Nos connaissances sur les mécanismes étiopathogéniques des cancers utérins (endomètre et col) sont en constante amélioration. Cependant, le dépistage précoce des lésions précancéreuses a été réalisé, jusqu'à présent, avec plus de succès pour le col que pour le corps utérin. En outre, un diagnostic histopathologique précis est obligatoire pour adopter la stratégie thérapeutique la plus appropriée. L'objectif général de ce travail a été de valider des marqueurs diagnostiques potentiels des cancers utérins en utilisant la technologie des « Tissus Puces» ou «Tissue Microarray» (TMA) qui permet l'examen uniforme et simultané d'un grand nombre d'échantillons déposés sur une même lame. Grâce à cette technologie, nous avons montré que la détection d'une série de marqueurs (ADN de papillomavirus humain, protéine p16, involucrine et antigène Ki67) peut améliorer le diagnostic histopathologique des différentes lésions (pré)néoplasiques cervicales. En outre, ces biomarqueurs pourraient aider à mieux comprendre la biologie des lésions épithéliales cervicales en les reliant à des critères morphologiques précis. Nous avons également évalué l'intérêt de marqueurs diagnostiques basés sur la méthylation de l'ADN dans la carcinogenèse endométriale. Notre démonstration d'une hyperméthylation des promoteurs de deux gènes suppresseurs de tumeur (RASSF1A et RARB2) au cours de la carcinogenèse endométriale et dans les tissus normaux adjacents aux tumeurs suggère un rôle important de la méthylation de l'ADN dans linitiation et la progression des lésions (pré) cancéreuses de lendomètre.

<p>The knowledge of the human genome sequence, as revealed in the HUGO project, has created exciting new possibilities for biomedical research. The Swedish Human Proteome Resource (HPR) program aims to make use of this information to gain further insight into the human proteome. Recombinant proteins are generated from coding sequences identified from the human genome sequence and used to produce specific antibodies to target proteins. Antibodies are subsequently utilized for functional analysis of the corresponding proteins using tissue micro arrays. The aim of my project was to investigate the possibility of distinguishing characteristic distribution patterns of intracellular proteins in the resolution capacity offered by light microscopy. A map of representative distribution patterns was created using immunohistological staining with commercially available antibodies toward well-characterised proteins in the cell. Such a map could then aid in interpreting the results of immunohistological staining of intracellular proteins using antibodies produced within the Human Proteome Resource program. Proteins manifested in nucleus, nuclear membrane and plasma membrane were clearly visible at the expected location. Proteins manifested in different organelles in the cytoplasm however, showed all a similar staining pattern, making determination of exact protein location uncertain. A possible explanation is the resolution of the light microscope not being sufficient to visualize certain proteins specific to organelles in the cytoplasm. Results may also have been influenced by the choice of secondary antibody, where the strenghtened signal generated by an enzyme labelled polymer may have a negative effect on depiction of details in the image generated.</p>

The knowledge of the human genome sequence, as revealed in the HUGO project, has created exciting new possibilities for biomedical research. The Swedish Human Proteome Resource (HPR) program aims to make use of this information to gain further insight into the human proteome. Recombinant proteins are generated from coding sequences identified from the human genome sequence and used to produce specific antibodies to target proteins. Antibodies are subsequently utilized for functional analysis of the corresponding proteins using tissue micro arrays. The aim of my project was to investigate the possibility of distinguishing characteristic distribution patterns of intracellular proteins in the resolution capacity offered by light microscopy. A map of representative distribution patterns was created using immunohistological staining with commercially available antibodies toward well-characterised proteins in the cell. Such a map could then aid in interpreting the results of immunohistological staining of intracellular proteins using antibodies produced within the Human Proteome Resource program. Proteins manifested in nucleus, nuclear membrane and plasma membrane were clearly visible at the expected location. Proteins manifested in different organelles in the cytoplasm however, showed all a similar staining pattern, making determination of exact protein location uncertain. A possible explanation is the resolution of the light microscope not being sufficient to visualize certain proteins specific to organelles in the cytoplasm. Results may also have been influenced by the choice of secondary antibody, where the strenghtened signal generated by an enzyme labelled polymer may have a negative effect on depiction of details in the image generated.

Für die Beschichtung von Bauelementen im Bereich der Elektronik erlangt das Beschichtungsverfahren der Atomlagenabscheidung zunehmend an Bedeutung. Dieses Verfahren überzeugt hier durch seine Fähigkeit sehr homogene Schichten mit einer Dicke von wenigen nm auch auf Strukturen mit hohen Aspektverhältnissen zu erzeugen. Diese Arbeit beschäftigt sich mit der Atomlagenabscheidung von Aluminiumoxid unter Verwendung der Präkursoren Trimethylaluminium und Wasser. Hauptaufgabe dieser Arbeit ist die Modellierung eines experimentellen Prozessaufbaus mit kommerzieller Simulationssoftware. Anhand der Simulationsergebnisse können Aussagen zur Optimierung des ALD-Prozesses getroffen werden. Die durchgeführten Untersuchungen zeigen, dass für die Simulation eines ALD-Prozesses sehr lange Rechenzeiten erforderlich sind. Insbesondere konnte ein tieferes Verständnis der automatischen Zeitschrittweitenregulierung der Software bei transienten Simulationen gewonnen werden. Die Dauer der Spülschritte wurde durch die Simulationsergebnisse als ausreichend bestätigt. Des Weiteren kann die Verwendung der zur Anlage gehörigen Gasdusche anhand der Simulationsergebnisse nicht empfohlen werden.

<p>ABSTRACT</p><p>The Swedish Human Proteome Resource (HPR) is a project about mapping of human genes and proteins. It aims to describe the function and distribution of all human genes and corresponding proteins, using in-house produced antibodies and tissue microarrays (TMA) for enzyme based immunohistochemistry. The mono-specific antibodies are used for immunostaining of human tissue. Specific predicted antigens named Protein Epitope Signature Tag (PrEST) are needed to produce mono-specific antibodies. PrEST are produced using recombinant technology from predicted genes and used as immunogens to produce (mono-specific) antibodies in rabbits. In this study, 84 mono-specific antibodies with known specificity to human proteins were used for immunohistochemical analysis of mouse tissues to determine the cross reactivity between mouse and human.</p><p>For 6 of the 84 antibodies the results differed between mouse and human tissue. A comparison between the PrEST used with the mouse proteome using database search programs showed homologies that were less than 100% in these six cases.</p><p>Thus, future studies on cross reactivity will focus on how to increase the accuracy in its prediction at the in silico stage of the experiment.</p>

ABSTRACT The Swedish Human Proteome Resource (HPR) is a project about mapping of human genes and proteins. It aims to describe the function and distribution of all human genes and corresponding proteins, using in-house produced antibodies and tissue microarrays (TMA) for enzyme based immunohistochemistry. The mono-specific antibodies are used for immunostaining of human tissue. Specific predicted antigens named Protein Epitope Signature Tag (PrEST) are needed to produce mono-specific antibodies. PrEST are produced using recombinant technology from predicted genes and used as immunogens to produce (mono-specific) antibodies in rabbits. In this study, 84 mono-specific antibodies with known specificity to human proteins were used for immunohistochemical analysis of mouse tissues to determine the cross reactivity between mouse and human. For 6 of the 84 antibodies the results differed between mouse and human tissue. A comparison between the PrEST used with the mouse proteome using database search programs showed homologies that were less than 100% in these six cases. Thus, future studies on cross reactivity will focus on how to increase the accuracy in its prediction at the in silico stage of the experiment.

In investigating ocean surface waves at a location, it is often to describe the waves with spectrum. A wave spectrum measures the distribution of wave energy from the wave trains in all different directions and all different periods at a location. Since the waves at a location contain seas and swells (which are the waves generated by local and remote wind systems respectively), a wave spectrum is viewed composing of different portions of the seas and swell spectrum. How to precisely partition a wave spectrum for each wave system (seas and swells) is of practical need in engineering practice, wave forecast, and coastal water management. At present, there are many different partitioning schemes, but not all are reliable and feasible enough for operational use. This report presents a wave system partition scheme followed by an identification scheme, which uses TMA spectrum, to identify different wave systems. This partition and identification scheme is intended for operationally use in partitioning the swell and wind sea in spectrum at finite water depth. Automated spectral partition and identification have been developed to evaluate swell systems in data during typhoon Meari.

The TMA Traffic Operations Survey was developed, which focused on traffic operations services and transportation system management practices of TMOs. The survey had the following structure: background, membership, services, and follow-up. The survey was emailed to 157 TMOs around the nation and 35 responses were received, a 22.2% response rate. Of the participating organizations only five (17%) organizations provided traffic services including traffic control improvements, signal timing, and collection of traffic data. These findings determined that a minority of organizations are involved in traffic operations. The multiple organizations that are involved in traffic operations provided data on their websites including incident alerts, live traffic views, and real-time traffic or shuttle information. Very few of the organizations that used data to provide traffic operations services generated the data themselves. The research results determined that few organizations are actively attempting to assume a role in traffic operations.

When a vehicle enters an intersection with insufficient space to exit on the opposite side the result is often the obstruction of pedestrians and other vehicles, this phenomenon is usually referred to as "blocking the box." The purpose of this study was to determine different characteristics of blocking that might be considered in determining the installment of a "Don't Block the Box" (DBTB) campaign. This study identified potentially problematic intersections in Atlanta, Georgia and collected information, such as the number of vehicles that block the intersection (box junction), the amount of green time with blocking, and the percentages in which approaches were blocked. Based on the results it was found the characteristics of the number of blockers, percentage of green time with blocking, and the percentage of lost capacity are excellent indicators for a possible DBTB campaign. Organizations interested in potentially starting a DBTB should consider these characteristics part of the determination of suitability of DBTB for an intersection. Within this study is was found that the intersections of Peachtree Road & Highland Drive, Peachtree Road & Stratford Road, Peachtree Road & Lenox Mall Entrance, and 10th Street & Williams Street showed to be potential candidates for a DBTB campaign in Atlanta, Georgia. During the study period these intersections had high percentages of lost capacity, high number of blocks, and high percentages of green time with blocking. In conjunction with the DBTB data analysis a "DBTB survey" was developed. The objective of this survey was to help gain a better understanding of the current trends in DBTB campaigns around the United States. The "DBTB Survey" received 75 responses from 415 organizations around the nation, a 18.1% response rate. Six (60%) of the ten participants that currently have a DBTB campaign found a sufficient level of improvement in traffic operations and 46 of the total respondents (60%) proclaimed that if DBTB campaigns were shown to be an economical alternative for traffic management they would consider starting one to help congestion and safety.

京都大学 / 0048 / 新制・課程博士 / 博士(人間健康科学) / 甲第20295号 / 人健博第43号 / 新制||人健||4(附属図書館) / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 高桑 徹也, 教授 藤井 康友, 教授 武藤 学 / 学位規則第4条第1項該当 / Doctor of Human Health Sciences / Kyoto University / DGAM