Resurrecting the Dead (Molecules)

Biological molecules, like organisms themselves, are subject to genetic drift and may even become “extinct”. Molecules that are no longer extant in living systems are of high interest for several reasons including insight into how existing life forms evolved and the possibility that they may have new and useful properties no longer available in currently functioning molecules. Predicting the sequence/structure of such molecules and synthesizing them so that their properties can be tested is the basis of “molecular resurrection” and may lead not only to a deeper understanding of evolution, but also to the production of artificial proteins with novel properties and even to insight into how life itself began

Semi-spectral Chebyshev method in Quantum Mechanics

Traditionally, finite differences and finite element methods have been by many regarded as the basic tools for obtaining numerical solutions in a variety of quantum mechanical problems emerging in atomic, nuclear and particle physics, astrophysics, quantum chemistry, etc. In recent years, however, an alternative technique based on the semi-spectral methods has focused considerable attention. The purpose of this work is first to provide the necessary tools and subsequently examine the efficiency of this method in quantum mechanical applications. Restricting our interest to time independent two-body problems, we obtained the continuous and discrete spectrum solutions of the underlying Schroedinger or Lippmann-Schwinger equations in both, the coordinate and momentum space. In all of the numerically studied examples we had no difficulty in achieving the machine accuracy and the semi-spectral method showed exponential convergence combined with excellent numerical stability.Comment: RevTeX, 12 EPS figure

QCD Evolution Equations: Numerical Algorithms from the Laguerre Expansion

A complete numerical implementation, in both singlet and non-singlet sectors, of a very elegant method to solve the QCD Evolution equations, due to Furmanski and Petronzio, is presented. The algorithm is directly implemented in x-space by a Laguerre expansion of the parton distributions. All the leading-twist distributions are evolved: longitudinally polarized, transversely polarized and unpolarized, to NLO accuracy. The expansion is optimal at finite x, up to reasonably small x-values ($x\approx 10^{-3}$), below which the convergence of the expansion slows down. The polarized evolution is smoother, due to the less singular structure of the anomalous dimensions at small-x. In the region of fast convergence, which covers most of the usual perturbative applications, high numerical accuracy is achieved by expanding over a set of approximately 30 polynomials, with a very modest running time.Comment: 30 pages, 13 figure

Inverse Probability Weighted Estimating Equations for Randomized Trials in Transfusion Medicine

This is the peer reviewed version of the following article: Cook, R. J., Lee, K.-A., Cuerden, M. and Cotton, C. A. (2013), Inverse probability weighted estimating equations for randomized trials in transfusion medicine. Statist. Med., 32: 4380–4399. doi:10.1002/sim.5827, which has been published in final form at http://dx.doi.org/10.1002/sim.5827. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.Thrombocytopenia is a condition characterized by extremely low platelet counts, which puts patients at elevated risk of morbidity and mortality because of bleeding. Trials in transfusion medicine are routinely designed to assess the effect of experimental platelet products on patients platelet counts. In such trials, patients may receive multiple platelet transfusions over a predefined period of treatment, and a response is available from each such administration. The resulting data comprised multiple responses per patient, and although it is natural to want to use this data in testing for treatment effects, naive analyses of the multiple responses can yield biased estimates of the probability of response and associated treatment effects. These biases arise because only subsets of the patients randomized contribute response data on the second and subsequent administrations of therapy and the balance between treatment groups with respect to potential confounding factors is lost. We discuss the design and analysis issues involved in this setting and make recommendations for the design of future platelet transfusion trials.Natural Sciences and Engineering Research Council of Canada (RJC RGPIN 155849, CAC RGPIN 402474); Canadian Institutes for Health Research (FRN 13887); Canada Research Chair (Tier 1) – CIHR funded (950-226626

Quark-Antiquark Bound States within a Dyson-Schwinger Bethe-Salpeter Formalism

Pion and kaon observables are calculated using a Dyson-Schwinger Bethe-Salpeter formalism. It is shown that an infrared finite gluon propagator can lead to quark confinement via generation of complex mass poles in quark propagators. Observables, including electromagnetic form factors, are calculated entirely in Euclidean metric for spacelike values of bound state momentum and final results are extrapolated to the physical region.Comment: Minor typographical corrections. Accepted for publication in Nucl. Phys.

Molecular details of quinolone–DNA interactions: solution structure of an unusually stable DNA duplex with covalently linked nalidixic acid residues and non-covalent complexes derived from it

Quinolones are antibacterial drugs that are thought to bind preferentially to disturbed regions of DNA. They do not fall into the classical categories of intercalators, groove binders or electrostatic binders to the backbone. We solved the 3D structure of the DNA duplex (ACGCGU-NA)(2), where NA denotes a nalidixic acid residue covalently linked to the 2′-position of 2′-amino-2′-deoxyuridine, by NMR and restrained torsion angle molecular dynamics (MD). In the complex, the quinolones stack on G:C base pairs of the core tetramer and disrupt the terminal A:U base pair. The displaced dA residues can stack on the quinolones, while the uracil rings bind in the minor groove. The duplex-bridging interactions of the drugs and the contacts of the displaced nucleotides explain the high UV-melting temperature for d(ACGCGU-NA)(2) of up to 53°C. Further, non-covalently linked complexes between quinolones and DNA of the sequence ACGCGT can be generated via MD using constraints obtained for d(ACGCGU-NA)(2). This is demonstrated for unconjugated nalidixic acid and its 6-fluoro derivative. The well-ordered and tightly packed structures thus obtained are compatible with a published model for the quinolone–DNA complex in the active site of gyrases

Maximum Upper Esophageal Sphincter (UES) Admittance: A Non-Specific Marker of UES Dysfunction

This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving'.© 2015 John Wiley & Sons LtdBackground Assessment of upper esophageal sphincter (UES) motility is challenging, as functionally, UES relaxation and opening are distinct. We studied novel parameters, UES admittance (inverse of nadir impedance), and 0.2-s integrated relaxation pressure (IRP), in patients with cricopharyngeal bar (CPB) and motor neuron disease (MND), as predictors of UES dysfunction. Methods Sixty-six healthy subjects (n = 50 controls 20–80 years; n = 16 elderly >80 years), 11 patients with CPB (51–83 years) and 16 with MND (58–91 years) were studied using pharyngeal high-resolution impedance manometry. Subjects received 5 × 5 mL liquid (L) and viscous (V) boluses. Admittance and IRP were compared by age and between groups. A p < 0.05 was considered significant. Key Results In healthy subjects, admittance was reduced (L: p = 0.005 and V: p = 0.04) and the IRP higher with liquids (p = 0.02) in older age. Admittance was reduced in MND compared to both healthy groups (Young: p < 0.0001 for both, Elderly L: p < 0.0001 and V: p = 0.009) and CPB with liquid (p = 0.001). Only liquid showed a higher IRP in MND patients compared to controls (p = 0.03), but was similar to healthy elderly and CPB patients. Only admittance differentiated younger controls from CPB (L: p = 0.0002 and V: p < 0.0001), with no differences in either parameter between CPB and elderly subjects. Conclusions & Inferences The effects of aging and pathology were better discriminated by UES maximum admittance, demonstrating greater statistical confidence across bolus consistencies as compared to 0.2-s IRP. Maximum admittance may be a clinically useful determinate of UES dysfunction

Quantum interference terms in nonmesonic weak decay of Λ\Lambda-hypernuclei within a RPA formalism

Single and double coincidence nucleon spectra in the $\Lambda$-hypernuclei weak decay are evaluated and discussed using a microscopic formalism. Nuclear matter is employed together with the local density approximation which allows us to analyze the $^{12}_{\Lambda}C$ hypernucleus non-mesonic weak decay. Final state interactions (FSI) are included via the first order (in the nuclear residual interaction) terms to the RPA, where the strong residual interaction is modelled by a Bonn potential. At this level of approximation, these FSI are pure quantum interference terms between the primary decay $(\Lambda N \to NN)$ and $(\Lambda N \to NN \to NN)$, where the strong interaction is responsible for the last piece in the second reaction. Also the Pauli exchange contributions are explicitly evaluated. We show that the inclusion of Pauli exchange terms is important. A comparison with data is made. We conclude that the limitations in phase space in the RPA makes this approximation inadequate to reproduce the nucleon spectra. This fact, does not allow us to draw a definite conclusion about the importance of the interference terms.Comment: 39 pages, 10 figure