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

LOS oligosaccharide modification enhances dendritic cell responses to meningococcal native outer membrane vesicles expressing a non toxic lipid A.

Outer membrane vesicles (OMV) are released by many bacteria, and contain immunogenic antigens in addition to harmful inflammatory factors, like lipopolysaccharides. Chemically detoxified OMV have been used in vaccines against Neisseria meningitidis (Nm), however little is known about their interaction with antigen presenting cells. In this study, we investigated the interaction of Nm OMV with human dendritic cells (DC) to gain further understanding of their biological activity. We engineered a novel serogroup B Nm that is unencapsulated (siaD), expresses pentacylated lipid A (lpxL1), hence conferring reduced toxicity, and expresses an lgtB oligosaccharide structure designed to target OMV to DC via DC-SIGN. We show that the lgtB moiety is critical for internalization of NOMV by DC. Furthermore, the lgtB moiety significantly enhances DC maturation, IL-10 and IL-23 production in the presence of a pentacylated lipid A. Whilst different DC phenotypes were observed for each NOMV, this had little effect on Th1 and Th2 cell differentiation, however lgtB significantly increased Th17 cell expansion in the presence of pentacylated lipid A. We believe that lgtB/lpxL1 NOMV should be considered further as a vaccine vector, particularly considering the importance of lgtB in antigen uptake and further human studies on antigen specific responses should be considered

BCR-ABL activity and its response to drugs can be determined in CD34+ CML stem cells by CrkL phosphorylation status using flow cytometry.

In chronic myeloid leukaemia, CD34(+) stem/progenitor cells appear resistant to imatinib mesylate (IM) in vitro and in vivo. To investigate the underlying mechanism(s) of IM resistance, it is essential to quantify Bcr-Abl kinase status at the stem cell level. We developed a flow cytometry method to measure CrkL phosphorylation (P-CrkL) in samples with <10(4) cells. The method was first validated in wild-type (K562) and mutant (BAF3) BCR-ABL(+) as well as BCR-ABL(-) (HL60) cell lines. In response to increasing IM concentration, there was a linear reduction in P-CrkL, which was Bcr-Abl specific and correlated with known resistance. The results were comparable to those from Western blotting. The method also proved to be reproducible with small samples of normal and Ph(+) CD34(+) cells and was able to discriminate between Ph(-), sensitive and resistant Ph(+) cells. This assay should now enable investigators to unravel the mechanism(s) of IM resistance in stem cells

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&lt;sup&gt;+&lt;/sup&gt;38&lt;sup&gt;lo&lt;/sup&gt;) by downregulation of Mcl-1 protein. In contrast to our previous findings with TKIs, omacetaxine did not accumulate undivided cells &lt;i&gt;in vitro&lt;/i&gt;. 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&lt;sup&gt;+&lt;/sup&gt; 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

The Suppression of Irrelevant Semantic Representations in Parkinson’s Disease

The impairment of lexical-semantic inhibition mechanisms in Parkinson’s disease (PD) remains a source of contention. In order to observe whether people with PD are able to suppress irrelevant semantic information during picture naming, the present study employed an object-based negative priming paradigm with 16 participants with PD and 13 healthy controls. The task required participants to name a red target image while ignoring a superimposed, green distractor image. The semantic relationship between the distractor image and the target image of the subsequent trial was manipulated, such that the distractor image was identical, semantically related, or semantically unrelated to said target image. The PD group and the control group were slower in naming a target image that had previously served as a distractor image, relative to naming a target image that was unrelated to the previous distractor image. Thus, a negative priming effect was present in both groups. Furthermore, no significant difference in the magnitude of this effect was observed between the control and PD groups. When considered in the context of existing literature surrounding negative priming in PD, these results suggest that inhibition is subserved by multiple, domain-specific mechanisms and that the inhibitory processing of visual-semantic stimuli is intact in PD

Aphasia Recovery: When, How and Who to Treat?

PURPOSE OF REVIEW: We now know that speech and language therapy (SALT) is effective in the rehabilitation of aphasia; however, there remains much individual variability in the response to interventions. So, what works for whom, when and how? RECENT FINDINGS: This review evaluates the current evidence for the efficacy of predominantly impairment-focused aphasia interventions with respect to optimal dose, intensity, timing and distribution or spacing of treatment. We conclude that sufficient dose of treatment is required to enable clinical gains and that e-therapies are a promising and practical way to achieve this goal. In addition, aphasia can be associated with other cognitive deficits and may lead to secondary effects such as low mood and social isolation. In order to personalise individual treatments to optimise recovery, we need to develop a greater understanding of the interactions between these factors

Soluble CD200 Correlates With Interleukin-6 Levels in Sera of COPD Patients: Potential Implication of the CD200/CD200R Axis in the Disease Course

BACKGROUND: COPD represents a multifactorial lung disorder with high morbidity and mortality. Despite intensive research concerning the underlying disease mechanisms, the involvement of the CD200/CD200R axis in supporting or preventing the onset of COPD has not yet been addressed. Since the CD200/CD200R axis is crucially implicated in the maintenance of pulmonary immune homeostasis, we hypothesized that it might be involved in controlling the onset of COPD. METHODS: To address this, we analyzed the serum samples from COPD patients and normal controls for soluble (s) CD200 and correlated the data to COPD-relevant clinical parameters. In addition, basic studies were conducted in CD200-deficient and wild-type mice in which COPD-like inflammation was induced with elastase/LPS followed by lung and serum component analysis. RESULTS: We observed a positive correlation between serum sCD200 and IL-6 levels as well as a trend toward a negative correlation of sCD200 with vitamin D3 in COPD patients. Further investigations in mice revealed that despite elevated serum concentration of MMP-9 in CD200KO mice, the early onset of COPD-like lung inflammation was similar in CD200-deficient and wild-type animals in terms of immune cell infiltration, emphysematous changes, and mucus overproduction. CONCLUSIONS: While our murine studies suggest that the co-inhibitory molecule CD200 does not appear to play a prominent role in the early onset of COPD-like features, correlation of sCD200 serum levels with COPD-related parameters in humans with established disease revealed that the CD200/CD200R axis may be mechanistically linked to the disease course in COPD patients

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

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 group’s 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

Glacier velocities and dynamic ice discharge from the Queen Elizabeth Islands, Nunavut, Canada

Recent studies indicate an increase in glacier mass loss from the Canadian Arctic Archipelago as a result of warmer summer air temperatures. However, no complete assessment of dynamic ice discharge from this region exists. We present the first complete surface velocity mapping of all ice masses in the Queen Elizabeth Islands and show that these ice masses discharged ~2.6 ± 0.8 Gt a−1 of ice to the oceans in winter 2012. Approximately 50% of the dynamic discharge was channeled through non surge-type Trinity and Wykeham Glaciers alone. Dynamic discharge of the surge-type Mittie Glacier varied from 0.90 ± 0.09 Gt a−1 during its 2003 surge to 0.02 ± 0.02 Gt a−1 during quiescence in 2012, highlighting the importance of surge-type glaciers for interannual variability in regional mass loss. Queen Elizabeth Islands glaciers currently account for ~7.5% of reported dynamic discharge from Arctic ice masses outside Greenland.We thank NSERC, Canada Foundation for Innovation, Ontario Research Fund, ArcticNet, Ontario Graduate Scholarship, University of Ottawa and the NSERC Canada Graduate Scholarship for funding. RADARSAT-2 data were provided by MacDonald, Dettwiler and Associates under the RADARSAT-2 Government Data Allocation administrated by the Canadian Space Agency. Support to DB is provided through the Climate Change Geosciences Program, Earth Sciences Sector, Natural Resources Canada (ESS Contribution #20130293). We also acknowledge support from U.K NERC for grants R3/12469 and NE/K004999 to JAD.This is the accepted version of an article published in Geophysical Research Letters. An edited version of this paper was published by AGU. Copyright (2014) American Geophysical Union. The final version is available at http://onlinelibrary.wiley.com/doi/10.1002/2013GL058558/abstract;jsessionid=6A3AD907C4383DA5D4E20C4924D6EC18.f02t02