4,116 research outputs found

    The Institutionalisation of Political Power in Africa

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    Evidently, the failure of Nigeria's President Obasanjo's third term bid and the process through which it was reached is indicative of a growing trend in Africa whereby the formal institutional rules are starting to constrain leaders' behavior and to shape political actors' strategies in new ways. In this case, the major challenge for limiting presidential power in Africa today is making certain that leaders adhere to constitutional limits on their continued eligibility to contest them.NESG Economic Indicators Vol. 13 (1) 2007: pp. 15-2

    Banking union in historical perspective: the initiative of the European Commission in the 1960s-1970s

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    This article shows that planning for the organization of EU banking regulation and supervision did not just appear on the agenda in recent years with discussions over the creation of the eurozone banking union. It unveils a hitherto neglected initiative of the European Commission in the 1960s and early 1970s. Drawing on extensive archival work, this article explains that this initiative, however, rested on a number of different assumptions, and emerged in a much different context. It first explains that the Commission's initial project was not crisis-driven; that it articulated the link between monetary integration and banking regulation; and finally that it did not set out to move the supervisory framework to the supranational level, unlike present-day developments

    RuleMonkey: software for stochastic simulation of rule-based models

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    <p>Abstract</p> <p>Background</p> <p>The system-level dynamics of many molecular interactions, particularly protein-protein interactions, can be conveniently represented using reaction rules, which can be specified using model-specification languages, such as the BioNetGen language (BNGL). A set of rules implicitly defines a (bio)chemical reaction network. The reaction network implied by a set of rules is often very large, and as a result, generation of the network implied by rules tends to be computationally expensive. Moreover, the cost of many commonly used methods for simulating network dynamics is a function of network size. Together these factors have limited application of the rule-based modeling approach. Recently, several methods for simulating rule-based models have been developed that avoid the expensive step of network generation. The cost of these "network-free" simulation methods is independent of the number of reactions implied by rules. Software implementing such methods is now needed for the simulation and analysis of rule-based models of biochemical systems.</p> <p>Results</p> <p>Here, we present a software tool called RuleMonkey, which implements a network-free method for simulation of rule-based models that is similar to Gillespie's method. The method is suitable for rule-based models that can be encoded in BNGL, including models with rules that have global application conditions, such as rules for intramolecular association reactions. In addition, the method is rejection free, unlike other network-free methods that introduce null events, i.e., steps in the simulation procedure that do not change the state of the reaction system being simulated. We verify that RuleMonkey produces correct simulation results, and we compare its performance against DYNSTOC, another BNGL-compliant tool for network-free simulation of rule-based models. We also compare RuleMonkey against problem-specific codes implementing network-free simulation methods.</p> <p>Conclusions</p> <p>RuleMonkey enables the simulation of rule-based models for which the underlying reaction networks are large. It is typically faster than DYNSTOC for benchmark problems that we have examined. RuleMonkey is freely available as a stand-alone application <url>http://public.tgen.org/rulemonkey</url>. It is also available as a simulation engine within GetBonNie, a web-based environment for building, analyzing and sharing rule-based models.</p

    Consumer credit information systems: A critical review of the literature. Too little attention paid by lawyers?

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    This paper reviews the existing literature on consumer credit reporting, the most extensively used instrument to overcome information asymmetry and adverse selection problems in credit markets. Despite the copious literature in economics and some research in regulatory policy, the legal community has paid almost no attention to the legal framework of consumer credit information systems, especially within the context of the European Union. Studies on the topic, however, seem particularly relevant in view of the establishment of a single market for consumer credit. This article ultimately calls for further legal research to address consumer protection concerns and inform future legislation

    Phase 1 dose-escalation study of S-222611, an oral reversible dual tyrosine kinase inhibitor of EGFR and HER2, in patients with solid tumours.

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    BACKGROUND: S-222611 is a reversible inhibitor of EGFR, HER2 and HER4 with preclinical activity in models expressing these proteins. We have performed a Phase 1 study to determine safety, maximum tolerated dose (MTD), pharmacokinetic profile (PK) and efficacy in patients with solid tumours expressing EGFR or HER2. PATIENTS AND METHODS: Subjects had advanced tumours not suitable for standard treatment, expressing EGFR or HER2, and/or with amplified HER2. Daily oral doses of S-222611 were escalated from 100mg to 1600 mg. Full plasma concentration profiles for drug and metabolites were obtained. RESULTS: 33 patients received S-222611. It was well tolerated, and the most common toxicities, almost all mild (grade 1 or 2), were diarrhoea, fatigue, rash and nausea. Only two dose-limiting toxicities occurred (diarrhoea and rash), which resolved on interruption. MTD was not reached. Plasma exposure increased with dose up to 800 mg, exceeding levels eliciting pre-clinical responses. The plasma terminal half-life was more than 24h, supporting once daily dosing. Responses were seen over a wide range of doses in oesophageal, breast and renal tumours, including a complete clinical response in a patient with HER2-positive breast carcinoma previously treated with lapatinib and trastuzumab. Four patients have remained on treatment for more than 12 months. Downregulation of pHER3 was seen in paired tumour biopsies from a responding patient. CONCLUSIONS: Continuous daily oral S-222611 is well tolerated, modulates oncogenic signalling, and has significant antitumour activity. The recommended Phase 2 dose, based on PK and efficacy, is 800 mg/day.The authors acknowledge financial support from the UK Department of Health via the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) award to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust (and NIHR Clinical Research Facility), and to The University of Cambridge and Cambridge University Hospital NHS Foundation Trust. Cambridge, King’s College London, and Newcastle are Experimental Cancer Medicine Centres.This is the accepted manuscript. The final version is available from http://www.sciencedirect.com/science/article/pii/S0959804914010922

    Shifting attention in viewer- and object-based reference frames after unilateral brain injury

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    The aims of the present study were to investigate the respective roles that object- and viewer-based reference frames play in reorienting visual attention, and to assess their influence after unilateral brain injury. To do so, we studied 16 right hemisphere injured (RHI) and 13 left hemisphere injured (LHI) patients. We used a cueing design that manipulates the location of cues and targets relative to a display comprised of two rectangles (i.e., objects). Unlike previous studies with patients, we presented all cues at midline rather than in the left or right visual fields. Thus, in the critical conditions in which targets were presented laterally, reorienting of attention was always from a midline cue. Performance was measured for lateralized target detection as a function of viewer-based (contra- and ipsilesional sides) and object-based (requiring reorienting within or between objects) reference frames. As expected, contralesional detection was slower than ipsilesional detection for the patients. More importantly, objects influenced target detection differently in the contralesional and ipsilesional fields. Contralesionally, reorienting to a target within the cued object took longer than reorienting to a target in the same location but in the uncued object. This finding is consistent with object-based neglect. Ipsilesionally, the means were in the opposite direction. Furthermore, no significant difference was found in object-based influences between the patient groups (RHI vs. LHI). These findings are discussed in the context of reference frames used in reorienting attention for target detection

    The future of social is personal: the potential of the personal data store

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    This chapter argues that technical architectures that facilitate the longitudinal, decentralised and individual-centric personal collection and curation of data will be an important, but partial, response to the pressing problem of the autonomy of the data subject, and the asymmetry of power between the subject and large scale service providers/data consumers. Towards framing the scope and role of such Personal Data Stores (PDSes), the legalistic notion of personal data is examined, and it is argued that a more inclusive, intuitive notion expresses more accurately what individuals require in order to preserve their autonomy in a data-driven world of large aggregators. Six challenges towards realising the PDS vision are set out: the requirement to store data for long periods; the difficulties of managing data for individuals; the need to reconsider the regulatory basis for third-party access to data; the need to comply with international data handling standards; the need to integrate privacy-enhancing technologies; and the need to future-proof data gathering against the evolution of social norms. The open experimental PDS platform INDX is introduced and described, as a means of beginning to address at least some of these six challenges

    Rapid detection of snakes modulates spatial orienting in infancy

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    Recent evidence for an evolved fear module in the brain comes from studies showing that adults, children and infants detect evolutionarily threatening stimuli such as snakes faster than non-threatening ones. A decisive argument for a threat detection system efficient early in life would come from data showing, in young infants, a functional threat-detection mechanism in terms of “what” and “where” visual pathways. The present study used a variant of Posner’s cuing paradigm, adapted to 7–11-month-olds. On each trial, a threat-irrelevant or a threat-relevant cue was presented (a flower or a snake, i.e., “what”). We measured how fast infants detected these cues and the extent to which they further influenced the spatial allocation of attention (“where”). In line with previous findings, we observed that infants oriented faster towards snake than flower cues. Importantly, a facilitation effect was found at the cued location for flowers but not for snakes, suggesting that these latter cues elicit a broadening of attention and arguing in favour of sophisticated “what–where” connections. These results strongly support the claim that humans have an early propensity to detect evolutionarily threat-relevant stimuli

    Learning physics in context: a study of student learning about electricity and magnetism

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    This paper re-centres the discussion of student learning in physics to focus on context. In order to do so, a theoretically-motivated understanding of context is developed. Given a well-defined notion of context, data from a novel university class in electricity and magnetism are analyzed to demonstrate the central and inextricable role of context in student learning. This work sits within a broader effort to create and analyze environments which support student learning in the sciencesComment: 36 pages, 4 Figure
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