Control of immune cell entry through the tumour vasculature: a missing link in optimising melanoma immunotherapy?

Metastatic melanoma remains a fatal disease to many worldwide, even after the breakthrough introduction of targeted therapies such as BRAF inhibitors and immune checkpoint blockade therapies such as CTLA-4 and PD-1 inhibitors. With advances in our understanding of this disease, as well as the increasing data gathered from patient studies, the significance of the host immune response to cancer progression and response to treatment is becoming clear. More specifically, the presence of intratumoral CD8⁺ cytotoxic T-cells correlates with better prognosis whereas the accumulation of monocytes/macrophages and neutrophils in the tumour is often associated with worse prognosis. Access and infiltration of circulating leukocytes into the tumour is governed by adhesion molecules and chemokines expressed by the endothelial cells of the vasculature. This review focuses on the adhesion molecules and chemokines which control the homing of CD8⁺ cytotoxic T-cells, monocytes and neutrophils to peripheral tissues, including tumours. We discuss the role of these leukocyte subsets in regulating melanoma growth, and detail the mechanisms used by tumours to selectively recruit or exclude these leukocytes for their own advantage. In doing so, we bring to light an underappreciated component of tumour biology which should be considered in combination with current treatments to selectively alter the leukocyte composition of tumours and ultimately enhance treatment outcome.Lih Yin Tan, Carmela Martini, Zvi G Fridlender, Claudine S Bonder, Michael P Brown and Lisa M Eber

Institutional pedagogical waypoints : reflections on doctoral journeys between Taiwan and Australia

Spatial, social and academic journeys undertaken between Taiwan and Australia for doctoral education are the focus of reflection here. The discussion centres on the authors’ experiences of, on the one hand, the development of a Faculty of Education’s doctoral pedagogies in the early 2000s to reflect its international PhD candidature profile – especially from Taiwan – and, on the other, of Taiwanese doctoral candidates’ journeys through their PhDs in the Faculty. The authors write from their particular perspectives: Evans as an Australian academic and a manager of doctoral studies, and Liou as a Taiwanese academic pursuing her doctorate in an Australian university. The article considers the Australian and Taiwanese doctoral contexts between which the students transited. The institutional pedagogical strategies, from pre-enrolment to completion, are examined as waypoints on the doctoral journey for both staff and candidates

Non Linear Current Response of a Many-Level Tunneling System: Higher Harmonics Generation

The fully nonlinear response of a many-level tunneling system to a strong alternating field of high frequency $\omega$ is studied in terms of the Schwinger-Keldysh nonequilibrium Green functions. The nonlinear time dependent tunneling current $I(t)$ is calculated exactly and its resonance structure is elucidated. In particular, it is shown that under certain reasonable conditions on the physical parameters, the Fourier component $I_{n}$ is sharply peaked at $n=\frac {\Delta E} {\hbar \omega}$, where $\Delta E$ is the spacing between two levels. This frequency multiplication results from the highly nonlinear process of $n$ photon absorption (or emission) by the tunneling system. It is also conjectured that this effect (which so far is studied mainly in the context of nonlinear optics) might be experimentally feasible.Comment: 28 pages, LaTex, 7 figures are available upon request from [email protected], submitted to Phys.Rev.

Photoproduction of pions and properties of baryon resonances from a Bonn-Gatchina partial wave analysis

Masses, widths and photocouplings of baryon resonances are determined in a coupled-channel partial wave analysis of a large variety of data. The Bonn-Gatchina partial wave formalism is extended to include a decomposition of t- and u-exchange amplitudes into individual partial waves. The multipole transition amplitudes for $\gamma p\to p\pi^0$ and $\gamma p\to n\pi^+$ are given and compared to results from other analyses.Comment: 18 pages, 14 figure

Exploration of hyperfine interaction between constituent quarks via eta productions

In this work, the different exchange freedom, one gluon, one pion or Goldstone boson, in constituent quark model is investigated, which is responsible to the hyperfine interaction between constituent quarks, via the combined analysis of the eta production processes, $\pi^{-}p\rightarrow\eta n$ and $\gamma p\rightarrow\eta p$. With the Goldstone-boson exchange, as well as the one-gluon or one-pion exchange, both the spectrum and observables, such as, the differential cross section and polarized beam asymmetry, are fitted to the suggested values of Particle Data Group and the experimental data. The first two types of exchange freedoms give acceptable description of the spectrum and observables while the one pion exchange can not describe the observables and spectrum simultaneously, so can be excluded. The experimental data for the two processes considered here strongly support the mixing angles for two lowest S11 sates and D13 states as about -30 and 6 degree respectively.Comment: 7 pages, 4 figures, 4 table

Using Enterprise Education to Prepare Healthcare Professional Graduates for the Real-world

Objectives: Every year, HEIs around the world provide an increasing number of graduates with professional degrees in various areas of healthcare including for example medicine, pharmacy, dentistry and podiatry. In most cases, these graduates will get the opportunity to develop a range of generic transferable skills during their HE. Yet, many of these become self-employed or responsible for managing a business, but are not always exposed to curricula that develop their awareness of the concepts of enterprise and entrepreneurship and their role in developing economies and societies, and, thus, do not have the necessary range of enterprise skills that they will need in the real-world, whether employed or self-employed. This paper investigates the extent to which Enterprise Education (EE) is applied at professional health schools at HEIs to develop graduates’ ‘soft’ and ‘functional’ enterprise skills, and how effective the process of delivering this education is. Prior work: Previous literature mainly deals with the application of EE through business and management schools, rather than professional ones. Yet, there is a call for researching EE and skills with more focus on exploring the methods and objectives of specific disciplines. At the same time, research investigating learning in professional degrees focuses almost entirely on the development of technical skills related to the discipline, without a general perspective on developing a wider range of enterprise skills. Approach: The study draws on a qualitative research study in the pharmacy education context. Personal interviews with pharmacy employers and academics were carried out, and thematic analysis was applied to identify themes and codes. Results: Despite that experiential and interactive learning approaches, which can support the development of graduates’ enterprise skills, are applied quite often at pharmacy schools, the application of these approaches is focused on discipline-related material and, therefore, can only support the development of graduates’ ‘soft’ enterprise skills. However, there appears to be resistance against developing graduates’ ‘functional’ enterprise skills in pharmacy disciplines, especially in light of the lack of awareness of the concept of EE among academics. The study offers some possible opportunities/propositions that could facilitate the development of more enterprising healthcare graduates, while highlighting the importance of raising the awareness of academics in this regard and embedding EE as part of schools’ philosophies. Implication: This study should help professional health schools at HEIs decide more accurately on how to develop their graduates’ ‘soft’ and ‘functional’ enterprise skills, and address the needs of the real-world. Value: This study directs the attention of HEIs to support developing professional graduates who are ready for the real-world, and who can support the growth and success of any organisation whether employed or self-employed

Intercalibration of the barrel electromagnetic calorimeter of the CMS experiment at start-up

Calibration of the relative response of the individual channels of the barrel electromagnetic calorimeter of the CMS detector was accomplished, before installation, with cosmic ray muons and test beams. One fourth of the calorimeter was exposed to a beam of high energy electrons and the relative calibration of the channels, the intercalibration, was found to be reproducible to a precision of about 0.3%. Additionally, data were collected with cosmic rays for the entire ECAL barrel during the commissioning phase. By comparing the intercalibration constants obtained with the electron beam data with those from the cosmic ray data, it is demonstrated that the latter provide an intercalibration precision of 1.5% over most of the barrel ECAL. The best intercalibration precision is expected to come from the analysis of events collected in situ during the LHC operation. Using data collected with both electrons and pion beams, several aspects of the intercalibration procedures based on electrons or neutral pions were investigated

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02