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We present a modified interferometry method based on local tangent-phase analysis, which corrects the cross-correlated data before summation. The approach makes it possible to synthesize virtual signals usually vanishing in the conventional seismic interferometry summation. For a given pair of receivers and a set of different source positions, a plurality of virtual traces is obtained at new stationary projected points located along the signal wavefronts passing through the real reference receiver. The position of the projected points is estimated by minimizing travel times using wavefront constraint and correlation-signal tangent information. The method uses mixed processing, which is partially based on velocity-model knowledge and on data-based blind interferometry. The approach can be used for selected events, including reflections with different stationary conditions and projected points with respect to those of the direct arrivals, to extend the interferometry representation in seismic exploration data where conventional illumination coverage is not sufficient to obtain the stationary-phase condition. We discuss possible applications in crosswell geometry with a velocity anomaly and a time lapse.

It has been estimated that nearly one-third of functional proteins contain a metal ion. These constitute a wide variety of possible drug targets including metalloproteinases, dehydrogenases, oxidoreductases, hydrolases, deacetylases, or many others in which the metal ion is either of catalytic or of structural nature. Despite the predominant role of a metal ion in so many classes of drug targets, current high-throughput screening techniques do not usually produce viable hits against these proteins, likely due to the lack of proper metal-binding pharmacophores in the current screening libraries. Herein, we describe a novel fragment-based drug discovery approach using a metal-targeting fragment library that is based on a variety of distinct classes of metal-binding groups designed to reliably anchor the fragments at the target’s metal ions. We show that the approach can effectively identify novel, potent and selective agents that can be readily developed into metalloprotein-targeted therapeutics.

We present the results of a seismic interferometry experiment in a shallow cased borehole. The experiment is an initial study for subsequent borehole seismic surveys in an instrumented well site, where we plan to test other surface/borehole seismic techniques. The purpose of this application is to improve the knowledge of the reflectivity sequence and to verify the potential of the seismic interferometry approach to retrieve high-frequency signals in the single well geometry, overcoming the loss and attenuation effects introduced by the overburden. We used a walkaway vertical seismic profile (VSP) geometry with a seismic vibrator to generate polarized vertical and horizontal components along a surface seismic line and an array of 3C geophones cemented outside the casing. The recorded traces are processed to obtain virtual sources in the borehole and to simulate single-well gathers with a variable sourcereceiver offset in the vertical array. We compare the results obtained by processing the field data with synthetic signals calculated by numerical simulation and analyse the signal bandwidth and amplitude versus offset to evaluate near-field effects in the virtual signals. The application provides direct and reflected signals with improved bandwidth after vibrator signal deconvolution. Clear reflections are detected in the virtual seismic sections in agreement with the geology and other surface and borehole seismic data recorded with conventional seismic exploration techniques.

PED/PEA-15 (phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes) is a ubiquitously expressed protein and a key regulator of cell growth and glucose metabolism. PED/PEA-15 mediates both homotypic and heterotypic interactions and is constituted by an N-terminal canonical death effector domain and a C-terminal tail. In the present study, the backbone dynamics of PED/PEA-15 via (15)N R(1) and R(2) and steady-state [(1)H]-(15)N NOE measurements is reported. The dynamic parameters were analyzed using both Lipari-Szabo model-free formalism and a reduced spectral density mapping approach. The results obtained define a polar and charged surface of the death effector domain characterized by internal motions in the micro- to millisecond timescale, which is crucial for the multiple heterotypic functional protein-protein interactions in which PED/PEA-15 is involved. The present study contributes to a better understanding of the molecular basis of the PED/PEA-15 functional interactions and provides a more detailed surface for the design and development of PED/PEA-15 binders.

We describe a method to process the seismic data generated by a plurality of sources and registered by an appropriate distribution of receivers, which provides new seismic signals as if in the position of the receivers (or sources) there was an ideal reflector, even if this reflector is not present there. The data provided by this method represent the signals of a virtual reflector. The proposed algorithm performs the convolution and the subsequent sum of the real traces without needing subsurface model information. The approach can be used in combination with seismic interferometry to separate wavefields and process the reflection events. The application is described with synthetic examples, including stationary phase analysis and with real data in which the virtual reflector signal can be appreciated.

Integrins are a large family of heterodimeric receptors critically engaged in pathological processes such as tumor progression and metastasis. Although they are validated therapeutic targets, the molecular determinants governing integrin-ligand interactions are not yet fully understood, leading to a scarcity of integrin sub-type exclusive antagonists. In the past decade, we have investigated the biological behavior of the RGDechi, a chimeric peptide able to specifically bind avb3 integrin without cross reacting with avb5 and aIIbb3 integrins. Here we have investigated the capability of the peptide to bind a5b1 integrin and characterized the molecular determinants governing this interaction through a combined experimental and computational approach. The detailed comparison of RGDechi-a5b1 structural model with that previously determined of RGDechi in complex with avb3 shows how the bifunctional nature of the peptide renders the molecule an important tool to recognize integrins with different recognition modalities, providing novel insight on the structural requirements needed to their specific recognition.

CLA, a natural, highly hydrophobic cyclic nonapeptide with sequence c(Pro(1)-Pro(2)-Phe(3)-Phe(4)-Leu(5)-Ile(6)-Ile(7)-Leu(8)-Val(9)-), isolated from linseed oil, was found to possess a strong immunosuppressive activity comparable, in low doses, with that of CsA, with a mechanism that depends on the inhibition of the interleukin-1 and interleukin-2 action. Structural analysis of CLA and its related compounds has underlined that the presence of the tetrapeptide Pro-Pro-Phe-Phe sequence, the Pro-Pro cis amide bond, and the 'edge-to-face' interaction are possible important features for the immunosuppressive activity of CLA. To evaluate the role and significance of 'edge-to-face' interaction in the process of molecular recognition by receptors, we have synthesised three linear precursors and three cyclic analogues of CLA, in which one or both Phe residues have been replaced by beta(3)Phe residues. A conformational analysis by NMR in CD(3)CN/H(2)O mixture has been carried out on the CLA analogue, in which Phe(3) has been replaced by a betaPhe, to study the influence of the mutation on the three-dimensional structure. All linear and cyclic CLA analogues containing betaPhe have been tested in the humoral and cellular immune response in vivo assays in mice. The peptide activities have been compared with CsA, as a reference drug.