Whole-genome screening in ankylosing spondylitis: Evidence of non-MHC genetic-susceptibility loci

Ankylosing spondylitis (AS) is a common inflammatory arthritis predominantly affecting the axial skeleton. Susceptibility to the disease is thought to be oligogenic. To identify the genes involved, we have performed a genomewide scan in 185 families containing 255 affected sibling pairs. Two-point and multipoint nonparametric linkage analysis was performed. Regions were identified showing "suggestive" or stronger linkage with the disease on chromosomes 1p, 2q, 6p, 9q, 10q, 16q, and 19q. The MHC locus was identified as encoding the greatest component of susceptibility, with an overall LOD score of 15.6. The strongest non-MHC linkage lies on chromosome 16q (overall LOD score 4.7). These results strongly support the presence of non-MHC genetic-susceptibility factors in AS and point to their likely locations.

Role of NOD2 variants in spondylarthritis

Objective. To investigate the role of the gene NOD2 in susceptibility to, and clinical manifestations of, ankylosing spondylitis (AS). Methods. A case-control study of NOD2 polymorphisms known to be associated with Crohn's disease (CD) (Pro268 Ser, Arg702 Trp, GlY908 Arg, and Len1007fsinsC) was performed in 229 cases of primary AS with no diagnosed inflammatory bowel disease (IBD), 197 cases of AS associated with IBD (referred to as colitic spondylarthritis; comprising 78 with CD and 119 with ulcerative colitis [UC]), and 229 ethnically matched, healthy controls. Associations between NOD2 polymorphisms and several clinical features of AS, including disease severity assessed by questionnaire and age at spondylarthritis onset, were also investigated. Exclusion linkage mapping of chromosome 16 was performed in a separate group of 185 multicase families with AS. Results. An association was identified between Gly908 Arg and UC spondylarthritis (P = 0.016, odds ratio [OR] 4.6, 95% confidence interval [95% CI] 1.316), and a nonsignificant trend with a similar magnitude was observed in association with CD spondylarthritis (P = 0.08, OR 3.9, 95% CI 0.8-18). The Pro268Ser variant was inversely associated with UC spondylarthritis (P = 0.003, OR 0.55, 95% CI 0.37-0.82), but not with CD spondylarthritis. No association was demonstrated between NOD2 variants and primary AS, or between other variants of NOD2 and either UC or CD spondylarthritis. Carriage of the Pro268 Ser polymorphism was associated with greater disease activity as measured by the Bath Ankylosing Spondylitis Disease Activity Index (P = 0.002). Although patients with CD had a younger age at spondylarthritis onset than did those with UC (22.4 years versus 26.4 years; P = 0.01), no association was noted between the NOD2 variants linked with CD and age at spondylarthritis onset. In primary AS, the presence of a gene with a magnitude of association >2.0 was excluded (exclusion logarithm of odds score less than -2.0), and no association was observed with the microsatellite D16S3136. Conclusion. NOD2 variants do not significantly affect the risk of developing primary AS, but may influence susceptibility to, and clinical manifestations of, colitic spondylarthritis.

Investigation of the role of ANKH in ankylosing spondylitis

Objective The ank/ank mouse develops a phenotype similar to ankylosing spondylitis (AS) in humans. ANKH, the human homolog of the mutated gene in the ank/ank mouse, has been implicated in familial autosomal-dominant chondrocalcinosis and autosomal-dominant craniometaphyseal dysplasia. This study was undertaken to investigate the role of ANKH in susceptibility to and clinical manifestations of AS. Methods Sequence variants were identified by genomic sequencing of the 12 ANKH exons and their flanking splice sites in 48 AS patients; variants were then screened in 233 patients and 478 controls. Linkage to the ANKH locus was assessed in 185 affected-sibling-pair families. Results Five single-nucleotide polymorphisms were identified within the coding region and flanking splice sites. No association between either susceptibility to AS or its clinical manifestations and these novel polymorphisms, or between disease susceptibility and 3 known promoter variants, was seen. No linkage between the ANKH locus and AS was observed. Multipoint exclusion mapping rejected the hypothesis of a locus of a magnitude λ≥1.4 (logarithm of odds score <-2) (equivalent to a genetic contribution of >10% to the AS sibling recurrence risk ratio) within this area contributing to AS. Conclusion These findings indicate that ANKH is not significantly involved in susceptibility to or clinical manifestations of AS.

Preparation of magnetic porous ceramsite and its application in biological aerated filters

Ceramsite plays a significant role as a biological aerated filter (BAF) in the treatment of wastewater. In this study, a mixture of goethite, sawdust and palygorskite clay was thermally treated to form magnetic porous ceramsite (MPC). An optimization experiment was conducted to measure the compressive strength of the MPC. X-ray diffraction (XRD), scanning electron microscopy (SEM), and polarizing microscopy (PM) characterized the pore structure of the MPC. The results show that a combination of goethite, sawdust and palygorskite clay with a mass ratio of 10:2:5 is suitable for the formation of MPC. The compressive strength of MPC conforms to the Chinese national industrial standard (CJ/T 299-2008) for wastewater treatment. The SEM and PM results also show that the uniform and interconnected pores in MPC were well suited for microbial growth. The MPC produced in this study can serve as a biomedium for advanced wastewater treatment.

Spatially explicit perceptions of ecosystem services and land cover change in forested regions of Borneo

Spatially explicit information on local perceptions of ecosystem services is needed to inform land use planning within rapidly changing landscapes. In this paper we spatially modelled local people's use and perceptions of benefits from forest ecosystem services in Borneo, from interviews of 1837 people in 185 villages. Questions related to provisioning, cultural/spiritual, regulating and supporting ecosystem services derived from forest, and attitudes towards forest conversion. We used boosted regression trees (BRTs) to combine interview data with social and environmental predictors to understand spatial variation of perceptions across Borneo. Our results show that people use a variety of products from intact and highly degraded forests. Perceptions of benefits from forests were strongest: in human-altered forest landscapes for cultural and spiritual benefits; in human-altered and intact forests landscapes for health benefits; intact forest for direct health benefits, such as medicinal plants; and in regions with little forest and extensive plantations, for environmental benefits, such as climatic impacts from deforestation. Forest clearing for small scale agriculture was predicted to be widely supported yet less so for large-scale agriculture. Understanding perceptions of rural communities in dynamic, multi-use landscapes is important where people are often directly affected by the decline in ecosystem services.

Evaluating the potential use of direct evaporative cooling in Australia

Greenhouse gas emissions and associated global climate change are a significant and growing concern for the world community. In order to improve building energy efficiency, the use of evaporative cooling systems is attracting growing attention. Using a climate assessment tool, the potential use of direct evaporative coolers over different Australian climates is evaluated. It is found that overall, the potential use of direct evaporative cooling is very significant in Australian climates. Among all the eight capital cities across Australia, except for Darwin, the need of hybrid cooling for other cities is found to be insignificant,and is less than 5% if appropriate air circulation is provided on hot/warm days. It is also found that the potential use of evaporative cooling can be significantly influenced by a change in the applications or design parameters. In Brisbane, it is estimated that with an increase of sensible cooling load from 30 W/m2 to 40 W/m2 in the conditioned space, the requirement in hours of hybrid cooling can increase significantly, from 4.06% to 14.89%.

Doing Digital Composition on the Social Web: Knowledge Processes in Literacy Learning

The power to influence others in ever-expanding social networks in the new knowledge economy is tied to capabilities with digital media production. This chapter draws on research in elementary classrooms to examine the repertoires of cross-disciplinary knowledge that literacy learners need to produce innovative digital media via the “social web”. It focuses on the knowledge processes that occurred when elementary students engaged in multimodal text production with new digital media. It draws on Kalantzis and Cope’s (2008) heuristic for theorizing “Knowledge Processes” in the Learning by Design approach to pedagogy. Learners demonstrate eight “Knowledge Processes” across different subject domains, skills areas, and sensibilities. Drawing data from media-based lessons across several classroom and schools, this chapter examines what kinds of knowledge students utilize when they produce digital, multimodal texts in the classroom. The Learning by Design framework is used as an analytic tool to theorize how students learn when they engaged in a specific domain of learning – digital media production.

A critical evaluation of literature on robot path planning in dynamic environment

Robot Path Planning (RPP) in dynamic environments is a search problem based on the examination of collision-free paths in the presence of dynamic and static obstacles. Many techniques have been developed to solve this problem. Trapping in a local minima and maintaining a Real-Time performance are known as the two most important challenges that these techniques face to solve such problem. This study presents a comprehensive survey of the various techniques that have been proposed in this domain. As part of this survey, we include a classification of the approaches and identify their methods.

Fusion transcript loci share many genomic features with non-fusion loci

Background Fusion transcripts are found in many tissues and have the potential to create novel functional products. Here, we investigate the genomic sequences around fusion junctions to better understand the transcriptional mechanisms mediating fusion transcription/splicing. We analyzed data from prostate (cancer) cells as previous studies have shown extensively that these cells readily undergo fusion transcription. Results We used the FusionMap program to identify high-confidence fusion transcripts from RNAseq data. The RNAseq datasets were from our (N = 8) and other (N = 14) clinical prostate tumors with adjacent non-cancer cells, and from the LNCaP prostate cancer cell line that were mock-, androgen- (DHT), and anti-androgen- (bicalutamide, enzalutamide) treated. In total, 185 fusion transcripts were identified from all RNAseq datasets. The majority (76 %) of these fusion transcripts were ‘read-through chimeras’ derived from adjacent genes in the genome. Characterization of sequences at fusion loci were carried out using a combination of the FusionMap program, custom Perl scripts, and the RNAfold program. Our computational analysis indicated that most fusion junctions (76 %) use the consensus GT-AG intron donor-acceptor splice site, and most fusion transcripts (85 %) maintained the open reading frame. We assessed whether parental genes of fusion transcripts have the potential to form complementary base pairing between parental genes which might bring them into physical proximity. Our computational analysis of sequences flanking fusion junctions at parental loci indicate that these loci have a similar propensity as non-fusion loci to hybridize. The abundance of repetitive sequences at fusion and non-fusion loci was also investigated given that SINE repeats are involved in aberrant gene transcription. We found few instances of repetitive sequences at both fusion and non-fusion junctions. Finally, RT-qPCR was performed on RNA from both clinical prostate tumors and adjacent non-cancer cells (N = 7), and LNCaP cells treated as above to validate the expression of seven fusion transcripts and their respective parental genes. We reveal that fusion transcript expression is similar to the expression of parental genes. Conclusions Fusion transcripts maintain the open reading frame, and likely use the same transcriptional machinery as non-fusion transcripts as they share many genomic features at splice/fusion junctions.

Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption

Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of approximately 2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene (AUTS2) was associated with alcohol consumption at genome-wide significance (P = 4 x 10(-8) to P = 4 x 10(-9)). We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples (P = 0.026) and significant (P < 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. Down-regulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila (P < 0.001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior.

A case of true hermaphroditism reveals an unusual mechanism of twinning

Traditionally twins are classified as dizygous or fraternal and monozygous or identical (Hall Twinning, 362, 2003 and 735-743). We report a rare case of 46,XX/46,XY twins: Twin A presented with ambiguous genitalia and Twin B was a phenotypically normal male. These twins demonstrate a third, previously unreported mechanism for twinning. The twins underwent initial investigation with 17-hydroxyprogesterone and testosterone levels, pelvic ultrasound and diagnostic laparoscopy. Cytogenetic analysis was performed on peripheral blood cells and skin fibroblasts. Histological examination and Fluorescence in situ hybridization studies on touch imprints were performed on gonadal biopsies. DNA analysis using more than 6,000 DNA markers was performed on skin fibroblast samples from the twins and on peripheral blood samples from both parents. Twin A was determined to be a true hermaphrodite and Twin B an apparently normal male. Both twins had a 46,XX/46,XY chromosome complement in peripheral lymphocytes, skin fibroblasts, and gonadal biopsies. The proportion of XX to XY cells varied between the twins and the tissues evaluated. Most significantly the twins shared 100% of maternal alleles and approximately 50% of paternal alleles in DNA analysis of skin fibroblasts. The twins are chimeric and share a single genetic contribution from their mother but have two genetic contributions from their father thus supporting the existence of a third, previously unreported type of twinning.

Automated feature engineering for HTTP tunnel detection

Generating discriminative input features is a key requirement for achieving highly accurate classifiers. The process of generating features from raw data is known as feature engineering and it can take significant manual effort. In this paper we propose automated feature engineering to derive a suite of additional features from a given set of basic features with the aim of both improving classifier accuracy through discriminative features, and to assist data scientists through automation. Our implementation is specific to HTTP computer network traffic. To measure the effectiveness of our proposal, we compare the performance of a supervised machine learning classifier built with automated feature engineering versus one using human-guided features. The classifier addresses a problem in computer network security, namely the detection of HTTP tunnels. We use Bro to process network traffic into base features and then apply automated feature engineering to calculate a larger set of derived features. The derived features are calculated without favour to any base feature and include entropy, length and N-grams for all string features, and counts and averages over time for all numeric features. Feature selection is then used to find the most relevant subset of these features. Testing showed that both classifiers achieved a detection rate above 99.93% at a false positive rate below 0.01%. For our datasets, we conclude that automated feature engineering can provide the advantages of increasing classifier development speed and reducing development technical difficulties through the removal of manual feature engineering. These are achieved while also maintaining classification accuracy.

Family mediation and women’s services: Towards effective referral

Central to Government’s strategy for separating families is the management and resolution of disputes away from courts and litigation processes wherever this is achievable. A key group of players in facilitating this vision are workers within the wide range of women’s services. This study surveyed workers at a number of Victorian women’s services that provide advice, support, and referral for women and explored their understanding of mediation processes and outcomes. The results indicate that, while generally supportive of mediation as a process that could assist their clients, workers were concerned about its appropriateness when family violence was an issue. Some of these concerns appeared to be based upon a good understanding of the limitations of mediation practices, but it is also apparent that some concerns were influenced by a misunderstanding and limited knowledge of contemporary mediation practice. It is recommended that family mediation services work proactively with women’s services in order to better inform each other of the possibilities and constraints in working with postseparation disputes.