Dans cette thèse, on donne une définition de la K-théorie topologique des espaces non-commutatifs de Kontsevich (c'est-à-dire des dg-catégories) définis sur les nombres complexes. L'introduction de ce nouvel invariant initie la recherche des invariants de nature topologique des espaces non-commutatifs, comme "simplifications" des invariants algébriques (K-théorie algébrique, homologie cyclique, périodique comme étudiés dans les travaux de Tsygan, Keller). La motivation principale vient de la théorie de Hodge non-commutative au sens de Katzarkov--Kontsevich--Pantev. En géométrie algébrique, la partie rationnelle de la structure de Hodge est donnée par la cohomologie de Betti rationnelle, qui est la cohomologie rationnelle de l'espace des points complexes du schéma. La recherche d'un espace associé à une dg-catégorie trouve une première réponse avec le champ (défini par Toën--Vaquié) classifiant les dg-modules parfaits sur cette dg-catégorie. La définition de la K-théorie topologique a pour ingrédient essentiel le foncteur de réalisation topologique des préfaisceaux en spectres sur le site des schémas de type fini sur les complexes. La partie connective de la K-théorie semi-topologique peut être définie comme la réalisation topologique du champ en monoïdes commutatifs des dg-modules parfaits. Cependant pour atteindre la K-théorie négative, on réalise le préfaisceau donné par la K-théorie algébrique non-connective. Un de nos résultats principaux énonce l'existence d'une équivalence naturelle entre ces deux définitions dans le cas connectif. On montre que la réalisation topologique du préfaisceau de K-théorie algébrique connective pour la dg-catégorie unité donne le spectre de K-théorie topologique usuel. Puis que c'est aussi vrai pour la K-théorie algébrique non-connective, en utilisant la propriété de restriction aux lisses de la réalisation topologique. En outre, cette propriété de restriction aux schémas lisses nécessite de montrer une généralisation de la descente propre cohomologique de Deligne, dans le cadre homotopique non-abélien.La K-théorie topologique est alors définie en localisant par rapport à l'élément de Bott. Cette définition repose donc sur des résultats non-triviaux. On montre alors que le caractère de Chern de la K-théorie algébrique vers l'homologie périodique se factorise par la K-théorie topologique, donnant un candidat naturel pour la partie rationnelle d'une structure de Hodge non-commutative sur l'homologie périodique, ceci étant énoncé sous la forme de la conjecture du réseau. Notre premier résultat de comparaison concerne le cas d'un schéma lisse de type fini sur les complexes -- la conjecture du réseau est alors vraie pour de tels schémas. On montre ensuite que cette conjecture est vraie dans le cas des algèbres associatives de dimension finie.

Fifty percent of solid cancers are treated with radiation therapy (RT). The dose used in RT is adjusted to the most sensitive individuals so that not more than 5% of the patients will have severe adverse healthy tissue effects. As a consequence, the majority of the patients will receive a suboptimal dose, as they would have tolerated a higher total dose and received a better tumor control. Thus, if RT could be individualized based on radiation sensitivity (RS), more patients would be cured and the most severe adverse reactions could be avoided. At present the mechanisms behind RS are not known. The long term aim of this thesis was to develop diagnostic tools to assess the individual RS of breast cancer patients and to better understand the mechanisms behind the RS and radiation effects after low dose exposures. The approach was based on the hypothesis that biomarkers of individual RS, in terms of acute adverse skin reactions after breast cancer RT, can be found in whole blood that has been stressed by low doses of ionizing radiation (IR).  To reach this goal two different approaches to identify biomarkers of RS have been investigated. A protocol for the analysis of differential protein expression in response to low dose in vitro irradiated whole blood was developed (paper I). This protocol was then used to investigate the proteomic profile of radiation sensitive and normo-sensitive patients, using isotope-coded protein labeled proteomics (ICPL). The results from the ICPL study (paper III) show that the two patient groups have different protein expression profiles both at the basal level and after IR. In paper II the potential biomarker 8-oxo-dG was investigated in serum after IR. The relative levels of IR induced 8-oxo-dG from radiation sensitive patients differ significantly from normo-sensitive patients. This indicates that the sensitive patients differ in their cellular response to IR and that 8-oxo-dG is a potential biomarker for RS. / <p>At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manuscript.</p>

Zugl.: Mainz, Univ., Diss., 2005

This diploma work is mainly a monography of a Czech author Pavel Zajicek. The base of this study is the analysis and the interpretation of his lifelong official and samizdat literary work. In the analysis of some of his prerevolutionary books as the main source I used mainly the critiques of the contemporary literary magazines. I also present the life of the author itself, especially in the context of the period he lived in. I will briefly mention two musical bands that are closely related to this personality {--} DG 307 and PPU. In my studies I use my personal e-mail with Pavel Z. and I do not forget to observe all accesible dialogues with this poet. This diploma work is mainly a monography of a Czech author Pavel Zajicek. The base of this study is the analysis and the interpretation of his lifelong official and samizdat literary work. In the analysis of some of his prerevolutionary books as the main source I used mainly the critiques of the contemporary literary magazines. I also present the life of the author itself, especially in the context of the period he lived in. I will briefly mention two musical bands that are closely related to this personality {--} DG 307 and PPU. In my studies I use my personal e-mail with Pavel Z. and I do not forget to observe all accesible dialogues with this poet. This diploma work is mainly a monography of a Czech author Pavel Zajicek. The base of this study is the analysis and the interpretation of his lifelong official and samizdat literary work. In the analysis of some of his prerevolutionary books as the main source I used mainly the critiques of the contemporary literary magazines. I also present the life of the author itself, especially in the context of the period he lived in. I will briefly mention two musical bands that are closely related to this personality {--} DG 307 and PPU. In my studies I use my personal e-mail with Pavel Z. and I do not forget to observe all accesible dialogues with this poet.

Chick embryo fibroblasts and rat kidney cells infected in vitro with Rous Sarcoma viruses were treated with 3-deazaguanine (3-DG). The findings revealed that 3-DG inhibited virus-induced cellular transformation. Degree of inhibition is dependent on concentration and frequency of media change. 3-DG at the concentrations tested will not reverse transformed cells to the untransformed state and does not have marked effect on replication of viruses. Upon removal of 3-DG, its effect was shown to be reversible. Cell growth was generally retarded in medium containing 3-DG. When xanthosine and inosine were added to the medium, cell growth was unaffected, but it increased in guanosine.

Genomic alterations may initiate cancer development as the consequence of endogenous or exogenous DNA damaging factors. Defects in DNA repair mechanisms may also facilitate cancer progression as well as accumulation of mutations which favor cancer cell survival. However, DNA repair pathways in cancer cells can be considered as their Achilles heel which are possible targets in order to compromise their survival. For instance, it has been demonstrated recently that inhibition of a protein called MTH1 via RNA interference (RNAi) or chemical inhibitors can stop tumor growth and triggers cell death by increasing the load of oxidative DNA damage. MTH1 is a hydrolase which converts 8-oxo-dGTP into 8-oxo-dGMP in order to prevent incorporation of oxidatively damaged nucleotides into DNA. In addition, DNA glycosylases which recognize and remove mismatched or damaged nucleotide pairs in DNA can also participate in repair of 8-oxo-dG, such as MUTYH repairing A:8-oxo-dG pair. The goal of the current study was to investigate the importance of MUTYH activity upon MTH1 depletion. The current study tried to answer whether simultaneous knock-down of MTH1 and MUTYH sensitizes cancer cells to oxidative stress and increases cell death. Both enzymes were simultaneously depleted in T cell acute lymphoblastic leukemia cells using RNAi. Then, we analyzed the efficiency of gene and protein knock-down by quantitative real-time-PCR and western blotting, respectively. Induction of cell death was also assessed by flow cytometric analysis of cell cycle. Afterwards, the effect of the treatments on DNA repair pathways was studied by analysis of gene expression of several DNA glycosylases and DNA polymerases using qRT-PCR. The results showed that concurrent depletion of both enzymes led to synergistic induction of cell death. Down-regulation of NEIL1 DNA glycosylase as well as POLQ and POLH DNA polymerases mRNAs adapted their DNA repair pathways to cope with induced damages under these conditions. Finally, the results of this study suggest that dual suppression of MTH1 and MUTYH may provide a new approach to reduce survival of T cell ALL.

This dissertation is a systematic study of electric power distribution system reliability evaluation and improvement. Reliability evaluation of electric power systems has traditionally been an integral part of planning and operation. Changes in the electric utility coupled with aging electric apparatus create a need for more realistic techniques for power system reliability modeling. This work presents a reliability evaluation technique that combines set theory and Graph Trace Analysis (GTA). Unlike the traditional Markov approach, this technique provides a fast solution for large system reliability evaluation by managing computer memory efficiently with iterators, assuming a single failure at a time. A reconfiguration for restoration algorithm is also created to enhance the accuracy of the reliability evaluation, considering multiple concurrent failures. As opposed to most restoration simulation methods used in reliability analysis, which convert restoration problems into mathematical models and only can solve radial systems, this new algorithm seeks the reconfiguration solution from topology characteristics of the network itself. As a result the new reconfiguration algorithm can handle systems with loops. In analyzing system reliability, this research takes into account time-varying load patterns, and seeks approaches that are financially justified. An exhaustive search scheme is used to calculate optimal locations for Distributed Generators (DG) from the reliability point of view. A Discrete Ascent Optimal Programming (DAOP) load shifting approach is proposed to provide low cost, reliability improvement solutions. As weather conditions have an important effect on distribution component failure rates, the influence of different types of storms has been incorporated into this study. Storm outage models are created based on ten years' worth of weather and power outage data. An observer is designed to predict the number of outages for an approaching or on going storm. A circuit corridor model is applied to investigate the relationship between power outages and lightning activity. / Ph. D.

Animals learn from past experience to guide future behavior and improve survival. This ability relies in part on specific episodic memories of past events encoded by neuronal activity and stored by updated connectivity between neurons. The unique architecture and activity of the hippocampus and related cortical regions are crucial for supporting these episodic memories. Hippocampal models propose the need for a pattern separation function to disambiguate similar memories and a pattern completion function to recall the full breadth of an experience from a partial cue. Past work suggests that neuronal activity in the dentate gyrus (DG) of hippocampus contributes to memory-guided navigation and plays a role in pattern separation. We tested the role of specific DG neuronal ensembles (i.e. engrams) in supporting the pattern separation function and altering downstream neural activity and, ultimately, behavior. To that end, we used an activity-dependent labeling paradigm to identify and manipulate engram ensembles during navigational and contextual fear conditioning (CFC) tasks. The results of our first experiment revealed that the DG partially disambiguates specific maze trajectories while still exhibiting greater overlap than chance levels. These findings suggest that the DG contributes to memory-guided navigation by both pattern separation and completion. Our second experiment manipulated nonspecific memory-related DG populations to assess the functional role of these cells in task generalization across contexts and ongoing spatial working memory. Optogenetic activation of these ensembles disrupted performance accuracy and exhibited a time-dependent impairment effect suggesting a role of the DG in task generalization between contexts. The final experiments investigated the physiological ramifications of artificial memory ensemble reactivation during ongoing navigation behavior. We recorded local field potential (LFP) and single unit responses in mouse DG and CA1 during artificial reactivation of a DG-mediated CFC memory engram. Stimulation of the DG entrained LFP and individual cell spiking in a subpopulation of CA1 pyramidal cells. Their spatial information was disrupted by stimulation despite stable navigational representation before and after the manipulation. Further, the presence of stimulation could be reliably decoded by the firing rate of the network, suggesting that engram reactivation forced the CA1 to adopt a repeatable state, perhaps to support behavioral expression of memories. In summary, my dissertation work presents empirical and theoretical evidence for the role of the dentate gyrus as a single node of an extended separation/completion circuit distributed anatomically and temporally as a neural mechanism supporting episodic memory.

No description available.

Within the past decade, talk has arisen of shifting the utility grid from centralized, radial sources to a distributed network of sources, also known as distributed generation (DG); in the wake of deregulation, the California energy crisis, and northeastern blackouts. Existing control techniques for DG systems are designed to operate a system either in the connected or disconnected (islanding) mode to the utility; thus not allowing for both modes to be implemented and transitioned between. Existing detection and re-closure algorithms can also be improved upon. Dependent upon the method implemented, detection algorithms can either cause distortions in the output or completely miss a disturbance. The present re-closure process to reconnect to the utility is to completely shutdown and wait five minutes. The proposed methods of this study improve upon existing methods, via simulation and hardware experimentation, for DG systems that can intentionally islanding themselves. The proposed, "switched-mode", control allows for continuous operation of the system during disturbances by transitioning the mode of control to reflect the change in the system mode (grid-connected or islanding). This allows for zero downtimes without detrimental transients. The proposed detection method can sense disturbances that other methods cannot; and within 25 ms (approximately 1.5 line-cycles at 60 Hz). This method is an improvement over other methods because it eliminates the need to purposely distort the outputs to sense a disturbance. The proposed re-closure method is an improvement over the existing method due to the fact that it does not require the system to de-energize before re-synchronizing and reconnecting to the utility. This allows for DGs to continuously supply power to the system without having to shut down. Results show that the system is generally ready to reconnect after 2 to 5 line cycles. / Master of Science