Efficient loading of dendritic cells following cryo and radiofrequency ablation in combination with immune modulation induces anti-tumour immunity

Dendritic cells (DC) are professional antigen-presenting cells that play a pivotal role in the induction of immunity. Ex vivo-generated, tumour antigen-loaded mature DC are currently exploited as cancer vaccines in clinical studies. However, antigen loading and maturation of DC directly in vivo would greatly facilitate the application of DC-based vaccines. We formerly showed in murine models that radiofrequency-mediated tumour destruction can provide an antigen source for the in vivo induction of anti-tumour immunity, and we explored the role of DC herein. In this paper we evaluate radiofrequency and cryo ablation for their ability to provide an antigen source for DC and compare this with an ex vivo-loaded DC vaccine. The data obtained with model antigens demonstrate that upon tumour destruction by radiofrequency ablation, up to 7% of the total draining lymph node (LN) DC contained antigen, whereas only few DC from the conventional vaccine reached the LN. Interestingly, following cryo ablation the amount of antigen-loaded DC is almost doubled. Analysis of surface markers revealed that both destruction methods were able to induce DC maturation. Finally, we show that in situ tumour ablation can be efficiently combined with immune modulation by anti-CTLA-4 antibodies or regulatory T-cell depletion. These combination treatments protected mice from the outgrowth of tumour challenges, and led to in vivo enhancement of tumour-specific T-cell numbers, which produced more IFN-γ upon activation. Therefore, in situ tumour destruction in combination with immune modulation creates a unique, ‘in situ DC-vaccine' that is readily applicable in the clinic without prior knowledge of tumour antigens

Intercultural communication in the context of Saudi Arab tertiary education

© Springer Science+Business Media Singapore 2015. This chapter is a case study of intercultural communication in a tertiary educational setting in Saudi Arabia. Given the fact that educational institutions adopt Western models of education and employ foreign professors, this study aims at shedding light on the patterns of communication in the classroom. The elements of Hofstede\u27s five dimensional model, namely, uncertainty avoidance, individualism/collectivism, and power distance dimensions were applied for the purpose of analysis. The study involved in-depth interviews with 17 female students of a private university in the Eastern Province. While assessing the perception of the students about the communication patterns, it provides recommendations on improving the educational experience of local students taught by Western professors. Ultimately, the findings will contribute in promoting a culturally responsible education characterized by critical thinking skills, individual creativity, and movement out of comfort zones, which will prepare students for the globalized job market\u27s challenges

Dissecting early-type dwarf galaxies into their multiple components

Early-type dwarf galaxies, once believed to be simple systems, have recently been shown to exhibit an intriguing diversity in structure and stellar content. To analyze this further, we started the SMAKCED project, and obtained deep H-band images for 101 early-type dwarf galaxies in the Virgo cluster in a brightness range of -19 \leq M_r \leq -16 mag, typically reaching a signal-to-noise of 1 per pixel of \sim0.25" at surface brightnesses \sim22.5 mag/arcsec^2 in the H-band. Here we present the first results of decomposing their two-dimensional light distributions. This is the first study dedicated to early-type dwarf galaxies using the two-dimensional multi-component decomposition approach, which has been proven to be important for giant galaxies. Armed with this new technique, we find more structural components than previous studies: only a quarter of the galaxies fall into the simplest group, namely those represented by a single S\'ersic function, optionally with a nucleus. Furthermore, we find a bar fraction of 18%. We detect also a similar fraction of lenses which appear as shallow structures with sharp outer edges. Galaxies with bars and lenses are found to be more concentrated towards the Virgo galaxy center than the other sample galaxies.Comment: Accepted by ApJL, 6 pages, 4 figures, 1 tabl

Stellar Kinematics and Structural Properties of Virgo Cluster Dwarf Early-Type Galaxies from the SMAKCED Project. I. Kinematically Decoupled Cores and Implications for Infallen Groups in Clusters

We present evidence for kinematically decoupled cores (KDCs) in two dwarf early-type (dE) galaxies in the Virgo cluster, VCC 1183 and VCC 1453, studied as part of the SMAKCED stellar absorption-line spectroscopy and imaging survey. These KDCs have radii of 1.8'' (0.14 kpc) and 4.2'' (0.33 kpc), respectively. Each of these KDCs is distinct from the main body of its host galaxy in two ways: (1) inverted sense of rotation; and (2) younger (and possibly more metal-rich) stellar population. The observed stellar population differences are probably associated with the KDC, although we cannot rule out the possibility of intrinsic radial gradients in the host galaxy. We describe a statistical analysis method to detect, quantify the significance of, and characterize KDCs in long-slit rotation curve data. We apply this method to the two dE galaxies presented in this paper and to five other dEs for which KDCs have been reported in the literature. Among these seven dEs, there are four significant KDC detections, two marginal KDC detections, and one dE with an unusual central kinematic anomaly that may be an asymmetric KDC.The frequency of occurence of KDCs and their properties provide important constraints on the formation history of their host galaxies. We discuss different formation scenarios for these KDCs in cluster environments and find that dwarf-dwarf wet mergers or gas accretion can explain the properties of these KDCs. Both of these mechanisms require that the progenitor had a close companion with a low relative velocity. This suggests that KDCs were formed in galaxy pairs residing in a poor group environment or in isolation whose subsequent infall into the cluster quenched star formation.Comment: 14 pages, accepted for publication in Ap

Barred Galaxies in the Coma Cluster

We use ACS data from the HST Treasury survey of the Coma cluster (z~0.02) to study the properties of barred galaxies in the Coma core, the densest environment in the nearby Universe. This study provides a complementary data point for studies of barred galaxies as a function of redshift and environment. From ~470 cluster members brighter than M_I = -11 mag, we select a sample of 46 disk galaxies (S0--Im) based on visual classification. The sample is dominated by S0s for which we find an optical bar fraction of 47+/-11% through ellipse fitting and visual inspection. Among the bars in the core of the Coma cluster, we do not find any very large (a_bar > 2 kpc) bars. Comparison to other studies reveals that while the optical bar fraction for S0s shows only a modest variation across low-to-intermediate density environments (field to intermediate-density clusters), it can be higher by up to a factor of ~2 in the very high-density environment of the rich Coma cluster core.Comment: Proceedings of the Bash symposium, to appear in the Astronomical Society of the Pacific Conference Series, eds. L. Stanford, L. Hao, Y. Mao, J. Gree

Resolved low-J 12^{12}CO excitation at 190 parsec resolution across NGC 2903 and NGC 3627

The low-$J$ rotational transitions of $^{12}$CO are commonly used to trace the distribution of molecular gas in galaxies. Their ratios are sensitive to excitation and physical conditions in the molecular gas. Spatially resolved studies of CO ratios are still sparse and affected by flux calibration uncertainties, especially since most do not have high angular resolution or do not have short-spacing information and hence miss any diffuse emission. We compare the low-$J$ CO ratios across the disk of two massive, star-forming spiral galaxies NGC2903 and NGC3627 to investigate whether and how local environments drive excitation variations at GMC scales. We use Atacama Large Millimeter Array (ALMA) observations of the three lowest-$J$ CO transitions at a common angular resolution of 4$''$ (190pc). We measure median line ratios of $R_{21}=0.67^{+0.13}_{-0.11}$, $R_{32}=0.33^{+0.09}_{-0.08}$, and $R_{31}=0.24^{+0.10}_{-0.09}$ across the full disk of NGC3627. We see clear CO line ratio variation across the galaxy consistent with changes in temperature and density of the molecular gas. In particular, toward the center, $R_{21}$, $R_{32}$, and $R_{31}$ increase by 35\%, 50\%, and 66\%, respectively compared to their average disk values. The overall line ratio trends suggest that CO(3-2) is more sensitive to changes in the excitation conditions than the two lower-$J$ transitions. Furthermore, we find a similar radial $R_{32}$ trend in NGC2903, albite a larger disk-wide average of $\langle R_{32}\rangle=0.47^{+0.14}_{-0.08}$. We conclude that the CO low-$J$ line ratios vary across environments in such a way that they can trace changes in the molecular gas conditions, with the main driver being changes in temperature.Comment: accepted for publication in MNRAS, 17 pages, 16 figure

Spisulosine (ES-285) given as a weekly three-hour intravenous infusion: results of a phase I dose-escalating study in patients with advanced solid malignancies

Spisulosine is a marine compound that showed antitumor activity in preclinical studies. We report results of a phase I trial performed in patients with advanced solid tumors with the marine compound, with the aim to determine the maximum tolerated dose (MTD) of a weekly 3-h intravenous (iv.) infusion, and to evaluate the safety, efficacy, and pharmacokinetics (PK) of the compound. Two centers contributed 25 patients to the trial, and 7 dose levels were explored. In dose levels ranging from 4 to 128 mg/mA(2)/day, no dose-limiting toxicities (DLT) were observed. One patient had DLT at 200 mg/mA(2), a reversible grade 3 ALT increase. The MTD was not reached due to early termination of the Spisulosine trial program but is considered to be likely in the range of 200 mg/mA(2) for this schedule. Drug-related adverse reactions included mild to moderate nausea, pyrexia, injection site reactions, and vomiting. One case of grade 4 peripheral motor and sensory neuropathy associated with general weakness and pain was observed during treatment cycle 4 and possibly contributed to the death of the patient. Grade 3 laboratory abnormalities included anemia and lymphopenia and increases in liver enzymes (alkaline phosphatase, transaminases, and bilirubin). Objective responses were not observed, and only four patients had short-lasting stable disease (< 3 months). The PK data indicated a wide distribution, a long residence time, and dose proportionality of the agent. Hepato- and neuro-toxicity are schedule independent dose-limiting adverse events for this marine compound, as illustrated by this and other early clinical trials

Californian Science Students' Perceptions of their Classoom Learning Environments.

This study utilised the What Is Happening In this Class (WIHIC) questionnaire to examine factors that influence Californian student perceptions of their learning environment. Data were collected from 665 USA middle school science students in 11 Californian schools. Several background variables were included in the study to investigate their effects on students’ perceptions, such as student and teacher gender, student ethnic background and socio-economic status (SES), and student age. Class and school variables, such as class ethnic composition, class size and school socioeconomic status were also collected. A hierarchical analysis of variance was conducted to investigate separate and joint effects of these variables. Results from this study indicate that some scales of the WIHIC are more inclined to measure personal or idiosyncratic features of student perceptions of their learning environment whereas other scales contain more variance at the class level. Also, it was found that different variables affect different scale scores. A variable that consistently affected students' perceptions, regardless of the element of interest in the learning environment was student gender. Generally speaking girls perceived their learning environment more positively than did boys