Yes / Dehydroabietic acid (DAA) promotes palladium(0)‐catalysed cyclisations of arene‐tethered 1,7‐enynols and 1,m‐enynoates (m=6,7) to give fused carbocyclic dienes. 6,6,6,5‐Tetracyclic lactones are accessible by one‐pot cycloisomerisation/Diels–Alder reaction/lactonisation from 1,7‐enynols. Furthermore, asymmetric counteranion‐directed catalysis has been developed, which afforded an indene derivative with an all‐carbon quaternary stereogenic center. / NSFC. Grant Number: 21462004 State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources. Grant Number: CMEMR2014A04 2015 GXNSFBA. Grant Number: 139032 GXNU

No / Smart mobile devices, which are hand-held electronic devices with an advanced operating system (such as the Android platform) connected via a wireless protocol, have become an integral and essential part of our everyday life, and support both social and workplace activities. However, adopting mobile technology within the workplace setting can give rise to challenges that impact user behaviour and performance. A study was carried out amongst 90 participants located in two countries, using internet connectivity as a case study. Confidence and frustration have previously been connected with technology competence, but this was not applied to a workplace scenario during problem-solving, when users are assigned an unfamiliar smart mobile device. This research focuses on identifying the link between workplace users' levels of confidence and frustration when seeking to independently solve problems whilst completing familiar tasks on new smart mobile devices. A detailed video analysis of users' attitudes and behaviour during problem-solving was conducted, emphasising a correlation between attitudes and behaviour towards completing a task.

Laser-based additive manufacturing is inherently associated with extreme, unprecedented, and rapid thermokinetics which impact the microstructural evolution in a built component. Such a unique, near to non-equilibrium microstructure/phase evolution in laser additively manufactured metallic components impact their properties in engineering application. In light of this, the present work investigates the unique microstructural traits as a result of process induced spatial and temporal variation in thermokinetic parameters in laser directed energy deposited CoCrMo biomedical alloy. The influence of such a unique microstructural evolution in laser directed energy deposited CoCrMo on electrochemical response in physiological media was elucidated and compared with a conventionally manufactured, commercially available CoCrMo component. Furthermore, while investigation of the electrochemical response, such a microstructural evolution in laser directed energy deposited CoCrMo led to in-situ surface modification of the built components in physiological media via selective, non-uniform electrochemical etching. Such in-situ surface modification resulted in enhanced biocompatibility in terms of mammalian cell growth, cell-substrate adhesion, blood compatibility, and antibacterial properties indicating improved osteointegration, compared to a conventionally manufactured, commercially available CoCrMo component.

Suicide is a significant public health issue in the US. Despite national and international prioritization since 1996, little definitive progress has been made in terms of identification and intervention in cases of elevated suicide risk. Forty percent of those who died by suicide attended an emergency department within a year of death. Therefore, universal suicide risk screening in emergency departments could prove a vital component to a national suicide prevention strategy. The present study empirically evaluated the universal suicide risk screening program recently implemented at Parkland Health and Hospital System. The sample consisted of patients over 18 years of age (N=333,855; Mage=42.7, 32% male) screened as part of routine clinical care from May 4th, 2015, through November 3rd, 2015. The Parkland Algorithm for Suicide Screening (PASS) is part of a clinical decision support system for responses to Columbia - Suicide Severity Rating Scale Clinical Practice Screener (C-SSRS) items, leading to an automated clinical response via three suicide risk stratification levels: no action for no risk identified, psychiatric social worker assessment for moderate risk identified, and psychiatrist/psychologist interview for high risk identified. The present study used receiver operating characteristic (ROC) curve analysis, which found the PASS predicted disposition (z=30.46, p<.001, AUC=.78, CI95=.77, .81). This study also evaluated the cutpoints separating suicide risk stratification and levels of clinical response. The results supported the first cutpoint and highlighted a need for additional data to address the second cutpoint. The results of the present study suggest that the universal suicide risk screening program at Parkland Health and Hospital System is an important step toward addressing suicide prevalence in the US.

Maitriser les coûts de fabrication des circuits intégrés tout en augmentant leur densité est d'une importance primordiale pour maintenir une certaine rentabilité dans l’industrie du semi-conducteur. Parmi les différents composants d’un circuit, nous nous intéressons aux connections verticales et métalliques, connues sous le nom de « vias ». Durant la fabrication, un processus de lithographie complexe est utilisé pour former une disposition de vias est formée sur une plaque de silicium, à l’aide d’un un masque optique. Pour des raisons de fabrication, une distance minimum entre les vias doit être respectée. Lorsque cette distance n’est pas respectée, nous parlons de « conflit ». Afin de supprimer ces conflits, l’industrie utilise une technique qui permet de décomposer une disposition de vias cible en plusieurs sous-ensembles, où les contraintes de distance minimum sont respectées : la formation des sous-ensembles individuels se fait en séquence sur la plaque de silicium en utilisant un masque optique par sous-ensemble. Cette technique est appelée Multiple Patterning (MP). Il y a de nombreuses façons de décomposer une disposition de vias et le but est d’assigner les vias à un nombre minimum de masques, car les masques sont coûteux. Minimiser le nombre de masques est équivalent à minimiser le nombre de couleurs dans un graphe disque unitaire. Ce problème est NP-difficile, mais un certain nombre de « bonnes » heuristiques existent. Une technique récente et prometteuse basée sur l’auto-assemblage et direction des molécules, aussi connue sous le nom Directed Self Assembly (DSA), permet de grouper les vias en conflits à condition de respecter certaines contraintes. L’objectif est de trouver la meilleure façon de grouper les vias afin de minimiser le nombre de masques tout en respectant les contraintes liées à DSA. Ce problème est un problème de coloration de graphes où les sommets de chaque couleurs définissent un ensemble de chemins « indépendants » de longueurs au plus k que nous appelons aussi le problème de coloration par k-chemins. Durant la modélisation, nous avons distingué deux problèmes de coloration par k-chemins pertinents: le problème général et le problème induit. Les deux problèmes sont connus pour être NP-difficile, ce qui explique l’utilisation d’heuristiques dans l’industrie pour trouver une décomposition valide en sous-ensembles. Dans cette étude, nous nous intéressons à des méthodes exactes afin de concevoir des solutions optimales et d’évaluer la qualité de l’heuristique développée en industrie (chez Mentor Graphics). Nous présentons différentes méthodes: une approche par programmation linéaire en nombre entier (ILP) où nous étudions plusieurs formulations, une approche par programmation dynamique pour résoudre le cas induit quand k=1 ou k=2 et lorsque les graphes ont une petite longueur arborescente ; enfin, nous étudions le cas particulier des graphes lignes. Les résultats des différentes études numériques montrent que les formulations ILP « naïves » sont les meilleures. Elles listent tous les chemins possibles de longueur au plus k. Les tests sur des données industrielles ayant au plus 2000 sommets (plus grande composante connexe parmi celles qui constituent une instance) ont montré que les deux problèmes, général et induit, sont résolus en moins de 6 secondes, pour k=1 et k=2. La programmation dynamique, appliquée au problème induit de coloration par k-chemins quand k=1 et k=2, montre des résultats équivalents à ceux de la formulation ILP naïve. Cependant, nous nous attendons à de meilleurs résultats par programmation dynamique quand la valeur de k augmente. Enfin, nous montrons qu’un cas particuliers des graphes lignes peut être résolu en temps polynomial en exploitant les propriétés de l’algorithme d'Edmonds et des couplages dans les graphes bipartis. / Controlling the manufacturing costs of integrated circuits while increasing their density is of a paramount importance to maintain a certain degree of profitability in the semi-conductor industry. Among various components of a circuit, we are interested in vertical metallic connections known as “vias”. During manufacturing, a complex lithography process is used to form an arrangement of vias on a silicon wafer support, using an optical mask. For manufacturing reasons, a minimum distance between the vias must be respected. Whenever this is not the case, we are talking about a “conflict”. In order to eliminate these conflicts, the industry uses a technique that decomposes an arrangement of vias in several subsets, where minimum distance constraints are respected: the formation of the individual subsets is done, in sequence, on a silicon wafer using one optical mask per subset. This technique is called Multiple Patterning (MP). There are several ways to decompose an arrangement of vias, the goal being to assign the vias to a minimum number of masks, since the masks are expensive. Minimizing the number of masks is equivalent to minimizing the number of colors in a unit disk graph. This is a NP-hard problem however, a number of “good” heuristics exist. A recent and promising technique is based on the direction and self-assembly of the molecules called Directed Self Assembly (DSA), allows to group vias in conflict according to certain conditions. The main challenge is to find the best way of grouping vias to minimize the number of masks while respecting the constraints related to DSA. This problem is a graph coloring problem where the vertices within each color define a set of independent paths of length at most k also called a k-path coloring problem. During the graph modeling, we distinguished two k-path coloring problems: a general problem and an induced problem. Both problems are known to be NP-hard, which explains the use of heuristics in the industry to find a valid decomposition into subsets. In this study, we are interested in exact methods to design optimal solutions and evaluate the quality of heuristics developed in the industry (at Mentor Graphics). We present different methods: an integer linear programming (ILP) approach where we study several formulations, a dynamic programming approach to solve the induced case when k=1 or k=2 and when the graphs have small tree-width; finally, we study a particular case of line graphs. The results of the various numerical studies show that the naïve ILP formulations are the best, they list all possible paths of length at most k. Tests on a snippet of industrial instances of at most 2000 vertices (a largest connected component among those constituting an instance) have shown that the two problems, general and induced, are solved in less than 6 seconds, for k=1 and k=2. Dynamic programming, applied to the induced k-path coloring when k=1 and k=2, shows results equivalent to those of the naïve ILP formulation, but we expect better results by dynamic programming when the value of k increases. Finally, we show that the particular case of line graphs can be solved in polynomial time by exploiting the properties of Edmonds’ algorithm and bipartite matching.

Flavonoids are secondary metabolites that are important in plant defense, protection and human health. Most naturally-occurring flavonoids are found in glucosylated form. Glucosyltransferases (GTs) are enzymes that catalyze the transfer of glucose from a high energy sugar donor to an acceptor molecule. A flavonol-specific 3-O-GT enzyme has been identified and cloned from leaf tissues of grapefruit. The enzyme shows rigid substrate specificity and regiospecificity. F3-O-GTs from grape (Vitis vinifera) and grapefruit (Citrus paradisi) were modeled against F7-O-GTs from Crocus sativus and Scrutellaria biacalensis, and several non-conservative amino acid differences were identified that may impact regioselectivity. This research is designed to test the hypothesis that specific amino acid residues impart the regiospecificity of the grapefruit enzyme. Site-directed mutagenesis was performed on three potentially key amino acid residues within the grapefruit F3-O-GT that were identified through homology modeling. Analyses of the enzyme activity of the mutant F3-O-GT proteins revealed that the single point mutations of serine 20 to leucine (S20L) and proline 297 to phenylalanine (P297F) rendered the recombinant enzyme inactive with flavonol substrates. Mutation of glycine 392 to glutamate (G392E) was active at 80% relative to the wild type. The mutant enzyme also did not show broadened acceptor specificity as it also favored flavonols as the preferred acceptor substrate. The glucosylation products of the active mutant enzyme will be analyzed to determine if this resulted in a change in regiospecificity.

Aujourd'hui, les outils de lithographie utilisés dans l'industrie arrivent à leur limite de résolution en simple exposition. Pour continuer à diminuer les dimensions, il faut utiliser des techniques de double exposition, mais cela entraîne une explosion des coûts de fabrication. Cette thèse se focalise sur les aspects de modélisation de deux techniques, Sidewall Image Transfer et Directed Self-Assembly, qui sont pressenties pour permettre à l'industrie de continuer la réduction des dimensions des transistors, tout en minimisant les coûts. / Today, the lithographic tools used in industry came to their resolution limit in single patterning. In order to continue the reduction of dimensions, it is necessary to use double patterning, but this increase drastically the cost of manufacturing. This thesis focus on the modelisation aspects of two techniques, Sidewal Image Transfer and Directed Self-Assembly, that can help the industry continuing making transistors even smaller, while keeping the costs manageable.

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No description available.

Die Aufgabe des Proteins Arrestin ist die Beendigung der Signalweitergabe über den GPCR Signalweg. In Stäbchenzellen bindet Arrestin an Licht-aktiviertes phosphoriliertes Rhodopsin um die Signalweitergabe zu unterdrücken. Die Bindung von Arrestin an Rhodopsin erfolgt in zwei Schritten. Zunächst wechselwirkt Arrestin mit dem phosphorilierten C-Terminus von Rhodopsin und bildet einen prä-Komplex, dies induziert Konformationsänderungen im Arrestin wodurch die Bildung eines High-affinity Komplex unter Kopplung an den helikalen Kern des aktivierten Rezeptors erfolgen kann. Biochemische Untersuchungen und Kristallstrukturen haben einen Einblick in die Konformation des Komplexes aus Arrestin und Rhodopsin ermöglicht. In dieser Arbeit werden site-directed Fluorezenz Experimente angewandt um die strukturellen Änderungen zu untersuchen, die bei der Bindung von Arrestin an Rhodopsin ablaufen und der nterschiedlichen Bindungsmodi innerhalb der Wechselwirkung zwischen Arrestin und Rhodopsin. Insbesondere wird hier eine, bisher nicht beschriebene, Assoziation von Arrestin an die Membran untersucht. Des Weiteren wurden Erkenntnisse über die Struktur des prä-Komplexes gewonnen. Die Konformation vom Arrestin im prä-Komplex scheint die Konformation im Basalzustand nachzubilden unter Beteiligung zweier Kontaktstellen: Interaktion mit dem phosphorilierten C-Terminus des Rezeptors und Assoziation mit der Membran. Beim Übergang in den High-affinity Komplex durchläuft Arrestin eine Konformationsänderung in eine aktivere Konformation: der C-Terminus wird verdrängt, es erfolgt eine Neuausrichtung der zentralen flexiblen Schleifen und die Orientierung des Membranankers ändert sich. Die Aufgabe des prä-Komplexes ist somit Arrestin und den Rezeptor zusammen zu bringen sowie die korrekte Orientierung sicherzustellen um einen schnellen Übergang in den High-affinity Komplex zu ermöglichen. / The protein arrestin is responsible for termination of GPCR signalling. In the rod cell, arrestin binds light-activated phosphorylated rhodopsin in order to block further signal transduction. The binding of arrestin to rhodopsin is a two-step process. Arrestin first interacts with the phosphorylated receptor C-terminus in a pre-complex, which induces conformational changes in arrestin that allow coupling to the helical core of the active receptor in a high-affinity complex. Biochemical studies and crystal structures have provided insights into the conformation of the arrestin-rhodopsin complex. This dissertation describes site-directed fluorescence experiments, which were carried out to further investigate the conformational changes occurring upon arrestin binding to rhodopsin and the nature of different binding modes of the arrestin-rhodopsin interaction. In particular this involved characterization of a previously unidentified association of arrestin with the membrane, as well as further elucidation of the structure of the pre-complex. The conformation of arrestin in the pre-complex is indicated to resemble that of the basal state of arrestin, and involves two sites of contact: interaction with the phosphorylated receptor C-terminus, and association with the membrane. Upon transition to the high-affinity complex, arrestin undergoes a conformational change to a more active conformation: the auto-inhibitory C-tail is displaced, there is movement within the central flexible loops, and the orientation of the membrane anchor changes. The pre-complex therefore most likely functions to bring arrestin and the receptor into close contact, and in the correct orientation, to allow for fast transition to the high-affinity complex.