A Budding-Defective M2 Mutant Exhibits Reduced Membrane Interaction, Insensitivity To Cholesterol, And Perturbed Interdomain Coupling

Influenza A M2 is a membrane-associated protein with a C-terminal amphipathic helix that plays a cholesterol-dependent role in viral budding. An M2 mutant with alanine substitutions in the C-terminal amphipathic helix is deficient in viral scission. With the goal of providing atomic-level understanding of how the wild-type protein functions, we used a multipronged site-directed spin labeling electron paramagnetic resonance spectroscopy (SDSL-EPR) approach to characterize the conformational properties of the alanine mutant. We spin-labeled sites in the transmembrane (TM) domain and the C-terminal amphipathic helix (AH) of wild-type (WT) and mutant M2, and collected information on line shapes, relaxation rates, membrane topology, and distances within the homotetramer in membranes with and without cholesterol. Our results identify marked differences in the conformation and dynamics between the WT and the alanine mutant. Compared to WT, the dominant population of the mutant AH is more dynamic, shallower in the membrane, and has altered quaternary arrangement of the C-terminal domain. While the AH becomes more dynamic, the dominant population of the TM domain of the mutant is immobilized. The presence of cholesterol changes the conformation and dynamics of the WT protein, while the alanine mutant is insensitive to cholesterol. These findings provide new insight into how M2 may facilitate budding. We propose the AH–membrane interaction modulates the arrangement of the TM helices, effectively stabilizing a conformational state that enables M2 to facilitate viral budding. Antagonizing the properties of the AH that enable interdomain coupling within M2 may therefore present a novel strategy for anti-influenza drug design

Nonlinear Dirac operator and quaternionic analysis

Properties of the Cauchy-Riemann-Fueter equation for maps between quaternionic manifolds are studied. Spaces of solutions in case of maps from a K3-surface to the cotangent bundle of a complex projective space are computed. A relationship between harmonic spinors of a generalized nonlinear Dirac operator and solutions of the Cauchy-Riemann-Fueter equation are established.Comment: Cosmetic changes onl

Influence of Collision Cascade Statistics on Pattern Formation of Ion-Sputtered Surfaces

Theoretical continuum models that describe the formation of patterns on surfaces of targets undergoing ion-beam sputtering, are based on Sigmund's formula, which describes the spatial distribution of the energy deposited by the ion. For small angles of incidence and amorphous or polycrystalline materials, this description seems to be suitable, and leads to the classic BH morphological theory [R.M. Bradley and J.M.E. Harper, J. Vac. Sci. Technol. A 6, 2390 (1988)]. Here we study the sputtering of Cu crystals by means of numerical simulations under the binary-collision approximation. We observe significant deviations from Sigmund's energy distribution. In particular, the distribution that best fits our simulations has a minimum near the position where the ion penetrates the surface, and the decay of energy deposition with distance to ion trajectory is exponential rather than Gaussian. We provide a modified continuum theory which takes these effects into account and explores the implications of the modified energy distribution for the surface morphology. In marked contrast with BH's theory, the dependence of the sputtering yield with the angle of incidence is non-monotonous, with a maximum for non-grazing incidence angles.Comment: 12 pages, 13 figures, RevTe

Substructure lensing in galaxy clusters as a constraint on low-mass sterile neutrinos in tensor-vector-scalar theory: The straight arc of Abell 2390

Certain covariant theories of the modified Newtonian dynamics paradigm seem to require an additional hot dark matter (HDM) component - in the form of either heavy ordinary neutrinos or more recently light sterile neutrinos (SNs) with a mass around 11eV - to be relieved of problems ranging from cosmological scales down to intermediate ones relevant for galaxy clusters. Here we suggest using gravitational lensing by galaxy clusters to test such a marriage of neutrino HDM and modified gravity, adopting the framework of tensor-vector-scalar theory (TeVeS). Unlike conventional cold dark matter (CDM), such HDM is subject to strong phase-space constraints, which allows one to check cluster lens models inferred within the modified framework for consistency. Since the considered HDM particles cannot collapse into arbitrarily dense clumps and only form structures well above the galactic scale, systems which indicate the need for dark substructure are of particular interest. As a first example, we study the cluster lens Abell 2390 and its impressive straight arc with the help of numerical simulations. Based on our results, we outline a general and systematic approach to model cluster lenses in TeVeS which significantly reduces the calculation complexity. We further consider a simple bimodal lens configuration, capable of producing the straight arc, to demonstrate our approach. We find that such a model is marginally consistent with the hypothesis of 11eV SNs. Future work including more detailed and realistic lens models may further constrain the necessary SN distribution and help to conclusively assess this point. Cluster lenses could therefore provide an interesting discriminator between CDM and such modified gravity scenarios supplemented by SNs or other choices of HDM.Comment: 22 pages, 14 figures, 2 tables; minor changes to match accepted versio

Optimization of the Kinematic Chain of the Thumb for a Hand Prosthesis Based on the Kapandji Opposition Test

Ponènica presentada a International Symposium on Computer Methods in Biomechanics and Biomedical Engineering - CMBBE 2019The thumb plays a key role in the performance of the hand for grasp-ing and manipulating objects. In artificial hands the complex thumb’s kinematic chain (TKC) is simplified and its five degrees of freedom are reduced to only one or two with the consequent loss of dexterity of the hand. The Kapandji op-position test (KOT) has been clinically used in pathological human hands for evaluating the thumb opposition and it has also been employed in some previ-ous studies as reference for the design of the TKC in artificial hands, but with-out a clearly stated methodology. Based on this approaches, in this study we present a computational method to optimize the whole TKC (base placement, link lengths and joint orientation angles) of an artificial hand based on its per-formance in the KOT. The cost function defined for the optimization (MPE) is a weighted mean position error when trying to reproduce the KOT postures and can be used also as a metric to quantify thumb opposition in the hand. As a case study, the method was applied to the improvement of the TKC of an artificial hand developed by the authors and the MPE was reduced to near one third of that of the original design, increasing significantly the number of reachable po-sitions in the KOT. The metric proposed based on the KOT can be used directly or in combination with other to improve the kinematic chain of artificial hands

On Five-dimensional Superspaces

Recent one-loop calculations of certain supergravity-mediated quantum corrections in supersymmetric brane-world models employ either the component formulation (hep-th/0305184) or the superfield formalism with only half of the bulk supersymmetry manifestly realized (hep-th/0305169 and hep-th/0411216). There are reasons to expect, however, that 5D supergraphs provide a more efficient setup to deal with these and more involved (in particular, higher-loop) calculations. As a first step toward elaborating such supergraph techniques, we develop in this letter a manifestly supersymmetric formulation for 5D globally supersymmetric theories with eight supercharges. Simple rules are given to reduce 5D superspace actions to a hybrid form which keeps manifest only the 4D, N=1 Poincare supersymmetry. (Previously, such hybrid actions were carefully worked out by rewriting the component actions in terms of simple superfields). To demonstrate the power of this formalism for model building applications, two families of off-shell supersymmetric nonlinear sigma-models in five dimensions are presented (including those with cotangent bundles of Kahler manifolds as target spaces). We elaborate, trying to make our presentation maximally clear and self-contained, on the techniques of 5D harmonic and projective superspaces used at some stages in this letter.Comment: 46 pages, 3 figures. V5: version published in JHE

A unification in the theory of linearization of second order nonlinear ordinary differential equations

In this letter, we introduce a new generalized linearizing transformation (GLT) for second order nonlinear ordinary differential equations (SNODEs). The well known invertible point (IPT) and non-point transformations (NPT) can be derived as sub-cases of the GLT. A wider class of nonlinear ODEs that cannot be linearized through NPT and IPT can be linearized by this GLT. We also illustrate how to construct GLTs and to identify the form of the linearizable equations and propose a procedure to derive the general solution from this GLT for the SNODEs. We demonstrate the theory with two examples which are of contemporary interest.Comment: 8 page