The physical properties of glycerophospholipids (GPLs) are not only determined by the head group (HG), but also by their fatty acid (FA) chains, which affect their distribution and function within membranes in the cell. Understanding the microheterogenity of lipid membranes on a molecular level requires qualitative and quantitative characterization of individual lipids and identification of their FA moieties. The aim of my study was to introduce the new technology of multiple precursor ion scanning (MPIS) on a QSTAR Pulsar time-of-flight mass spectrometer (QqTOF) to analyze lipids. Detailed information on fatty acid composition of individual GPL molecules could be obtained in parallel with conventional profiling of lipid classes, and this could be done by direct analysis of total lipid extracts. This method was termed Fatty Acid Scanning (FAS) and Head Group Scanning HGS, respectively. In this way the molecular GPL composition of total lipid extracts could be charted in a single analysis accurately and rapidly at a low picomole concentration level. Furthermore, combining FAS and HGS together with ion trap MS3 analysis allowed complete charting of the molecular composition of PCs, including quantification of their positional isomers, thus providing a detailed and comprehensive characterization of molecular composition of the pool of PCs. Development of the Lipid Profiler software allowed full automation and rapid processing of complex data, including identification and quantification of molecular GPLs. This approach was evaluated by preliminary applications. First, the molecular composition of PCs of total lipid extracts of MDCK cells and of human red blood cells (RBC) could accurately be charted. Significant presence of positional isomers was observed increasing the total number of individual PC species close to one hundred. Secondly, the molecular PC and SM species distribution in detergent resistant membranes (DRMs) prepared by Triton X-100 DRMs were analyzed and were found to be enriched in distinct GPLs. The distribution in PCs and SMs of Triton X-100 DRMs of RBC were compared with those of the DRMs of MDCK cells. Finally, combining the use of a 96 well plate and a robotic system demonstrated that these analyses can be automated and analyzed with high throughput. This system we termed Shotgun Lipidomics. Taken together, this mass spectrometric methodology provides rapid and detailed insight into the distribution of the molecular GPLs of membranes and membrane sub-fractions.

Pseudoexfoliation (PEX) syndrome is an age-related condition characterized by the production and accumulation of extracellular fibrillary material in the anterior segment of the eye. PEX predisposes for several pathological conditions, such as glaucoma and complications during and after cataract surgery. The pathogenesis of PEX is not yet fully understood. It is multifactorial with genetics and ageing as contributing factors. We aimed to study the proteome in aqueous humor (AH) in PEX in order to increase the knowledge about its pathophysiology. Therefore, we developed sampling techniques and evaluated separation methods necessary for analyzing small sample volumes. Other objectives were to study the lens capsule in eyes with PEX regarding small molecules, and to investigate the association between PEX and cataract surgery in a population-based 30-year follow-up study. Samples of AH from eyes with PEX and control eyes were collected during cataract surgery. In pooled, and individual samples, various liquid based separation techniques and high resolution mass spectrometry were utilized. For quantitation, various methods for labeling, and label free techniques were applied. Lens capsules were collected from some of the patients, and analysed by imaging mass spectrometry. A cohort of 1,471 elderly individuals underwent a comprehensive ophthalmological examination at baseline. Medical information was obtained by questionnaires, and from medical records. Incident cases of cataract surgery were identified by review of medical records. In the initial study, several techniques were explored for protein detection, and a number of proteins were identified as differentially expressed. In the individually labelled samples, changes in the proteome were observed. Eyes with PEX contained higher levels of proteins involved in inflammation, oxidative stress, and coagulation, suggesting that these mechanisms are involved in the pathogenesis in PEX. The levels of β/γ-crystallins were significantly increased in PEX, which is a novel finding. In the lens capsules from individuals with PEX, changes in the lipid composition was observed with time-of-flight secondary ion mass spectrometry. These changes remain to be elucidated. By multivariate analysis, lens opacities were the first, and PEX the second most important predictor for cataract surgery, the later accounting for a 2.38-fold increased risk for cataract surgery.

Durch die Fokussierung eines ultrakurzen und hochintensiven Laserpulses auf ein Festkörpertarget können Pulse von Protonen und anderen positiv geladenen Ionen mit Teilchenenergien von einigen MeV pro Nukleon erzeugt werden. Die Charakterisierung dieser Teilchenstrahlung erfordert die Identifizierung der Ionenspezies und die Bestimmung ihrer spektralen Verteilung möglichst nach jedem Puls. Im Rahmen dieser Diplomarbeit wurden zwei Spektrometer entwickelt und am DRACO-Lasersystem des Forschungszentrums Dresden implementiert. Neben der Inbetriebnahme eines Thomson-Spektrometers mit einer Mikrokanalplatte und einem Fluoreszenzschirm als Auslese erfolgte die Entwicklung eines Flugzeitspektrometers. Die Verwendung einer Mikrokanalplatte mit nur 180ps Anstiegszeit als Signalverstärker sorgt darin für eine verbesserte Energieauflösung und einen flexibleren Einsatz im Experimentierbetrieb. Ein dem Flugzeitsignal überlagertes Störsignal, welches durch die Einstreuungen eines elektromagnetischen Impulses in den Aufbau verursacht wurde, konnte erfolgreich durch die Anwendung verschiedener Filter unterdrückt werden. Als Ergebnis dieser Arbeit steht eine anwendungsbereite Diagnostik für laserbeschleunigte Protonen und Ionen zur Verfügung. / By focusing an ultra-short high-intensity laser pulse on a solid target, pulses of protons and other positive charged ions with energies of several MeV per nucleon are generated. It is necessary to identify the species of those particles and obtain their energy spectra in a single-shot regime. Within this diploma thesis two spectrometers have been developed and implemented in the DRACO-laboratory of the Forschungszentrum Dresden. Besides a Thomson spectrometer with read-out via microchannel plate and phosphor screen, a time-of-flight spectrometer was developed. The usage of a microchannel plate with 180ps rise time as a signal amplifier leads therein to a better energy resolution and a more flexible handling in experimental operation. A noise signal generated by stray pick-up of an electromagnetic pulse and superimposing the time-of-flight signal was considerably reduced by the application of different filters. As a result of this work a ready-to-use diagnostic for laser accelerated protons and ions is available.

The subject of this thesis is high-precision mass-measurements performed with Penning trap mass spectrometers (PTMS). In particular it describes the SMILETRAP I PTMS and the final results obtained with it, the masses of 40Ca and that of the proton. The mass of 40Ca is an indispensible input in the evaluation of measurements of the bound electron g-factor, used to test quantum electrodynamical calculations in strong fields. The value obtained agrees with available literature values but has a ten times higher precision. The measurement of the proton mass, considered a fundamental physical constant, was performed with the aim of validating other Penning trap results and to test the limit of SMILETRAP I. It was also anticipated that a measurement at a relative precision close to 10-10 would give insight in how to treat certain systematic uncertainties. The result is a value of the proton mass in agreement with earlier measurements and with an unprecedented precision of 1.8×10-10. Vital for the achieved precision of the proton mass measurement was the use of the Ramsey excitation technique. This technique, how it was implemented at SMILETRAP I and the benefits from it is discussed in the thesis and in one of the included papers. The second part of the thesis describes the improved SMILETRAP II setup at the S-EBIT laboratory, AlbaNova. All major changes and upgrades compared to SMILETRAP I are discussed. This includes, apart from the Ramsey excitation technique, higher ionic charge states, improved temperature stabilization, longer run times, different reference ions, stronger and more stable magnetic field and a more efficient ion detection. Altogether these changes should reduce the uncertainty in future mass determinations by an order of magnitude, possibly down to 10-11. / At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 9: Accepted.

Background To investigate vascular-related pathophysiological characteristics of two human lung cancers with modifiable vascularisation using MRI and CT. Methods Tumour xenografts with modifiable vascularisation were established in 71 rats (approval by the Animal Care Committee was obtained) by subcutaneous transplantation of two human non-small-cell lung cancer (NSCLC) cells (A549, H1299) either alone or co-transplanted with vascular growth promoters. The vascularity of the tumours was assessed noninvasively by MRI diffusion-weighted-imaging (DWI), T2-weighted, and time-of-flight (TOF) sequences) as well as contrast-enhanced CT (CE-CT), using clinical scanners. As a reference standard, histological examinations (CD-31, fluorescent beads) were done after explantation. Results Microvessel density (MVD) was higher in co-transplanted tumours (171 ± 19 number/mm2) than in non-co-transplanted tumours (111 ± 11 number/mm2; p = 0.002). Co-transplanted tumours showed higher growth rates and larger tumour vessels at TOF-MRI as well as larger necrotic areas at CE-CT. In co-transplanted tumours, DWI revealed higher cellularity (lower minimal ADCdiff 166 ± 15 versus 346 ± 27 mm2/s × 10−6; p < 0.001), highly necrotic areas (higher maximal ADCdiff 1695 ± 65 versus 1320 ± 59 mm2/s × 10−6; p < 0.001), and better-perfused tumour stroma (higher ADCperf 723 ± 36 versus 636 ± 51 mm2/s × 10−6; p = 0.005). Significant correlations were found using qualitative and quantitative parameters: maximal ADCperf and MVD (r = 0.326); maximal ADCdiff and relative necrotic volume on CE-CT (r = 0.551); minimal ADCdiff and MVD (r = −0.395). Conclusions Pathophysiological differences related to vascular supply in two human lung cancer cell lines with modifiable vascularity are quantifiable with clinical imaging techniques. Imaging parameters of vascularisation correlated with the results of histology. DWI was able to characterise both the extent of necrosis and the level of perfusion.

Pour agir de manière autonome et intelligente dans un environnement, un robot mobile doit disposer de cartes. Une carte contient les informations spatiales sur l’environnement. La géométrie 3D ainsi connue par le robot est utilisée non seulement pour éviter la collision avec des obstacles, mais aussi pour se localiser et pour planifier des déplacements. Les robots de prochaine génération ont besoin de davantage de capacités que de simples cartographies et d’une localisation pour coexister avec nous. La quintessence du robot humanoïde de service devra disposer de la capacité de voir comme les humains, de reconnaître, classer, interpréter la scène et exécuter les tâches de manière quasi-anthropomorphique. Par conséquent, augmenter les caractéristiques des cartes du robot à l’aide d’attributs sémiologiques à la façon des humains, afin de préciser les types de pièces, d’objets et leur aménagement spatial, est considéré comme un plus pour la robotique d’industrie et de services à venir. Une carte sémantique enrichit une carte générale avec les informations sur les entités, les fonctionnalités ou les événements qui sont situés dans l’espace. Quelques approches ont été proposées pour résoudre le problème de la cartographie sémantique en exploitant des scanners lasers ou des capteurs de temps de vol RGB-D, mais ce sujet est encore dans sa phase naissante. Dans cette thèse, une tentative de reconstruction sémantisée d’environnement d’intérieur en utilisant une caméra temps de vol qui ne délivre que des informations de profondeur est proposée. Les caméras temps de vol ont modifié le domaine de l’imagerie tridimensionnelle discrète. Elles ont dépassé les scanners traditionnels en termes de rapidité d’acquisition des données, de simplicité fonctionnement et de prix. Ces capteurs de profondeur sont destinés à occuper plus d’importance dans les futures applications robotiques. Après un bref aperçu des approches les plus récentes pour résoudre le sujet de la cartographie sémantique, en particulier en environnement intérieur. Ensuite, la calibration de la caméra a été étudiée ainsi que la nature de ses bruits. La suppression du bruit dans les données issues du capteur est menée. L’acquisition d’une collection d’images de points 3D en environnement intérieur a été réalisée. La séquence d’images ainsi acquise a alimenté un algorithme de SLAM pour reconstruire l’environnement visité. La performance du système SLAM est évaluée à partir des poses estimées en utilisant une nouvelle métrique qui est basée sur la prise en compte du contexte. L’extraction des surfaces planes est réalisée sur la carte reconstruite à partir des nuages de points en utilisant la transformation de Hough. Une interprétation sémantique de l’environnement reconstruit est réalisée. L’annotation de la scène avec informations sémantiques se déroule sur deux niveaux : l’un effectue la détection de grandes surfaces planes et procède ensuite en les classant en tant que porte, mur ou plafond; l’autre niveau de sémantisation opère au niveau des objets et traite de la reconnaissance des objets dans une scène donnée. A partir de l’élaboration d’une signature de forme invariante à la pose et en passant par une phase d’apprentissage exploitant cette signature, une interprétation de la scène contenant des objets connus et inconnus, en présence ou non d’occultations, est obtenue. Les jeux de données ont été mis à la disposition du public de la recherche universitaire. / Intelligent autonomous actions in an ordinary environment by a mobile robot require maps. A map holds the spatial information about the environment and gives the 3D geometry of the surrounding of the robot to not only avoid collision with complex obstacles, but also selflocalization and for task planning. However, in the future, service and personal robots will prevail and need arises for the robot to interact with the environment in addition to localize and navigate. This interaction demands the next generation robots to understand, interpret its environment and perform tasks in human-centric form. A simple map of the environment is far from being sufficient for the robots to co-exist and assist humans in the future. Human beings effortlessly make map and interact with environment, and it is trivial task for them. However, for robots these frivolous tasks are complex conundrums. Layering the semantic information on regular geometric maps is the leap that helps an ordinary mobile robot to be a more intelligent autonomous system. A semantic map augments a general map with the information about entities, i.e., objects, functionalities, or events, that are located in the space. The inclusion of semantics in the map enhances the robot’s spatial knowledge representation and improves its performance in managing complex tasks and human interaction. Many approaches have been proposed to address the semantic SLAM problem with laser scanners and RGB-D time-of-flight sensors, but it is still in its nascent phase. In this thesis, an endeavour to solve semantic SLAM using one of the time-of-flight sensors which gives only depth information is proposed. Time-of-flight cameras have dramatically changed the field of range imaging, and surpassed the traditional scanners in terms of rapid acquisition of data, simplicity and price. And it is believed that these depth sensors will be ubiquitous in future robotic applications. In this thesis, an endeavour to solve semantic SLAM using one of the time-of-flight sensors which gives only depth information is proposed. Starting with a brief motivation in the first chapter for semantic stance in normal maps, the state-of-the-art methods are discussed in the second chapter. Before using the camera for data acquisition, the noise characteristics of it has been studied meticulously, and properly calibrated. The novel noise filtering algorithm developed in the process, helps to get clean data for better scan matching and SLAM. The quality of the SLAM process is evaluated using a context-based similarity score metric, which has been specifically designed for the type of acquisition parameters and the data which have been used. Abstracting semantic layer on the reconstructed point cloud from SLAM has been done in two stages. In large-scale higher-level semantic interpretation, the prominent surfaces in the indoor environment are extracted and recognized, they include surfaces like walls, door, ceiling, clutter. However, in indoor single scene object-level semantic interpretation, a single 2.5D scene from the camera is parsed and the objects, surfaces are recognized. The object recognition is achieved using a novel shape signature based on probability distribution of 3D keypoints that are most stable and repeatable. The classification of prominent surfaces and single scene semantic interpretation is done using supervised machine learning and deep learning systems. To this end, the object dataset and SLAM data are also made publicly available for academic research.

Made available in DSpace on 2016-08-17T14:52:59Z (GMT). No. of bitstreams: 1 Jose Igor Santos de Oliveira.pdf: 3257339 bytes, checksum: 08e579c1308bf514ca6256e089894a3b (MD5) Previous issue date: 2005-09-21 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The level measurement, besides the applications in reservoirs of industrial processes, as in the industries chemical, pharmaceutical, chemical petroleum, of I refine of alumina etc, it is applicable also in reservoirs exposed outdoors, such as dikes, lakes and ponds, dams and other. To measure level in most of the cases has great impact in the people's safety, of the environment, and of the involved process, besides influencing in the quality of the final product. Level in several ways can be measured that space from a simple float to a sophisticated system for time of flight of waves that processes the information that returns after the emission of a sign. System as that can use several types of waves to take the information of the transmission, the most common are microwaves, infrared and the ultrasonic ones. In that work a method is described that is used of the technique of the time of flight with the use of ultrasonic waves in association with the adaptive filtering to determine the location of the levels of the liquids contained in a container of known height. It is made a study of robustness of the method with base in simulations, through the variation of the relationship sign noise and of the sampling tax, in comparison with the results obtained with the use of Hilbert Transform, Fourier Transform and Wavelet Transform, considering the time of processing and the measurement uncertainty. / A medição de nível, além das aplicações em reservatórios de processos industriais, como nas indústrias químicas, farmacêuticas, petroquímicas, de refino de alumina etc., é aplicável também em reservatórios expostos ao ar livre, tais como diques, lagos e lagoas, barragens e outros. Medir nível na maioria dos casos tem grande impacto na segurança das pessoas, do meio ambiente, e do processo envolvido, além de influenciar na qualidade do produto final. Pode-se medir nível de diversas formas que vão desde um simples flutuador até um sofisticado sistema por Tempo de Vôo de ondas que processa a informação que retorna na forma de eco refletido após a emissão de um sinal. Um Sistema como esse pode utilizar diversos tipos de ondas para levar a informação da transmissão, as mais comuns são microondas, infravermelhas e as ultra-sônicas. Nesse trabalho descreve-se um método que se utiliza da técnica do Tempo de Vôo com o uso de ondas ultra-sônicas em associação com a filtragem adaptativa para determinar a localização dos níveis dos líquidos contidos em um recipiente de altura conhecida. É feito um estudo de robustez do método com base em simulações, através da variação da relação sinal ruído e da taxa de amostragem. Compara-se com os resultados obtidos com o uso da Transformada de Hilbert, Transformada de Fourier e da Transformada Wavelets, considerando o tempo de processamento e a incerteza na medição.

Made available in DSpace on 2016-08-17T14:53:14Z (GMT). No. of bitstreams: 1 Mauro Sergio Silva Pinto.pdf: 649420 bytes, checksum: 2659c3409645c14d4672fc5713698782 (MD5) Previous issue date: 2006-10-27 / The time of flight method for determining the wind speed using ultrasonic transducers is presented in this work. The techniques of phase difference and threshold detection for determining the time of flight are presented. A more detailed study of the phase difference technique is carried out in order to determine the design specifications using this method with respect to the noise sensitivity, dependence of the measurement range with the medium temperature and measurement resolution. A design specification example is presented in order to illustrate the proposed procedures. / Apresenta-se neste trabalho o método do tempo de trânsito para determinação da velocidade do vento utilizando transdutores ultra-sônicos. Apresentam-se as técnicas da diferença de fase e detecção de limiar para determinação do tempo de trânsito deste método. Um estudo mais aprofundado é realizado para o método da diferença de fase de forma a determinar as especificações de projeto usando esse método, com relação à sensibilidade ao ruído, dependência da faixa de medição com temperatura do meio e resolução de medição. Um exemplo de especificação de projeto é apresentado de forma a ilustrar os procedimentos desenvolvidos.

A espectrometria de massas baseada na tecnologia MALDI-TOF (do inglês, matrix-assisted laser desorption ionization-time of flight) (MALDI-TOF MS) tem sido cada vez mais incorporada à rotina de identificações microbiológicas nos laboratórios farmacêuticos de controle de qualidade, principalmente para as atividades do Programa de Monitoramento Ambiental de Salas Limpas. Isso porque o longo tempo necessário para a obtenção dos resultados por meio de métodos convencionais tem incentivado a procura por técnicas que permitam métodos rápidos. O objetivo deste trabalho foi avaliar a adequação da técnica MALDI-TOF MS para a identificação de bactérias isoladas do ambiente de salas limpas utilizadas em algumas etapas da produção de uma vacina viral. Treze espécies bacterianas conhecidas, normalmente isoladas das salas limpas estudadas, e cinco cepas ATCC foram identificadas pela técnica MALDI-TOF MS e por uma técnica bioquímica (BBL Crystal®). O desempenho da técnica MALDI-TOF MS foi superior ao da técnica bioquímica na identificação correta das espécies bacterianas (88,89% e 38,89%, respectivamente) e produziu menos identificações não confiáveis (5,55% e 22,22%, respectivamente). Os resultados evidenciaram que a técnica MALDI-TOF MS pode ser implementada para identificação rotineira de bactérias em um laboratório de controle de qualidade farmacêutico. Entretanto, a dependência de bases de dados exige estudos adicionais de isolados não identificados e, se apropriado, a adição destes a uma base de dados interna. O aperfeiçoamento de métodos de identificação microbiana é muito relevante no contexto de salas limpas, pois permitem ações corretivas e proativas essenciais para garantir a segurança microbiológica do processamento asséptico. / Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has been increasingly introduced in routine microbiological identifications of pharmaceutical quality control laboratories, mainly for the activities of the Environmental Monitoring Program of Clean Rooms. The long time needed to obtain the results through conventional methods has stimulated the search for techniques that allow rapid methods, as MALDI-TOF MS. Thus, the objective of this work was to evaluate the suitability of the MALDI-TOF MS technique for the identification of bacteria isolated from the environment of clean rooms used in some stages of the production of a viral vaccine. Thirteen bacterial species commonly isolated from clean rooms studied and five strains ATCC were identified by MALDI-TOF MS technique and by a biochemical technique (BBL Crystal® System). Performance of MALDI-TOF MS was better than biochemical technique for correct species identifications (88.89% and 38.89%, respectively) and produced fewer unreliable identifications (5.55% and 22.22%, respectively). MALDI-TOF MS can be implemented for routine identification of bacteria in a pharmaceutical quality control laboratory. However, as a database-dependent system, maybe some isolated not identified by this technique must be additionally studied and, if appropriate, added to an in-house database.

Abstract In this thesis, a new type of laser diode transmitter using enhanced gain-switching suitable for use with a single photon avalanche diode (SPAD) detector was developed and tested in the pulsed time-of-flight laser range finding (lidar) application. Several laser diode versions were tested and the driving electronics were developed. The driving electronics improvements enabled a pulsing frequency of up to 1 MHz, while the maximum laser output power was about 5–40 W depending on the laser diode dimensions. The large output power is advantageous especially in conditions of strong photon noise emerging from ambient light outdoors. The length of the laser pulse matches the jitter of a typical SPAD detector providing several advantages. The new laser pulser structure enables a compact rangefinder for 50 m distance measurement outdoors in sunny conditions with sub-centimeter precision (σ-value) at a valid distance measurement rate of more than 10 kHz, for example. Single photon range finding techniques were also shown to enable a char bed level measurement of a recovery boiler containing highly attenuating and dispersing flue gas. In addition, gated single photon detector techniques were shown to provide a rejection of fluorescent photons in a Raman spectroscope leading to a greatly improved signal-to-noise ratio. Photonic effects were also studied in the case of a pulsed time-of-flight laser rangefinder utilizing a linear photodetector. It was shown that signal photon noise has an effect on the optimum detector configuration, and that pulse detection jitter can be minimized with an appropriate timing discriminator. / Tiivistelmä Tässä työssä kehitettiin uudentyyppinen, tehostettua "gain-switchingiä" hyödyntävä laserdiodilähetin käytettäväksi yksittäisten fotonien avalanche-ilmaisimien (SPAD) kanssa, ja sitä testattiin pulssin lentoaikaan perustuvassa laseretäisyysmittaussovelluksessa. Useita laserdiodiversioita testattiin ja ohjauselektroniikkaa kehitettiin. Ohjauselektroniikan parannukset mahdollistivat jopa 1 MHz pulssitustaajuuden, kun taas laserin maksimiteho oli noin 5–40 W riippuen laserdiodin dimensioista. Suuri lähtöteho on edullinen varsinkin vahvoissa taustafotoniolosuhteissa ulkona. Laserpulssin pituus vastaa tyypillisen SPAD-ilmaisimen jitteriä tarjoten useita etuja. Uusi laserpulssitinrakenne mahdollistaa esimerkiksi kompaktin etäisyysmittarin 50 m mittausetäisyydelle ulkona aurinkoisessa olosuhteessa mm–cm -mittaustarkkuudella (σ-arvo) yli 10 kHz mittaustahdilla. Yksittäisten fotonien lentoaikamittaustekniikan osoitettiin myös mahdollistavan soodakattilan keon korkeuden mittauksen, jossa on voimakkaasti vaimentavaa ja dispersoivaa savukaasua. Lisäksi portitetun yksittäisten fotonien ilmaisutekniikan osoitettiin hylkäävän fluoresenssin synnyttämiä fotoneita Raman-spektroskoopissa, joka johtaa selvästi parempaan signaali-kohinasuhteeseen. Fotoni-ilmiöitä tutkittiin myös lineaarista valoilmaisinta hyödyntävän pulssin kulkuaikamittaukseen perustuvan lasertutkan tapauksessa. Osoitettiin, että signaalin fotonikohina vaikuttaa optimaaliseen ilmaisinkonfiguraatioon, ja että pulssin ilmaisujitteri voidaan minimoida sopivalla ajoitusdiskriminaattorilla.