Synthesis and SAR of novel, non-MPEP chemotype mGluR5 NAMs identified by functional HTS

This Letter describes the discovery and SAR of three novel series of mGluR5 non-competitive antagonists/negative allosteric modulators (NAMs) not based on manipulation of an MPEP/MTEP chemotype identified by a functional HTS approach. This work demonstrates fundamentally new mGluR5 NAM chemotypes with submicromolar potencies, and further examples of a mode of pharmacology 'switch' to provide PAMs with a non-MPEP scaffold. (C) 2009 Elsevier Ltd. All rights reserved.

Applying an International Human Rights Framework to State Budget Allocations: Rights and Resources

Human rights based budget analysis projects have emerged at a time when the United Nations has asserted the indivisibility of all human rights and attention is increasingly focused on the role of non-judicial bodies in promoting and protecting human rights. This book seeks to develop the human rights framework for such budget analyses, by exploring the international law obligations of the International Covenant on Economic, Social and Cultural Rights (ICESCR) in relation to budgetary processes. The book outlines international experiences and comparative practice in relation to economic and social rights budget analysis and budgeting.

The book sets out an ICESCR-based methodology for analysing budget and resource allocations and focuses on the legal obligation imposed on state parties by article 2(1) of ICESCR to progressively realise economic and social rights to 'the maximum of available resources'. Taking Northern Ireland as a key case study, the book demonstrates and promotes the use of a ‘rights-based’ approach in budgetary decision-making.

The book will be relevant to a global audience currently considering how to engage in the budget process from a human rights perspective. It will be of interest to students and researchers of international human rights law and public law, as well as economic and social rights advocacy and lobbying groups.

Combining preference ordering and contingent valuation methods to assess non market benefit of alternative afforestation projects

The application of the contingent valuation method (CVM) in this paper incorporates a prior preference ordering of several alternative future afforestation programmes which could be implemented in Ireland over the next decade. This particular experimental design is thereby shown to reveal the potentially conflicting preferences of different groups within society. These findings are used to devise appropriate CVM scenarios to take account, not only of the efficiency gains of choosing a single policy alternative over others, but also the effects on the distribution of non market benefit between different groups within society, arising from choice between alternatives. (C) 1998 Elsevier Science Ltd. All rights reserved.

Unitarism and Employer Resistance to Trade Unionism

Active employer resistance to trade union recognition is often explained through the rubric of the unitary ideology. Yet, little attention has been devoted to an examination of unitarism as an explanatory construct for active employer hostility. This paper contributes to current knowledge and understanding on contemporary ideological opposition to unions, by placing unitarism under analytical scrutiny. Using empirical data from the Republic of Ireland, the paper applies a conceptual framework to a sample of non-union employers who actively resisted unionisation. The paper concludes by examining the ideological commitments uncovered and relevant implications.

Courts and Consociations: Human Rights versus Power-sharing

Consociations are power-sharing arrangements, increasingly used to manage ethno-nationalist, ethno-linguistic, and ethno-religious conflicts. Current examples include Belgium, Bosnia, Northern Ireland, Burundi, and Iraq. Despite their growing popularity, they have begun to be challenged before human rights courts as being incompatible with human rights norms, particularly equality and non-discrimination.

Courts and Consociations examines the use of power-sharing agreements, their legitimacy, and their compatibility with human rights law. Key questions include to what extent, if any, consociations conflict with the liberal individualist preferences of international human rights institutions, and to what extent consociational power-sharing may be justified to preserve peace and the integrity of political settlements.

In three critical cases, the European Court of Human Rights has considered equality challenges to important consociational practices, twice in Belgium and then in Sejdic and Finci v Bosnia regarding the constitution established for Bosnia Herzegovina under the Dayton Agreement. The Court's decision in Sejdic and Finci has significantly altered the approach it previously took to judicial review of consociational arrangements in Belgium. This book accounts for this change and assess its implications. The problematic aspects of the current state of law are demonstrated. Future negotiators in places riven by potential or actual bloody ethnic conflicts may now have less flexibility in reaching a workable settlement, which may unintentionally contribute to sustaining such conflicts and make it more likely that negotiators will consider excluding regional and international courts from reviewing these political settlements.

Courts and Consociations:How human rights courts may destabilize power-sharing settlements

We consider the use of consociational arrangements to manage ethno-nationalist, ethno-linguistic, and ethno-religious conflicts, and their compatibility with non-discrimination and equality norms. Key questions include to what extent, if any, consociations conflict with the dictates of global justice and the liberal individualist preferences of international human rights institutions, and to what extent consociational power-sharing may be justified to preserve peace and the integrity of political settlements. In three critical cases, the European Court of Human Rights has considered equality challenges to important consociational practices, twice in Belgium and, most recently, in Sejdic and Finci, concerning the constitutional arrangements established for Bosnia Herzegovina under the Dayton Agreement. The Court’s recent decision in Sejdic and Finci has significantly altered the approach it previously took to judicial review of consociational arrangements in the Belgian cases. We seek to account for this change and assess its implications. We identify problematic aspects of the judgment and conclude that, although the Court’s decision indicates one possible trajectory of human rights courts’ reactions to consociations, this would be an unfortunate development because it leaves future negotiators in places riven by potential or manifest bloody ethnic conflicts with considerably less flexibility in reaching a settlement. That in turn may unintentionally contribute to sustaining such conflicts and make it more likely that advisors to negotiators will advise them to exclude regional and international courts from having standing in the management of political settlements.

Hierarchical Bayesian models in ecology: Reconstructing species interaction networks from non-homogeneous species abundance data

The relationships among organisms and their surroundings can be of immense complexity. To describe and understand an ecosystem as a tangled bank, multiple ways of interaction and their effects have to be considered, such as predation, competition, mutualism and facilitation. Understanding the resulting interaction networks is a challenge in changing environments, e.g. to predict knock-on effects of invasive species and to understand how climate change impacts biodiversity. The elucidation of complex ecological systems with their interactions will benefit enormously from the development of new machine learning tools that aim to infer the structure of interaction networks from field data. In the present study, we propose a novel Bayesian regression and multiple changepoint model (BRAM) for reconstructing species interaction networks from observed species distributions. The model has been devised to allow robust inference in the presence of spatial autocorrelation and distributional heterogeneity. We have evaluated the model on simulated data that combines a trophic niche model with a stochastic population model on a 2-dimensional lattice, and we have compared the performance of our model with L1-penalized sparse regression (LASSO) and non-linear Bayesian networks with the BDe scoring scheme. In addition, we have applied our method to plant ground coverage data from the western shore of the Outer Hebrides with the objective to infer the ecological interactions. (C) 2012 Elsevier B.V. All rights reserved.

From non-porous crystalline to amorphous microporous metal(IV) bisphosphonates

Porous layered hybrid materials have been prepared by the reaction of organo-bisphosphonate ligands, 4-(4'-phosphonophenoxy)phenylphosphonic, 4,4'-biphenylenbisphosphonic and phenylphosphonic acids, with metal(IV) cations (Zr and Sn). Crystalline Zr(IV) and Sn(IV) layered bisphosphonates were also prepared, which were non-porous. The amorphous M(IV) bisphosphonates showed variable compositions and textural properties ranging from mainly mesoporous to highly microporous solids with BET surface areas varying from 300 to 480 m(2) g(-1), micropore volumes ranging 0.10-0.20 cm(3)/g, and narrow porous size distributions for some materials. N-2 isotherms suggest that Sn(IV) derivatives show a comparatively higher micropore contribution than the Zr(IV) analogous at least for the ether-bisphosphonate hybrids. Sn(IV) bisphosphonates exhibit high microporosities without the need of using harmful DMSO as solvent. If ether-bisphosphonic acid is partially replaced by less expensive phenylphosphonic ligand, porous products are also obtained. P-31 and F-17 MAS NMR and XPS data revealed the presence of hydrogen-phosphonate groups and small (F-, Cl- and OH-) anions, which act as spacer ligands within the inorganic layers, in these hybrid materials. The complexity of the inorganic layers is higher for the Sn(IV) bisphosphonates likely due to the larger amount of small bridging anions including fluorides. It is suggested that the presence of these small inorganic ligands may be a key factor influencing both, the interaction of the inorganic layer with the bisphosphonate groups, which bridge the inorganic layers, and the generation of internal voids within a given inorganic layer. Preliminary studies of gases adsorption (H-2 and NO) have been carried out for selected Sn(IV) bisphosphonates. The H-2 adsorption capacity at 77 K and 1 bar was low, 0.26 wt%, but the NO adsorption capacity at similar to 1 bar and 298 K was relatively high, 4.2 wt%. Moreover, the hysteresis in the NO isotherms is indicative of partial strong irreversible adsorption of NO. (C) 2008 Elsevier Inc. All rights reserved.

Arbuscular mycorrhizal fungi and collembola non-additively increase soil aggregation

Soil aggregation is a principal ecosystem process mediated by soil biota. Collembola and arbuscular mycorrhizal (AM) fungi are important groups in the soil, and can interact in various ways. Few studies have examined collembola effects on soil aggregation, while many have quantified AM effects. Here, we asked if collembola have any effect on soil aggregation, and if they alter AM fungi-mediated effects on soil aggregation.

We carried out a factorial greenhouse study, manipulating the presence of both collembola and AM fungi, using two different plant species, Sorghum vulgare and Daucus carota. We measured root length and biomass, AMF (and non-AMF) soil hyphal length, root colonization, and collembolan populations, and quantified water stable soil aggregates (WSA) in four size classes.

Soil exposed to growth of AMF hyphae and collembola individually had higher WSA than control treatments. Moreover, the interaction effects between AMF and collembola were significant, with nonadditive increases in the combined application compared to the single treatments.

Our findings show that collembola can play a crucial role in maintaining ecological sustainability through promoting soil aggregation, and point to the importance of considering organism interactions in understanding formation of soil structure. (C) 2011 Elsevier Ltd. All rights reserved.

GSP+ and Human Rights::Is the EU's Approach the Right One?

Among the purposes of the EU’s GSP+ programme is to link human rights to trade incentives, with the idea of using such incentives to promote developing countries’ adoption of the values found in core human rights treaties. With the re-renewal of the GSP (and GSP+) programmes to take effect in January 2014, it is fruitful to examine their efficacy and consistency with WTO law. In this article, I argue the GSP+ programme is not only ineffective in obtaining an improvement in human rights conditions for the vast majority of the world’s population, but it is also incompatible with WTO law. A stick-based regime where human rights abuses are linked to trade sanctions is a better way to proceed. After outlining the GSP+ system, and its linkage of human rights and trade, I analyse its efficacy and WTO consistency. Having shown that it is ineffective and contrary to WTO law, I argue that trade sanctions based on a PPM distinction and/or GATT XX(a) may be the appropriate means of linking trade and human rights. The article ends with some concluding remarks on the need for the careful design of such a system.

Infrared non-detection of fomalhaut b: Implications for the planet interpretation

The nearby A4-type star Fomalhaut hosts a debris belt in the form of an eccentric ring, which is thought to be caused by dynamical influence from a giant planet companion. In 2008, a detection of a point source inside the inner edge of the ring was reported and was interpreted as a direct image of the planet, named Fomalhaut b. The detection was made at 600-800nm, but no corresponding signatures were found in the near-infrared range, where the bulk emission of such a planet should be expected. Here, we present deep observations of Fomalhaut with Spitzer/IRAC at 4.5 µm, using a novel point-spread function subtraction technique based on angular differential imaging and Locally Optimized Combination of Images, in order to substantially improve the Spitzer contrast at small separations. The results provide more than an order ofmagnitude improvement in the upper flux limit of Fomalhaut b and exclude the possibility that any flux from a giant planet surface contributes to the observed flux at visible wavelengths. This renders any direct connection between the observed light source and the dynamically inferred giant planet highly unlikely. We discuss several possible interpretations of the total body of observations of the Fomalhaut system and find that the interpretation that best matches the available data for the observed source is scattered light from a transient or semi-transient dust cloud. © 2012 The American Astronomical Society. All rights reserved.

Non-apologies and prolonged silences in post-conflict settings: The case of post-colonial Cyprus

Despite the growing use of apologies in post-conflict settings, cases of non-apology remain unaddressed and continue to puzzle scholars. This article focuses on the absence of apology by non-state and anti-state actors by examining the case of the Cypriot armed group EOKA, which has refused to offer an apology to the civilian victims of its ‘anti-colonial’ struggle (1955–1959). Using field data and parliamentary debates, and drawing on comparisons, this article analyses the factors that contributed to a lack of apology. It is argued that the inherited timelessness of Greek nationalism, and the impression of a perpetual need for defence, set up textbook conditions for the development of a hegemonic discourse and prevented an apology for human rights violations.

Bills of Rights:A Comparative Perspective

Bills of rights are currently a much debated topic in various jurisdictions throughout the world. Almost all democratic nations, with the exception of Australia, now have a bill of rights. These take a variety of forms, ranging from constitutionally entrenched bills of rights, such as those of the United States and South Africa, to non-binding statements of rights. Falling between these approaches are non-entrenched, statutory bills of rights. As regards the latter, a model which has become increasingly popular is that of bills of rights based on interpretative obligations, whereby duties are placed upon courts to interpret national legislation in accordance with human rights standards. The aim of this book is to provide a comparative analysis of the bills of rights of a number of jurisdictions which have chosen to adopt such an approach. The jurisdictions considered are New Zealand, the United Kingdom, the Australian Capital Territory and the Australian state of Victoria.

There have been very few books published to date which contain a detailed comparative analysis of the bills of rights which this book addresses. The book adopts a unique thematic approach, whereby six aspects of the bills of rights in question have been selected for comparative analysis and a chapter is allocated to each aspect. This approach serves to facilitate the comparative discussion and emphasise the centrality of the comparative methodology.

Model checking support for conflict resolution in multiple non-functional concern management

When implementing autonomic management of multiple non-functional concerns a trade-off must be found between the ability to develop independently management of the individual concerns (following the separation of concerns principle) and the detection and resolution of conflicts that may arise when combining the independently developed management code. Here we discuss strategies to establish this trade-off and introduce a model checking based methodology aimed at simplifying the discovery and handling of conflicts arising from deployment-within the same parallel application-of independently developed management policies. Preliminary results are shown demonstrating the feasibility of the approach.