Murine HPV16 E7-expressing transgenic skin effectively emulates the cellular and molecular features of human high-grade squamous intraepithelial lesions.

Currently available vaccines prevent HPV infection and development of HPV-associated malignancies, but do not cure existing HPV infections and dysplastic lesions. Persistence of infection(s) in immunocompetent patients may reflect induction of local immunosuppressive mechanisms by HPV, providing a target for therapeutic intervention. We have proposed that a mouse, expressing HPV16 E7 oncoprotein under a Keratin 14 promoter (K14E7 mice), and which develops epithelial hyperplasia, may assist with understanding local immune suppression mechanisms that support persistence of HPV oncogene-induced epithelial hyperplasia. K14E7 skin grafts recruit immune cells from immunocompetent hosts, but consistently fail to be rejected. Here, we review the literature on HPV-associated local immunoregulation, and compare the findings with published observations on the K14E7 transgenic murine model, including comparison of the transcriptome of human HPV-infected pre-malignancies with that of murine K14E7 transgenic skin. We argue from the similarity of i) the literature findings and ii) the transcriptome profiles that murine K14E7 transgenic skin recapitulates the cellular and secreted protein profiles of high-grade HPV-associated lesions in human subjects. We propose that the K14E7 mouse may be an appropriate model to further study the immunoregulatory effects of HPV E7 expression, and can facilitate development and testing of therapeutic vaccines

Modelling Oscillator synchronisation during vertebrate axis segmentation

he somitogenesis clock regulates the periodicity with which somites form in the posterior pre-somitic mesoderm. Whilst cell heterogeneity results in noisy oscillation rates amongst constituent cells, synchrony within the population is maintained as oscillators are entrained via juxtracine signalling mechanisms. Here we consider a population of phase-coupled oscillators and investigate how biologically motivated perturbations to the entrained state can perturb synchrony within the population. We find that the ratio of mitosis length to clock period can influence levels of desynchronisation. Moreover, we observe that random cell movement, and hence change of local neighbourhoods, increases synchronisation

Continuum sensitivity and design optimization of superconducting systems under critical current densities with magnetic field dependence

Funder: sungkyunkwan university; doi: http://dx.doi.org/10.13039/501100002647AbstractThis paper presents an approach for deriving the continuum sensitivity of superconducting systems operating at critical current densities and an optimization method based on the continuum sensitivity. In the sensitivity problem, the superconducting systems is represented by a variational state equation, wherein the magnetic permeability depends on the magnetic field, which is transformed from a state equation with a field-dependent source. The design sensitivity is derived using the material derivative concept of continuum mechanics and the adjoint variable method. The adjoint system has a material property represented as a symmetric tensor that contains the sensitivity of the current density with respect to the magnetic field. The design sensitivity is represented in the analytical form of a surface integral on the interface between the superconducting material and its surroundings, which depends on the sensitivity of the current density. The optimization scheme is constructed based on the continuum design sensitivity. In the design optimization, the level set method is used to express the shape variation of the superconducting materials. The numerical example of infinite solenoids demonstrates that the design sensitivity provides an accurate design solution considering the critical current condition. In addition, the design example of a magnetic resonance imaging solenoid shows that the derived design sensitivity has the inherent ability for attaining the compact design by treating the input current of a superconducting system as a critical condition.</jats:p

Hot new directions for quasi-Monte Carlo research in step with applications

This article provides an overview of some interfaces between the theory of quasi-Monte Carlo (QMC) methods and applications. We summarize three QMC theoretical settings: first order QMC methods in the unit cube $[0,1]^s$ and in $\mathbb{R}^s$, and higher order QMC methods in the unit cube. One important feature is that their error bounds can be independent of the dimension $s$ under appropriate conditions on the function spaces. Another important feature is that good parameters for these QMC methods can be obtained by fast efficient algorithms even when $s$ is large. We outline three different applications and explain how they can tap into the different QMC theory. We also discuss three cost saving strategies that can be combined with QMC in these applications. Many of these recent QMC theory and methods are developed not in isolation, but in close connection with applications

Holographic Approach to Regge Trajectory and Rotating D5 brane

We study the Regge trajectories of holographic mesons and baryons by considering rotating strings and D5 brane, which is introduced as the baryon vertex. Our model is based on the type IIB superstring theory with the background of asymptotic $AdS_5\times S^5$. This background is dual to a confining supersymmetric Yang-Mills theory (SYM) with gauge condensate, $$, which determines the tension of the linear potential between the quark and anti-quark. Then the slope of the meson trajectory ($\alpha'_{M}$) is given by this condensate as $\alpha'_{M}=1/\sqrt{\pi }$ at large spin $J$. This relation is compatible with the other theoretical results and experiments. For the baryon, we show the importance of spinning baryon vertex to obtain a Regge slope compatible with the one of $N$ and $\Delta$ series. In both cases, mesons and baryons, the trajectories are shifted to large mass side with the same slope for increasing current quark mass.Comment: 28 pages, 7 figure

The relationship between web enjoyment and student perceptions and learning using a web-based tutorial

Web enjoyment has been regarded as a component of system experience. However, there has been little targeted research considering the role of web enjoyment alone in student learning using web-based systems. To address this gap, this study aims to examine the influence of web enjoyment on learning performance and perceptions by controlling system experience as a variable in the study. 74 students participated in the study, using a web-based tutorial covering subject matter in the area of 'Computation and algorithms'. Their learning performance was assessed with a pre-test and a post-test and their learning perceptions were evaluated with a questionnaire. The results indicated that there are positive relationships between the levels of web enjoyment and perceived usefulness and non-linear navigation for users with similar, significant levels of system experience. The implications of these findings in relation to web-based learning are explored and ways in which the needs of students who report different levels of web enjoyment might be met are discussed

High-Bandwidth Low-Cost High-Speed Optical Fiber Links using Organic Light Emitting Diodes

Record-high 200 Mbps transmission using an OLED with a 31 MHz 3 dB bandwidth using a 3-tap feedforward equaliser is achieved, demonstrating the potential of such devices for use in low-cost polymer optical fiber links.EPSRC Ultra Parallel Visible Light Communication Project (EP/K00042X/1) EPSRC Studentship 146672

When the path is never shortest: a reality check on shortest path biocomputation

Shortest path problems are a touchstone for evaluating the computing performance and functional range of novel computing substrates. Much has been published in recent years regarding the use of biocomputers to solve minimal path problems such as route optimisation and labyrinth navigation, but their outputs are typically difficult to reproduce and somewhat abstract in nature, suggesting that both experimental design and analysis in the field require standardising. This chapter details laboratory experimental data which probe the path finding process in two single-celled protistic model organisms, Physarum polycephalum and Paramecium caudatum, comprising a shortest path problem and labyrinth navigation, respectively. The results presented illustrate several of the key difficulties that are encountered in categorising biological behaviours in the language of computing, including biological variability, non-halting operations and adverse reactions to experimental stimuli. It is concluded that neither organism examined are able to efficiently or reproducibly solve shortest path problems in the specific experimental conditions that were tested. Data presented are contextualised with biological theory and design principles for maximising the usefulness of experimental biocomputer prototypes.Comment: To appear in: Adamatzky, A (Ed.) Shortest path solvers. From software to wetware. Springer, 201