Matthew Anderson - Academia.edu (original) (raw)

Book Chapter by Matthew Anderson

Research paper thumbnail of New Ways of Seeing: Evaluating Interactive User Experiences in Virtual Art Galleries

Analyzing Art, Culture, and Design in the Digital Age , Jan 2015

As computer-driven display technology becomes more powerful and accessible, the online, virtual a... more As computer-driven display technology becomes more powerful and accessible, the online, virtual art gallery may provide a new platform for artists to exhibit their work. Virtual exhibits may afford opportunities for both the artist and the patron to display, view and perhaps purchase various digital art forms. The aim of this paper is to examine user interaction with digital artworks inside a virtual gallery space. We use a range of criteria to describe conditions for both the designer and the user of such a virtual display system. The paper describes a number of experiments where users interacted with a virtual art gallery and were then extensively interviewed and surveyed. Measures of what Manovich (2002) describes as ‘immersion’ and what Slater et al (1994) would term ‘presence’ are observed in relation to the user experience. The gallery is a three-dimensional graphic digital construction built in Second Life. The experiment aimed to describe and delineate the user’s perception and navigation of space and compares their perception of art objects in the virtual environment to digital objects in a ‘real world’ gallery. The data collected in this study provide the basis for a discussion of how users may perceive and navigate virtual objects and spaces in an online environment such as a game or art gallery. The results may be of use to those designing interactive three-dimensional environments.

Papers by Matthew Anderson

Research paper thumbnail of Roman Portraiture and Biometric Identification

This project utilised three-dimensional scanning technology in the study of ancient Roman art and... more This project utilised three-dimensional scanning technology in the study of ancient Roman art and archaeology: Roman representations of faces executed in marble. In the cultural heritage sector, three-dimensional (3D) scanning finds its primary application in documenting and reconstructing objects and structures mostly of simple geometry: bones, pottery, architecture or the imprint of whole archaeological sites (Adolf 2011). In forensic science, the face is interesting from investigative and probative perspectives, including both recognition and identification. Biometric methods of facial recognition have been part of a plethora of computer science-based applications used in the verification of identity (Davy et al. 2005, Goodwin, Evison and Schofield 2010). The aim of this initial project is to provide objective relevant measurements of key facial features from the two ancient Roman portrait statue three-dimensional scans, which will allow the delineation of relationships between individual portraits including formal and stylistics aspects. The work described in this paper proposal is truly multidisciplinary, it touches on many fields including : Classical archaeologies (specifically ancient art history in the period of the Roman Empire 31BC-AD400), Forensic Anthropology (specifically physical anthropology and human osteology, Facial Biometrics (specifically uniquely recognising humans based upon their intrinsic physical traits and features) and Computer Science and Statistics (specifically the analysis of large complex multi-dimensional data sets). Visualising ideas and concepts. Imaging and images in museums and galleries. Reconstructive archaeology and architecture. Visualisation in museums. historic sites and buildings. Technologies of digitization. 2D, 3D and high definition imaging.

Research paper thumbnail of Ways of Viewing and Interacting : User Experience in a Virtual Art Gallery

As computer-driven display technology becomes more powerful and accessible, the online, virtual a... more As computer-driven display technology becomes more powerful and accessible, the online, virtual art gallery may provide a new platform for artists to exhibit their work. Virtual exhibits may afford opportunities for both the artist and the patron to display, view and perhaps purchase various digital art forms. The aim of this chapter is to examine user interaction with digital artworks inside a virtual gallery space along a metric based on a virtuality continuum. The chapter describes a number of experiments where users interacted with a virtual art gallery and were then extensively interviewed and surveyed. The gallery is a three-dimensional graphic digital construction within the RMIT University virtual campus in Second Life. Users take on the form of online avatars to access the Second Life online environment and experience various colourful art objects in a simulated gallery environment. The experiment initially employs the taxonomy of Milgram and Kishino (1994) to assist the di...

Research paper thumbnail of TCreERT2, a transgenic mouse line for temporal control of Cre-mediated recombination in lineages emerging from the primitive streak or tail bud

PloS one, 2013

The study of axis extension and somitogenesis has been greatly advanced through the use of geneti... more The study of axis extension and somitogenesis has been greatly advanced through the use of genetic tools such as the TCre mouse line. In this line, Cre is controlled by a fragment of the T (Brachyury) promoter that is active in progenitor cells that reside within the primitive streak and tail bud and which give rise to lineages emerging from these tissues as the embryonic axis extends. However, because TCre-mediated recombination occurs early in development, gene inactivation can result in an axis truncation that precludes the study of gene function in later or more posterior tissues. To address this limitation, we have generated an inducible TCre transgenic mouse line, called TCreERT2, that provides temporal control, through tamoxifen administration, in all cells emerging from the primitive streak or tail bud throughout development. TCreERT2 activity is mostly silent in the absence of tamoxifen and, in its presence, results in near complete recombination of emerging mesoderm from E...

Research paper thumbnail of Immunoassays in a porous silicon interferometric biosensor combined with sensitive signal processing

Physica Status Solidi A-applications and Materials Science, 2005

Orthogonal subspace signal processing algorithms (OSPA) have been developed to extract the optica... more Orthogonal subspace signal processing algorithms (OSPA) have been developed to extract the optical thickness of a porous silicon layer to within one part in 105 from its reflectivity spectrum. This is equivalent to a limit of detection (LOD) of 40 pm change in optical thickness for a 3 mum thick layer, or an LOD of 1/2000 of a monolayer coverage

Research paper thumbnail of Observation of modulated Hanle resonances in phase-diffusing optical fields

Physical Review A, 1991

We report an experiment on the observation of Hanle resonances in weakly sinusoidally amplitude m... more We report an experiment on the observation of Hanle resonances in weakly sinusoidally amplitude modulated, nonsaturating, phase-diffusing optical fields. The ¹{ital S}â to ¹{ital P}⁠transition ({ital J}=0 to 1) in an atomic beam of ¹³⁸Ba was probed with a frequency stabilized dye laser, whose bandwidth and band shape were precisely controlled with an extra-cavity noise modulation system. Phase-sensitive detection

Research paper thumbnail of Tuning the Pore Size and Surface Chemistry of Porous Silicon for Immunoassays

physica status solidi (a), 2000

To use porous silicon as an optical interferometric biosensor, the pores must be sufficiently lar... more To use porous silicon as an optical interferometric biosensor, the pores must be sufficiently large to allow easy ingress of reagents and the layer must also display Fabry-Perot optical cavity modes. Here the detection antibody is rabbit IgG and the analyte is a-rabbit IgG conjugated to horseradish peroxidase (HRP). For this model system, the pores should be >50 nm in diameter. Such diameters have been obtained in 0.05 W cm n-type silicon using anodisation followed by chemical etching in ethanolic KOH and also by anodising 0.005 W cm p-type material. The latter also displays optical cavity modes. The silicon surface is oxidised in ozone, silanised using aminopropylmethoxysilanes with one, two or three methoxy groups, and cross linked to IgG using glutaraldehyde. High specific binding is found for mono-, di-and tri-methoxy silanes, but the lowest nonspecific binding is found for silanisation with the tri-methoxy silane.

Research paper thumbnail of Small-footprint Lidar Estimations of Sagebrush Canopy Characteristics

Photogrammetric Engineering & Remote Sensing, 2011

Page 1. Abstract The height and shape of shrub canopies are critical meas-urements for characteri... more Page 1. Abstract The height and shape of shrub canopies are critical meas-urements for characterizing shrub steppe rangelands. Remote sensing technologies might provide an efficient method to acquire these measurements across large areas. ...

Research paper thumbnail of Whole-genome characterization of chemoresistant ovarian cancer

Nature, Jan 28, 2015

Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in over... more Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and standard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To understand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline DNA samples from 92 patients with primary refractory, resistant, sensitive and matched acquired resistant disease. We show that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance. CCNE1 amplification was common in primary resistant and refractory disease. We observed several molecular events associated with acquired resistance, including multiple independent reversions of germline BRCA1 or BRCA2 mutations in individual patients, loss of BRCA1 promoter methylation, an alteration in molecular subtype, and recurrent promoter fusion associated with overexpress...

Research paper thumbnail of Whole genomes redefine the mutational landscape of pancreatic cancer

Nature, Jan 25, 2015

Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We pe... more Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of D...

Research paper thumbnail of A workflow to increase verification rate of chromosomal structural rearrangements using high-throughput next-generation sequencing

BioTechniques, 2014

Somatic rearrangements, which are commonly found in human cancer genomes, contribute to the progr... more Somatic rearrangements, which are commonly found in human cancer genomes, contribute to the progression and maintenance of cancers. Conventionally, the verification of somatic rearrangements comprises many manual steps and Sanger sequencing. This is labor intensive when verifying a large number of rearrangements in a large cohort. To increase the verification throughput, we devised a high-throughput workflow that utilizes benchtop next-generation sequencing and in-house bioinformatics tools to link the laboratory processes. In the proposed workflow, primers are automatically designed. PCR and an optional gel electrophoresis step to confirm the somatic nature of the rearrangements are performed. PCR products of somatic events are pooled for Ion Torrent PGM and/or Illumina MiSeq sequencing, the resulting sequence reads are assembled into consensus contigs by a consensus assembler, and an automated BLAT is used to resolve the breakpoints to base level. We compared sequences and breakpo...

Research paper thumbnail of Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis

Nature communications, 2014

Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better u... more Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. The...

Research paper thumbnail of Professional Traders as Intuitive Bayesians

Organizational Behavior and Human Decision Processes, 1995

Research paper thumbnail of Loss of unc45a precipitates arteriovenous shunting in the aortic arches

Developmental Biology, 2008

Aortic arch malformations are common congenital disorders that are frequently of unknown etiology... more Aortic arch malformations are common congenital disorders that are frequently of unknown etiology. To gain insight into the factors that guide branchial aortic arch development, we examined the process by which these vessels assemble in wild type zebrafish embryos and in kurzschluss tr12 (kus tr12 ) mutants. In wild type embryos, each branchial aortic arch first appears as an island of angioblasts in the lateral pharyngeal mesoderm, then elaborates by angiogenesis to connect to the lateral dorsal aorta and ventral aorta. In kus tr12 mutants, angioblast formation and initial sprouting are normal, but aortic arches 5 and 6 fail to form a lumenized connection to the lateral dorsal aorta. Blood enters these blind-ending vessels from the ventral aorta, distending the arteries and precipitating fusion with an adjacent vein. This arteriovenous malformation (AVM), which shunts nearly all blood directly back to the heart, is not exclusively genetically programmed, as its formation correlates with blood flow and aortic arch enlargement. By positional cloning, we have identified a nonsense mutation in unc45a in kus tr12 mutants. Our results are the first to ascribe a role for Unc45a, a putative myosin chaperone, in vertebrate development, and identify a novel mechanism by which an AVM can form.

Research paper thumbnail of Functional evidence for differences in sperm competition in humans and chimpanzees

American Journal of Physical Anthropology, 2007

Sperm competition occurs when the gametes of or more males compete for opportunities to fertilize... more Sperm competition occurs when the gametes of or more males compete for opportunities to fertilize a given set of ova. Previous studies have demonstrated that certain morphological characteristics are affected by sperm competition intensity (e.g. relative testes size and sperm midpiece volume). This study examined whether aspects of sperm energetics may also be affected by sexual selection. We compared the membrane potential of mitochondria in live sperm between H. sapiens (single partner mating system) and P. troglodytes (multiple partner mating system). Flow cytometry of sperm stained with the carbocyanine fluorescent dye JC-1 (an assay for mitochondrial membrane potential) revealed marked differences in red fluorescence intensity. P. troglodytes sperm showed significantly higher mitochondrial membrane potential. Mitochondria provide a substantial part of the energy required for sperm motility. A higher mitochondrial loading may therefore be associated with enhanced sperm motility and/or longevity. Additionally, examination of JC-1 red fluorescence levels before and after in vitro capacitation revealed further differences. Whereas chimpanzee sperm showed maintenance of membrane potential after capacitation (in some cases even an increase), sperm from humans consistently showed reduction in membrane potential. These results indicate that the sperm of human beings and chimpanzees exhibit marked differences in mitochondrial function, which are affected by selection pressures relating to sperm competition and that these pressures differ significantly between humans and chimpanzees. Am J Phys Anthropol 134: 274-280, 2007. in Wiley InterScience (www.interscience.wiley.com). MJ, Dixson AF. 2002. Sperm competition: motility and the midpiece in primates. Nature 416:496. Anderson MJ, Nyholt J, Dixson AF. 2005. Sperm competition and the evolution of sperm midpiece volume in mammals. J Zool 267:135-142. Bedford JM. 1974. Biology of primate spermatozoa. Contrib Primatol 3:97-139.

Research paper thumbnail of New Ways of Seeing: Evaluating Interactive User Experiences in Virtual Art Galleries

Analyzing Art, Culture, and Design in the Digital Age , Jan 2015

As computer-driven display technology becomes more powerful and accessible, the online, virtual a... more As computer-driven display technology becomes more powerful and accessible, the online, virtual art gallery may provide a new platform for artists to exhibit their work. Virtual exhibits may afford opportunities for both the artist and the patron to display, view and perhaps purchase various digital art forms. The aim of this paper is to examine user interaction with digital artworks inside a virtual gallery space. We use a range of criteria to describe conditions for both the designer and the user of such a virtual display system. The paper describes a number of experiments where users interacted with a virtual art gallery and were then extensively interviewed and surveyed. Measures of what Manovich (2002) describes as ‘immersion’ and what Slater et al (1994) would term ‘presence’ are observed in relation to the user experience. The gallery is a three-dimensional graphic digital construction built in Second Life. The experiment aimed to describe and delineate the user’s perception and navigation of space and compares their perception of art objects in the virtual environment to digital objects in a ‘real world’ gallery. The data collected in this study provide the basis for a discussion of how users may perceive and navigate virtual objects and spaces in an online environment such as a game or art gallery. The results may be of use to those designing interactive three-dimensional environments.

Research paper thumbnail of Roman Portraiture and Biometric Identification

This project utilised three-dimensional scanning technology in the study of ancient Roman art and... more This project utilised three-dimensional scanning technology in the study of ancient Roman art and archaeology: Roman representations of faces executed in marble. In the cultural heritage sector, three-dimensional (3D) scanning finds its primary application in documenting and reconstructing objects and structures mostly of simple geometry: bones, pottery, architecture or the imprint of whole archaeological sites (Adolf 2011). In forensic science, the face is interesting from investigative and probative perspectives, including both recognition and identification. Biometric methods of facial recognition have been part of a plethora of computer science-based applications used in the verification of identity (Davy et al. 2005, Goodwin, Evison and Schofield 2010). The aim of this initial project is to provide objective relevant measurements of key facial features from the two ancient Roman portrait statue three-dimensional scans, which will allow the delineation of relationships between individual portraits including formal and stylistics aspects. The work described in this paper proposal is truly multidisciplinary, it touches on many fields including : Classical archaeologies (specifically ancient art history in the period of the Roman Empire 31BC-AD400), Forensic Anthropology (specifically physical anthropology and human osteology, Facial Biometrics (specifically uniquely recognising humans based upon their intrinsic physical traits and features) and Computer Science and Statistics (specifically the analysis of large complex multi-dimensional data sets). Visualising ideas and concepts. Imaging and images in museums and galleries. Reconstructive archaeology and architecture. Visualisation in museums. historic sites and buildings. Technologies of digitization. 2D, 3D and high definition imaging.

Research paper thumbnail of Ways of Viewing and Interacting : User Experience in a Virtual Art Gallery

As computer-driven display technology becomes more powerful and accessible, the online, virtual a... more As computer-driven display technology becomes more powerful and accessible, the online, virtual art gallery may provide a new platform for artists to exhibit their work. Virtual exhibits may afford opportunities for both the artist and the patron to display, view and perhaps purchase various digital art forms. The aim of this chapter is to examine user interaction with digital artworks inside a virtual gallery space along a metric based on a virtuality continuum. The chapter describes a number of experiments where users interacted with a virtual art gallery and were then extensively interviewed and surveyed. The gallery is a three-dimensional graphic digital construction within the RMIT University virtual campus in Second Life. Users take on the form of online avatars to access the Second Life online environment and experience various colourful art objects in a simulated gallery environment. The experiment initially employs the taxonomy of Milgram and Kishino (1994) to assist the di...

Research paper thumbnail of TCreERT2, a transgenic mouse line for temporal control of Cre-mediated recombination in lineages emerging from the primitive streak or tail bud

PloS one, 2013

The study of axis extension and somitogenesis has been greatly advanced through the use of geneti... more The study of axis extension and somitogenesis has been greatly advanced through the use of genetic tools such as the TCre mouse line. In this line, Cre is controlled by a fragment of the T (Brachyury) promoter that is active in progenitor cells that reside within the primitive streak and tail bud and which give rise to lineages emerging from these tissues as the embryonic axis extends. However, because TCre-mediated recombination occurs early in development, gene inactivation can result in an axis truncation that precludes the study of gene function in later or more posterior tissues. To address this limitation, we have generated an inducible TCre transgenic mouse line, called TCreERT2, that provides temporal control, through tamoxifen administration, in all cells emerging from the primitive streak or tail bud throughout development. TCreERT2 activity is mostly silent in the absence of tamoxifen and, in its presence, results in near complete recombination of emerging mesoderm from E...

Research paper thumbnail of Immunoassays in a porous silicon interferometric biosensor combined with sensitive signal processing

Physica Status Solidi A-applications and Materials Science, 2005

Orthogonal subspace signal processing algorithms (OSPA) have been developed to extract the optica... more Orthogonal subspace signal processing algorithms (OSPA) have been developed to extract the optical thickness of a porous silicon layer to within one part in 105 from its reflectivity spectrum. This is equivalent to a limit of detection (LOD) of 40 pm change in optical thickness for a 3 mum thick layer, or an LOD of 1/2000 of a monolayer coverage

Research paper thumbnail of Observation of modulated Hanle resonances in phase-diffusing optical fields

Physical Review A, 1991

We report an experiment on the observation of Hanle resonances in weakly sinusoidally amplitude m... more We report an experiment on the observation of Hanle resonances in weakly sinusoidally amplitude modulated, nonsaturating, phase-diffusing optical fields. The ¹{ital S}â to ¹{ital P}⁠transition ({ital J}=0 to 1) in an atomic beam of ¹³⁸Ba was probed with a frequency stabilized dye laser, whose bandwidth and band shape were precisely controlled with an extra-cavity noise modulation system. Phase-sensitive detection

Research paper thumbnail of Tuning the Pore Size and Surface Chemistry of Porous Silicon for Immunoassays

physica status solidi (a), 2000

To use porous silicon as an optical interferometric biosensor, the pores must be sufficiently lar... more To use porous silicon as an optical interferometric biosensor, the pores must be sufficiently large to allow easy ingress of reagents and the layer must also display Fabry-Perot optical cavity modes. Here the detection antibody is rabbit IgG and the analyte is a-rabbit IgG conjugated to horseradish peroxidase (HRP). For this model system, the pores should be >50 nm in diameter. Such diameters have been obtained in 0.05 W cm n-type silicon using anodisation followed by chemical etching in ethanolic KOH and also by anodising 0.005 W cm p-type material. The latter also displays optical cavity modes. The silicon surface is oxidised in ozone, silanised using aminopropylmethoxysilanes with one, two or three methoxy groups, and cross linked to IgG using glutaraldehyde. High specific binding is found for mono-, di-and tri-methoxy silanes, but the lowest nonspecific binding is found for silanisation with the tri-methoxy silane.

Research paper thumbnail of Small-footprint Lidar Estimations of Sagebrush Canopy Characteristics

Photogrammetric Engineering & Remote Sensing, 2011

Page 1. Abstract The height and shape of shrub canopies are critical meas-urements for characteri... more Page 1. Abstract The height and shape of shrub canopies are critical meas-urements for characterizing shrub steppe rangelands. Remote sensing technologies might provide an efficient method to acquire these measurements across large areas. ...

Research paper thumbnail of Whole-genome characterization of chemoresistant ovarian cancer

Nature, Jan 28, 2015

Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in over... more Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and standard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To understand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline DNA samples from 92 patients with primary refractory, resistant, sensitive and matched acquired resistant disease. We show that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance. CCNE1 amplification was common in primary resistant and refractory disease. We observed several molecular events associated with acquired resistance, including multiple independent reversions of germline BRCA1 or BRCA2 mutations in individual patients, loss of BRCA1 promoter methylation, an alteration in molecular subtype, and recurrent promoter fusion associated with overexpress...

Research paper thumbnail of Whole genomes redefine the mutational landscape of pancreatic cancer

Nature, Jan 25, 2015

Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We pe... more Pancreatic cancer remains one of the most lethal of malignancies and a major health burden. We performed whole-genome sequencing and copy number variation (CNV) analysis of 100 pancreatic ductal adenocarcinomas (PDACs). Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A and ROBO2) and new candidate drivers of pancreatic carcinogenesis (KDM6A and PREX2). Patterns of structural variation (variation in chromosomal structure) classified PDACs into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered and unstable. A significant proportion harboured focal amplifications, many of which contained druggable oncogenes (ERBB2, MET, FGFR1, CDK6, PIK3R3 and PIK3CA), but at low individual patient prevalence. Genomic instability co-segregated with inactivation of DNA maintenance genes (BRCA1, BRCA2 or PALB2) and a mutational signature of D...

Research paper thumbnail of A workflow to increase verification rate of chromosomal structural rearrangements using high-throughput next-generation sequencing

BioTechniques, 2014

Somatic rearrangements, which are commonly found in human cancer genomes, contribute to the progr... more Somatic rearrangements, which are commonly found in human cancer genomes, contribute to the progression and maintenance of cancers. Conventionally, the verification of somatic rearrangements comprises many manual steps and Sanger sequencing. This is labor intensive when verifying a large number of rearrangements in a large cohort. To increase the verification throughput, we devised a high-throughput workflow that utilizes benchtop next-generation sequencing and in-house bioinformatics tools to link the laboratory processes. In the proposed workflow, primers are automatically designed. PCR and an optional gel electrophoresis step to confirm the somatic nature of the rearrangements are performed. PCR products of somatic events are pooled for Ion Torrent PGM and/or Illumina MiSeq sequencing, the resulting sequence reads are assembled into consensus contigs by a consensus assembler, and an automated BLAT is used to resolve the breakpoints to base level. We compared sequences and breakpo...

Research paper thumbnail of Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis

Nature communications, 2014

Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better u... more Oesophageal adenocarcinoma (EAC) incidence is rapidly increasing in Western countries. A better understanding of EAC underpins efforts to improve early detection and treatment outcomes. While large EAC exome sequencing efforts to date have found recurrent loss-of-function mutations, oncogenic driving events have been underrepresented. Here we use a combination of whole-genome sequencing (WGS) and single-nucleotide polymorphism-array profiling to show that genomic catastrophes are frequent in EAC, with almost a third (32%, n=40/123) undergoing chromothriptic events. WGS of 22 EAC cases show that catastrophes may lead to oncogene amplification through chromothripsis-derived double-minute chromosome formation (MYC and MDM2) or breakage-fusion-bridge (KRAS, MDM2 and RFC3). Telomere shortening is more prominent in EACs bearing localized complex rearrangements. Mutational signature analysis also confirms that extreme genomic instability in EAC can be driven by somatic BRCA2 mutations. The...

Research paper thumbnail of Professional Traders as Intuitive Bayesians

Organizational Behavior and Human Decision Processes, 1995

Research paper thumbnail of Loss of unc45a precipitates arteriovenous shunting in the aortic arches

Developmental Biology, 2008

Aortic arch malformations are common congenital disorders that are frequently of unknown etiology... more Aortic arch malformations are common congenital disorders that are frequently of unknown etiology. To gain insight into the factors that guide branchial aortic arch development, we examined the process by which these vessels assemble in wild type zebrafish embryos and in kurzschluss tr12 (kus tr12 ) mutants. In wild type embryos, each branchial aortic arch first appears as an island of angioblasts in the lateral pharyngeal mesoderm, then elaborates by angiogenesis to connect to the lateral dorsal aorta and ventral aorta. In kus tr12 mutants, angioblast formation and initial sprouting are normal, but aortic arches 5 and 6 fail to form a lumenized connection to the lateral dorsal aorta. Blood enters these blind-ending vessels from the ventral aorta, distending the arteries and precipitating fusion with an adjacent vein. This arteriovenous malformation (AVM), which shunts nearly all blood directly back to the heart, is not exclusively genetically programmed, as its formation correlates with blood flow and aortic arch enlargement. By positional cloning, we have identified a nonsense mutation in unc45a in kus tr12 mutants. Our results are the first to ascribe a role for Unc45a, a putative myosin chaperone, in vertebrate development, and identify a novel mechanism by which an AVM can form.

Research paper thumbnail of Functional evidence for differences in sperm competition in humans and chimpanzees

American Journal of Physical Anthropology, 2007

Sperm competition occurs when the gametes of or more males compete for opportunities to fertilize... more Sperm competition occurs when the gametes of or more males compete for opportunities to fertilize a given set of ova. Previous studies have demonstrated that certain morphological characteristics are affected by sperm competition intensity (e.g. relative testes size and sperm midpiece volume). This study examined whether aspects of sperm energetics may also be affected by sexual selection. We compared the membrane potential of mitochondria in live sperm between H. sapiens (single partner mating system) and P. troglodytes (multiple partner mating system). Flow cytometry of sperm stained with the carbocyanine fluorescent dye JC-1 (an assay for mitochondrial membrane potential) revealed marked differences in red fluorescence intensity. P. troglodytes sperm showed significantly higher mitochondrial membrane potential. Mitochondria provide a substantial part of the energy required for sperm motility. A higher mitochondrial loading may therefore be associated with enhanced sperm motility and/or longevity. Additionally, examination of JC-1 red fluorescence levels before and after in vitro capacitation revealed further differences. Whereas chimpanzee sperm showed maintenance of membrane potential after capacitation (in some cases even an increase), sperm from humans consistently showed reduction in membrane potential. These results indicate that the sperm of human beings and chimpanzees exhibit marked differences in mitochondrial function, which are affected by selection pressures relating to sperm competition and that these pressures differ significantly between humans and chimpanzees. Am J Phys Anthropol 134: 274-280, 2007. in Wiley InterScience (www.interscience.wiley.com). MJ, Dixson AF. 2002. Sperm competition: motility and the midpiece in primates. Nature 416:496. Anderson MJ, Nyholt J, Dixson AF. 2005. Sperm competition and the evolution of sperm midpiece volume in mammals. J Zool 267:135-142. Bedford JM. 1974. Biology of primate spermatozoa. Contrib Primatol 3:97-139.