Perturbative calculation of quasi-normal modes of Schwarzschild black holes

We discuss a systematic method of analytically calculating the asymptotic form of quasi-normal frequencies of a four-dimensional Schwarzschild black hole by expanding around the zeroth-order approximation to the wave equation proposed by Motl and Neitzke. We obtain an explicit expression for the first-order correction and arbitrary spin. Our results are in agreement with the results from WKB and numerical analyses in the case of gravitational waves.Comment: 11 pages; references added and a sign error corrected; to appear in CQ

Symmetry of massive Rarita-Schwinger fields

We derive the general lagrangian and propagator for a vector-spinor field in $d$-dimensions and show that the physical observables are invariant under the so-called point transformation symmetry. Until now the symmetry has not been exploited in any non-trival way, presumably because it is not an invariance of the classical action nor is it a gauge symmetry. Nevertheless, we develop a technique for exploring the consequences of the symmetry leading to a conserved vector current and charge. The current and charge are identically zero in the free field case and only contribute in a background such as a electromagnetic or gravitational field. The current can couple spin-3/2 fields to vector and scalar fields and may have important consequences in intermediate energy hadron physics as well as linearized supergravity. The consistency problem which plagues higher spin field theories is then discussed and and some ideas regarding the possiblity of solutions are presented.Comment: 26 pages, 1 figure; revised using referee comments, Journal ref. adde

Application of Raman Microspectroscopic and Raman imaging techniques for cell biological studies

Raman spectroscopy is being used to study biological molecules for some three decades now. Thanks to continuing advances in instrumentation more and more applications have become feasible in which molecules are studied in situ, and this has enabled Raman spectroscopy to enter the realms of biomedicine and cell biology [1-5].\ud Here we will describe some of the recent work carried out in our laboratory, concerning studies of human white blood cells and further instrumentational developments

Artificial Antigen-Presenting Cell Topology Dictates T Cell Activation

Contains fulltext : 283270.pdf (Publisher’s version ) (Open Access

‘The war is a money making show’: Working-Class Attitudes to World War II and Australian Nationalism

This paper will address the conference themes of ‘class, power and social structure’ through examining industrial and ideological conflict during World War II. The paper will also address the theme of ‘class and culture’ through an examination of working-class cultural expression as a means of resistance to the government’s wartime offensive. What is overlooked in most histories of World War II is the working-class experience of the war and their understanding of nationalism, particularly as nationalism was cynically exploited by the government to undermine working-class identity and solidarity. The paper will investigate the experience of one of the most militant sections of the Australian working class: the Miners. Primary source material such as the Miners’ journal Common Cause and union records reveal opposition to the war and a much more ambiguous attitude to the national sentiment used to justify Australia’s involvement. The Miners provide an interesting case study as the union was led by the Communist Party. Therefore the union leadership initially opposed to the war then became enthusiastic supporters when Russia entered the war on the allied side. It is clear that the Miners’ union leadership found it difficult to convince the rank and file to support the war. The paper will focus upon rank and file attitudes to the war and Australian nationalism particularly during times of industrial unrest.The symposium is organised on behalf of AAHANZBS by the Business and Labour History Group, The University of Sydney, with the financial support of the University’s Faculty of Economics and Business

Long Overall Survival After Dendritic Cell Vaccination in Metastatic Uveal Melanoma Patients

Purpose: To assess the safety and efficacy of dendritic cell vaccination in metastatic uveal melanoma. Design: Interventional case series. Methods: We analyzed 14 patients with metastatic uveal melanoma treated with dendritic cell vaccination. Patients with metastatic uveal melanoma received at least 3 vaccinations with autologous dendritic cells, professional antigen-presenting cells loaded with melanoma antigens gp100 and tyrosinase. The main outcome measures were safety, immunologic response, and overall survival. Results: Tumor-specific immune responses were induced with dendritic cell vaccination in 4 (29%) of14 patients. Dendritic cell-vaccinated patients showed a median overall survival with metastatic disease of 19.2months, relatively long compared with that reported in the literature. No severe treatment-related toxicities (common toxicity criteria grade 3 or 4) were observed. Conclusions: Dendritic cell vaccination is feasible and safe in metastatic uveal melanoma. Dendritic cell-based immunotherapy is potent to enhance the host's antitumor immunity against uveal melanoma in approximately one third of patients. Compared with other prospective studies with similar inclusion criteria, dendritic cell vaccination may be associated with longer than average overall survival in patients with metastatic uveal melanoma

Harnessing RNA sequencing for global, unbiased evaluation of two new adjuvants for dendritic-cell immunotherapy

Effective stimulation of immune cells is crucial for the success of cancer immunotherapies. Current approaches to evaluate the efficiency of stimuli are mainly defined by known flow cytometry-based cell activation or cell maturation markers. This method however does not give a complete overview of the achieved activation state and may leave important side effects unnoticed. Here, we used an unbiased RNA sequencing (RNA-seq)-based approach to compare the capacity of four clinical-grade dendritic cell (DC) activation stimuli used to prepare DC-vaccines composed of various types of DC subsets; the already clinically applied GM-CSF and Frühsommer meningoencephalitis (FSME) prophylactic vaccine and the novel clinical grade adjuvants protamine-RNA complexes (pRNA) and CpG-P. We found that GM-CSF and pRNA had similar effects on their target cells, whereas pRNA and CpG-P induced stronger type I interferon (IFN) expression than FSME. In general, the pathways most affected by all stimuli were related to immune activity and cell migration. GMCSF stimulation, however, also induced a significant increase of genes related to nonsense-mediated decay, indicating a possible deleterious effect of this stimulus. Taken together, the two novel stimuli appear to be promising alternatives. Our study demonstrates how RNA-seq based investigation of changes in a large number of genes and gene groups can be exploited for fast and unbiased, global evaluation of clinicalgrade stimuli, as opposed to the general limited evaluation of a pre-specified set of genes, by which one might miss important biological effects that are detrimental for vaccine efficacy

Human CD1c+ DCs are critical cellular mediators of immune responses induced by immunogenic cell death

Chemotherapeutics, including the platinum compounds oxaliplatin (OXP) and cisplatin (CDDP), are standard care of treatment for cancer. Although chemotherapy has long been considered immunosuppressive, evidence now suggests that certain cytotoxic agents can efficiently stimulate antitumor responses, through the induction of a form of apoptosis, called immunogenic cell death (ICD). ICD is characterized by exposure of calreticulin and heat shock proteins (HSPs), secretion of ATP and release of high-mobility group box 1 (HMGB1). Proper activation of the immune system relies on the integration of these signals by dendritic cells (DCs). Studies on the crucial role of DCs, in the context of ICD, have been performed using mouse models or human in vitro-generated monocyte-derived DCs (moDCs), which do not fully recapitulate the in vivo situation. Here, we explore the effect of platinum-induced ICD on phenotype and function of human blood circulating DCs. Tumor cells were treated with OXP or CDDP and induction of ICD was investigated. We show that both platinum drugs triggered translocation of calreticulin and HSP70, as well as the release of ATP and HMGB1. Platinum treatment increased phagocytosis of tumor fragments by human blood DCs and enhanced phenotypic maturation of blood myeloid and plasmacytoid DCs. Moreover, upon interaction with platinum-treated tumor cells, CD1c+ DCs efficiently stimulated allogeneic proliferation of T lymphocytes. Together, our observations indicate that platinum-treated tumor cells may exert an active stimulatory effect on human blood DCs. In particular, these data suggest that CD1c+ DCs are critical mediators of immune responses induced by ICD

Survival of metastatic melanoma patients after dendritic cell vaccination correlates with expression of leukocyte phosphatidylethanolamine-binding protein 1/Raf kinase inhibitory protein

Immunotherapy for metastatic melanoma offers great promise but, to date, only a subset of patients have responded. There is an urgent need to identify ways of allocating patients to the most beneficial therapy, to increase survival and decrease therapy-associated morbidity and costs. Blood-based biomarkers are of particular interest because of their straightforward implementation in routine clinical care. We sought to identify markers for dendritic cell (DC) vaccine-based immunotherapy against metastatic melanoma through gene expression analysis of peripheral blood mononuclear cells. A large-scale microarray analysis of 74 samples from two treatment centers, taken directly after the first round of DC vaccination, was performed. We found that phosphatidylethanolamine binding protein 1 (_PEBP1_)/ Raf Kinase inhibitory protein (RKIP) expression can be used to identify a significant proportion of patients who performed poorly after DC vaccination. This result was validated by q-PCR analysis on blood samples from a second cohort of 95 patients treated with DC vaccination in four different centers. We conclude that low _PEBP1_ expression correlates with poor overall survival after DC vaccination. Intriguingly, this was only the case for expression of _PEBP1_ after, but not prior to, DC vaccination. Moreover, the change in _PEBP1_ expression upon vaccination correlated well with survival. Further analyses revealed that _PEBP1_ expression positively correlated with genes involved in T cell responses but inversely correlated with genes associated with myeloid cells and aberrant inflammation including _STAT3, NOTCH1,_ and _MAPK1_. Concordantly, _PEBP1_ inversely correlated with the myeloid/ lymphoid-ratio and was suppressed in patients suffering from chronic inflammatory disease

Intracellular Galectin-9 Controls Dendritic Cell Function by Maintaining Plasma Membrane Rigidity

Biological Sciences; Molecular Biology; Cell BiologyEndogenous extracellular Galectins constitute a novel mechanism of membrane protein organization at the cell surface. Although Galectins are also highly expressed intracellularly, their cytosolic functions are poorly understood. Here, we investigated the role of Galectin-9 in dendritic cell (DC) surface organization and function. By combining functional, super-resolution and atomic force microscopy experiments to analyze membrane stiffness, we identified intracellular Galectin-9 to be indispensable for plasma membrane integrity and structure in DCs. Galectin-9 knockdown studies revealed intracellular Galectin-9 to directly control cortical membrane structure by modulating Rac1 activity, providing the underlying mechanism of Galectin-9-dependent actin cytoskeleton organization. Consequent to its role in maintaining plasma membrane structure, phagocytosis studies revealed that Galectin-9 was essential for C-type-lectin receptor-mediated pathogen uptake by DCs. This was confirmed by the impaired phagocytic capacity of Galectin-9-null murine DCs. Together, this study demonstrates a novel role for intracellular Galectin-9 in modulating DC function, which may be evolutionarily conserved