254 research outputs found

    Zone-plate focusing of Bose-Einstein condensates for atom optics and erasable high-speed lithography of quantum electronic components

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    We show that Fresnel zone plates, fabricated in a solid surface, can sharply focus atomic Bose-Einstein condensates that quantum reflect from the surface or pass through the etched holes. The focusing process compresses the condensate by orders of magnitude despite inter-atomic repulsion. Crucially, the focusing dynamics are insensitive to quantum fluctuations of the atom cloud and largely preserve the condensates' coherence, suggesting applications in passive atom-optical elements, for example zone plate lenses that focus atomic matter waves and light at the same point to strengthen their interaction. We explore transmission zone-plate focusing of alkali atoms as a route to erasable and scalable lithography of quantum electronic components in two-dimensional electron gases embedded in semiconductor nanostructures. To do this, we calculate the density profile of a two-dimensional electron gas immediately below a patch of alkali atoms deposited on the surface of the nanostructure by zone-plate focusing. Our results reveal that surface-induced polarization of only a few thousand adsorbed atoms can locally deplete the electron gas. We show that, as a result, the focused deposition of alkali atoms by existing zone plates can create quantum electronic components on the 50 nm scale, comparable to that attainable by ion beam implantation but with minimal damage to either the nanostructure or electron gas.Comment: 13 pages, 7 figure

    Appreciative inquiry as a method of transforming identity and power in Pakistani women

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    This paper describes a three-year action research project that used Appreciative Inquiry to work with marginalised Pakistani women living in Sheffield. The research encountered many of the difficulties and dilemmas that have been previously identified in the theory and practice of Appreciative Inquiry. However, it also empowered the participants to develop critical thinking, particularly around issues of power and identity. Through generating authentic and untold stories, Appreciative Inquiry enabled participants to discuss, subvert and challenge the identities that had been constructed for them by sources of power within their community and culture. The paper describes the innovative application of Appreciative Inquiry, offers a theoretical response to criticisms of Appreciative Inquiry and suggests how it may be effective in enabling marginalised people to critically address issues of powe

    Gut evacuation rate and grazing impact of the krill Thysanoessa raschii and T. inermis

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    Gut evacuation rates and ingestion rates were measured for the krill Thysanoessa raschii and T. inermis in Godthåbsfjord, SW Greenland. Combined with biomass of the krill community, the grazing potential on phytoplankton along the fjord was estimated. Gut evacuation rates were 3.9 and 2.3 h−1 for T. raschii and T. inermis, respectively. Ingestion rates were 12.2 ± 7.5 µg C mg C−1 day−1 (n = 4) for T. inermis and 4.9 ± 3.2 µg C mg C−1 day−1 (n = 4) for T. raschii, corresponding to daily rations of 1.2 and 0.5 % body carbon day−1. Clearance experiments conducted in parallel to the gut evacuation experiment gave similar results for ingestion rates and daily rations. Krill biomass was highest in the central part of the fjord’s length, with T. raschii dominating. Community grazing rates from krill and copepods were comparable; however, their combined impact was low, estimated as <1 % of phytoplankton standing stock being removed per day during this late spring study

    Differentiation of Chronic Lymphocytic Leukemia B Cells into Immunoglobulin Secreting Cells Decreases LEF-1 Expression

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    Lymphocyte enhancer binding factor 1 (LEF-1) plays a crucial role in B lineage development and is only expressed in B cell precursors as B cell differentiation into mature B and plasma cells silences its expression. Chronic lymphocytic leukemia (CLL) cells aberrantly express LEF-1 and its expression is required for cellular survival. We hypothesized that modification of the differentiation status of CLL cells would result in loss of LEF-1 expression and eliminate the survival advantage provided by its aberrant expression. In this study, we first established a methodology that induces CLL cells to differentiate into immunoglobulin (Ig) secreting cells (ISC) using the TLR9 agonist, CpG, together with cytokines (CpG/c). CpG/c stimulation resulted in dramatic CLL cell phenotypic and morphologic changes, expression of cytoplasmic Ig, and secretion of light chain restricted Ig. CpG/c stimulation also resulted in decreased CLL cell LEF-1 expression and increased Blimp-1 expression, which is crucial for plasma cell differentiation. Further, Wnt pathway activation and cellular survival were impaired in differentiated CLL cells compared to undifferentiated CLL cells. These data support the notion that CLL can differentiate into ISC and that this triggers decreased leukemic cell survival secondary to the down regulation of LEF-1 and decreased Wnt pathway activation

    Abnormal accumulation of autophagic vesicles correlates with axonal and synaptic pathology in young Alzheimer’s mice hippocampus

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    Dystrophic neurites associated with amyloid plaques precede neuronal death and manifest early in Alzheimer’s disease (AD). In this work we have characterized the plaque-associated neuritic pathology in the hippocampus of young (4- to 6-month-old) PS1M146L/APP751SL mice model, as the initial degenerative process underlying functional disturbance prior to neuronal loss. Neuritic plaques accounted for almost all fibrillar deposits and an axonal origin of the dystrophies was demonstrated. The early induction of autophagy pathology was evidenced by increased protein levels of the autophagosome marker LC3 that was localized in the axonal dystrophies, and by electron microscopic identification of numerous autophagic vesicles filling and causing the axonal swellings. Early neuritic cytoskeletal defects determined by the presence of phosphorylated tau (AT8-positive) and actin–cofilin rods along with decreased levels of kinesin-1 and dynein motor proteins could be responsible for this extensive vesicle accumulation within dystrophic neurites. Although microsomal Aβ oligomers were identified, the presence of A11-immunopositive Aβ plaques also suggested a direct role of plaque-associated Aβ oligomers in defective axonal transport and disease progression. Most importantly, presynaptic terminals morphologically disrupted by abnormal autophagic vesicle buildup were identified ultrastructurally and further supported by synaptosome isolation. Finally, these early abnormalities in axonal and presynaptic structures might represent the morphological substrate of hippocampal dysfunction preceding synaptic and neuronal loss and could significantly contribute to AD pathology in the preclinical stages

    Beyond the public and private divide: Remapping transnational climate governance in de 21th century

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    This article provides a first step towards a better theoretical and empirical knowledge of the emerging arena of transnational climate governance. The need for such a re-conceptualization emerges from the increasing relevance of non-state and transnational approaches towards climate change mitigation at a time when the intergovernmental negotiation process has to overcome substantial stalemate and the international arena becomes increasingly fragmented. Based on a brief discussion of the increasing trend towards transnationalization and functional segmentation of the global climate governance arena, we argue that a remapping of climate governance is necessary and needs to take into account different spheres of authority beyond the public and international. Hence, we provide a brief analysis of how the public/private divide has been conceptualized in Political Science and International Relations. Subsequently, we analyse the emerging transnational climate governance arena. Analytically, we distinguish between different manifestations of transnational climate governance on a continuum ranging from delegated and shared public-private authority to fully non-state and private responses to the climate problem. We suggest that our remapping exercise presented in this article can be a useful starting point for future research on the role and relevance of transnational approaches to the global climate crisis

    Effect of TENS on pain in relation to central sensitization in patients with osteoarthritis of the knee: study protocol of a randomized controlled trial

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    <p>Abstract</p> <p>Background</p> <p>Central sensitization has recently been documented in patients with knee osteoarthritis (OAk). So far, the presence of central sensitization has not been considered as a confounding factor in studies assessing the pain inhibitory effect of tens on osteoarthritis of the knee. The purpose of this study is to explore the pain inhibitory effect of burst tens in OAk patients and to explore the prognostic value of central sensitization on the pain inhibitory effect of tens in OAk patients.</p> <p>Methods</p> <p>Patients with knee pain due to OAk will be recruited through advertisements in local media. Temporal summation, before and after a heterotopic noxious conditioning stimulation, will be measured. In addition, pain on a numeric rating score, WOMAC subscores for pain and function and global perceived effect will be assessed. Patients will be randomly allocated to one of two treatment groups (tens, sham tens). Follow-up measurements will be scheduled after a period of 6 and 12 weeks.</p> <p>Discussion</p> <p>Tens influences pain through the electrical stimulation of low-threshold A-beta cutaneous fibers. The responsiveness of central pain-signaling neurons of centrally sensitized OAk patients may be augmented to the input of these electrical stimuli. This would encompass an adverse therapy effect of tens. To increase treatment effectiveness it might be interesting to identify a subgroup of symptomatic OAk patients, i.e., non-sensitized patients, who are likely to benefit from burst tens.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01390285">NCT01390285</a></p

    Developmental expression of COE across the Metazoa supports a conserved role in neuronal cell-type specification and mesodermal development

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    The transcription factor COE (collier/olfactory-1/early B cell factor) is an unusual basic helix–loop–helix transcription factor as it lacks a basic domain and is maintained as a single copy gene in the genomes of all currently analysed non-vertebrate Metazoan genomes. Given the unique features of the COE gene, its proposed ancestral role in the specification of chemosensory neurons and the wealth of functional data from vertebrates and Drosophila, the evolutionary history of the COE gene can be readily investigated. We have examined the ways in which COE expression has diversified among the Metazoa by analysing its expression from representatives of four disparate invertebrate phyla: Ctenophora (Mnemiopsis leidyi); Mollusca (Haliotis asinina); Annelida (Capitella teleta and Chaetopterus) and Echinodermata (Strongylocentrotus purpuratus). In addition, we have studied COE function with knockdown experiments in S. purpuratus, which indicate that COE is likely to be involved in repressing serotonergic cell fate in the apical ganglion of dipleurula larvae. These analyses suggest that COE has played an important role in the evolution of ectodermally derived tissues (likely primarily nervous tissues) and mesodermally derived tissues. Our results provide a broad evolutionary foundation from which further studies aimed at the functional characterisation and evolution of COE can be investigated

    Circadian Desynchrony Promotes Metabolic Disruption in a Mouse Model of Shiftwork

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    Shiftwork is associated with adverse metabolic pathophysiology, and the rising incidence of shiftwork in modern societies is thought to contribute to the worldwide increase in obesity and metabolic syndrome. The underlying mechanisms are largely unknown, but may involve direct physiological effects of nocturnal light exposure, or indirect consequences of perturbed endogenous circadian clocks. This study employs a two-week paradigm in mice to model the early molecular and physiological effects of shiftwork. Two weeks of timed sleep restriction has moderate effects on diurnal activity patterns, feeding behavior, and clock gene regulation in the circadian pacemaker of the suprachiasmatic nucleus. In contrast, microarray analyses reveal global disruption of diurnal liver transcriptome rhythms, enriched for pathways involved in glucose and lipid metabolism and correlating with first indications of altered metabolism. Although altered food timing itself is not sufficient to provoke these effects, stabilizing peripheral clocks by timed food access can restore molecular rhythms and metabolic function under sleep restriction conditions. This study suggests that peripheral circadian desynchrony marks an early event in the metabolic disruption associated with chronic shiftwork. Thus, strengthening the peripheral circadian system by minimizing food intake during night shifts may counteract the adverse physiological consequences frequently observed in human shift workers
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