Pilot study: is there an influence of lower limb positioning during magnetic resonance imaging on muscle cross section shape assessment in the thigh?

Positioning in an MRI can influence quantitative measures of the muscle. The goal of this pilot study was to assess the influence of different levels of knee elevation during MRI on the predicted cross-sectional muscle shape in the thigh. Data were acquired in three healthy male participants (age: 29.3 ± 5.1y, height: 181.3 ± 6.4cm, weight: 85.1 ± 3.7kg). For each participant, three MRI scans were taken by a trained radiographer with low, moderate and high knee elevation. The shape of the anatomical cross-sectional areas of the hamstrings and quadriceps in three leg positionings were compared by fitting ellipsoidal functions to the segmented MRI data and calculating the so-called J index for every image slice using the Python scripting language. Different levels of knee elevation resulted in apparent changes in J index for all muscles except vastus medialis. Thereby, the changes were overall more pronounced in the hamstrings compared to the quadriceps. Particularly, by elevating the knee from 8 to 15 degree, the percentage changes in J index were between 7.2 and 13.6% for the hamstrings and between 0.5 and 3.3% for the quadriceps, respectively. For assessing the musculoskeletal properties by means of MRI, a standardized positioning of the leg is required and the knee joint angle should be controlled.

Nightingale: web components for protein feature visualization.

Motivation: The visualization of biological data is a fundamental technique that enables researchers to understand and explain biology. Some of these visualizations have become iconic, for instance: tree views for taxonomy, cartoon rendering of 3D protein structures or tracks to represent features in a gene or protein, for instance in a genome browser. Nightingale provides visualizations in the context of proteins and protein features. Results: Nightingale is a library of re-usable data visualization web components that are currently used by UniProt and InterPro, among other projects. The components can be used to display protein sequence features, variants, interaction data, 3D structure, etc. These components are flexible, allowing users to easily view multiple data sources within the same context, as well as compose these components to create a customized view. Availability and implementation: Nightingale examples and documentation are freely available at https://ebi-webcomponents.github.io/nightingale/. It is distributed under the MIT license, and its source code can be found at https://github.com/ebi-webcomponents/nightingale.

InterPro in 2022.

The InterPro database (https://www.ebi.ac.uk/interpro/) provides an integrative classification of protein sequences into families, and identifies functionally important domains and conserved sites. Here, we report recent developments with InterPro (version 90.0) and its associated software, including updates to data content and to the website. These developments extend and enrich the information provided by InterPro, and provide a more user friendly access to the data. Additionally, we have worked on adding Pfam website features to the InterPro website, as the Pfam website will be retired in late 2022. We also show that InterPro's sequence coverage has kept pace with the growth of UniProtKB. Moreover, we report the development of a card game as a method of engaging the non-scientific community. Finally, we discuss the benefits and challenges brought by the use of artificial intelligence for protein structure prediction.

The InterPro protein families and domains database: 20 years on.

The InterPro database (https://www.ebi.ac.uk/interpro/) provides an integrative classification of protein sequences into families, and identifies functionally important domains and conserved sites. InterProScan is the underlying software that allows protein and nucleic acid sequences to be searched against InterPro's signatures. Signatures are predictive models which describe protein families, domains or sites, and are provided by multiple databases. InterPro combines signatures representing equivalent families, domains or sites, and provides additional information such as descriptions, literature references and Gene Ontology (GO) terms, to produce a comprehensive resource for protein classification. Founded in 1999, InterPro has become one of the most widely used resources for protein family annotation. Here, we report the status of InterPro (version 81.0) in its 20th year of operation, and its associated software, including updates to database content, the release of a new website and REST API, and performance improvements in InterProScan.

Enhanced protein adsorption upon bulk phase separation.

In all areas related to protein adsorption, from medicine to biotechnology to heterogeneous nucleation, the question about its dominant forces and control arises. In this study, we used ellipsometry and quartz-crystal microbalance with dissipation (QCM-D), as well as density-functional theory (DFT) to obtain insight into the mechanism behind a wetting transition of a protein solution. We established that using multivalent ions in a net negatively charged globular protein solution (BSA) can either cause simple adsorption on a negatively charged interface, or a (diverging) wetting layer when approaching liquid-liquid phase separation (LLPS) by changing protein concentration (cp) or temperature (T). We observed that the water to protein ratio in the wetting layer is substantially larger compared to simple adsorption. In the corresponding theoretical model, we treated the proteins as limited-valence (patchy) particles and identified a wetting transition for this complex system. This wetting is driven by a bulk instability introduced by metastable LLPS exposed to an ion-activated attractive substrate.

High Velocity Suspension Flame Spraying (HVSFS) of Metal Suspensions.

Thermal spraying of metal materials is one of the key applications of this technology in industry for over a hundred years. The variety of metal-based feedstocks (powders and wires) used for thermal spray is incredibly large and utilization covers abrasion and corrosion protection, as well as tribological and electrical applications. Spraying metals using suspension- or precursor-based thermal spray methods is a relatively new and unusual approach. This publication deals with three metal types, a NiCr 80/20, copper (Cu), and silver (Ag), sprayed as fine-grained powders dispersed in aqueous solvent. Suspensions were sprayed by means of high-velocity suspension spraying (HVSFS) employing a modified TopGun system. The aim was to prepare thin and dense metal coatings (10-70 µm) and to evaluate the process limits regarding the oxygen content of the coatings. In case of Cu and Ag, possible applications demand high purity with low oxidation of the coating to achieve for instance a high electrical conductivity or catalytic activity. For NiCr however, it was found that coatings with a fine dispersion of oxides can be usable for applications where a tunable resistivity is in demand. The paper describes the suspension preparation and presents results of spray experiments performed on metal substrates. Results are evaluated with respect to the phase composition and the achieved coating morphology. It turns out that the oxidation content and spray efficiency is strongly controlled by the oxygen fuel ratio and spray distance.

A comprehensive resource for retrieving, visualizing, and integrating functional genomics data.

The enormous amount of freely accessible functional genomics data is an invaluable resource for interrogating the biological function of multiple DNA-interacting players and chromatin modifications by large-scale comparative analyses. However, in practice, interrogating large collections of public data requires major efforts for (i) reprocessing available raw reads, (ii) incorporating quality assessments to exclude artefactual and low-quality data, and (iii) processing data by using high-performance computation. Here, we present qcGenomics, a user-friendly online resource for ultrafast retrieval, visualization, and comparative analysis of tens of thousands of genomics datasets to gain new functional insight from global or focused multidimensional data integration.

Living standards and inequality in the industrial revolution: Evidence from the height of University of Edinburgh students in the 1830s.

Trends in living standards during the Industrial Revolution is a core debate in economic history. Studies using anthropometric records from institutional sources have found downward trends in living standards during the first half of the nineteenth century. This paper contributes to this literature by utilising an overlooked source of middle and upper class anthropometric data: the height and weight of university students. Combined with more traditional anthropometric sources these data give us a snapshot into the range of living standards experienced by different sections of society in the United Kingdom. Our findings suggest that inequality was most pronounced in Ireland, followed by England. Height inequality in Scotland was still substantial, but somewhat lower in comparison.

InterPro in 2019: improving coverage, classification and access to protein sequence annotations.

The InterPro database (http://www.ebi.ac.uk/interpro/) classifies protein sequences into families and predicts the presence of functionally important domains and sites. Here, we report recent developments with InterPro (version 70.0) and its associated software, including an 18% growth in the size of the database in terms on new InterPro entries, updates to content, the inclusion of an additional entry type, refined modelling of discontinuous domains, and the development of a new programmatic interface and website. These developments extend and enrich the information provided by InterPro, and provide greater flexibility in terms of data access. We also show that InterPro's sequence coverage has kept pace with the growth of UniProtKB, and discuss how our evaluation of residue coverage may help guide future curation activities.

Epimetheus - a multi-profile normalizer for epigenomic sequencing data.

BACKGROUND: Exponentially increasing numbers of NGS-based epigenomic datasets in public repositories like GEO constitute an enormous source of information that is invaluable for integrative and comparative studies of gene regulatory mechanisms. One of today's challenges for such studies is to identify functionally informative local and global patterns of chromatin states in order to describe the regulatory impact of the epigenome in normal cell physiology and in case of pathological aberrations. Critically, the most preferred Chromatin ImmunoPrecipitation-Sequencing (ChIP-Seq) is inherently prone to significant variability between assays, which poses significant challenge on comparative studies. One challenge concerns data normalization to adjust sequencing depth variation. RESULTS: Currently existing tools either apply linear scaling corrections and/or are restricted to specific genomic regions, which can be prone to biases. To overcome these restrictions without any external biases, we developed Epimetheus, a genome-wide quantile-based multi-profile normalization tool for histone modification data and related datasets. CONCLUSIONS: Epimetheus has been successfully used to normalize epigenomics data in previous studies on X inactivation in breast cancer and in integrative studies of neuronal cell fate acquisition and tumorigenic transformation; Epimetheus is freely available to the scientific community.

Antibody performance in ChIP-sequencing assays: From quality scores of public data sets to quantitative certification.

We have established a certification system for antibodies to be used in chromatin immunoprecipitation assays coupled to massive parallel sequencing (ChIP-seq). This certification comprises a standardized ChIP procedure and the attribution of a numerical quality control indicator (QCi) to biological replicate experiments. The QCi computation is based on a universally applicable quality assessment that quantitates the global deviation of randomly sampled subsets of ChIP-seq dataset with the original genome-aligned sequence reads. Comparison with a QCi database for >28,000 ChIP-seq assays were used to attribute quality grades (ranging from 'AAA' to 'DDD') to a given dataset. In the present report we used the numerical QC system to assess the factors influencing the quality of ChIP-seq assays, including the nature of the target, the sequencing depth and the commercial source of the antibody.  We have used this approach specifically to certify mono and polyclonal antibodies obtained from Active Motif directed against the histone modification marks H3K4me3, H3K27ac and H3K9ac for ChIP-seq. The antibodies received the grades AAA to BBC ( www.ngs-qc.org). We propose to attribute such quantitative grading of all antibodies attributed with the label "ChIP-seq grade".

LOGIQA: a database dedicated to long-range genome interactions quality assessment.

BACKGROUND: Proximity ligation-mediated methods are essential to study the impact of three-dimensional chromatin organization on gene programming. Albeit significant progress has been made in the development of computational tools that assess long-range chromatin interactions, next to nothing is known about the quality of the generated datasets. METHOD: We have developed LOGIQA ( www.ngs-qc.org/logiqa ), a database hosting quality scores for long-range genome interaction assays, accessible through a user-friendly web-based environment. RESULTS: Currently, LOGIQA harbors QC scores for >900 datasets, which provides a global view of their relative quality and reveals the impact of genome size, coverage and other technical aspects. LOGIQA provides a user-friendly dataset query panel and a genome viewer to assess local genome-interaction maps at different resolution and quality-assessment conditions. CONCLUSIONS: LOGIQA is the first database hosting quality scores dedicated to long-range chromatin interaction assays, which in addition provides a platform for visualizing genome interactions made available by the scientific community.

NGS-QC Generator: A Quality Control System for ChIP-Seq and Related Deep Sequencing-Generated Datasets.

The combination of massive parallel sequencing with a variety of modern DNA/RNA enrichment technologies provides means for interrogating functional protein-genome interactions (ChIP-seq), genome-wide transcriptional activity (RNA-seq; GRO-seq), chromatin accessibility (DNase-seq, FAIRE-seq, MNase-seq), and more recently the three-dimensional organization of chromatin (Hi-C, ChIA-PET). In systems biology-based approaches several of these readouts are generally cumulated with the aim of describing living systems through a reconstitution of the genome-regulatory functions. However, an issue that is often underestimated is that conclusions drawn from such multidimensional analyses of NGS-derived datasets critically depend on the quality of the compared datasets. To address this problem, we have developed the NGS-QC Generator, a quality control system that infers quality descriptors for any kind of ChIP-sequencing and related datasets. In this chapter we provide a detailed protocol for (1) assessing quality descriptors with the NGS-QC Generator; (2) to interpret the generated reports; and (3) to explore the database of QC indicators (www.ngs-qc.org) for >21,000 publicly available datasets.

Estimating male and female height inequality.

This study investigates the coefficient of variation (CV) of height of males and females as a measure of inequality. We have collected a data set on corresponding male and female height CVs from 124 populations, spanning the period between the 1840s and 1980s. The results suggest that the R(2) between the two CVs is 0.39, with the male CV being greater, indicating higher plasticity.

miRmap web: Comprehensive microRNA target prediction online.

MicroRNAs (miRNAs) posttranscriptionally repress the expression of protein-coding genes. Based on the partial complementarity between miRNA and messenger RNA pairs with a mandatory so-called 'seed' sequence, many thousands of potential targets can be identified. Our open-source software library, miRmap, ranks these potential targets with a biologically meaningful criterion, the repression strength. MiRmap combines thermodynamic, evolutionary, probabilistic and sequence-based features, which cover features from TargetScan, PITA, PACMIT and miRanda. Our miRmap web application offers a user-friendly and feature-rich resource for browsing precomputed miRNA target predictions for model organisms, as well as for predicting and ranking targets for user-submitted sequences. MiRmap web integrates sorting, filtering and exporting of results from multiple queries, as well as providing programmatic access, and is available at http://mirmap.ezlab.org.

The influence of inequality on the standard of living: worldwide anthropometric evidence from the 19th and 20th centuries.

We provide empirical evidence on the existence of the Pigou-Dalton principle. The latter indicates that aggregate welfare is - ceteris paribus - maximized when incomes of all individuals are equalized (and therefore marginal utility from income is as well). Using anthropometric panel data on 101 countries during the 19th and 20th centuries, we determine that there is a systematic negative and concave relationship between height inequality and average height. The robustness of this relationship is tested by means of several robustness checks, including two instrument variable regressions. These findings help to elucidate the impact of economic inequality on welfare.