Augmenting the 6-3-5 method with design information

This paper describes a comparative study between the 6-3-5 Method and the ICR Grid. The ICR Grid is an evolved variant of 6-3-5 intended to better integrate information into the concept generation process. Unlike a conventional 6-3-5 process where participants continually sketch concepts, using the ICR Grid (the name derived from its Inform, Create, Reflect activities and structured, grid-like output) participants are additionally required to undertake information search tasks, use specific information items for concept development, and reflect on the merit of concepts as the session progresses. The results indicate that although the quantity of concepts was lower, the use of information had a positive effect in a number of areas, principally the quality and variety of output. Although grounded in the area of product development, this research is applicable to any organisation undertaking idea generation and problem solving. As well as providing insights on the transference of information to concepts, it holds additional interest for studies on the composition and use of digital libraries

Epistemic Schmagency?

Constructivist approaches in epistemology and ethics offer a promising account of normativity. But constructivism faces a powerful Schmagency Objection, raised by David Enoch. While Enoch’s objection has been widely discussed in the context of practical norms, no one has yet explored how the Schmagency Objection might undermine epistemic constructivism. In this paper, I rectify that gap. First, I develop the objection against a prominent form of epistemic constructivism, Belief Constitutivism. Belief Constitutivism is susceptible to a Schmagency Objection, I argue, because it locates the source of normativity in the belief rather than the agent. In the final section, I propose a version of epistemic constructivism that locates epistemic normativity as constitutive of agency. I argue that this version has the resources to respond to the Schmagency Objection

NRF2-driven miR-125B1 and miR-29B1 transcriptional regulation controls a novel anti-apoptotic miRNA regulatory network for AML survival

Transcription factor NRF2 is an important regulator of oxidative stress. It is involved in cancer progression, and has abnormal constitutive expression in acute myeloid leukaemia (AML). Posttranscriptional regulation by microRNAs (miRNAs) can affect the malignant phenotype of AML cells. In this study, we identified and characterised NRF2-regulated miRNAs in AML. An miRNA array identified miRNA expression level changes in response to NRF2 knockdown in AML cells. Further analysis of miRNAs concomitantly regulated by knockdown of the NRF2 inhibitor KEAP1 revealed the major candidate NRF2-mediated miRNAs in AML. We identified miR-125B to be upregulated and miR-29B to be downregulated by NRF2 in AML. Subsequent bioinformatic analysis identified putative NRF2 binding sites upstream of the miR-125B1 coding region and downstream of the mir-29B1 coding region. Chromatin immunoprecipitation analyses showed that NRF2 binds to these antioxidant response elements (AREs) located in the 5′ untranslated regions of miR-125B and miR-29B. Finally, primary AML samples transfected with anti-miR-125B antagomiR or miR-29B mimic showed increased cell death responsiveness either alone or co-treated with standard AML chemotherapy. In summary, we find that NRF2 regulation of miR-125B and miR-29B acts to promote leukaemic cell survival, and their manipulation enhances AML responsiveness towards cytotoxic chemotherapeutics

Normative Alethic Pluralism

Some philosophers have argued that truth is a norm of judgement and have provided a variety of formulations of this general thesis. In this paper, I shall side with these philosophers and assume that truth is a norm of judgement. What I am primarily interested in here are two core questions concerning the judgement-truth norm: (i) what are the normative relationships between truth and judgement? And (ii) do these relationships vary or are they constant? I argue for a pluralist picture—what I call Normative Alethic Pluralism (NAP)—according to which (i) there is more than one correct judgement-truth norm and (ii) the normative relationships between truth and judgement vary in relation to the subject matter of the judgement. By means of a comparative analysis of disagreement in three areas of the evaluative domain—refined aesthetics, basic taste and morality—I show that there is an important variability in the normative significance of disagreement—I call this the variability conjecture. By presenting a variation of Lynch’s scope problem for alethic monism, I argue that a monistic approach to the normative function of truth is unable to vindicate the conjecture. I then argue that normative alethic pluralism provides us with a promising model to account for it

A study of the perceived risks, benefits and barriers to the use of SDD in adult critical care units (the SuDDICU study)

Peer reviewedPublisher PD

Quantitative principles of cis-translational control by general mRNA sequence features in eukaryotes.

BackgroundGeneral translational cis-elements are present in the mRNAs of all genes and affect the recruitment, assembly, and progress of preinitiation complexes and the ribosome under many physiological states. These elements include mRNA folding, upstream open reading frames, specific nucleotides flanking the initiating AUG codon, protein coding sequence length, and codon usage. The quantitative contributions of these sequence features and how and why they coordinate to control translation rates are not well understood.ResultsHere, we show that these sequence features specify 42-81% of the variance in translation rates in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Arabidopsis thaliana, Mus musculus, and Homo sapiens. We establish that control by RNA secondary structure is chiefly mediated by highly folded 25-60 nucleotide segments within mRNA 5' regions, that changes in tri-nucleotide frequencies between highly and poorly translated 5' regions are correlated between all species, and that control by distinct biochemical processes is extensively correlated as is regulation by a single process acting in different parts of the same mRNA.ConclusionsOur work shows that general features control a much larger fraction of the variance in translation rates than previously realized. We provide a more detailed and accurate understanding of the aspects of RNA structure that directs translation in diverse eukaryotes. In addition, we note that the strongly correlated regulation between and within cis-control features will cause more even densities of translational complexes along each mRNA and therefore more efficient use of the translation machinery by the cell

A tolerance analysis and optimization methodology: the combined use of 3D CAT, a dimensional hierarchization matrix and an optimization algorithm

We propose a methodology in this study for the analysis and the optimization of assembly tolerances. A combination of three components, it involves the use of 3D CAT software, a table referred to as a “dimensional hierarchization matrix” and a tolerance optimization algorithm. The Antolin Group, a Spanish multinational in the automobile components sector, employs this system to optimize tolerance values and to reduce manufacturing costs. The matrix was designed to enable easy identification, in a single table, of all requirements that fail to meet the specifications in the different approximations, prior to the definition of the dimensional and the geometric tolerances that comply with the functional requirements, and to identify which tolerances contribute most to variations in all of the functional conditions of the mechanism. Through its different iterations, this matrix allows us to see which of the tolerances should first be modified to optimize the design requirement specifications. A tolerance optimization algorithm was also defined, which functions with the data from the dimensional hierarchization matrix

Factors associated with crisis pregnancies in Ireland: Findings from three nationally representative sexual health surveys

Background: Findings on the demographic and sexual health characteristics associated with the experience of a crisis pregnancy is important to inform the public health policy of a country, including Ireland. Findings from other jurisdictions have suggested that certain demographic groups are at risk for unintended pregnancies and the disparity between the groups have been growing in recent years. Ireland is a country which experienced much economic and societal change in the first decade of the 21st century, changes which are likely to have affected demographic variables pertaining to sexual health. The current study had two aims: to investigate changes in the socioeconomic characteristics associated with crisis pregnancies over a seven year period [2003 to 2010], and to investigate the recent [2010] socioeconomic risk factors associated with crisis pregnancies in Ireland. Methods: The study compared the results from 18-45 year old women using data from three broadly similar nationally representative Irish sexual health surveys carried out in 2003, 2004-2006 and 2010. Chi square analysis compared of the socioeconomic characteristics across the seven year period and found that a higher proportion of women with two or more children and women for whom religion was not important reported a crisis pregnancy in 2010 compared with earlier years. A logistic regression then investigated the sexual health history and socioeconomic factors associated with the experience of a recent crisis pregnancy using the most recent 2010 data. Results: Receipt of sex education and contraception use at first sex significantly predicted the experiencing of a recent crisis pregnancy. Younger women and those with a lower level of education were more likely to report having experienced a recent crisis pregnancy. Conclusion: Similar demographic groups are at risk for experiencing a crisis pregnancy in Ireland compared with international research, yet the disparities between demographic groups who have experienced a crisis pregnancy appear to be decreasing rather than increasing over a seven year period. Recommendations are made with regard to the provision of continued sex education throughout the lifespan, particularly for those women who are at an increased risk of experiencing a crisis pregnancy