Developing an IS-Impact decision tool : a literature based design science roadmap

This paper derives from research-in-progress intending both Design Research (DR) and Design Science (DS) outputs; the former a management decision tool based in IS-Impact (Gable et al. 2008) kernel theory; the latter being methodological learnings deriving from synthesis of the literature and reflection on the DR ‘case study’ experience. The paper introduces a generic, detailed and pragmatic DS ‘Research Roadmap’ or methodology, deriving at this stage primarily from synthesis and harmonization of relevant concepts identified through systematic archival analysis of related literature. The scope of the Roadmap too has been influenced by the parallel study aim to undertake DR applying and further evolving the Roadmap. The Roadmap is presented in attention to the dearth of detailed guidance available to novice Researchers in Design Science Research (DSR), and though preliminary, is expected to evolve and gradually be substantiated through experience of its application. A key distinction of the Roadmap from other DSR methods is its breadth of coverage of published DSR concepts and activities; its detail and scope. It represents a useful synthesis and integration of otherwise highly disparate DSR-related concepts.

Is Dawkins a modern-day Nicodemus?

This article applies a Wittgensteinian approach to the examination of the intelligibility of religious belief, in the wake of the recent attack on the Judeo-Christian religion by Richard Dawkins's book The God Delusion. The article attempts to show that Dawkins has confused religion with superstition, and that while Dawkins's arguments are decisive in the case of superstition, they do not successfully show religion to be a delusion. Religious belief in God is not like belief in the existence of a planet, and genuine religious faith is not like the belief in something for which there is not yet enough evidence, like belief in dark matter. The Christian doctrines of the resurrection and eternal life are misconstrued if they are understood as factual claims because they are then merely shallow superstitions, and not the great religious riddles they are meant to be.

A variant of the KLK4 gene is expressed as a cis sense-antisense chimeric transcript in prostate cancer cells

In humans, more than 30,000 chimeric transcripts originating from 23,686 genes have been identified. The mechanisms and association of chimeric transcripts arising from chromosomal rearrangements with cancer are well established, but much remains unknown regarding the biogenesis and importance of other chimeric transcripts that arise from nongenomic alterations. Recently, a SLC45A3–ELK4 chimera has been shown to be androgen-regulated, and is overexpressed in metastatic or high-grade prostate tumors relative to local prostate cancers. Here, we characterize the expression of a KLK4 cis sense–antisense chimeric transcript, and show other examples in prostate cancer. Using non-protein-coding microarray analyses, we initially identified an androgen-regulated antisense transcript within the 3′ untranslated region of the KLK4 gene in LNCaP cells. The KLK4 cis-NAT was validated by strand-specific linker-mediated RT-PCR and Northern blotting. Characterization of the KLK4 cis-NAT by 5′ and 3′ rapid amplification of cDNA ends (RACE) revealed that this transcript forms multiple fusions with the KLK4 sense transcript. Lack of KLK4 antisense promoter activity using reporter assays suggests that these transcripts are unlikely to arise from a trans-splicing mechanism. 5′ RACE and analyses of deep sequencing data from LNCaP cells treated ±androgens revealed six high-confidence sense–antisense chimeras of which three were supported by the cDNA databases. In this study, we have shown complex gene expression at the KLK4 locus that might be a hallmark of cis sense–antisense chimeric transcription.

What once was old is new again: reviving an early-modern form of interdisciplinarity for socio-legal studies

Socio-legal studies are an essentially interdisciplinary enterprise. However, there is currently only one form of interdisciplinarity that most socio-legal scholars (and criminologists) recognise and work with. This form is derived from the idea that 'society itself' - and by this most scholars mean 'civil society' - drives the law. However, another, rival understanding of society, which we term the authoritarian-liberal statist understanding that slipped from view in the late seventeenth century and remained obscure from then until now, may be used to generate another form of interdisciplinarity for sOcio-legal studies (and for criminology). However, this rival understanding of society does not simply allow us to reconfigure our notion of 'society'; it radically changes the role society plays in relation to the law. Two crucial points emerge from this rival account: first, society can no longer be understood as separable from (even though interacting with) the law; and second, society can no longer be understood as driving the law.

Co-expression of CD147 (EMMPRIN), CD44v3-10, MDR1 and monocarboxylate transporters is associated with prostate cancer drug resistance and progression

Background: The aim of this study is to seek an association between markers of metastatic potential, drug resistance-related protein and monocarboxylate transporters in prostate cancer (CaP). Methods: We evaluated the expression of invasive markers (CD147, CD44v3-10), drug-resistance protein (MDR1) and monocarboxylate transporters (MCT1 and MCT4) in CaP metastatic cell lines and CaP tissue microarrays (n=140) by immunostaining. The co-expression of CD147 and CD44v3-10 with that of MDR1, MCT1 and MCT4 in CaP cell lines was evaluated using confocal microscopy. The relationship between the expression of CD147 and CD44v3-10 and the sensitivity (IC50) to docetaxel in CaP cell lines was assessed using MTT assay. The relationship between expression of CD44v3-10, MDR1 and MCT4 and various clinicopathological CaP progression parameters was examined. Results: CD147 and CD44v3-10 were co-expressed with MDR1, MCT1 and MCT4 in primary and metastatic CaP cells. Both CD147 and CD44v3-10 expression levels were inversely related to docetaxel sensitivity (IC50) in metastatic CaP cell lines. Overexpression of CD44v3-10, MDR1 and MCT4 was found in most primary CaP tissues, and was significantly associated with CaP progression. Conclusions: Our results suggest that the overexpression of CD147, CD44v3-10, MDR1 and MCT4 is associated with CaP progression. Expression of both CD147 and CD44v3-10 is correlated with drug resistance during CaP metastasis and could be a useful potential therapeutic target in advanced disease.

Expression of PSA-RP2, an alternatively spliced variant from the PSA gene, is increased in prostate cancer tissues but the protein is not secreted from prostate cancer cells

PSA-RP2 is a variant transcript expressed from the PSA gene that is conserved in gorillas, chimpanzees and humans suggesting a particular relevance for this transcript in these primates. We demonstrated by qRT-PCR that PSA-RP2 is upregulated in prostate cancer compared with benign prostatic hyperplasia tissues. The PSA-RP2 protein was not detected in seminal fluid and was cytoplasmically localised but not secreted from LNCaP or transfected PC3 prostate cells, despite secretion from transfected Cos-7 and HEK293 kidney cell lines. PSA-RP2-transfected PC3 cells showed slightly decreased proliferation and increased migration towards PC3-conditioned medium that could suggest a functional role in prostate cancer.