Agency or Dependency?: The Mixed Peppers Theatre Arts Training Project for young people with disabilities

This article provides a reflection on my past practice as Creative Director of The Mixed Peppers Theatre Arts Training Programme. Drawing upon discourses of Disability Studies it considers how this ostensibly emancipatory project that sought to provide access to theatre activity for young people with physical disabilities living in Northern Ireland was flawed, and was eventually disbanded, partly due to a failure on the part of its non-disabled leadership to address imbalances of power in its relationship with its young disabled constituency. The article is framed within a survey of recent debates that focus upon the historical lack of a sustained, indigenous, disability-led theatre activity in Northern Ireland and the recent efforts by non-disabled professional arts practitioners to establish such activity in the region. It offers, as an exemplar to current discussion, an analysis of how the choice and agency of the young members of The Mixed Peppers were compromised by the well-meaning but potentially oppressive practices of its leadership. It questions whether the project was unduly influenced by parental desire to see their disabled children `normalized' in a high-profile theatrical production. Finally, it considers how The Mixed Peppers' institutional situation, as a project controlled and administered by a disability charity, was implicated in the premature demise of the initiative.

Th1 not Th17 cells drive spontaneous MS-like disease despite a functional regulatory T cell response

Multiple sclerosis is considered a disease of complex autoimmune etiology, yet there remains a lack of consensus as to specific immune effector mechanisms. Recent analyses of experimental autoimmune encephalomyelitis, the common mouse model of multiple sclerosis, have investigated the relative contribution of Th1 and Th17 CD4 T cell subsets to initial autoimmune central nervous system (CNS) damage. However, inherent in these studies are biases influenced by the adjuvant and toxin needed to break self-tolerance. We investigated spontaneous CNS disease in a clinically relevant, humanized, T cell receptor transgenic mouse model. Mice develop spontaneous, ascending paralysis, allowing unbiased characterization of T cell immunity in an HLA-DR15-restricted T cell repertoire. Analysis of naturally progressing disease shows that IFN?(+) cells dominate disease initiation with IL-17(+) cells apparent in affected tissue only once disease is established. Tregs accumulate in the CNS but are ultimately ineffective at halting disease progression. However, ablation of Tregs causes profound acceleration of disease, with uncontrolled infiltration of lymphocytes into the CNS. This synchronous, severe disease allows characterization of the responses that are deregulated in exacerbated disease: the correlation is with increased CNS CD4 and CD8 IFN? responses. Recovery of the ablated Treg population halts ongoing disease progression and Tregs extracted from the central nervous system at peak disease are functionally competent to regulate myelin specific T cell responses. Thus, in a clinically relevant mouse model of MS, initial disease is IFN? driven and the enhanced central nervous system responses unleashed through Treg ablation comprise IFN? cytokine production by CD4 and CD8 cells, but not IL-17 responses.

Multiple Regulatory Pathways Associated with High-Level Ciprofloxacin and Multidrug Resistance in Salmonella enterica Serovar Enteritidis: Involvement of ramA and Other Global Regulators

Mechanisms of antibiotic resistance were examined in nalidixic acid-resistant Salmonella enterica serovar Enteritidis field isolates displaying decreased susceptibility to ciprofloxacin and in in vitro-derived ciprofloxacin-resistant mutants (104-cip and 5408-cip). All field isolates harbored a single gyrA mutation (D87Y). Deletion of acrB and complementation with wild-type gyrA increased quinolone susceptibility. Selection for ciprofloxacin resistance was associated with the development of an additional gyrA (S83F) mutation in 104-cip, novel gyrB (E466D) and parE (V461G) mutations in 5408-cip, overexpression of acrB and decreased susceptibility to nonquinolone antibiotics in both mutants, and decreased OmpF production and altered lipopoly- saccharide in 104-cip. Complementation of mutated gyrA and gyrB with wild-type alleles restored susceptibility to quinolones in 104-cip and significantly decreased the ciprofloxacin MIC in 5408-cip. Complementation of parE had no effect on quinolone MICs. Deletion of acrB restored susceptibility to ciprofloxacin and other antibiotics tested. Both soxS and marA were overexpressed in 104-cip, and ramA was overexpressed in 5408-cip. Inactivation of each of these global regulators lowered ciprofloxacin MICs, decreased expression of acrB, and restored susceptibility to other antibiotics. Mutations were found in soxR (R20H) and in soxS (E52K) in 104-cip and in ramR (G25A) in 5408-cip. In conclusion, both efflux activity and a single gyrA mutation contribute to nalidixic acid resistance and reduced ciprofloxacin sensitivity. Ciprofloxacin resistance and decreased susceptibility to multiple antibiotics can result from different genetic events leading to development of target gene mutations, increased efflux activity resulting from differential expression of global regulators associated with mutations in their regulatory genes, and possible altered membrane permeability.

Victims and Transitional Justice: Voice, Agency and Blame

This article explores the construction of victimhood in transitional societies. Drawn from fieldwork in a dozen jurisdictions as well as elements of criminological, feminist, sociological, philosophical and postcolonial literature, the article focuses in particular on how victimhood is interpreted and acted upon in transitional contexts. It explores the ways in which victims’ voice and agency are realised, impeded or in some cases co-opted in transitional justice. It also examines the role of blame in the construction of victimhood. In particular, it focuses upon the ways in which the importance of blame may render victimhood contingent upon ‘blamelessness’, encourage hierarchies between deserving and undeserving victims and require the reification of blameworthy perpetrators. The article concludes by suggesting that the increased voice and agency associated with the deployment of rights discourses by victims comes at a price – a willingness to acknowledge the rights and humanity of the ‘other’ and to be subject to the same respectful critical inquiry as other social and political actors in a post-conflict society.

Influence of the experimental design of gene expression studies on the inference of gene regulatory networks: environmental factors

The inference of gene regulatory networks gained within recent years a considerable interest in the biology and biomedical community. The purpose of this paper is to investigate the influence that environmental conditions can exhibit on the inference performance of network inference algorithms. Specifically, we study five network inference methods, Aracne, BC3NET, CLR, C3NET and MRNET, and compare the results for three different conditions: (I) observational gene expression data: normal environmental condition, (II) interventional gene expression data: growth in rich media, (III) interventional gene expression data: normal environmental condition interrupted by a positive spike-in stimulation. Overall, we find that different statistical inference methods lead to comparable, but condition-specific results. Further, our results suggest that non-steady-state data enhance the inferability of regulatory networks.

Attitudes and Ethics: Evaluating Knowledge and Regulatory Constructs in Planning Enforcement Practice

The departure point for the paper is the need to scrutinise previously unconsidered dimensions which are fundamental to understanding the dynamics of the planning enforcement system. Drawing upon emerging themes in regulation theory the paper fuses these with knowledge constructs. The rationale is that regulatory regimes must be informed by knowledge imparted from a range of sources and the resultant quality of decision making is inextricably linked to the robustness and completeness of the evidence base collated.
The theoretical analysis, coupled with proposed radical legislative changes, provides a lens for an empirical investigation which scrutinises tactics, strategies, operational mechanisms, attitudinal dimensions and ethics with a view to identifying key factors impacting upon enforcement efficacy. Prizes and pitfalls are identified in the course of the analysis and evaluation, with evidence-based remedies suggested where appropriate. The paper concludes by reflecting on the importance of theoretical synergy, epistemological advancement, taking cognisance of ethical and attitudinal challenges facing the planning profession; and, stresses the importance of identifying and bringing to book those who flagrantly breach the Code of Professional Conduct.

Inter-Agency Evidence Sharing in Competition Law Enforcement

While transnational antitrust enforcement is becoming only more common, the access to foreign-based evidence remains a considerable practical challenge. This article appraises considerations and concerns surrounding confidentiality, and looks into ways of their possible accommodation. It further identifies and critically evaluates the existing mechanisms allowing for inter-agency confidential information/ evidence sharing in competition law enforcement. The article outlines the shortcomings of the current framework and points to novel unilateral approaches. In the latter regard the focus is devoted to Australia, where the competition agency is empowered to share confidential information with foreign counterparts, also without any underlying bilateral agreement and on a non-reciprocal basis. This solution shows that a pragmatic and workable approach to inter-agency evidence sharing can be achieved.

In pursuit of regulatory compliance: a study of planning enforcement structures in Northern Ireland

As devolution expands across the UK, Northern Ireland (NI) is witnessing the development of new architecture to devolve planning powers. With serious criticism targeted at the legislative provisions for enforcement, this investigation endeavours to assess the robustness of the planning framework through a synergy of theory, law and practice. The paper demonstrates the value of theory in not only supplying a lens that allows both legislative frameworks and praxis to be deconstructed, but also in enabling the identification and scrutiny of underlying problems that pervade the system.

Discursive Control, Non-Domination and Hegelian Recognition Theory: Marrying Pettit’s Account(s) of Freedom with a Pippinian/Brandomian Reading of Hegelian Agency

The aim of this article is to combine Pettit’s account(s) of freedom, both his work on discursive control and on non-domination, with Pippin’s and Brandom’s reinterpretation of Hegelian rational agency and the role of recognition theory within it. The benefits of combining these two theories lie, as the article hopes to show, in three findings: first, re-examining Hegelian agency in the spirit of Brandom and Pippin in combination with Pettit’s views on freedom shows clearly why and in which way a Hegelian account of rational agency can ground an attractive socio-political account of freedom; second, the reconciling of discursive control and non-domination with Hegelian agency shows how the force and scope of recognition become finally tangible, without either falling into the trap of overburdening the concept, or merely reducing it to the idea of simple respect; third, the arguments from this article also highlight the importance of freedom as non-domination and how this notion is, indeed, as Pettit himself claims, an agency-freedom which aims at successfully securing the social, political, economic and even (some) psychological conditions for free and autonomous agency.

Interferon regulatory factor (IRF) 3 is critical for the development of experimental autoimmune encephalomyelitis.

BACKGROUND: Experimental autoimmune encephalomyelitis (EAE) is an animal model of autoimmune inflammatory demyelination that is mediated by Th1 and Th17 cells. The transcription factor interferon regulatory factor 3 (IRF3) is activated by pathogen recognition receptors and induces interferon-beta production.

METHODS: To determine the role of IRF3 in autoimmune inflammation, we immunised wild-type (WT) and irf3-/- mice to induce EAE. Splenocytes from WT and irf3-/- mice were also activated in vitro in Th17-polarising conditions.

RESULTS: Clinical signs of disease were significantly lower in mice lacking IRF3, with reduced Th1 and Th17 cells in the central nervous system. Peripheral T-cell responses were also diminished, including impaired proliferation and Th17 development in irf3-/- mice. Myelin-reactive CD4+ cells lacking IRF3 completely failed to transfer EAE in Th17-polarised models as did WT cells transferred into irf3-/- recipients. Furthermore, IRF3 deficiency in non-CD4+ cells conferred impairment of Th17 development in antigen-activated cultures.

CONCLUSION: These data show that IRF3 plays a crucial role in development of Th17 responses and EAE and warrants investigation in human multiple sclerosis.

Explaining the Stunted Rise of Macroprudential Regulatory Philosophies

In the aftermath of the financial crash of 2008, policy makers operating in international financial regulatory networks discovered macroprudential regulation (MPR), but macroprudential regulation has had a stunted or arrested development that can be explained with reference to five factors that are recounted in this article