RESPECT: A personal development programme for young people at risk of social exclusion - Final Report

This is the final, summary report in the series of reports written on the RESPECT evaluation.The RESPECT programme was funded for three years from the Government’s Invest to Save initiative. It brought together a number of elements of Cheshire Fire and Rescue Service’s earlier work with young people in a concerted attempt to tackle wider challenges pertinent to the fire services and partner agencies. RESPECT was a targeted intervention for young people living in Cheshire, Halton and Warrington who were aged 11 to 16 years and who were disaffected and/or displayed antisocial behaviour.The RESPECT programme was funded for three years from the Government’s 'Invest to Save' initiative. The RESPECT partnership was made up of the following organisations: Cheshire Fire Service; The Youth Federation; Cheshire County Council; Halton Borough Council; Warrington Borough Council; and Cheshire & Warrington Connexions

Sure Start Blacon reach report, April 2004 - March 2005

This project report discusses Sure Start computerised records (covering personal details of all registrations within the Sure Start programme and records of each serivce and which service users have accessed them) which allow the 'reach' of the local programme across Blacon to be established between 1 April 2004 and 31 March 2005

Mapping and gapping services for children, young people and families in Blacon

This research report provides a map of the services available to children and families in Blacon and explores whether there are any gaps in provision.Blacon Education Villag

Improving the worthiness of the Elder problem as a benchmark for buoyancy driven convection models

An important trapping mechanism associated with the geosequestration of CO~2~ is that of dissolution into the formation water. Although supercritical CO~2~ is significantly less dense than water, experimental data reported in the literature show that the density of an aqueous solution of CO~2~ could be slightly greater. Under normal situations, the transfer of gas to solution is largely controlled by the relatively slow process of molecular diffusion. However, the presence of variable densities can trigger off gravity instabilities leading to much larger-scale convection processes. Such processes can potentially enhance rates of dissolution by an order of magnitude. Consequently there is a need for future performance assessment models to incorporate buoyancy driven convection (BDC). A major issue associated with BDC models is that of grid convergence when benchmarking to the Elder problem. The Elder problem originates from a heat convection experiment whereby a rectangular Hele-Shaw cell was heated over the central half of its base. A quarter of the way through the experiment, Elder (1967) observed six plumes, with four narrow plumes in the center and two larger plumes at the edges. As the experiment progressed, only four plumes remained. The issue is that depending on the grid resolution used when seeking to model this problem, modelers have found that different schemes yield steady states with either one, two or three plumes. The aim of this paper is to clarify and circumvent the issue of multiple steady state solutions in the Elder problem using a pseudospectral method

Simulating star formation in molecular cloud cores I. The influence of low levels of turbulence on fragmentation and multiplicity

We present the results of an ensemble of simulations of the collapse and fragmentation of dense star-forming cores. We show that even with very low levels of turbulence the outcome is usually a binary, or higher-order multiple, system. We take as the initial conditions for these simulations a typical low-mass core, based on the average properties of a large sample of observed cores. All the simulated cores start with a mass of $M = 5.4 M_{\odot}$, a flattened central density profile, a ratio of thermal to gravitational energy $\alpha_{\rm therm} = 0.45$ and a ratio of turbulent to gravitational energy $\alpha_{\rm turb} = 0.05$. Even this low level of turbulence is sufficient to produce multiple star formation in 80% of the cores; the mean number of stars and brown dwarfs formed from a single core is 4.55, and the maximum is 10. At the outset, the cores have no large-scale rotation. The only difference between each individual simulation is the detailed structure of the turbulent velocity field. The multiple systems formed in the simulations have properties consistent with observed multiple systems. Dynamical evolution tends preferentially to eject lower mass stars and brown dwarves whilst hardening the remaining binaries so that the median semi-major axis of binaries formed is $\sim 30$ au. Ejected objects are usually single low-mass stars and brown dwarfs, yielding a strong correlation between mass and multiplicity. Our simulations suggest a natural mechanism for forming binary stars that does not require large-scale rotation, capture, or large amounts of turbulence.Comment: 20 pages, 12 figures submitted to A&

Auditing file system permissions using Association Rule Mining

Identifying irregular file system permissions in large, multi-user systems is challenging due to the complexity of gaining structural understanding from large volumes of permission information. This challenge is exacerbated when file systems permissions are allocated in an ad-hoc manner when new access rights are required, and when access rights become redundant as users change job roles or terminate employment. These factors make it challenging to identify what can be classed as an irregular file system permission, as well as identifying if they are irregular and exposing a vulnerability. The current way of finding such irregularities is by performing an exhaustive audit of the permission distribution; however, this requires expert knowledge and a significant amount of time. In this paper a novel method of modelling file system permissions which can be used by association rule mining techniques to identify irregular permissions is presented. This results in the creation of object-centric model as a by-product. This technique is then implemented and tested on Microsoft's New Technology File System permissions (NTFS). Empirical observations are derived by making comparisons with expert knowledge to determine the effectiveness of the proposed technique on five diverse real-world directory structures extracted from different organisations. The results demonstrate that the technique is able to correctly identify irregularities with an average accuracy rate of 91%, minimising the reliance on expert knowledge. Experiments are also performed on synthetic directory structures which demonstrate an accuracy rate of 95% when the number of irregular permissions constitutes 1% of the total number. This is a significant contribution as it creates the possibility of identifying vulnerabilities without prior knowledge of how to file systems permissions are implemented within a directory structure

TDP1/TOP1 ratio as a promising indicator for the response of small cell lung cancer to topotecan

BACKGROUND AND OBJECTIVE Small cell lung cancer (SCLC) is one of the most challenging tumors to treat due to high proliferation rate, early metastatic dissemination and rapid development of chemotherapy resistance. The current treatment protocols involve the use of topoisomerase 1 (TOP1) poisons such as irinotecan and topotecan in combination with platinum-based compounds. TOP1 poisons kill cancer cells by trapping TOP1 on DNA, generating lethal DNA double-strand breaks. A potential mechanism employed by cancer cells to resist killing by TOP1 poisons is to overexpress enzymes involved in the repair of TOP1-DNA breaks. Tyrosyl DNA phosphodiesterase 1 (TDP1) is a key player in this process and despite its importance, no data is currently available to correlate TDP1 protein and mRNA levels with catalytic activity in SCLC. In addition, it is not known if TDP1 and TOP1 protein levels correlate with the cellular response of SCLC to TOP1 based therapies. METHODS AND RESULTS We report a remarkable variation in TDP1 and TOP1 protein levels in a panel of SCLC cell lines. TDP1 protein level correlates well with TDP1 mRNA and TDP1 catalytic activity, as measured by two newly developed independent activity assays, suggesting the potential utility of immunohistochemistry in assessing TDP1 levels in SCLC tissues. We further demonstrate that whilst TDP1 protein level alone does not correlate with topotecan sensitivity, TDP1/TOP1 ratio correlates well with sensitivity in 8 out of 10 cell lines examined. CONCLUSION This study provides the first cellular analyses of TDP1 and TOP1 in SCLC and suggests the potential utility of TDP1/TOP1 ratio to assess the response of SCLC to topotecan. The establishment and validation of an easy-to-use TDP1 enzymatic assay in cell extracts could be exploited as a diagnostic tool in the clinic. These findings may help in stratifying patients that are likely to benefit from TOP1 poisons and TDP1 inhibitors currently under development

‘Smart Cities’ – Dynamic Sustainability Issues and Challenges for ‘Old World’ Economies: A Case from the United Kingdom

The rapid and dynamic rate of urbanization, particularly in emerging world economies, has resulted in a need to find sustainable ways of dealing with the excessive strains and pressures that come to bear on existing infrastructures and relationships. Increasingly during the twenty-first century policy makers have turned to technological solutions to deal with this challenge and the dynamics inherent within it. This move towards the utilization of technology to underpin infrastructure has led to the emergence of the term ‘Smart City’. Smart cities incorporate technology based solutions in their planning development and operation. This paper explores the organizational issues and challenges facing a post-industrial agglomeration in the North West of England as it attempted to become a ‘Smart City’. In particular the paper identifies and discusses the factors that posed significant challenges for the dynamic relationships residents, policymakers and public and private sector organizations and as a result aims to use these micro-level issues to inform the macro-debate and context of wider Smart City discussions. In order to achieve this, the paper develops a range of recommendations that are designed to inform Smart City design, planning and implementation strategies

An atom-efficient and convergent approach to the preparation of NS5A inhibitors by C-H activation

A novel approach of the convergent functionalisation of aryl dibromides to form NS5A type inhibitors using C–H activation is reported. The focus of investigation was to reduce the formation of homodimeric side product, as well as to investigate the scope of different aryl dibromides that were tolerated under the reaction conditions. The C–H activation methodology was found to give a viable synthetic route to NS5A inhibitors, with late stage functionalisation of the core portion of the molecule, albeit with some chemical functionalities not tolerated