Biomarkers of oxidative stress: methods and measures of oxidative DNA damage (COMET assay) and telomere shortening

Oxidative stress is fast becoming the nutritional and medical buzzword for the twenty-first century. The theoretical importance of oxidative stress in diabetes is highlighted by its potential double impact on metabolic dysfunction on one hand and the vascular system on the other hand. The new concept of oxidative stress, being an important trigger in the onset and progression of diabetes and its complications, emphasizes the need for measurement of markers of oxidation to assess the degree of oxidative stress. While we have been routinely measuring biomarkers in our molecular epidemiology projects, here we discuss the utility of two assays, (a) DNA damage assessment by COMET measurement and (b) telomere length measurement. As DNA damage is efficiently repaired by cellular enzymes, its measurement gives a snapshot view of the level of oxidative stress. The protocol allows for measurement of oxidative DNA damage (FPG-sensitive DNA strand breaks). Telomere length measured by Southern blotting technique allows one to estimate the chronic burden of oxidative stress at the molecular level and is now considered as biomarker of biological aging

Evidence-based practice 'on-the-go': using ViaTherapy as a tool to enhance clinical decision making in upper limb rehabilitation after stroke, a quality improvement initiative.

Recovery of upper limb function after stroke is currently sub-optimal, despite good quality evidence showing that interventions enabling repetitive practice of task-specific activity are effective in improving function. Therapists need to access and engage with such evidence to optimise outcomes with people with stroke, but this is challenging in fast-paced stroke rehabilitation services. This quality improvement project aimed to investigate acceptability and service impact of a new, international tool for accessing evidence on upper limb rehabilitation after stroke-'ViaTherapy'-in a team of community rehabilitation therapists. Semi-structured interviews were undertaken at baseline to determine confidence in, and barriers to, evidence-based practice (EBP) to support clinical decision making. Reported barriers included time, lack of access to evidence and a research-practice disconnect. The clinicians then integrated use of 'ViaTherapy' into their practice for 4 weeks. Follow-up interviews explored the accessibility of the tool in community rehabilitation practice, and its impact on clinician confidence, treatment planning and provision. Clinicians found the tool, used predominantly in mobile device app format, to be concise and simple to use, providing evidence 'on-the-go'. Confidence in accessing and using EBP grew by 22% from baseline. Clinicans reported changes in intensity of delivery of interventions, as rapid access to recommended doses via the tool was available. Following this work, the participating health and social care service provider changed provision of therapists' technology to enable use of apps. Barriers to use of EBP in stroke rehabilitation persist; the baseline situation here supported the need for more accessible means of integrating best evidence into clinical processes. This quality improvement project successfully integrated ViaTherapy into clinical practice, and found that the tool has potential to underpin positive changes in upper limb therapy service delivery after stroke, by increasing accessibility to, use of and confidence in EBP. Definitive evaluation is now indicated

Energy Relaxation in Nonlinear One-Dimensional Lattices

We study energy relaxation in thermalized one-dimensional nonlinear arrays of the Fermi-Pasta-Ulam type. The ends of the thermalized systems are placed in contact with a zero-temperature reservoir via damping forces. Harmonic arrays relax by sequential phonon decay into the cold reservoir, the lower frequency modes relaxing first. The relaxation pathway for purely anharmonic arrays involves the degradation of higher-energy nonlinear modes into lower energy ones. The lowest energy modes are absorbed by the cold reservoir, but a small amount of energy is persistently left behind in the array in the form of almost stationary low-frequency localized modes. Arrays with interactions that contain both a harmonic and an anharmonic contribution exhibit behavior that involves the interplay of phonon modes and breather modes. At long times relaxation is extremely slow due to the spontaneous appearance and persistence of energetic high-frequency stationary breathers. Breather behavior is further ascertained by explicitly injecting a localized excitation into the thermalized array and observing the relaxation behavior

Holographic principle in the BDL brane cosmology

We study the holographic principle in the brane cosmology. Especially we describe how to accommodate the 5D anti de Sitter Schwarzschild (AdSS$_5$) black hole in the Binetruy-Deffayet-Langlois (BDL) approach of brane cosmology. It is easy to make a connection between a mass $M$ of the AdSS$_5$ black hole and a conformal field theory (CFT)-radiation dominated universe on the brane in the moving domain wall approach. But this is not established in the BDL approach. In this case we use two parameters $C_1, C_2$ in the Friedmann equation. These arise from integration and are really related to the choice of initial bulk matter. If one chooses a bulk energy density $\rho_B$ to account for a mass $M$ of the AdSS$_5$ black hole and the static fifth dimension, a CFT-radiation term with $\rho_{CFT} \sim M/a^{4}$ comes out from the bulk matter without introducing a localized matter distribution on the brane. This means that the holographic principle can be established in the BDL brane cosmology.Comment: 9 pages, a version to appear in PR

Brane cosmology with curvature corrections

We study the cosmology of the Randall-Sundrum brane-world where the Einstein-Hilbert action is modified by curvature correction terms: a four-dimensional scalar curvature from induced gravity on the brane, and a five-dimensional Gauss-Bonnet curvature term. The combined effect of these curvature corrections to the action removes the infinite-density big bang singularity, although the curvature can still diverge for some parameter values. A radiation brane undergoes accelerated expansion near the minimal scale factor, for a range of parameters. This acceleration is driven by the geometric effects, without an inflaton field or negative pressures. At late times, conventional cosmology is recovered.Comment: RevTex4, 8 pages, no figures, minor change

Overexpression of HvCslF6 in barley grain alters carbohydrate partitioning plus transfer tissue and endosperm development

In cereal grain sucrose is converted into storage carbohydrates; mainly starch, fructan and (1,3;1,4)-β-glucan (MLG). Previously, endosperm-specific overexpression of the HvCslF6 gene in hull-less barley resulted in high MLG and low starch content in mature grains. Morphological changes included inwardly elongated aleurone cells, irregular cell shapes of peripheral endosperm and smaller starch granules of starchy endosperm. Here we explored the physiological basis for these defects by investigating how changes in carbohydrate composition of developing grain impact mature grain morphology. Augmented MLG coincided with increased levels of soluble carbohydrates in the cavity and endosperm at the storage phase. Transcript levels of genes relating to cell wall, starch, sucrose and fructan metabolism were perturbed in all tissues. The cell walls of endosperm transfer cells (ETC) in transgenic grain were thinner and showed reduced mannan labelling relative to wild type. At the early storage phase rupture of the non-uniformly developed ETC and disorganization of adjacent endosperm cells was observed. Soluble sugars accumulated in the developing grain cavity, suggesting a disturbance of carbohydrate flow from the cavity towards the endosperm, resulting in a shrunken mature grain phenotype. Our findings demonstrate the importance of regulating carbohydrate partitioning in maintenance of grain cellularization and filling processes.Wai Li Lim, Helen M. Collins, Caitlin S. Byrt, Jelle Lahnstein, Neil J. Shirley, Matthew K. Aubert, Matthew R. Tucker, Manuela Peukert, Andrea Matros, and Rachel A. Burto

Spherically Symmetric Braneworld Solutions with R_{4} term in the Bulk

An analysis of a spherically symmetric braneworld configuration is performed when the intrinsic curvature scalar is included in the bulk action; the vanishing of the electric part of the Weyl tensor is used as the boundary condition for the embedding of the brane in the bulk. All the solutions outside a static localized matter distribution are found; some of them are of the Schwarzschild-(A)dS_{4} form. Two modified Oppenheimer-Volkoff interior solutions are also found; one is matched to a Schwarzschild-(A)dS_{4} exterior, while the other does not. A non-universal gravitational constant arises, depending on the density of the considered object; however, the conventional limits of the Newton's constant are recovered. An upper bound of the order of TeV for the energy string scale is extracted from the known solar system measurements (experiments). On the contrary, in usual brane dynamics, this string scale is calculated to be larger than TeV.Comment: 23 pages, 1 figure, one minor chang

An integrated approach to the assessment of long range correlation in time series data

To assess whether a given time series can be modeled by a stochastic process possessing long range correlation one usually applies one of two types of analysis methods: the spectral method and the random walk analysis. The first objective of this work is to show that each one of these methods used alone can be susceptible to producing false results. We thus advocate an integrated approach which requires the use of both methods in a consistent fashion. We provide the theoretical foundation of this approach and illustrate the main ideas using examples. The second objective relates to the observation of long range anticorrelation (Hurst exponent H < 1/2) in real world time series data. The very peculiar nature of such processes is emphasized in light of the stringent condition under which such processes can occur. Using examples we discuss the possible factors that could contribute to the false claim of long range anticorrelations and demonstrate the particular importance of the integrated approach in this case.Comment: 15 pages, 33 figure

Challenges and Obstacles for a Bouncing Universe in Brane Models

A Brane evolving in the background of a charged AdS black-hole displays in general a bouncing behaviour with a smooth transition from a contracting to an expanding phase. We examine in detail the conditions and consequences of this behaviour in various cases. For a cosmological-constant-dominated Brane, we obtain a singularity-free, inflationary era which is shown to be compatible only with an intermediate-scale fundamental Planck mass. For a radiation-dominated Brane, the bouncing behaviour can occur only for background-charge values exceeding those allowed for non-extremal black holes. For a matter-dominated Brane, the black-hole mass affects the proper volume or the expansion rate of the Brane. We also consider the Brane evolving in an asymmetric background of two distinct charged AdS black hole spacetimes being bounded by the Brane and find that, in the case of an empty critical Brane, bouncing behaviour occurs only if the black-hole mass difference is smaller than a certain value. The effects of a Brane curvature term on the bounce at early and late times are also investigated.Comment: 23 pages, Latex file, comments and references added, version to appear in Phys. Rev.