Design, Synthesis, and Characterization of Stapled Oligosaccharides

Stapling short peptides to lock specific conformations and thereby obtain superior pharmacological properties is well established. However, similar concepts have not been applied to oligosaccharides. Here, we describe the design, synthesis, and characterization of the first stapled oligosaccharides. Automated assembly of β-(1,6)-glucans equipped with two alkenyl side chains was followed by on-resin Grubbs metathesis for efficient ring closure with a variety of cross-linkers of different sizes. Oligosaccharide stapling increases enzymatic stability and cell penetration, therefore opening new opportunities for the use of glycans in medicinal chemistry

The hyperon-nucleon interaction: conventional versus effective field theory approach

Hyperon-nucleon interactions are presented that are derived either in the conventional meson-exchange picture or within leading order chiral effective field theory. The chiral potential consists of one-pseudoscalar-meson exchanges and non-derivative four-baryon contact terms. With regard to meson-exchange hyperon-nucleon models we focus on the new potential of the Juelich group, whose most salient feature is that the contributions in the scalar--isoscalar (\sigma) and vector--isovector (\rho) exchange channels are constrained by a microscopic model of correlated \pi\pi and KKbar exchange.Comment: 28 pages, 8 figures, submitted to Lecture Notes in Physic

Strangeness S=-2 baryon-baryon interactions using chiral effective field theory

We derive the leading order strangeness S=-2 baryon-baryon interactions in chiral effective field theory. The potential consists of contact terms without derivatives and of one-pseudoscalar-meson exchanges. The contact terms and the couplings of the pseudoscalar mesons to the baryons are related via SU(3) flavor symmetry to the S=-1 hyperon-nucleon channels. We show that the chiral effective field theory predictions with natural values for the low-energy constants agree with the experimental information in the S=-2 sector.Comment: 10 pages, 2 PostScript figure

Pion-Lambda-Sigma Coupling Extracted from Hyperonic Atoms

The latest measurements of the atomic level width in Sigma-hyperonic Pb atom offer the most accurate datum in the region of low-energy Sigma-hyperon physics. Atomic widths are due to the conversion of Sigma-nucleon into Lambda-nucleon. In high angular momentum states this conversion is dominated by the one-pion exchange. A joint analysis of the data of the scattering of negative-Sigma on proton converting into a Lambda and a neutron and of the atomic widths allows to extract a pseudovector pion-hyperon-Sigma coupling constant of 0.048 with a statistical error of +-0.005 and a systematic one of +-0.004. This corresponds to a pseudoscalar coupling constant of 13.3 with a statistical uncertainty of 1.4 and a systematic one of 1.1.Comment: 12 pages, 1 figure, Use of Revtex.st

What Does Free Space Lambda-Lambda Interaction Predict for Lambda-Lambda Hypernuclei?

Data on Lambda-Lambda hypernuclei provide a unique method to learn details on the strangeness S =-2 sector of the baryon-baryon interaction. From the free space Bonn-Julich potentials, determined from data on baryon-baryon scattering in the S=0,-1 channels, we construct an interaction in the S =-2 sector to describe the experimentally known Lambda-Lambda hypernuclei. After including short--range (Jastrow) and RPA correlations, we find masses for these Lambda-Lambda hypernuclei in a reasonable agreement with data, taking into account theoretical and experimental uncertainties. Thus, we provide a natural extension, at low energies, of the Bonn-Julich OBE potentials to the S =-2 channel.Comment: 4 pages, 2 figures, revtex4 style. Minor changes in conclusions. References updated. Accepted in Phys. Rev. Let

Lambda flow in heavy-ion collisions: the role of final-state interactions

Lambda flow in Ni+Ni collisions at SIS energies is studied in the relativistic transport model (RVUU 1.0). It is found that for primordial lambdas the flow is considerably weaker than proton flow. The inclusion of final-state interactions, especially the propagation of lambdas in mean-field potential, brings the lambda flow close to that of protons. An accurate determination of lambda flow in heavy-ion experiments is shown to be very useful for studying lambda properties in dense matter.Comment: 14 pages, LaTeX, figures available from [email protected], to appear in Phys. Rev.

Physio4FMD: protocol for a multicentre randomised controlled trial of specialist physiotherapy for functional motor disorder

Background Patients with functional motor disorder (FMD) experience persistent and disabling neurological symptoms such as weakness, tremor, dystonia and disordered gait. Physiotherapy is usually considered an important part of treatment; however, sufficiently-powered controlled studies are lacking. Here we present the protocol of a randomised controlled trial (RCT) that aims to evaluate the clinical and cost effectiveness of a specialist physiotherapy programme for FMD. Methods/design The trial is a pragmatic, multicentre, single blind parallel arm randomised controlled trial (RCT). 264 Adults with a clinically definite diagnosis of FMD will be recruited from neurology clinics and randomised to receive either the trial intervention (a specialist physiotherapy protocol) or treatment as usual control (referral to a community physiotherapy service suitable for people with neurological symptoms). Participants will be followed up at 6 and 12 months. The primary outcome is the Physical Function domain of the Short Form 36 questionnaire at 12 months. Secondary domains of measurement will include participant perception of change, mobility, health-related quality of life, health service utilisation, anxiety and depression. Health economic analysis will evaluate the cost impact of trial and control interventions from a health and social care perspective as well as societal perspective. Discussion This trial will be the first adequately-powered RCT of physical-based rehabilitation for FMD. Trial registration International Standard Randomised Controlled Trials Number ISRCTN56136713. Registered 27 March 2018

Characterising spoken responses to an intelligent virtual agent by persons with mild cognitive impairment

The diagnosis of Mild Cognitive Impairment (MCI) characterises patients at risk of dementia and may provide an opportunity for disease-modifying interventions. Identifying persons with MCI (PwMCI) from adults of a similar age without cognitive complaints is a significant challenge. The main aims of this study were to determine whether generic speech differences were evident between PwMCI and healthy controls (HC), whether such differences were identifiable in responses to recent or remote memory questions, and to determine which speech variables showed the clearest between group differences. This study analysed recordings of 8 PwMCI (5 female, 3 male) and 14 HC of a similar age (8 female, 6 male). Participants were recorded interacting with an intelligent virtual agent: a computer-generated talking head on a computer screen which asks pre-recorded questions when prompted by the interviewee through pressing the next key on a computer keyboard. Responses to recent and remote memory questions were analysed. Mann-Whitney U tests were used to test for statistically significant differences between PwMCI and HC on each of twelve speech variables, relating to temporal characteristics, number of words produced and pitch. It was found that compared to HC, PwMCI produce speech for less time and in shorter chunks, they pause more often and for longer, take longer to begin speaking and produce fewer words in their answers. It was also found that the PwMCI and HC were more alike when responding to remote memory questions than when responding to recent memory questions. These findings show great promise and suggest that detailed speech analysis can make an important contribution to diagnostic and stratification systems in patients with memory complaints

Physio4FMD: protocol for a multicentre randomised controlled trial of specialist physiotherapy for functional motor disorder.

BACKGROUND: Patients with functional motor disorder (FMD) experience persistent and disabling neurological symptoms such as weakness, tremor, dystonia and disordered gait. Physiotherapy is usually considered an important part of treatment; however, sufficiently-powered controlled studies are lacking. Here we present the protocol of a randomised controlled trial (RCT) that aims to evaluate the clinical and cost effectiveness of a specialist physiotherapy programme for FMD. // METHODS/DESIGN: The trial is a pragmatic, multicentre, single blind parallel arm randomised controlled trial (RCT). 264 Adults with a clinically definite diagnosis of FMD will be recruited from neurology clinics and randomised to receive either the trial intervention (a specialist physiotherapy protocol) or treatment as usual control (referral to a community physiotherapy service suitable for people with neurological symptoms). Participants will be followed up at 6 and 12 months. The primary outcome is the Physical Function domain of the Short Form 36 questionnaire at 12 months. Secondary domains of measurement will include participant perception of change, mobility, health-related quality of life, health service utilisation, anxiety and depression. Health economic analysis will evaluate the cost impact of trial and control interventions from a health and social care perspective as well as societal perspective. // DISCUSSION: This trial will be the first adequately-powered RCT of physical-based rehabilitation for FMD