Alkyl‐Bridged Nitropyrazoles – Adjustment of Performance and Sensitivity Parameters

Starting from 3,5-dinitro-4-methylaminopyrazole (2), six different energetic salts and three new derivatives of methylene bridged nitropyrazoles were synthesized. The derivatives bear a methylamino (4), methylnitramino (5), and azido group (7). All compounds were intensively characterized using single crystal X-ray diffraction, multinuclear NMR spectroscopy, IR spectroscopy, mass spectrometry, elemental analysis and DTA/TGA measurements. The sensitivities were determined according to BAM standard methods and the energetic properties calculated using the EXPLO5 code. The energetic salts were compared with each other and with ANTA in terms of their energetic properties. On the basis of the methyl- and ethyl bridged derivatives, it was shown how the introduction of methylamino (4) and methylnitramino (5) groups in an alkyl-bridged nitropyrazole system modify its properties (performance & sensitivities). In addition, azido compound 7 was contrasted with its literature-known constitutional isomer and investigated for its suitability as a potential metal-free primary explosive

Targeted modulation of protein liquid-liquid phase separation by evolution of amino-acid sequence.

Rationally and efficiently modifying the amino-acid sequence of proteins to control their ability to undergo liquid-liquid phase separation (LLPS) on demand is not only highly desirable, but can also help to elucidate which protein features are important for LLPS. Here, we propose a computational method that couples a genetic algorithm to a sequence-dependent coarse-grained protein model to evolve the amino-acid sequences of phase-separating intrinsically disordered protein regions (IDRs), and purposely enhance or inhibit their capacity to phase-separate. We validate the predicted critical solution temperatures of the mutated sequences with ABSINTH, a more accurate all-atom model. We apply the algorithm to the phase-separating IDRs of three naturally occurring proteins, namely FUS, hnRNPA1 and LAF1, as prototypes of regions that exist in cells and undergo homotypic LLPS driven by different types of intermolecular interaction, and we find that the evolution of amino-acid sequences towards enhanced LLPS is driven in these three cases, among other factors, by an increase in the average size of the amino acids. However, the direction of change in the molecular driving forces that enhance LLPS (such as hydrophobicity, aromaticity and charge) depends on the initial amino-acid sequence. Finally, we show that the evolution of amino-acid sequences to modulate LLPS is strongly coupled to the make-up of the medium (e.g. the presence or absence of RNA), which may have significant implications for our understanding of phase separation within the many-component mixtures of biological systems

Physical activity in 9–15 year-old pediatric cancer survivors compared to a nationwide sample

Introduction: Sufficient physical activity (PA) has the potential to mitigate late effects of cancer, but objective data of PA levels in adolescents are scarce. The aim of this study was to investigate differences in PA behavior between childhood cancer survivors (CCS) and healthy peers. Methods: PA levels of n = 74 CCS and n = 1304 healthy peers from the MoMo study aged 9–15 years were assessed with validated objective accelerometry and group means were compared. A binary multiple logistic regression was performed to investigate the potential predictors of PA. Results: CCS spent significantly more time sedentary (p < 0.001) and less time in moderate-to-vigorous physical activity (p = 0.002) compared to the healthy cohort. Subgroup analysis revealed the largest deviations of PA levels for CCS aged 9–11 years who fulfilled international PA recommendations on significantly fewer days than MoMo (p < 0.01). Health conditions seem to be a predictor concerning the fulfillment of international PA recommendations by the WHO (p = 0.015). Conclusions: Our study identified vulnerable groups which seem to require targeted exercise and health behavior change programs to increase physical activity and reduce sedentary time. The presence of treatment sequelae as a significant predictor of insufficient physical activity underlines the need of multidisciplinary supportive care approaches

Representation of a complex Green function on a real basis: I. General Theory

When the Hamiltonian of a system is represented by a finite matrix, constructed from a discrete basis, the matrix representation of the resolvent covers only one branch. We show how all branches can be specified by the phase of a complex unit of time. This permits the Hamiltonian matrix to be constructed on a real basis; the only duty of the basis is to span the dynamical region of space, without regard for the particular asymptotic boundary conditions that pertain to the problem of interest.Comment: about 40 pages with 5 eps-figure

Comparison of Image Registration Based Measures of Regional Lung Ventilation from Dynamic Spiral CT with Xe-CT

Purpose: Regional lung volume change as a function of lung inflation serves as an index of parenchymal and airway status as well as an index of regional ventilation and can be used to detect pathologic changes over time. In this article, we propose a new regional measure of lung mechanics --- the specific air volume change by corrected Jacobian. Methods: 4DCT and Xe-CT data sets from four adult sheep are used in this study. Nonlinear, 3D image registration is applied to register an image acquired near end inspiration to an image acquired near end expiration. Approximately 200 annotated anatomical points are used as landmarks to evaluate registration accuracy. Three different registration-based measures of regional lung mechanics are derived and compared: the specific air volume change calculated from the Jacobian (SAJ); the specific air volume change calculated by the corrected Jacobian (SACJ); and the specific air volume change by intensity change (SAI). Results: After registration, the mean registration error is on the order of 1 mm. For cubical ROIs in cubes with size 20 mm $\times$ 20 mm $\times$ 20 mm, the SAJ and SACJ measures show significantly higher correlation (linear regression, average $r^2=0.75$ and $r^2=0.82$) with the Xe-CT based measure of specific ventilation (sV) than the SAI measure. For ROIs in slabs along the ventral-dorsal vertical direction with size of 150 mm $\times$ 8 mm $\times$ 40 mm, the SAJ, SACJ, and SAI all show high correlation (linear regression, average $r^2=0.88$, $r^2=0.92$ and $r^2=0.87$) with the Xe-CT based sV without significant differences when comparing between the three methods. Conclusion: Given a deformation field by an image registration algorithm, significant differences between the SAJ, SACJ, and SAI measures were found at a regional level compared to the Xe-CT sV in four sheep that were studied

7 Essays on Impact

Edited by Dr Andrew Dean, Dr Michael Wykes & Hilary Stevens, University of ExeterThrough the Jisc-funded DESCRIBE Project we have sought to undertake a rigorous assessment of current standards relating to the evidence of impacts arising from Higher Education research. This document contains seven valuable essays each exploring the topic of Impact. Each essay is distinct and we have sought to enable selected thought-leaders and Impact experts to both review the status quo, and to look to the future, making suggestions and recommendations for the development of Impact in the sector. DESCRIBE has been managed by the University of Exeter’s Research and Knowledge Transfer team in partnership with the Marchmont Observatory. We have sought to combine the latest thinking on research Impact with examples and recommendations which are practical and rooted in the art of the possible.JISC DIINN1

Analytical Treatment of the Oscillating Yukawa Potential

Using a suitable Laguerre basis set that ensures a tridiagonal matrix representation of the reference Hamiltonian, we were able to evaluate in closed form the matrix elements of the generalized Yukawa potential with complex screening parameter. This enabled us to treat analytically both the cosine and sine-like Yukawa potentials on equal footing and compute their bound states spectrum as the eigenvalues of the associated analytical matrix representing their Hamiltonians. Finally we used a carefully designed complex scaling method to evaluate the resonance energies and compared our results satisfactorily with those obtained in the literature.Comment: 8 pages 2 table