Augmentic Compositional Models for Knowledge Base Completion Using Gradient Representations

Neural models of Knowledge Base data have typically employed compositional representations of graph objects: entity and relation embeddings are systematically combined to evaluate the truth of a candidate Knowedge Base entry. Using a model inspired by Harmonic Grammar, we propose to tokenize triplet embeddings by subjecting them to a process of optimization with respect to learned well-formedness conditions on Knowledge Base triplets. The resulting model, known as Gradient Graphs, leads to sizable improvements when implemented as a companion to compositional models. Also, we show that the supracompositional triplet token embeddings it produces have interpretable properties that prove helpful in performing inference on the resulting triplet representations

From Selection to Instruction and Back: Competing Conformational Selection and Induced Fit Pathways in Abiotic Hosts

Two limiting cases of molecular recognition, induced fit (IF) and conformational selection (CS), play a central role in allosteric regulation of natural systems. The IF paradigm states that a substrate “instructs” the host to change its shape after complexation, while CS asserts that a guest “selects” the optimal fit from an ensemble of preexisting host conformations. With no studies that quantitatively address the interplay of two limiting pathways in abiotic systems, we herein and for the first time describe the way by which twisted capsule M-1, encompassing two conformers M-1(+) and M-1(−), trap CX4 (X=Cl, Br) to give CX4⊂M-1(+) and CX4⊂M-1(−), with all four states being in thermal equilibrium. With the assistance of 2D EXSY, we found that CBr4 would, at its lower concentrations, bind M-1 via a M-1(+)→M-1(−)→CBr4⊂M-1(−) pathway corresponding to conformational selection. For M-1 complexing CCl4 though, data from 2D EXSY measurements and 1D NMR line-shape analysis suggested that lower CCl4 concentrations would favor CS while the IF pathway prevailed at higher proportions of the guest. Since CS and IF are not mutually exclusive, we reason that our work sets the stage for characterizing the dynamics of a wide range of already existing hosts to broaden our fundamental understanding of their action. The objective is to master the way in which encapsulation takes place for designing novel and allosteric sequestering agents, catalysts and chemosensors akin to those found in nature

Dielectric function and plasmonic behavior of Ga(II) and Ga(III)

In order to exploit gallium´s (Ga) rich polymorphism in the design of phase-change plasmonic systems, accurate understanding of the dielectric function of the different Ga-phases is crucial. The dielectric dispersion profiles of those phases appearing at atmospheric pressure have been reported in the literature, but there is no information on the dielectric function of the high-pressure Ga-phases. Through first principles calculations we present a comprehensive analysis of the interdependence of the crystal structure, band structure, and dielectric function of two high-pressure Ga phases (Ga(II) and Ga(III)). The plasmonic behavior of these high-pressure Ga-phases is compared to those stable (liquid- and α-Ga) and metastable (β-, γ- and δ-Ga) at atmospherics pressure. This analysis can have important implications in the design of pressure-driven phase-change Ga plasmonic devices and high-pressure SERS substrates.Y.G. and F.M. acknowledges the support by the Army Research Laboratory under Cooperative Agreement Number W911NF-17-2-0023 and by SODERCAN (Sociedad para el Desarrollo de Cantabria) and the Research Vicerrectorate of the University of Cantabria through project 4JU2864661. Y.G. thanks the University of Cantabria for her FPU grant. P.G.-F. and J.J. acknowledge financial support from the Spanish Ministry of Economy and Competitiveness through grant number PGC2018-096955-B-C41

The Kinetics of the Hydrogen/Deuterium Exchange of Epidermal Growth Factor Receptor Ligands

Five highly homologous epidermal growth factor receptor ligands were studied by mass spectral analysis, hydrogen/deuterium (H/D) exchange via attenuated total reflectance Fourier transform-infrared spectroscopy, and two-dimensional correlation analysis. These studies were performed to determine the order of events during the exchange process, the extent of H/D exchange, and associated kinetics of exchange for a comparative analysis of these ligands. Furthermore, the secondary structure composition of amphiregulin (AR) and heparin-binding-epidermal growth factor (HB-EGF) was determined. All ligands were found to have similar contributions of 310-helix and random coil with varying contributions of β-sheets and β-turns. The extent of exchange was 40%, 65%, 55%, 65%, and 98% for EGF, transforming growth factor-α (TGF-α), AR, HB-EGF, and epiregulin (ER), respectively. The rate constants were determined and classified as fast, intermediate, and slow: for EGF the 0.20 min−1 (Tyr), 0.09 min−1 (Arg, β-turns), and 1.88 × 10−3 min−1 (β-sheets and 310-helix); and for TGF-α 0.91 min−1 (Tyr), 0.27 min−1 (Arg, β-turns), and 1.41 × 10−4 min−1 (β-sheets). The time constants for AR 0.47 min−1 (Tyr), 0.04 min−1 (Arg), and 1.00 x 10−4 min−1 (buried 310-helix, β-turns, and β-sheets); for HB-EGF 0.89 min−1 (Tyr), 0.14 min−1 (Arg and 310-helix), and 1.00 x 10−3 min−1 (buried 310-helix, β-sheets, and β-turns); and for epiregulin 0.16 min−1 (Tyr), 0.03 min−1 (Arg), and 1.00 x 10−4 min−1 (310-helix and β-sheets). These results provide essential information toward understanding secondary structure, H/D exchange kinetics, and solvation of these epidermal growth factor receptor ligands in their unbound state

Thermal optimization of plasmonic nanostructures : conception, simulation and characterization

Un des défis majeurs auquel la communauté de la nano-optique aura à répondre dans les années à venir sera de concentrer l'énergie lumineuse à l'échelle du nanomètre de façon à créer une nanosource optique ou thermique intense à même d'alimenter de futurs dispositifs. Les nanoparticules métalliques, supportant une résonance plasmon de surface, sont idéales pour de telles applications. Dans ce contexte, cette thèse a pour vocation d'apporter un élément de réponse aux problématiques d'optimisation thermique aux échelles nanométriques et de proposer une nouvelle technique de nanothermométrie. A l'aide de simulations numériques, nous avons pu mettre en évidence les propriétés de génération de chaleur des nitrures de titane et de zirconium, dépassant celle de l'or, qui en font alors des matériaux de choix pour concevoir et fabriquer des nanosources thermiques dans le visible. Nous avons également obtenu une morphologie de particules induisant un échauffement maximal pour une longueur d'onde donnée : une nanoétoile à trois branches. Nous avons ensuite fabriqué des nanostructures d'or par lithographie électronique afin de les caractériser par holographie photothermique. En utilisant les deux types d'informations accessibles avec cette technique, l'amplitude et la phase optique, nous nous sommes alors efforcés à quantifier l'élévation de température de nanobâtonnets d'or. L'holographie photothermique d'amplitude a permis d'obtenir des mesures de température semi-quantitatives et, la technique de phase, encore préliminaire, se révèle intéressante et innovante pour étudier les propriétés thermoplasmoniques de nanostructures plasmoniques.Focusing light on the nanoscale in order to create intense optical or thermal nanosources is probably the main challenge facing the nano-optics community, in order to power up future devices. Metallic nanoparticles and their surface plasmon resonance are ideal optical or thermal nanosources.In this context, this thesis aims at providing a possible solution to the issues of thermal optimization at the nanoscale and nanothermometry.By carrying out numerical simulations, we were able to highlight the heat generation properties of titanium and zirconium nitrides, exceeding those of gold, which make them ideally suited in order to conceive and fabricate heat nanosources in the visible. We also managed to obtain a particle morphology inducing a maximum heating at a given wavelength : a three-branchs nanostar.We fabricated gold nanostructures by e-beam lithography in order to characterize them with photothermal holography. By exploiting the two kind of informations available with this far-field optical technique, the amplitude and the optical phase, we strove to quantify the temperature variations of gold nanorods. The photothermal holography setup based on amplitude delivered semi-quantitative temperature measurements, and the phase based-technique, still at a preliminary stage of developpement, proves to be a new and promising tool for the study of optical and thermal properties of plasmonic nanostructures

Analysis of purinergic signaling in nervous system diseases : roles of neuronal P2X receptors

Les récepteurs purinergiques P2X sont des canaux ioniques activés par l’ATP. Ils sont exprimés très largement dans l’organisme, et possèdent de nombreux rôles physiologiques et pathologiques. Les récepteurs P2X4 en particulier ont été impliqués dans les processus de douleur chronique. Suite à une lésion nerveuse, l’expression des récepteurs P2X4 est induite de novo dans la microglie spinale activée, où ils sont responsables de l’hypersensibilité mécanique caractéristique des douleurs neuropathiques.Notre étude montre que les récepteurs P2X4 neuronaux sont également des acteurs centraux dans plusieurs processus pathologiques, et notamment dans la douleur inflammatoire périphérique chronique. Les récepteurs P2X4 sont exprimés par les neurones sensoriels des ganglions rachidiens et semblent impliqués dans la libération du BDNF dans la corne dorsale de la moëlle épinière. Cette libération conduit à l’activation des voies de signalisation de la voie BDNF/TrkB, et en particulier à la diminution de l’expression de KCC2. Ce processus est en partie responsable de l’allodynie tactile et de l’hyperalgésie mécanique observée en cas de douleur inflammatoire chronique. Notre étude a également permis d’étendre cette hypothèse à un modèle d’excitotoxicité in vitro dans l’hippocampe, mimant une activité épileptiforme. Nos résultats indiquent que les récepteurs P2X4 neuronaux pourraient être des acteurs importants de la libération de BDNF dans l’hippocampe lors d’un évènement excitotoxique.Purinergic receptors P2X are ATP-gated ion channels widely expressed in the organism and involved in many physiological and pathological states. Particularly, P2X4 receptors have been involved in chronic pain. Following nerve injury, their expression is induced de novo in activated spinal cord microglia where they are responsible for the BDNF release leading to tactile allodynia, a characteristic of neuropathic pain. Our study shows that neuronal P2X4 receptors are crucial actors of other pathological processes, including inflammatory pain. We show that P2X4R are expressed in sensory neurons in dorsal root ganglions and seem involved in BDNF release in the spinal cord. This release leads to activation of BDNF/TrkB signalization pathways, and particularly to the downregulation of KCC2. This process underlies the spinal hyperexcitability in chronic inflammatory pain states. These results have been extended to model of excitotoxicity in the hippocampus mimicking the lesions caused by an epileptic activity. Our preliminary results suggest that neuronal P2X4 receptors are likely major actors in the BDNF release in the hippocampus following an excitotoxicitic insult

La revue chilienne Mandrágora, 1938-1943 : naissance d'une polémique autour de « manifestes »

Lalisse-Delcourt Nathalie. La revue chilienne Mandrágora, 1938-1943 : naissance d'une polémique autour de « manifestes ». In: América : Cahiers du CRICCAL, n°21, 1998. Polémiques et manifestes aux XIXe et XXe siècles en Amérique latine. pp. 351-358

Optimisation thermique de nanostructures plasmoniques : conception, modélisation et caractérisation

Focusing light on the nanoscale in order to create intense optical or thermal nanosources is probably the main challenge facing the nano-optics community, in order to power up future devices. Metallic nanoparticles and their surface plasmon resonance are ideal optical or thermal nanosources.In this context, this thesis aims at providing a possible solution to the issues of thermal optimization at the nanoscale and nanothermometry.By carrying out numerical simulations, we were able to highlight the heat generation properties of titanium and zirconium nitrides, exceeding those of gold, which make them ideally suited in order to conceive and fabricate heat nanosources in the visible. We also managed to obtain a particle morphology inducing a maximum heating at a given wavelength : a three-branchs nanostar.We fabricated gold nanostructures by e-beam lithography in order to characterize them with photothermal holography. By exploiting the two kind of informations available with this far-field optical technique, the amplitude and the optical phase, we strove to quantify the temperature variations of gold nanorods. The photothermal holography setup based on amplitude delivered semi-quantitative temperature measurements, and the phase based-technique, still at a preliminary stage of developpement, proves to be a new and promising tool for the study of optical and thermal properties of plasmonic nanostructures.Un des défis majeurs auquel la communauté de la nano-optique aura à répondre dans les années à venir sera de concentrer l'énergie lumineuse à l'échelle du nanomètre de façon à créer une nanosource optique ou thermique intense à même d'alimenter de futurs dispositifs. Les nanoparticules métalliques, supportant une résonance plasmon de surface, sont idéales pour de telles applications. Dans ce contexte, cette thèse a pour vocation d'apporter un élément de réponse aux problématiques d'optimisation thermique aux échelles nanométriques et de proposer une nouvelle technique de nanothermométrie. A l'aide de simulations numériques, nous avons pu mettre en évidence les propriétés de génération de chaleur des nitrures de titane et de zirconium, dépassant celle de l'or, qui en font alors des matériaux de choix pour concevoir et fabriquer des nanosources thermiques dans le visible. Nous avons également obtenu une morphologie de particules induisant un échauffement maximal pour une longueur d'onde donnée : une nanoétoile à trois branches. Nous avons ensuite fabriqué des nanostructures d'or par lithographie électronique afin de les caractériser par holographie photothermique. En utilisant les deux types d'informations accessibles avec cette technique, l'amplitude et la phase optique, nous nous sommes alors efforcés à quantifier l'élévation de température de nanobâtonnets d'or. L'holographie photothermique d'amplitude a permis d'obtenir des mesures de température semi-quantitatives et, la technique de phase, encore préliminaire, se révèle intéressante et innovante pour étudier les propriétés thermoplasmoniques de nanostructures plasmoniques

STRUCTURE ASSEMBLY IN KNOWLEDGE BASE REPRESENTATION

A primary goal of connectionist cognitive science is to provide the technical apparatus for modeling cognitive processes as implemented in brainlike systems. From the structure of classical cognitive theories--alphabets of discrete symbols along with algebraic operations on those primitive symbols|one can derive key properties attributed to "higher-order cognition" by authors like Fodor and Pylyshyn--systematicity, productivity, and compositionality. This fact has led to theories of that type to serve as the enduring backbone of cognitive science. Connectionist networks differ from these classical systems not just in that they are implemented in real numbers while the former operate over discrete sets, but also in that they can represent system-states that cannot be factored into algebraic combinations of primitive symbols that are, in a formal sense, noncompositional. This dissertation develops, examines, and evaluates a series of models that straddle that divide. Cognitively-oriented connectionist models in the tradition of Vector Symbolic Architectures (VSAs) provide a framework by which neural network models can integrate Fodor and Pylyshyn's insights, as well as the corresponding architectural commitments of cognitive theory. Other processes, based in Harmony Maximization, that adjust these structured representations to satisfy learned constraints. We present three models that use Tensor Product Representations (TPRs) and other VSAs closely related to them, placing these in a common formal framework and then applying them to Knowledge Base Completion: the task of storing large-scale inventories of facts (e.g. WordNet, Freebase, Wikidata) in representations that allow those databases to be extended via inexact inference. In typical approaches, graph representations are obtained compositionally by taking static vector representations of graph elements (entities and relations) and combining them systematically in order to derive a score. The first two models combine the compositional operations of VSAs with context-modulation processes based in Harmonic Grammar. A third model examines the proposition that spatial structure implicit in TPRs--with a number of spatial directions equal to the order of the tensor--can be used as an organizing principle for the features encoded in the trilinear tensors occurring in the graph representation setting. Each of the models, we show, performs at the state of the art in Knowledge Base Completion, and we explore the qualitative aspects of the representations that they learn