Modeling axial spinal segments of the salamander central pattern generator for locomotion

Poster presentationInternational audiencen.

Azulene-based compounds for targeting orexin receptors

A library of 70 000 synthetically accessible azulene-based compounds was virtually screened at the OX2 receptor. Based on the results, a series of azulene derivatives was synthesized and the binding to and activation of both orexin receptor subtypes were assessed. Two most promising binders were determined to have inhibition constants in the 3-9 mu M range and two other compounds showed weak OX2 receptor agonism. Furthermore, three compounds exhibited a concentration-dependent potentiation of the response to orexin-A at the OX1 but not the OX2 receptors. Altogether this data opens new approaches for further development of antagonists, agonists, and potentiators of orexin response based on the azulene scaffold. (C) 2018 Elsevier Masson SAS. All rights reserved.Peer reviewe

Stapled truncated orexin peptides as orexin receptor agonists

The peptides orexin-A and -B, the endogenous agonists of the orexin receptors, have similar 19-amino-acid C-termini which retain full maximum response as truncated peptides with only marginally reduced potency, while further N-terminal truncations successively reduce the activity. The peptides have been suggested to bind in an α‐helical conformation, and truncation beyond a certain critical length is likely to disrupt the overall helical structure. In this study, we set out to stabilize the α‐helical conformation of orexin‐A15–33 via peptide stapling at four different sites. At a suggested hinge region, we varied the length of the cross-linker as well as replaced the staple with two α-aminoisobutyric acid residues. Modifications close to the peptide C‐terminus, which is crucial for activity, were not allowed. However, central and N‐terminal modifications yielded bioactive peptides, albeit with decreased potencies. This provides evidence that the orexin receptors can accommodate and be activated by α-helical peptides. The decrease in potency is likely linked to a stabilization of suboptimal peptide conformation or blocking of peptide backbone–receptor interactions at the hinge region by the helical stabilization or the modified amino acids.Peer reviewe

Status of COLDDIAG: A Cold Vacuum Chamber for Diagnostics

One of the still open issues for the development of superconducting insertion devices is the understanding of the beam heat load. With the aim of measuring the beam heat load to a cold bore and the hope to gain a deeper understanding in the beam heat load mechanisms, a cold vacuum chamber for diagnostics is under construction. The following diagnostics will be implemented: i) retarding field analyzers to measure the electron energy and flux, ii) temperature sensors to measure the total heat load, iii) pressure gauges, iv) and mass spectrometers to measure the gas content. The inner vacuum chamber will be removable in order to test different geometries and materials. This will allow the installation of the cryostat in different synchrotron light sources. COLDDIAG will be built to fit in a short straight section at ANKA. A first installation at the synchrotron light source Diamond is foreseen in June 2011. Here we describe the technical design report of this device and the planned measurements with beam.Comment: Presented at First International Particle Accelerator Conference, IPAC'10, Kyoto, Japan, from 23 to 28 May 201

Chromatin modifier developmental pluripotency associated factor 4 (DPPA4) is a candidate gene for alcohol-induced developmental disorders

Peer reviewe

Validity of the Polar V800 heart rate monitor to measure RR intervals at rest

Purpose To assess the validity of RR intervals and short-term heart rate variability (HRV) data obtained from the Polar V800 heart rate monitor, in comparison to an electrocardiograph (ECG). Method Twenty participants completed an active orthostatic test using the V800 and ECG. An improved method for the identification and correction of RR intervals was employed prior to HRV analysis. Agreement of the data was assessed using intra-class correlation coefficients (ICC), Bland–Altman limits of agreement (LoA), and effect size (ES). Results A small number of errors were detected between ECG and Polar RR signal, with a combined error rate of 0.086 %. The RR intervals from ECG to V800 were significantly different, but with small ES for both supine corrected and standing corrected data (ES 0.999 for both supine and standing corrected intervals. When analysed with the same HRV software no significant differences were observed in any HRV parameters, for either supine or standing; the data displayed small bias and tight LoA, strong ICC (>0.99) and small ES (≤0.029). Conclusions The V800 improves over previous Polar models, with narrower LoA, stronger ICC and smaller ES for both the RR intervals and HRV parameters. The findings support the validity of the Polar V800 and its ability to produce RR interval recordings consistent with an ECG. In addition, HRV parameters derived from these recordings are also highly comparable

Improved Linear Cryptanalysis of SOSEMANUK

Abstract. The SOSEMANUK stream cipher is one of the finalists of the eSTREAM project. In this paper, we improve the linear cryptanalysis of SOSEMANUK presented in Asiacrypt 2008. We apply the generalized linear masking technique to SOSEMANUK and derive many linear approximations holding with the correlations of up to 2 −25.5. We show that the data complexity of the linear attack on SOSEMANUK can be reduced by a factor of 2 10 if multiple linear approximations are used. Since SOSEMANUK claims 128-bit security, our attack would not be a real threat on the security of SOSEMANUK. Keywords: Stream Ciphers, Linear Cryptanalysis, SOSEMANUK, SOBER-128.

2-Imidazole as a Substitute for the Electrophilic Group Gives Highly Potent Prolyl Oligopeptidase Inhibitors

Different five-membered nitrogen-containing heteroaromatics in the position of the typical electrophilic group in prolyl oligopeptidase (PREP) inhibitors were investigated and compared to tetrazole. The 2-imidazoles were highly potent inhibitors of the proteolytic activity. The binding mode for the basic imidazole was studied by molecular docking as it was expected to differ from the acidic tetrazole. A new putative noncovalent binding mode with an interaction to His680 was found for the 2-imidazoles. Inhibition of the proteolytic activity did not correlate with the modulating effect on protein-protein-interaction-derived functions of PREP (i.e., dimerization of alpha-synuclein and autophagy). Among the highly potent PREP inhibiting 2-imidazoles, only one was also a potent modulator of PREP-catalyzed alpha-synuclein dimerization, indicating that the linker length on the opposite side of the molecule from the five-membered heteroaromatic is critical for the disconnected structure-activity relationships