Amino Acids Modification to Improve and Fine-Tune Peptide- Based Hydrogels

Among all the materials used in industry, gels play an increasingly important role. These so-called soft-matter materials are defined by their ability to fix a large amount of solvent, either organic (organogels) or aqueous (hydrogels). The large majority of hydrogels are made of natural or synthetic polymers, or natural proteins. However, a new kind of hydrogel has appeared: the peptide-based hydrogels, developed from short amino acids sequences (<20 amino acids). Due to their exceptional qualities in term of biocompatibility, biodegradability, and atom economy, these peptide-based hydrogels open new horizons in term of applications. They are mainly considered in the biomedical domain as injectable hydrogels, or as an extracellular culture matrix to support cell culture. While important, the possibilities of peptide design can exponentially grow using modified and non-natural amino acids instead of the “only” twenty natural ones. Thus, chemical modifications virtually offer infinite opportunities both to improve applications window and to fine-tune properties of the resulting hydrogels. In this context, this chapter proposes to review peptide and amino acid modifications reported to impact the resulting hydrogel

Native and Synthetic G-quartet-based DNAzyme Systems – Artificial Enzymes for Biotechnological Applications

Catalysis of chemical reactions is crucial for both chemical industry and research. However, scientists are not the first ones to use catalysts in their laboratory. In fact, they are also essential for nature which designs plenty of biocatalysts, playing a pivotal role in living systems. For a long time, it was thought that only enzymes had this property. However, since the beginning of the 1980s, it is known that ribonucleic acids (also termed RNA) can acquire this ability, making them compulsory for key reactions (e.g., for the translation of messenger RNA in the ribosome). Based on that, chemists designed several synthetic DNA catalysts (termed DNAzymes) for a large variety of reactions and applications. Among the DNA structures used, G-quadruplexes are guanine-rich noncanonical DNA structures (i.e., differing from duplex DNA) composed of native G-quartets and particularly interesting for their ability to catalyze reactions of peroxidation. This peroxidase-mimicking system found plenty of applications detailed in this chapter. Moreover, optimizations of experimental conditions are also discussed and highlight the versatility and easy-to-use characteristics of G-quadruplexes DNA. Also, synthetic G-quartets, mainly TASQ (for template-assembled synthetic G-quartets), developed by chemists showed their ability to mimic G-quadruplexes, thanks to the presence of a G-quartet. Thus, synthetic G-quartets proved their capability to catalyze peroxidase-mimicking reactions, and these new exciting nature-mimicking catalytic systems are presented in detail in this chapter

A modal-based approach to the nonlinear vibration of strings against a unilateral obstacle:Simulations and experiments in the pointwise case

International audienceThis article is concerned with the vibration of a stiff linear string in the presence of a rigid obstacle. A numerical method for unilateral and arbitrary-shaped obstacles is developed, based on a modal approach in order to take into account the frequency dependence of losses in strings. The contact force of the barrier interaction is treated using a penalty approach, while a conservative scheme is derived for time integration, in order to ensure long-term numerical stability. In this way, the linear behaviour of the string when not in contact with the barrier can be controlled via a mode by mode fitting, so that the model is particularly well suited for comparisons with experiments. An experimental configuration is used with a point obstacle either centered or near an extremity of the string. In this latter case, such a pointwise obstruction approximates the end condition found in the tanpura, an Indian stringed instrument. The second polarisation of the string is also analysed and included in the model. Numerical results are compared against experiments, showing good accuracy over a long time scale

A modal approach to the numerical simulation of a string vibrating against an obstacle:Applications to sound synthesis

International audienceA number of musical instruments (electric basses, tanpuras, si-tars...) have a particular timbre due to the contact between a vibrating string and an obstacle. In order to simulate the motion of such a string with the purpose of sound synthesis, various technical issues have to be resolved. First, the contact phenomenon, inherently nonlinear and producing high frequency components, must be described in a numerical manner that ensures stability. Second, as a key ingredient for sound perception, a fine-grained frequency-dependent description of losses is necessary. In this study, a new conservative scheme based on a modal representation of the displacement is presented, allowing the simulation of a stiff, damped string vibrating against an obstacle with an arbitrary geometry. In this context, damping parameters together with eigenfrequencies of the system can be adjusted individually, allowing for complete control over loss characteristics. Two cases are then numerically investigated: a point obstacle located in the vicinity of the boundary , mimicking the sound of the tanpura, and then a parabolic obstacle for the sound synthesis of the sitar

Supramolecular amplification of amyloid self-assembly by iodination

Amyloid supramolecular assemblies have found widespread exploitation as ordered nanomaterials in a range of applications from materials science to biotechnology. New strategies are, however, required for understanding and promoting mature fibril formation from simple monomer motifs through easy and scalable processes. Noncovalent interactions are key to forming and holding the amyloid structure together. On the other hand, the halogen bond has never been used purposefully to achieve control over amyloid self-assembly. Here we show that single atom replacement of hydrogen with iodine, a halogen-bond donor, in the human calcitonin-derived amyloidogenic fragment DFNKF results in a super-gelator peptide, which forms a strong and shape-persistent hydrogel at 30-fold lower concentration than the wild-type pentapeptide. This is remarkable for such a modest perturbation in structure. Iodination of aromatic amino acids may thus develop as a general strategy for the design of new hydrogels from unprotected peptides and without using organic solvents

Leveraging Random Forests for Interactive Exploration of Large Histological Images

International audienceThelargesizeofhistologicalimagescombinedwiththeirvery challenging appearance are two main difficulties which considerably com- plicate their analysis. In this paper, we introduce an interactive strategy leveraging the output of a supervised random forest classifier to guide a user through such large visual data. Starting from a forest-based pixel- wise estimate, subregions of the images at hand are automatically ranked and sequentially displayed according to their expected interest. After each region suggestion, the user selects among several options a rough es- timate of the true amount of foreground pixels in this region. From these one-click inputs, the region scoring function is updated in real time using an online gradient descent procedure, which corrects on-the-fly the short- comings of the initial model and adapts future suggestions accordingly. Experimental validation is conducted for extramedullary hematopoesis localization and demonstrates the practical feasibility of the procedure as well as the benefit of the online adaptation strategy

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In this article, we describe and interpret a set of acoustic and linguistic features that characterise emotional/emotion-related user states – confined to the one database processed: four classes in a German corpus of children interacting with a pet robot. To this end, we collected a very large feature vector consisting of more than 4000 features extracted at different sites. We performed extensive feature selection (Sequential Forward Floating Search) for seven acoustic and four linguistic types of features, ending up in a small number of ‘most important ’ features which we try to interpret by discussing the impact of different feature and extraction types. We establish different measures of impact and discuss the mutual influence of acoustics and linguistics

Surgical therapy of thymic tumours with pleural involvement: an ESTS Thymic Working Group Project

OBJECTIVES Surgery for thymic epithelial tumours (TETs) with pleural involvement is infrequently performed. Thus, the value of surgical therapy for primary or recurrent TETs with pleural involvement is not sufficiently defined yet. METHODS Twelve institutions contributed retrospective data on 152 patients undergoing surgery (1977-2014) on behalf of the ESTS Thymic Working group. Outcome measures included overall (OS), cause-specific (CSS) and disease-free (DFS) survival as well as freedom from recurrence (FFR). RESULTS In 70.4% of cases, pleural involvement was present at the time of primary intervention, whereas 29.6% had surgery for recurrent disease involving the pleura. Pleural involvement resulted from thymomas (88.8%) and thymic carcinomas (11.2%). Forty extrapleural pneumonectomies (EPPs), 23 total pleurectomies (TPs), and 88 local pleurectomies (LPs) were performed (completeness of resection in 76.8%). OS for the entire patient population at 1, 3, 5 and 10 years was 96.4%, 91.0%, 87.2% and 62.7%, respectively. There was no statistically significant difference regarding FFR and OS for patients with local or advanced disease undergoing EPP, TP or LP. Thymic carcinomas in comparison with thymomas had a negative impact on OS [hazard ratio 6.506, P  = 0.002], CSS and FFR. Incomplete resections predicted worse OS [hazard ratio 6.696, P  = 0.003]. CONCLUSIONS Complete resection remains the mainstay of treatment for TETs with pleural involvement. Study populations treated with EPP, TP and LP had similar survival that may be factual as observed, but in the presence of selection bias, we can further conclude from the results that EPP, TP and LP are equally effective procedures. Procedural choice depends upon the extent of tumour distribution. EPPs, TPs and LPs performed within a multimodality setting seem to be efficient procedures for local control of disease, as they yield excellent results regarding OS, DFS, CSS and FFR

Design and implementation of a seismic Newtonian-noise cancellation system for the Virgo gravitational-wave detector

Terrestrial gravity perturbations caused by seismic fields produce the so-called Newtonian noise in gravitational-wave detectors, which is predicted to limit their sensitivity in the upcoming observing runs. In the past, this noise was seen as an infrastructural limitation, i.e., something that cannot be overcome without major investments to improve a detector's infrastructure. However, it is possible to have at least an indirect estimate of this noise by using the data from a large number of seismometers deployed around a detector's suspended test masses. The noise estimate can be subtracted from the gravitational-wave data; a process called Newtonian-noise cancellation (NNC). In this article, we present the design and implementation of the first NNC system at the Virgo detector as part of its AdV+ upgrade. It uses data from 110 vertical geophones deployed inside the Virgo buildings in optimized array configurations. We use a separate tiltmeter channel to test the pipeline in a proof-of-principle. The system has been running with good performance over months