Master-Arbeit Univ. St. Gallen, 2008.

Beim akuten ischämischen Schlaganfall ist die Größe der initialen DWI-Läsion (Diffusions-gewichtete Sequenz) in der zerebralen MRT zur Abschätzung der Prognose des Patienten umstritten. Die Beobachtung des Verlaufs der DWI-Läsion in den ersten Tagen nach einem Schlaganfall scheint hierfür besser geeignet. Hierbei zeigt sich, dass ein Infarktwachstum eher mit einem schlechteren klinischen Ergebnis korreliert. Ein mögliches Infarktwachstum vorherzusagen ist deshalb von großem Interesse. Bei nicht-lakunären Infarkten, die durch Verschlüsse größerer Arterien verursacht werden, ist die Ausbreitung des Infarktkerns in zuvor minderperfundierte Areale (d.h. in die Penumbra), als Ursache eines Wachstums anerkannt. Die Penumbra wird als die Differenz zwischen DWI- und PWI-Läsionen (Perfusions-gewichtete Sequenz) angesehen, was als PWI/DWI-Mismatch bezeichnet wird. Unklar ist, ob dieses Mismatch-Konzept auch auf lakunäre Ischämien (DWI-Läsionen < 2 cm Ø) angewandt werden kann. Ziel dieser prospektiven Studie war, den Zusammenhang zwischen dem initialen DWI/PWI-Mismatch und der Infarktentwicklung im kurzfristigen Verlauf bei 100 konservativ behandelten Patienten zu untersuchen. Das Patientenkollektiv war hinsichtlich der Infarktsubtypen (lakunäre und nicht-lakunäre) als inhomogen einzustufen. Am Tag der Aufnahme und an Tag 7 wurden anhand eines MRT-Schlaganfallprotokolls die Volumina der DWI und PWI-Läsionen, die Mismatch-Volumina, das Infarktwachstum, das relative Mismatch und das relative Infarktwachstum untersucht. Das Infarktwachstum zeigte einen engen Zusammenhang mit dem initialen DWI/PWI-Mismatch. Dies traf vor allem dann zu, wenn man die relativen Werte betrachtete. Hieraus ergibt sich, dass ein großes initiales Mismatch ein späteres Infarktwachstum wahrscheinlicher macht. Für die Zukunft könnte man daher davon ausgehen, dass das relative Mismatch, bezogen auf die relative Infarktentwicklung, einen besseren prognostischen Wert aufweist, als die absoluten Werte.

Concevoir un circuit numérique en technologie CMOS inferieur à 100nm se heurte à de multiples défis en termes de variation de process, voltage et temperature. L'attention s'est portée essentiellement sur les variations " inter-die " qui forme la plus grande partie des variations de process. Dans cette étude, nous nous sommes attachés sur deux formes particulières de variations : les divergences "Inter-die NMOS a PMOS " et les divergences aléatoires "Intra-die local". Aucune d'elles n'avait jusqu'alors d'effet notable durant les conceptions industrielles et sont désormais toutes deux source de soucis majeurs. Le travail en academia se concentre principalement sur le changement de process ou sur les améliorations architecturales. Notre action s'est orientée vers l'amélioration de la conception au niveau porte logique et au niveau chemin. Notre attention s'est portée sur les systèmes synchrones, i.e. system de distribution d'horloge qui est fortement impacté par ces variations. Nous avons proposé quelques méthodes de conception et des stratégies d'optimisation pour fabriquer des circuits plus robustes. La plupart de ces méthodes sont exploitables au sein même du flot de design existant ce qui minimise le cout et permet son adoption rapide dans l'industrie. Nous avons inclus l'effet des changements de voltage et de température sur ces deux variations pour élaborer une compréhension globale. Nous avons aussi proposé des méthodes pour vérifier les bases de notre travail en le comparant vis à vis des résultats de test sur silicium. Les résultats de ce travail ont permis de façonner la politique de comment gérer les divergences locales dans la conception industrielle.

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Essays in this dissertation address three research questions. (1) What types of persons hold dual jobs and what are their motives for doing so? In essay 1, I investigate multiple factors that affect the decision to hold more than a single job. Using data from the Current Population Survey (CPS), the first essay documents the characteristics of second jobs and multiple job holders in the U.S. I characterize the types of people who hold dual jobs and use additional information from the BLS to find out workers’ motives for holding multiple jobs. I examine how multiple job holding differs with respect to age, education, race and ethnicity, sex, foreign-born status, marital status, public-private worker status, broad industry and occupation. (2) How does dual job holding vary with the business cycle and state of the labor market? Essay 2 explores a large micro data set for 1998-2013 that covers most U.S. urban labor markets. We find clear-cut evidence that multiple job holding across labor markets and over time is weakly cyclical, thus (slightly) exacerbating rather than mitigating the severity of business cycles. Much of the cyclicality in multiple job holding seen across labor markets, however, is not causal, dropping sharply after accounting for MSA fixed effects. Using longitudinal worker data, there is minimal response to unemployment changes within labor markets over time. Our large CPS sample size produces precise estimates, albeit ones close to zero, helping explain conflicting results in prior studies based on far smaller data sets. (3) How might one explain the persistent geographical differences in multiple job holding? Essay 3 documents what are systematic (i.e., long-run) differences in multiple job holding across labor markets (MSAs) and explores possible explanations for these differences. Geographical differences in multiple job holding rates have received little attention, although the multiple job holding rates in some regions of the country are substantially higher than in other regions, and these differences have been persistent over time. Examining correlates of these labor market differences in multiple job holding provides us with a better understanding of the determinants of labor supply and how local labor markets work.

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PCNA and RPA are required for DNA mismatch repair (MMR), but their rolesin the pathway are not fully understood. Using an affinity pull-down approach, weshow that (1) increased PCNA binding to DNA heteroduplexes is associated withthe appearance and accumulation of excision products; and (2) RPAphosphorylation occurs when DNA polymerase ?? binds to the DNA substrate. Wetherefore hypothesize that PCNA plays an important role in mismatch-provokedexcision and that RPA phosphorylation plays an important role in DNA resynthesis.To determine the role of PCNA in MMR, mismatch-provoked and nick-directedexcision was assayed in a cell-free system in the presence of the PCNA inhibitor,p21CIP1/WAF. We show that whereas PCNA is essential for 3' directed excision, it isdispensable for the 5' directed reaction, suggesting a differential role for PCNA inMMR. We further find that the PCNA-dependent pathway is the only pathway for3' directed excision, but there are at least two pathways for 5' directed excision,one of which is a PCNA-independent 5' excision pathway. To determine if RPAphosphorylation facilitates DNA resynthesis, a gap-filling assay was developedusing both a cell-free system and a purified system, and we demonstrate that RPAphosphorylation stimulates DNA polymerase ??-catalyzed resynthesis in bothsystems. Kinetic studies indicate that phosphorylated RPA has a lower affinity forDNA compared with un-phosphorylated RPA. Therefore, the stimulation ofresynthesis by phosphorylated RPA is likely due to the fact that phosphorylationpromotes the release of RPA from DNA, thereby making DNA template availablefor resynthesis.

As the rapid evolution in semiconductor technology, transistors’ feature size has reached to 22nm and below, which brings great impact to analog and mixed-signal circuits. As the significant bridge connecting the analog world and digital system, data converter suffers from nonlinearity resulting from mismatch among its unit components. The smaller transistors are, the larger relative mismatch among them becomes. However, using larger transistors leads to more area cost and power consumption. Therefore, researchers have been working hard on how to alleviate the mismatch issue. In recent years, Dynamic Element Matching (DEM) becomes a popular approach that can significantly improve linearity, especially Spurious-free Dynamic Range (SFDR), of a data converter system. The basic idea of DEM is to shuffle the usage pattern of unit elements so that the mismatch error is no longer correlated to the input signal. Thus, DAC’s linearity will be improved. Generally, DEM Nyquist-rate DAC does mismatch scrambling, which smooths distortions resulting from mismatch into white noise. DEM Delta-Sigma DAC does mismatch shaping, which pushes distortions away from the signal band, typically lower frequencies. In this thesis, we focused on mismatch-shaping Delta-Sigma DACs. Two of those various algorithms are implemented logically and physically. With placement and routing information, we got more accurate result on the speed and power dissipation. The comparison shows the tradeoff among number of quantization levels, mismatch-shaping order, and hardware complexity. / text

Conjugation is a fundamentally important mechanism of horizontal DNA transfer between bacteria, bacteria x archea, and bacteria x eukaryotes. This work has concentrated on conjugation between bacteria x eukaryotes, specifically Escherichia coli x Saccharomyces cerevisiae. Four hypotheses were tested, investigating the barriers to this particular form of DNA transfer. The first investigated if a mutation that altered the cell-surface of the recipient S. cerevisiae could inhibit DNA transfer. The final three utilised a recombination-dependent-conjugation assay to investigate the barrier to DNA transmission through recombination. The hypotheses tested if the frequency of recombination, in this recombination-dependent-conjugation assay, differed when using similar or diverged DNA substrates, if a mismatch repair mutation within the recipient could affect the frequencies of recombination observed, and if the position on the plasmid of the gene of interest affected the frequency of transmission. Transmission of the Ura3 DNA sequence in the recipient S. cerevisiae was used to test all four hypotheses. The cell wall mutants mnn9, knr4, fks1 and kre6 were utilised to investigate if the cell-surface of the recipient could affect the frequency of transmission. The similar and diverged substrates utilised in the investigation of the affect of sequence similarity on recombination were the DNA sequences of ura3 from S. cerevisiae and Saccharomyces carlsbergensis, respectively and the MMR mutants utilised were msh2, pms1 and pol30-52. Cell wall mutants were not found to limit the frequency of transfer once donor-recipient contact was induced through the solid surface mating procedure. Sequence similarity, MMR and the relative position of the ura3 DNA sequence on the conjugative plasmids were shown to have little effect on the frequency of transmission in S. cerevisiae. This suggests that any DNA that enters the nucleus of S. cerevisiae (eukaryotes) can recombine with the chromosome and alter it to the same extent. However, trends within the data also suggest that DNA is transferred into the recipient and then transported to the nucleus to recombine with the chromosome as a single-stranded DNA molecule.