Reise-Protokoll der Reichstagsdeputation nach Innsbruck: Deputations-Mitglieder: 1. Herr Franz Schmitt, für Nieder-Oesterreich ...: Die drei sub 3 bis 5 verzeichneten Deputations-Mitglieder reiseten Montags den 31. Juli 1848 ...

Welsch (Projektbearbeiter): Eingehende Schilderung der Reise einer Reichstagsdeputation nach Innsbruck (31. Juli - 9. August 1848) anläßlich der bevorstehenden Rückkehr Kaiser Ferdinands I. nach Wien

Molecular consequences of the loss of 3'→5' exonuclease activity of DNA polymerases delta and epsilon

The DNA replication polymerases δ and ϵ have an inherent proofreading mechanism in the form of a 3'→5' exonuclease. Upon recognition of errant deoxynucleotide incorporation into DNA, the nascent primer terminus is partitioned to the exonuclease active site where the incorrectly paired nucleotide is excised before resumption of polymerization. The goal of this project was to identify the cellular and molecular consequences of an exonuclease deficiency. The proofreading capability of model system MEFs with EXOII mutations was abolished without altering polymerase function.^ It was hypothesized that 3'→5' exonucleases of polymerases δ and ϵ are critical for prevention of replication stress and important for sensitization to nucleoside analogs. To test this hypothesis, two aims were formulated: Determine the effect of the exonuclease active site mutation on replication related molecular signaling and identify the molecular consequences of an exonuclease deficiency when replication is challenged with nucleoside analogs.^ Via cell cycle studies it was determined that larger populations of exonuclease deficient cells are in the S-phase. There was an increase in levels of replication proteins, cell population growth and DNA synthesis capacity without alteration in cell cycle progression. These findings led to studies of proteins involved in checkpoint activation and DNA damage sensing. Finally, collective modifications at the level of DNA replication likely affect the strand integrity of DNA at the chromosomal level.^ Gemcitabine, a DNA directed nucleoside analog is a substrate of polymerases δ and ϵ and exploits replication to become incorporated into DNA. Though accumulation of gemcitabine triphosphate was similar in all cell types, incorporation into DNA and rates of DNA synthesis were increased in exonuclease defective cells and were not consistent with clonogenic survival. This led to molecular signaling investigations which demonstrated an increase in S-phase cells and activation of a DNA damage response upon gemcitabine treatment.^ Collectively, these data indicate that the loss of exonuclease results in a replication stress response that is likely required to employ other repair mechanisms to remove unexcised mismatches introduced into DNA during replication. When challenged with nucleoside analogs, this ongoing stress response coupled with repair serves as a resistance mechanism to cell death.^

IV Jornadas de Graduados - Jóvenes Investigadores : La Plata, Facultad de Humanidades y Ciencias de la Educación de la UNLP, 3 a 5 de octubre de 2012

Fil: Cairo, María Emilia. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina.

IV Jornadas de Graduados - Jóvenes Investigadores : La Plata, Facultad de Humanidades y Ciencias de la Educación de la UNLP, 3 a 5 de octubre de 2012

Fil: Cairo, María Emilia. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina.

Análisis empírico del tráfico en las autopistas de peaje radiales 3 y 5 de Madrid

El propósito de la presente investigación es determinar si, a través del estudio y análisis de los estudios de tráfico en autopistas de peaje, se pueden determinar las razones de los incumplimientos en las previsiones de estos estudios. La metodología se basa en un análisis empírico ex- post facto de los estudios de tráfico contenidos en los anteproyectos de las autopistas Radial 3 y Radial 5 y los datos realmente verificados. Tras una introducción para presentar las principales características de las autopistas de peaje, se realiza una revisión de la bibliografía sobre el cumplimiento de las previsiones de tráfico. Lo anterior permite establecer una serie de aspectos que pueden contribuir a estos incumplimientos, así como una serie de medidas encontradas para mejorar las futuras previsiones. Ya en el núcleo fundamental de la investigación, esta se centra en el análisis del cumplimiento de las previsiones de tráfico contenidas en los anteproyectos de la Radial 3 y Radial 5. Se realiza un análisis crítico de la metodología adoptada, así como de las variables e hipótesis realizadas. Tras este primer análisis, se profundiza en la fase de asignación de los estudios. Siempre con base a los tráficos reales y para el año 2006, se cuantifica el efecto en los incumplimientos, por un lado de las variables utilizadas, y por otro, del propio método ó curva de asignación. Finalmente, y con base en los hallazgos anteriores, se determinan una serie de limitaciones en el método de asignación de tráficos entre recorridos alternativos para el caso de entornos urbanos usado. El planteamiento con base a las teorías del agente racional y maximización de la utilidad esperada es criticado desde la perspectiva de la teoría de decisión bajo condiciones de riesgo planteada por Kahneman y Tversky. Para superar las limitaciones anteriores, se propone una nueva curva de asignación semi empírica que relaciona la proporción del tráfico que circula por la autopista de peaje con la velocidad media en la autovía libre alternativa. ABSTRACT The aim of this research is to confirm whether the forensic analysis of the traffic forecast studies for tolled highways may bring to light the reasons behind the lack of accuracy. The methodology used on this research is empirical and is based on the ex –post facto analysis of the real traffic numbers compared to the forecasted for the tolled highways Radial 3 and Radial 5. Firstly the main features of tolled highways are presented as an introductory chapter. Secondly a broad bibliographic search is presented, this is done from a global perspective and from the Spanish perspective too. From this review, a list of the main causes behind the systematic inaccuracy together with measures to improve future traffic forecast exercises are shown. In what we could consider as the core of the research, it focuses on the ratios of actual / forecast traffic for the tolled highways Radial 3 y Radial 5 in Madrid outskirts. From a critical perspective, the methodology and inputs used in the traffic studies are analysed. In a further step, the trip assignment stage is scrutinised to quantify the influence of the inputs and the assignment model itself in the accuracy of the traffic studies. This exercise is bases on the year 2006. Finally, the assignment model used is criticised for its application in tolled urban highways. The assumptions behind the model, rational agent and expected utility maximization theories, are questioned under the theories presented by Kahneman and Tversky (Prospect Theory). To overcome these assignment model limitations, the author presents a semi empiric new diversion curve. This curve links the traffic proportion using the tolled highway and the average speed in the toll free alternative highway.