Bios2mds: an R package for comparing orthologous protein families by metric multidimensional scaling

BACKGROUND: The distance matrix computed from multiple alignments of homologous sequences is widely used by distance-based phylogenetic methods to provide information on the evolution of protein families. This matrix can also be visualized in a low dimensional space by metric multidimensional scaling (MDS). Applied to protein families, MDS provides information complementary to the information derived from tree-based methods. Moreover, MDS gives a unique opportunity to compare orthologous sequence sets because it can add supplementary elements to a reference space. RESULTS: The R package bios2mds (from BIOlogical Sequences to MultiDimensional Scaling) has been designed to analyze multiple sequence alignments by MDS. Bios2mds starts with a sequence alignment, builds a matrix of distances between the aligned sequences, and represents this matrix by MDS to visualize a sequence space. This package also offers the possibility of performing K-means clustering in the MDS derived sequence space. Most importantly, bios2mds includes a function that projects supplementary elements (a.k.a. "out of sample" elements) onto the space defined by reference or "active" elements. Orthologous sequence sets can thus be compared in a straightforward way. The data analysis and visualization tools have been specifically designed for an easy monitoring of the evolutionary drift of protein sub-families. CONCLUSIONS: The bios2mds package provides the tools for a complete integrated pipeline aimed at the MDS analysis of multiple sets of orthologous sequences in the R statistical environment. In addition, as the analysis can be carried out from user provided matrices, the projection function can be widely used on any kind of data

Structural evolution of G-protein-coupled receptors: a sequence space approach

Class A G-protein-coupled receptors (GPCRs) provide a fascinating example of evolutionary success. In this review, we discuss how metric multidimensional scaling (MDS), a multivariate analysis method, complements traditional tree-based phylogenetic methods and helps decipher the mechanisms that drove the evolution of class A GPCRs. MDS provides low-dimensional representations of a distance matrix. Applied to a multiple sequence alignment, MDS represents the sequences in a Euclidean space as points whose interdistances are as close as possible to the distances in the alignment (the so-called sequence space). We detail how to perform the MDS analysis of a multiple sequence alignment and how to analyze and interpret the resulting sequence space. We also show that the projection of supplementary data (a property of the MDS method) can be used to straightforwardly monitor the evolutionary drift of specific subfamilies. The sequence space of class A GPCRs reveals the key role of mutations at the level of the TM2 and TM5 proline residues in the evolution of class A GPCRs

Optimization of Energy Harvesting Systems for RFID Applications

To avoid battery assisted tags with limited lifetime batteries, it is proposed here to replace them by energy harvesting systems, able to feed from local environment. This would allow total independence to RFID systems, very interesting for applications where tag removal from its location is not possible. Example is here described for luggage safety in airports, and is easily extendable to similar situation in terms of operation constraints. The idea is to fix RFID tag with energy harvesting system not only to identify luggage but also to supply an embedded microcontroller with a sensor delivering luggage weight making it impossible to add or to remove anything from the luggage during transit phases. The aim is to optimize the harvested energy for such RFID applications, and to study in which limits these applications are theoretically possible. Proposed energy harvester is based on two energy sources: piezoelectricity and electromagnetic waves, so that when the luggage is moving on ground transportation to airline counters, the piezo module supplies the tag and its microcontroller, while the RF module operates during luggage transit thanks to readers located along the way. Tag location on the luggage is analyzed to get best vibrations, as well as harvester better choice for optimizing the energy supply depending on applications and the amount of energy harvested during a period of time. Effects of system parameters (RFID UHF frequencies, limit distance between the tag and the antenna necessary to harvest energy, produced voltage and voltage threshold) are discussed and working conditions for such system are delimited

Small optic suspensions for Advanced LIGO input optics and other precision optical experiments

We report on the design and performance of small optic suspensions developed to suppress seismic motion of out-of-cavity optics in the Input Optics subsystem of the Advanced LIGO interferometric gravitational wave detector. These compact single stage suspensions provide isolation in all six degrees of freedom of the optic, local sensing and actuation in three of them, and passive damping for the other three

Optimization of Energy Harvesting Systems for RFID Applications

To avoid battery assisted tags with limited lifetime batteries, it is proposed here to replace them by energy harvesting systems, able to feed from local environment. This would allow total independence to RFID systems, very interesting for applications where tag removal from its location is not possible. Example is here described for luggage safety in airports, and is easily extendable to similar situation in terms of operation constraints. The idea is to fix RFID tag with energy harvesting system not only to identify luggage but also to supply an embedded microcontroller with a sensor delivering luggage weight making it impossible to add or to remove anything from the luggage during transit phases. The aim is to optimize the harvested energy for such RFID applications, and to study in which limits these applications are theoretically possible. Proposed energy harvester is based on two energy sources: piezoelectricity and electromagnetic waves, so that when the luggage is moving on ground transportation to airline counters, the piezo module supplies the tag and its microcontroller, while the RF module operates during luggage transit thanks to readers located along the way. Tag location on the luggage is analyzed to get best vibrations, as well as harvester better choice for optimizing the energy supply depending on applications and the amount of energy harvested during a period of time. Effects of system parameters (RFID UHF frequencies, limit distance between the tag and the antenna necessary to harvest energy, produced voltage and voltage threshold) are discussed and working conditions for such system are delimited

Fast Optimal Transport Averaging of Neuroimaging Data

Knowing how the Human brain is anatomically and functionally organized at the level of a group of healthy individuals or patients is the primary goal of neuroimaging research. Yet computing an average of brain imaging data defined over a voxel grid or a triangulation remains a challenge. Data are large, the geometry of the brain is complex and the between subjects variability leads to spatially or temporally non-overlapping effects of interest. To address the problem of variability, data are commonly smoothed before group linear averaging. In this work we build on ideas originally introduced by Kantorovich to propose a new algorithm that can average efficiently non-normalized data defined over arbitrary discrete domains using transportation metrics. We show how Kantorovich means can be linked to Wasserstein barycenters in order to take advantage of an entropic smoothing approach. It leads to a smooth convex optimization problem and an algorithm with strong convergence guarantees. We illustrate the versatility of this tool and its empirical behavior on functional neuroimaging data, functional MRI and magnetoencephalography (MEG) source estimates, defined on voxel grids and triangulations of the folded cortical surface.Comment: Information Processing in Medical Imaging (IPMI), Jun 2015, Isle of Skye, United Kingdom. Springer, 201

Stretch-Activated Piezo1 Channel in Endothelial Cells Relaxes Mouse Intrapulmonary Arteries

In intrapulmonary artery (IPA), endothelial cells (EC) respond to mechanical stimuli by releasing vasoactive factors to set the vascular tone. Piezo1, a stretch-activated calcium permeable channel is a sensor of mechanical stress in EC. The present study was undertaken to investigate the implication of Piezo1 in the endothelium-dependent regulation of IPA tone and its potential involvement in pulmonary hypertension, the main disease of this circulation. IPA tone was quantified by means of a myograph in control Piezo1+/+ mouse and in mouse lacking endothelial Piezo1 (EC-Piezo1-/-). Endothelial intracellular calcium concentration ([Ca2+]i) and nitric oxide (NO) production were measured, in mouse or human EC, with fluo-4 and DAF-fm probes, respectively. Immunofluorescence labeling and patch-clamp experiments revealed the presence of Piezo1 channels in EC. Yoda1, a Piezo1 agonist, induced an endothelium-dependent relaxation that was significantly reduced in pulmonary arteries in EC-Piezo1-/- compared to Piezo1+/+ mouse. Yoda1 as well as mechanical stimulation (by osmotic stress) increased [Ca2+]i in mouse or human EC. Consequently, both stimuli increased the production of NO. NO and [Ca2+]i increases were reduced in EC from Piezo1-/- mouse or in the presence of Piezo1 inhibitors. Furthermore, deletion of Piezo1 increased alpha-adrenergic mediated contraction. Finally, in chronically hypoxic mice, a model of pulmonary hypertension, Piezo1 still mediated arterial relaxation and deletion of this channel did not impair the development of the disease. The present study thus demonstrates that endothelial Piezo1 contributes to intrapulmonary vascular relaxation by controlling endothelial [Ca2+]i and NO production and that this effect is still present in pulmonary hypertension

Reducing scattered light in LIGO\u27s third observing run

Noise due to scattered light has been a frequent disturbance in the advanced LIGO gravitational wave detectors, hindering the detection of gravitational waves. The non stationary scatter noise caused by low frequency motion can be recognized as arches in the time-frequency plane of the gravitational wave channel. In this paper, we characterize the scattering noise for LIGO and Virgo\u27s third observing run O3 from April, 2019 to March, 2020. We find at least two different populations of scattering noise and we investigate the multiple origins of one of them as well as its mitigation. We find that relative motion between two specific surfaces is strongly correlated with the presence of scattered light and we implement a technique to reduce this motion. We also present an algorithm using a witness channel to identify the times this noise can be present in the detecto

Altered splicing of the BIN1 muscle-specific exon in humans and dogs with highly progressive centronuclear myopathy

Amphiphysin 2, encoded by BIN1, is a key factor for membrane sensing and remodelling in different cell types. Homozygous BIN1 mutations in ubiquitously expressed exons are associated with autosomal recessive centronuclear myopathy (CNM), a mildly progressive muscle disorder typically showing abnormal nuclear centralization on biopsies. In addition, misregulation of BIN1 splicing partially accounts for the muscle defects in myotonic dystrophy (DM). However, the muscle-specific function of amphiphysin 2 and its pathogenicity in both muscle disorders are not well understood. In this study we identified and characterized the first mutation affecting the splicing of the muscle-specific BIN1 exon 11 in a consanguineous family with rapidly progressive and ultimately fatal centronuclear myopathy. In parallel, we discovered a mutation in the same BIN1 exon 11 acceptor splice site as the genetic cause of the canine Inherited Myopathy of Great Danes (IMGD). Analysis of RNA from patient muscle demonstrated complete skipping of exon 11 and BIN1 constructs without exon 11 were unable to promote membrane tubulation in differentiated myotubes. Comparative immunofluorescence and ultrastructural analyses of patient and canine biopsies revealed common structural defects, emphasizing the importance of amphiphysin 2 in membrane remodelling and maintenance of the skeletal muscle triad. Our data demonstrate that the alteration of the muscle-specific function of amphiphysin 2 is a common pathomechanism for centronuclear myopathy, myotonic dystrophy, and IMGD. The IMGD dog is the first faithful model for human BIN1-related CNM and represents a mammalian model available for preclinical trials of potential therapies