The averaged null energy condition for general quantum field theories in two dimensions

It is shown that the averaged null energy condition is fulfilled for a dense, translationally invariant set of vector states in any local quantum field theory in two-dimensional Minkowski spacetime whenever the theory has a mass gap and possesses an energy-momentum tensor. The latter is assumed to be a Wightman field which is local relative to the observables, generates locally the translations, is divergence-free, and energetically bounded. Thus the averaged null energy condition can be deduced from completely generic, standard assumptions for general quantum field theory in two-dimensional flat spacetime.Comment: LateX2e, 16 pages, 1 eps figur

Bounds on negative energy densities in flat spacetime

We generalise results of Ford and Roman which place lower bounds -- known as quantum inequalities -- on the renormalised energy density of a quantum field averaged against a choice of sampling function. Ford and Roman derived their results for a specific non-compactly supported sampling function; here we use a different argument to obtain quantum inequalities for a class of smooth, even and non-negative sampling functions which are either compactly supported or decay rapidly at infinity. Our results hold in $d$-dimensional Minkowski space ($d\ge 2$) for the free real scalar field of mass $m\ge 0$. We discuss various features of our bounds in 2 and 4 dimensions. In particular, for massless field theory in 2-dimensional Minkowski space, we show that our quantum inequality is weaker than Flanagan's optimal bound by a factor of 3/2.Comment: REVTeX, 13 pages and 2 figures. Minor typos corrected, one reference adde

Evaluation of known and novel inhibitors of Orai1-mediated store operated Ca2+ entry in MDA-MB-231 breast cancer cells using a Fluorescence Imaging Plate Reader assay

The Orai1 Ca2+ permeable ion channel is an important component of store operated Ca2+ entry (SOCE) in cells. It's over-expression in basal molecular subtype breast cancers has been linked with poor prognosis, making it a potential target for drug development. We pharmacologically characterised a number of reported inhibitors of SOCE in MDA-MB-231 breast cancer cells using a convenient Fluorescence Imaging Plate Reader (FLIPR) assay, and show that the rank order of their potencies in this assay is the same as those reported in a wide range of published assays. The assay was also used in a screening project seeking novel inhibitors. Following a broad literature survey of classes of calcium channel inhibitors we used simplified ligand structures to query the ZINC on-line database, and following two iterations of refinement selected a novel Orai1-selective dichlorophenyltriazole hit compound. Analogues of this were synthesized and evaluated in the FLIPR assay to develop structure-activity relationships (SAR) for the three domains of the hit; triazole (head), dichlorophenyl (body) and substituted phenyl (tail). For this series, the results suggested the need for a lipophilic tail domain and an out-of-plane twist between the body and tail domains. (C) 2016 Elsevier Ltd. All rights reserved

Restrictions on negative energy density in a curved spacetime

Recently a restriction ("quantum inequality-type relation") on the (renormalized) energy density measured by a static observer in a "globally static" (ultrastatic) spacetime has been formulated by Pfenning and Ford for the minimally coupled scalar field, in the extension of quantum inequality-type relation on flat spacetime of Ford and Roman. They found negative lower bounds for the line integrals of energy density multiplied by a sampling (weighting) function, and explicitly evaluate them for some specific spacetimes. In this paper, we study the lower bound on spacetimes whose spacelike hypersurfaces are compact and without boundary. In the short "sampling time" limit, the bound has asymptotic expansion. Although the expansion can not be represented by locally invariant quantities in general due to the nonlocal nature of the integral, we explicitly evaluate the dominant terms in the limit in terms of the invariant quantities. We also make an estimate for the bound in the long sampling time limit.Comment: LaTex, 23 Page

Assessment of patient-derived tumour xenografts (PDXs) as a discovery tool for cancer epigenomics

Background: The use of tumour xenografts is a well-established research tool in cancer genomics but has not yet been comprehensively evaluated for cancer epigenomics. Methods: In this study, we assessed the suitability of patient-derived tumour xenografts (PDXs) for methylome analysis using Infinium 450 K Beadchips and MeDIP-seq. Results: Controlled for confounding host (mouse) sequences, comparison of primary PDXs and matching patient tumours in a rare (osteosarcoma) and common (colon) cancer revealed that an average 2.7% of the assayed CpG sites undergo major (Δβ ≥ 0.51) methylation changes in a cancer-specific manner as a result of the xenografting procedure. No significant subsequent methylation changes were observed after a second round of xenografting between primary and secondary PDXs. Based on computational simulation using publically available methylation data, we additionally show that future studies comparing two groups of PDXs should use 15 or more samples in each group to minimise the impact of xenografting-associated changes in methylation on comparison results. Conclusions: Our results from rare and common cancers indicate that PDXs are a suitable discovery tool for cancer epigenomics and we provide guidance on how to overcome the observed limitations

Systems analysis of cancer cell heterogeneity in caspase-dependent apoptosis subsequent to mitochondrial outer membrane permeabilization.

Deregulation of apoptosis is a hallmark of carcinogenesis. We here combine live cell imaging and systems modeling to investigate caspase-dependent apoptosis execution subsequent to mitochondrial outer membrane permeabilization (MOMP) in several cancer cell lines. We demonstrate that, although most cell lines that underwent MOMP also showed robust and fast activation of executioner caspases and apoptosis, the colorectal cancer cell lines LoVo and HCT-116 Smac(-/-), similar to X-linked inhibitor of apoptosis protein (XIAP)-overexpressing HeLa (HeLa XIAP(Adv)) cells, only showed delayed and often no caspase activation, suggesting apoptosis impairment subsequent to MOMP. Employing APOPTO-CELL, a recently established model of apoptosis subsequent to MOMP, this impairment could be understood by studying the systemic interaction of five proteins that are present in the apoptosis pathway subsequent to MOMP. Using APOPTO-CELL as a tool to study detailed molecular mechanisms during apoptosis execution in individual cell lines, we demonstrate that caspase-9 was the most important regulator in DLD-1, HCT-116, and HeLa cells and identified additional cell line-specific co-regulators. Developing and applying a computational workflow for parameter screening, systems modeling identified that apoptosis execution kinetics are more robust against changes in reaction kinetics in HCT-116 and HeLa than in DLD-1 cells. Our systems modeling study is the first to draw attention to the variability in cell specific protein levels and reaction rates and to the emergent effects of such variability on the efficiency of apoptosis execution and on apoptosis impairment subsequent to MOMP

Wave function of the radion in the brane background with a massless scalar field and a self-tuning problem

We consider flat solutions in the brane background with a massless scalar field appearing in 5D $H^2_{MNPQ}$. Since there exist bulk singularities or arises the divergent 4D Planck mass, we should introduce a compact extra dimension, the size of which is then fixed by brane tension(s) and a bulk cosmological constant. Inspecting scalar perturbations around the flat solutions, we find that the flat solutions are stable vacua from the positive mass spectrum of radion. We show that the massless radion mode is projected out by the boundary condition arising in cutting off the extra dimension. Thus, the fixed extra dimension is not alterable, which is not useful toward a self-tuning of the cosmological constant.Comment: Latex file of 18 pages including 1 eps figur

How to return to subjectivity? Natorp, Husserl, and Lacan on the limits of reflection

This article discusses the recent call within contemporary phenomenology to return to subjectivity in response to certain limitations of naturalistic explanations of the mind. The meaning and feasibility of this call is elaborated by connecting it to a classical issue within the phenomenological tradition concerning the possibility of investigating the first-person perspective through reflection. We will discuss how this methodological question is respectively treated and reconfigured in the works of Natorp, Husserl, and Lacan. Finally, we will lay out some possible consequences of such a cross-reading for the conception of subjectivity and the concomitant effort to account for this dimension of first-person experience in response and in addition to its omission within the standard third-person perspective of psychological research

'Reaching the hard to reach' - lessons learned from the VCS (voluntary and community Sector). A qualitative study.

Background The notion 'hard to reach' is a contested and ambiguous term that is commonly used within the spheres of social care and health, especially in discourse around health and social inequalities. There is a need to address health inequalities and to engage in services the marginalized and socially excluded sectors of society. Methods This paper describes a pilot study involving interviews with representatives from eight Voluntary and Community Sector (VCS) organisations . The purpose of the study was to explore the notion of 'hard to reach' and perceptions of the barriers and facilitators to accessing services for 'hard to reach' groups from a voluntary and community sector perspective. Results The 'hard to reach' may include drug users, people living with HIV, people from sexual minority communities, asylum seekers, refugees, people from black and ethnic minority communities, and homeless people although defining the notion of the 'hard to reach' is not straight forward. It may be that certain groups resist engaging in treatment services and are deemed hard to reach by a particular service or from a societal stance. There are a number of potential barriers for people who may try and access services, including people having bad experiences in the past; location and opening times of services and how services are funded and managed. A number of areas of commonality are found in terms of how access to services for 'hard to reach' individuals and groups could be improved including: respectful treatment of service users, establishing trust with service users, offering service flexibility, partnership working with other organisations and harnessing service user involvement. Conclusions: If health services are to engage with groups that are deemed 'hard to reach' and marginalised from mainstream health services, the experiences and practices for engagement from within the VCS may serve as useful lessons for service improvement for statutory health services