79 research outputs found
High-level expression and reconstitution of active Cfr, a radical-SAM rRNA methyltransferase that confers resistance to ribosome-acting antibiotics
No full textCfr is a radical-SAM (S-adenosyl-l-methionine) enzyme that methylates the 8 position of 23S rRNA residue A2503 to confer resistance to multiple antibiotic classes acting upon the large subunit of the bacterial ribosome. Radical-SAM enzymes use an Fe–S cluster to generate the 5?-deoxyadenosyl (DOA) radical from SAM, enabling them to modify intrinsically unreactive centres such as adenosine C8. However, despite its mechanistic interest and clinical relevance, until recently Cfr remained little characterised. Accordingly we have used co-expression with the Azotobacter vinelandii isc operon, encoding genes responsible for Fe–S cluster biosynthesis, to express hexahistidine-tagged Cfr in Escherichia coli BL21Star, and purified the recombinant protein in a yield more than 20 times greater than has been previously reported. As aerobically purified, Cfr contains secondary structure, is monomeric in solution and has an absorbance spectrum suggestive of a 2Fe–2S cluster. After anaerobic purification a 4Fe–4S cluster is indicated, while on reconstitution with excess iron and sulphide a further increase in metal content suggests that an additional, most likely 4Fe–4S, cluster is formed. Acquisition of additional secondary structure under these conditions indicates that Fe–S clusters are of structural, as well as functional, importance to Cfr. In the presence of sodium dithionite reconstituted Cfr is both reducible and able to cleave SAM to 5?-deoxyadeonsine (DOA), demonstrating that the purified reconstituted enzyme has radical-SAM activity. Co-expression with isc proteins thus enables recombinant active Cfr to be obtained in yields that facilitate its future spectroscopic and structural characterisation.<br/
Pedogenesis on the Sefton Coastal Dunes, NW England
No full textA thesis submitted in partial fulfilment of the requirements of the University of Wolverhampton for the degree of Doctor of PhilosophyThis work examines the use of pedo-properties to identify dune soil system responses to environmental change on the Sefton coast, based on the development of conceptual pedogenic models. Previous environmental change and shoreline dynamics are determined through O.S. maps and aerial photographs, while present day processes are investigated through a dune-toe photographic survey and seasonal monitoring by fixed point photography. Topsoil (0-5 cm) physico-chemical characteristics are presented in a series of baseline GIS maps, displaying spatial pedo-property variation across the dune landscape. Combined with vegetation data, topsoil analysis identifies 10 distinct pedo-environments. Physico-chemical characteristics of associated National Soil Resources Institute (NSRI) soil profile classifications and an exposed stratigraphic section are presented graphically in a proposed sequence of development. Topsoil and soil profile samples are analysed for soil pH, soil organic matter (SOM) content, particle size, geochemical composition and mineral magnetism. Significant differences (p <0.05) are apparent for the suite of topsoil characteristics collated, indicating discrete dune environments are influenced by specific soil properties. Distinct down-profile variations in soil characteristics are also apparent between dune environments, highlighting pedological dynamism. Multivariate Factor analysis groups bare sand and mobile dune communities into ‘frontal dunes’ and fixed dune community, pasture, scrub, deciduous woodland and coniferous plantations into ‘hind dunes’, separating these topsoil environments from heath and slack communities. Factor analysis also identifies linkages between pedo-characteristics within soil profile horizons, suggesting pedogenesis on the Sefton dunes initiates as raw sand, progressing to sand-pararendzinas through leaching of nutrients. Desalinization and decalcification processes lead to brown earth development, followed by increased acidicification, subsequently, resulting in micro-podzol formation. Groundwater gley soils are associated with dune slacks, where drainage is inhibited and anaerobic conditions prevail. Analysis of buried soils suggests such pedo-environment formations are cyclic, responding to phases of shoreline regression/transgression, dune activity and stabilization. Conceptual models are designed to graphically demonstrate pedogenesis under both erosion and deposition regimes on the Sefton coast. Regression equations and correlation coefficients between pedo-properties and distance from mean high water are used as a proxy for soil age, which represent lateral soil maturity from the unstable frontal dunes to the stable hind dunes inland. The models simulate formation and process of the full array of soil properties, accounting for geomorphological impacts and anthropogenic influences. This has great implications for dune managers by raising awareness of pedogenesis as an integral part of nature and associated habitats, which could be incorporated in future shoreline management plans (SMPs)
Designing a VR Lobby for Remote Opera Social Experiences
No full textSeveral social VR platforms support virtual entertainment events, however their value for post-show activities remains unclear. Through a user-centered approach, we design a social VR lobby experience to enrich four motivations of theatre-goers: social, intellectual, emotional, and spiritual engagement. We ran a context-mapping focus group session with professionals (N=6) to conceptualize the social VR space for digital opera experiences. Based on our findings, we propose a social VR lobby consisting of four rooms: 1) a Bar for social engagement, 2) an Info Booth for intellectual engagement, 3) a Photo Zone for emotional engagement, and 4) an Interactive Stage for spiritual engagement. Based on this work, we plan to experimentally evaluate audience experiences in each room in order to create a social VR lobby template for theater experiences. Multimedia Computin
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
No full textMultiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis
Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis
No full textUsing the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10−4). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10−8), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals
Changing British attitudes to China and the Chinese, 1928-1931
No full textSIGLEAvailable from British Library Document Supply Centre-DSC:DX195604 / BLDSC - British Library Document Supply CentreGBUnited Kingdo
Author Correction: A detailed map of Higgs boson interactions by the ATLAS experiment ten years after the discovery
No full textIn the version of this article initially published, the ATLAS Collaboration
author names, affiliations and acknowledgements were omitted and
have now been included in the HTML and PDF versions of the article
Empowering Ni-Vanuatu women: Amplifying Wantok authority and achieving fair market access
No full textThe Republic of Vanuatu (2004) report on Vanuatu’s implementation of the United Nations Convention on the Elimination of All Forms of Discrimination against Women (CEDAW) notes that many urban disenfranchised Ni-Vanuatu women live in poverty and have little access to paid employment. The women who do gain paid employment in formal jobs rarely gain access to positions of authority. The United Nations (UN) offered two strategies to improve the position of Ni-Vanuatu women in Vanuatu. The first is informed by CEDAW in Article Eleven on Employment. The “Equity Desk of the Vanuatu Department of Strategic Management” and the “Vanuatu Department of Women’s Affairs Gender Planner” (The Republic of Vanuatu, 2004, pp. 12-13) have been charged with the responsibility of implementing Article Eleven and developing Equal Employment Opportunities (EEO) programmes for the public sector. This strategy aims to increase women’s access to paid employment in the formal employment sector and encourage women to achieve positions of authority. The second strategy offered by the UN is the establishment of microfinance projects aimed at providing disenfranchised urban women unable to find employment with a means to own and run microfinance businesses to earn a living. Both these strategies have the overarching aim of improving the well-being of Ni-Vanuatu women.
This study has investigated the extent to which access to formal sector jobs and the implementation of microfinance businesses in the informal sector addresses the well-being of Ni-Vanuatu women. These programmes are being implemented within a complex historical, socio-political cultural and economic environment (Van Trease, 1995). This complexity includes the continuance of Wantok systems of governance in the form of matrilineality (predominant in Vanuatu) and patrilineality (adopted from Christian influences in 1800s and colonial legacy in 1906) (Van Trease, 1987; Facey, 1981; Allen, 1981 & Macdonald-Milne & Thomas, 1981). Matrilineal cultural values bequeath patrimony and legacy of lineage and land inheritance from mothers to daughters. Matrilineal women share power with men in community affairs (Maltali, Sandy & Tamashiro, 2009). In patrilineal communities, patrimony and legacy of lineage and land inheritance is passed from fathers to sons (Van Trease, 1987). Patrilineal mothers and daughters have no lineage, land inheritance, or power-sharing rights (Stege, Maetala, Naupa & Simo 2008). Both Wantok systems are based on communal values practised primarily in the rural sector. Urban centres are organised around a modern-cash and market-economy and a governance framework based on the British Westminster model and the French Head of State model (ILO, 2006). This European generated governance system is underpinned by values informed by liberal competitive individualism and an assumed commitment to meritocracy. It is, however, a system of governance steeped in patriarchal nuances as a direct legacy of the colonial regime now adapted and administered by the Vanuatu’s ruling elite, referred as Vanuatu’s urban patriarchy throughout this thesis.
The theoretical frameworks used in this research draw on both liberal feminist studies and on an adaptation of subaltern scholarship (Thomas & Humphries, 2010 & 2011). The focus is on the legacy of imperialism and colonisation, the politics of power and hegemony, and the expressions of equal rights, emancipation and empowerment as these pertain to the well-being of women in Vanuatu.
Three sets of qualitative empirical observations were collected: i) a focus group discussion with 20 employer and employee representatives; ii) 36 conversations with women employed in the formal employment sector who held positions of authority within their respective organisations; and iii) 39 conversations with women who owned a microfinance business. My field notes were analysed thematically using a point and counterpoint framework crafted from my interest in the work of Huxley (cf Baker & James, 2000a & 2000b & Dawson, 2009). The point is informed by a liberal feminist lens (Gamble, 1999 & Heywood, 2000). A counterpoint to this liberal feminist interpretation is generated from a post-colonial feminist perspective through an adaptation of subaltern studies (Thomas & Humphries 2010 & 2011; Gamble, 1999 & Spivak, 1988). I draw on my Matrilineal Wantok Feminist Voice (MWFV) to form a standpoint in the discussion and to frame insights drawn from the ideas associated with the solidarity economy (Allard, Davidson & Matthaei, 2009; Harvey, 2006 & Harding, 2004).
Point/counterpoint/standpoint for the research as a whole
Point: Liberal feminist strategies for the emancipation of women (and the intended improvement and well-being of their families associated with this perspective) encourage women to pursue better living standards, achieve empowerment in the home, and seek formal jobs or other market-based income opportunities. If in formal jobs, women are encouraged to seek positions of authority. For these women, the major transition in orientation is the move from Wantok-related patterns of responsibilities and opportunities to those made available in the formal Western-generated economy. These Western ways, with emphasis on individualized opportunity, appear to offer financial gain and familial influences, particularly to women born into patrilineal lineage descent groups.
Counterpoint: Viewed through the adaptation of subaltern perspectives that I have applied to the liberal feminist remedies for the enhancement of well-being for the women of Vanuatu, it appears that the women of Vanuatu are involved in multiple and simultaneous complex master/slave relationships (Kohn, 2005 & Honderich, 1995). These relationships are exemplified in salaried/professional occupations held by women, between the women and their employers and work-place cultures, between women and rural and urban patriarchal hegemonies, and between women and the cash and market economy. While EEO activities can be seen to make a difference in the lives of some women, taken together, these interventions are reducing the overall well-being for Ni-Vanuatu women more generally. For the Vanwods microfinance women entrepreneurs, master/slave relationships could be discerned between the Vanwods MFI’s social control of the Mamas, the Vanuatu Government’s imposition of high business licence fees to the Mamas, the Mamas and their greater dependence on the cash and market economy, and the Mamas and their relationship with rural and urban patriarchal hegemonies (Thomas & Humphries, 2010 & 2011). These forms of systemic subservience interpreted from the women’s narratives provide a caution against the uncritical adoption of Western liberal feminist ideals (DeVault, 1990). It is matrilineal women; however, who appear to suffer the most from their move into the urban centres as there they must contend with an urban patriarchal hegemony, an impediment which they had not encountered in their former rural communities governed in accordance with matrilineal Wantok values.
Standpoint: The research findings suggest that all women in this study worked long hours, experiencing discrimination and oppression, received low pay, and experienced increased financial obligations as a result of their engagement in formal and informal jobs. As well as being increasingly dependent on inadequate and unsustainable livelihoods in the urban areas, family and Wantok social relations were challenged and diminished as a consequence of their necessary commitment to their jobs and the demands of urban living. Access to traditional forms of authority and sustenance was undermined.
I conclude that, overall, the implementation of CEDAW-EEO programmes along with the establishment of microfinance projects devised for the emancipation of the disenfranchised women of Vanuatu, while apparently proving beneficial from a liberal feminist interpretation in granting urban women with access to incomes, property and power-sharing, may provide an element of liberation for women of patrilineal descent groups but add new dimensions of patriarchal inhibitors for women of matrilineal descent groups who take up employment under the Westminster rules of governance. The remedies taken as a whole, while promising improved well-being through market-based income generation, remove women from the Wantok kinship social support networks embedded in their indigenous Wantok governance frameworks causing complex problems and hardships for them. Drawing on my Matrilineal Wantok Feminist standpoint position, I suggest that the Solidarity Economy, which combines aspects of market access while still engaging in the traditional systems of social organization, offers an alternative organisational and economic framework for developing and enhancing community well-being in both the rural and urban areas of Vanuatu
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