Implications of the Dirac CP phase upon parametric resonance for sub-GeV neutrinos

We perform an analytic and numerical study of parametric resonance in a three-neutrino framework for sub-GeV neutrinos which travel through a periodic density profile. Commensurate with the initial level of approximation, we develop a parametric resonance condition similar to the exact condition for two-neutrino systems. For a castle-wall density profile, the νe→νμ oscillation probability is enhanced significantly and bounded by cos2θ23. The CP phase δ enters into the oscillation probability as a phase shift. For several cases, we examine the interplay between the characteristics of the castle-wall profile and the CP phase and determine which profiles maximize the separation between oscillations with δ=0,±π2,π. We also consider neutrinos which travel along a chord through the Earth, passing from the mantle to core and back to mantle again. Significant enhancement of the oscillation probability is seen even in the case in which the neutrino energy is far from the MSW resonant energies. At 500 GeV, the difference between oscillation probabilities with δ=0 and δ=π2 is maximized

Downward shortwave surface irradiance from 17 sites for the FIRE/SRB Wisconsin experiment

A field experiment was conducted in Wisconsin during Oct. to Nov. 1986 for purposes of both intensive cirrus cloud measurments and SRB algorithm validation activities. The cirrus cloud measurements were part of the FIRE. Tables are presented which show data from 17 sites in the First ISCCP (International Satellite Cloud Climatology Project) Regional Experiment/Surface Radiation Budget (FIRE/SRB) Wisconsin experiment region. A discussion of intercomparison results and calibration inconsistencies is also included

Over-the-counter analgesics during pregnancy : a comprehensive review of global prevalence and offspring safety

Funding This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC)/EASTBIO studentship to A.Z. (Grant Number: 1942576). RTM is supported by UKRI Future Leaders Fellowship (MR/S017151/1). The MRC Centre for Reproductive Health is supported by MRC Centre Grant (MR/N022556/1).Peer reviewedPostprin

The role of ECL2 in CGRP receptor activation: a combined modelling and experimental approach

The calcitonin gene-related peptide (CGRP) receptor is a complex of a calcitonin receptor-like receptor (CLR), which is a family B G-protein-coupled receptor (GPCR) and receptor activity modifying protein 1. The role of the second extracellular loop (ECL2) of CLR in binding CGRP and coupling to Gs was investigated using a combination of mutagenesis and modelling. An alanine scan of residues 271–294 of CLR showed that the ability of CGRP to produce cAMP was impaired by point mutations at 13 residues; most of these also impaired the response to adrenomedullin (AM). These data were used to select probable ECL2-modelled conformations that are involved in agonist binding, allowing the identification of the likely contacts between the peptide and receptor. The implications of the most likely structures for receptor activation are discussed.</jats:p

Decoupled Associative and Dissociative Processes in Strong yet Highly Dynamic Host-Guest Complexes.

Kinetics and thermodynamics in supramolecular systems are intimately linked, yet both are independently important for application in sensing assays and stimuli-responsive switching/self-healing of materials. Host-guest interactions are of particular interest in many water-based materials, sensing, and drug delivery applications. Herein we investigate the binding dynamics of a variety of electron-rich aromatic moieties forming hetero-ternary complexes with the macrocycle cucurbit[8]uril (CB[8]) and an auxiliary guest, dimethyl viologen, with high selectivity and equilibrium binding constants (Keq up to 1014 M-2). Using stopped-flow spectrofluorimetry, association rate constants were observed to approach the diffusion limit and were found to be insensitive to the structure of the guest. Conversely, the dissociation rate constants of the ternary complexes varied dramatically with the guest structure and were correlated with the thermodynamic binding selectivity. Hence differing molecular features were found to contribute to the associative and dissociative processes, mimicking naturally occurring reactions and giving rise to a decoupling of these kinetic parameters. Moreover, we demonstrate the ability to exploit these phenomena and selectively perturb the associative process with external stimuli (e.g., viscosity and pressure). Significantly, these complexes exhibit increased binding equilibria with increasing pressure, with important implications for the application of the CB[8] ternary complex for the formation of hydrogels, as these gels exhibit unprecedented pressure-insensitive rheological properties. A high degree of flexibility therefore exists in the design of host-guest systems with tunable kinetic and thermodynamic parameters for tailor-made applications across a broad range of fields

Computational Design of Metal Ion Sequestering Agents

Organic ligands that exhibit a high degree of metal ion recognition are essential precursors for developing separation processes and sensors for metal ions. Since the beginning of the nuclear era, much research has focused on discovering ligands that target specific radionuclides. Members of the Group 1A and 2A cations (e.g., Cs, Sr, Ra) and the f-block metals (actinides and lanthanides) are of primary concern to the U.S. Department of Energy (DOE). Although there has been some success in identifying ligand architectures that exhibit a degree of metal ion recognition, the ability to control binding affinity and selectivity remains a significant challenge. The traditional approach for discovering such ligands has involved lengthy programs of organic synthesis and testing that, in the absence of reliable methods for screening compounds before synthesis, have resulted in much wasted research effort. This project seeks to enhance and strengthen the traditional approach through computer-aided design of new and improved host molecules. Accurate electronic structure calculations are coupled with experimental data to provide fundamental information about ligand structure and the nature of metal-donor group interactions (design criteria). This fundamental information then is used in a molecular mechanics model (MM3) that helps us rapidly screen proposed ligand architectures and select the best members from a set of potential candidates. By using combinatorial methods, molecule building software has been developed that generates large numbers of candidate architectures for a given set of donor groups. The specific objectives of this project are as follows: (1) Further understand the structural and energetic aspects of individual donor group- metal ion interactions and incorporate this information within the framework of MM3. (2) Further develop and evaluate approaches for correlating ligand structure with reactivity toward metal ions, in other words, screening capability. (3) Use molecule structure building software to generate large numbers of candidate ligand architectures for given sets of donor groups. (4) Screen candidates and identify ligand architectures that will exhibit enhanced metal ion recognition. These new capabilities are being applied to ligand systems identified under other DOE sponsored projects in which studies have suggested that modifying existing architectures will lead to dramatic enhancements in metal ion binding affinity and selectivity. With this in mind, we are collaborating with researchers at the University of New Mexico, University of California at Berkeley, University of Oregon, and Oak Ridge National Laboratory to obtain experimental validation of the predicted new ligand structures. Successful completion of this study will yield molecular-level insight into the role that ligand architecture plays in controlling metal ion complexation and will provide a computational approach to ligand design

Measures of sun exposure and sun protection practices for behavioural and epidemiological research

Objective: To develop, in a collaborative project, core measures of sun exposure and sun protection habits, since the lack of standard outcome measures hampers comparison of population surveys and interventions used in skin cancer prevention research. Design: A work group of investigators evaluated available questionnaire measures of sun exposure and protection. Their deliberations led to a proposed set of core questionnaire items for adults, adolescents aged 11 to 17 years, and children 10 years or younger. These core items were used in cognitive testing by the investigators. Cross-site summaries of methods, response samples, and descriptive data were prepared. Setting: Nine locations across the United States. Participants: The study population comprised 81 individuals. Results: No unusual response patterns were detected in any of the respondent groups or for any specific question. Some revisions to the survey items resulted from the need for clarification or emphasis of frames of reference such as adding or underlining key phrases in a question. Conclusions: The combination of expert review followed by cognitive interviewing yielded standardized core survey items with good clarity and applicability for measuring sun exposure and sun protection behaviors across a broad range of populations. They are appropriate for studies tracking morbidity and/or mortality and evaluating prevention program effects

Pharmacological profile of vascular activity of human stem villous arteries

© 2019 Introduction: The function of the placental vasculature differs considerably from other systemic vascular beds of the human body. A detailed understanding of the normal placental vascular physiology is the foundation to understand perturbed conditions potentially leading to placental dysfunction. Methods: Behaviour of human stem villous arteries isolated from placentae at term pregnancy was assessed using wire myography. Effects of a selection of known vasoconstrictors and vasodilators of the systemic vasculature were assessed. The morphology of stem villous arteries was examined using IHC and TEM. Results: Contractile effects in stem villous arteries were caused by U46619, 5-HT, angiotensin II and endothelin-1 (p ≤ 0.05), whereas noradrenaline and AVP failed to result in a contraction. Dilating effects were seen for histamine, riluzole, nifedipine, papaverine, SNP and SQ29548 (p ≤ 0.05) but not for acetylcholine, bradykinin and substance P. Discussion: Stem villous arteries behave differently to vessels of the systemic vasculature and results indicate that the placenta is cut off from the systemic maternal vascular regulation. Particularly, endothelium-dependent processes were attenuated in the placental vasculature, creating a need to determine the role of the endothelium in the placenta in future studies