Oxide-apertured microcavity single-photon emitting diode

We have developed a microcavity single-photon source based on a single quantum dot within a planar cavity in which wet-oxidation of a high-aluminium content layer provides lateral confinement of both the photonic mode and the injection current. Lateral confinement of the optical mode in optically pumped structures produces a strong enhancement of the radiative decay rate. Using microcavity structures with doped contact layers, we demonstrate a single-photon emitting diode where current may be injected into a single dot

Incorporating chemical signalling factors into cell-based models of growing epithelial tissues

In this paper we present a comprehensive computational framework within which the effects of chemical signalling factors on growing epithelial tissues can be studied. The method incorporates a vertex-based cell model, in conjunction with a solver for the governing chemical equations. The vertex model provides a natural mesh for the finite element method (FEM), with node movements determined by force laws. The arbitrary Lagrangian–Eulerian formulation is adopted to account for domain movement between iterations. The effects of cell proliferation and junctional rearrangements on the mesh are also examined. By implementing refinements of the mesh we show that the finite element (FE) approximation converges towards an accurate numerical solution. The potential utility of the system is demonstrated in the context of Decapentaplegic (Dpp), a morphogen which plays a crucial role in development of the Drosophila imaginal wing disc. Despite the presence of a Dpp gradient, growth is uniform across the wing disc. We make the growth rate of cells dependent on Dpp concentration and show that the number of proliferation events increases in regions of high concentration. This allows hypotheses regarding mechanisms of growth control to be rigorously tested. The method we describe may be adapted to a range of potential application areas, and to other cell-based models with designated node movements, to accurately probe the role of morphogens in epithelial tissues

Externally mode-matched cavity quantum electrodynamics with charge-tunable quantum dots

We present coherent reflection spectroscopy on a charge and DC Stark tunable quantum dot embedded in a high-quality and externally mode-matched microcavity. The addition of an exciton to a single-electron charged quantum dot forms a trion that interacts with the microcavity just below strong coupling regime of cavity quantum electrodynamics. Such an integrated, monolithic system is a crucial step towards the implementation of scalable hybrid quantum information schemes that are based on an efficient interaction between a single photon and a confined electron spin.Comment: 10 pages, 4 figure

Violation of pseudospin symmetry in nucleon-nucleus scattering: exact relations

An exact determination of the size of the pseudospin symmetry violating part of the nucleon-nucleus scattering amplitude from scattering observables is presented. The approximation recently used by Ginocchio turns out to underestimate the violation of pseudospin symmetry. Nevertheless the conclusion of a modestly broken pseudospin symmetry in proton-208Pb scattering at EL=800MeV remains valid.Comment: 8 pages, 2 figure

Ibrutinib directly reduces CD8+T cell exhaustion independent of BTK

Introduction: Cytotoxic CD8+ T cell (CTL) exhaustion is a dysfunctional state of T cells triggered by persistent antigen stimulation, with the characteristics of increased inhibitory receptors, impaired cytokine production and a distinct transcriptional profile. Evidence from immune checkpoint blockade therapy supports that reversing T cell exhaustion is a promising strategy in cancer treatment. Ibrutinib, is a potent inhibitor of BTK, which has been approved for the treatment of chronic lymphocytic leukemia. Previous studies have reported improved function of T cells in ibrutinib long-term treated patients but the mechanism remains unclear. We investigated whether ibrutinib directly acts on CD8+ T cells and reinvigorates exhausted CTLs. Methods: We used an established in vitro CTL exhaustion system to examine whether ibrutinib can directly ameliorate T cell exhaustion. Changes in inhibitory receptors, transcription factors, cytokine production and killing capacity of ibrutinib-treated exhausted CTLs were detected by flow cytometry. RNA-seq was performed to study transcriptional changes in these cells. Btk deficient mice were used to confirm that the effect of ibrutinib was independent of BTK expression. Results: We found that ibrutinib reduced exhaustion-related features of CTLs in an in vitro CTL exhaustion system. These changes included decreased inhibitory receptor expression, enhanced cytokine production, and downregulation of the transcription factor TOX with upregulation of TCF1. RNA-seq further confirmed that ibrutinib directly reduced the exhaustion-related transcriptional profile of these cells. Importantly, using btk deficient mice we showed the effect of ibrutinib was independent of BTK expression, and therefore mediated by one of its other targets. Discussion: Our study demonstrates that ibrutinib directly ameliorates CTL exhaustion, and provides evidence for its synergistic use with cancer immunotherapy.</p

A cross dialectal view of the Arabic dative alternation

This paper is concerned with the syntax of ditransitive verbs in Arabic.We concentrate on the vernaculars, focussing in particular on three geographically spread dialects: Egyptian Cairene Arabic, the dominant vernacular in Egypt, Hijazi Arabic, spoken in Western Saudi Arabia and Maltese, a mixed language with a Magrebi/Siculo-Arabic stratum. We show that all three exhibit an alternation (the dative alternation) between a ditransitive ('double object') construction and a corresponding prepositional dative construction, and outline a number of differences between these constructions in the different varieties of Arabic. We consider the distribution of verbs exhibiting the dative alternation in the light of Ryding's (2011) observations concerning Modern Standard Arabic

Comparison of Techniques for Bonding VCSELs Directly to Ics

This paper reports the successful bonding of 8 x 8 and 4 x 4 VCSEL arrays to Si CMOS and GaAs MESFET integrated circuits and to GaAs substrates. Three different bonding techniques are demonstrated and their electrical, optical and mechanical characteristics are compared. All three techniques remove the substrate from the VCSEL wafer, leaving individual VCSELs bonded directly to locations within the integrated circuit

Overcoming immune checkpoint blockade resistance in solid tumors with intermittent ITK inhibition

Cytotoxic CD8 + T cell (CTL) exhaustion is driven by chronic antigen stimulation. Reversing CTL exhaustion with immune checkpoint blockade (ICB) has provided clinical benefits in different types of cancer. We, therefore, investigated whether modulating chronic antigen stimulation and T-cell receptor (TCR) signaling with an IL2-inducible T-cell kinase (ITK) inhibitor, could confer ICB responsiveness to ICB resistant solid tumors. In vivo intermittent treatment of 3 ICB-resistant solid tumor (melanoma, mesothelioma or pancreatic cancer) with ITK inhibitor significantly improved ICB therapy. ITK inhibition directly reinvigorate exhausted CTL in vitro as it enhanced cytokine production, decreased inhibitory receptor expression, and downregulated the transcription factor TOX. Our study demonstrates that intermittent ITK inhibition can be used to directly ameliorate CTL exhaustion and enhance immunotherapies even in solid tumors that are ICB resistant.</p

Cell-Sorting at the A/P Boundary in the Drosophila Wing Primordium: A Computational Model to Consolidate Observed Non-Local Effects of Hh Signaling

Non-intermingling, adjacent populations of cells define compartment boundaries; such boundaries are often essential for the positioning and the maintenance of tissue-organizers during growth. In the developing wing primordium of Drosophila melanogaster, signaling by the secreted protein Hedgehog (Hh) is required for compartment boundary maintenance. However, the precise mechanism of Hh input remains poorly understood. Here, we combine experimental observations of perturbed Hh signaling with computer simulations of cellular behavior, and connect physical properties of cells to their Hh signaling status. We find that experimental disruption of Hh signaling has observable effects on cell sorting surprisingly far from the compartment boundary, which is in contrast to a previous model that confines Hh influence to the compartment boundary itself. We have recapitulated our experimental observations by simulations of Hh diffusion and transduction coupled to mechanical tension along cell-to-cell contact surfaces. Intriguingly, the best results were obtained under the assumption that Hh signaling cannot alter the overall tension force of the cell, but will merely re-distribute it locally inside the cell, relative to the signaling status of neighboring cells. Our results suggest a scenario in which homotypic interactions of a putative Hh target molecule at the cell surface are converted into a mechanical force. Such a scenario could explain why the mechanical output of Hh signaling appears to be confined to the compartment boundary, despite the longer range of the Hh molecule itself. Our study is the first to couple a cellular vertex model describing mechanical properties of cells in a growing tissue, to an explicit model of an entire signaling pathway, including a freely diffusible component. We discuss potential applications and challenges of such an approach