to resolution methods which have a maximum single pass yield of 50 %. Efficient methods have been developed to adapt the biocatalyst used in this process towards new target compounds and to optimise key factors which improve the process efficiency and offer competitive economics at scale.

Colloidal semiconductor nanocrystals : controlled synthesis and surface chemistry in organic media

Colloidal semiconductor nanocrystals (CS-NCs) possess compelling benefits of low-cost, large-scale solution processing, and tunable optoelectronic properties through controlled synthesis and surface chemistry engineering. These merits make them promising candidates for a variety of applications. This review focuses on the general strategies and recent developments of the controlled synthesis of CS-NCs in terms of crystalline structure, particle size, dominant exposed facet, and their surface passivation. Highlighted are the organic-media based synthesis of metal chalcogenide (including cadmium, lead, and copper chalcogenide) and metal oxide (including titanium oxide and zinc oxide) nanocrystals. Current challenges and thus future opportunities are also pointed out in this review.

A Framework of Issues in Large Process Modelling Projects

As process management projects have increased in size due to globalised and company-wide initiatives, a corresponding growth in the size of process modeling projects can be observed. Despite advances in languages, tools and methodologies, several aspects of these projects have been largely ignored by the academic community. This paper makes a first contribution to a potential research agenda in this field by defining the characteristics of large-scale process modeling projects and proposing a framework of related issues. These issues are derived from a semi -structured interview and six focus groups conducted in Australia, Germany and the USA with enterprise and modeling software vendors and customers. The focus groups confirm the existence of unresolved problems in business process modeling projects. The outcomes provide a research agenda which directs researchers into further studies in global process management, process model decomposition and the overall governance of process modeling projects. It is expected that this research agenda will provide guidance to researchers and practitioners by focusing on areas of high theoretical and practical relevance.

Fundamental sounds

Fundamental Sounds was a live, intercultural and multidisciplinary concert that presented a new synthesis of music, performance & visual arts addressing the imperative of sustainability in a new and evocative form. The outcome was a ninety-minute concert, performed at a major concert hall venue, involving four live musicians, numerous performers & large-scale projections. The images and the concert were scripted in three key phases that spoke to three epochs of human evolution identified by ontological designer and futurist Tony Fry - ‘Pre-Settlement’, ‘Settlement’ and the era that he suggests that we have now entered – ‘Unsettlement’ (in mind body and spirit). The entire work was professionally recorded for presentation on DVD and audio CD.----- Fundamental Sounds achieved a new synthesis between quality performance forms and cogent critical ideas, engendering an increasingly reflective position for audiences around today’s “era of unsettlement” – an epoch Fry has recognized that we must now move to quickly displace through adopting fundamentally sustainable modes of being and becoming.----- The concert was well attended and evoked a range of strong, reflective reactions from its audiences who were also invited to join and participate within a subsequent ‘community of change’ initiated at that time.

Concurrent multi-scale modeling of civil infrastructures for analyses on structural deterioration—Part I : Modeling methodology and strategy

This paper aims to develop the methodology and strategy for concurrent finite element modeling of civil infrastructures at the different scale levels for the purposes of analyses of structural deteriorating. The modeling strategy and method were investigated to develop the concurrent multi-scale model of structural behavior (CMSM-of-SB) in which the global structural behavior and nonlinear damage features of local details in a large complicated structure could be concurrently analyzed in order to meet the needs of structural-state evaluation as well as structural deteriorating. In the proposed method, the “large-scale” modeling is adopted for the global structure with linear responses between stress and strain and the “small-scale” modeling is available for nonlinear damage analyses of the local welded details. A longitudinal truss in steel bridge decks was selected as a case to study how a CMSM-of-SB was developed. The reduced-scale specimen of the longitudinal truss was studied in the laboratory to measure its dynamic and static behavior in global truss and local welded details, while the multi-scale models using constraint equations and substructuring were developed for numerical simulation. The comparison of dynamic and static response between the calculated results by different models indicated that the proposed multi-scale model was found to be the most efficient and accurate. The verification of the model with results from the tested truss under the specific loading showed that, responses at the material scale in the vicinity of local details as well as structural global behaviors could be obtained and fit well with the measured results. The proposed concurrent multi-scale modeling strategy and implementation procedures were applied to Runyang cable-stayed bridge (RYCB) and the CMSM-of-SB of the bridge deck system was accordingly constructed as a practical application.

Power system stability analysis based on descriptive study of electrical indices

In a power network, when a propagation energy wave caused by a disturbance hits a weak link, a reflection is appeared and some of energy is transferred across the link. In this work, an analytical descriptive methodology is proposed to study the dynamical stability of a large scale power system. For this purpose, the measured electrical indices (angle, or voltage/frequency) following a fault in different points among the network are used, and the behaviors of the propagated waves through the lines, nodes and buses are studied. This work addresses a new tool for power system stability analysis based on a descriptive study of electrical measurements. The proposed methodology is also useful to detect the contingency condition and synthesis of an effective emergency control scheme.