Liquid-phase synthesis of 2′-methyl-RNA on a homostar support through organic-solvent nanofiltration

Due to the discovery of RNAi, oligonucleotides (oligos) have re-emerged as a major pharmaceutical target that may soon be required in ton quantities. However, it is questionable whether solid-phase oligo synthesis (SPOS) methods can provide a scalable synthesis. Liquid-phase oligo synthesis (LPOS) is intrinsically scalable and amenable to standard industrial batch synthesis techniques. However, most reported LPOS strategies rely upon at least one precipitation per chain extension cycle to separate the growing oligonucleotide from reaction debris. Precipitation can be difficult to develop and control on an industrial scale and, because many precipitations would be required to prepare a therapeutic oligonucleotide, we contend that this approach is not viable for large-scale industrial preparation. We are developing an LPOS synthetic strategy for 2′-methyl RNA phosphorothioate that is more amenable to standard batch production techniques, using organic solvent nanofiltration (OSN) as the critical scalable separation technology. We report the first LPOS-OSN preparation of a 2′-Me RNA phosphorothioate 9-mer, using commercial phosphoramidite monomers, and monitoring all reactions by HPLC, (31)P NMR spectroscopy and MS

How people with dementia and their families decide about moving to a care home and support their needs: development of a decision aid, a qualitative study

yesBackground: People with dementia and their relatives find decisions about the person with dementia living in a care home difficult. Methods: We interviewed 20 people with dementia or family carers around the time of this decision in order to design a decision-aid. Results: Decision-makers balanced the competing priorities of remaining somewhere familiar, family’s wish they remain at home, reduction of risk and effects on carer’s and person with dementia’s physical health. The person with dementia frequently resented their lack of autonomy as decisions about care home moves were made after insight and judgment were impaired. Family consultation usually helped carers but sometimes exacerbated tensions. Direct professional support was appreciated where it was available. There is a need for healthcare professionals to facilitate these conversations around decision-making and to include more than signposting to other organisations. Conclusions: There is a need for a healthcare professional facilitated decision-aid. This should detail what might change for the person with dementia and their carer, possible resources and alternatives and assist in facilitating discussion with the wider family; further research will develop and test a tool to facilitate decision making about place of care needs

Quantum Fluctuations in the Chirped Pendulum

An anharmonic oscillator when driven with a fast, frequency chirped voltage pulse can oscillate with either small or large amplitude depending on whether the drive voltage is below or above a critical value-a well studied classical phenomenon known as autoresonance. Using a 6 GHz superconducting resonator embedded with a Josephson tunnel junction, we have studied for the first time the role of noise in this non-equilibrium system and find that the width of the threshold for capture into autoresonance decreases as the square root of T, and saturates below 150 mK due to zero point motion of the oscillator. This unique scaling results from the non-equilibrium excitation where fluctuations, both quantum and classical, only determine the initial oscillator motion and not its subsequent dynamics. We have investigated this paradigm in an electrical circuit but our findings are applicable to all out of equilibrium nonlinear oscillators.Comment: 5 pages, 4 figure

π+\pi^+ photoproduction on the proton for photon energies from 0.725 to 2.875 GeV

Differential cross sections for the reaction $\gamma p \to n \pi^+$ have been measured with the CEBAF Large Acceptance Spectrometer (CLAS) and a tagged photon beam with energies from 0.725 to 2.875 GeV. Where available, the results obtained here compare well with previously published results for the reaction. Agreement with the SAID and MAID analyses is found below 1 GeV. The present set of cross sections has been incorporated into the SAID database, and exploratory fits have been made up to 2.7 GeV. Resonance couplings have been extracted and compared to previous determinations. With the addition of these cross sections to the world data set, significant changes have occurred in the high-energy behavior of the SAID cross-section predictions and amplitudes.Comment: 18 pages, 10 figure

Differential cross sections and spin density matrix elements for the reaction gamma p -> p omega

High-statistics differential cross sections and spin density matrix elements for the reaction gamma p -> p omega have been measured using the CLAS at Jefferson Lab for center-of-mass (CM) energies from threshold up to 2.84 GeV. Results are reported in 112 10-MeV wide CM energy bins, each subdivided into cos(theta_CM) bins of width 0.1. These are the most precise and extensive omega photoproduction measurements to date. A number of prominent structures are clearly present in the data. Many of these have not previously been observed due to limited statistics in earlier measurements

Measurement of Beam-Spin Asymmetries for Deep Inelastic π+\pi^+ Electroproduction

We report the first evidence for a non-zero beam-spin azimuthal asymmetry in the electroproduction of positive pions in the deep-inelastic region. Data have been obtained using a polarized electron beam of 4.3 GeV with the CLAS detector at the Thomas Jefferson National Accelerator Facility (JLab). The amplitude of the $\sin\phi$ modulation increases with the momentum of the pion relative to the virtual photon, $z$, with an average amplitude of $0.038 \pm 0.005 \pm 0.003$ for $0.5 < z < 0.8$ range.Comment: 5 pages, RevTEX4, 3 figures, 2 table

Two-Nucleon Momentum Distributions Measured in 3He(e,e'pp)n

We have measured the 3He(e,e'pp)n reaction at 2.2 GeV over a wide kinematic range. The kinetic energy distribution for `fast' nucleons (p > 250 MeV/c) peaks where two nucleons each have 20% or less, and the third nucleon has most of the transferred energy. These fast pp and pn pairs are back-to-back with little momentum along the three-momentum transfer, indicating that they are spectators. Experimental and theoretical evidence indicates that we have measured distorted two-nucleon momentum distributions by striking the third nucleon and detecting the spectator correlated pair.Comment: 6 pages, 5 figures, submitted to PR

Combining motivational and volitional approaches to reducing excessive alcohol consumption in pre-drinkers: A theory-based intervention protocol

Background: Pre-drinking refers to the consumption of alcohol at home or a private residence prior to attending a subsequent social event. We present the study protocol of an online theory-based intervention to reduce pre-drinking and related harm in pre-drinking undergraduates, using behavior change techniques targeting the motivational and volitional phases of behaviour. Design: A fully randomized 2 (autonomy support: present vs. absent) x 2 (implementation intention: present vs. absent) between-participants design will be used to ascertain the effectiveness of the intervention in reducing pre-drinking alcohol consumption and alcohol-related harm. Participants will complete a range of theory-based measures prior to being allocated to one of the four experimental conditions. Four weeks later, participants will complete a follow-up questionnaire comprised of theoretical and behavioral measures. Analyses: The main and interactive effects of the intervention components in reducing our primary dependent variables, namely, pre-drinking alcohol consumption and alcohol-related harm at four-week follow-up will be tested. Baseline alcohol consumption and demographic information will be included in the analysis as covariates. Discussion: This online intervention is the first to be developed to reduce pre-drinking alcohol consumption, a behaviour linked to increased risk of alcohol-related harm. The intervention targets motivational and volitional components of the behaviour change process and is therefore likely to lead to greater reductions in pre-drinking alcohol consumption and experience of alcohol-related harm compared to either approach in isolation. If successful, the intervention can be implemented across various contexts and in populations where pre-drinking is prevalent. © 2016 Caudwell et al

Single pi+ Electroproduction on the Proton in the First and Second Resonance Regions at 0.25GeV^2 < Q^2 < 0.65GeV^2 Using CLAS

The ep -> e'pi^+n reaction was studied in the first and second nucleon resonance regions in the 0.25 GeV^2 < Q^2 < 0.65 GeV^2 range using the CLAS detector at Thomas Jefferson National Accelerator Facility. For the first time the absolute cross sections were measured covering nearly the full angular range in the hadronic center-of-mass frame. The structure functions sigma_TL, sigma_TT and the linear combination sigma_T+epsilon*sigma_L were extracted by fitting the phi-dependence of the measured cross sections, and were compared to the MAID and Sato-Lee models.Comment: Accepted for publication in PR

Exclusive ρ0\rho^0 electroproduction on the proton at CLAS

The $e p\to e^\prime p \rho^0$ reaction has been measured, using the 5.754 GeV electron beam of Jefferson Lab and the CLAS detector. This represents the largest ever set of data for this reaction in the valence region. Integrated and differential cross sections are presented. The $W$, $Q^2$ and $t$ dependences of the cross section are compared to theoretical calculations based on $t$-channel meson-exchange Regge theory on the one hand and on quark handbag diagrams related to Generalized Parton Distributions (GPDs) on the other hand. The Regge approach can describe at the $\approx$ 30% level most of the features of the present data while the two GPD calculations that are presented in this article which succesfully reproduce the high energy data strongly underestimate the present data. The question is then raised whether this discrepancy originates from an incomplete or inexact way of modelling the GPDs or the associated hard scattering amplitude or whether the GPD formalism is simply inapplicable in this region due to higher-twists contributions, incalculable at present.Comment: 29 pages, 29 figure