Cell therapies in ovarian cancer.

Epithelial ovarian cancer (EOC) is the most important cause of gynecological cancer-related mortality. Despite improvements in medical therapies, particularly with the incorporation of drugs targeting homologous recombination deficiency, EOC survival rates remain low. Adoptive cell therapy (ACT) is a personalized form of immunotherapy in which autologous lymphocytes are expanded, manipulated ex vivo, and re-infused into patients to mediate cancer rejection. This highly promising novel approach with curative potential encompasses multiple strategies, including the adoptive transfer of tumor-infiltrating lymphocytes, natural killer cells, or engineered immune components such as chimeric antigen receptor (CAR) constructs and engineered T-cell receptors. Technical advances in genomics and immuno-engineering have made possible neoantigen-based ACT strategies, as well as CAR-T cells with increased cell persistence and intratumoral trafficking, which have the potential to broaden the opportunity for patients with EOC. Furthermore, dendritic cell-based immunotherapies have been tested in patients with EOC with modest but encouraging results, while the combination of DC-based vaccination as a priming modality for other cancer therapies has shown encouraging results. In this manuscript, we provide a clinically oriented historical overview of various forms of cell therapies for the treatment of EOC, with an emphasis on T-cell therapy

Cinematic and aesthetic cartographies of subjective mutation

This article exmaines the use of cinema as a mapping of subjective mutation in the work of Deleuze, Gauttari and Berardi. Drawing on Deleuze's distinciton between the reduction of the art-work to the symptom and the idea of art as symptomatology, the article focuses on Berardi's use of cinematic examples, posing the quesiton in each case of to what extent they function as symptomatologies or mere symptoms of cultural and subjective mutations in examples ranging from Bergman's Persona to Van Sant's Elephant to finish on speculations about Fincher's The Social Network as a cirtical engagement with subjective mutation in the 21st Century

Constructive pointfree topology eliminates non-constructive representation theorems from Riesz space theory

In Riesz space theory it is good practice to avoid representation theorems which depend on the axiom of choice. Here we present a general methodology to do this using pointfree topology. To illustrate the technique we show that almost f-algebras are commutative. The proof is obtained relatively straightforward from the proof by Buskes and van Rooij by using the pointfree Stone-Yosida representation theorem by Coquand and Spitters

Integrable Generalisations of the 2-dimensional Born Infeld Equation

The Born-Infeld equation in two dimensions is generalised to higher dimensions whilst retaining Lorentz Invariance and complete integrability. This generalisation retains homogeneity in second derivatives of the field.Comment: 11 pages, Latex, DTP/93/3

MitoNeoD:a mitochondria-targeted superoxide probe

Mitochondrial superoxide (O2⋅−) underlies much oxidative damage and redox signaling. Fluorescent probes can detect O2⋅−, but are of limited applicability in vivo, while in cells their usefulness is constrained by side reactions and DNA intercalation. To overcome these limitations, we developed a dual-purpose mitochondrial O2⋅− probe, MitoNeoD, which can assess O2⋅− changes in vivo by mass spectrometry and in vitro by fluorescence. MitoNeoD comprises a O2⋅−-sensitive reduced phenanthridinium moiety modified to prevent DNA intercalation, as well as a carbon-deuterium bond to enhance its selectivity for O2⋅− over non-specific oxidation, and a triphenylphosphonium lipophilic cation moiety leading to the rapid accumulation within mitochondria. We demonstrated that MitoNeoD was a versatile and robust probe to assess changes in mitochondrial O2⋅− from isolated mitochondria to animal models, thus offering a way to examine the many roles of mitochondrial O2⋅−production in health and disease

An algorithmic approach to the existence of ideal objects in commutative algebra

The existence of ideal objects, such as maximal ideals in nonzero rings, plays a crucial role in commutative algebra. These are typically justified using Zorn's lemma, and thus pose a challenge from a computational point of view. Giving a constructive meaning to ideal objects is a problem which dates back to Hilbert's program, and today is still a central theme in the area of dynamical algebra, which focuses on the elimination of ideal objects via syntactic methods. In this paper, we take an alternative approach based on Kreisel's no counterexample interpretation and sequential algorithms. We first give a computational interpretation to an abstract maximality principle in the countable setting via an intuitive, state based algorithm. We then carry out a concrete case study, in which we give an algorithmic account of the result that in any commutative ring, the intersection of all prime ideals is contained in its nilradical

HMM based scenario generation for an investment optimisation problem

This is the post-print version of the article. The official published version can be accessed from the link below - Copyright @ 2012 Springer-Verlag.The Geometric Brownian motion (GBM) is a standard method for modelling financial time series. An important criticism of this method is that the parameters of the GBM are assumed to be constants; due to this fact, important features of the time series, like extreme behaviour or volatility clustering cannot be captured. We propose an approach by which the parameters of the GBM are able to switch between regimes, more precisely they are governed by a hidden Markov chain. Thus, we model the financial time series via a hidden Markov model (HMM) with a GBM in each state. Using this approach, we generate scenarios for a financial portfolio optimisation problem in which the portfolio CVaR is minimised. Numerical results are presented.This study was funded by NET ACE at OptiRisk Systems

Reading Videogames as (authorless) Literature

This article presents the outcomes of research, funded by the Arts and Humanities Research Council in England and informed by work in the fields of new literacy research, gaming studies and the socio-cultural framing of education, for which the videogame L.A. Noire (Rockstar Games, 2011) was studied within the orthodox framing of the English Literature curriculum at A Level (pre-University) and Undergraduate (degree level). There is a plethora of published research into the kinds of literacy practices evident in videogame play, virtual world engagement and related forms of digital reading and writing (Gee, 2003; Juul, 2005; Merchant, Gillen, Marsh and Davies, 2012; Apperley and Walsh, 2012; Bazalgette and Buckingham, 2012) as well as the implications of such for home / school learning (Dowdall, 2006; Jenkins, 2006; Potter, 2012) and for teachers’ own digital lives (Graham, 2012). Such studies have tended to focus on younger children and this research is also distinct from such work in the field in its exploration of the potential for certain kinds of videogame to be understood as 'digital transformations' of conventional ‘schooled’ literature. The outcomes of this project raise implications of such a conception for a further implementation of a ‘reframed’ literacy (Marsh, 2007) within the contemporary curriculum of a traditional and conservative ‘subject’. A mixed methods approach was adopted. Firstly, students contributing to a gamplay blog requiring them to discuss their in-game experience through the ‘language game’ of English Literature, culminating in answering a question constructed with the idioms of the subject’s set text ‘final examination’. Secondly, students taught their teachers to play L.A. Noire, with free choice over the context for this collaboration. Thirdly, participants returned to traditional roles in order to work through a set of study materials provided, designed to reproduce the conventions of the ‘study guide’ for literature education. Interviews were conducted after each phase and the outcomes informed a redrafting of the study materials which are now available online for teachers – this being the ‘practical’ outcome of the research (Berger and McDougall, 2012). In the act of inserting the study of L.A. Noire into the English Literature curriculum as currently framed, this research moves, through a practical ‘implementation’ beyond longstanding debates around narratology and ludology (Frasca, 2003; Juul, 2005) in the field of game studies (Leaning, 2012) through a direct connection to new literacy studies and raises epistemological questions about ‘subject identity’, informed by Bernstein (1996) and Bourdieu (1986) and the implications for digital transformations of texts for both ideas about cultural value in schooled literacy (Kendall and McDougall, 2011) and the politics of ‘expertise’ in pedagogic relations (Ranciere, 2009, Bennett, Kendall and McDougall, 2012a)

Structural studies of (rac)-BIPHEN organomagnesiates and intermediates in the halogen-metal exchange of 2-Bromopyridine

Four lithium magnesiate complexes (2−5) containing the dianionic (rac)-BIPHEN ligand have been prepared and characterized using X-ray crystallography and NMR spectroscopy. (THF)3·Li2Mg{(rac)-BIPHEN}nBu2, 2, (THF)3·Li2Mg{(rac)-BIPHEN}(CH2SiMe3)2, 3, and (THF)2·Li2Mg{(rac)-BIPHEN}neoPe2, 4, have been prepared by complexation of the appropriate dialkylmagnesium compound with in situ prepared Li(rac)-BIPHEN in a mixture of hydrocarbon/THF. For all structures, the Mg centers are four-coordinate (and retain the alkyl groups); however, in 2 and 3 the two Li centers have different coordination spheres (one binding to one THF molecule, the other to two). The solid-state structures of 2 and 3 are essentially isostructural with that of 4 except that both Li atoms in this molecule have equivalent coordination spheres. The solution behaviors of these three molecules have been studied by 1H, 13C, and DOSY NMR spectroscopy. During the synthesis of 2, it was discovered that a (rac)-BIPHEN-rich (or n-butyl-free) lithium magnesiate, (THF)4Li2Mg{(rac)-BIPHEN}fo2, 2b, could be isolated. The lithium precursor to 2−5, (THF)4·Li4{(rac)-BIPHEN)}2, 1, has also been isolated. Within the molecular structure of this tetranuclear complex, there are three different Li coordination environments. Finally, 2 has already shown promise as a reagent in a halogen−metal exchange reaction with 2-bromopyridine. The structural chemistry at play in this reaction was probed by X-ray crystallography and NMR spectroscopy. The organometallic intermediate pyridyl-magnesiated 5, (THF)2·Li2Mg{(rac)-BIPHEN}(2-pyridyl)2, was isolated in high yield

A topos for algebraic quantum theory

The aim of this paper is to relate algebraic quantum mechanics to topos theory, so as to construct new foundations for quantum logic and quantum spaces. Motivated by Bohr's idea that the empirical content of quantum physics is accessible only through classical physics, we show how a C*-algebra of observables A induces a topos T(A) in which the amalgamation of all of its commutative subalgebras comprises a single commutative C*-algebra. According to the constructive Gelfand duality theorem of Banaschewski and Mulvey, the latter has an internal spectrum S(A) in T(A), which in our approach plays the role of a quantum phase space of the system. Thus we associate a locale (which is the topos-theoretical notion of a space and which intrinsically carries the intuitionistic logical structure of a Heyting algebra) to a C*-algebra (which is the noncommutative notion of a space). In this setting, states on A become probability measures (more precisely, valuations) on S(A), and self-adjoint elements of A define continuous functions (more precisely, locale maps) from S(A) to Scott's interval domain. Noting that open subsets of S(A) correspond to propositions about the system, the pairing map that assigns a (generalized) truth value to a state and a proposition assumes an extremely simple categorical form. Formulated in this way, the quantum theory defined by A is essentially turned into a classical theory, internal to the topos T(A).Comment: 52 pages, final version, to appear in Communications in Mathematical Physic