Proximal and distal control for ligand binding in neuroglobin: role of the CD loop and evidence for His64 gating

Neuroglobin (Ngb) is predominantly expressed in neurons of the central and peripheral nervous systems and it clearly seems to be involved in neuroprotection. Engineering Ngb to observe structural and dynamic alterations associated with perturbation in ligand binding might reveal important structural determinants, and could shed light on key features related to its mechanism of action. Our results highlight the relevance of the CD loop and of Phe106 as distal and proximal controls involved in ligand binding in murine neuroglobin. We observed the effects of individual and combined mutations of the CD loop and Phe106 that conferred to Ngb higher CO binding velocities, which we correlate with the following structural observations: the mutant F106A shows, upon CO binding, a reduced heme sliding hindrance, with the heme present in a peculiar double conformation, whereas in the CD loop mutant "Gly-loop", the original network of interactions between the loop and the heme was abolished, enhancing binding via facilitated gating out of the distal His64. Finally, the double mutant, combining both mutations, showed a synergistic effect on CO binding rates. Resonance Raman spectroscopy and MD simulations support our findings on structural dynamics and heme interactions in wild type and mutated Ngbs

Proximal and distal control for ligand binding in neuroglobin: role of the CD loop and evidence for His64 gating

Neuroglobin (Ngb) is predominantly expressed in neurons of the central and peripheral nervous systems and it clearly seems to be involved in neuroprotection. Engineering Ngb to observe structural and dynamic alterations associated with perturbation in ligand binding might reveal important structural determinants, and could shed light on key features related to its mechanism of action. Our results highlight the relevance of the CD loop and of Phe106 as distal and proximal controls involved in ligand binding in murine neuroglobin. We observed the effects of individual and combined mutations of the CD loop and Phe106 that conferred to Ngb higher CO binding velocities, which we correlate with the following structural observations: the mutant F106A shows, upon CO binding, a reduced heme sliding hindrance, with the heme present in a peculiar double conformation, whereas in the CD loop mutant “Gly-loop”, the original network of interactions between the loop and the heme was abolished, enhancing binding via facilitated gating out of the distal His64. Finally, the double mutant, combining both mutations, showed a synergistic effect on CO binding rates. Resonance Raman spectroscopy and MD simulations support our findings on structural dynamics and heme interactions in wild type and mutated Ngbs

Compressive sensing imaging of non-sparse 2D scatterers by a total-variation approach within the Born approximation

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A total variation compressive sensing technique for imaging large scatterers

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Tomographic Imaging of Sparse Low-Contrast Targets in Harsh Environments Through Matrix Completion

International audienceA new methodology that exploits the matrix completion (MC) paradigm is proposed to image weak and sparse scatterers in heavy noise conditions. The 2-D inverse problem, mathematically formulated under the first-order Born approximation, is addressed with a three-phase algorithm that consists of: 1) an initial estimation step where a preliminary reconstruction of the distribution of the contrast and the associated “confidence map” are computed by means of a Bayesian compressive sensing method; 2) a filtering step devoted to identify and discard the less reliable contrast coefficients; and 3) a final dielectric profile completion step aimed at recovering a faithful image of the whole scattering scenario by exploiting a customized MC procedure. Representative numerical results and comparisons with competitive state-of-the-art inversion techniques are reported and discussed to assess the accuracy, the robustness, and the numerical efficiency of the proposed approach

Synthesis of clustered linear arrays through a total variation compressive sensing approach

International audienceIn this work the problem of synthesizing the excitations of a linear array, clustered into contiguous sub-arrays of irregular length, is addressed. By suitably exploiting the behavior of clustered array aperture distributions (i.e., step-wise discrete functions), the problem has been formulated as the minimization of the total variation (TV) of the excitations, satisfying a matching condition on a predefined reference pattern. In virtue of the sparse nature of the unknowns, the minimization problem has been solved by means of an efficient total variation compressive sensing (TV-CS) optimization approach. A simple example validating the proposed technique is finally reported

Synthesis of multi-layer WAIM coatings for planar phased arrays within the system-by-design framework

International audienceThe synthesis of multilayer wide-angle impedance-matching (WAIM) structures for waveguide-fed planar phased array antennas is addressed. Under multifrequency constraints and assuming arbitrary array layouts, the synthesis problem is formulated within the system-by-design (SbD) framework. An iterative strategy is implemented by combining a fast EM modeling tool for the computation of the voltage reflection coefficient at the array surface and a solution-space sampling loop driven by the set of physical constraints describing both the synthesis objectives and the range boundaries for the degrees-of-freedom (DoFs) of the problem at hand. Thanks to the effectiveness and the reliability of such an integrated approach, it is possible to deal with multilayer multifrequency WAIM structures with uniaxially anisotropic permittivity and permeability tensors. Selected numerical results are presented to assess the potentialities and the reliability of the proposed approach also in comparison with state-of-the-art techniques

Material-by-Design Synthesis of Conformal Miniaturized Linear Phased Arrays

International audienceIn this paper, the design of high performance conformal radiating structures is addressed within the Material-by-Design (MbD) paradigm. Toward this end, a new synthesis technique based on the innovative integration of a generalized quasi-conformal transformation optics and a source inversion procedure is proposed to fit linear phased arrays to smaller and arbitrarily-shaped surfaces. To the best of our knowledge, it is the first time that a design methodology simultaneously achieves (i) a simplification of the antenna layout through the reduction of its aperture and number of elements and (ii) its conformal transformation in order to match the aerodynamics of the hosting structure without affecting the required radiation features. It is worth remarking that the synthesized architectures are not only conformal, but they also provide the same performances of larger and straight layouts that could not be directly fitted to the available support. Some representative results are shown and discussed in order to validate the effectiveness of the proposed MbD methodology, as well as to highlight its current limitations