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

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

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

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

Wall-Crossing in Coupled 2d-4d Systems

We introduce a new wall-crossing formula which combines and generalizes the Cecotti-Vafa and Kontsevich-Soibelman formulas for supersymmetric 2d and 4d systems respectively. This 2d-4d wall-crossing formula governs the wall-crossing of BPS states in an N=2 supersymmetric 4d gauge theory coupled to a supersymmetric surface defect. When the theory and defect are compactified on a circle, we get a 3d theory with a supersymmetric line operator, corresponding to a hyperholomorphic connection on a vector bundle over a hyperkahler space. The 2d-4d wall-crossing formula can be interpreted as a smoothness condition for this hyperholomorphic connection. We explain how the 2d-4d BPS spectrum can be determined for 4d theories of class S, that is, for those theories obtained by compactifying the six-dimensional (0,2) theory with a partial topological twist on a punctured Riemann surface C. For such theories there are canonical surface defects. We illustrate with several examples in the case of A_1 theories of class S. Finally, we indicate how our results can be used to produce solutions to the A_1 Hitchin equations on the Riemann surface C.Comment: 170 pages, 45 figure

Nonlocal symmetries of a class of scalar and coupled nonlinear ordinary differential equations of any order

In this paper we devise a systematic procedure to obtain nonlocal symmetries of a class of scalar nonlinear ordinary differential equations (ODEs) of arbitrary order related to linear ODEs through nonlocal relations. The procedure makes use of the Lie point symmetries of the linear ODEs and the nonlocal connection to deduce the nonlocal symmetries of the corresponding nonlinear ODEs. Using these nonlocal symmetries we obtain reduction transformations and reduced equations to specific examples. We find the reduced equations can be explicitly integrated to deduce the general solutions for these cases. We also extend this procedure to coupled higher order nonlinear ODEs with specific reference to second order nonlinear ODEs.Comment: Accepted for publication in J. Phys. A Math. Theor. 201

Side-channel Attacks on Blinded Scalar Multiplications Revisited

In a series of recent articles (from 2011 to 2017), Schindler et al. show that exponent/scalar blinding is not as effective a countermeasure as expected against side-channel attacks targeting RSA modular exponentiation and ECC scalar multiplication. Precisely, these works demonstrate that if an attacker is able to retrieve many randomizations of the same secret, this secret can be fully recovered even when a significative proportion of the blinded secret bits are erroneous. With a focus on ECC, this paper improves the best results of Schindler et al. in the specific case of structured-order elliptic curves. Our results show that larger blinding material and higher error rates can be successfully handled by an attacker in practice. This study also opens new directions in this line of work by the proposal of a three-steps attack process that isolates the attack critical path (in terms of complexity and success rate) and hence eases the development of future solutions

FourQ on Embedded Devices with Strong Countermeasures Against Side-Channel Attacks

This work deals with the energy-efficient, high-speed and high-security implementation of elliptic curve scalar multiplication, elliptic curve Diffie-Hellman (ECDH) key exchange and elliptic curve digital signatures on embedded devices using FourQ and incorporating strong countermeasures to thwart a wide variety of side-channel attacks. First, we set new speed records for constant-time curve-based scalar multiplication, DH key exchange and digital signatures at the 128-bit security level with implementations targeting 8, 16 and 32-bit microcontrollers. For example, our software computes a static ECDH shared secret in 6.9 million cycles (or 0.86 seconds @8MHz) on a low-power 8-bit AVR microcontroller which, compared to the fastest Curve25519 and genus-2 Kummer implementations on the same platform, offers 2x and 1.4x speedups, respectively. Similarly, it computes the same operation in 496 thousand cycles on a 32-bit ARM Cortex-M4 microcontroller, achieving a factor-2.9 speedup when compared to the fastest Curve25519 implementation targeting the same platform. A similar speed performance is observed in the case of digital signatures. Second, we engineer a set of side-channel countermeasures taking advantage of FourQ\u27s rich arithmetic and propose a secure implementation that offers protection against a wide range of sophisticated side-channel attacks, including differential power analysis (DPA). Despite the use of strong countermeasures, the experimental results show that our FourQ software is still efficient enough to outperform implementations of Curve25519 that only protect against timing attacks. Finally, we perform a differential power analysis evaluation of our software running on an ARM Cortex-M4, and report that no leakage was detected with up to 10 million traces. These results demonstrate the potential of deploying FourQ on low-power applications such as protocols for the Internet of Things