Band Distributions for Quantum Chaos on the Torus

Band distributions (BDs) are introduced describing quantization in a toral phase space. A BD is the uniform average of an eigenstate phase-space probability distribution over a band of toral boundary conditions. A general explicit expression for the Wigner BD is obtained. It is shown that the Wigner functions for {\em all} of the band eigenstates can be reproduced from the Wigner BD. Also, BDs are shown to be closer to classical distributions than eigenstate distributions. Generalized BDs, associated with sets of adjacent bands, are used to extend in a natural way the Chern-index characterization of the classical-quantum correspondence on the torus to arbitrary rational values of the scaled Planck constant.Comment: 12 REVTEX page

Smoothed universal correlations in the two-dimensional Anderson model

We report on calculations of smoothed spectral correlations in the two-dimensional Anderson model for weak disorder. As pointed out in (M. Wilkinson, J. Phys. A: Math. Gen. 21, 1173 (1988)), an analysis of the smoothing dependence of the correlation functions provides a sensitive means of establishing consistency with random matrix theory. We use a semiclassical approach to describe these fluctuations and offer a detailed comparison between numerical and analytical calculations for an exhaustive set of two-point correlation functions. We consider parametric correlation functions with an external Aharonov-Bohm flux as a parameter and discuss two cases, namely broken time-reversal invariance and partial breaking of time-reversal invariance. Three types of correlation functions are considered: density-of-states, velocity and matrix element correlation functions. For the values of smoothing parameter close to the mean level spacing the semiclassical expressions and the numerical results agree quite well in the whole range of the magnetic flux.Comment: 12 pages, 14 figures submitted to Phys. Rev.

Effect of Finite Mass on Primordial Nucleosynthesis

We have calculated the small effect of finite nucleon mass on the weak-interaction rates that interconvert protons and neutrons in the early Universe. We have modified the standard code for primordial nucleosynthesis to include these corrections and find a small, systematic increase in the 4He yield, $\delta Y / Y \simeq (0.47 - 0.50)$, depending slightly on the baryon-to-photon ratio. The fractional changes in the abundances of the other light elements are a few percent or less for interesting values of the baryon-to-photon ratio.Comment: 15 pages, 8 figures, uses psfig.st

Mesobot : An Autonomous Underwater Vehicle for Tracking and Sampling Midwater Targets

Mesobot, a new class of autonomous underwater vehicle, will address specific unmet needs for observing slow-moving targets in the midwater ocean. Mesobot will track targets such as zooplankton, fish, and descending particle aggregates using a control system based on stereo cameras and a combination of thrusters and a variable buoyancy system. The vehicle will also be able to collect biogeochemical and environmental DNA (eDNA) samples using a pumped filter sampler

Precision Prediction for the Big-Bang Abundance of Primordial Helium

Within the standard models of particle physics and cosmology we have calculated the big-bang prediction for the primordial abundance of \he to a theoretical uncertainty of less than 0.1 \pct $(\delta Y_P < \pm 0.0002)$, improving the current theoretical precision by a factor of 10. At this accuracy the uncertainty in the abundance is dominated by the experimental uncertainty in the neutron mean lifetime, $\tau_n = 885.4 \pm 2.0 sec$. The following physical effects were included in the calculation: the zero and finite-temperature radiative, Coulomb and finite-nucleon-mass corrections to the weak rates; order-$\alpha$ quantum-electrodynamic correction to the plasma density, electron mass, and neutrino temperature; and incomplete neutrino decoupling. New results for the finite-temperature radiative correction and the QED plasma correction were used. In addition, we wrote a new and independent nucleosynthesis code designed to control numerical errors to be less than 0.1\pct. Our predictions for the \EL[4]{He} abundance are presented in the form of an accurate fitting formula. Summarizing our work in one number, $Y_P(\eta = 5\times 10^{-10}) = 0.2462 \pm 0.0004 (expt) \pm < 0.0002 (theory)$. Further, the baryon density inferred from the Burles-Tytler determination of the primordial D abundance, $\Omega_B h^2 = 0.019\pm 0.001$, leads to the prediction: $Y_P = 0.2464 \pm 0.0005 (D/H) \pm < 0.0002 (theory) \pm 0.0005 (expt)$. This ``prediction'' and an accurate measurement of the primeval \he abundance will allow an important consistency test of primordial nucleosynthesis.Comment: Replaced fitting formulas - new versions differ by small but significant amount. Other minor changes. 30 pages, 17 figures, 5 table

Benznidazole biotransformation and multiple targets in <i>Trypanosoma</i> cruzi revealed by metabolomics

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; The first line treatment for Chagas disease, a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, involves administration of benznidazole (Bzn). Bzn is a 2-nitroimidazole pro-drug which requires nitroreduction to become active, although its mode of action is not fully understood. In the present work we used a non-targeted MS-based metabolomics approach to study the metabolic response of T. cruzi to Bzn.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methodology/Principal findings&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Parasites treated with Bzn were minimally altered compared to untreated trypanosomes, although the redox active thiols trypanothione, homotrypanothione and cysteine were significantly diminished in abundance post-treatment. In addition, multiple Bzn-derived metabolites were detected after treatment. These metabolites included reduction products, fragments and covalent adducts of reduced Bzn linked to each of the major low molecular weight thiols: trypanothione, glutathione, γ-glutamylcysteine, glutathionylspermidine, cysteine and ovothiol A. Bzn products known to be generated in vitro by the unusual trypanosomal nitroreductase, TcNTRI, were found within the parasites, but low molecular weight adducts of glyoxal, a proposed toxic end-product of NTRI Bzn metabolism, were not detected.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions/significance&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Our data is indicative of a major role of the thiol binding capacity of Bzn reduction products in the mechanism of Bzn toxicity against T. cruzi

Vascular inflammation and aortic stiffness: potential mechanisms of increased vascular risk in chronic obstructive pulmonary disease

Abstract Background Chronic obstructive pulmonary disease (COPD) is a complex inflammatory condition in which an important extra-pulmonary manifestation is cardiovascular disease. We hypothesized that COPD patients would have increased aortic inflammation and stiffness, as candidate mechanisms mediating increased cardiovascular risk, compared to two negative control groups: healthy never-smokers and smokers without COPD. We also studied patients with COPD due to alpha− 1 antitrypsin deficiency (α1ATD) as a comparator lung disease group. Methods Participants underwent 18F-Fluorodeoxyglucose (FDG) positron emission tomography imaging to quantify aortic inflammation as the tissue-to-blood-ratio (TBR) of FDG uptake. Aortic stiffness was measured by carotid-femoral aortic pulse wave velocity (aPWV). Results Eighty-five usual COPD (COPD due to smoking), 12 α1ATD-COPD patients and 12 each smokers and never-smokers were studied. There was no difference in pack years smoked between COPD patients and smokers (45 ± 25 vs 37 ± 19, p = 0.36), but α1ATD patients smoked significantly less (19 ± 11, p < 0.001 for both). By design, spirometry measures were lower in COPD and α1ATD-COPD patients compared to smokers and never-smokers. Aortic inflammation and stiffness were increased in COPD (TBR: 1.90 ± 0.38, aPWV: 9.9 ± 2.6 m/s) and α1ATD patients (TBR: 1.94 ± 0.43, aPWV: 9.5 ± 1.8 m/s) compared with smokers (TBR: 1.74 ± 0.30, aPWV: 7.8 ± 1.8 m/s, p < 0.05 all) and never-smokers (TBR: 1.71 ± 0.34, aPWV: 7.9 ± 1.7 m/s, p ≤ 0.05 all). Conclusions In this cross-sectional prospective study, novel findings were that both usual COPD and α1ATD-COPD patients have increased aortic inflammation and stiffness compared to smoking and never-smoking controls, regardless of smoking history. These findings suggest that the presence of COPD lung disease per se may be associated with adverse aortic wall changes, and aortic inflammation and stiffening are potential mechanisms mediating increased vascular risk observed in COPD patients

The actin-myosin regulatory MRCK kinases: regulation, biological functions and associations with human cancer

The contractile actin-myosin cytoskeleton provides much of the force required for numerous cellular activities such as motility, adhesion, cytokinesis and changes in morphology. Key elements that respond to various signal pathways are the myosin II regulatory light chains (MLC), which participate in actin-myosin contraction by modulating the ATPase activity and consequent contractile force generation mediated by myosin heavy chain heads. Considerable effort has focussed on the role of MLC kinases, and yet the contributions of the myotonic dystrophy-related Cdc42-binding kinases (MRCK) proteins in MLC phosphorylation and cytoskeleton regulation have not been well characterized. In contrast to the closely related ROCK1 and ROCK2 kinases that are regulated by the RhoA and RhoC GTPases, there is relatively little information about the CDC42-regulated MRCKα, MRCKβ and MRCKγ members of the AGC (PKA, PKG and PKC) kinase family. As well as differences in upstream activation pathways, MRCK and ROCK kinases apparently differ in the way that they spatially regulate MLC phosphorylation, which ultimately affects their influence on the organization and dynamics of the actin-myosin cytoskeleton. In this review, we will summarize the MRCK protein structures, expression patterns, small molecule inhibitors, biological functions and associations with human diseases such as cancer

Influence of surface geometry on the culture of human cell lines: a comparative study using flat, round-bottom and v-shaped 96 well plates

© 2017 Shafaie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.In vitro cell based models have been invaluable tools for studying cell behaviour and for investigating drug disposition, toxicity and potential adverse effects of administered drugs. Within this drug discovery pipeline, the ability to assess and prioritise candidate compounds as soon as possible offers a distinct advantage. However, the ability to apply this approach to a cell culture study is limited by the need to provide an accurate, in vitro-like, microenvironment in conjunction with a low cost and high-throughput screening (HTS) methodology. Although the geometry and/or alignment of cells has been reported to have a profound influence on cell growth and differentiation, only a handful of studies have directly compared the growth of a single cell line on different shaped multiwell plates the most commonly used substrate for HTS, in vitro, studies. Herein, the impact of various surface geometries (flat, round and v-shaped 96 well plates), as well as fixed volume growth media and fixed growth surface area have been investigated on the characteristics of three commonly used human cell lines in biopharmaceutical research and development, namely ARPE-19 (retinal epithelial), A549 (alveolar epithelial) and Malme-3M (dermal fibroblastic) cells. The effect of the surface curvature on cells was characterised using a combination of a metabolic activity assay (CellTiter AQ/MTS), LDH release profiles (CytoTox ONE) and absolute cell counts (Guava ViaCount), respectively. In addition, cell differentiation and expression of specific marker proteins were determined using flow cytometry. These in vitro results confirmed that surface topography had a significant effect (p < 0.05) on cell activity and morphology. However, although specific marker proteins were expressed on day 1 and 5 of the experiment, no significant differences were seen between the different plate geometries (p < 0.05) at the later time point. Accordingly, these results highlight the impact of substrate geometry on the culture of a cell line and the influence it has on the cells' correct growth and differentiation characteristics. As such, these results provide important implications in many aspects of cell biology the development of a HTS, in vitro, cell based systems to further investigate different aspects of toxicity testing and drug delivery.Peer reviewedFinal Published versio

Feasibility of trial procedures for a randomised controlled trial of a community based group exercise intervention for falls prevention for visually impaired older people: the VIOLET study

Background Visually impaired older people (VIOP) have a higher risk of falling than their sighted peers, and are likely to avoid physical activity. The aim was to adapt the existing Falls Management Exercise (FaME) programme for VIOP, delivered in the community, and to investigate the feasibility of conducting a definitive randomised controlled trial (RCT) of this adapted intervention. Methods Two-centre randomised mixed methods pilot trial and economic evaluation of the adapted group-based FaME programme for VIOP versus usual care. A one hour exercise programme ran weekly over 12 weeks at the study sites (Newcastle and Glasgow), delivered by third sector (voluntary and community) organisations. Participants were advised to exercise at home for an additional two hours over the week. Those randomised to the usual activities group received no intervention. Outcome measures were completed at baseline, 12 and 24 weeks. The potential primary outcome was the Short Form Falls Efficacy Scale – International (SFES-I). Participants’ adherence was assessed by reviewing attendance records and self-reported compliance to the home exercises. Adherence with the course content (fidelity) by instructors was assessed by a researcher. Adverse events were collected in a weekly phone call. Results Eighteen participants, drawn from community-living VIOP were screened; 68 met the inclusion criteria; 64 participants were randomised with 33 allocated to the intervention and 31 to the usual activities arm. 94% of participants provided data at the 12 week visit and 92% at 24 weeks. Adherence was high. The intervention was found to be safe with 76% attending nine or more classes. Median time for home exercise was 50 min per week. There was little or no evidence that fear of falling, balance and falls risk, physical activity, emotional, attitudinal or quality of life outcomes differed between trial arms at follow-up. Conclusions The intervention, FaME, was implemented successfully for VIOP and all progression criteria for a main trial were met. The lack of difference between groups on fear of falling was unsurprising given it was a pilot study but there may have been other contributory factors including suboptimal exercise dose and apparent low risk of falls in participants. These issues need addressing for a future trial