The string partition function in Hull's doubled formalism

T-duality is one of the essential elements of string theory. Recently, Hull has developed a formalism where the dimension of the target space is doubled so as to make T-duality manifest. This is then supplemented with a constraint equation that allows the connection to the usual string sigma model. This paper analyses the partition function of the doubled formalism by interpreting the constraint equation as that of a chiral scalar and then using holomorphic factorisation techniques to determine the partition function. We find there is quantum equivalence to the ordinary string once the topological interaction term is included.Comment: 16 pages, latex, v2 typos corrected, v3 some comments adde

The leukaemia stem cell: similarities, differences and clinical prospects in CML and AML

For two decades, leukaemia stem cells (LSCs) in chronic myeloid leukaemia (CML) and acute myeloid leukaemia (AML) have been advanced paradigms for the cancer stem cell field. In CML, the acquisition of the fusion tyrosine kinase BCR–ABL1 in a haematopoietic stem cell drives its transformation to become a LSC. In AML, LSCs can arise from multiple cell types through the activity of a number of oncogenic drivers and pre-leukaemic events, adding further layers of context and genetic and cellular heterogeneity to AML LSCs not observed in most cases of CML. Furthermore, LSCs from both AML and CML can be refractory to standard-of-care therapies and persist in patients, diversify clonally and serve as reservoirs to drive relapse, recurrence or progression to more aggressive forms. Despite these complexities, LSCs in both diseases share biological features, making them distinct from other CML or AML progenitor cells and from normal haematopoietic stem cells. These features may represent Achilles’ heels against which novel therapies can be developed. Here, we review many of the similarities and differences that exist between LSCs in CML and AML and examine the therapeutic strategies that could be used to eradicate them

Foxp3 molecular dynamics in Treg in juvenile idiopathic arthritis

Since the identification of the regulatory T-cell (Treg)-associated transcription factor Foxp3, there have been intensive research efforts to understand its biology and roles in maintaining immune homeostasis. It is well established that thymic selection of a repertoire of self-reactive Foxp3+ T-cells provides an essential mechanism to minimize reactions to self-antigens in the periphery, and thus aid in the prevention of autoimmunity. It is clear from both genetic and immunological analyses of juvenile idiopathic arthritis (JIA) patients that T-cells have a strong role to play in both the initiation and propagation of disease. The current paradigm is to view autoimmunity as a consequence of an imbalance between inflammatory and immunoregulatory mechanisms. This view has led to the assigning of cells and inflammatory mediators to different classes based on their assumed pro- or anti-inflammatory roles. This is typically reported as ratios of effector T-cells to Treg cells. Problematically, many analyses are based on static “snapshots-in-time,” even though both mouse models and human patient studies have highlighted the dynamic nature of Foxp3+ T-cells in vivo, which can exhibit plasticity and time-dependent functional states. In this review, we discuss the role of Foxp3 dynamics in the control of T-cell responses in childhood arthritis, by reviewing evidence in humans and relevant mouse models of inflammatory disease. Whilst the cellular dynamics of Treg have been well evaluated—leading to standard data outputs such as frequency, quantity and quality (often assessed by in vitro suppressive capacity)—we discuss how recent insights into the molecular dynamics of Foxp3 transcription and its post-translational control may open up tantalizing new avenues for immunotherapies to treat autoimmune arthritis

Substitutional and Interstitial Diffusion in alpha2-Ti3Al(O)

The reaction between Al2O3 and alpha2-Ti3Al was studied with a series of Al2O3/alpha2-Ti3Al multiphase diffusion couples annealed at 900, 1000 and 1100 C. The diffusion-paths were found to strongly depend on alpha2- Ti3Al(O) composition. For alloys with low oxygen concentrations the reaction involved the reduction of Al2O3, the formation of a gamma-TiAl reaction-layer and diffusion of Al and O into the alpha2-Ti3Al substrate. Measured concentration profiles across the interaction-zone showed "up-hill" diffusion of O in alpha2-Ti3Al(O) indicating a significant thermodynamic interaction between O and Al, Ti or both. Diffusion coefficients for the interstitial O in alpha2-Ti3Al(O) were determined independently from the interdiffusion of Ti and Al on the substitutional lattice. Diffusion coefficients are reported for alpha2-Ti3Al(O) as well as gamma-TiAl. Interpretation of the results were aided with the subsequent measurement of the activities of Al, Ti and O in alpha 2-Ti3Al(O) by Knudsen effusion-cell mass spectrometry

A note on the M2-M5 brane system and fuzzy spheres

This note covers various aspects of recent attempts to describe membranes ending on fivebranes using fuzzy geometry. In particular, we examine the Basu-Harvey equation and its relation to the Nahm equation as well as the consequences of using a non-associative algebra for the fuzzy three-sphere. This produces the tantalising result that the fuzzy funnel solution corresponding to Q coincident membranes ending on a five-brane has $Q^{3/2}$ degrees of freedom.Comment: 17 pages, late

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

Treatment of diabetic retinopathy through neuropeptide Y-mediated enhancement of neurovascular microenvironment

Diabetic retinopathy (DR) is one of the most severe clinical manifestations of diabetes mellitus and a major cause of blindness. DR is principally a microvascular disease, although the pathogenesis also involves metabolic reactive intermediates which induce neuronal and glial activation resulting in disruption of the neurovascular unit and regulation of the microvasculature. However, the impact of neural/glial activation in DR remains controversial, notwithstanding our understanding as to when neural/glial activation occurs in the course of disease. The objective of this study was to determine a potential protective role of neuropeptide Y (NPY) using an established model of DR permissive to N‐methyl‐D‐aspartate (NMDA)‐induced excitotoxic apoptosis of retinal ganglion cells (RGC) and vascular endothelial growth factor (VEGF)‐induced vascular leakage. In vitro evaluation using primary retinal endothelial cells demonstrates that NPY promotes vascular integrity, demonstrated by maintained tight junction protein expression and reduced permeability in response to VEGF treatment. Furthermore, ex vivo assessment of retinal tissue explants shows that NPY can protect RGC from excitotoxic‐induced apoptosis. In vivo clinical imaging and ex vivo tissue analysis in the diabetic model permitted assessment of NPY treatment in relation to neural and endothelial changes. The neuroprotective effects of NPY were confirmed by attenuating NMDA‐induced retinal neural apoptosis and able to maintain inner retinal vascular integrity. These findings could have important clinical implications and offer novel therapeutic approaches for the treatment in the early stages of DR

Five-brane Calibrations and Fuzzy Funnels

We present a generalisation of the Basu-Harvey equation that describes membranes ending on intersecting five-brane configurations corresponding to various calibrated geometries.Comment: 20 pages, latex, v2: typos fixed and refs adde

Therapeutic effect of an intensive, comprehensive aphasia program: Aphasia LIFT

The development of intensive, comprehensive aphasia programs (ICAPs) is increasing due to evidence in favour of greater treatment intensity (Cherney, Patterson, Raymer, Frymark, & Schooling, 2008), the adoption of a broad, holistic, biopsychosocial approach in aphasia rehabilitation (Byng & Duchan, 2005; Kagan et al., 2008; Martin, Thompson, & Worrall, 2008; Simmons-Mackie & Kagan, 2007), and the desire to meet the needs of people with aphasia and their family members in therapy (Howe et al., 2012; Worrall et al., 2012). ICAPs comprise a range of therapy approaches (individual therapy, group therapy, patient/family education, technology), delivered at high intensity (minimum of three hours per day over at least two weeks), to a defined group of participants within a specified amount of time (Cherney, Worrall, & Rose, 2012). Aphasia LIFT (Language Impairment and Functioning Therapy) is a research-based ICAP that uses evidence-based therapy approaches to target language and functioning across the World Health Organization’s International Classification of Functioning, Disability and Health (ICF) domains (WHO, 2001). The aim of this study was to determine the therapeutic effect of Aphasia LIFT on language impairment, functional communication, and communication-related quality of life (QOL)