A device to investigate the axial strain dependence of the critical current density in superconductors

We have developed an instrument to study the behavior of the critical current density (J(c)) in superconducting wires and tapes as a function of field (mu(0)H), temperature (T), and axial applied strain (epsilon(a)). The apparatus is an improvement of similar devices that have been successfully used in our institute for over a decade. It encompasses specific advantages such as a simple sample layout, a well defined and homogeneous strain application, the possibility of investigating large compressive strains and the option of simple temperature variation, while improving the main drawback in our previous systems by increasing the investigated sample length by approximately a factor of 10. The increase in length is achieved via a design change from a straight beam section to an initially curved beam, placed perpendicular to the applied field axis in the limited diameter of a high field magnet bore. This article describes in detail the mechanical design of the device and its calibrations. Additionally initial J(c)(epsilon(a)) data, measured at liquid helium temperature, are presented for a bronze processed and for a powder-in-tube Nb3Sn superconducting wire. Comparisons are made with earlier characterizations, indicating consistent behavior of the instrument. The improved voltage resolution, resulting from the increased sample length, enables J(c) determinations at an electric field criterion E-c=10 muV/m, which is substantially lower than a criterion of E-c=100 muV/m which was possible in our previous systems. (C) 2004 American Institute of Physics.

Management of polycythaemia vera: a critical review of current data

Polycythaemia vera (PV) is a chronic blood cancer; its clinical features are dominated by myeloproliferation (erythrocytosis, often leucocytosis and/or thrombocytosis) and a tendency for thrombosis and transformation to myelofibrosis or acute myeloid leukaemia. In the past 10 years the pathophysiology of this condition has been defined as JAK/STAT pathway activation, almost always due to mutations in JAK2 exons 12 or 14 (JAK2 V617F). In the same time period our understanding of the optimal management of PV has expanded, most recently culminating in the approval of JAK inhibitors for the treatment of PV patients who are resistant or intolerant to therapy with hydroxycarbamide. It has also been demonstrated that life expectancy for many patients with PV is not normal, nor is their quality of life. We critically explore these findings and discuss their impact. In addition, we highlight persisting gaps in our current management strategy; for example, what is the optimal first line cytoreductive therapy and, indeed, which patients need cytoreductive drugs.

Muscle-specific variations in use-dependent crossed-facilitation of corticospinal pathways mediated by transcranial direct current (DC) stimulation

The tendency for contractions of muscles in the upper limb to give rise to increases in the excitability of corticospinal projections to the homologous muscles of the opposite limb is well known. Although the suppression of this tendency is integral to tasks of daily living, its exploitation may prove to be critical in the rehabilitation of acquired hemiplegias. Transcranial direct current (DC) stimulation induces changes in cortical excitability that outlast the period of application. We present evidence that changes in the reactivity of the corticospinal pathway induced by DC stimulation of the motor cortex interact systematically with those brought about by contraction of the muscles of the ipsilateral limb. During the application of flexion torques (up to 50% of maximum) applied at the left wrist, motor evoked potentials (MEPs) were evoked in the quiescent muscles of the right arm by magnetic stimulation of the left motor cortex (M1). The MEPs were obtained prior to and following 10 min of anodal, cathodal or sham DC stimulation of left M1. Cathodal stimulation counteracted increases in the crossed-facilitation of projections to the (right) wrist flexors that otherwise occurred as a result of repeated flexion contractions at the left wrist. In addition, cathodal stimulation markedly decreased the excitability of corticospinal projections to the wrist extensors of the right limb. Thus changes in corticospinal excitability induced by DC stimulation can be shaped (i.e. differentiated by muscle group) by focal contractions of muscles in the limb ipsilateral to the site of stimulation. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Erythrocytosis-associated HIF-2alpha mutations demonstrate a critical role for residues C-terminal to the hydroxylacceptor proline.

Abstract A classic physiologic response to hypoxia in humans is the up-regulation of the ERYTHROPOIETIN (EPO) gene, which is the central regulator of red blood cell mass. The EPO gene, in turn, is activated by hypoxia inducible factor (HIF). HIF is a transcription factor consisting of an alpha subunit (HIF-alpha) and a beta subunit (HIF-beta). Under normoxic conditions, prolyl hydroxylase domain protein (PHD, also known as HIF prolyl hydroxylase and egg laying-defective nine protein) site specifically hydroxylates HIF-alpha in a conserved LXXLAP motif (where underlining indicates the hydroxylacceptor proline). This provides a recognition motif for the von Hippel Lindau protein, a component of an E3 ubiquitin ligase complex that targets hydroxylated HIF-alpha for degradation. Under hypoxic conditions, this inherently oxygen-dependent modification is arrested, thereby stabilizing HIF-alpha and allowing it to activate the EPO gene. We previously identified and characterized an erythrocytosis-associated HIF2A mutation, G537W. More recently, we reported two additional erythrocytosis-associated HIF2A mutations, G537R and M535V. Here, we describe the functional characterization of these two mutants as well as a third novel erythrocytosis-associated mutation, P534L. These mutations affect residues C-terminal to the LXXLAP motif. We find that all result in impaired degradation and thus aberrant stabilization of HIF-2alpha. However, each exhibits a distinct profile with respect to their effects on PHD2 binding and von Hippel Lindau interaction. These findings reinforce the importance of HIF-2alpha in human EPO regulation, demonstrate heterogeneity of functional defects arising from these mutations, and point to a critical role for residues C-terminal to the LXXLAP motif in HIF-alpha.

Choose Life not Economic Growth: Critical Social Theory for People, Planet and Flourishing in the ‘Age of Nature’

Choose a fucking big television Choose washing machines, cars, compact disc players, and electrical tin openers... Choose leisure wear and matching luggage. Choose a three piece suite on hire purchase in a range of fucking fabrics. Choose DIY and wondering who you are on a Sunday morning. Choose sitting on that couch watching mind-numbing sprit-crushing game shows Stuffing fucking junk food into your mouth. Choose your future. Choose life. (Irvine Welsh, Trainspotting, 1996) Anyone who believes exponential growth can go on forever in a finite world is either a madman or an economist (Kenneth Boulding)

Type XVIII collagen degradation products in acute lung injury

Introduction In acute lung injury, repair of the damaged alveolar-capillary barrier is an essential part of recovery. Endostatin is a 20 to 28 kDa proteolytic fragment of the basement membrane collagen XVIII, which has been shown to inhibit angiogenesis via action on endothelial cells. We hypothesised that endostatin may have a role in inhibiting lung repair in patients with lung injury. The aims of the study were to determine if endostatin is elevated in the plasma/bronchoalveolar lavage fluid of patients with acute lung injury and ascertain whether the levels reflect the severity of injury and alveolar inflammation, and to assess if endostatin changes occur early after the injurious lung stimuli of one lung ventilation and lipopolysaccharide (LPS) challenge.

From Aspiration to Action: A Learning Intentions Model to Promote Critical Engagement with Science in the Print-Based Media

Science programmes which prepare students to read critically and respond thoughtfully to science-based reports in the media could play an important role in promoting informed participation in the public debate about issues relating to science, technology and society. Evidence based guidance about the practice and pattern of use of science-based media in the classroom is limited. This study sought to identify learning intentions that teachers believe ought to underpin the development of programmes of study designed to achieve this end-result. Teachers views of knowledge, skills and attitudes required to engage critically with science-based news served as a basis for this study. Teachers developed a pedagogical model by selecting appropriate statements of learning intentions, grouping these into coherent and manageable themes and coding them according to perceived level of difficulty. The model is largely compatible with current curricular provision in the UK, highlights opportunities for interdisciplinary collaboration and illustrates the developmental nature of the topic.

Approaches to the Implementation of the Water Framework Directive: Targeting Mitigation Measures at Critical Source Areas of Diffuse Phosphorus in Irish Catchments

The Water Framework Directive (WFD) has initiated a shift towards a targeted approach to implementation through its focus on river basin districts as management units and the natural ecological characteristics of waterbodies. Due to its role in eutrophication, phosphorus (P) has received considerable attention, resulting in a significant body of research, which now forms the evidence base for the programme of measures (POMs) adopted in WFD River Basin Management Plans (RBMP). Targeting POMs at critical sources areas (CSAs) of P could significantly improve environmental efficiency and cost effectiveness of proposed mitigation strategies. This paper summarises the progress made towards targeting mitigation measures at CSAs in Irish catchments. A review of current research highlights that knowledge related to P export at field scale is relatively comprehensive however; the availability of site-specific data and tools limits widespread identification of CSA at this scale. Increasing complexity of hydrological processes at larger scales limits accurate identification of CSA at catchment scale. Implementation of a tiered approach, using catchment scale tools in conjunction with field-by-field surveys could decrease uncertainty and provide a more practical and cost effective method of delineating CSA in a range of catchments. Despite scientific and practical uncertainties, development of a tiered CSA-based approach to assist in the development of supplementary measures would provide a means of developing catchment-specific and cost-effective programmes of measures for diffuse P. The paper presents a conceptual framework for such an approach, which would have particular relevance for the development of supplementary measures in High Status Waterbodies (HSW). The cost and resources necessary for implementation are justified based on HSWs’ value as undisturbed reference condition ecosystems.

A Critical Review of Screening Methods for the Detection of Chloramphenicol, Thiamphenicol, and Florfenicol Residues in Foodstuffs

This article gives an extensive overview of the wide range of analytical procedures developed for the detection of amphenicol antibiotic residues (chloramphenicol, thiamphenicol, and florfenicol) in many different types of foodstuffs (milk, meat, eggs, honey, seafood). Screening methods such as microbial inhibition methods, antibody-based immunoassays using conventional and biosensor-based detection systems, and some methods based on alternative recognition systems are described. The relative advantages and disadvantages of these methods are discussed and compared. The current status and future trends and developments in the need for accurate and rapid detection of this group of antimicrobials are also discussed.

London 2012 and Climate Change. Examining the potential impact of the current economic crisis in the environmental legacy of the Games

The International Olympic Committee (IOC) declares environmental protection to be the third dimension of the Olympic movement. That, in effect, means that nations wishing to host the Games have to present themselves as reliable practitioners of environmental sustainability (ES) in their applications. The greening of sports mega-events, and the hosting of Olympic Games in particular, is now reasonably well established. Yet evidence from the first decade of environmentally-conscious Olympics points to diverging patterns of achievement in the operationalisation of the IOC’s ‘third pillar’. As is now common knowledge, for example, Sydney 2000 was the first ‘Green Olympics’ in the history of the Games; yet four years later, Athens provided a stark contrast, and was the subject of highly critical assessment reports by environmental organisations. Yet Athens has not stopped the Bid Committee for the Beijing 2008 Games claiming that it would ‘leave the greatest Olympic Games environmental legacy ever’ (UNEP 2007: 26), while the London 2012 promotes the concept of the ‘One Planet Olympics’.

In this context and in light of the current global economic crisis, can we claim that London 2012 has the capacity to fulfil its environmental ambitions? This question is adopted in continuity with similar framed questions that have been posed in relation to the most recent Olympics and it is tackled by adopting an investigative model that is placed within discourses of ‘reflexive modernisation’.

Understanding the Effects of Ionicity in Salts, Solvates, Co-Crystals, Ionic Co-Crystals, and Ionic Liquids, Rather than Nomenclature, Is Critical to Understanding Their Behavior

The incorporation of active pharmaceutical ingredients (APIs) into multicomponent solid forms (such as salts and co-crystals) or liquid forms (such as ionic liquids (ILs) or deep eutectic mixtures) is important in optimizing the efficacy and delivery of APIs. However, there is a current debate regarding the classification of these multicomponent systems based on their ionicity which could interfere with their consideration in important applications. Multicomponent systems of intermediate ionicity can show a combination of properties, leading to behavior that is neither strictly typical of either purely ionic or purely neutral compounds, nor easily described as intermediate between the two. In this perspective, we attempt to illustrate the problems in classifying multicomponent APIs based on one of two categories by discussing selected literature regarding solid and liquid multicomponent APIs and presenting the crystal structures of some relevant systems as case studies. It is clear that a focus on restrictive nomenclature carries with it the risk that a thorough examination of the physicochemical properties of the compounds will be overlooked.

Topical Review: The current understanding on the diamond machining of silicon carbide

The Glenn Research Centre of NASA, USA (www.grc.nasa.gov/WWW/SiC/, silicon carbide electronics) is in pursuit of realizing bulk manufacturing of silicon carbide (SiC), specifically by mechanical means. Single point diamond turning (SPDT) technology which employs diamond (the hardest naturally-occurring material realized to date) as a cutting tool to cut a workpiece is a highly productive manufacturing process. However, machining SiC using SPDT is a complex process and, while several experimental and analytical studies presented to date aid in the understanding of several critical processes of machining SiC, the current knowledge on the ductile behaviour of SiC is still sparse. This is due to a number of simultaneously occurring physical phenomena that may take place on multiple length and time scales. For example, nucleation of dislocation can take place at small inclusions that are of a few atoms in size and once nucleated, the interaction of these nucleations can manifest stresses on the micrometre length scales. The understanding of how stresses manifest during fracture in the brittle range, or dislocations/phase transformations in the ductile range, is crucial in understanding the brittle–ductile transition in SiC. Furthermore, there is a need to incorporate an appropriate simulation-based approach in the manufacturing research on SiC, owing primarily to the number of uncertainties in the experimental research that includes wear of the cutting tool, poor controllability of the nano-regime machining scale (effective thickness of cut), and coolant effects (interfacial phenomena between the tool, workpiece/chip and coolant), etc. In this review, these two problems are combined together to posit an improved understanding on the current theoretical knowledge on the SPDT of SiC obtained from molecular dynamics simulation.

Targeting the ubiquitin proteasome system in haematological malignancies

The ubiquitin proteasome system (UPS) plays a central role in cellular protein homeostasis through the targeted destruction of damaged/misfolded proteins and regulatory proteins that control critical cellular functions. The UPS comprises a sequential series of enzymatic activities to covalently attach ubiquitin to proteins to target them for degradation through the proteasome. Aberrancies within this system have been associated with transformation and tumourigenesis and thus, the UPS represents an attractive target for the development of anti-cancer therapies. The use of the first-in-class proteasome inhibitor, bortezomib, in the treatment of Plasma Cell Myeloma and Mantle Cell Lymphoma has validated the UPS as a therapeutic target. Following on its success, efforts are focused on the development of second-generation proteasome inhibitors and small molecule inhibitors of other components of the UPS. This review will provide an overview of the UPS and discuss current and novel therapies targeting the UPS.

Palynological perspectives on vegetation survey: a critical step for model-based reconstruction of Quaternary land cover

1. Quantitative reconstruction of past vegetation distribution and abundance from sedimentary pollen records provides an important baseline for understanding long term ecosystem dynamics and for the calibration of earth system process models such as regional-scale climate models, widely used to predict future environmental change. Most current approaches assume that the amount of pollen produced by each vegetation type, usually expressed as a relative pollen productivity term, is constant in space and time.
2. Estimates of relative pollen productivity can be extracted from extended R-value analysis (Parsons and Prentice, 1981) using comparisons between pollen assemblages deposited into sedimentary contexts, such as moss polsters, and measurements of the present day vegetation cover around the sampled location. Vegetation survey method has been shown to have a profound effect on estimates of model parameters (Bunting and Hjelle, 2010), therefore a standard method is an essential pre-requisite for testing some of the key assumptions of pollen-based reconstruction of past vegetation; such as the assumption that relative pollen productivity is effectively constant in space and time within a region or biome.
3. This paper systematically reviews the assumptions and methodology underlying current models of pollen dispersal and deposition, and thereby identifies the key characteristics of an effective vegetation survey method for estimating relative pollen productivity in a range of landscape contexts.
4. It then presents the methodology used in a current research project, developed during a practitioner workshop. The method selected is pragmatic, designed to be replicable by different research groups, usable in a wide range of habitats, and requiring minimum effort to collect adequate data for model calibration rather than representing some ideal or required approach. Using this common methodology will allow project members to collect multiple measurements of relative pollen productivity for major plant taxa from several northern European locations in order to test the assumption of uniformity of these values within the climatic range of the main taxa recorded in pollen records from the region.

Asking the Critical Questions: An Evaluation of Social Work Students' Experiences in an International Placement

Preparing social work students for the demands of changing social environments and to promote student mobility and interest in overseas employment opportunities have resulted in an increasing demand for international social work placements. The literature describes numerous examples of social work programmes that offer a wide variety of international placements. However, research about the actual benefit of undertaking an overseas placement is scant with limited empirical evidence on the profile of students participating, their experience of the tasks offered, the supervisory practice and the outcomes for students' professional learning and career. This study contributes to the existing body of literature by exploring the relevance of international field placements for students and is unique in that it draws its sample from students who have graduated so provides a distinctive perspective in which to compare their international placement with their other placement/s as well as evaluating what were the benefits and drawbacks for them in terms of their careers, employment opportunities and current professional practice.