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.

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.

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.

Government decisions before and during the First World War and the living standards in Germany during a drastic natural experiment

The First World War hit Germany severely, particularly the agricultural sector, because the outbreak came unexpected and its duration exceeded all expectations. Many resources necessary for agricultural production were required by the war economy and led to shortages and shrinking supplies. Many agricultural laborers were drafted and the blockade imposed by the allies prevented Germany from a great deal of imports. As a consequence, the nutritional situation was devastating, particularly after 1916, and hit all groups of the German society. The period under observation provides one of most drastic natural experiments in the 20th century. This study uses anthropometric data from German soldiers who served in the Second World War to trace living standards between the 1900s and the 1920s. In contrast to other approaches, this paper is able to distinguish between social groups by occupation, religious denominatio\n, regional origin, and city size. The results suggest that although all social strata were hit by famine conditions, the height of farmers, urban citizens, Catholics, and especially individuals born in the highly integrated food-import regions along the coast and the banks of the Rhine declined most.

Clinical Trials Abroad: The Marketable Ethics, Weak Protections and Vulnerable Subjects of EU Law

This chapter explores how the EU is a largely overlooked exporter of normative power through its facilitation and use of clinical trials data produced abroad for the marketing of safe pharmaceuticals at home; a move that helps to foster the growing resort to pharmaceuticals as a fix for public health problems. This is made possible by the EU’s (de)selection of international ethical frameworks in preference to the international technical standards it co-authors with other global regulators. Clinical trials abroad underscore how ethics are contingent and revisable in light of market needs, producing weak protections for the vulnerable subjects of EU law. I argue that these components and effects of the regime are ultimately about that which undergirds, shapes and directs regulatory design. That is, I point to the use, infiltration, perpetuation and extension of market-oriented ideas, values and rationalities into formally non-market domains like biomedical knowledge production and public health. I explain how these are central to efforts at producing and legitimating the EU, its related imagined socio-political order based on a more innovative, profitable and competitive pharmaceutical sector in order to foster economic growth, jobs and prosperity, and with them the project of European integration. ‘Bioethics as risk’ is highlighted as a way to reshape and redirect the regulatory regime in ways that are more consistent with the spirit and letter of the ethical standards (and through them the human rights) the EU claims to uphold.

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