Target Spaces from Chiral Gauge Theories

Chiral gauge theories in two dimensions with (0,2) supersymmetry are central in the study of string compactifications. Remarkably little is known about generic (0,2) theories. We consider theories with branches on which multiplets with a net gauge anomaly become massive. The simplest example is a relevant perturbation of the gauge theory that flows to the CP(n) model. To compute the effective action, we derive a useful set of Feynman rules for (0,2) supergraphs. From the effective action, we see that the infra-red geometry reflects the gauge anomaly by the presence of a boundary at finite distance. In generic examples, there are boundaries, fluxes and branes; the resulting spaces are non-Kahler

Promoting Exercise Performance in Adults with Intellectual Disabilities Through Visual Schedules and Systematic Prompting

Please download pdf version here

Optimal discrete stopping times for reliability growth tests

Often, the duration of a reliability growth development test is specified in advance and the decision to terminate or continue testing is conducted at discrete time intervals. These features are normally not captured by reliability growth models. This paper adapts a standard reliability growth model to determine the optimal time for which to plan to terminate testing. The underlying stochastic process is developed from an Order Statistic argument with Bayesian inference used to estimate the number of faults within the design and classical inference procedures used to assess the rate of fault detection. Inference procedures within this framework are explored where it is shown the Maximum Likelihood Estimators possess a small bias and converges to the Minimum Variance Unbiased Estimator after few tests for designs with moderate number of faults. It is shown that the Likelihood function can be bimodal when there is conflict between the observed rate of fault detection and the prior distribution describing the number of faults in the design. An illustrative example is provided

Efficacy and cost-effectiveness of a community-based model of care for older patients with complex needs: A study protocol for a multicentre randomised controlled trial using a stepped wedge cluster design

© 2018 The Author(s). Background: Community-dwelling older persons with complex care needs may deteriorate rapidly and require hospitalisation if they receive inadequate support for their conditions in the community. Intervention: A comprehensive, multidimensional geriatric assessment with care coordination was performed in a community setting - Older Persons ENablement And Rehabilitation for Complex Health conditions (OPEN ARCH). Objectives: This study will assess the acceptability and determine the impact of the OPEN ARCH intervention on the health and quality of life outcomes, health and social services utilisation of older people with multiple chronic conditions and emerging complex care needs. An economic evaluation will determine whether OPEN ARCH is cost-effective when compared to the standard care. Methods/design: This multicentre randomised controlled trial uses a stepped wedge cluster design with repeated cross-sectional samples. General practitioners (GPs; n ≥ 10) will be randomised as 'clusters' at baseline using simple randomisation. Each GP cluster will recruit 10-12 participants. Data will be collected on each participant at 3-month intervals (- 3, 0, 3, 6 and 9 months). The primary outcome is health and social service utilisation as measured by Emergency Department presentations, hospital admissions, in-patient bed days, allied health and community support services. Secondary outcomes include functional status, quality of life and participants' satisfaction. Cost-effectiveness of the intervention will be assessed as the change to cost outcomes, including the cost of implementing the intervention and subsequent use of services, and the change to health benefits represented by quality adjusted life years. Discussion: The results will have direct implications for the design and wider implementation of this new model of care for community-dwelling older persons with complex care needs. Additionally, it will contribute to the evidence base on acceptability, efficacy and cost-effectiveness of the intervention for this high-risk group of older people. Trial registration: Australian New Zealand Clinical Trials Registry, ACTRN12617000198325p. Registered on 6 February 2017

Cell Surface Remodeling by Plasmin: A New Function for an Old Enzyme

Plasmin, one of the most potent and reactive serine proteases, is involved in various physiological processes, including embryo development, thrombolysis, wound healing and cancer progression. The proteolytic activity of plasmin is tightly regulated through activation of its precursor, plasminogen, only at specific times and in defined locales as well as through inhibition of active plasmin by its abundant natural inhibitors. By exploiting the plasminogen activating system and overexpressing distinct components of the plasminogen activation cascade, such as pro-uPA, uPAR and plasminogen receptors, malignant cells can enhance the generation of plasmin which in turn, modifies the tumor microenvironment to sustain cancer progression. While plasmin-mediated degradation and modification of extracellular matrix proteins, release of growth factors and cytokines from the stroma as well as activation of several matrix metalloproteinase zymogens, all have been a focus of cancer research studies for decades, the ability of plasmin to cleave transmembrane molecules and thereby to generate functionally important cleaved products which induce outside-in signal transduction, has just begun to receive sufficient attention. Herein, we highlight this relatively understudied, but important function of the plasmin enzyme as it is generated de novo at the interface between cross-talking cancer and host cells

One-Loop MHV Amplitudes in Supersymmetric Gauge Theories

Using CSW rules for constructing scalar Feynman diagrams from MHV vertices, we compute the contribution of $\mathcal {N}=1$ chiral multiplet to one-loop MHV gluon amplitude. The result agrees with the one obtained previously using unitarity-based methods, thereby demonstrating the validity of the MHV-diagram technique, in the case of one-loop MHV amplitudes, for all massless supersymmetric theories.Comment: 20 pages, 5 figure

Scalar diagrammatic rules for Born amplitudes in QCD

We show that all Born amplitudes in QCD can be calculated from scalar propagators and a set of three- and four-valent vertices. In particular, our approach includes amplitudes with any number of quark pairs. The quarks may be massless or massive. The proof of the formalism is given entirely within quantum field theory.Comment: 20 pages, references adde

A gp41 MPER-specific llama VHH requires a hydrophobic CDR3 for neutralization but not for antigen recognition

The membrane proximal external region (MPER) of the HIV-1 glycoprotein gp41 is targeted by the broadly neutralizing antibodies 2F5 and 4E10. To date, no immunization regimen in animals or humans has produced HIV-1 neutralizing MPER-specific antibodies. We immunized llamas with gp41-MPER proteoliposomes and selected a MPER-specific single chain antibody (VHH), 2H10, whose epitope overlaps with that of mAb 2F5. Bi-2H10, a bivalent form of 2H10, which displayed an approximately 20-fold increased affinity compared to the monovalent 2H10, neutralized various sensitive and resistant HIV-1 strains, as well as SHIV strains in TZM-bl cells. X-ray and NMR analyses combined with mutagenesis and modeling revealed that 2H10 recognizes its gp41 epitope in a helical conformation. Notably, tryptophan 100 at the tip of the long CDR3 is not required for gp41 interaction but essential for neutralization. Thus bi-2H10 is an anti-MPER antibody generated by immunization that requires hydrophobic CDR3 determinants in addition to epitope recognition for neutralization similar to the mode of neutralization employed by mAbs 2F5 and 4E10

Electrical stimulation using conductive polymer polypyrrole promotes differentiation of human neural stem cells: a biocompatible platform for translational neural tissue engineering

Conductive polymers (CPs) are organic materials that hold great promise for biomedicine. Potential applications include in vitro or implantable electrodes for excitable cell recording and stimulation, and conductive scaffolds for cell support and tissue engineering. Here we demonstrate the utility of electroactive CP Polypyrrole (PPy) containing the anionic dopant dodecylbenzenesulfonate (DBS) to differentiate novel clinically relevant human neural stem cells (hNSCs). Electrical stimulation of PPy(DBS) induced hNSCs to predominantly β-III Tubulin (Tuj1) expressing neurons, with lower induction of glial fibrillary acidic protein (GFAP) expressing glial cells. In addition, stimulated cultures comprised nodes or clusters of neurons with longer neurites and greater branching than unstimulated cultures. Cell clusters showed a similar spatial distribution to regions of higher conductivity on the film surface. Our findings support the use of electrical stimulation to promote neuronal induction and the biocompatibility of PPy(DBS) with hNSCs, and opens up the possibility of identifying novel mechanisms of fate determination of differentiating human stem cells for advanced in vitro modelling, translational drug discovery and regenerative medicine

Wet-Spun Trojan Horse Cell Constructs for Engineering Muscle

Engineering of 3D regenerative skeletal muscle tissue constructs (skMTCs) using hydrogels containing muscle precursor cells (MPCs) is of potential benefit for repairing Volumetric Muscle Loss (VML) arising from trauma (e.g., road/industrial accident, war injury) or for restoration of functional muscle mass in disease (e.g., Muscular Dystrophy, muscle atrophy). Additive Biofabrication (AdBiofab) technologies make possible fabrication of 3D regenerative skMTCs that can be tailored to specific delivery requirements of VML or functional muscle restoration. Whilst 3D printing is useful for printing constructs of many tissue types, the necessity of a balanced compromise between cell type, required construct size and material/fabrication process cyto-compatibility can make the choice of 3D printing a secondary alternative to other biofabrication methods such as wet-spinning. Alternatively, wet-spinning is more amenable to formation of fibers rather than (small) layered 3D-Printed constructs. This study describes the fabrication of biosynthetic alginate fibers containing MPCs and their use for delivery of dystrophin-expressing cells to dystrophic muscle in the mdx mouse model of Duchenne Muscular Dystrophy (DMD) compared to poly(DL-lactic-co-glycolic acid) copolymer (PLA:PLGA) topically-seeded with myoblasts. In addition, this study introduces a novel method by which to create 3D layered wet-spun alginate skMTCs for bulk mass delivery of MPCs to VML lesions. As such, this work introduces the concept of “Trojan Horse” Fiber MTCs (TH-fMTCs) and 3d Mesh-MTCs (TH-mMTCs) for delivery of regenerative MPCs to diseased and damaged muscle, respectively