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.

Distillable entanglement and area laws in spin and harmonic-oscillator systems

We address the presence of nondistillable (bound) entanglement in natural many-body systems. In particular, we consider standard harmonic and spin-1/2 chains, at thermal equilibrium and characterized by few interaction parameters. The existence of bound entanglement is addressed by calculating explicitly the negativity of entanglement for different partitions. This allows us to individuate a range of temperatures for which no entanglement can be distilled by means of local operations, despite the system being globally entangled. We discuss how the appearance of bound entanglement can be linked to entanglement-area laws, typical of these systems. Various types of interactions are explored, showing that the presence of bound entanglement is an intrinsic feature of these systems. In the harmonic case, we analytically prove that thermal bound entanglement persists for systems composed by an arbitrary number of particles. Our results strongly suggest the existence of bound entangled states in the macroscopic limit also for spin-1/2 systems.

Area laws and entanglement distillability of thermal states

We study the entanglement distillability properties of thermal states of many-body systems Following the ideas presented in [6, A Ferraro et al., Phys. Rev Lett 100, 080502 (2008)], we first discuss the appearance of bound entanglement in those systems satisfying an entanglement area law Then, we extend these results to other topologies, not necessarily satisfying an entanglement area law We also study whether bound entanglement survives in the macroscopic limit of an infinite number of particles.

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.

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

Massive MIMO with Non-Ideal Arbitrary Arrays: Hardware Scaling Laws and Circuit-Aware Design

Massive multiple-input multiple-output (MIMO) systems are cellular networks where the base stations (BSs) are equipped with unconventionally many antennas, deployed on colocated or distributed arrays. Huge spatial degrees-of-freedom are achieved by coherent processing over these massive arrays, which provide strong signal gains, resilience to imperfect channel knowledge, and low interference. This comes at the price of more infrastructure; the hardware cost and circuit power consumption scale linearly/affinely with the number of BS antennas N. Hence, the key to cost-efficient deployment of large arrays is low-cost antenna branches with low circuit power, in contrast to today’s conventional expensive and power-hungry BS antenna branches. Such low-cost transceivers are prone to hardware imperfections, but it has been conjectured that the huge degrees-of-freedom would bring robustness to such imperfections. We prove this claim for a generalized uplink system with multiplicative phasedrifts, additive distortion noise, and noise amplification. Specifically, we derive closed-form expressions for the user rates and a scaling law that shows how fast the hardware imperfections can increase with N while maintaining high rates. The connection between this scaling law and the power consumption of different transceiver circuits is rigorously exemplified. This reveals that one can make the circuit power increase as p N, instead of linearly, by careful circuit-aware system design.

Regulating Services Trade Agreements - A Comparative Analysis of Regulatory Disciplines Included in EU and US Free Trade Agreements

Developed countries, led by the EU and the US, have consistently called for ‘deeper integration’ over the course of the past three decades i.e., the convergence of ‘behind-the-border’ or domestic polices and rules such as services, competition, public procurement, intellectual property (“IP”) and so forth. Following the collapse of the Doha Development Round, the EU and the US have pursued this push for deeper integration by entering into deep and comprehensive free trade agreements (“DCFTAs”) that are comprehensive insofar as they are not limited to tariffs but extend to regulatory trade barriers. More recently, the EU and the US launched negotiations on a Transatlantic Trade and Investment Partnership (“TTIP”) and a Trade in Services Agreement (“TISA”), which put tackling barriers resulting from divergences in domestic regulation in the area of services at the very top of the agenda. Should these agreements come to pass, they may well set the template for the rules of international trade and define the core features of domestic services market regulation. This article examines the regulatory disciplines in the area of services included in existing EU and US DCFTAs from a comparative perspective in order to delineate possible similarities and divergences and assess the extent to which these DCFTAs can shed some light into the possible outcome and limitations of future trade negotiations in services. It also discusses the potential impact of such negotiations on developing countries and, more generally, on the multilateral process.

Autonomous collective agreements as a regulatory device in European labour law:How to read Article 139 EC

This article discusses whether European social partners can derive the competence to autonomously devise European collective labour agreements from Article 139 EC (equals Article III-212 Constitution of Europe). Placing the question in the context of discussions of EU governance and private lawmaking in general, the author starts with a comparative overview of legal conceptions for collective labour agreements in Europe, focusing on three Member States' orders where their effects are not or only partly regulated by state legislation. Based on this comparison, she analyses Article 139(2) and offers a new interpretation of its provisions concerning autonomous implementation of European social partner agreements. She concludes that European social partners do have the competence to agree on a basic agreement stating the rules for European collective bargaining autonomously.

Enforcing Employment Discrimination Law - Potential Transplants from Italy to Britain and Vice Versa?

While substantive EU non-discrimination law has been harmonized in great detail, the enforcement regime for EU non-discrimination law consists merely of a few isolated elements. Thus, the pursuit of unity through harmonization in substantive EU law is accompanied by considerable regulatory autonomy for Member States in securing the efficiency of those laws, reflecting the diversity of national enforcement regimes, and resulting in twenty-seven different national models for enforcing discrimination law in labour markets. This article pursues two connected arguments through a comparison of rules for enforcing non-discrimination law in labour markets in Britain and Italy. First, it argues that enforcing non-discrimination law in labour markets is best achieved when responsive governance, repressive regulation and mainstreaming equality law are combined. Second, the article submits that diversity of national legal orders within the EU is not necessarily detrimental, as it offers opportunities for mutual learning across legal systems.The notion of mutual learning across systems is proposed in order to analyse the transnational migration of legal ideas within the EU. Such migration has been criticized in debates about the ‘transplantation’ of legal concepts or legal irritation through foreign legal ideas, in particular by comparative labour lawyers. However, EU harmonization policies in the field of non-discrimination law aim to impact on national labour laws. The article develops the notion of mutual learning across legal systems in order to establish conditions for transnational migration of legal ideas, and demonstrates the viability of these concepts by applying them to the field of non-discrimination law

Partitioning Heritability of Regulatory and Cell-Type-Specific Variants across 11 Common Diseases

Regulatory and coding variants are known to be enriched with associations identified by genome-wide association studies (GWASs) of complex disease, but their contributions to trait heritability are currently unknown. We applied variance-component methods to imputed genotype data for 11 common diseases to partition the heritability explained by genotyped SNPs () across functional categories (while accounting for shared variance due to linkage disequilibrium). Extensive simulations showed that in contrast to current estimates from GWAS summary statistics, the variance-component approach partitions heritability accurately under a wide range of complex-disease architectures. Across the 11 diseases DNaseI hypersensitivity sites (DHSs) from 217 cell types spanned 16% of imputed SNPs (and 24% of genotyped SNPs) but explained an average of 79% (SE = 8%) of  from imputed SNPs (5.1× enrichment; p = 3.7 × 10⁻¹⁷) and 38% (SE = 4%) of  from genotyped SNPs (1.6× enrichment, p = 1.0 × 10⁻⁴). Further enrichment was observed at enhancer DHSs and cell-type-specific DHSs. In contrast, coding variants, which span 1% of the genome, explained <10% of  despite having the highest enrichment. We replicated these findings but found no significant contribution from rare coding variants in independent schizophrenia cohorts genotyped on GWAS and exome chips. Our results highlight the value of analyzing components of heritability to unravel the functional architecture of common disease.

Pitfalls in Protection: How Theory Can Enrich Our Understanding of Regulatory Compliance Problems in Planning Practice

This paper responds to demands for greater academic investigation into environmental protection, specifically the practical and structural problems which underpin regulatory compliance in the planning system. It critiques traditional theories of regulation and answers calls for the development of a thematic lens to facilitate the scrutiny of not only operational practice, but also the broader institutional regime. An empirical investigation builds upon the construct of really responsive regulation to study planning control and it becomes apparent that not only are there significant procedural planning difficulties facing regulatory compliance, but also that a much wider raft of issues must be considered if the complex equation is to be solved. The findings demonstrate how theory can be applied to enrich our rudimentary understanding of deep-seated problems and foster insights into areas of structural importance which are relevant to both planning and the wider regulatory arena.