A critical role for the Sp1-binding sites in the transforming growth factor-β-mediated inhibition of lipoprotein lipase gene expression in macrophages

Increasing evidence suggests that the cytokine transforming growth factor-β (TGF-β) inhibits the development of atherosclerosis. The lipoprotein lipase (LPL) enzyme expressed by macrophages has been implicated in the pathogenesis of atherosclerosis by stimulating the uptake of lipoprotein particles. Unfortunately, the action of TGF-β on the expression of LPL in macrophages remains largely unclear. We show that TGF-β inhibits LPL gene expression at the transcriptional level. Transient transfection assays reveal that the −31/+187 sequence contains the minimal TGF-β-responsive elements. Electrophoretic mobility shift assays show that Sp1 and Sp3 interact with two regions in the −31/+187 sequence. Mutations of these Sp1/Sp3 sites abolish the TGF-β-mediated suppression whereas multimers of the sequence impart the response to a heterologous promoter. TGF-β has no effect on the binding or steady-state polypeptide levels of Sp1 and Sp3. These results, therefore, suggest a novel mechanism for the TGF-β-mediated repression of LPL gene transcription that involves regulation of the action of Sp1 and Sp3

Faking like a woman? Towards an interpretative theorization of sexual pleasure.

This article explores the possibility of developing a feminist approach to gendered and sexual embodiment which is rooted in the pragmatist/interactionist tradition derived from G.H. Mead, but which in turn develops this perspective by inflecting it through more recent feminist thinking. In so doing we seek to rebalance some of the rather abstract work on gender and embodiment by focusing on an instance of 'heterosexual' everyday/night life - the production of the female orgasm. Through engaging with feminist and interactionist work, we develop an approach to embodied sexual pleasure that emphasizes the sociality of sexual practices and of reflexive sexual selves. We argue that sexual practices and experiences must be understood in social context, taking account of the situatedness of sex as well as wider socio-cultural processes the production of sexual desire and sexual pleasure (or their non-production) always entails interpretive, interactional processes

Narratives of self and identity in women's prisons: stigma and the struggle for self-definition in penal regimes

A concern with questions of selfhood and identity has been central to penal practices in women's prisons, and to the sociology of women's imprisonment. Studies of women's prisons have remained preoccupied with women prisoners’ social identities, and their apparent tendency to adapt to imprisonment through relationships. This article explores the narratives of women in two English prisons to demonstrate the importance of the self as a site of meaning for prisoners and the central place of identity in micro-level power negotiations in prisons

The Century Survey Galactic Halo Project III: A Complete 4300 deg^2 Survey of Blue Horizontal Branch Stars in the Metal-Weak Thick Disk and Inner Halo

We present a complete spectroscopic survey of 2414 2MASS-selected blue horizontal branch (BHB) candidates selected over 4300 deg^2 of the sky. We identify 655 BHB stars in this non-kinematically selected sample. We calculate the luminosity function of field BHB stars and find evidence for very few hot BHB stars in the field. The BHB stars located at a distance from the Galactic plane |Z|<4 kpc trace what is clearly a metal-weak thick disk population, with a mean metallicity of [Fe/H]= -1.7, a rotation velocity gradient of dv_{rot}/d|Z|= -28+-3.4 km/s in the region |Z|<6 kpc, and a density scale height of h_Z= 1.26+-0.1 kpc. The BHB stars located at 5<|Z|<9 kpc are a predominantly inner-halo population, with a mean metallicity of [Fe/H]= -2.0 and a mean Galactic rotation of -4+-31 km/s. We infer the density of halo and thick disk BHB stars is 104+-37 kpc^-3 near the Sun, and the relative normalization of halo to thick-disk BHB stars is 4+-1% near the Sun.Comment: 12 pages in emulateapj format, accepted for publication in February A

Complex, but not quite complex enough : The turn to the complexity sciences in evaluation scholarship

This document is the Accepted Manuscript version of the following article: Chris Mowles, ‘Complex, but not quite complex enough: The turn to the complexity sciences in evaluation scholarship’. The final, definitive version of this paper has been published in Evaluation, Vol. 20 (2): 160-175, April 2014, doi: https://doi.org/10.1177/1356389014527885 , published by SAGE Publishing. All rights reserved.This article offers a critical review of the way in which some scholars have taken up the complexity sciences in evaluation scholarship. I argue that there is a tendency either to over-claim or under-claim their importance because scholars are not always careful about which of the manifestations of the complexity sciences they are appealing to, nor do they demonstrate how they understand them in social terms. The effect is to render ‘complexity’ just another volitional tool in the evaluator’s toolbox subsumed under the dominant understanding of evaluation, as a logical, rational activity based on systems thinking and design. As an alternative I argue for a radical interpretation of the complexity sciences, which understands human interaction as always complex and emergent. The interweaving of intentions in human activity will always bring about outcomes that no one has intended including in the activity of evaluation itself.Peer reviewe

Researching underwater: a submerged study

This chapter explores the unknown territory of a lost project: an ethnography of a public swimming pool. The discussion is contextualised within my broader sociological theory of ‘nothing’, as a category of unmarked, negative social phenomena, including no-things, no-bodies, no-wheres, non-events and non-identities. These meaningful symbolic objects are constituted through social interaction, which can take two forms: acts of commission and acts of omission. I tell the story of how this project did not happen, through the things I did not do or that did not materialise, and how I consequently did not become a certain type of researcher. I identify three types of negative phenomena that I did not observe and document – invisible figures, silent voices and empty vessels – and, consequently, the knowledge I did not acquire. However, nothing is also productive, generating new symbolic objects as substitutes, alternatives and replacements: the somethings, somebodies and somewheres that are done or made instead. Thus finally, I reflect on how not doing this project led me to pursue others, cultivating a different research identity that would not otherwise have existed

From Producer Innovation to User and Open Collaborative Innovation

In this paper we assess the economic viability of innovation by producers relative to two increasingly important alternative models: innovations by single user individuals or firms, and open collaborative innovation. We analyze the design costs and architectures and communication costs associated with each model. We conclude that both innovation by individual users and open collaborative innovation increasingly compete with and may displace producer innovation in many parts of the economy. We explain why this represents a paradigm shift with respect to innovation research, policymaking, and practice. We discuss important implications and offer suggestions for further research

Uninhibited Institutionalisms

Institutional theory (IT) is a very influential set of approaches in organization studies. There is increasing critique that the set is becoming uninhibited: too broad, dispersed, and confusing. Efforts to rejuvinate the field(s) have led to all-embracing definitions and efforts to account for too much, which makes it difficult to identify what is distinct about the assembly of research. This article discusses critically the state of IT and suggests some reconceptualizations of institution and institutional theory and points at some alternative lines of development

Investigating the global genomic diversity of Escherichia coli using a multi-genome DNA microarray platform with novel gene prediction strategies

<p>Abstract</p> <p>Background</p> <p>The gene content of a diverse group of 183 unique <it>Escherichia coli </it>and <it>Shigella </it>isolates was determined using the Affymetrix GeneChip^®<it>E. coli </it>Genome 2.0 Array, originally designed for transcriptome analysis, as a genotyping tool. The probe set design utilized by this array provided the opportunity to determine the gene content of each strain very accurately and reliably. This array constitutes 10,112 independent genes representing four individual <it>E. coli </it>genomes, therefore providing the ability to survey genes of several different pathogen types. The entire ECOR collection, 80 EHEC-like isolates, and a diverse set of isolates from our FDA strain repository were included in our analysis.</p> <p>Results</p> <p>From this study we were able to define sets of genes that correspond to, and therefore define, the EHEC pathogen type. Furthermore, our sampling of 63 unique strains of O157:H7 showed the ability of this array to discriminate between closely related strains. We found that individual strains of O157:H7 differed, on average, by 197 probe sets. Finally, we describe an analysis method that utilizes the power of the probe sets to determine accurately the presence/absence of each gene represented on this array.</p> <p>Conclusions</p> <p>These elements provide insights into understanding the microbial diversity that exists within extant <it>E. coli </it>populations. Moreover, these data demonstrate that this novel microarray-based analysis is a powerful tool in the field of molecular epidemiology and the newly emerging field of microbial forensics.</p