Unique structural properties associated with mouse prion Δ105-125 protein

Murine prion protein deleted for residues 105-125 is intrinsically neurotoxic and mediates a TSE-like phenotype in transgenic mice. Equivalent and overlapping deletions were expressed in E.coli, purified and analyzed. Among mutants spanning the region 95-135, a construct lacking solely residues 105-125 had distinct properties when compared with the full-length prion protein 23-231 or other deletions. This distinction was also apparent followed expression in eukaryotic cells. Unlike the full-length protein, all deletion mutants failed to bind to synthetic membranes in vitro. These data suggest a novel structure for the 105-125 deleted variant that may relate to its biological properties

Healing the wounds of war: memories of violence and the making of history in Zimbabwe's most recent past.

How does a society less than two decades after a liberation war which involved large sections of the population come to terms with the memories of violence and war — a war in which there was no clear distinction between insurgent and counter‐insurgent, liberator and oppressor and in which the majority of the casualties can be found among the rural civilian population? This was a predicament not exclusive to Zimbabwe, but one which also applies to Mozambique, South Africa and, more recently, to Rwanda. Since its independence Zimbabwe has been a prime example of successful reconciliation. Ranger has argued that spiritual healing has contributed importantly to coming to terms with the trauma of war through turning violence into history. Here it will be argued that an analysis of the intersections between memories of violence, healing, and history reveals a twofold process. Social healing is made possible by a shift from conviction and compensation to revealing without convicting. At the same time healing provides an arena for communities in which competing and contesting memories of violence are renegotiated. Through these processes sense is being made of the past; history is being made.

Realism and reality formats

The chapter focuses on the relationships between 'Reality TV' and other ‘realist’ forms and genres of television. This issue is connected to larger debates about ‘televisuality’, and the understanding of the distinctiveness of the medium. Television processes and worries over reality in all of its genres, so that realism becomes a particularly ambiguous term. One meaning focuses on the actual scenes, places and people are represented rather than imagined. A second meaning refers to television’s representation of recognisable and often contemporary experience. Another meaning of realism refers to the development of new and different forms to give access to the real. Furthermore, the establishment of category distinctions in television, such as between factual and fictional forms, or between drama and documentary, could be seen as increasingly problematic in contemporary television. Reality TV can thought of as the trying-out of forms and modes of address in one genre or form that are adopted from apparently different genres and forms, thus creating connection and distinction simultaneously. This chapter addresses these distinctions and ambiguities within Reality TV, using examples including One Born Every Minute and The Only Way is Essex.

fMRI evidence for the involvement of the procedural memory system in morphological processing of a second language

Behavioural evidence suggests that English regular past tense forms are automatically decomposed into their stem and affix (played  = play+ed) based on an implicit linguistic rule, which does not apply to the idiosyncratically formed irregular forms (kept). Additionally, regular, but not irregular inflections, are thought to be processed through the procedural memory system (left inferior frontal gyrus, basal ganglia, cerebellum). It has been suggested that this distinction does not to apply to second language (L2) learners of English; however, this has not been tested at the brain level. This fMRI study used a masked-priming task with regular and irregular prime-target pairs (played-play/kept-keep) to investigate morphological processing in native and highly proficient late L2 English speakers. No between-groups differences were revealed. Compared to irregular pairs, regular pairs activated the pars opercularis, bilateral caudate nucleus and the right cerebellum, which are part of the procedural memory network and have been connected with the processing of morphologically complex forms. Our study is the first to provide evidence for native-like involvement of the procedural memory system in processing of regular past tense by late L2 learners of English.

Hydrophilic interaction chromatography–mass spectrometry for anionic metabolic profiling of urine from antibiotic-treated rats

Hydrophilic interaction chromatography–mass spectrometry (HILIC–MS) was used for anionic metabolic profiling of urine from antibiotic-treated rats to study microbial–host co-metabolism. Rats were treated with the antibiotics penicillin G and streptomycin sulfate for four or eight days and compared to a control group. Urine samples were collected at day zero, four and eight, and analyzed by HILIC–MS. Multivariate data analysis was applied to the urinary metabolic profiles to identify biochemical variation between the treatment groups. Principal component analysis found a clear distinction between those animals receiving antibiotics and the control animals, with twenty-nine discriminatory compounds of which twenty were down-regulated and nine up-regulated upon treatment. In the treatment group receiving antibiotics for four days, a recovery effect was observed for seven compounds after cessation of antibiotic administration. Thirteen discriminatory compounds could be putatively identified based on their accurate mass, including aconitic acid, benzenediol sulfate, ferulic acid sulfate, hippuric acid, indoxyl sulfate, penicillin G, phenol and vanillin 4-sulfate. The rat urine samples had previously been analyzed by capillary electrophoresis (CE) with MS detection and proton nuclear magnetic resonance (1H NMR) spectroscopy. Using CE–MS and 1H NMR spectroscopy seventeen and twenty-five discriminatory compounds were found, respectively. Both hippuric acid and indoxyl sulfate were detected across all three platforms. Additionally, eight compounds were observed with both HILIC–MS and CE–MS. Overall, HILIC–MS appears to be highly complementary to CE–MS and 1H NMR spectroscopy, identifying additional compounds that discriminate the urine samples from antibiotic-treated and control rats.

Potential-based achievement goals

Background: Self-based achievement goals use one’s own intrapersonal trajectory as a standard of evaluation, and this intrapersonal trajectory may be grounded in one’s past (past-based goals) or one’s future potential potential-based goals). Potential-based goals have been overlooked in the literature to date. Aims: The primary aim of the present research is to address this oversight within the context of the 3 x 2 achievement goal framework. Samples: The Study 1 sample was 381 U.S. undergraduates; the Study 2 sample was 310 U.S. undergraduates. Methods: In Study 1, we developed scales to assess otential-approach and potential-avoidance goals, and tested their factorial validity with exploratory and confirmatory factor analyses. In Study 2, we used confirmatory factor analysis to test both the separability of past-based and potential-based goals and their higher order integration within the self-based category. Results: Study 1 supported the factorial validity of the potential-approach and potential-avoidance goal scales. Study 2 supported the separability of past-based and potential-based goals, as well as their higher order integration within the self-based category. Conclusions: This research documents the utility of the proposed distinction, and paves the way for subsequent work on antecedent and consequences of potential-approach and potential-avoidance goals. It highlights the importance

On a resurgence of management simulations and games

The past few years have seen a significant resurgence of interest in ‘management games’ and ‘management flight simulators’, one particularly active source of such work being the system dynamics community. After proposing a distinction between games and simulations, this paper provides some background to these developments by briefly describing the historical roots of the field and the fundamental ideas of the system dynamics community, which are now giving rise to ‘microworlds’. The training advantages of management simulations and games are then discussed. The paper closes with a note on the research and findings of the system dynamics field and by offering some words of warning on the perils of simulation and game use. Two scenarios for how the use of simulations and games as management education devices might develop in the future are proposed. An Appendix describes five examples of very different types of management simulations and games.

Early, late or very late? Timing acquisition and bilingualism

Research on child bilingualism accounts for differences in the course and the outcomes of monolingual and different types of bilingual language acquisition primarily from two perspectives: age of onset of exposure to the language(s) and the role of the input (Genesee, Paradis, & Crago, 2004; Meisel, 2009; Unsworth et al., 2014). Some findings suggest that early successive bilingual children may pattern similarly to simultaneous bilingual children, passing through different trajectories from child L2 learners due to a later age of onset in the latter group. Studies on bilingual development have also shown that input quantity in bilingual acquisition is considerably reduced, i.e., in each of their two languages, bilingual children are likely exposed to much less input than their monolingual peers (Paradis & Genesee, 1996; Unsworth, 2013b). At the same time, simultaneous bilingual children develop and attain competence in the two languages, sometimes without even an attested age delay compared to monolingual children (Paradis, Genesee & Crago, 2011). The implication is that even half of the input suffices for early language development, at least with respect to ‘core’ aspects of language, in whatever way ‘core’ is defined.My aim in this article is to consider how an additional, linguistic variable interacts with age of onset and input in bilingual development, namely, the timing in L1 development of the phenomena examined in bilingual children’s performance. Specifically, I will consider timing differences attested in the monolingual development of features and structures, distinguishing between early, late or ‘very late’ acquired phenomena. I will then argue that this three-way distinction reflects differences in the role of narrow syntax: early phenomena are core, parametric and narrowly syntactic, in contrast to late and very late phenomena, which involve syntax-external or even language-external resources too. I explore the consequences of these timing differences in monolingual development for bilingual development. I will review some findings from early (V2 in Germanic, grammatical gender in Greek), late (passives) and very late (grammatical gender in Dutch) phenomena in the bilingual literature and argue that early phenomena can differentiate between simultaneous and (early) successive bilingualism with an advantage for the former group, while the other two reveal similarly (high or low) performance across bilingual groups, differentiating them from monolinguals. The paper proposes that questions about the role of age of onset and language input in early bilingual development can only be meaningfully addressed when the properties and timing of the phenomena under investigation are taken into account.

The agile governance of business IT projects

Organisations typically define and execute their selected strategy by developing and managing a portfolio of projects. The governance of this portfolio has proved to be a major challenge, particularly for large organisations. Executives and managers face even greater pressures when the nature of the strategic landscape is uncertain. This paper explores approaches for dealing with different levels of certainty in business IT projects and provides a contingent governance framework. Historically business IT projects have relied on a structured sequential approach, also referred to as a waterfall method. There is a distinction between the development stages of a solution and the management stages of a project that delivers the solution although these are often integrated in a business IT systems project. Prior research has demonstrated that the level of certainty varies between development projects. There can be uncertainty on what needs to be developed and also on how this solution should be developed. The move to agile development and management reflects a greater level of uncertainty often on both dimensions and this has led the adoption of more iterative approaches. What has been less well researched is the impact of uncertainty on the governance of the change portfolio and the corresponding implications for business executives. This paper poses this research question and proposes a govemance framework to address these aspects. The governance framework has been reviewed in the context of a major anonymous organisation, FinOrg. Findings are reported in this paper with a focus on the need to apply different approaches. In particular, the governance of uncertain business change is contrasted with the management approach for defined IT projects. Practical outputs from the paper include a consideration of some innovative approaches that can be used by executives. It also investigates the role of the business change portfolio group in evaluating and executing the appropriate level of governance. These results lead to recommendations for executives and also proposed further research.

The source population for the cusp and cleft/LLBL for southward IMF

The distinction between plasma properties in different dayside regions in the Earth's magnetosphere is of strong interest as it is often indicative of specific physical processes. This is certainly true for the distinction between low latitude boundary layer (LLBL) and cusp plasma, which has been attributed to the effects of plasma diffusion across the magnetopause (LLBL) versus more direct entry of magnetosheath plasma(cusp). It is also the case, however, that quite different plasma regions can result more simply from a common source plasma, and from different stages of temporal evolution of the plasma associated with magnetospheric convection. In this paper, we show that, for southward interplanetary magnetic field (IMF) conditions, the distinction between the cusp and cleft/LLBL at low altitudes may result from;the single process of magnetosheath plasma entry into the magnetosphere on reconnected field lines. The different plasma characteristics of the two regions result from the properties of the source magnetosheath ion distribution and the effects of magnetic reconnection. Using well known properties of the magnetosheath, several predictions concerning the cusp and cleft/ LLBL precipitation are readily derived.

Dynamic auroral structure in the vicinity of the polar cusp - multipoint observations during southward and northward IMF

The low- and high-latitude boundary layers of the earth's magnetosphere [low-latitude boundary layer (LLBL) and mantle] play important roles in transferring momentum and energy from the solar wind to the magnetosphere-ionosphere system. Particle precipitation, field-aligned current, auroral emission, ionospheric ion drift and ground magnetic perturbations are among the low-altitude parameters that show signatures of various plasma processes in the LLBL and the magnetopause current layer. Magnetic merging events, Kelvin-Helmholtz waves, and pressure pulses excited by the variable solar wind/magnetosheath plasma are examples of boundary phenomena that may be coupled to the ionosphere via field-aligned currents. Optical auroral observation, by photometry and all-sky TV cameras, is a unique technique for investigating the spatial and temporal structure of the electron precipitation associated with such phenomena. However, the distinction between the different boundary layer plasma populations cannot in general be unambiguously determined by optics alone. Additional information, such as satellite observations of particle boundaries and field-aligned currents, is needed in order to identify the plasma source(s) and the magnetosphere-ionosphere coupling mode(s). Two categories of auroral activity/structure in the vicinity of the polar cusp are discussed in this paper, based on combined ground and satellite data. In one case, the quasi-periodic sequence of auroral events at the polar cap boundary involves accelerated electrons (< 1 keV) moving poleward (< 1 km s-1) and azimuthally along the persistent cusp/cleft arc poleward boundary with velocities (< 4 km s-1), comparable to the local ionospheric ion drift during periods of southward IMF. A critical question is whether or not the optical events signify a corresponding plasma flow across the open/closed field line boundary in such cases. Near-simultaneous observations of magnetopause flux transfer events (FTEs) and such optical/ion drift events are reported. The reverse pattern of motion of discrete auroral forms is observed during positive interplanetary magnetic field (IMF) B(Z), i.e. equatorward motion into the cusp/cleft background arc from the poleward edge. Combined satellite and ground-based information for the latter cases indicate a source mechanism, poleward of the cusp at the high-latitude magnetopause or plasma mantle, giving rise to strong momentum transfer and electron precipitation structures within a approximately 200 km-wide latitudinal zone at the cusp/cleft poleward boundary. The striking similarities of auroral electrodynamics in the cleft/mantle region during northward and southward IMF indicate that a qualitatively similar solar wind-magnetosphere coupling mode is operating. It is suggested that, in both cases, the discrete auroral forms represent temporal/spatial structure of larger-scale convection over the polar magnetosphere.

The ionospheric signatures of flux transfer events and solar wind dynamic pressure changes

The generation of flow and current vortices in the dayside auroral ionosphere has been predicted for two processes ocurring at the dayside magnetopause. The first of these mechanisms is time-dependent magnetic reconnection, in “flux transfer events” (FTEs); the second is the action of solar wind dynamic pressure changes. The ionospheric flow signature of an FTE should be a twin vortex, with the mean flow velocity in the central region of the pattern equal to the velocity of the pattern as a whole. On the other hand, a pulse of enhanced or reduced dynamic pressure is also expected to produce a twin vortex, but with the central plasma flow being generally different in speed from, and almost orthogonal to, the motion of the whole pattern. In this paper, we make use of this distinction to discuss recent observations of vortical flow patterns in the dayside auroral ionosphere in terms of one or other of the proposed mechanisms. We conclude that some of the observations reported are consistent only with the predicted signature of FTEs. We then evaluate the dimensions of the open flux tubes required to explain some recent simultaneous radar and auroral observations and infer that they are typically 300 km in north–south extent but up to 2000 km in longitudinal extent (i.e., roughly 5 hours of MLT). Hence these observations suggest that recent theories of FTEs which invoke time-varying reconnection at an elongated neutral line may be correct. We also present some simultaneous observations of the interplanetary magnetic field (IMF) and solar wind dynamic pressure (observed using the IMP8 satellite) and the ionospheric flow (observed using the EISCAT radar) which are also only consistent with the FTE model. We estimate that for continuously southward IMF ( ≈ 5 nT) these FTEs contribute about 30 kV to the mean total transpolar voltage (∼30%).

Superthermal ion signatures of auroral acceleration processes

The retarding ion mass spectrometer on the Dynamics Explorer 1 spacecraft has generated a unique data set which documents, among other things, the occurrence of non-Maxwellian superthermal features in the auroral topside ionosphere distribution functions. In this paper, we provide a representative sampling of the observed features and their spatial morphology as observed at altitudes in the range from a few thousand kilometers to a few earth radii. At lower altitudes, these features appear at auroral latitudes separating regions of polar cap and subauroral light ion polar wind. The most common signature is the appearance of an upgoing energetic tail having conical lobes representing significant ion heat and number flux in all species, including O+. Transverse ion heating below the observation point at several thousand kilometers is clearly associated with O+ outflows. In some events observed, transverse acceleration apparently involves nearly the entire thermal plasma, the distribution function becomes highly anisotropic with T⊥ > T∥, and may actually develop a minimum at zero velocity, i.e., become a torus having as its axis the local magnetic field direction. At higher altitudes, the localized dayside source region appears as a field aligned flow which is dispersed tailward across the polar cap according to parallel velocity by antisunward convective flow, so that upflowing low energy O+ ions appear well within the polar cap region. While this flow can appear beamlike in a given location, the energy dispersion observed implies a very broad energy distribution at the source, extending from a few tenths of an eV to in excess of 50 eV. On the nightside, upgoing ion beams are found to be latitudinally bounded by regions of ion conics whose half angles increase with increasing separation from the beam region, indicating low altitude transverse acceleration in immediate proximity to, and below, the parallel acceleration region. These observations reveal a clear distinction between classical polar wind ion outflow and O+ enhanced superthermal flows, and confirm the importance of low altitude transverse acceleration in ionospheric plasma transport, as suggested by previous observations.

Health care rights and NHS rationing: turning theory into practice

How should we understand the nature of patients’ right in public health care systems? Are health care rights different to rights under a private contract for car insurance? This article distinguishes between public and private rights and the relevance of community interests and notions of social solidarity. It discusses the distinction between political and civil rights, and social and economic rights and the inherently political and redistributive nature of the latter. Nevertheless, social and economic rights certainly give rise to “rights” enforceable by the courts. In the UK (as in many other jurisdictions), the courts have favoured a “procedural” approach to the question, in which the courts closely scrutinise decisions and demand high standards of rationality from decision-makers. However, although this is the general rule, the article also discusses a number of exceptional cases where “substantive” remedies are available which guarantee patients access to the care they need.

Humanitarian law, human rights law and the bifurcation of armed conflict

This article offers a fresh examination of the distinction drawn in international humanitarian law (IHL) between international and non-international armed conflicts. In particular, it considers this issue from the under-explored perspective of the influence of international human rights law (IHRL). It is demonstrated how, over time, the effect of IHRL on this distinction in IHL has changed dramatically. Whereas traditionally IHRL encouraged the partial elimination of the distinction between types of armed conflict, more recently it has been invoked in debates in a manner that would preserve what remains of the distinction. By exploring this important issue, it is hoped that the present article will contribute to the ongoing debates regarding the future development of the law of non-international armed conflict.