Multivariate Statistical Analysis Applied to an IL6 Signal Transduction Model in Hepatocytes

This paper introduces the application of linear multivariate statistical techniques, including partial least squares (PLS), canonical correlation analysis (CCA) and reduced rank regression (RRR), into the area of Systems Biology. This new approach aims to extract the important proteins embedded in complex signal transduction pathway models.The analysis is performed on a model of intracellular signalling along the janus-associated kinases/signal transducers and transcription factors (JAK/STAT) and mitogen activated protein kinases (MAPK) signal transduction pathways in interleukin-6 (IL6) stimulated hepatocytes, which produce signal transducer and activator of transcription factor 3 (STAT3).A region of redundancy within the MAPK pathway that does not affect the STAT3 transcription was identified using CCA. This is the core finding of this analysis and cannot be obtained by inspecting the model by eye. In addition, RRR was found to isolate terms that do not significantly contribute to changes in protein concentrations, while the application of PLS does not provide such a detailed picture by virtue of its construction.This analysis has a similar objective to conventional model reduction techniques with the advantage of maintaining the meaning of the states prior to and after the reduction process. A significant model reduction is performed, with a marginal loss in accuracy, offering a more concise model while maintaining the main influencing factors on the STAT3 transcription.The findings offer a deeper understanding of the reaction terms involved, confirm the relevance of several proteins to the production of Acute Phase Proteins and complement existing findings regarding cross-talk between the two signalling pathways.

Association of gene expression with sequential proliferation, differentiation and tumor formation in murine skin

Differential gene expression in two established initiation and promotion skin carcinogenesis models during promotion and tumor formation was determined by microarray technology with the purpose of distinguishing the genes more associated with neoplastic transformation from those linked with proliferation and differentiation. The first model utilized dimethylbenz[a]anthracene initiation and 12-O-tetradecanoylphorbol 13-acetate (TPA) promotion in the FVB/N mouse, and the second TPA promotion of the Tg.Ac mouse, which is endogenously initiated by virtue of an activated Ha-ras transgene. Comparison of gene expression profiles across the two models identified genes whose altered expression was associated with papilloma formation rather than TPA-induced proliferation and differentiation. DMBA suppressed TPA-induced differentiation which allowed identification of those genes associated more specifically with differentiation rather than proliferation. EASE (Expression Analysis Systemic Explorer) indicated a correlation between muscle-associated genes and skin differentiation, whereas genes involved with protein biosynthesis were strongly correlated with proliferation. For verification the altered expression of selected genes were confirmed by RT-PCR; Carbonic anhydrase 2, Thioredoxin 1 and Glutathione S-transferase omega 1 associated with papilloma formation and Enolase 3, Cystatin 6 and Filaggrin associated with TPA-induced proliferation and differentiation. In situ analysis located the papillomas Glutathione S-transferase omega 1 expression to the proliferating areas of the papillomas. Thus we have identified profiles of differential gene expression associated with the tumorigenesis and promotion stages for skin carcinogenesis in the mouse.

Who is susceptible to conjunction fallacies in category-based induction?

Recent evidence suggests that the conjunction fallacy observed in people's probabilistic reasoning is also to be found in their evaluations of inductive argument strength. We presented 130 participants with materials likely to produce a conjunction fallacy either by virtue of a shared categorical or a causal relationship between the categories in the argument. We also took a measure of participants' cognitive ability. We observed conjunction fallacies overall with both sets of materials but found an association with ability for the categorical materials only. Our results have implications for accounts of individual differences in reasoning, for the relevance theory of induction, and for the recent claim that causal knowledge is important in inductive reasoning.

‘Doing it with men’: feminist research practice and patriarchal inheritance practices in Welsh family farming

Internationally, the gender relations of the family farming ‘way of life’ have beenshown to be stubbornly persistent in their adherence to patriarchal inheritancepractices. This article demonstrates how such ‘agri-cultural’ practices are situated bothwithin the subjective sphere of farming individuals’ and within global agri-economics,bringing new challenges to patrilineal farm survival. It is suggested here that the recenttendency for post-structuralist theorisation in rural studies has underestimated theexistence and impact of patrilineal patterns in family farming. Such patterns mean thatwomen are shown to largely occupy relational gender identities as the ‘helper’, whilstmen are strongly identified as the ‘farmer’. Drawing on repeated life-history interviewsconducted with farming men and women from Powys, Mid Wales, the aim of thisarticle is to generate debate as to the extent to which men can be brought into feministresearch practice in order to reveal patriarchy to a greater degree. The article begins bysituating the near-exclusion of men from feminist research practice within theoreticaldevelopments in feminist geography. This discussion also assists in deriving issues ofresearch methods, positionality and interpretive power which focus the integration ofempirical material in the methodological reflections provided in section three. In sectiontwo, the rationale for the epistemological stance taken in the research is provided. Thearticle provides an example of the successful integration of men into a feminist researchframe, suggests avenues for theoretical development and identifies future researchdirections which can be informed by ‘doing it with men’.

Keywords: epistemology; family farming; feminist res

Architecture, memory and historical continuity in Old Cairo

The hawari (local communities) of Old Cairo resemble a unique societal context whose history is actively involved in the contemporary everyday production of local habits, traditions and social practice. By the virtue of its durability and ability to survive, Architecture brings events and traditions of the past alive into the present through the spatial transformation, social practice and the value of the historical-fabric. The presence of buildings and houses from different historical periods has helped the local community’s memory to carry social practices over from one generation to another. This article explores the relationship between architecture, memory and everyday social practices through determining the way architecture moderates community experiences and communicates narratives among generations in haret al-Darb al-Asfar in old Cairo. Architecture emerges as a moderator of cross-time communication and as physical elements that help visualize history, situate values and materialize local traditions in old Cairo. Architecture, as process and product this article reports, works as agent of continuity, which in conjunction with the narrators, brings the full experience of the past alive in the present and helps guide future generations.

On being a good nurse: reflections on the past and preparing for the future

On being a good nurse: reflections on the past and preparing for the future. The objectives of this paper include reflecting on the attributes of the ‘good’ nurse in the past, outlining thematically the essential attributes (virtues) required by the ‘good’ nurse today and presenting an original four- point framework for ethics in practice. While there is no doubt that nurses in the past were highly professional, the culture within which they practiced tended to stifle the emergence of autonomy, assertiveness, advocacy and accountability. An original table of contemporary attributes, which is congruent with a neo Aristotelian virtue ethical approach, is arranged in themes of Intellectual and Practical Attributes, Dispositional Attributes and Moral Attributes. A framework for professional practice, the ‘Four As’ is then extrapolated from these themes. These four key professional attributes, autonomy, advocacy, accountability and assertiveness, along with the virtues listed in the themes, exemplify the ‘good’ nurse and are identified as the linchpins of modern professional ethics and good conduct.

The good, the bad and the 'not so bad': reflecting on moral appraisal in practice

The aim of this paper is to facilitate reflection on the moral merit of practitioners in various contexts. Insight is gained from Aristotelian and Kantian accounts of moral character and an original framework for reflection is presented as an adjunct to ethical theory and principles considered when appraising others. In relation to states of character there is an irreconcilable difference between Kantian (deontic) and Aristotelian (aretaic) conceptions of the nature of full virtue (excellence of character), but at the same time it can be argued that in relation to practice their approaches complement each other. It is also argued that in relation to caring for the vulnerable, Aristotle’s conception of full virtue is more compelling than Kant’s. On the other hand, Kant’s notion of self - serving action is important in nursing and it therefore needs to be considered when reflecting on professional conduct. The conclusion reached is that Aristotelian and Kantian accounts of character appraisal should be used in a combined approach to moral appraisal. This approach draws on the accounts of both philosophers and offers valuable insight into moral character, professional conduct and, in a more formal setting, fitness to practise.

The Sacred and the Obscure: Greek in the Carolingian Reception of Martianus Capella

Carolingian scholars paid considerable attention to the Greek found in Martianus Capella’s De nuptiis Philologiae et Mercurii, a late antique Latin work full of obscurities in language and imagery. This article, focusing on glosses on De nuptiis from the oldest gloss tradition, demonstrates that a range of material was available to ninth-century scholars to elucidate Martianus’s Greek and that Greek seems, at times, to have served as a means to obscure. I argue that their interest in obscurity reflects a widespread epistemology and strategy of concealment, hence their intellectual investment in Martianus. For ninth-century readers, then, the Greek in the glossed Martianus manuscripts, however decorative it may have been, also operated at the core of medieval hermeneutics.

Quality factor of E-plane periodically loaded waveguide resonators and filter applications

The quality factor of microwave resonators miniaturised by virtue of periodic loading is assessed. Five X-band resonators in E-plane technology with different miniaturisation factors have been designed to resonate at approximately the same frequency. The loaded quality factor is extracted from the fractional bandwidth and subsequently employed to estimate the unloaded quality factor. The study reveals that the unloaded quality factor drops approximately linearly with the miniaturisation. Subsequently design guidelines for E-plane filters with periodically loaded resonators are provided by means of an example involving a fifth-order filter. Full-wave simulated and experimental results are presented to validate the study.

Confined Site Construction: A qualitative investigation of critical issues affecting management of Health and Safety

The construction industry is inherently risky, with a significant number of accidents and disasters occurring, particularly on confined construction sites. This research investigates and identifies the various issues affecting successful management of health and safety in confined construction sites. The rationale is that identifying the issues would assist the management of health and safety particularly in inner city centres which are mostly confined sites. Using empiricism epistemology, the methodology was based on qualitative research approach by means of multiple case studies in three different geographical locations of Ireland, UK and USA. Data on each case study were collected through individual interviews and focus group discussion with project participants. The findings suggest that three core issues are the underlying factors affecting management of health and safety on confined construction sites. It include, (i) lack of space, (ii) problem of co-ordination and management of site personnel, and (iii) overcrowding of workplace. The implication of this is that project teams and their organisations should see project processes from a holistic point of view, as a unified single system, where quick intervention in solving a particular issue should be the norm, so as not to adversely affect interrelated sequence of events in project operations. Proactive strategies should be devised to mitigate these issues and may include detail project programming, space management, effective constructability review and efficient co-ordination of personnel, plant and materials among others. The value of this research is to aid management and operation of brownfield sites by identifying issues impacting on health and safety management in project process.

Just how controversial is evidential holism?

This paper is an examination of evidential holism, a prominent position in epistemology and the philosophy of science which claims that experiments only ever confirm or refute entire theories. The position is historically associated with W.V. Quine, and it is at once both popular and notorious, as well as being largely under-described. But even though there’s no univocal statement of what holism is or what it does, philosophers have nevertheless made substantial assumptions about its content and its truth. Moreover they have drawn controversial and important conclusions from these assumptions. In this paper I distinguish three types of evidential holism and argue that the most oft-cited and controversial thesis is entirely unmotivated. The other two theses are much overlooked, but are well-motivated and free from controversial implications.

“ Humanitarian Competition: An Intellectual History in Perspective”.

Competition has become the mantra for survival in a globalised world where meaningful existence is fraught with demands, which go beyond the material to the immaterial ‘byte-size’. This has been exemplified by our obsession with illusions of immediate fame and fortune. This paper contextualises and extends the debate about the role of competition in general. Here the four major myths of competition are explored and deconstructed, from a Darwinian perspective to a more demonstrably engaged perspective on ‘capabilities’ (Sen, 1999). The second section deals particularly with the key debates, theories that influenced Tsunesaburo Makiguchi’s seminal ideas of ‘humanitarian competition’ in 1903. The final part of the paper seeks to decipher the relevance of the key ideas of ‘humanitarian competition’ as proposed by Dr Daisaku Ikeda in his 2009 peace proposal. Here the transition from competition to cooperation is explored by tying together the key principles of global coexistence enunciated by both Makiguchi and Ikeda in the context of expanding spiritual influence by the forces of culture, morality and virtue. To engage with humanitarian competition calls for a major shift from hard power to soft power, from subordination to one of engagement. In other words this concept advances the Buddhist principle of peaceful co-existence, or Panchsheel, as a norm for human behaviour of love, kindness, sacrifice and peace through cooperation, where equality and mutual benefit are critical. Humanitarian competition provides the essential framework to establish a new world order as highlighted by both Makiguchi and Ikeda.

Anisotropic Impedance Surfaces for Linear to Circular Polarization Conversion

Anisotropic impedance surfaces are employed as low-profile and broadband reflectors that convert orthogonal linear to right- and left-handed circular polarization respectively. By virtue of anisotropy, it is possible to independently control the reflection characteristics of two orthogonal linearly polarized incident plane waves and therefore achieve linear to circular polarization conversion. Equivalent circuits for anisotropic impedance surfaces with arbitrarily shaped elements are employed to demonstrate the operating principle and a design procedure is proposed. The proposed design procedure is demonstrated by means of an example involving a dipole array. A prototype is designed and its performance characteristics are evaluated. The 3-dB relative axial ratio bandwidth exceeds 60%, while low loss and angular stability are also reported. Numerical and experimental results on a fabricated prototype are presented to validate the synthesis and the performance. © 2006 IEEE.

MeV negative ion source from ultra-intense laser-matter interaction

Experimental demonstration of negative ion acceleration to MeV energies from sub-micron size droplets of water spray irradiated by ultra-intense laser pulses is presented. Thanks to the specific target configuration and laser parameters, more than 109 negative ions per steradian solid angle in 5% energy bandwidth are accelerated in a stable and reliable manner. To our knowledge, by virtue of the ultra-short duration of the emission, this is by far the brightest negative ion source reported. The data also indicate the existence of beams of neutrals with at least similar numbers and energies.