Fine-mapping the HOXB region detects common variants tagging a rare coding allele : evidence for synthetic association in prostate cancer

The HOXB13 gene has been implicated in prostate cancer (PrCa) susceptibility. We performed a high resolution fine-mapping analysis to comprehensively evaluate the association between common genetic variation across the HOXB genetic locus at 17q21 and PrCa risk. This involved genotyping 700 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of 3195 SNPs in 20,440 PrCa cases and 21,469 controls in The PRACTICAL consortium. We identified a cluster of highly correlated common variants situated within or closely upstream of HOXB13 that were significantly associated with PrCa risk, described by rs117576373 (OR 1.30, P = 2.62×10(-14)). Additional genotyping, conditional regression and haplotype analyses indicated that the newly identified common variants tag a rare, partially correlated coding variant in the HOXB13 gene (G84E, rs138213197), which has been identified recently as a moderate penetrance PrCa susceptibility allele. The potential for GWAS associations detected through common SNPs to be driven by rare causal variants with higher relative risks has long been proposed; however, to our knowledge this is the first experimental evidence for this phenomenon of synthetic association contributing to cancer susceptibility.

Component modeling for SCADA network mapping

Supervisory Control and Data Acquisition systems (SCADA) are widely used to control critical infrastructure automatically. Capturing and analyzing packet-level traffic flowing through such a network is an essential requirement for problems such as legacy network mapping and fault detection. Within the framework of captured network traffic, we present a simple modeling technique, which supports the mapping of the SCADA network topology via traffic monitoring. By characterizing atomic network components in terms of their input-output topology and the relationship between their data traffic logs, we show that these modeling primitives have good compositional behaviour, which allows complex networks to be modeled. Finally, the predictions generated by our model are found to be in good agreement with experimentally obtained traffic.

Mapping the unmappable

Mapping the Unmappable? the Choreography Shared Material on Dying through the Lens of the Technogenetic Dancer. If choreographic movement is a trace, which is already behind at the moment of its appearance, the impulses that move the dancer could be understood to reside in the virtual. Whether they are the internalized instructions of the choreographer, the inscriptions of concepts on the dancing body which shape how the dancer moves, or movement material that has been incorporated over time, this gestalt is somewhat mapped before is materialized. Erin Manning describes the moment before it manifests as the preacceleration of the movement, when the potentialities of the gesture collapse and stabilize into form. This form is transient, appearing as a trace that is dissolving as soon as it appears. In her critique of some approaches to collaborations between dance and technology she describes technology as a prosthetic that constrains the dancer's movement by inducing this collapse into stability and thus limiting the potentiality of the technogenetic body of the dancer. Thus the technology becomes the focus rather than the sophisticated sensorial skills of the dancer in movement. Using this challenge as a provocation, I have explored methods for mapping a choreographed phrase of movement from the piece entitled Shared Material on Dying by Irish choreographer, Liz Roche. I will explore the virtual space before this dance is materialized, through the frame of a technogenetic body. I will uncover, through phenomenological enquiry, the constituent elements that are embedded in this virtual map, that is, the associations, sensations and spatio-temporal reference points that have been incorporated over time. The purpose is to point to possible directions in mapping the virtual dance space and to understand choreographed movements not just in terms of their material trace but also in terms of the associations, sensations and perceptions that give a specific choreography its identity. This undertaking has relevance for archiving dance. This presentation will involve danced choreography alongside documented material to explore multiple perspectives on the piece and the experience of dancing it.

Mind the insolvency gap : lessons to be learned from audit expectations gap theory

There is a general perception that public confidence in the insolvency profession is low as the result of the recent unethical practices of a few high profile liquidators. As a result, the effectiveness of the current regulatory mechanisms has been questioned, leading to a review of the performance of insolvency practitioners and subsequent regulation proposals. The challenge for the insolvency profession is balancing the expectations of the general public whilst ensuring that the obligations and duties imposed upon them are performed to acceptable and realistic standards. It is difficult (if not impossible) for the profession to meet this challenge in the absence of a cohesive framework which identifies those issues that require further regulation as opposed to those that relate to general education on the insolvency process. This paper will examine the audit expectations gap theory in the context of insolvency practitioners and suggests that a model based on this theory provides an effective framework for evaluating the regulation of the insolvency industry.

Mapping mountains : a morphological study of traditional highland settlements in Chittagong Hill tracts of Bangladesh

This thesis is a morphological study of the settlement patterns of the diverse hill groups in Chittagong Hill Tracts – a mountainous borderland of Bangladesh in South Asia. It examines the settlement morphology of a hill town, using a combination of both quantitative and qualitative methods, and explains the recurrent neighbourhood types of the highland groups in relation to their urbanisation. The research findings related to the settlements of diverse cultural groups in a cross-border region of the Asian uplands are also relevant to similar contexts and enquiries. Furthermore, the developed methodological framework that facilitated the data collection process in CHT's culturally diverse regions is also applicable to the investigation of geographic areas with similar socio-cultural complexities. Finally, this research specifically contributes to the literature of cross-cultural studies of highland towns and vernacular settlements in the Asian context.

On mind, mediation and meaning-making

This paper takes inspiration from the integrative model of human mind proposed by Brinkmann (2011, 2012) and argues that the kind of integration that he seeks to attain can only be achieved if the model focuses on the processes that underlie the functioning of the human mind and not on the entities that these processes produce or function by. An alternative integrative model is thus proposed. In the first part of the paper the process of meaning-making will be explored. It will be argued that an integrative conceptualisation of human mind needs to take into account pre-reflective and unmediated as well as reflective and mediated states through which meanings become constructed. In the second part of the paper the idea of semiotic mediation will be explored. It will be argued that an integrative model of human mind needs to focus not only on different kinds of mediators, but also explain how these are used reflectively and non-reflectively by individuals themselves and visibly or invisibly by others in our everyday interactions.

A methodology for mapping Instagram hashtags

While social media research has provided detailed cumulative analyses of selected social media platforms and content, especially Twitter, newer platforms, apps, and visual content have been less extensively studied so far. This paper proposes a methodology for studying Instagram activity, building on established methods for Twitter research by initially examining hashtags, as common structural features to both platforms. In doing so, we outline methodological challenges to studying Instagram, especially in comparison to Twitter. Finally, we address critical questions around ethics and privacy for social media users and researchers alike, setting out key considerations for future social media research.

Multiple iterations : mapping the trace

This paper explores the concept that individual dancers leave traces in a choreographer’s body of work and similarly, that dancers carry forward residue of embodied choreographies into other working processes. This presentation will be grounded in a study of the multiple iterations of a programme of solo works commissioned in 2008 from choreographers John Jasperse, Jodi Melnick, Liz Roche and Rosemary Butcher and danced by the author. This includes an exploration of the development by John Jasperse of themes from his solo into the pieces PURE (2008) and Truth, Revised Histories, Wishful Thinking and Flat Out Lies (2009); an adaptation of the solo Business of the Bloom by Jodi Melnick in 2008 and a further adaptation of Business of the Bloom by this author in 2012. It will map some of the developments that occurred through a number of further performances over five years of the solo Shared Material on Dying by Liz Roche and the working process of the (uncompleted) solo Episodes of Flight by Rosemary Butcher. The purpose is to reflect back on authorship in dance, an art form in which lineages of influence can often be clearly observed. Normally, once a choreographic work is created and performed, it is archived through video recording, notation and/or reviews. The dancer is no longer called upon to represent the dance piece within the archive and thus her/his lived presence and experiential perspective disappears. The author will draw on the different traces still inhabiting her body as pathways towards understanding how choreographic movement circulates beyond this moment of performance. This will include the interrogation of ownership of choreographic movement, as once it becomes integrated in the body of the dancer, who owns the dance? Furthermore, certain dancers, through their individual physical characteristics and moving identities, can deeply influence the formation of choreographic signatures, a proposition that challenges the sole authorship role of the choreographer in dance production. This paper will be delivered in a presentation format that will bleed into movement demonstrations alongside video footage of the works and auto-ethnographic accounts of dancing experience. A further source of knowledge will be drawn from extracts of interviews with other dancers including Sara Rudner, Rebecca Hilton and Catherine Bennett.

Characterization and Mapping of Patterned Ground in the Saginaw Lowlands, Michigan: Possible Evidence for Late-Wisconsin Permafrost

We identified, mapped, and characterized a widespread area (gt;1,020 km2) of patterned ground in the Saginaw Lowlands of Michigan, a wet, flat plain composed of waterlain tills, lacustrine deposits, or both. The polygonal patterned ground is interpreted as a possible relict permafrost feature, formed in the Late Wisconsin when this area was proximal to the Laurentide ice sheet. Cold-air drainage off the ice sheet might have pooled in the Saginaw Lowlands, which sloped toward the ice margin, possibly creating widespread but short-lived permafrost on this glacial lake plain. The majority of the polygons occur between the Glacial Lake Warren strandline (~14.8 cal. ka) and the shoreline of Glacial Lake Elkton (~14.3 cal. ka), providing a relative age bracket for the patterned ground. Most of the polygons formed in dense, wet, silt loam soils on flat-lying sites and take the form of reticulate nets with polygon long axes of 150 to 160 m and short axes of 60 to 90 m. Interpolygon swales, often shown as dark curvilinears on aerial photographs, are typically slightly lower than are the polygon centers they bound. Some portions of these interpolygon swales are infilled with gravel-free, sandy loam sediments. The subtle morphology and sedimentological characteristics of the patterned ground in the Saginaw Lowlands suggest that thermokarst erosion, rather than ice-wedge replacement, was the dominant geomorphic process associated with the degradation of the Late-Wisconsin permafrost in the study area and, therefore, was primarily responsible for the soil patterns seen there today.

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.

Spatial mapping of proteoglycan content in articular cartilage using near-infrared (NIR) spectroscopy

Diagnosis of articular cartilage pathology in the early disease stages using current clinical diagnostic imaging modalities is challenging, particularly because there is often no visible change in the tissue surface and matrix content, such as proteoglycans (PG). In this study, we propose the use of near infrared (NIR) spectroscopy to spatially map PG content in articular cartilage. The relationship between NIR spectra and reference data (PG content) obtained from histology of normal and artificially induced PG-depleted cartilage samples was investigated using principal component (PC) and partial least squares (PLS) regression analyses. Significant correlation was obtained between both data (R2 = 91.40%, p<0.0001). The resulting correlation was used to predict PG content from spectra acquired from whole joint sample, this was then employed to spatially map this component of cartilage across the intact sample. We conclude that NIR spectroscopy is a feasible tool for evaluating cartilage contents and mapping their distribution across mammalian joint