Inverse Statistical Physics of Protein Sequences: A Key Issues Review

In the course of evolution, proteins undergo important changes in their amino acid sequences, while their three-dimensional folded structure and their biological function remain remarkably conserved. Thanks to modern sequencing techniques, sequence data accumulate at unprecedented pace. This provides large sets of so-called homologous, i.e.~evolutionarily related protein sequences, to which methods of inverse statistical physics can be applied. Using sequence data as the basis for the inference of Boltzmann distributions from samples of microscopic configurations or observables, it is possible to extract information about evolutionary constraints and thus protein function and structure. Here we give an overview over some biologically important questions, and how statistical-mechanics inspired modeling approaches can help to answer them. Finally, we discuss some open questions, which we expect to be addressed over the next years.Comment: 18 pages, 7 figure

Selection of sequence motifs and generative Hopfield-Potts models for protein familiesilies

Statistical models for families of evolutionary related proteins have recently gained interest: in particular pairwise Potts models, as those inferred by the Direct-Coupling Analysis, have been able to extract information about the three-dimensional structure of folded proteins, and about the effect of amino-acid substitutions in proteins. These models are typically requested to reproduce the one- and two-point statistics of the amino-acid usage in a protein family, {\em i.e.}~to capture the so-called residue conservation and covariation statistics of proteins of common evolutionary origin. Pairwise Potts models are the maximum-entropy models achieving this. While being successful, these models depend on huge numbers of {\em ad hoc} introduced parameters, which have to be estimated from finite amount of data and whose biophysical interpretation remains unclear. Here we propose an approach to parameter reduction, which is based on selecting collective sequence motifs. It naturally leads to the formulation of statistical sequence models in terms of Hopfield-Potts models. These models can be accurately inferred using a mapping to restricted Boltzmann machines and persistent contrastive divergence. We show that, when applied to protein data, even 20-40 patterns are sufficient to obtain statistically close-to-generative models. The Hopfield patterns form interpretable sequence motifs and may be used to clusterize amino-acid sequences into functional sub-families. However, the distributed collective nature of these motifs intrinsically limits the ability of Hopfield-Potts models in predicting contact maps, showing the necessity of developing models going beyond the Hopfield-Potts models discussed here.Comment: 26 pages, 16 figures, to app. in PR

Image Slicer Performances from a Demonstrator for the SNAP/JDEM Mission - Part I: Wavelength Accuracy

A well-adapted visible and infrared spectrograph has been developed for the SNAP (SuperNova/Acceleration Probe) experiment proposed for JDEM. The instrument should have a high sensitivity to see faint supernovae but also a good redshift determination better than 0.003(1+z) and a precise spectrophotometry (2%). An instrument based on an integral field method with the powerful concept of imager slicing has been designed. A large prototyping effort has been performed in France which validates the concept. In particular a demonstrator reproducing the full optical configuration has been built and tested to prove the optical performances both in the visible and in the near infrared range. This paper is the first of two papers. The present paper focus on the wavelength measurement while the second one will present the spectrophotometric performances. We adress here the spectral accuracy expected both in the visible and in the near infrared range in such configuration and we demonstrate, in particular, that the image slicer enhances the instrumental performances in the spectral measurement precision by removing the slit effect. This work is supported in France by CNRS/INSU/IN2P3 and by the French spatial agency (CNES) and in US by the University of California.Comment: Submitted to PAS

Building with Drones: Accurate 3D Facade Reconstruction using MAVs

Automatic reconstruction of 3D models from images using multi-view Structure-from-Motion methods has been one of the most fruitful outcomes of computer vision. These advances combined with the growing popularity of Micro Aerial Vehicles as an autonomous imaging platform, have made 3D vision tools ubiquitous for large number of Architecture, Engineering and Construction applications among audiences, mostly unskilled in computer vision. However, to obtain high-resolution and accurate reconstructions from a large-scale object using SfM, there are many critical constraints on the quality of image data, which often become sources of inaccuracy as the current 3D reconstruction pipelines do not facilitate the users to determine the fidelity of input data during the image acquisition. In this paper, we present and advocate a closed-loop interactive approach that performs incremental reconstruction in real-time and gives users an online feedback about the quality parameters like Ground Sampling Distance (GSD), image redundancy, etc on a surface mesh. We also propose a novel multi-scale camera network design to prevent scene drift caused by incremental map building, and release the first multi-scale image sequence dataset as a benchmark. Further, we evaluate our system on real outdoor scenes, and show that our interactive pipeline combined with a multi-scale camera network approach provides compelling accuracy in multi-view reconstruction tasks when compared against the state-of-the-art methods.Comment: 8 Pages, 2015 IEEE International Conference on Robotics and Automation (ICRA '15), Seattle, WA, US

Lectin ligands: New insights into their conformations and their dynamic behavior and the discovery of conformer selection by lectins

The mysteries of the functions of complex glycoconjugates have enthralled scientists over decades. Theoretical considerations have ascribed an enormous capacity to store information to oligosaccharides, In the interplay with lectins sugar-code words of complex carbohydrate structures can be deciphered. To capitalize on knowledge about this type of molecular recognition for rational marker/drug design, the intimate details of the recognition process must be delineated, To this aim the required approach is garnered from several fields, profiting from advances primarily in X-ray crystallography, nuclear magnetic resonance spectroscopy and computational calculations encompassing molecular mechanics, molecular dynamics and homology modeling. Collectively considered, the results force us to jettison the preconception of a rigid ligand structure. On the contrary, a carbohydrate ligand may move rather freely between two or even more low-energy positions, affording the basis for conformer selection by a lectin. By an exemplary illustration of the interdisciplinary approach including up-to-date refinements in carbohydrate modeling it is underscored why this combination is considered to show promise of fostering innovative strategies in rational marker/drug design

Ab initio study of element segregation and oxygen adsorption on PtPd and CoCr binary alloy surfaces

The segregation behavior of the bimetallic alloys PtPd and CoCr in the case of bare surfaces and in the presence of an oxygen ad-layer has been studied by means of first-principles modeling based on density-functional theory (DFT). For both systems, change of the d-band filling due to charge transfer between the alloy components, resulting in a shift of the d-band center of surface atoms compared to the pure components, drives the surface segregation and governs the chemical reactivity of the bimetals. In contrast to previous findings but consistent with analogous PtNi alloy systems, enrichment of Pt atoms in the surface layer and of Pd atoms in the first subsurface layer has been found in Pt-rich PtPd alloy, despite the lower surface energy of pure Pd compared to pure Pt. Similarly, Co surface and Cr subsurface segregation occurs in Co-rich CoCr alloys. However, in the presence of adsorbed oxygen, Pd and Cr occupy preferentially surface sites due to their lower electronegativity and thus stronger oxygen affinity compared to Pt and Co, respectively. In either cases, the calculated oxygen adsorption energies on the alloy surfaces are larger than on the pure components when the more noble components are present in the subsurface layers

Expertise effects in memory recall: A reply to Vicente and Wang

This article may not exactly replicate the final version published in the APA journal. It is not the copy of record.In the January 1998 Psychological Review, Vicente and Wang propose a "constraint attunement hypothesis" to explain the large effects of domain expertise upon memory recall observed in a number of task domains. They claim to find serious defects in alternative explanations of these effects which their theory overcomes. Re-examination of the evidence shows that their theory is not novel, but has been anticipated by those they criticize, and that other current published theories of the phenomena do not have the defects Vicente and Wang attribute to them. Vicente and Wang's views reflect underlying differences (a) about emphasis upon performance versus process in psychology, and (b) about how theories and empirical knowledge interact and progress with the development of a science

Method to Look for Imprints of Ultrahigh Energy Nuclei Sources

We propose a new method to search for heavy nuclei sources, on top of background, in the Ultra-High Energy Cosmic Ray data. We apply this method to the 69 events recently published by the Pierre Auger Collaboration and find a tail of events for which it reconstructs the source at a few degrees from the Virgo galaxy cluster. The reconstructed source is located at ~ 8.5 degrees from M87. The probability to have such a cluster of events in some random background and reconstruct the source position in any direction of the sky is about 7 x 10^(-3). The probability to reconstruct the source at less than 10 degrees from M87 in a data set already containing such a cluster of events is about 4 x 10^(-3). This may be a hint at the Virgo cluster as a bright ultra-high energy nuclei source. We investigate the ability of current and future experiments to validate or rule out this possibility, and discuss several alternative solutions which could explain the existing anisotropy in the Auger data.Comment: 12 pages (2 columns), 10 figures. Published in Physical Review

A planning approach to the automated synthesis of template-based process models

The design-time specification of flexible processes can be time-consuming and error-prone, due to the high number of tasks involved and their context-dependent nature. Such processes frequently suffer from potential interference among their constituents, since resources are usually shared by the process participants and it is difficult to foresee all the potential tasks interactions in advance. Concurrent tasks may not be independent from each other (e.g., they could operate on the same data at the same time), resulting in incorrect outcomes. To tackle these issues, we propose an approach for the automated synthesis of a library of template-based process models that achieve goals in dynamic and partially specified environments. The approach is based on a declarative problem definition and partial-order planning algorithms for template generation. The resulting templates guarantee sound concurrency in the execution of their activities and are reusable in a variety of partially specified contextual environments. As running example, a disaster response scenario is given. The approach is backed by a formal model and has been tested in experiment