Hierarchical structuring of Cultural Heritage objects within large aggregations

Huge amounts of cultural content have been digitised and are available through digital libraries and aggregators like Europeana.eu. However, it is not easy for a user to have an overall picture of what is available nor to find related objects. We propose a method for hier- archically structuring cultural objects at different similarity levels. We describe a fast, scalable clustering algorithm with an automated field selection method for finding semantic clusters. We report a qualitative evaluation on the cluster categories based on records from the UK and a quantitative one on the results from the complete Europeana dataset.Comment: The paper has been published in the proceedings of the TPDL conference, see http://tpdl2013.info. For the final version see http://link.springer.com/chapter/10.1007%2F978-3-642-40501-3_2

Extraction of Accurate Biomolecular Parameters from Single-Molecule Force Spectroscopy Experiments

The atomic force microscope (AFM) is able to manipulate biomolecules and their complexes with exquisite force sensitivity and distance resolution. This capability, complemented by theoretical models, has greatly improved our understanding of the determinants of mechanical strength in proteins and revealed the diverse effects of directional forces on the energy landscape of biomolecules. In unbinding experiments, the interacting partners are usually immobilized on their respective substrates via extensible linkers. These linkers affect both the force and contour length (Lc) of the complex at rupture. Surprisingly, while the former effect is well understood, the latter is largely neglected, leading to incorrect estimations of Lc, a parameter that is often used as evidence for the detection of specific interactions and remodeling events and for the inference of interaction regions. To address this problem, a model that predicts contour length measurements from single-molecule forced-dissociation experiments is presented that considers attachment position on the AFM tip, geometric effects, and polymer dynamics of the linkers. Modeled data are compared with measured contour length distributions from several different experimental systems, revealing that current methods underestimate contour lengths. The model enables nonspecific interactions to be identified unequivocally, allows accurate determination of Lc, and, by comparing experimental and modeled distributions, enables partial unfolding events before rupture to be identified unequivocally

Exploiting Available Memory and Disk for Scalable Instant Overview Search

Abstract. Search-As-You-Type (or Instant Search) is a recently intro-duced functionality which shows predictive results while the user types a query letter by letter. In this paper we generalize and propose an ex-tension of this technique which apart from showing on-the-fly the first page of results, it shows various other kinds of information, e.g. the outcome of results clustering techniques, or metadata-based groupings of the results. Although this functionality is more informative than the classic search-as-you type, since it combines Autocompletion, Search-As-You-Type, and Results Clustering, the provision of real-time interaction is more challenging. To tackle this issue we propose an approach based on pre-computed information and we comparatively evaluate various in-dex structures for making real-time interaction feasible, even if the size of the available memory space is limited. This comparison reveals the mem-ory/performance trade-off and allows deciding which index structure to use according to the available main memory and desired performance. Furthermore we show that an incremental algorithm can be used to keep the index structure fresh.

Non-invasive ventilation in patients with an altered level of consciousness. A clinical review and practical insights

Non-invasive ventilation has gained an increasingly pivotal role in the treatment of acute hypoxemic and/or hypercapnic respira-tory failure and offers multiple advantages over invasive mechanical ventilation. Some of these advantages include the preserva-tion of airway defense mechanisms, a reduced need for sedation, and an avoidance of complications related to endotracheal intubation.Despite its advantages, non-invasive ventilation has some contraindications that include, among them, severe encephalopathy. In this review article, the rationale, evidence, and drawbacks of the use of noninvasive ventilation in the context of hypercapnic and non-hypercapnic patients with an altered level of consciousness are analyzed

A chicken bioreactor for efficient production of functional cytokines

The global market for protein drugs has the highest compound annual growth rate of any pharmaceutical class but their availability, especially outside of the US market, is compromised by the high cost of manufacture and validation compared to traditional chemical drugs. Improvements in transgenic technologies allow valuable proteins to be produced by genetically-modified animals; several therapeutic proteins from such animal bioreactors are already on the market after successful clinical trials and regulatory approval. Chickens have lagged behind mammals in bioreactor development, despite a number of potential advantages, due to the historic difficulty in producing transgenic birds, but the production of therapeutic proteins in egg white of transgenic chickens would substantially lower costs across the entire production cycle compared to traditional cell culture-based production systems. This could lead to more affordable treatments and wider markets, including in developing countries and for animal health applications. Here we report the efficient generation of new transgenic chicken lines to optimize protein production in eggs. As proof-of-concept, we describe the expression, purification and functional characterization of three pharmaceutical proteins, the human cytokine interferon α2a and two species-specific Fc fusions of the cytokine CSF1. Our work optimizes and validates a transgenic chicken system for the cost-effective production of pure, high quality, biologically active protein for therapeutics and other applications

ELGAR - A European Laboratory for Gravitation and Atom-interferometric Research

Gravitational waves (GWs) were observed for the first time in 2015, one century after Einstein predicted their existence. There is now growing interest to extend the detection bandwidth to low frequency. The scientific potential of multi-frequency GW astronomy is enormous as it would enable to obtain a more complete picture of cosmic events and mechanisms. This is a unique and entirely new opportunity for the future of astronomy, the success of which depends upon the decisions being made on existing and new infrastructures. The prospect of combining observations from the future space-based instrument LISA together with third generation ground based detectors will open the way toward multi-band GW astronomy, but will leave the infrasound (0.1–10 Hz) band uncovered. GW detectors based on matter wave interferometry promise to fill such a sensitivity gap. We propose the European Laboratory for Gravitation and Atom-interferometric Research (ELGAR), an underground infrastructure based on the latest progress in atomic physics, to study space–time and gravitation with the primary goal of detecting GWs in the infrasound band. ELGAR will directly inherit from large research facilities now being built in Europe for the study of large scale atom interferometry and will drive new pan-European synergies from top research centers developing quantum sensors. ELGAR will measure GW radiation in the infrasound band with a peak strain sensitivity of 3.3 x 10 [hoch]-20 / [Wurzel] Hz at 1.7 Hz. The antenna will have an impact on diverse fundamental and applied research fields beyond GW astronomy, including gravitation, general relativity, and geology

ELGAR—a European Laboratory for Gravitation and Atom-interferometric Research

Gravitational waves (GWs) were observed for the first time in 2015, one century after Einstein predicted their existence. There is now growing interest to extend the detection bandwidth to low frequency. The scientific potential of multi-frequency GW astronomy is enormous as it would enable to obtain a more complete picture of cosmic events and mechanisms. This is a unique and entirely new opportunity for the future of astronomy, the success of which depends upon the decisions being made on existing and new infrastructures. The prospect of combining observations from the future space-based instrument LISA together with third generation ground based detectors will open the way toward multi-band GW astronomy, but will leave the infrasound (0.1–10 Hz) band uncovered. GW detectors based on matter wave interferometry promise to fill such a sensitivity gap. We propose the European Laboratory for Gravitation and Atom-interferometric Research (ELGAR), an underground infrastructure based on the latest progress in atomic physics, to study space–time and gravitation with the primary goal of detecting GWs in the infrasound band. ELGAR will directly inherit from large research facilities now being built in Europe for the study of large scale atom interferometry and will drive new pan-European synergies from top research centers developing quantum sensors. ELGAR will measure GW radiation in the infrasound band with a peak strain sensitivity of $3.3{\times}1{0}^{-22}/\sqrt{\text{Hz}}$ at 1.7 Hz. The antenna will have an impact on diverse fundamental and applied research fields beyond GW astronomy, including gravitation, general relativity, and geology.AB acknowledges support from the ANR (project EOSBECMR), IdEx Bordeaux—LAPHIA (project OE-TWR), theQuantERA ERA-NET (project TAIOL) and the Aquitaine Region (projets IASIG3D and USOFF).XZ thanks the China Scholarships Council (No. 201806010364) program for financial support. JJ thanks ‘AssociationNationale de la Recherche et de la Technologie’ for financial support (No. 2018/1565).SvAb, NG, SL, EMR, DS, and CS gratefully acknowledge support by the German Space Agency (DLR) with funds provided by the Federal Ministry for Economic Affairs and Energy (BMWi) due to an enactment of the German Bundestag under Grants No. DLR∼50WM1641 (PRIMUS-III), 50WM1952 (QUANTUS-V-Fallturm), and 50WP1700 (BECCAL), 50WM1861 (CAL), 50WM2060 (CARIOQA) as well as 50RK1957 (QGYRO)SvAb, NG, SL, EMR, DS, and CS gratefully acknowledge support by ‘Niedersächsisches Vorab’ through the ‘Quantum- and Nano-Metrology (QUANOMET)’ initiative within the project QT3, and through ‘Förderung von Wissenschaft und Technik in Forschung und Lehre’ for the initial funding of research in the new DLR-SI Institute, the CRC 1227 DQ-mat within the projects A05 and B07DS gratefully acknowledges funding by the Federal Ministry of Education and Research (BMBF) through the funding program Photonics Research Germany under contract number 13N14875.RG acknowledges Ville de Paris (Emergence programme HSENS-MWGRAV), ANR (project PIMAI) and the Fundamental Physics and Gravitational Waves (PhyFOG) programme of Observatoire de Paris for support. We also acknowledge networking support by the COST actions GWverse CA16104 and AtomQT CA16221 (Horizon 2020 Framework Programme of the European Union).The work was also supported by the German Space Agency (DLR) with funds provided by the Federal Ministry for Economic Affairs and Energy (BMWi) due to an enactment of the German Bundestag under Grant Nos.∼50WM1556, 50WM1956 and 50WP1706 as well as through the DLR Institutes DLR-SI and DLR-QT.PA-S, MN, and CFS acknowledge support from contracts ESP2015-67234-P and ESP2017-90084-P from the Ministry of Economy and Business of Spain (MINECO), and from contract 2017-SGR-1469 from AGAUR (Catalan government).SvAb, NG, SL, EMR, DS, and CS gratefully acknowledge support by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy—EXC-2123 QuantumFrontiers—390837967 (B2) andCRC1227 ‘DQ-mat’ within projects A05, B07 and B09.LAS thanks Sorbonne Universités (Emergence project LORINVACC) and Conseil Scientifique de l'Observatoire de Paris for funding.This work was realized with the financial support of the French State through the ‘Agence Nationale de la Recherche’ (ANR) in the frame of the ‘MRSEI’ program (Pre-ELGAR ANR-17-MRS5-0004-01) and the ‘Investissement d'Avenir’ program (Equipex MIGA: ANR-11-EQPX-0028, IdEx Bordeaux—LAPHIA: ANR-10-IDEX-03-02).Peer Reviewe

ELGAR -- a European Laboratory for Gravitation and Atom-interferometric Research

Gravitational Waves (GWs) were observed for the first time in 2015, one century after Einstein predicted their existence. There is now growing interest to extend the detection bandwidth to low frequency. The scientific potential of multi-frequency GW astronomy is enormous as it would enable to obtain a more complete picture of cosmic events and mechanisms. This is a unique and entirely new opportunity for the future of astronomy, the success of which depends upon the decisions being made on existing and new infrastructures. The prospect of combining observations from the future space-based instrument LISA together with third generation ground based detectors will open the way towards multi-band GW astronomy, but will leave the infrasound (0.1 Hz to 10 Hz) band uncovered. GW detectors based on matter wave interferometry promise to fill such a sensitivity gap. We propose the European Laboratory for Gravitation and Atom-interferometric Research (ELGAR), an underground infrastructure based on the latest progress in atomic physics, to study space-time and gravitation with the primary goal of detecting GWs in the infrasound band. ELGAR will directly inherit from large research facilities now being built in Europe for the study of large scale atom interferometry and will drive new pan-European synergies from top research centers developing quantum sensors. ELGAR will measure GW radiation in the infrasound band with a peak strain sensitivity of $4.1 \times 10^{-22}/\sqrt{\text{Hz}}$ at 1.7 Hz. The antenna will have an impact on diverse fundamental and applied research fields beyond GW astronomy, including gravitation, general relativity, and geology

Consequences of inducing intrinsic disorder in a high-affinity protein-protein interaction

The kinetic and thermodynamic consequences of intrinsic disorder in protein-protein recognition are controversial. We address this by inducing one partner of the high-affinity colicin E3 rRNase domain-Im3 complex (Kd ≈ 10(-12) M) to become an intrinsically disordered protein (IDP). Through a variety of biophysical measurements, we show that a single alanine mutation at Tyr507 within the hydrophobic core of the isolated colicin E3 rRNase domain causes the enzyme to become an IDP (E3 rRNase(IDP)). E3 rRNase(IDP) binds stoichiometrically to Im3 and forms a structure that is essentially identical to the wild-type complex. However, binding of E3 rRNase(IDP) to Im3 is 4 orders of magnitude weaker than that of the folded rRNase, with thermodynamic parameters reflecting the disorder-to-order transition on forming the complex. Critically, pre-steady-state kinetic analysis of the E3 rRNase(IDP)-Im3 complex demonstrates that the decrease in affinity is mostly accounted for by a drop in the electrostatically steered association rate. Our study shows that, notwithstanding the advantages intrinsic disorder brings to biological systems, this can come at severe kinetic and thermodynamic cost