A Many-Cornered Thing: The Role of Heritage in Indian Nation-Building

India is a large and extremely diverse multination state that is constantly faced with the challenge of maintaining its unity. In the past two decades the Hindu nationalist movement has become a significant factor in Indian politics, and has systematically leveraged heritage to create communal tensions. This has resulted in short-term political gain, but is also tied to longer-term goals of establishing a homogenously Hindu state in South Asia. This article argues that instead of being in decline, this movement is actually progressively expanding, and that the case of Ayodhya is only one part of a much larger programme in which heritage academics play a significant role, and that their collective actions will be pivotal to the future stability of the country

Modelling the implementation and acceptance of the Police National Database in UK police forces

The Police National Database (PND) was launched in June 2011 as a direct recommendation from the Bichard Inquiry. Its main purpose is to provide a national platform to share police information and for the first time, the PND will provide a single view of data held in police intelligence, custody, crime, child and domestic abuse systems across the UK. The PND will not replace local police systems, but it will allow all forces to see and share information - that until now has only been available within individual force boundaries

From CoA ester supply to a yeast communication toolkit in Saccharomyces cerevisiae

Saccharomyces cerevisiae is the most widely used eukaryotic chassis in synthetic biology, as hu-manity and yeast share a long and fruitful history. For synthetic biology applications, S. cerevisiae was extensively used for metabolic engineering as well as for the construction of artificial net-works. To contribute to the metabolic engineering achievements conducted in S. cerevisiae, we extended its metabolic capacities by providing non-native short-chain acyl-coenzyme A esters as metabolic precursors. In order to advance the construction of artificial networks to multicel-lular systems we provided a comprehensive yeast communication toolkit (YCTK), and demon-strated its usability for the rapid assembly of synthetic cell-cell communication systems. Engineered production of short-chain acyl-coenzyme A esters in Saccharomyces cerevisiae Globally, S. cerevisiae is one of the most commonly used chassis organisms in modern biotech-nology and constitutes a high economic value to the growing bioecomomy. With the objective to produce novel natural products in S. cerevisiae a bottleneck of the chassis was uncovered. Short-chain acyl-coenzyme A esters serve as intermediate compounds in fatty acid biosynthesis, and are building blocks for the production of polyketides, biopolymers, and other value-added chemicals. However, S. cerevisiae’s limited repertoire of short-chain acyl-CoAs effectively pre-vents its application as a production host for a plethora of natural products. To address and re-solve this limitation, we introduced metabolic pathways to five different acyl-CoA esters into S. cerevisiae. We engineered plasmid-based yeast strains that provide propionyl-CoA, methylmalonyl-CoA, n-butyryl-CoA, isovaleryl-CoA, and n-hexanoyl-CoA. For the production of propionyl-CoA and methylmalonyl-CoA, we reestablished a published feeding-dependent pro-duction route using the PrpE and Pcc enzymes to serve as benchmark for our feeding-independent production pathways that provided in our study comparable product concentra-tions. To ensure efficient extraction of the produced metabolites we established a yeast-specific metabolite extraction protocol to determine the intracellular acyl-CoA concentrations in the engineered strains. For the production of isovaleryl-CoA, we tested two different pathways but only obtained product formation from the alternative isovaleryl-CoA biosynthetic (AIB) pathway originating from Myxococcus xanthus and obtained 5.5±1.2 µM isovaleryl-CoA. To our knowledge, this is the first reported functional heterologous expression of this pathway in S. cerevisiae. For the production of n-butyryl-CoA and n-hexanoyl-CoA, we adapted the butanol production pathway for our purposes and measured approximately 6 µM intracellular concen-tration of butyryl-CoA and hexanoyl-CoA. For the feeding-dependent pathway towards propio-nyl-CoA we obtained intracellular concentrations of 5.3 ± 2.4 µM while the feeding independ-ent 3-hydroxypropionate (3HP) pathway produced 8.5 ± 3.7 µM. The extension of both propio-nyl-CoA pathways to produce methylmalonyl-CoA resulted only into production of 0.5 ± 0.1 µM and 0.3 ± 0.3 µM methylmalonyl-CoA. Not only but particularly for the production of methylmalonyl-CoA further optimization is required. To allow rapid pathway prototyping, op-timization and testing of alternative enzymes, we established a short-chain acyl-CoA Golden Gate collection. This collection enables together with the well-known Dueber yeast toolkit YTK collection the examination of different enzymes variants and to investigate optimized expres-sion of the corresponding genes. We conclude that the acyl-CoAs produced here, that are common building blocks of secondary metabolites, prepared the ground for prospective engineered production of a variety of natural products in S. cerevisiae. These acyl-CoA producing strains together with the short-chain acyl-CoA collection lay the foundation to further explore S. cerevisiae as a heterologous production host for high-value secondary metabolite production. Yeast communication toolkit The construction of multicellular networks was a proposed aim already early on in synthetic biology. Today, they still hold many promises like the division of labor or the performance of more complex tasks. Most of the systems so far were implemented in bacterial chassis and only a few examples exist for the eukaryotic chassis S. cerevisiae. Especially for gram-negative bacterial chassis, the quorum sensing system provides a large diversity of ready to use communication systems. Also, yeast species evolved a communication system using peptide-based pheromones to interact with the opposite mating type. Here, we employed the natural diversity of the pep-tide α-factor pheromones, the corresponding GPCR receptors, as well as of barrier proteases, that function similarly to quorum quenching enzymes. With the establishment of the Golden Gate yeast communication toolkit (YCTK) we provide a standardized collection of parts that al-low the rapid construction of multicellular networks in the model organism S. cerevisiae. The feasible designs are limitless as well as the number of envisioned applications. The YCTK collec-tion consists of responder (pheromone-responsive promoters), sender (mfα1 genes – α-factors), receiver (Ste2 receptors) and barrier (Bar1 proteases) parts. We characterized the dynamics of the pheromone-inducible promoters in the different mating-type strain backgrounds and de-termined the dose-response to the α-factor as well as their temporal response. The different promoters exhibited a range of different dynamics and properties that enable the implementa-tion of different prospective network design motives. The characterization results of the Ste2 receptors indicated that our collection is comprised of receptors with high α-factor promiscuity and of receptors with high substrate specificity for their cognate α-factor. Further we found that different Ste2 receptors exhibit different sensitivities towards the cognate as well as to non-cognate α-factors. The promiscuity of the Ste2 receptors did not correlate with the α-factor se-quences. Our likelihood analysis of the Ste2 receptors indicated that the ones closer related to S. cerevisiae tend to be stimulated by the α-factors of related species. Our likelihood analysis of the Ste2 receptors coincided with the phylogenetic relationships of the species. Interesting is also the finding that α-factors of species for which the receptor exhibited high α-factor promis-cuity stimulated only a few receptors. Even though only five of the selected barrier proteases were functionally expressed the characterization of the protease promiscuity was to our knowledge the most comprehensive study of its kind so far. Similar to the receptors we identi-fied promiscuous and substrate specific barrier proteases. The proposed model of a coevolution between the receptor and barrier proteases to recognize similar sequence motives of the α-factor was partly validated, however, the model is not universally applicable according to our results. The extended knowledge of the pheromone-inducible promoters, the crosstalk be-tween α-factors, receptors and barrier proteases, and an initial tunability test enabled proof of principle construction of multicellular systems using the YTCK collection. We engineered mul-ticellular logic gate-like population networks that allow the receiver cells to conditionally re-spond to the population composition. While the α-factor signaling motif is functional and was used to successfully establish OR and AND gate-like systems, signal disruption by a barrier pro-tease of a self-stimulating or a signaling motif requires further optimization. Overall, the reali-zation of multicellular networks using the YCTK was proven to be successful. To summarize, with the YCTK we provide a set of comprehensively characterized sender, re-ceiver, and barrier parts to facilitate the implementation of cell-cell and thus multicellular communication networks in S. cerevisiae

The biological diversity complex: a history of environmental government

The thesis understands biodiversity as a complex consisting of a form of environmentalism, a mode of governance for the global South, and a set of policy prescriptions all mobilized by the guiding idea of ‘genetic gold,’ the belief that biodiversity possesses significant latent economic value. The thesis primarily analyses the historical origins of biodiversity and the formation of a rationality of governing centred on genetic gold, deploying tools and methods from the work of Michel Foucault. It further applies these insights into the examination of two specific regulatory mechanisms developed within this project of environmental governance: the mechanism for securing access to genetic resources and the fair and equitable sharing of benefits arising from their utilisation, and local and indigenous community participation in biodiversity conservation and utilisation. The aim of this research is a dual critique. First, the unpacking of the complexity of the biodiversity concept and its integrative rendering of biodiversity loss as a governance problem constitutes a critique of environmental law’s enthusiastic acceptance and subsequent regulation of biodiversity as genetic gold. Secondly, the conception of a broader governance complex pervaded by non-legal forms of knowledge, expertise and practices challenges an international environmental law that continues to regard itself as the instrumental centre of environmental concern and discourse

Using the archive to formulate a chronology of rock art in the South-Western Cape, South Africa

Includes bibliographical references.With absolute dating still limited, relative chronologies remain useful in contextualising painting interpretations. This study vouches for the archival capacity of rock art and hence the archival perspective can be used to analyse paintings sites to build a framework their chronological and interpretative formulations. The sequence of paintings in the south-western Cape is customarily accepted to span hunter-gatherer phase from over 10,000 B.P.; then herding/pastoralism from ca. 2,000 B.P., and finally the historical-cum-colonial period several centuries ago. Several painting traditions with distinct depiction manners and content are conventionally linked to these periods. This study does not replace but evaluates this schema in order to refine the diverse hunter-gatherer, herder and colonial era painting contexts and history. Using superpositions as one of my analytical tools, the notion of datum aided the referencing and correlation of layered image categories into relative sequence. Visible differences occur between painting traditions, but indistinguishable within a single tradition. Some themes such as elephants, fat-tailed sheep, handprints and possibly geometric forms and dots were found to occur in various levels, even as parts of different traditions. Such divergences were analysed through the archival concept of respect des fonds to clarify graphic variations through the chronology. Probing other sources of information revealed that change from earlier to later imagery phases reflected shifts in the socio-economic, cultural and political circumstances of the region. These histories through time are indicated by the choice and sustenance of particular thematic subjects although their meaning and form changed. The ensuing sequence and interpretation of selected painted themes is a descriptive template reflecting the organic character in the creation, the order of painting phases and cultural continuities and disjunctions in the use of symbolism. This agenda in part reviews the changing social and historical landscape in order to understand variation of painting over time and to project possible interpretative transformations in the sequence. Painting sequences and cultural (dis)continuities are thus intricately entwined and can be disentangled through an analysis that uses the recursive relationship between the archaeological, ethnographic, and historical sources. This amalgamated approach has the ability to produce historicised past narratives and contextual image meanings. The chronology can be understood through first accepting the social, economic, political, and cultural subtleties of painting production

Using systems biology to investigate how age-related changes in TGFβ signalling alter pro-inflammatory stimuli

PhD ThesisOsteoarthritis (OA) is a degenerative condition caused by dysregulation of multiple molecular signalling pathways. This dysregulation results in damage to cartilage, a smooth and protective tissue that enables low friction articulation of synovial joints. Matrix metalloproteinases (MMPs), especially MMP13, are key enzymes in the cleavage of type II collagen which is a vital component for cartilage integrity. Various stimuli have been identified as inducers of MMP expression such as excessive load, injury and inflammation. Although previously considered a non-inflammatory arthritis, recent research has shown that inflammation may play an important role in OA development. A novel meta-analysis of microarray data from OA patients was used to create a cytoscape network representative of human OA. This enabled the identification of key processes in OA development, of which inflammation was prominent. Examining various different signalling pathways highlighted a role for transforming growth factor beta (TGFβ) in protecting against pro-inflammatory cytokine-mediated MMP expression. Indeed, TGFβ plays key roles in all facets of cartilage biology including development and maintenance of cartilage integrity. With age there is a change in the ratio of two TGFβ type I receptors (ALK1/ALK5), a shift that results in TGFβ losing its protective role in cartilage homeostasis. Instead, TGFβ promotes cartilage degradation and this correlates with the spontaneous development of OA in murine models. However, the mechanism by which TGFβ protects against pro-inflammatory responses and how this changes with age has not been extensively studied. Mathematical modelling has previously revealed how stochastic changes in TGFβ signalling during ageing led to the upregulation of MMPs. I have expanded the TGFβ section of this model to incorporate the pro-inflammatory stimulus interleukin-1 (IL-1) + oncostatin M (OSM) in order to investigate how TGFβ mediates MMP repression, specifically MMP-13. TGFβ signalling appears to interact with the activator protein 1 (AP-1) complex, which has an important role in MMP upregulation. However, the model indicates this interaction alone is insufficient to mediate the full effect of TGFβ, predicting it may also reduce MMP-13 mRNA stability. Furthermore, the model enabled me to predict how age alters these interactions; it suggested TGFβ would provide limited repression with a prolonged inflammatory response. Combining the modelled genes with the microarray network provided a global overview of how alterations in one pathway can affect others and lead to OA development. This study therefore demonstrates the power of combining computational biology with experimentally-derived data to provide insight into the importance of TGFβ signalling, and how age-related changes can lead to cartilage damage and OA development.Centre of Integrated Research into Musculoskeletal Ageing (CIMA), Arthritis research UK and the Medical Research Counci

In the Business of Trauma: An intersectional-materialist feminist analysis of ‘trauma informed’ women’s refuges and crisis accommodation services in Sydney and Vancouver

This study is informed by intersectional and materialist feminist theories and utilises a qualitative feminist methodology to explore the implementation of ‘trauma informed care' and the ‘trauma informed’ principle of ‘cultural safety’ in women’s refuges and crisis accommodation services located in Sydney and Vancouver. This theoretical framework guided a critical exploration of the trauma informed practice framework in the context of the dominant political economies operating in Sydney and Vancouver; settler colonialism and neoliberalism. Trauma informed care aims to increase staff members’ understanding of the high prevalence of ‘trauma’ experienced by women who are 'homeless' (experiencing housing injustice). Staff are also trained to understand the correlation between ‘trauma’ and alcohol and other drug use, mental health concerns, aggressive and self-harming behaviours. This model aims to improve outcomes for women who are experiencing housing injustice by reducing the potential for services to re-traumatise victims/survivors. This thesis was guided by the following research questions: 1) How do staff understand and experience ‘trauma informed care’ in women’s refuges and crisis accommodation services? 2) How do these understandings shape their work with women who are victims/survivors of gendered violence, systemic racism and housing injustice? 3) How do staff understand ‘cultural safety’ (a key principle of trauma informed care) in women’s refuges and crisis accommodation services and how do these understandings influence their work with women? 4) How does an espoused trauma informed care/cultural safety model shape women’s experiences in women’s refuges and crisis accommodation services? 5) What service gaps and contradictions are addressed or unaddressed by the implementation of trauma informed care? Research data were collected through one women’s refuge and two crisis accommodation services located in either Sydney or Vancouver and involved 32 in-depth interviews with key informants (N=2), staff (N=22) and women (N=8) who had worked within or accessed at least one of the participating services. Interview data were analysed using a thematic analysis in two stages. Key findings indicate that trauma informed care was broadly interpreted across participating services. Two findings chapters report on a continuum of trauma informed care and cultural safety ranging from politicised to behaviour management models of practice. A third findings chapter reports on women’s experiences of trauma informed services and their ongoing experiences of housing injustice. While all models of trauma informed care were constrained by settler-colonial and neoliberal processes, resistance from First Nations, feminist, and peer identifying staff suggests that trauma informed care is a site of social and political struggle with significant implications for women surviving gender-based violence, systemic racism and housing injustice

Mathematical Modelling in Engineering & Human Behaviour 2018

This book includes papers in cross-disciplinary applications of mathematical modelling: from medicine to linguistics, social problems, and more. Based on cutting-edge research, each chapter is focused on a different problem of modelling human behaviour or engineering problems at different levels. The reader would find this book to be a useful reference in identifying problems of interest in social, medicine and engineering sciences, and in developing mathematical models that could be used to successfully predict behaviours and obtain practical information for specialised practitioners. This book is a must-read for anyone interested in the new developments of applied mathematics in connection with epidemics, medical modelling, social issues, random differential equations and numerical methods