The work in this thesis has demonstrated the chiral recognition through the adaptation of chromatographically derived chiral recognition systems by electrospray ionization mass spectrometry (ESI-MS). Mass-labeled, pseudoenantiomeric chiral selectors (where each pseudoenantiomer had the opposite stereochemistry, but was slightly different in mass due to labeling of one enantiomer) were prepared as soluble analogues of Pirkle type chiral stationary phases. When mixed with a chiral analyte, solutions containing these pseudoenantiomeric selectors afforded selector-analyte complexes in the ESI-MS, and the relative peak intensities of the complexes could be related back to the enantiomeric composition of the analyte. In each case of this study, the complex intensity fraction for either of the selector-analyte complexes in the ESI-MS varies linearly with the enantiomeric composition of the analyte. This linear relationship provides a measure of the extent of enantioselectivity and allows quantitative analysis of the enantiomeric composition of analyte.

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This thesis describes the development and use of a new class of molecular tools called Selector probes, and its potential for investigations of genetic variation. The Selector technology provides multiplex amplification of targeted DNA sequences with a high specificity, and an enrichment factor in the same order of magnitude as PCR. A common feature in this thesis work is to focus the analysis on DNA regions of interest. For example, this technique can be implemented in analysing candidate regions found by whole genome studies that need validation (global to local analysis), and applications requiring detection of rare alleles (common to rare allele), important in for example cancer samples. An assay is presented that allows for fast and simple quantification of relative copy-number variations. The method was proven to be able to detect aneuploidy in chromosome 13, 18, 21 and X, with a resolution enough to distinguish between 4 and 5 copies. The method was successfully applied to solve a biological question regarding a copy-number variation, that explains the Ridge phenotype typical for the dog bread Rhodesian Ridgebacks. The Selector strategy was able to detect and map a tandem duplication with a size of 133 kb, which was characterized with base-pair resolution. A readout platform that facilitates simultaneous digital quantitative analysis of a large numbers of biomolecules is further introduced. The work involves arraying amplified product from successful selection and decoding each molecule by hybridization of fluorophore labeled oligonucleotides. Finally, a genome partitioning method which is applied upstream of next generation sequencing platforms is presented. It is shown that the method provides successful enrichment with 98 % coverage and 94 % specificity and high enrichment uniformity. The technique was applied for mutation analysis of 26 cancer-related genes in tumor cell-lines and tissue.

Three dimensional visualisation achieves tremendous savings in time and costs during the design process. Due to these circumstances this methods are gaining in importance. For example improvement in performance and the product security or enabling the operative optimization of a production sequence. By the virtual testing it is possible to validate a product in the whole developing process and product lifecycle. The flight simulator ATILa at Airbus Defence and Space in Friedrichshafen uses these advantages for own products. ATILa is used to test intelligent assistance systems for helicopter pilots. Here the graphic implementation of the virtual earth plays a key role when practicing realistical scenarios. This approach is implemented with the Common Database (CDB) which is enabled by the definition of specifications and standards. Different commercial software packages by Presagis are used to implement the aforementioned database. The software Terra Vista is used for the database generation, including the compilation. For the CDB implementation the software Vega Prime is used to prepare the data with the help of the RTP. The software Vega Prime is not able to display 3D models with LODs, due to a software error. Therefore a third software named Creator is used to modify them. The 3D models are available in the OpenFlight Format. This OpenFlight format consists of different kind of nodes with a complex hierarchical structure. Other software solutions, such as Autodesk or Blender, are not able to provide access to the specific structure. The edited models can be integrated in the virtual environment and have to defined by unambiguous indices. Various settings are used to implement the objects automatically. The compilation of the area of interest takes place by the definition of a geotile with a specific size depending on the latitude. The CDB ouput will be transferred by Vega Prime and with the help of the RTP into the simulator. In addition, there is the possibility to render various CDB databases in the simulator to enable a visualisation of the complete earth. Finally, any errors occurring will be described and methods of resolution explained. The complexity of the generation process of a CDB database could be represented with this thesis. However, the whole workflow of the visualisation of the earth is still in its initial stages, since among other things there are errors in the software. To sum up; the potential of the CDB can be evaluated as above average. / Die 3D Visualisierung vereinfacht den Planungsprozess und geht somit mit einer Zeit- und Kosten- einsparung einher. Aufgrund dieser Sachverhalte gewinnt sie immer weiter an Bedeutung, um zum Beispiel eine verbesserte und sichere Benutzung eines Produktes oder einen optimierten Betrieb einer Produktionskette zu ermöglichen. Durch vorherige virtuelle Erprobung und Vali- dierung eines Produktes können Kosten für den gesamten Entwicklungsprozess und den Pro- duktlebenszyklus gering gehalten werden. Im Flugsimulator für Helikopter namens ATILa in Friedrichshafen (Airbus Defence and Space) versucht man die genannten Vorteile für die eigenen Produkte zu nutzen. Im ATILa werden Assistenzsysteme geprüft, welche die Helikopterpiloten während ihres Fluges unterstützen sollen. Hierbei spielt die grafische Umsetzung der virtuellen Erde in dem Simulator eine entscheidende Rolle, um die Szenarien realitätsnah durchführen zu können. Dies kann mit Hilfe einer sogenannten Common Database (CDB), die durch Spezi- fikationen und Standards definiert ist, umgesetzt werden. Mittels verschiedener kommerzieller Softwarepakete der Firma Presagis lässt sich die oben genannte Datenbank erstellen. Die Gener- ierung und Kompilierung wird mit dem Softwareprogramm Terra Vista vorgenommen. Die Imple- mentierung der CDB in den Flugsimulator erfolgt mit der Software Vega Prime, welche die Daten über einen RTP zur Verfügung stellt. Da dieses Programm durch einen Softwarefehler nicht in der Lage ist, 3D Modelle mit verschiedenen Detaillierungsgraden darzustellen, muss eine dritte Soft- ware namens Creator genutzt werden. Die 3D Modelle liegen im OpenFlight Format vor. Dieses OpenFlight Format weist eine komplexe hierarchische Struktur aus verschiedenen Knoten auf. Andere Softwarelösungen, wie Autodesk oder Blender, sind nicht in der Lage einen Einblick in die spezielle Struktur zu geben. Die bearbeiteten Modelle können dann in der virtuellen Umgebung eingebunden und müssen durch eindeutige Indizes definiert werden. Verschiedene Einstellun- gen werden genutzt, um Objekte automatisch einzubinden. Die Kompilierung des Interessenge- bietes erfolgt über die Definition einer Geokachel mit einer bestimmten Größe, die abhängig vom Breitengrad ist. Die ausgegebene CDB wird mit Vega Prime und mit Hilfe des RTPs in den Simu- lator übertragen. Des Weiteren gibt es die Möglichkeit verschiedene CDB Datenbanken im Sim- ulator simultan zu rendern, was eine vollständige Visualisierung der kompletten Erde ermöglicht. Abschließend werden aufgetretene Fehler näher beschrieben und Lösungsansätze erläutert. Mit der vorliegenden Arbeit konnte die Komplexität der Entstehung einer CDB Datenbank dargestellt werden. Dennoch befindet sich der gesamte Arbeitsablauf der Visualisierung der Erde noch am Anfang, da u.a. Softwarefehler zu bemängeln sind. Zusammenfassend kann das Potenzial einer CDB als überdurchschnittlich bewertet werden.

Dans cette thèse nous traitons deux sujets. Le premier sujet concerne l'apprentissage statistique en grande dimension, i.e. les problèmes où le nombre de paramètres potentiels est beaucoup plus grand que le nombre de données à disposition. Dans ce contexte, l'hypothèse généralement adoptée est que le nombre de paramètres intervenant effectivement dans le modèle est petit par rapport au nombre total de paramètres potentiels et aussi par rapport au nombre de données. Cette hypothèse est appelée ``\emph{sparsity assumption}''. Nous étudions les propriétés statistiques de deux types de procédures : les procédures basées sur la minimisation du risque empirique muni d'une pénalité $l_{1}$ sur l'ensemble des paramètres potentiels et les procédures à poids exponentiels. Le second sujet que nous abordons concerne l'étude de procédures d'agrégation dans un modèle de densité. Nous établissons des inégalités oracles pour la norme $L^{\pi}$, $1\leqslant \pi \leqslant \infty$. Nous proposons ensuite une application à l'estimation minimax et adaptative en la régularité de la densité.

<p>Three chiral selectors (diketogulonic acid, benzoxycarbonylglycylproline and ketopinic acid) have been introduced for enantioseparation of pharmacologically active amines in non-aqueous capillary electrophoresis. The use of organic solvents, instead of aqueous buffers in the background electrolyte facilitated ion-pair formation between the analytes and the chiral selectors. The enantioresolution was strongly affected by the choice of selector and organic solvent but also depended on the other electrolytes. The most important parameter for the enantioresolution, apart from the choice of chiral selector, was the direction and magnitude of the electro-osmosis. Thus, covalently coated capillaries were used to suppress and to reverse this flow. Furthermore, the alkali metal hydroxide added to the background electrolyte had a great influence on the electro-osmosis. Exchanging LiOH for NaOH, was found to decrease the electro-osmotic flow. Interestingly, the flow was altered from cathodic to anodic, with KOH, RbOH or CsOH added to the ethanolic BGE. The occurrence of a reversed electro-osmosis had a great positive effect on the enantioresolution. An appropriate choice of solvent and electrolytes promoted also fast chiral separations, e.g., the enantiomers of isoprenaline were resolved within one minute. </p><p>The capillary electrophoresis systems developed within this work were applied for enantiomeric purity determinations of different pharmaceutical forms of drug products. A detection limit of 0.033 % was achieved for <i>1S,2R</i>-ephedrine, the enantiomeric impurity in Efedrin®, when diketogulonic acid was used as the selector. </p><p>By using the pre-concentration technique, transient isotachophoresis, the peak efficiency was enhanced for the enantiomers of timolol. This facilitated the introduction of a higher concentration of the sample into the capillary electrophoretic system containing ketopinic acid as the selector, and lowered the detection limit from 2.5 % to 0.2 % for the enantiomeric impurity <i>R</i>-timolol compared with injection without transient isotachophoresis.</p><p>The volatility of the non-aqueous media in capillary electrophoresis facilitated the hyphenation to mass spectrometry. The partial filling technique ensured that the selector did not contaminate the mass spectrometer, and the separated enantiomers of e.g., pronethalol were detected in the selector-free zone. </p>

Three chiral selectors (diketogulonic acid, benzoxycarbonylglycylproline and ketopinic acid) have been introduced for enantioseparation of pharmacologically active amines in non-aqueous capillary electrophoresis. The use of organic solvents, instead of aqueous buffers in the background electrolyte facilitated ion-pair formation between the analytes and the chiral selectors. The enantioresolution was strongly affected by the choice of selector and organic solvent but also depended on the other electrolytes. The most important parameter for the enantioresolution, apart from the choice of chiral selector, was the direction and magnitude of the electro-osmosis. Thus, covalently coated capillaries were used to suppress and to reverse this flow. Furthermore, the alkali metal hydroxide added to the background electrolyte had a great influence on the electro-osmosis. Exchanging LiOH for NaOH, was found to decrease the electro-osmotic flow. Interestingly, the flow was altered from cathodic to anodic, with KOH, RbOH or CsOH added to the ethanolic BGE. The occurrence of a reversed electro-osmosis had a great positive effect on the enantioresolution. An appropriate choice of solvent and electrolytes promoted also fast chiral separations, e.g., the enantiomers of isoprenaline were resolved within one minute. The capillary electrophoresis systems developed within this work were applied for enantiomeric purity determinations of different pharmaceutical forms of drug products. A detection limit of 0.033 % was achieved for 1S,2R-ephedrine, the enantiomeric impurity in Efedrin®, when diketogulonic acid was used as the selector. By using the pre-concentration technique, transient isotachophoresis, the peak efficiency was enhanced for the enantiomers of timolol. This facilitated the introduction of a higher concentration of the sample into the capillary electrophoretic system containing ketopinic acid as the selector, and lowered the detection limit from 2.5 % to 0.2 % for the enantiomeric impurity R-timolol compared with injection without transient isotachophoresis. The volatility of the non-aqueous media in capillary electrophoresis facilitated the hyphenation to mass spectrometry. The partial filling technique ensured that the selector did not contaminate the mass spectrometer, and the separated enantiomers of e.g., pronethalol were detected in the selector-free zone.

Šio magistrinio darbo tikslas yra teoriškai ir praktiškai išnagrinėti kaip ir kokius žinomus užklausų srautų aptarnavimo sprendimo būdus galima realizuoti JAVA programavimo kalbos priemonėmis. Darbo metu iškeltus uždavinius sudaro konkurentiškumą valdančių modelių išnagrinėjimas, jų realizavimo JAVA programavimo kalbos priemonėmis analizė, realiai veikiančių komponentų sumodeliavimas ir sukūrimas, sukurtų konkurentiškumą valdančių komponentų tyrimas, išvadų bei rekomendacijų pateikimas siekiant perteikti darbo metu įgytas žinias kaip galima parametrizuoti užklausų srautų aptarnavimo komponentą užtikrinant optimalų išteklių panaudojimo, pralaidumo bei uždelsimo balansą. Darbo metu buvo nagrinėjami dviejų tipų konkurentiškumą valdantys modeliai, t.y. gijos pagrindu bei du įvykių išskyrimo ir reagavimo pagrindu realizuoti modeliai, kur pastarieji du buvo suprojektuoti atsižvelgiant į Douglas Schmidto siūlomas reaktoriaus ir proaktoriaus projektavimo schemas. Išanalizavus JAVA programavimo kalbos galimybes, paaiškėjo, kad visus modelius galima kuo puikiausiai sumodeliuoti ir realizuoti panaudojant sinchroninį besiblokuojantį įvedimo ir išvedimo posistemį, sinchroninį nesiblokuojantį įvedimo ir išvedimo posistemį (NIO) ir asinchroninį įvedimo ir išvedimo posistemį (AIO4J). Minėtas aukščiau konkurentiškumą valdantis komponentas buvo realiai panaudotas ir išbandytas sukurtame supaprastintame HTTP serveryje, kaip komponentas atsakingas už ryšio užmezgimą bei užklausų apdorojimą... [toliau žr. visą tekstą] / The purpose of this master thesis is to analyze how many of known solutions for request stream handling can be implemented in JAVA programming language. Also, in addition to it, this master thesis analyzes the way those solutions can be implemented using JAVA programming language. There are defined tasks to investigate in the scope of this thesis, which include following: exploration of well known concurrency managing models; analysis of their implementation possibilities in JAVA by designing and creating real working components; their implementation workflow research under various stress loaded conditions and, finally, supply recommendations for optimal parameterization for mentioned component to gain the best possible balance of resource utilization, throughput and latency. There were analyzed basically two types of concurrency managing models in this work, i.e. thread based and two models based on event notification principle, designed using Douglas Schmidt reactor and proactor design patterns. During exploration of JAVA programming language possibilities to implement above mentioned models a special attention was paid to the new input/output system (NIO) which provides synchronous non-blocking input/output operations, whereas to process operations asynchronously there was explored asynchronous execution of input/output operations by using JAVA non-native external AIO4J library created by IBM corporation. In order to perform stress and performance benchmarks for created... [to full text]

Sneak path current is a significant remaining obstacle to the utilization of large crossbar arrays for non-volatile memories and other applications of memristors. A two-terminal selector device with an extremely large current-voltage nonlinearity and low leakage current could solve this problem. We present here a Ag/oxide-based threshold switching (TS) device with attractive features such as high current-voltage nonlinearity (~1010), steep turn-on slope (less than 1 mV/dec), low OFF-state leakage current (~10-14 A), fast turn ON/OFF speeds (<75/250 ns), and good endurance (>108 cycles). The feasibility of using this selector with a typical memristor has been demonstrated by physically integrating them into a multilayered 1S1R cell. Structural analysis of the nanoscale crosspoint device suggests that elongation of a Ag nanoparticle under voltage bias followed by spontaneous reformation of a more spherical shape after power off is responsible for the observed threshold switching of the device. Such mechanism has been quantitatively verified by the Ag nanoparticle dynamics simulation based on thermal diffusion assisted by bipolar electrode effect and interfacial energy minimization.

The aim of the theoretical part of this thesis is to describe the system of the aluminium casting alloys, with focus on the aluminium castings used for die casting. In this part of the thesis the different methods of the quality management are described. The practical application of these methods is described in the experimental part of this thesis, in which we focus on the evaluation of the statistical quality management and the process stability of the die casting parts of the selector mechanism cover. This part of the thesis also contains suggestion for the QFD method for this cast.