Extending genetic linkage analysis to diffusion tensor images to map single gene effects on brain fiber architecture

We extended genetic linkage analysis - an analysis widely used in quantitative genetics - to 3D images to analyze single gene effects on brain fiber architecture. We collected 4 Tesla diffusion tensor images (DTI) and genotype data from 258 healthy adult twins and their non-twin siblings. After high-dimensional fluid registration, at each voxel we estimated the genetic linkage between the single nucleotide polymorphism (SNP), Val66Met (dbSNP number rs6265), of the BDNF gene (brain-derived neurotrophic factor) with fractional anisotropy (FA) derived from each subject's DTI scan, by fitting structural equation models (SEM) from quantitative genetics. We also examined how image filtering affects the effect sizes for genetic linkage by examining how the overall significance of voxelwise effects varied with respect to full width at half maximum (FWHM) of the Gaussian smoothing applied to the FA images. Raw FA maps with no smoothing yielded the greatest sensitivity to detect gene effects, when corrected for multiple comparisons using the false discovery rate (FDR) procedure. The BDNF polymorphism significantly contributed to the variation in FA in the posterior cingulate gyrus, where it accounted for around 90-95% of the total variance in FA. Our study generated the first maps to visualize the effect of the BDNF gene on brain fiber integrity, suggesting that common genetic variants may strongly determine white matter integrity.

Brain fiber architecture, genetics, and intelligence: a high angular resolution diffusion imaging (HARDI) study

We developed an analysis pipeline enabling population studies of HARDI data, and applied it to map genetic influences on fiber architecture in 90 twin subjects. We applied tensor-driven 3D fluid registration to HARDI, resampling the spherical fiber orientation distribution functions (ODFs) in appropriate Riemannian manifolds, after ODF regularization and sharpening. Fitting structural equation models (SEM) from quantitative genetics, we evaluated genetic influences on the Jensen-Shannon divergence (JSD), a novel measure of fiber spatial coherence, and on the generalized fiber anisotropy (GFA) a measure of fiber integrity. With random-effects regression, we mapped regions where diffusion profiles were highly correlated with subjects' intelligence quotient (IQ). Fiber complexity was predominantly under genetic control, and higher in more highly anisotropic regions; the proportion of genetic versus environmental control varied spatially. Our methods show promise for discovering genes affecting fiber connectivity in the brain.

Mapping genetic influences on brain fiber architecture with high angular resolution diffusion imaging (HARDI)

We report the first 3D maps of genetic effects on brain fiber complexity. We analyzed HARDI brain imaging data from 90 young adult twins using an information-theoretic measure, the Jensen-Shannon divergence (JSD), to gauge the regional complexity of the white matter fiber orientation distribution functions (ODF). HARDI data were fluidly registered using Karcher means and ODF square-roots for interpol ation; each subject's JSD map was computed from the spatial coherence of the ODFs in each voxel's neighborhood. We evaluated the genetic influences on generalized fiber anisotropy (GFA) and complexity (JSD) using structural equation models (SEM). At each voxel, genetic and environmental components of data variation were estimated, and their goodness of fit tested by permutation. Color-coded maps revealed that the optimal models varied for different brain regions. Fiber complexity was predominantly under genetic control, and was higher in more highly anisotropic regions. These methods show promise for discovering factors affecting fiber connectivity in the brain.

Genetics of brain fiber architecture and intellectual performance

The study is the first to analyze genetic and environmental factors that affect brain fiber architecture and its genetic linkage with cognitive function. We assessed white matter integrity voxelwise using diffusion tensor imaging at high magnetic field (4 Tesla), in 92 identical and fraternal twins. White matter integrity, quantified using fractional anisotropy (FA), was used to fit structural equation models (SEM) at each point in the brain, generating three-dimensional maps of heritability. We visualized the anatomical profile of correlations between white matter integrity and full-scale, verbal, and performance intelligence quotients (FIQ, VIQ, and PIQ). White matter integrity (FA) was under strong genetic control and was highly heritable in bilateral frontal (a 2 = 0.55, p = 0.04, left; a 2 = 0.74, p = 0.006, right), bilateral parietal (a 2 = 0.85, p < 0.001, left; a 2 = 0.84, p < 0.001, right), and left occipital (a 2 = 0.76, p = 0.003) lobes, and was correlated with FIQ and PIQ in the cingulum, optic radiations, superior fronto- occipital fasciculus, internal capsule, callosal isthmus, and the corona radiata (p = 0.04 for FIQ and p = 0.01 for PIQ, corrected for multiple comparisons). In a cross-trait mapping approach, common genetic factors mediated the correlation between IQ and white matter integrity, suggesting a common physiological mechanism for both, and common genetic determination. These genetic brain maps reveal heritable aspects of white matter integrity and should expedite the discovery of single-nucleotide polymorphisms affecting fiber connectivity and cognition.

The multivariate A/C/E model and the genetics of fiber architecture

We present a new algorithm to compute the voxel-wise genetic contribution to brain fiber microstructure using diffusion tensor imaging (DTI) in a dataset of 25 monozygotic (MZ) twins and 25 dizygotic (DZ) twin pairs (100 subjects total). First, the structural and DT scans were linearly co-registered. Structural MR scans were nonlinearly mapped via a 3D fluid transformation to a geometrically centered mean template, and the deformation fields were applied to the DTI volumes. After tensor re-orientation to realign them to the anatomy, we computed several scalar and multivariate DT-derived measures including the geodesic anisotropy (GA), the tensor eigenvalues and the full diffusion tensors. A covariance-weighted distance was measured between twins in the Log-Euclidean framework [2], and used as input to a maximum-likelihood based algorithm to compute the contributions from genetics (A), common environmental factors (C) and unique environmental ones (E) to fiber architecture. Quanititative genetic studies can take advantage of the full information in the diffusion tensor, using covariance weighted distances and statistics on the tensor manifold.

Scalar connectivity measures from fast-marching tractography reveal heritability of white matter architecture

Recent advances in diffusion-weighted MRI (DWI) have enabled studies of complex white matter tissue architecture in vivo. To date, the underlying influence of genetic and environmental factors in determining central nervous system connectivity has not been widely studied. In this work, we introduce new scalar connectivity measures based on a computationally-efficient fast-marching algorithm for quantitative tractography. We then calculate connectivity maps for a DTI dataset from 92 healthy adult twins and decompose the genetic and environmental contributions to the variance in these metrics using structural equation models. By combining these techniques, we generate the first maps to directly examine genetic and environmental contributions to brain connectivity in humans. Our approach is capable of extracting statistically significant measures of genetic and environmental contributions to neural connectivity.

Genetic architecture of subcortical brain regions: Common and region-specific genetic contributions

Understanding the aetiology of patterns of variation within and covariation across brain regions is key to advancing our understanding of the functional, anatomical and developmental networks of the brain. Here we applied multivariate twin modelling and principal component analysis (PCA) to investigate the genetic architecture of the size of seven subcortical regions (caudate nucleus, thalamus, putamen, pallidum, hippocampus, amygdala and nucleus accumbens) in a genetically informative sample of adolescents and young adults (N=1038; mean age=21.6±3.2years; including 148 monozygotic and 202 dizygotic twin pairs) from the Queensland Twin IMaging (QTIM) study. Our multivariate twin modelling identified a common genetic factor that accounts for all the heritability of intracranial volume (0.88) and a substantial proportion of the heritability of all subcortical structures, particularly those of the thalamus (0.71 out of 0.88), pallidum (0.52 out of 0.75) and putamen (0.43 out of 0.89). In addition, we also found substantial region-specific genetic contributions to the heritability of the hippocampus (0.39 out of 0.79), caudate nucleus (0.46 out of 0.78), amygdala (0.25 out of 0.45) and nucleus accumbens (0.28 out of 0.52). This provides further insight into the extent and organization of subcortical genetic architecture, which includes developmental and general growth pathways, as well as the functional specialization and maturation trajectories that influence each subcortical region. This multivariate twin study identifies a common genetic factor that accounts for all the heritability of intracranial volume (0.88) and a substantial proportion of the heritability of all subcortical structures, particularly those of the thalamus (0.71 out of 0.88), pallidum (0.52 out of 0.75) and putamen (0.43 out of 0.89). In parallel, it also describes substantial region-specific genetic contributions to the heritability of the hippocampus (0.39 out of 0.79), caudate nucleus (0.46 out of 0.78), amygdala (0.25 out of 0.45) and nucleus accumbens (0.28 out of 0.52).

Towards adaptive management of QoS-aware service compositions - Functional architecture

Service compositions enable users to realize their complex needs as a single request. Despite intensive research, especially in the area of business processes, web services and grids, an open and valid question is still how to manage service compositions in order to satisfy both functional and non-functional requirements as well as adapt to dynamic changes. In this paper we propose an (functional) architecture for adaptive management of QoS-aware service compositions. Comparing to the other existing architectures this one offers two major advantages. Firstly, this architecture supports various execution strategies based on dynamic selection and negotiation of services included in a service composition, contracting based on service level agreements, service enactment with flexible support for exception handling, monitoring of service level objectives, and profiling of execution data. Secondly, the architecture is built on the basis of well know existing standards to communicate and exchange data, which significantly reduces effort to integrate existing solutions and tools from different vendors. A first prototype of this architecture has been implemented within an EU-funded Adaptive Service Grid project. © 2006 Springer-Verlag.

A service-oriented architecture for text analytics enabled business applications

Experiences showed that developing business applications that base on text analysis normally requires a lot of time and expertise in the field of computer linguistics. Several approaches of integrating text analysis systems with business applications have been proposed, but so far there has been no coordinated approach which would enable building scalable and flexible applications of text analysis in enterprise scenarios. In this paper, a service-oriented architecture for text processing applications in the business domain is introduced. It comprises various groups of processing components and knowledge resources. The architecture, created as a result of our experiences with building natural language processing applications in business scenarios, allows for the reuse of text analysis and other components, and facilitates the development of business applications. We verify our approach by showing how the proposed architecture can be applied to create a text analytics enabled business application that addresses a concrete business scenario. © 2010 IEEE.

Architecture for service profiling

Service oriented architecture is gaining momentum. However, in order to be successful, the proper and up-to-date description of services is required. Such a description may be provided by service profiling mechanisms, such as one presented in this article. Service profile can be defined as an up-to-date description of a subset of non-functional properties of a service. It allows for service comparison on the basis of non-functional parameters, and choosing the service which is most suited to the needs of a user. In this article the notion of a service profile along with service profiling mechanism is presented as well as the architecture of a profiling system. © 2006 IEEE.

Urban informatics beyond data: Media architecture, placemaking, and citizen action

Since 2006, we have been conducting urban informatics research that we define as “the study, design, and practice of urban experiences across different urban contexts that are created by new opportunities of real-time, ubiquitous technology and the augmentation that mediates the physical and digital layers of people networks and urban infrastructures” [1]. Various new research initiatives under the label “urban informatics” have been started since then by universities (e.g., NYU’s Center for Urban Science and Progress) and industry (e.g., Arup, McKinsey) worldwide. Yet, many of these new initiatives are limited to what Townsend calls, “data-driven approaches to urban improvement” [2]. One of the key challenges is that any quantity of aggregated data does not easily translate directly into quality insights to better understand cities. In this talk, I will raise questions about the purpose of urban informatics research beyond data, and show examples of media architecture, participatory city making, and citizen activism. I argue for (1) broadening the disciplinary foundations that urban science approaches draw on; (2) maintaining a hybrid perspective that considers both the bird’s eye view as well as the citizen’s view, and; (3) employing design research to not be limited to just understanding, but to bring about actionable knowledge that will drive change for good.

Curtains and the Soft Architecture of the American Postwar Domestic Environment

This article investigates the role of “soft architecture” and interior effects—including window treatments, textiles, and electric lighting—in the physcial and social construction of the postwar domestic environment in the USA. In this period the American home became an increasingly visual and visible space, defined more by the view out and the view in than by traditional conditions of domestic enclosure. Popular how-to columns and home decoration articles offered homemakers a variety of mechanisms for sustaining the appearance and psychological comfort of the modern domestic setting. Examining a range of popular decorative strategies used to mediate residential picture windows and window walls, this study challenges the deep-seated cultural and disciplinary biases associated with both the design and study of domestic architecture and interiors. Drawing upon historical documents and contemporary theorizations of the interior, this paper argues for the agency of “soft architecture” in the domestication of modern residential architecture.

Genomic architecture of ecologically divergent body shape in a pair of sympatric crater lake cichlid fishes

Determining the genetic bases of adaptations and their roles in speciation is a prominent issue in evolutionary biology. Cichlid fish species flocks are a prime example of recent rapid radiations, often associated with adaptive phenotypic divergence from a common ancestor within a short period of time. In several radiations of freshwater fishes, divergence in ecomorphological traits - including body shape, colour, lips and jaws - is thought to underlie their ecological differentiation, specialization and, ultimately, speciation. The Midas cichlid species complex (Amphilophus spp.) of Nicaragua provides one of the few known examples of sympatric speciation where species have rapidly evolved different but parallel morphologies in young crater lakes. This study identified significant QTL for body shape using SNPs generated via ddRAD sequencing and geometric morphometric analyses of a cross between two ecologically and morphologically divergent, sympatric cichlid species endemic to crater Lake Apoyo: an elongated limnetic species (Amphilophus zaliosus) and a high-bodied benthic species (Amphilophus astorquii). A total of 453 genome-wide informative SNPs were identified in 240 F-2 hybrids. These markers were used to construct a genetic map in which 25 linkage groups were resolved. Seventy-two segregating SNPs were linked to 11 QTL. By annotating the two most highly supported QTL-linked genomic regions, genes that might contribute to divergence in body shape along the benthic-limnetic axis in Midas cichlid sympatric adaptive radiations were identified. These results suggest that few genomic regions of large effect contribute to early stage divergence in Midas cichlids.

Landscape Architecture History Seminar Notes 2015

These notes cover landscape design from ancient times to the early 20th century and were compiled from seminars delivered by the author for the DEB202 Introducing Design History unit at QUT.

Overview of design concepts of traditional Iranian architecture and its reflections in Iranian contemporary architecture

This article has attempted to investigate the patterns of traditional architecture in Iran's warm and dry climate and whether these patterns have been attended to in Iran's contemporary architecture or not. Since the two elements of culture and climate are much significant in Iran's traditional constructions, this article aimed at dealing with subjects such as the causes of the shapes of traditional buildings in Iran's warm and dry climate in constructions like houses, schools, mosques and bazaars, and why they were constructed in those shapes, and also considering their patterns in these places in the light of cultural and climatic aspects, and their cultural and climatic relationships and investigating cultural-climatic causes of the directions and situations designed for the spaces present in these buildings and finally it is intended to classify the conceptual patterns of the traditional architecture of Iran's warm and dry climate. The article is going to consider the amount of using these patterns in Iran's contemporary architecture. The study has been conducted using library and field method.