506 research outputs found
Holographic Thermalization
Using the AdS/CFT correspondence, we probe the scale-dependence of
thermalization in strongly coupled field theories following a quench, via
calculations of two-point functions, Wilson loops and entanglement entropy in
d=2,3,4. In the saddlepoint approximation these probes are computed in AdS
space in terms of invariant geometric objects - geodesics, minimal surfaces and
minimal volumes. Our calculations for two-dimensional field theories are
analytical. In our strongly coupled setting, all probes in all dimensions share
certain universal features in their thermalization: (1) a slight delay in the
onset of thermalization, (2) an apparent non-analyticity at the endpoint of
thermalization, (3) top-down thermalization where the UV thermalizes first. For
homogeneous initial conditions the entanglement entropy thermalizes slowest,
and sets a timescale for equilibration that saturates a causality bound over
the range of scales studied. The growth rate of entanglement entropy density is
nearly volume-independent for small volumes, but slows for larger volumes.Comment: 39 pages, 24 figure
Omacetaxine may have a role in chronic myeloid leukaemia eradication through downregulation of Mcl-1 and induction of apoptosis in stem/progenitor cells
Chronic myeloid leukaemia (CML) is maintained by a rare population of tyrosine kinase inhibitor (TKI)-insensitive malignant stem cells. Our long-term aim is to find a BcrAbl-independent drug that can be combined with a TKI to improve overall disease response in chronic-phase CML. Omacetaxine mepesuccinate, a first in class cetaxine, has been evaluated by clinical trials in TKI-insensitive/resistant CML. Omacetaxine inhibits synthesis of anti-apoptotic proteins of the Bcl-2 family, including (myeloid cell leukaemia) Mcl-1, leading to cell death. Omacetaxine effectively induced apoptosis in primary CML stem cells (CD34<sup>+</sup>38<sup>lo</sup>) by downregulation of Mcl-1 protein. In contrast to our previous findings with TKIs, omacetaxine did not accumulate undivided cells <i>in vitro</i>. Furthermore, the functionality of surviving stem cells following omacetaxine exposure was significantly reduced in a dose-dependant manner, as determined by colony forming cell and the more stringent long-term culture initiating cell colony assays. This stem cell-directed activity was not limited to CML stem cells as both normal and non-CML CD34<sup>+</sup> cells were sensitive to inhibition. Thus, although omacetaxine is not leukaemia stem cell specific, its ability to induce apoptosis of leukaemic stem cells distinguishes it from TKIs and creates the potential for a curative strategy for persistent disease
Analysis of model rotor blade pressures during parallel interaction with twin vortices
This paper presents and provides analysis of unsteady surface pressures measured on a model rotor blade as the blade experienced near parallel blade vortex interaction with a twin vortex system. To provide a basis for analysis, the vortex system was characterized by hot-wire measurements made in the interaction plane but in the absence of the rotor. The unsteady pressure response resulting from a single vortex interaction is then presented to provide a frame of reference for the twin vortex results. A series of twin vortex interaction cases are then presented and analyzed. It is shown that the unsteady blade pressures and forces are very sensitive to the inclination angle and separation distance of the vortex pair. When the vortex cores lie almost parallel to the blade chord, the interaction is characterized by a two-stage response associated with the sequential passage of the two cores. Conversely, when the cores lie on a plane that is almost perpendicular to the blade chord, the response is similar to that of a single vortex interaction. In all cases, the normal force response is consistent with the distribution of vertical velocity in the flow field of the vortex system. The pitching moment response, on the other hand, depends on the localized suction associated with the vortex cores as they traverse the blade chord
Single Eye mRNA-Seq Reveals Normalisation of the Retinal Microglial Transcriptome Following Acute Inflammation
Background: Whether retinal microglia can maintain or restore immune homeostasis during and after inflammation is unclear. We performed single-eye mRNA-sequencing on microglia at different timepoints following a single inflammatory stimulus to characterise their transcriptome during and after resolution of endotoxin-induced uveitis (EIU).
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Experimental Approach: Cx3cr1CreER:R26-tdTomato (C57BL/6) male heterozygotes were administered tamoxifen via different regimes at 4â5 weeks of age. Four weeks post-tamoxifen, mice were injected intravitreally with 10 ng lipopolysaccharide (endotoxin induced uveitis, EIU). Six-hundred retinal microglia were obtained by FACS from individual naĂŻve retinas and at 4 h, 18 h, and 2 weeks following EIU induction. Samples were sequenced to a depth of up to 16.7 million reads using the SMART-Seq v4 Ultra Low Input RNA kit. The data was analysed using Partek software and Ingenuity Pathway Analysis. Genes were considered differentially-expressed (DEG) if the FDR step-up p-value was â€0.05 and the fold-change was ℱ2.
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Results: Flow cytometric analysis indicates that the Cx3cr1CreER:R26-tdTomato strain is both sensitive (>95% tagging) and specific (>95% specificity) for microglia when tamoxifen is administered topically to the eye for 3 days. During âearlyâ activation, 613 DEGs were identified. In contrast, 537 DEGs were observed during peak cellular infiltrate and none at 2 weeks, compared to baseline controls (1,069 total unique DEGs). Key marker changes were validated by qPCR, flow cytometry, and fluorescence microscopy. C5AR1 was identified and validated as a robust marker of differentiating microglial subsets during an LPS response.
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Conclusion: Using EIU to provide a single defined inflammatory stimulus, mRNA-Seq identified acute transcriptional changes in retinal microglia which returned to their original transcriptome after 2 weeks. Yolk-sac derived microglia are capable of restoring their homeostatic state after acute inflammation
Shaping electron wave functions in a carbon nanotube with a parallel magnetic field
A magnetic field, through its vector potential, usually causes measurable
changes in the electron wave function only in the direction transverse to the
field. Here we demonstrate experimentally and theoretically that in carbon
nanotube quantum dots, combining cylindrical topology and bipartite hexagonal
lattice, a magnetic field along the nanotube axis impacts also the longitudinal
profile of the electronic states. With the high (up to 17T) magnetic fields in
our experiment the wave functions can be tuned all the way from "half-wave
resonator" shape, with nodes at both ends, to "quarter-wave resonator" shape,
with an antinode at one end. This in turn causes a distinct dependence of the
conductance on the magnetic field. Our results demonstrate a new strategy for
the control of wave functions using magnetic fields in quantum systems with
nontrivial lattice and topology.Comment: 5 figure
A Double Sigma Model for Double Field Theory
We define a sigma model with doubled target space and calculate its
background field equations. These coincide with generalised metric equation of
motion of double field theory, thus the double field theory is the effective
field theory for the sigma model.Comment: 26 pages, v1: 37 pages, v2: references added, v3: updated to match
published version - background and detail of calculations substantially
condensed, motivation expanded, refs added, results unchange
Native-English-Speaking Teachers:Disconnections Between Theory, Research, and Practice
Native-English-speaking teachers (NESTs) have long been in demand for perceived benefits of the skills they bring to the classroom. However, the notion that native speakers provide the best models of the target language and thus make the best teachers of the language has been criticised in the literature. This article reports on the disconnection between academic literature on NESTs and the realities they report. Drawing on data from an investigation into NEST schemes globally, the article suggests that lived classroom experiences of NESTs are complex, They are also often bilingual, experienced, and qualified, and regard local English teachers (LETs) they work with as experts and in control of how English is practised in the classroom. These characteristics contrast with much of the academic literature, which explores the concept of native speakerism, which tends to view NESTs negatively. The article proposes that one reason for the disconnection between theory and practice is the parallel lives of researchers and teachers, whether NESTs or LETs. Thus, each groupâs realities and concerns are not always understood by the other. The article suggests that a substantial group of bilingual and bicultural NESTs consider the country where work home, so future theorisations of NESTs and native speakerism should take account of these teachers
The relationship between the perception of distributed leadership in secondary schools and teachers' and teacher leaders' job satisfaction and organizational commitment
This study investigates the relation between distributed leadership, the cohesion of the leadership team, participative decision-making, context variables, and the organizational commitment and job satisfaction of teachers and teacher leaders. A questionnaire was administered to teachers and teacher leaders (n=1770) from 46 large secondary schools. Multiple regression analyses and path analyses revealed that the study variables explained significant variance in organizational commitment. The degree of explained variance for job satisfaction was considerably lower compared to organizational commitment. Most striking was that the cohesion of the leadership team and the amount of leadership support was strongly related to organizational commitment, and indirectly to job satisfaction. Decentralization of leadership functions was weakly related to organizational commitment and job satisfaction
Quantitative Assessment of Experimental Ocular Inflammatory Disease
Ocular inflammation imposes a high medical burden on patients and substantial costs on the health-care systems that mange these often chronic and debilitating diseases. Many clinical phenotypes are recognized and classifying the severity of inflammation in an eye with uveitis is an ongoing challenge. With the widespread application of optical coherence tomography in the clinic has come the impetus for more robust methods to compare disease between different patients and different treatment centers. Models can recapitulate many of the features seen in the clinic, but until recently the quality of imaging available has lagged that applied in humans. In the model experimental autoimmune uveitis (EAU), we highlight three linked clinical states that produce retinal vulnerability to inflammation, all different from healthy tissue, but distinct from each other. Deploying longitudinal, multimodal imaging approaches can be coupled to analysis in the tissue of changes in architecture, cell content and function. This can enrich our understanding of pathology, increase the sensitivity with which the impacts of therapeutic interventions are assessed and address questions of tissue regeneration and repair. Modern image processing, including the application of artificial intelligence, in the context of such models of disease can lay a foundation for new approaches to monitoring tissue health
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