Local versus Global Search in Channel Graphs

Previous studies of search in channel graphs has assumed that the search is global; that is, that the status of any link can be probed by the search algorithm at any time. We consider for the first time local search, for which only links to which an idle path from the source has already been established may be probed. We show that some well known channel graphs may require exponentially more probes, on the average, when search must be local than when it may be global.Comment: i+13 pages, 2 figure

Implementation of Directive 2004/38 in the United Kingdom

This article discusses the implementation of Directive 2004/38/EC (the Directive) within the UK’s legal system. After a section which summarises the historical, political and legal context, the article considers firstly the implementing legislation, then administrative practice and, finally, the response of the courts

New light on the ‘Drummer of Tedworth’: conflicting narratives of witchcraft in Restoration England

This paper presents a definitive text of hitherto little-known early documents concerning ‘The Drummer of Tedworth’, a poltergeist case that occurred in 1662-3 and became famous not least due to its promotion by Joseph Glanvill in his demonological work, Saducismus Triumphatus. On the basis of these and other sources, it is shown how responses to the events at Tedworth evolved from anxious piety on the part of their victim, John Mompesson, to confident apologetic by Glanvill, before they were further affected by the emergence of articulate scepticism about the case

Attracted Diffusion-Limited Aggregation

In this paper, we present results of extensive Monte Carlo simulations of diffusion-limited aggregation (DLA) with a seed placed on an attractive plane as a simple model in connection with the electrical double layers. We compute the fractal dimension of the aggregated patterns as a function of the attraction strength \alpha. For the patterns grown in both two and three dimensions, the fractal dimension shows a significant dependence on the attraction strength for small values of \alpha, and approaches to that of the ordinary two-dimensional (2D) DLA in the limit of large \alpha. For non-attracting case with \alpha=1, our results in three dimensions reproduce the patterns of 3D ordinary DLA, while in two dimensions our model leads to formation of a compact cluster with dimension two. For intermediate \alpha, the 3D clusters have quasi-2D structure with a fractal dimension very close to that of the ordinary 2D-DLA. This allows one to control morphology of a growing cluster by tuning a single external parameter \alpha.Comment: 6 pages, 6 figures, to appear in Phys. Rev. E (2012

Effective Electrostatic Interactions in Suspensions of Polyelectrolyte Brush-Coated Colloids

Effective electrostatic interactions between colloidal particles, coated with polyelectrolyte brushes and suspended in an electrolyte solvent, are described via linear response theory. The inner cores of the macroions are modeled as hard spheres, the outer brushes as spherical shells of continuously distributed charge, the microions (counterions and salt ions) as point charges, and the solvent as a dielectric continuum. The multi-component mixture of macroions and microions is formally mapped onto an equivalent one-component suspension by integrating out from the partition function the microion degrees of freedom. Applying second-order perturbation theory and a random phase approximation, analytical expressions are derived for the effective pair interaction and a one-body volume energy, which is a natural by-product of the one-component reduction. The combination of an inner core and an outer shell, respectively impenetrable and penetrable to microions, allows the interactions between macroions to be tuned by varying the core diameter and brush thickness. In the limiting cases of vanishing core diameter and vanishing shell thickness, the interactions reduce to those derived previously for star polyelectrolytes and charged colloids, respectively.Comment: 20 pages, 5 figures, Phys. Rev. E (in press

Label-free proteomics identifies Calreticulin and GRP75/Mortalin as peripherally accessible protein biomarkers for spinal muscular atrophy

BACKGROUND: Spinal muscular atrophy (SMA) is a neuromuscular disease resulting from mutations in the survival motor neuron 1 (SMN1) gene. Recent breakthroughs in preclinical research have highlighted several potential novel therapies for SMA, increasing the need for robust and sensitive clinical trial platforms for evaluating their effectiveness in human patient cohorts. Given that most clinical trials for SMA are likely to involve young children, there is a need for validated molecular biomarkers to assist with monitoring disease progression and establishing the effectiveness of therapies being tested. Proteomics technologies have recently been highlighted as a potentially powerful tool for such biomarker discovery. METHODS: We utilized label-free proteomics to identify individual proteins in pathologically-affected skeletal muscle from SMA mice that report directly on disease status. Quantitative fluorescent western blotting was then used to assess whether protein biomarkers were robustly changed in muscle, skin and blood from another mouse model of SMA, as well as in a small cohort of human SMA patient muscle biopsies. RESULTS: By comparing the protein composition of skeletal muscle in SMA mice at a pre-symptomatic time-point with the muscle proteome at a late-symptomatic time-point we identified increased expression of both Calreticulin and GRP75/Mortalin as robust indicators of disease progression in SMA mice. We report that these protein biomarkers were consistently modified in different mouse models of SMA, as well as across multiple skeletal muscles, and were also measurable in skin biopsies. Furthermore, Calreticulin and GRP75/Mortalin were measurable in muscle biopsy samples from human SMA patients. CONCLUSIONS: We conclude that label-free proteomics technology provides a powerful platform for biomarker identification in SMA, revealing Calreticulin and GRP75/Mortalin as peripherally accessible protein biomarkers capable of reporting on disease progression in samples of muscle and skin

Effects of Elevated H\u3csup\u3e+\u3c/sup\u3e And P\u3csub\u3ei\u3c/sub\u3e on The Contractile Mechanics of Skeletal Muscle Fibres From Young and Old Men: Implications for Muscle Fatigue in Humans

The present study aimed to identify the mechanisms responsible for the loss in muscle power and increased fatigability with ageing by integrating measures of whole‐muscle function with single fibre contractile mechanics. After adjusting for the 22% smaller muscle mass in old (73–89 years, n = 6) compared to young men (20–29 years, n = 6), isometric torque and power output of the knee extensors were, respectively, 38% and 53% lower with age. Fatigability was ∼2.7‐fold greater with age and strongly associated with reductions in the electrically‐evoked contractile properties. To test whether cross‐bridge mechanisms could explain age‐related decrements in knee extensor function, we exposed myofibres (n = 254) from the vastus lateralis to conditions mimicking quiescent muscle and fatiguing levels of acidosis (H+) (pH 6.2) and inorganic phosphate (Pi) (30 mm). The fatigue‐mimicking condition caused marked reductions in force, shortening velocity and power and inhibited the low‐ to high‐force state of the cross‐bridge cycle, confirming findings from non‐human studies that these ions act synergistically to impair cross‐bridge function. Other than severe age‐related atrophy of fast fibres (−55%), contractile function and the depressive effects of the fatigue‐mimicking condition did not differ in fibres from young and old men. The selective loss of fast myosin heavy chain II muscle was strongly associated with the age‐related decrease in isometric torque (r = 0.785) and power (r = 0.861). These data suggest that the age‐related loss in muscle strength and power are primarily determined by the atrophy of fast fibres, but the age‐related increased fatigability cannot be explained by an increased sensitivity of the cross‐bridge to H+ and Pi

Type I Superconductivity in YbSb2 Single Crystals

We present evidence of type I superconductivity in YbSb2 single crystals, from DC and AC magnetization, heat capacity and resistivity measurements. The critical temperature and critical field are determined to be $T_c\approx$ 1.3 K and $H_c\approx$ 55 Oe. A small Ginzburg-Landau parameter \kappa = 0.05, together with typical magnetization isotherms of type I superconductors, small critical field values, a strong Differential Paramagnetic Effect (DPE) signal, and a field-induced change from second to first order phase transition, confirm the type I nature of the superconductivity in YbSb2. A possible second superconducting state is observed in the radiofrequency (RF) susceptibility measurements, with $T_{c}^{(2)}\approx$ 0.41 K and $H_{c}^{(2)}\approx$ 430 Oe.Comment: 6 pages, 10 figure

Piloting a manualised weight management programme (Shape Up-LD) for overweight and obese persons with mild-moderate learning disabilities: study protocol for a pilot randomised controlled trial

National obesity rates have dramatically risen over the last decade. Being obese significantly reduces life expectancy, increases the risk of a range of diseases, and compromises quality of life. Costs to both the National Health Service and society are high. An increased prevalence of obesity in people with learning disabilities has been demonstrated. The consequences of obesity are particularly relevant to people with learning disabilities who are already confronted by health and social inequalities. In order to provide healthcare for all, and ensure equality of treatment for people with learning disabilities, services must be developed specifically with this population in mind. The aim of this project is to pilot the evaluation of a manualised weight management programme for overweight and obese persons with mild-moderate learning disabilities (Shape Up-LD)