A DRD2 polymorphism predicts PANSS score variability in schizophrenia patients treated with antipsychotics

Antipsychotic medications act as either antagonists or partial agonists of the dopamine D2 receptor (DRD2) and antipsychotic drugs vary widely in their binding affinity for the D2 receptor (Kapur and Seeman, 2000). The DRD2 957CNT (rs6277) polymorphism has previously been associated with schizophrenia (Lawford et al., 2005) and the T-allele of the 957CNT polymorphism is associated with reduced mRNA stability and synthesis of the dopamine D2 receptor (Duan et al., 2003). The aim of the study was to determine if the rs6277 polymorphism predicts some of the variability of positive and negative symptoms observed in schizophrenia patients being treated with antipsychotic medication.

HapMap tag-SNP analysis confirms a role for COMT in schizophrenia risk and reveals a novel association

Catechol-O-methyl transferase (COMT) encodes an enzyme involved in the metabolism of dopamine and maps to a commonly deleted region that increases schizophrenia risk. A non-synonymous polymorphism (rs4680) in COMT has been previously found to be associated with schizophrenia and results in altered activity levels of COMT. Using a haplotype block-based gene-tagging approach we conducted an association study of seven COMT single nucleotide polymorphisms (SNPs) in 160 patients with a DSM-IV diagnosis of schizophrenia and 250 controls in an Australian population. Two polymorphisms including rs4680 and rs165774 were found to be significantly associated with schizophrenia. The rs4680 results in a Val/Met substitution but the strongest association was shown by the novel SNP, rs165774, which may still be functional even though it is located in intron five. Individuals with schizophrenia were more than twice as likely to carry the GG genotype compared to the AA genotype for both the rs165774 and rs4680 SNPs. This association was slightly improved when males were analysed separately possibly indicating a degree of sexual dimorphism. Our results confirm that COMT is a good candidate for schizophrenia risk, by replicating the association with rs4680 and identifying a novel SNP association.

Approximate Bayesian computation using indirect inference

We present a novel approach for developing summary statistics for use in approximate Bayesian computation (ABC) algorithms by using indirect inference. ABC methods are useful for posterior inference in the presence of an intractable likelihood function. In the indirect inference approach to ABC the parameters of an auxiliary model fitted to the data become the summary statistics. Although applicable to any ABC technique, we embed this approach within a sequential Monte Carlo algorithm that is completely adaptive and requires very little tuning. This methodological development was motivated by an application involving data on macroparasite population evolution modelled by a trivariate stochastic process for which there is no tractable likelihood function. The auxiliary model here is based on a beta–binomial distribution. The main objective of the analysis is to determine which parameters of the stochastic model are estimable from the observed data on mature parasite worms.

A polymorphism in the dysbindin gene (DTNBP1) associated with multiple psychiatric disorders including schizophrenia

Background A number of studies have found associations between dysbindin (DTNBP1) polymorphisms and schizophrenia. Recently we identified a DTNBP1 SNP (rs9370822) that is strongly associated with schizophrenia. Individuals diagnosed with schizophrenia were nearly three times as likely to carry the CC genotype compared to the AA genotype. Methods To investigate the importance of this SNP in the function of DTNBP1, a number of psychiatric conditions including addictive behaviours and anxiety disorders were analysed for association with rs9370822. Results The DTNBP1 polymorphism was significantly associated with post-traumatic stress disorder (PTSD) as well as nicotine and opiate dependence but not alcohol dependence. Individuals suffering PTSD were more than three times as likely to carry the CC genotype compared to the AA genotype. Individuals with nicotine or opiate dependence were more than twice as likely to carry the CC genotype compared to the AA genotype. Conclusions This study provides further support for the importance of DTNBP1 in psychiatric conditions and suggests that there is a common underlying molecular defect involving DTNBP1 that contributes to the development of several anxiety and addictive disorders that are generally recognised as separate clinical conditions. These disorders may actually be different expressions of a single metabolic pathway perturbation. As our participant numbers are limited our observations should be viewed with caution until they are independently replicated.

Raman spectroscopy of selected borate minerals of the pinakiolite group

The Raman spectra of a series of related minerals of the pinakiolite group of minerals have been collected and the spectra related to the mineral structure. These minerals are based upon an isolated BO33- ion. The site symmetry is reduced from D3h to C1. Intense Raman bands are observed for the minerals takeuchiite, pinakiolite, fredrikssonite and azoproite at 1084, 1086, 1086 and 1086 cm-1. These bands are assigned to the ν1 BO33- symmetric stretching mode. Low intensity Raman bands are observed for the minerals at 1345, 1748; 1435, 1748; 1435, 1750; 1436, 1749 cm-1. One probable assignment is to ν3 BO33- antisymmetric stretching mode. Intense Raman bands of takeuchiite, pinakiolite, fredrikssonite and azoproite at 712 cm-1 attributed to the ν2 out-of-plane bending mode. Importantly, through the comparison of the Raman spectra, the molecular structure of borate minerals with ill-defined structures can be obtained.

Genome-wide identification and expression analysis of the NF-Y family of transcription factors in Triticum aestivum

Nuclear Factor Y (NF-Y) is a trimeric complex that binds to the CCAAT box, a ubiquitous eukaryotic promoter element. The three subunits NF-YA, NF-YB and NF-YC are represented by single genes in yeast and mammals. However, in model plant species (Arabidopsis and rice) multiple genes encode each subunit providing the impetus for the investigation of the NF-Y transcription factor family in wheat. A total of 37 NF-Y and Dr1 genes (10 NF-YA, 11 NF-YB, 14 NF-YC and 2 Dr1) in Triticum aestivum were identified in the global DNA databases by computational analysis in this study. Each of the wheat NF-Y subunit families could be further divided into 4-5 clades based on their conserved core region sequences. Several conserved motifs outside of the NF-Y core regions were also identified by comparison of NF-Y members from wheat, rice and Arabidopsis. Quantitative RT-PCR analysis revealed that some of the wheat NF-Y genes were expressed ubiquitously, while others were expressed in an organ-specific manner. In particular, each TaNF-Y subunit family had members that were expressed predominantly in the endosperm. The expression of nine NF-Y and two Dr1 genes in wheat leaves appeared to be responsive to drought stress. Three of these genes were up-regulated under drought conditions, indicating that these members of the NF-Y and Dr1 families are potentially involved in plant drought adaptation. The combined expression and phylogenetic analyses revealed that members within the same phylogenetic clade generally shared a similar expression profile. Organ-specific expression and differential response to drought indicate a plant-specific biological role for various members of this transcription factor family.

TaNF-YC11, one of the light-upregulated NF-YC members in Triticum aestivum, is co-regulated with photosynthesis-related genes

NF-Y is a heterotrimeric transcription factor complex. Each of the NF-Y subunits (NF-YA, NF-YB and NF-YC) in plants is encoded by multiple genes. Quantitative RT-PCR analysis revealed that five wheat NF-YC members (TaNF-YC5, 8, 9, 11 & 12) were upregulated by light in both the leaf and seedling shoot. Co-expression analysis of Affymetrix wheat genome array datasets revealed that transcript levels of a large number of genes were consistently correlated with those of the TaNF-YC11 and TaNF-YC8 genes in 3-4 separate Affymetrix array datasets. TaNF-YC11-correlated transcripts were significantly enriched with the Gene Ontology term photosynthesis. Sequence analysis in the promoters of TaNF-YC11-correlated genes revealed the presence of putative NF-Y complex binding sites (CCAAT motifs). Quantitative RT-PCR analysis of a subset of potential TaNF-YC11 target genes showed that ten out of the thirteen genes were also light-upregulated in both the leaf and seedling shoot and had significantly correlated expression profiles with TaNF-YC11. The potential target genes for TaNF-YC11 include subunit members from all four thylakoid membrane bound complexes required for the conversion of solar energy into chemical energy and rate limiting enzymes in the Calvin cycle. These data indicate that TaNF-YC11 is potentially involved in regulation of photosynthesis-related genes.

TaNF-YB3 is involved in the regulation of photosynthesis genes in Triticum aestivum

Nuclear Factor Y (NF-Y) transcription factor is a heterotrimer comprised of three subunits: NF-YA, NF-YB and NF-YC. Each of the three subunits in plants is encoded by multiple genes with differential expression profiles, implying the functional specialisation of NF-Y subunit members in plants. In this study, we investigated the roles of NF-YB members in the light-mediated regulation of photosynthesis genes. We identified two NF-YB members from Triticum aestivum (TaNF-YB3 & 7) which were markedly upregulated by light in the leaves and seedling shoots using quantitative RT-PCR. A genome-wide coexpression analysis of multiple Affymetrix Wheat Genome Array datasets revealed that TaNF-YB3-coexpressed transcripts were highly enriched with the Gene Ontology term photosynthesis. Transgenic wheat lines constitutively overexpressing TaNF-YB3 had a significant increase in the leaf chlorophyll content, photosynthesis rate and early growth rate. Quantitative RT-PCR analysis showed that the expression levels of a number of TaNF-YB3-coexpressed transcripts were elevated in the transgenic wheat lines. The mRNA level of TaGluTR encoding glutamyl-tRNA reductase, which catalyses the rate limiting step of the chlorophyll biosynthesis pathway, was significantly increased in the leaves of the transgenic wheat. Significant increases in the expression level in the transgenic plant leaves were also observed for four photosynthetic apparatus genes encoding chlorophyll a/b-binding proteins (Lhca4 and Lhcb4) and photosystem I reaction center subunits (subunit K and subunit N), as well as for a gene coding for chloroplast ATP synthase  subunit. These results indicate that TaNF-YB3 is involved in the positive regulation of a number of photosynthesis genes in wheat.

Overview of the INEX 2010 XML mining track : clustering and classification of XML documents

The XML Document Mining track was launched for exploring two main ideas: (1) identifying key problems and new challenges of the emerging field of mining semi-structured documents, and (2) studying and assessing the potential of Machine Learning (ML) techniques for dealing with generic ML tasks in the structured domain, i.e., classification and clustering of semi-structured documents. This track has run for six editions during INEX 2005, 2006, 2007, 2008, 2009 and 2010. The first five editions have been summarized in previous editions and we focus here on the 2010 edition. INEX 2010 included two tasks in the XML Mining track: (1) unsupervised clustering task and (2) semi-supervised classification task where documents are organized in a graph. The clustering task requires the participants to group the documents into clusters without any knowledge of category labels using an unsupervised learning algorithm. On the other hand, the classification task requires the participants to label the documents in the dataset into known categories using a supervised learning algorithm and a training set. This report gives the details of clustering and classification tasks.

Hylaluronan-based heparin-incorporated hydrogels for generation of axially vascularized bioartificial bone tissues : in vitro and in vivo evaluation in a PLDLLA-TCP-PCL-composite system

Smart matrices are required in bone tissueengineered grafts that provide an optimal environment for cells and retain osteo-inductive factors for sustained biological activity. We hypothesized that a slow-degrading heparin-incorporated hyaluronan (HA) hydrogel can preserve BMP-2; while an arterio–venous (A–V) loop can support axial vascularization to provide nutrition for a bioartificial bone graft. HA was evaluated for osteoblast growth and BMP-2 release. Porous PLDLLA–TCP–PCL scaffolds were produced by rapid prototyping technology and applied in vivo along with HA-hydrogel, loaded with either primary osteoblasts or BMP-2. A microsurgically created A–V loop was placed around the scaffold, encased in an isolation chamber in Lewis rats. HA-hydrogel supported growth of osteoblasts over 8 weeks and allowed sustained release of BMP-2 over 35 days. The A–V loop provided an angiogenic stimulus with the formation of vascularized tissue in the scaffolds. Bone-specific genes were detected by real time RT-PCR after 8 weeks. However, no significant amount of bone was observed histologically. The heterotopic isolation chamber in combination with absent biomechanical stimulation might explain the insufficient bone formation despite adequate expression of bone-related genes. Optimization of the interplay of osteogenic cells and osteo-inductive factors might eventually generate sufficient amounts of axially vascularized bone grafts for reconstructive surgery.

Commissioning of a Geant4 based treatment plan simulation tool : linac model and dicom-rt interface

A Geant4 based simulation tool has been developed to perform Monte Carlo modelling of a 6 MV VarianTM iX clinac. The computer aided design interface of Geant4 was used to accurately model the LINAC components, including the Millenium multi-leaf collimators (MLCs). The simulation tool was verified via simulation of standard commissioning dosimetry data acquired with an ionisation chamber in a water phantom. Verification of the MLC model was achieved by simulation of leaf leakage measurements performed using GafchromicTM film in a solid water phantom. An absolute dose calibration capability was added by including a virtual monitor chamber into the simulation. Furthermore, a DICOM-RT interface was integrated with the application to allow the simulation of treatment plans in radiotherapy. The ability of the simulation tool to accurately model leaf movements and doses at each control point was verified by simulation of a widely used intensity-modulated radiation therapy (IMRT) quality assurance (QA) technique, the chair test.

Characterisation of public mobile data networks for aeronautical telemetry purposes

This paper describes the characterisation for airborne uses of the public mobile data communication systems known broadly as 3G. The motivation for this study was to explore how this mature public communication systems could be used for aviation purposes. An experimental system was fitted to a light aircraft to record communication latency, line speed, RF level, packet loss and cell tower identifier. Communications was established using internet protocols and connection was made to a local server. The aircraft was flown in both remote and populous areas at altitudes up to 8500ft in a region located in South East Queensland, Australia. Results show that the average airborne RF levels are better than those on the ground by 21% and in the order of -77 dbm. Latencies were in the order of 500 ms (1/2 the latency of Iridium), an average download speed of 0.48 Mb/s, average uplink speed of 0.85 Mb/s, a packet of information loss of 6.5%. The maximum communication range was also observed to be 70km from a single cell station. The paper also describes possible limitations and utility of using such a communications architecture for both manned and unmanned aircraft systems.

A quasi four dimensional radiation detector

Techniques for the accurate measurement of ionising radiation have been evolving since Roentgen first discovered x-rays in 1895; until now experimental measurements of radiation fields in the three spatial dimensions plus time have not been successfully demonstrated. In this work, we embed an organic plastic scintillator in a polymer gel dosimeter to obtain the first quasi-4D experimental measurement of a radiation field.

Impact of traffic oscillations on freeway crash occurrences

Traffic oscillations are typical features of congested traffic flow that are characterized by recurring decelerations followed by accelerations (stop-and-go driving). The negative environmental impacts of these oscillations are widely accepted, but their impact on traffic safety has been debated. This paper describes the impact of freeway traffic oscillations on traffic safety. This study employs a matched case-control design using high-resolution traffic and crash data from a freeway segment. Traffic conditions prior to each crash were taken as cases, while traffic conditions during the same periods on days without crashes were taken as controls. These were also matched by presence of congestion, geometry and weather. A total of 82 cases and about 80,000 candidate controls were extracted from more than three years of data from 2004 to 2007. Conditional logistic regression models were developed based on the case-control samples. To verify consistency in the results, 20 different sets of controls were randomly extracted from the candidate pool for varying control-case ratios. The results reveal that the standard deviation of speed (thus, oscillations) is a significant variable, with an average odds ratio of about 1.08. This implies that the likelihood of a (rear-end) crash increases by about 8% with an additional unit increase in the standard deviation of speed. The average traffic states prior to crashes were less significant than the speed variations in congestion.

Determinants and consequences of information sharing with key suppliers

The economic environment of today can be characterized as highly dynamic and competitive if not being in a constant flux. Globalization and the Information Technology (IT) revolution are perhaps the main contributing factors to this observation. While companies have to some extent adapted to the current business environment, new pressures such as the recent increase in environmental awareness and its likely effects on regulations are underway. Hence, in the light of market and competitive pressures, companies must constantly evaluate and if necessary update their strategies to sustain and increase the value they create for shareholders (Hunt and Morgan, 1995; Christopher and Towill, 2002). One way to create greater value is to become more efficient in producing and delivering goods and services to customers, which can lead to a strategy known as cost leadership (Porter, 1980). Even though Porter (1996) notes that in the long run cost leadership may not be a sufficient strategy for competitive advantage, operational efficiency is certainly necessary and should therefore be on the agenda of every company. ----- ----- ----- Better workflow management, technology, and resource utilization can lead to greater internal operational efficiency, which explains why, for example, many companies have recently adopted Enterprise Resource Planning (ERP) Systems: integrated softwares that streamline business processes. However, as today more and more companies are approaching internal operational excellence, the focus for finding inefficiencies and cost saving opportunities is moving beyond the boundaries of the firm. Today many firms in the supply chain are engaging in collaborative relationships with customers, suppliers, and third parties (services) in an attempt to cut down on costs related to for example, inventory, production, as well as to facilitate synergies. Thus, recent years have witnessed fluidity and blurring regarding organizational boundaries (Coad and Cullen, 2006). ----- ----- ----- The Information Technology (IT) revolution of the late 1990’s has played an important role in bringing organizations closer together. In their efforts to become more efficient, companies first integrated their information systems to speed up transactions such as ordering and billing. Later collaboration on a multidimensional scale including logistics, production, and Research & Development became evident as companies expected substantial benefits from collaboration. However, one could also argue that the recent popularity of the concepts falling under Supply Chain Management (SCM) such as Vendor Managed Inventory, Collaborative Planning, Replenishment, and Forecasting owe to the marketing efforts of software vendors and consultants who provide these solutions. Nevertheless, reports from professional organizations as well as academia indicate that the trend towards interorganizational collaboration is gaining wider ground. For example, the ARC Advisory Group, a research organization on supply chain solutions, estimated that the market for SCM, which includes various kinds of collaboration tools and related services, is going to grow at an annual rate of 7.4% during the years 2004-2008, reaching to $7.4 billion in 2008 (Engineeringtalk 2004).