The stars of the galactic center

We consider the origin of the so-called S stars orbiting the supermassive black hole at the very center of the Galaxy. These are usually assumed to be massive main-sequence stars. We argue instead that they are the remnants of low-to-intermediate mass red giants which have been scattered on to near-radial orbits and tidally stripped as they approach the central black hole. Such stars retain only low-mass envelopes and thus have high effective temperatures. Our picture simultaneously explains why S stars have tightly-bound orbits, and the observed depletion of red giants in the very center of the Galaxy.Comment: 9 pages, 1 figure, ApJ Letters, in pres

Galaxy mergers can initiate quenching by unlocking an AGN-driven transformation of the baryon cycle

We use zoom simulations to show how merger-driven disruption of the gas disc in a galaxy provides its central active galactic nucleus (AGN) with fuel to drive outflows that entrain and expel a significant fraction of the circumgalactic medium (CGM). This in turn suppresses replenishment of the interstellar medium, causing the galaxy to quench up to several Gyr after the merger. We start by performing a zoom simulation of a present-day star-forming disc galaxy with the EAGLE galaxy formation model. Then, we re-simulate the galaxy with controlled changes to its initial conditions, using the genetic modification technique. These modifications either increase or decrease the stellar mass ratio of the galaxy’s last significant merger, which occurs at z ≈ 0.74. The halo reaches the same present-day mass in all cases, but changing the mass ratio of the merger yields markedly different galaxy and CGM properties. We find that a merger can unlock rapid growth of the central supermassive black hole if it disrupts the co-rotational motion of gas in the black hole’s vicinity. Conversely, if a less disruptive merger occurs and gas close to the black hole is not disturbed, the AGN does not strongly affect the CGM, and consequently the galaxy continues to form stars. Our result illustrates how a unified view of AGN feedback, the baryon cycle and the interstellar medium is required to understand how mergers and quenching are connected over long timescales

Origin of magnetic moments in carbon nanofoam

A range of carbon nanofoam samples was prepared by using a high-repetition-rate laser ablation technique under various Ar pressures. Their magnetic properties were systematically investigated by dc magnetization measurements and continuous wave (cw) as well as pulsed EPR techniques. In all samples we found very large zero-field cooled-field-cooled thermal hysteresis in the susceptibility measurements extending up to room temperature. Zero-field cooled (ZFC) susceptibility measurements also display very complex behavior with a susceptibility maximum that strongly varies in temperature from sample to sample. Low-temperature magnetization curves indicate a saturation magnetization MS ≈0.35 emu g at 2 K and can be well fitted with a classical Langevin function. MS is more than an order of magnitude larger than any possible iron impurity, proving that the observed magnetic phenomena are an intrinsic effect of the carbon nanofoam. Magnetization measurements are consistent with a spin-glass type ground state. The cusps in the ZFC susceptibility curves imply spin freezing temperatures that range from 50 K to the extremely high value of >300 K. Further EPR measurements revealed three different centers that coexist in all samples, distinguished on the basis of g -factor and relaxation time. Their possible origin and the role in the magnetic phenomena are discussed

Effects of retail employees' behaviours on customers' service evaluation

Purpose – The purpose of this paper is to test a conceptual model of the effects of customer and service orientation (SO) behaviours of individual retail employees on individual customers’ perceptions of service encounter quality (SEQ), service quality (SQ), value, satisfaction, and behavioural intentions (BI). Design/methodology/approach – The sample (n ¼ 271) was customers of a supermarket in central India, and they completed questionnaires following mall intercept. To test the hypotheses, structural equation modelling using LISREL 8.7 was employed. Findings – It was found that: service and customer orientation (CO) behaviours are positively related to SEQ and SQ; SEQ is positively related to SQ and customer satisfaction; SQ is positively related to value perceptions and customer satisfaction; and customer satisfaction is positively related to retail customers’ BI. However, value is not related to customer satisfaction. Research limitations/implications – More research is needed on customer perceptions of value in non-Western contexts and service evaluation frameworks in other cross-cultural contexts. Practical implications – Retail managers need to train or select retail personnel who are able to perform their roles in a service-oriented and customer-oriented way, and value does not appear to be as important to Indian retail customers as it is to Western retail customers. Originality/value – This paper extends current service evaluation frameworks by including SO and CO as antecedents, and it analyses an Indian retail context. Keywords India, Retailing, Customer satisfaction, Service levels, Employee behaviour

Co-targeting HGF/cMET Signaling with MEK Inhibitors in Metastatic Uveal Melanoma.

Patients with metastatic uveal melanoma usually die within 1 year of diagnosis, emphasizing an urgent need to develop new treatment strategies. The liver is the most common site of metastasis. Mitogen-activated protein kinase kinase (MEK) inhibitors improve survival in V600 BRAF-mutated cutaneous melanoma patients but have limited efficacy in patients with uveal melanoma. Our previous work showed that hepatocyte growth factor (HGF) signaling elicits resistance to MEK inhibitors in metastatic uveal melanoma. In this study, we demonstrate that expression of two BH3-only family proteins, Bim-EL and Bmf, contributes to HGF-mediated resistance to MEK inhibitors. Targeting HGF/cMET signaling with LY2875358, a neutralizing and internalizing anti-cMET bivalent antibody, and LY2801653, a dual cMET/RON inhibitor, overcomes resistance to trametinib provided by exogenous HGF and by conditioned medium from primary hepatic stellate cells. We further determined that activation of PI3Kα/γ/δ isoforms mediates the resistance to MEK inhibitors by HGF. Combination of LY2801653 with trametinib decreases AKT phosphorylation and promotes proapoptotic PARP cleavage in metastatic uveal melanoma explants. Together, our data support the notion that selectively blocking cMET signaling or PI3K isoforms in metastatic uveal melanoma may break the intrinsic resistance to MEK inhibitors provided by factors from stromal cells in the liver

Undoing a weak quantum measurement of a solid-state qubit

We propose an experiment which demonstrates the undoing of a weak continuous measurement of a solid-state qubit, so that any unknown initial state is fully restored. The undoing procedure has only a finite probability of success because of the non-unitary nature of quantum measurement, though it is accompanied by a clear experimental indication of whether or not the undoing has been successful. The probability of success decreases with increasing strength of the measurement, reaching zero for a traditional projective measurement. Measurement undoing (``quantum un-demolition'') may be interpreted as a kind of a quantum eraser, in which the information obtained from the first measurement is erased by the second measurement, which is an essential part of the undoing procedure. The experiment can be realized using quantum dot (charge) or superconducting (phase) qubits.Comment: 5 page

Commensal-derived OMVs elicit a mild proinflammatory response in intestinal epithelial cells

Under normal physiological conditions, the intestinal immunity remains largely hyporesponsive to the commensal microbiota, yet also retains the inherent ability to rapidly respond to pathogenic antigens. However, immunomodulatory activities of extracellular products from commensal bacteria have been little studied, with previous investigations generally utilising the live bacterium to study microbiota-epithelial interactions. In this study, we demonstrate that extracellular products of a commensal bacterium, Escherichia coli C25, elicit a moderate release of proinflammatory IL-8 and stimulate transcriptional up-regulation of Toll-like receptors (TLRs) in intestinal epithelial cell lines, HT29-19A and Caco-2. Additionally, we show that removal of outer membrane vesicles (OMVs) diminishes the proinflammatory effect of secreted products from E. coli C25. Furthermore, we show that isolated OMVs have a dose-dependent proinflammatory effect on IECs. Interestingly, a relatively high concentration (10x culture concentration) of OMVs had no significant regulatory effects on TLR mRNA expression in both cell lines. Finally, we also demonstrate a that pre-incubation with E. coli C25-derived OMVs subsequently inhibited the internalisation of the bacterium itself in both cell lines. Taken together, our results suggest that commensal-derived extracellular products, in particular OMVs, could significantly contribute to intestinal homeostasis. We also demonstrate a unique interaction between commensal-derived OMVs and host cells

GPCRTree: online hierarchical classification of GPCR function

Background: G protein-coupled receptors (GPCRs) play important physiological roles transducing extracellular signals into intracellular responses. Approximately 50% of all marketed drugs target a GPCR. There remains considerable interest in effectively predicting the function of a GPCR from its primary sequence. Findings: Using techniques drawn from data mining and proteochemometrics, an alignment-free approach to GPCR classification has been devised. It uses a simple representation of a protein's physical properties. GPCRTree, a publicly-available internet server, implements an algorithm that classifies GPCRs at the class, sub-family and sub-subfamily level. Conclusion: A selective top-down classifier was developed which assigns sequences within a GPCR hierarchy. Compared to other publicly available GPCR prediction servers, GPCRTree is considerably more accurate at every level of classification. The server has been available online since March 2008 at URL: http://igrid-ext.cryst.bbk.ac.uk/gpcrtree

Drying of complex suspensions

We investigate the 3D structure and drying dynamics of complex mixtures of emulsion droplets and colloidal particles, using confocal microscopy. Air invades and rapidly collapses large emulsion droplets, forcing their contents into the surrounding porous particle pack at a rate proportional to the square of the droplet radius. By contrast, small droplets do not collapse, but remain intact and are merely deformed. A simple model coupling the Laplace pressure to Darcy's law correctly estimates both the threshold radius separating these two behaviors, and the rate of large-droplet evacuation. Finally, we use these systems to make novel hierarchical structures.Comment: 4 pages, 4 figure

FOXD3 Regulates VISTA Expression in Melanoma.

Immune checkpoint inhibitors have improved patient survival in melanoma, but the innate resistance of many patients necessitates the investigation of alternative immune targets. Many immune checkpoint proteins lack proper characterization, including V-domain Ig suppressor of T cell activation (VISTA). VISTA expression on immune cells can suppress T cell activity; however, few studies have investigated its expression and regulation in cancer cells. In this study, we observe that VISTA is expressed in melanoma patient samples and cell lines. Tumor cell-specific expression of VISTA promotes tumor onset in vivo, associated with increased intratumoral T regulatory cells, and enhanced PDL-1 expression on tumor-infiltrating macrophages. VISTA transcript levels are regulated by the stemness factor Forkhead box D3 (FOXD3). BRAF inhibition upregulates FOXD3 and reduces VISTA expression. Overall, this study demonstrates melanoma cell expression of VISTA and its regulation by FOXD3, contributing to the rationale for therapeutic strategies that combine targeted inhibitors with immune checkpoint blockade