Neural correlates of task switching in paternal 15q11-q13 deletion Prader-Willi syndrome

We report a first study of brain activity linked to task switching in individuals with Prader-Willi syndrome (PWS) PWS individuals show a specific cognitive deficit in task switching which may be associated with the display of temper outbursts and repetitive questioning The performance of participants with PWS and typically developing controls was matched in a cued task switching procedure and brain activity was contrasted on switching and non switching blocks using SARI Individuals with PWS did not show the typical frontal-parietal pattern of neural activity associated with switching blocks, with significantly reduced activation in regions of the posterior parietal and ventromedial prefrontal cortices We suggest that this is linked to a difficulty in PWS in setting appropriate attentional weights to enable task set reconfiguration In addition to this, PWS individuals did not show the typical pattern of deactivation, with significantly less deactivation in an anterior region of the ventromedial prefrontal cortex One plausible explanation for this is that individuals with PWS show dysfunction within the default mode network which has been linked to attentional control The data point to functional changes in the neural circuitry supporting task switching in PWS even when behavioural performance is matched to controls and thus highlight neural mechanisms that may be involved in a specific pathway between genes cognition and behaviour (C) 2010 Elsevier B V All rights reserved

Thermal bound entanglement in macroscopic systems and area law

Does bound entanglement naturally appear in quantum many-body systems? We address this question by showing the existence of bound-entangled thermal states for harmonic oscillator systems consisting of an arbitrary number of particles. By explicit calculations of the negativity for different partitions, we find a range of temperatures for which no entanglement can be distilled by means of local operations, despite the system being globally entangled. We offer an interpretation of this result in terms of entanglement-area laws, typical of these systems. Finally, we discuss generalizations of this result to other systems, including spin chains.

Stability of 71 degrees stripe domains in epitaxial BiFeO3 films upon repeated electrical switching

The 71 degrees stripe domain patterns of epitaxial BiFeO3 thin films are frequently being explored to achieve new functional properties, dissimilar from the BiFeO3 bulk properties. We show that in-plane switching and out-of-plane switching of these domains behave very differently. In the in-plane configuration the domains are very stable, whereas in the out-of-plane configuration the domains change their size and patterns, depending on the applied switching voltage frequency.

An Analysis of Soft Law Applicable to Humanitarian Assistance: Relative Normativity in Action?

There is limited binding international law specifically covering the provision of humanitarian assistance in response to natural and human-made disasters. Yet a variety of authoritative soft law texts have been developed in the past 20 years, including the UN Guiding Principles on Internal Displacement, the Red Cross Red Crescent Code of Conduct and the Sphere Project’s Humanitarian Charter and Minimum Standards in Disaster Response. While such ‘non-binding normative standards’ do not carry the weight of international law, they play an essential role in the provision of humanitarian assistance albeit subject to their limited enforceability vis-à-vis intended beneficiaries and to their voluntary application by humanitarian actors. Notwithstanding a lack of legal compulsion, certain non-binding normative standards may directly influence the actions of States and non-State actors, and so obtain a strongly persuasive character. Analysis of texts that influence the practice of humanitarian assistance advances our understanding of humanitarian principles and performance standards for disaster response. As the International Law Commission debates draft articles on the Protection of Persons in the Event of Disasters, such non-binding normative standards are crucial to the development of an internationally accepted legal framework to protect victims of disasters.

'"These schemes will win for themselves the confidence of the people": Irish independence, poor law reform and hospital provision'

This article examines hospital provision in Ireland during the early twentieth century. It examines attempts by the newly independent Irish Free State to reform and de-stigmatise medical relief in former workhouse infirmaries. Such reforms were designed to move away from nineteenth century welfare regimes which were underpinned by principles of deterrence. The reform initiated in independent Ireland - the first attempted break-up of the New Poor Law in Great Britain or Ireland - was partly successful. Many of the newly named County and District Hospitals provided solely for medical cases and managed to dissociate such health care provision from the relief of poverty. However, some hospitals continued to act as multifunctional institutions and provided for various categories including the sick, the aged and infirm, 'unmarried mothers' and 'harmless lunatics'. Such institutions often remained associated with the relief of poverty. This article also examines patient fee-payment and outlines how fresh terms of entitlement and means-testing were established. Such developments were even more pronounced in voluntary hospitals where the majority of patients made a financial contribution to their treatment. The article argues that the ability to pay at times determined the type of provision, either voluntary or rate-aided, available to the sick. However, it concludes that the clinical condition of patients often determined whether they entered a more prestigious voluntary hospital or the former workhouse. Although this article concentrates on two Irish case studies, County Kerry and Cork City; it is conceptualised within wider developments with particular reference to the British context.

ARTICLE: Anarchy and International Law: The Approaches of Hedley Bull and Noam Chomsky

Are anarchy and the law antithetical? Not so, as for more than 350 years international law has governed a legal order based on anarchy; wherein no central authority exists and law functions not on the basis of coercion but on cooperation whereby States must agree to each specific laws before it is bound by its obligations. This article contemplates two manners in which an anarchist might consider international law interesting: first, as a legal system which governs an anarchical society as described by Hedley Bull in line with the English School of International Relations; and second, as a manifestation of a State system which, though illegitimate can be utilized, as Noam Chomsky does, for tactical reasons to demonstrate its inconsistencies and thus weakening the system with the ultimate aim being its implosion

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.

Polymorphism in Sulfadimidine/4-Aminosalicylic Acid Cocrystals: Solid-State Characterization and Physicochemical Properties

Polymorphism of crystalline drugs is a common phenomenon. However, the number of reported polymorphic cocrystals is very limited. In this work, the synthesis and solid-state characterization of a polymorphic cocrystal composed of sulfadimidine (SD) and 4-aminosalicylic acid (4-ASA) is reported for the first time. By liquid-assisted milling, the SD:4-ASA 1:1 form I cocrystal, the structure of which has been previously reported, was formed. By spray drying, a new polymorphic form (form II) of the SD:4-ASA 1:1 cocrystal was discovered which could also be obtained by solvent evaporation from ethanol and acetone. Structure determination of the form II cocrystal was calculated using high-resolution X-ray powder diffraction. The solubility of the SD:4-ASA 1:1 cocrystal was dependent on the pH and predicted by a model established for a two amphoteric component cocrystal. The form I cocrystal was found to be thermodynamically more stable in aqueous solution than form II, which showed transformation to form I. Dissolution studies revealed that the dissolution rate of SD from both cocrystals was enhanced when compared with a physical equimolar mixture and pure SD.

European Union Non-Discrimination Law: Comparative Perspectives on Multidimensional Equality Law

EU equality law is multidimensional in being based on different rationales and concepts. Consequently, the concept of discrimination has become fragmented, with different instruments envisaging different scopes of protection. This raises questions as to the ability of EU law to address the situation of persons excluded on a number of grounds. This edited collection addresses the increasing complexity of European Equality Law from jurisprudential, sociological and political science perspectives. Internationally renowned researchers from Scandinavian, Continental and Central European countries and Britain analyse consequences of multiplying discrimination grounds within EU equality law, considering its multidimensionality and intersectionality. The contributors to the volume theorise the move from formal to substantive equality law and its interrelation to new forms of governance, demonstrating the specific combination of non-discrimination law with welfare state models which reveal the global implications of the European Union. The book will be of interest to academics and policy makers all over the world, in particular to those researching and studying law, political sciences and sociology with an interest in human rights, non discrimination law, contract and employment law or European studies.

Beyond Attribution: Responsibility of Armed Non-State Actors for Reparations in Northern Ireland, Colombia and Uganda

This chapter explores the responsibility of armed non-state actors for reparations to victims. Traditionally international law has focused on the responsibility of the state, and more recently the responsibility of convicted individuals before the International Criminal Court, to provide reparations for international crimes. Yet despite the prevalence of internal armed conflict over the past few decades, there responsibility of armed groups for reparations has been neglected in international law. Although there is a tentative emerging basis for armed groups to provide reparations under international law, such developments have not yet crystallized into hard law. However, when considering the more substantive practice of states in Northern Ireland, Colombia and Uganda, a greater effort can be discerned in ensuring that such organizations are responsible for reparations. This paper finds that not only can armed non-state actors be held collectively responsible for reparations, but due to the growing number of internal armed conflict they can play an important role in ensuring the effectiveness of reparations in remedying victims’ harm. Yet, finding armed groups responsible for reparations is no panacea for accountability, due to the nature of armed conflicts, responsibility may not be distinct, but overlapping and joint, and such groups may face difficulties in meeting their obligations, thus requiring a holistic approach and subsidiary role for the state.

State architecture: subsidiarity, devolution, federalism and independence

This chapter examines the current ‘architecture’ of the British state, in particular the way in which governmental power is distributed among the nations of the United Kingdom. The theme of this chapter will be to show how the continuing (and, as James Bryce argued, inevitable) tension between centripetal and centrifugal forces can be usefully applied to power relations between the various nations of the United Kingdom, and between these nations and Europe, providing a basis for analyzing how these nations are drawn or impelled by some forces towards a centralized unitary polity, whilst at the same time other forces tend towards dispersion of power. The resulting pattern might be analyzed along a spectrum from centralization to independence, with subsidiarity, devolution and federalism being seen as weigh stations along the way, but given how complex the variations in the distribution of power between these nations and the centre have become over time, the construction of any static architectural blueprint of the British state is bound to be misleading. Indeed, the architectural metaphor, with its implications of stability might usefully be rethought.

Increased expression of the RIα subunit of the cAMP-dependent protein kinase A is associated with advanced stage ovarian cancer

The primary element in the cAMP signal transduction pathway is the cAMP-dependent protein kinase (PKA). Expression of the RIα subunit of type I PKA is elevated in a variety of human tumours and cancer cell lines. The purpose of this study was to assess the prognostic importance of RIα expression in patients with ovarian cancer. We have evaluated the expression of RIα in a panel of human ovarian tumours (n = 40) and five human ovarian cancer cell lines using quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. The human ovarian cell lines OAW42 and OTN14 express high endogenous levels of RIα mRNA and protein (at significantly higher mRNA levels than high tissue expressors, P < 0.05). The ovarian cell line A2780 expresses low endogenous levels of RIα mRNA and protein (also at higher mRNA levels than low tissue expressors, P < 0.05). Quantitative RT-PCR revealed no significant difference in RIα mRNA expression between different ovarian histological subtypes in this study. No associations were found between RIα mRNA expression and differentiation state. RIα mRNA expression was significantly associated with tumour stage (P = 0.0036), and this remained significant in univariate analysis (P = 0.0002). A trend emerged between RIα mRNA expression levels and overall survival in univariate analysis (P = 0.051), however, by multivariate analysis, stage remained the major determinant of overall survival (P = 0.0001). This study indicates that in ovarian epithelial tumours high RIα mRNA expression is associated with advanced stage disease. RIα expression may be of predictive value in ovarian cancer and may be associated with dysfunctional signalling pathways in this cancer type.

ER stress-mediated autophagy promotes Myc-dependent transformation and tumor growth

The proto-oncogene c-Myc paradoxically activates both proliferation and apoptosis. In the pathogenic state, c-Myc-induced apoptosis is bypassed via a critical, yet poorly understood escape mechanism that promotes cellular transformation and tumorigenesis. The accumulation of unfolded proteins in the ER initiates a cellular stress program termed the unfolded protein response (UPR) to support cell survival. Analysis of spontaneous mouse and human lymphomas demonstrated significantly higher levels of UPR activation compared with normal tissues. Using multiple genetic models, we demonstrated that c-Myc and N-Myc activated the PERK/eIF2α/ATF4 arm of the UPR, leading to increased cell survival via the induction of cytoprotective autophagy. Inhibition of PERK significantly reduced Myc-induced autophagy, colony formation, and tumor formation. Moreover, pharmacologic or genetic inhibition of autophagy resulted in increased Myc-dependent apoptosis. Mechanistically, we demonstrated an important link between Myc-dependent increases in protein synthesis and UPR activation. Specifically, by employing a mouse minute (L24+/-) mutant, which resulted in wild-type levels of protein synthesis and attenuation of Myc-induced lymphomagenesis, we showed that Myc-induced UPR activation was reversed. Our findings establish a role for UPR as an enhancer of c-Myc-induced transformation and suggest that UPR inhibition may be particularly effective against malignancies characterized by c-Myc overexpression.