Protein sequence entropy is closely related to packing density and hydrophobicity

We investigated the correlation between the Shannon information entropy, ‘sequence entropy’, with respect to the local flexibility of native globular proteins as described by inverse packing density. These are determined at each residue position for a total set of 130 query proteins, where sequence entropies are calculated from each set of aligned residues. For the accompanying aggregate set of 130 alignments, a strong linear correlation is observed between the calculated sequence entropy and the corresponding inverse packing density determined at an associated residue position. This region of linearity spans the range of Cα packing densities from 12 to 25 amino acids within a sphere of 9 Å radius. Three different hydrophobicity scales all mimic the behavior of the sequence entropies. This confirms the idea that the ability to accommodate mutations is strongly dependent on the available space and on the propensity for each amino acid type to be buried. Future applications of these types of methods may prove useful in identifying both core and flexible residues within a protein

How well-proportioned are lens and prism spaces?

The CMB anisotropies in spherical 3-spaces with a non-trivial topology are analysed with a focus on lens and prism shaped fundamental cells. The conjecture is tested that well proportioned spaces lead to a suppression of large-scale anisotropies according to the observed cosmic microwave background (CMB). The focus is put on lens spaces L(p,q) which are supposed to be oddly proportioned. However, there are inhomogeneous lens spaces whose shape of the Voronoi domain depends on the position of the observer within the manifold. Such manifolds possess no fixed measure of well-proportioned and allow a predestined test of the well-proportioned conjecture. Topologies having the same Voronoi domain are shown to possess distinct CMB statistics which thus provide a counter-example to the well-proportioned conjecture. The CMB properties are analysed in terms of cyclic subgroups Z_p, and new point of view for the superior behaviour of the Poincar\'e dodecahedron is found

Breaking up the band: European regulatory cooperation in a post-Brexit world

Since 1995, the European Medicines Agency (EMA) has progressed from harmonising regulation for human and veterinary medicines across the European Union Member State national competent authorities, to galvanising one of the most successful cooperative initiatives for regulation globally. Although the EMA is the focal point for stakeholders, regulation is delivered through the European medicines regulatory network, in which national authorities, like the UK’s Medicines & Healthcare products Regulatory Agency (MHRA), contribute. As with any collaboration, contributions by individual members vary, and the MHRA has been noted as an innovative and highly productive member of the network. Progress in regulation not only in Europe – but also around the world through convergence – can be attributed to this unique European cooperation. The decision by the UK to leave the European Union threatens to mark the end of this cooperation; we argue here that the best decision is to maintain regulatory cooperation under new structures

Common peroneal nerve palsy complicating knee dislocation and bicruciate ligaments tears

SummaryIntroductionThe occurrence rate of common peroneal nerve (CPN) palsy associated with knee dislocation or bicruciate ligament injury ranges from 10 to 40%. The present study sought first to describe the anatomic lesions encountered and their associated prognoses and second to recommend adequate treatment strategy based on a prospective multicenter observational series of knee ligament trauma cases.Material and methodsTwelve out of 67 knees treated for dislocation or bicruciate lesion presented associated CPN palsy: two females, 10 males; mean age, 32 years. Four sports injuries, three traffic accidents and five other etiologies led to seven complete dislocations and five bicruciate ruptures. Four cases involved associated popliteal artery laceration ischemia; one of the dislocations was open. Paralysis was total in eight cases and partial in four. There were two complete ruptures, three contusions with CPN in continuity stretch lesions and three macroscopically normal aspects.ResultsAt a minimum 1 year's follow-up, regardless of the initial surgical technique performed, recovery was complete in six cases, partial (in terms of motor function) in one and absent in five. Without specific CPN surgery, spontaneous recovery was partial in one case, complete in two and absent in none. Following simple emergency or secondary neurolysis, remission was total in four cases and absent in one. Three nerve grafts were all associated with non-recovery.DiscussionThe present results agree with literature findings. Palsy rates varied with trauma circumstances and departmental recruitment. Neurologic impairment was commensurate to ligamentary damages. The anatomic status of the CPN, subjected to violent traction by dislocation, was the most significant prognostic factor for neurologic recovery. In about 25% of dislocations, contusion-elongation over several centimeters was associated with as poor a prognosis as total rupture. CPN neurolysis is recommended when early clinical and EMG recovery fails to progress and/or in case of lateral ligamentary reconstruction. Possible peripheral nerve impairment needs to be included in the overall functional assessment of treatment for severe ligaments injuries and knee dislocation.Level of evidenceLevel IV, prospective study

Cosmic Topology of Prism Double-Action Manifolds

The cosmic microwave background (CMB) anisotropies in spherical 3-spaces with a non-trivial topology are studied. This paper discusses the special class of the so-called double-action manifolds, which are for the first time analysed with respect to their CMB anisotropies. The CMB anisotropies are computed for all prism double-action manifolds generated by a binary dihedral and a cyclic group with a group order of up to 180 leading to 33 different topologies. Several spaces are found which show a suppression of the CMB anisotropies on large angular distances as it is found on the real CMB sky. It turns out that two of these spaces possess Dirichlet domains which are not very far from highly symmetric polyhedra like Platonic or Archimedean ones

Cosmic Topology of Polyhedral Double-Action Manifolds

A special class of non-trivial topologies of the spherical space S^3 is investigated with respect to their cosmic microwave background (CMB) anisotropies. The observed correlations of the anisotropies on the CMB sky possess on large separation angles surprising low amplitudes which might be naturally be explained by models of the Universe having a multiconnected spatial space. We analysed in CQG 29(2012)215005 the CMB properties of prism double-action manifolds that are generated by a binary dihedral group D^*_p and a cyclic group Z_n up to a group order of 180. Here we extend the CMB analysis to polyhedral double-action manifolds which are generated by the three binary polyhedral groups (T^*, O^*, I^*) and a cyclic group Z_n up to a group order of 1000. There are 20 such polyhedral double-action manifolds. Some of them turn out to have even lower CMB correlations on large angles than the Poincare dodecahedron

Hot pixel contamination in the CMB correlation function?

Recently, it was suggested that the map-making procedure, which is applied to the time-ordered CMB data by the WMAP team, might be flawed by hot pixels. This could lead to a bias in the pixels having an angular distance of about 141 degrees from hot pixels due to the differential measuring process of the satellite WMAP. Here, the bias is confirmed, and the temperature two-point correlation function C(theta) is reevaluated by excluding the affected pixels. It is shown that the most significant effect occurs in C(theta) at the largest angles near theta = 180 degrees. Furthermore, the corrected correlation function C(theta) is applied to the cubic topology of the Universe, and it is found that such a multi-connected universe matches the temperature correlation better than the LCDM concordance model, provided the cubic length scale is close to L=4 measured in units of the Hubble length

Cosmic microwave anisotropies in an inhomogeneous compact flat universe

The anisotropies of the cosmic microwave background (CMB) are computed for the half-turn space E_2 which represents a compact flat model of the Universe, i.e. one with finite volume. This model is inhomogeneous in the sense that the statistical properties of the CMB depend on the position of the observer within the fundamental cell. It is shown that the half-turn space describes the observed CMB anisotropies on large scales better than the concordance model with infinite volume. For most observer positions it matches the temperature correlation function even slightly better than the well studied 3-torus topology

The nonlinear time-dependent response of isotactic polypropylene

Tensile creep tests, tensile relaxation tests and a tensile test with a constant rate of strain are performed on injection-molded isotactic polypropylene at room temperature in the vicinity of the yield point. A constitutive model is derived for the time-dependent behavior of semi-crystalline polymers. A polymer is treated as an equivalent network of chains bridged by permanent junctions. The network is modelled as an ensemble of passive meso-regions (with affine nodes) and active meso-domains (where junctions slip with respect to their positions in the bulk medium with various rates). The distribution of activation energies for sliding in active meso-regions is described by a random energy model. Adjustable parameters in the stress--strain relations are found by fitting experimental data. It is demonstrated that the concentration of active meso-domains monotonically grows with strain, whereas the average potential energy for sliding of junctions and the standard deviation of activation energies suffer substantial drops at the yield point. With reference to the concept of dual population of crystalline lamellae, these changes in material parameters are attributed to transition from breakage of subsidiary (thin) lamellae in the sub-yield region to fragmentation of primary (thick) lamellae in the post-yield region of deformation.Comment: 29 pages, 12 figure

Eigenspectra: A Framework for Identifying Spectra from 3D Eclipse Mapping

Planetary atmospheres are inherently 3D objects that can have strong gradients in latitude, longitude, and altitude. Secondary eclipse mapping is a powerful way to map the 3D distribution of the atmosphere, but the data can have large correlations and errors in the presence of photon and instrument noise. We develop a technique to mitigate the large uncertainties of eclipse maps by identifying a small number of dominant spectra to make them more tractable for individual analysis via atmospheric retrieval. We use the eigencurves method to infer a multi-wavelength map of a planet from spectroscopic secondary eclipse light curves. We then apply a clustering algorithm to the planet map to identify several regions with similar emergent spectra. We combine the similar spectra together to construct an "eigenspectrum" for each distinct region on the planetary map. We demonstrate how this approach could be used to isolate hot from cold regions and/or regions with different chemical compositions in observations of hot Jupiters with the James Webb Space Telescope (JWST). We find that our method struggles to identify sharp edges in maps with sudden discontinuities, but generally can be used as a first step before a more physically motivated modeling approach to determine the primary features observed on the planet.Comment: 13 pages, 17 figures, accepted to MNRA