Special issue on best papers from the "BPM 2012" workshops

Business Process Management (BPM) (Dumas et al. 2013) investigates how organizations function and can be improved on the basis of their business processes. The starting point for BPM is that organizational performance is a function of process performance. Thus, BPM proposes a set of methods, techniques and tools to discover, analyze, implement, monitor and control business processes, with the ultimate goal of improving these processes. Most importantly, BPM is not just an organizational management discipline. BPM also studies how technology, and particularly information technology, can effectively support the process improvement effort. In the past two decades the field of BPM has been the focus of extensive research, which spans an increasingly growing scope and advances technology in various directions. The main international forum for state-of-the-art research in this field is the International Conference on Business Process Management, or “BPM” for short—an annual meeting of the aca ...

Scripted drama: The long wait for football to be taken seriously as a literary subject

This article is a work of non-fiction which draws on my research in football fiction.

Biliverdin modulates the expression of C5aR in response to endotoxin in part via mTOR signaling

Macrophages play a crucial role in the maintenance and resolution of inflammation and express a number of pro- and anti-inflammatory molecules in response to stressors. Among them, the complement receptor 5a (C5aR) plays an integral role in the development of inflammatory disorders. Biliverdin and bilirubin, products of heme catabolism, exert anti-inflammatory effects and inhibit complement activation. Here, we define the effects of biliverdin on C5aR expression in macrophages and the roles of Akt and mammalian target of rapamycin (mTOR) in these responses. Biliverdin administration inhibited lipopolysaccharide (LPS)-induced C5aR expression (without altering basal expression), an effect partially blocked by rapamycin, an inhibitor of mTOR signaling. Biliverdin also reduced LPS-dependent expression of the pro-inflammatory cytokines TNF-alpha and IL-6. Collectively, these data indicate that biliverdin regulates LPS-mediated expression of C5aR via the mTOR pathway, revealing an additional mechanism underlying biliverdin's anti-inflammatory effects.

The tumour-promoting receptor tyrosine kinase, EphB4, regulates expression of Integrin-β8 in prostate cancer cells

Background The EphB4 receptor tyrosine kinase is overexpressed in many cancers including prostate cancer. The molecular mechanisms by which this ephrin receptor influences cancer progression are complex as there are tumor-promoting ligand-independent mechanisms in place as well as ligand-dependent tumor suppressive pathways. Methods We employed transient knockdown of EPHB4 in prostate cancer cells, coupled with gene microarray analysis, to identify genes that were regulated by EPHB4 and may represent linked tumor-promoting factors. We validated target genes using qRT-PCR and employed functional assays to determine their role in prostate cancer migration and invasion. Results We discovered that over 500 genes were deregulated upon EPHB4 siRNA knockdown, with integrin β8 (ITGB8) being the top hit (29-fold down-regulated compared to negative non-silencing siRNA). Gene ontology analysis found that the process of cell adhesion was highly deregulated and two other integrin genes, ITGA3 and ITGA10, were also differentially expressed. In parallel, we also discovered that over-expression of EPHB4 led to a concomitant increase in ITGB8 expression. In silico analysis of a prostate cancer progression microarray publically available in the Oncomine database showed that both EPHB4 and ITGB8 are highly expressed in prostatic intraepithelial neoplasia, the precursor to prostate cancer. Knockdown of ITGB8 in PC-3 and 22Rv1 prostate cancer cells in vitro resulted in significant reduction of cell migration and invasion. Conclusions These results reveal that EphB4 regulates integrin β8 expression and that integrin β8 plays a hitherto unrecognized role in the motility of prostate cancer cells and thus targeting integrin β8 may be a new treatment strategy for prostate cancer.

The culture wars of climate change

Of late, there has been a growth in cultural expression about climate change – with the rise of climate fiction (‘cli-fi’); art and photography responding to changes in nature; musical anthems about climate change; plays and dramas about climate change; and environmental documentaries, and climate cinema. Drawing comparisons to past controversies over cultural funding, this paper considers the cultural wars over climate change. This article considers a number of cultural fields. Margaret Atwood made an important creative and critical contribution to the debate over climate change. The work examines Ian McEwan's novel, Solar, a tragi-comedy about authorship, invention, intellectual property, and climate science. After writing a history of Merchants of Doubt, Naomi Oreskes and Erik Conway have experimented with fiction – as well as history. This article focuses upon artistic works about climate change. It analyses James Balog’s work with the Extreme Ice Survey, which involved photography of glaciers under retreat in a warming world. The work was turned into a documentary called Chasing Ice. It also considers the artistic project of 350.org 'to transform the human rights and environmental issues connected to climate change into powerful art that gets people to stop, think and act.' The paper examines musical storytelling in respect of climate change. The paper explores dramatic works about climate change including Steve Waters' The Contingency Plan, Stephen Emmott's Ten Billion, and Andrew Bovell's When the Rain Stops Falling and Hannie Rayson’s Extinction. The paper also examines the role of documentary film-making. It also considers the cinematographic film, Beasts of the Southern Wild. Such a survey will enable a consideration of the larger question of whether creative art about climate change matters; and whether it is deserving of public funding.

Expression and characterization of digestive enzyme genes from hepatopancreatic transcripts from redclaw crayfish (Cherax quadricarinatus)

Redclaw crayfish, Cherax quadricarinatus, possess a number of biological and commercial attributes that make them ideal for commercial aquaculture. While some studies have investigated digestive enzyme activity and nutritional requirements of this species, little information exists about the expression of digestive enzyme genes and their role in regulating digestive capacity. The current study therefore sequenced and annotated a RNASeq library constructed from a redclaw hepatopancreas to identify genes involved in digestive enzyme production. We observed that most of the transcripts that were annotated as digestive enzyme genes are associated with carbohydrate metabolism, thus confirming that redclaw have an innate capacity to digest a range of carbohydrate substrates. While endoglucanases were the most abundant group of digestive enzymes found, a number of novel transcripts were also detected. Here, we provide the first report for the presence and expression of endo-b-mannanase in freshwater crayfish. This novel gene showed significant alignment with a GH5 family protein from marine Limnoriids, wood borers that do not possess symbiotic microbes in their gut system. Overall, the data generated here provide an important resource to better understand the suite of digestive enzymes in redclaw that are very useful to fully utilize the species’ digestive capacity and will assist development of specific artificial feeds.

Analysis, characterisation and expression of gill-expressed carbonic anhydrase genes in the freshwater crayfish Cherax quadricarinatus

Changes in water quality parameters such as pH and salinity can have a significant effect on productivity of aquaculture species. Similarly, relative osmotic pressure influences various physiological processes and regulates expression of a number of osmoregulatory genes. Among those, carbonic anhydrase (CA) plays a key role in systemic acid–base balance and ion regulation. Redclaw crayfish (Cherax quadricarinatus) are unique in their ability to thrive in environments with naturally varied pH levels, suggesting unique adaptation to pH stress. To date, however, no studies have focused on identification and characterisation of CA or other osmoregulatory genes in C. quadricarinatus. Here, we analysed the redclaw gill transcriptome and characterized CA genes along with a number of other key osmoregulatory genes that were identified in the transcriptome. We also examined patterns of gene expression of these CA genes when exposed to three pH treatments. In total, 72,382,710 paired end Illumina reads were assembled into 36,128 contigs with an average length of 800 bp. Approximately 37% of contigs received significant BLAST hits and 22% were assigned gene ontology terms. Three full length CA isoforms; cytoplasmic CA (ChqCAc), glycosyl-phosphatidylinositol-linked CA (ChqCAg), and β-CA (ChqCA-beta) as well as two partial CA gene sequences were identified. Both partial CA genes showed high similarity to ChqCAg and appeared to be duplicated from the ChqCAg. Full length coding sequences of Na+/K+-ATPase, V-type H+-ATPase, sarcoplasmic Ca+-ATPase, arginine kinase, calreticulin and Cl− channel protein 2 were also identified. Only the ChqCAc gene showed significant differences in expression across the three pH treatments. These data provide valuable information on the gill expressed CA genes and their expression patterns in freshwater crayfish. Overall our data suggest an important role for the ChqCAc gene in response to changes in pH and in systemic acid–base balance in freshwater crayfish.

Under this Sky: Logan's Musical Celebration

A creative practice as research, UNDER THIS SKY is the latest investigation in a 12-year study into the “QMF Model”, an application of principles of community and cultural practice that generates large-scale, music spectacle events that derive their narrative and expression from the communities in which they are performed. UNDER THIS SKY is a large-scale musical specially commissioned for the city of Logan (Queensland) as the signature work of the 2015 Queensland Musical Festival. The investigation centres around the capacity of the “QMF Model” to engage with performers and musicians of Logan and then, through community consultation, create a narrative based on idiosyncratic stories and themes that would culminate in a performance event in August 2015. Previous creative projects, Boomtown (Gladstone), Behind the Cane (Bowen) and The Road We’re On (Charleville), were conducted in relatively small communities, Gladstone being the largest. In UNDER THIS SKY, the model is being tested in a large metropolitan city (Logan – 300,000). The core principles of CACD (community arts and cultural development) are being interrogated and adapted to fit this large-scale, whole of community environment. The purpose is to refine and further validate the “QMF Model” as a viable and effective process for community/artistic partnerships. Since February 2014, professional artists and managers have facilitated and shaped the work, up-skilling performers over a periods of 12 months, developing new relationships and creating opportunities for participation at all levels of experience. The research methodology involved creative practice through a continuous cycle of action, reflection, adaptation and application.

Development of a new design expression for the in-plane shear capacity of the partially grouted concrete masonry walls

Partially grouted masonry walls subjected to in-plane shear exhibit a complex behaviour because of the influence of the aspect ratio, the pre-compression, the grouting pattern, the ratios of the horizontal and the vertical reinforcements, the boundary conditions and the characteristics of the constituent materials. The existing in-plane shear expressions for the partially grouted masonry are formulated as sum of strength of three parameters, namely, the masonry, the reinforcement and the axial force. The parameter ‘masonry’ includes the wall aspect ratio and the masonry compressive strength; the aspect ratio of the unreinforced panel inscribed into the grouted cores and bond beams are not considered, although failure is often dominated by these unreinforced masonry panels. This paper describes the dominance of these panels, particularly those that are squat, to the shear capacity of whole of shear walls. Further, the current design formulae are shown highly un-conservative by many researchers; this paper provides a potential reason for this un-conservativeness. It is shown that by including an additional term of the unreinforced panel aspect ratio a rational design formula could be established. This new expression is validated with independent test results reported in the literature – both Australian and overseas; the predictions are shown to be conservative.

The MS risk allele of CD40 is associated with reduced cell-membrane bound expression in antigen presenting cells: Implications for gene function

Human genetic and animal studies have implicated the costimulatory molecule CD40 in the development of multiple sclerosis (MS). We investigated the cell specific gene and protein expression variation controlled by the CD40 genetic variant(s) associated with MS, i.e. the T-allele at rs1883832. Previously we had shown that the risk allele is expressed at a lower level in whole blood, especially in people with MS. Here, we have defined the immune cell subsets responsible for genotype and disease effects on CD40 expression at the mRNA and protein level. In cell subsets in which CD40 is most highly expressed, B lymphocytes and dendritic cells, the MS-associated risk variant is associated with reduced CD40 cell-surface protein expression. In monocytes and dendritic cells, the risk allele additionally reduces the ratio of expression of full-length versus truncated CD40 mRNA, the latter encoding secreted CD40. We additionally show that MS patients, regardless of genotype, express significantly lower levels of CD40 cell-surface protein compared to unaffected controls in B lymphocytes. Thus, both genotype-dependent and independent down-regulation of cell-surface CD40 is a feature of MS. Lower expression of a co-stimulator of T cell activation, CD40, is therefore associated with increased MS risk despite the same CD40 variant being associated with reduced risk of other inflammatory autoimmune diseases. Our results highlight the complexity and likely individuality of autoimmune pathogenesis, and could be consistent with antiviral and/or immunoregulatory functions of CD40 playing an important role in protection from MS. © 2015 Field et al.

Expression profiling in spondyloarthropathy synovial biopsies highlights changes in expression of inflammatory genes in conjunction with tissue remodelling genes

Background: In the spondyloarthropathies, the underlying molecular and cellular pathways driving disease are poorly understood. By undertaking a study in knee synovial biopsies from spondyloarthropathy (SpA) and ankylosing spondylitis (AS) patients we aimed to elucidate dysregulated genes and pathways. Methods RNA was extracted from six SpA, two AS, three osteoarthritis (OA) and four normal control knee synovial biopsies. Whole genome expression profiling was undertaken using the Illumina DASL system, which assays 24000 cDNA probes. Differentially expressed candidate genes were then validated using quantitative PCR and immunohistochemistry. Results: Four hundred and sixteen differentially expressed genes were identified that clearly delineated between AS/SpA and control groups. Pathway analysis showed altered gene-expression in oxidoreductase activity, B-cell associated, matrix catabolic, and metabolic pathways. Altered «myogene» profiling was also identified. The inflammatory mediator, MMP3, was strongly upregulated (5-fold) in AS/SpA samples and the Wnt pathway inhibitors DKK3 (2.7-fold) and Kremen1 (1.5-fold) were downregulated. Conclusions: Altered expression profiling in SpA and AS samples demonstrates that disease pathogenesis is associated with both systemic inflammation as well as local tissue alterations that may underlie tissue damaging modelling and remodelling outcomes. This supports the hypothesis that initial systemic inflammation in spondyloarthropathies transfers to and persists in the local joint environment, and might subsequently mediate changes in genes directly involved in the destructive tissue remodelling.

Gene expression profiling reveals a downregulation in immune-associated genes in patients with AS

Objective: To identify differentially expressed genes in peripheral blood mononuclear cells (PBMCs) from patients with ankylosing spondylitis (AS) compared with healthy individuals. Methods: RNA was extracted from PBMCs collected from 18 patients with active disease and 18 gender-matched and age-matched controls. Expression profiles of these cells were determined using microarray. Candidate genes with differential expressions were confirmed in the same samples using quantitative reverse transcription-PCR (qRT-PCR). These genes were then validated in a different sample cohort of 35 patients with AS and 18 controls by qRT-PCR. Results: Microarray analysis identified 452 genes detected with 485 probes which were differentially expressed between patients with AS and controls. Underexpression of NR4A2, tumour necrosis factor AIP3 (TNFAIP3) and CD69 was confirmed. These genes were further validated in a different sample group in which the patients with AS had a wider range of disease activity. Predictive algorithms were also developed from the expression data using receiver-operating characteristic curves, which demonstrated that the three candidate genes have ∼80% power to predict AS according to their expression levels. Conclusions: The findings show differences in global gene expression patterns between patients with AS and controls, suggesting an immunosuppressive phenotype in the patients. Furthermore, downregulated expression of three immune-related genes was confirmed. These candidate genes were also shown to be strong predictive markers for AS.

Association of sporadic chondrocalcinosis with a -4-basepair G-to-A transition in the 5′-untranslated region of ANKH that promotes enhanced expression of ANKH protein and excess generation of extracellular inorganic pyrophosphate

Objective Certain mutations in ANKH, which encodes a multiple-pass transmembrane protein that regulates inorganic pyrophosphate (PPi) transport, are linked to autosomal-dominant familial chondrocalcinosis. This study investigated the potential for ANKH sequence variants to promote sporadic chondrocalcinosis. Methods ANKH variants identified by genomic sequencing were screened for association with chondrocalcinosis in 128 patients with severe sporadic chondrocalcinosis or pseudogout and in ethnically matched healthy controls. The effects of specific variants on expression of common markers were evaluated by in vitro transcription/translation. The function of these variants was studied in transfected human immortalized CH-8 articular chondrocytes. Results Sporadic chondrocalcinosis was associated with a G-to-A transition in the ANKH 5′-untranslated region (5′-UTR) at 4 bp upstream of the start codon (in homozygotes of the minor allele, genotype relative risk 6.0, P = 0.0006; overall genotype association P = 0.02). This -4-bp transition, as well as 2 mutations previously linked with familial and sporadic chondrocalcinosis (+14 bp C-to-T and C-terminal GAG deletion, respectively), but not the French familial chondrocalcinosis kindred 143-bp T-to-C mutation, increased reticulocyte ANKH transcription/ANKH translation in vitro. Transfection of complementary DNA for both the wild-type ANKH and the -4-bp ANKH protein variant promoted increased extracellular PPi in CH-8 cells, but unexpectedly, these ANKH mutants had divergent effects on the expression of extracellular PPi and the chondrocyte hypertrophy marker, type X collagen. Conclusion A subset of sporadic chondrocalcinosis appears to be heritable via a -4-bp G-to-A ANKH 5′-UTR transition that up-regulates expression of ANKH and extracellular PPi in chondrocyte cells. Distinct ANKH mutations associated with heritable chondrocalcinosis may promote disease by divergent effects on extracellular PPi and chondrocyte hypertrophy, which is likely to mediate differences in the clinical phenotypes and severity of the disease.

Molecular cloning, expression and immunological characterisation of Pas n 1, the major allergen of Bahia grass Paspalum notatum pollen

Bahia grass, Paspalum notatum, is a clinically important subtropical grass with a prolonged pollination season from spring to autumn. We aimed to clone and characterise the major Bahia grass pollen allergen, Pas n 1. Grass pollen-allergic patients presenting to a tertiary hospital allergy clinic were tested for IgE reactivity with Bahia grass pollen extract by skin prick testing, ImmunoCAP, ELISA and immunoblotting. Using primers deduced from the N-terminal peptide sequence of a group 1 allergen of Bahia grass pollen extract separated by two-dimensional gel electrophoresis, the complete Pas n 1 cDNA was obtained by rapid amplification of cDNA ends and cloned. Biological relevance of recombinant Pas n 1 expressed in Escherichia coli was assessed by serum IgE reactivity and basophil activation. Twenty-nine of 34 (85%) consecutive patients presenting with grass pollen allergy were skin prick test positive to Bahia grass pollen. The Pas n 1 cDNA has sequence homology with the β-expansin 1 glycoprotein family and is more closely related to the maize pollen group 1 allergen (85% identity) than to ryegrass Lol p 1 or Timothy grass Phl p 1 (64 and 66% identity, respectively). rPas n 1 reacted with serum IgE in 47 of 55 (85%) Bahia grass pollen-allergic patients, activated basophils and inhibited serum IgE reactivity with the 29 kDa band of Bahia grass pollen extract. In conclusion the cDNA for the major group 1 allergen of the subtropical Bahia grass pollen, Pas n 1, was identified and cloned. rPas n 1 is immunologically active and is a valuable reagent for diagnosis and specific immunotherapy of grass pollen allergy.

Cytokine mRNA expression and IFN-γ production of immunised nematode resistant and susceptible lambs against natural poly-generic challenge

IL-2, IL-4 and IFN-γ mRNA expression, and production of IFN-γ was examined in mesenteric lymph node cells (MLNC) and CD4+ enriched T cell populations of nematode resistant (R) and susceptible (S) line lambs by use of RT-PCR and ELISA. Five R and S line lambs that were immunised by repeated oxfendazole-abbreviated infections and 5 non-immunised R and S line lambs were used. All lambs grazed nematode infected pasture for 107 days. Immunisation enhanced the resistant status in both R and S lambs. MLNC obtained from slaughtered animals were stimulated with Con A or T. colubriformis specific antigen. Non-stimulated MLNC of immunised lambs expressed higher levels of IL-4 mRNA and lower levels of IL-2 mRNA than non-immunised lambs. MLNC of immunised R and S line lambs stimulated with antigen for 24 h expressed detectable amounts of IL-4 mRNA that was not seen in non-immunised controls. CD4+ T cell enriched cell populations of immunised R and S lambs and non-immunised R lambs expressed moderate to high levels of IL-4 mRNA. Con A stimulated MLNC of immunised R and S lambs expressed high levels IFN-γ mRNA and produced high amounts of IFN-γ. Lower levels were present in non-immunised controls. The results indicate that R line lambs and immunised S line lambs respond to natural nematode challenge with a predominating IL-4 cytokine response when compared to non-immunised S lambs.