Microflow of fluorescently labelled red blood cells in tumours expressing single isoforms of VEGF and their response to VEGF-R tyrosine kinase inhibition

This paper was presented at the 2nd Micro and Nano Flows Conference (MNF2009), which was held at Brunel University, West London, UK. The conference was organised by Brunel University and supported by the Institution of Mechanical Engineers, IPEM, the Italian Union of Thermofluid dynamics, the Process Intensification Network, HEXAG - the Heat Exchange Action Group and the Institute of Mathematics and its Applications.In this work we studied the functional differences between the microcirculation of murine tumours that only express single isoforms of vascular endothelial growth factor-A (VEGF), VEGF120 and VEGF188, and the effect of VEGF receptor tyrosine kinase (VEGF-R TK) inhibition on their functional response to the vascular disrupting agent, combretastatin A-4 phosphate (CA-4-P). We used measurement of fluorescentlylabelled red blood cell (RBC) velocities in tumour microvessels to study this functional response. RBC velocity for control VEGF120-expressing tumours was over 50% slower than for control VEGF188-expressing tumours, which may be due to the immature and haemorrhagic vasculature of the VEGF120 tumour. After chronic treatment with a VEGF-R tyrosine kinase inhibitor, SU5416, RBC velocities in VEGF120 tumours were significantly increased compared to control VEGF120 tumours, and similar to velocities in both VEGF188 treatment groups. Control and SU5416 treated VEGF188 tumours were not different from each other. Treatment of VEGF120 tumours with SU5416 reduced their vascular response to CA-4-P to a similar level to the VEGF188 tumours. Differential expression of VEGF isoforms not only affected vascular function in untreated tumours but also impacted on response to a vascular disrupting drug, CA-4-P, alone and in combination with an anti-angiogenic approach involving VEGF-R TK inhibition. Analysis of RBC velocities is a useful tool in measuring functional responses to vascular targeted treatments.This study is funded by the Cancer Research UK

Assessment for learning : a model for the development of a child’s self competence in the early years of education

In recent years policy documents, curricula and other educational initiatives have promoted a pedagogy founded on the concept of independent learning. This is broadly defined as ‘having the belief in yourself to think through learning activities, problems or challenges, make decisions about your learning and act upon those decisions (Blandford and Knowles, 2009:336). The central role of Assessment for Learning (AfL) in this process is often overlooked in practice. By considering the findings from a small scale research study this article addresses the central role of the teacher /practitioner in developing effective AfL in the early years classroom (3-5 years)

Toroidal automorphic forms, Waldspurger periods and double Dirichlet series

The space of toroidal automorphic forms was introduced by Zagier in the 1970s: a GL_2-automorphic form is toroidal if it has vanishing constant Fourier coefficients along all embedded non-split tori. The interest in this space stems (amongst others) from the fact that an Eisenstein series of weight s is toroidal for a given torus precisely if s is a non-trivial zero of the zeta function of the quadratic field corresponding to the torus. In this paper, we study the structure of the space of toroidal automorphic forms for an arbitrary number field F. We prove that it decomposes into a space spanned by all derivatives up to order n-1 of an Eisenstein series of weight s and class group character omega precisely if s is a zero of order n of the L-series corresponding to omega at s, and a space consisting of exactly those cusp forms the central value of whose L-series is zero. The proofs are based on an identity of Hecke for toroidal integrals of Eisenstein series and a result of Waldspurger about toroidal integrals of cusp forms combined with non-vanishing results for twists of L-series proven by the method of double Dirichlet series.Comment: 14 page

Casimir Dispersion Forces and Orientational Pairwise Additivity

A path integral formulation is used to study the fluctuation-induced interactions between manifolds of arbitrary shape at large separations. It is shown that the form of the interactions crucially depends on the choice of the boundary condition. In particular, whether or not the Casimir interaction is pairwise additive is shown to depend on whether the ``metallic'' boundary condition corresponds to a ``grounded'' or an ``isolated'' manifold.Comment: 6 pages, RevTe

Existence of a phase transition under finite magnetic field in the long-range RKKY Ising spin glass Dyx_{x}Y1−x_{1-x}Ru2_{2}Si2_{2}

A phase transition of a model compound of the long-range Ising spin glass (SG) Dy$_{x}$Y$_{1-x}$Ru$_{2}$Si$_{2}$, where spins interact via the RKKY interaction, has been investigated. The static and the dynamic scaling analyses reveal that the SG phase transition in the model magnet belongs to the mean-field universality class. Moreover, the characteristic relaxation time in finite magnetic fields exhibits a critical divergent behavior as well as in zero field, indicating a stability of the SG phase in finite fields. The presence of the SG phase transition in field in the model magnet strongly syggests that the replica symmetry is broken in the long-range Ising SG.Comment: 4 pages, 4 figures, to be published in JPSJ (2010

Current conservation in two-dimensional AC-transport

The electric current conservation in a two-dimensional quantum wire under a time dependent field is investigated. Such a conservation is obtained as the global density of states contribution to the emittance is balanced by the contribution due to the internal charge response inside the sample. However when the global partial density of states is approximately calculated using scattering matrix only, correction terms are needed to obtain precise current conservation. We have derived these corrections analytically using a specific two-dimensional system. We found that when the incident energy $E$ is near the first subband, our result reduces to the one-dimensional result. As $E$ approaches to the $n$-th subband with $n>1$, the correction term diverges. This explains the systematic deviation to precise current conservation observed in a previous numerical calculation.Comment: 12 pages Latex, submitted to Phys. Rev.

Evidence accumulation models with R: A practical guide to hierarchical Bayesian methods

Evidence accumulation models are a useful tool to allow researchers to investigate the latent cognitive variables that underlie response time and response accuracy. However, applying evidence accumulation models can be difficult because they lack easily computable forms. Numerical methods are required to determine the parameters of evidence accumulation that best correspond to the fitted data. When applied to complex cognitive models, such numerical methods can require substantial computational power which can lead to infeasibly long compute times. In this paper, we provide efficient, practical software and a step-by-step guide to fit evidence accumulation models with Bayesian methods. The software, written in C++, is provided in an R package: 'ggdmc'. The software incorporates three important ingredients of Bayesian computation, (1) the likelihood functions of two common response time models, (2) the Markov chain Monte Carlo (MCMC) algorithm (3) a population-based MCMC sampling method. The software has gone through stringent checks to be hosted on the Comprehensive R Archive Network (CRAN) and is free to download. We illustrate its basic use and an example of fitting complex hierarchical Wiener diffusion models to four shooting-decision data sets

Cell adhesion molecules nectins and associating proteins: Implications for physiology and pathology

Nectins have recently been identified as new cell adhesion molecules (CAMs) consisting of four members. They show immunoglobulin-like structures and exclusively localize at adherens junctions (AJs) between two neighboring cells. During the formation of cell–cell junctions, nectins function in cooperation with or independently of cadherins, major CAMs at AJs. Similar to cadherins, which are linked to the actin cytoskeleton by binding to catenins, nectins also bind to afadin through their C-terminal region and are linked to the actin cytoskeleton. In addition to nectins, there are nectin-like molecules (Necls), which resemble nectins in their structures and consist of five members. Nectins and Necls are involved in the formation of various kinds of cell–cell adhesion, and also play key roles in diverse cellular functions including cell movement, proliferation, survival, and differentiation. Thus, nectins and Necls are crucial for physiology and pathology of multicellular organisms

Teaching Writing: a situated dynamic

publication-status: Publishedtypes: ArticleThe paper is theoretically grounded in Cultural Historical Activity Theory (CHAT) which holds that human development is founded within participation in social and cultural practices. In particular, the teaching of literacy is shaped not only by the curriculum as designated by policy makers and the institution in which it is located but also by the individuals’ understanding of what literacy and learning involves and how they act to achieve their goals. The paper explores data from a project that investigated the relationship between classroom talk and the teaching of writing in six early years classrooms. Participants’ own understandings of teaching and learning need to be taken into account by researchers and policy makers. CHAT has been used to explore the dynamic relationship between activity at societal, institutional and individual levels. It is argued that researchers and policy makers need to take account of the wider socio-cultural context in planning and evaluating curriculum development initiatives