Benchmark calculations for the validation of the coupled neutron kinetics/thermohydraulic code complex DYN3D-ATHLET are described. Two benchmark problems concerning hypothetical accident scenarios with leaks in the steam system for a VVER-440 type reactor and the TMI-1 PWR have been solved. The first benchmark task has been defined by FZR in the frame of the international association "Atomic Energy Research" (AER), the second exercise has been organised under the auspices of the OECD. While in the first benchmark the break of the main steam collector in the sub-critical hot zero power state of the reactor was considered, the break of one of the two main steam lines at full reactor power was assumed in the OECD benchmark. Therefore, in this exercise the mixing of the coolant from the intact and the defect loops had to be considered, while in the AER benchmark the steam collector break causes a homogeneous overcooling of the primary circuit. In the AER benchmark, each participant had to use its own macroscopic cross section libraries. In the OECD benchmark, the cross sections were given in the benchmark definition. The main task of both benchmark problems was to analyse the re-criticality of the scrammed reactor due to the overcooling. For both benchmark problems, a good agreement of the DYN3D-ATHLET solution with the results of other codes was achieved. Differences in the time of re-criticality and the height of the power peak between various solutions of the AER benchmark can be explained by the use of different cross section data. Significant differences in the thermohydraulic parameters (coolant temperature, pressure) occurred only at the late stage of the transient during the emergency injection of highly borated water. In the OECD benchmark, a broader scattering of the thermohydraulic results can be observed, while a good agreement between the various 3D reactor core calculations with given thermohydraulic boundary conditions was achieved. Reasons for the differences in the thermohydraulics were assumed in the difficult modelling of the vertical once-through steam generator with steam superheating. Sensitivity analyses which considered the influence of the nodalisation and the impact of the coolant mixing model were performed for the DYN3D-ATHLET solution of the OECD benchmark. The solution of the benchmarks essentially contributed to the qualification of the code complex DYN3D-ATHLET as an advanced tool for the accident analysis for both VVER type reactors and Western PWRs.

The Mre11/Rad50 complex has been implicated in the early steps of DNA double-strand break (DSB) repair through homologous recombination in several organisms. However, the enzymatic properties of this complex are incompatible with the generation of 3’ single-stranded DNA for recombinase loading and strand exchange. In thermophilic Archaea, the mre11 and rad50 genes cluster in an operon with genes encoding a bidirectional DNA helicase, HerA, and a 5’ to 3’ exonuclease, NurA, suggesting these four enzymes function in a common pathway. I show that purified Mre11 and Rad50 from Pyrococcus furiosus act cooperatively with HerA and NurA to resect the 5’ strand at a DNA end under physiological conditions in vitro where HerA and NurA alone do not show detectable activity. Furthermore, I demonstrate that HerA and NurA physically interact, and this interaction stimulates both helicase and nuclease activities. The products of HerA/NurA long-range resection are oligonucleotide products and HerA/NurA activity demonstrates both sequence specificity and a preference to cut at a specific distance from the DNA end. I demonstrate a novel activity of Mre11/Rad50 to make an endonucleolytic cut on the 5’ strand, which is consistent with a role for the Mre11 nuclease in the removal of 5’ protein conjugates. I also show that Mre11/Rad50 stimulates HerA/NurA-mediated resection through two different mechanisms. The first involves an initial Mre11 nucleolytic processing event of the DNA to generate a 3’ ssDNA overhang, which is then resected by HerA/NurA in the absence of Mre11/Rad50. The second mechanism likely involves local unwinding of the DNA end in a process dependent on Rad50 ATPase activity. I propose that this unwinding step facilitates binding of HerA/NurA to the DNA end and efficient resection of the break. Furthermore, the binding affinity of NurA for 3’ overhang and unwound DNA end substrates partially explains the efficiency of the two resection mechanisms. Lastly, 3’ single-stranded DNA generated by these enzymes can be used by the Archaeal RecA homolog RadA to catalyze strand exchange. This work elucidates how the conserved Mre11/Rad50 complex promotes DNA end resection in Archaea, and may serve as a model for DSB processing in eukaryotes. / text

Βασικός σκοπός της παρούσας εργασίας είναι η ανίχνευση και αποτύπωση των στοιχείων που συγκροτούν το ελεύθερο παιχνίδι των παιδιών στο διάλειμμα, σύμφωνα με τις θεωρητικές αρχές και τα μεθοδολογικά εργαλεία (παρατήρηση, καταγραφή και συνέντευξη) της εθνογραφίας. Συγκεκριμένα, μετά την παρατήρηση και καταγραφή των ελεύθερων δράσεων των παιδιών μιας ομάδας νηπιαγωγείου κατά τη διάρκεια του διαλείμματος, αναλύονται οι κατηγορίες και υποκατηγορίες παιχνιδιών όπως αυτές προέκυψαν από τα δεδομένα του υλικού μας και οι παράγοντες που επηρεάζουν αυτούς τους τύπους παιχνιδιών. Η έρευνά μας επιπρόσθετα εστιάζει και στις δυνατότητες εισαγωγής του παραδοσιακού ομαδικού παιχνιδιού ή στοιχείων αυτού στο ελεύθερο παιχνίδι των παιδιών στο διάλειμμα μετά την υλοποίηση μιας οργανωμένης από την εκπαιδευτικό-ερευνήτρια διδακτικής συνθήκης. Όπως προέκυψε από την ανάλυση της παρατήρησης που ακολούθησε την διεξαγωγή της διδακτικής παρέμβασης και των αποτελεσμάτων που αφορούν στη διεξαγωγή συνεντεύξεων από την εκπαιδευτικό-ερευνήτρια στα παιδιά, η αδυναμία εισαγωγής οργανωμένου παραδοσιακού ομαδικού παιχνιδιού ή στοιχείων αυτού στις ελεύθερες δράσεις των παιδιών είναι απόρροια ποικίλων παραγόντων που χρήζουν περαιτέρω διερεύνηση η οποία δεν μπορεί να εξαντληθεί στα όρια της παρούσας μελέτης. Σε κάθε περίπτωση η αξιοποίηση της εθνογραφίας για τη μελέτη του φαινομένου του παιχνιδιού σε σχέση με μία συγκεκριμένη ομάδα παιδιών νηπιαγωγείου θεωρούμε ότι προσφέρει πολύτιμα στοιχεία τόσο για την ίδια την εκπαιδευτικό-ερευνήτρια (αποκάλυψη πτυχών της εκπαιδευτικής πραγματικότητας), όσο γενικότερα και για τη μελέτη ενός σύνθετου φαινομένου, του παιδικού παιχνιδιού. / The main objective of this study is to detect and identify the components of children free play during break, according to the theoretical principles and methodological tools (observation, recording and interview) of ethnography. Specifically, after observation and recording of the free actions of a group of kindergarten children, during school break, the categories and subcategories of games that emerged and the factors that affect these types of games are being analyzed. The research also focuses on the possibility of introducing traditional team play or elements of it in children free play during the break within a set didactic project by the teacher - researcher. As resulted from the analysis of observation that followed the didactic intervention and outcomes related to interviews to children conducted by the teacher - researcher, the impossibility to introduce traditional team play or elements of it in the free activities of children is due to various factors that require further investigation which can not be exhausted within the limits of this study. In any case, the use of ethnography in the study of the phenomenon of play in relation to a specific group of kindergarten children is believed to provide valuable information both for the teacher - researcher (revealing aspects of the educational reality), as well as for the study of the complex phenomenon of children play.

Resulting from the deregulation and prosperity of the economic and financial sectors in Asia during 1980s, a significant increase in cross-bordered financial transactions ultimately accelerated the region of Southeast Asia to be on a process of financial integration and consequently diminished opportunities for portfolio diversification. Financial Integration is a multidimensional process through which allocation of financial assets becomes lastly borderless. This purpose of this paper is to examine a progress thus far in capital market integration or preferentially, the co-movement of the equity markets between the U.S. and the Southeast Asian nations: Thailand, Indonesia, Malaysia, and the Philippines by employing the methodology of Gregory and Hansen Cointegration and Error Correction Analysis (ECM). The consequence of the U.S. market performance on each Southeast Asian national markets are extensively analyzed by decomposing monthly price-index time series into three distinct sub-periods based on an occurrence of the Subprime Mortgage Financial Crisis in 2007. The results indicate that these four emerging markets had been considerable influenced by the U.S. market performance, regardless of crisis or non-crisis periods. Nevertheless, some countries like Indonesia and the Philippines acted differently during the pre-crisis and crisis sub-periods respectively due to their domestic market infrastructure and regulation adjustment. However, these two markets had eventually turned to share an interdependent long-run relationship with the U.S. equity market since the ending of the Subprime financial downturn. Moreover, this finding suggests that ongoing capital market integration in the Southeast Asian region would mitigate portfolio diversification benefits for investors by virtue of increasing in correlation among securities and assets. Therefore, more exhaustive investigation about equity market integration is significantly beneficial in macroeconomic and financial perspective.

Recently, Hudson Bay experienced unidirectional trends in temperature, sea-ice extent, time of break-up, and length of the open-water season. Predicted impacts on population dynamics of ice-associated species include habitat loss and shift in prey availability. The ringed seal (Phoca hispida) depends on a stable ice platform with sufficient snow depth and a productive open-water season for reproduction and survival. Evidence of ringed seal sensitivity to environmental variations has been reported, but mechanisms involved were poorly understood. In western Hudson Bay, density, life-history traits, and diet of ringed seals were monitored over two decades, providing an opportunity to understand the effects of climatic variations on the population dynamics of this long-lived carnivore. Ringed seal density was estimated through strip-transect analyses after aerial surveys were flown in western Hudson Bay in late spring during the annual moult in the 1990s and 2000s. During these periods, ringed seals were also sampled from Inuit subsistence fall harvests In Arviat, NU, and ages, reproductive status, percentage of pups in the harvest, body condition, and diet were assessed. Strong inter-annual variations in these parameters were observed, and a decadal cycle was suggested and related to variations in the sea-ice regime. The cold and heavy ice conditions that prevailed in western Hudson Bay in 1991-92 likely induced a decrease in pelagic productivity, reducing the availability to ringed seals of sand lances (Ammodytes sp.), their major prey. The nutritional stress endured, combined with a strong predation pressure, led to a decrease in ringed seal reproductive performances, pup survival, and density during the 1990s. The recovery of ringed seal demographic parameters and number in the 2000s was associated with the immigration of pups, juveniles, and young adults into western Hudson Bay. Impact of current climatic trends on ringed seal population dynamics was not apparent, but considering the limited range of environmental variations tolerated by ringed seals, the response of this species to climate warming might be of a catastrophic type. Ringed seals were found to be good indicators of ecosystem changes, and long-term monitoring of the species in Hudson Bay should be a priority.

In the doctoral dissertation, we consider problems of testing and estimating changed segment with unknown starting position and duration of epidemic state in the autoregressive first-order model. The proposed tests are based on partial sums of model residuals and model-parameter partial-estimator polygonal line processes. We derive asymptotic results for these processes in Holder spaces. The behavior of test statistics under the null hypothesis of no change and alternative is provided. Empirical power analysis has shown that tests are more powerful when absolute values of model parameter are quite large or autoregressive process changes from a stationary state to a nonstationary one. We prove the consistency of the least square changed-segment estimators and provide their convergence rates. / Disertacijoje nagrinėjamas pirmos eilės autoregresinio modelio pasikeitusio segmento testavimo ir vertinimo uždavinys. Aprašomo modelio epideminio pasikeitimo pradžia ir ilgis nėra žinomi. Pasiūlyti kriterijai pasikeitusio segmento testavimui, kurie pagrįsti modelio paklaidų įvertinių dalinių sumų ir modelio parametro dalinių įvertinių laužčių procesais. Šiems procesams gautos ribinės teoremos Hiolderio erdvėse. Nurodomas testų statistikų ribinis elgesys esant teisingai nulinei ir alternatyviajai hipotezėms. Iš empirinio kriterijų galios tyrimo rezultatų matyti, kad pasiūlytų testų galia didžiausia aptinkant pasikeitimus iš stacionarios būklės į nestacionarią arba esant artimoms vienetui modelio parametro reikšmėms. Taip pat įrodoma, kad mažiausių kvadratų metodu gauti pasikeitusio segmento pradžios ir ilgio įverčiai bei autoregresinio modelio su pasikeitusiu segmentu parametrų įverčiai yra suderintieji bei pateikiamas jų konvergavimo greitis.

Disertacijoje nagrinėjamas pirmos eilės autoregresinio modelio pasikeitusio segmento testavimo ir vertinimo uždavinys. Aprašomo modelio epideminio pasikeitimo pradžia ir ilgis nėra žinomi. Pasiūlyti kriterijai pasikeitusio segmento testavimui, kurie pagrįsti modelio paklaidų įvertinių dalinių sumų ir modelio parametro dalinių įvertinių laužčių procesais. Šiems procesams gautos ribinės teoremos Hiolderio erdvėse. Nurodomas testų statistikų ribinis elgesys esant teisingai nulinei ir alternatyviajai hipotezėms. Iš empirinio kriterijų galios tyrimo rezultatų matyti, kad pasiūlytų testų galia didžiausia aptinkant pasikeitimus iš stacionarios būklės į nestacionarią arba esant artimoms vienetui modelio parametro reikšmėms. Taip pat įrodoma, kad mažiausių kvadratų metodu gauti pasikeitusio segmento pradžios ir ilgio įverčiai bei autoregresinio modelio su pasikeitusiu segmentu parametrų įverčiai yra suderintieji bei pateikiamas jų konvergavimo greitis. / In the doctoral dissertation, we consider problems of testing and estimating changed segment with unknown starting position and duration of epidemic state in the autoregressive first-order model. The proposed tests are based on partial sums of model residuals and model-parameter partial-estimator polygonal line processes. We derive asymptotic results for these processes in Holder spaces. The behavior of test statistics under the null hypothesis of no change and alternative is provided. Empirical power analysis has shown that tests are more powerful when absolute values of model parameter are quite large or autoregressive process changes from a stationary state to a nonstationary one. We prove the consistency of the least square changed-segment estimators and provide their convergence rates.

Recently, Hudson Bay experienced unidirectional trends in temperature, sea-ice extent, time of break-up, and length of the open-water season. Predicted impacts on population dynamics of ice-associated species include habitat loss and shift in prey availability. The ringed seal (Phoca hispida) depends on a stable ice platform with sufficient snow depth and a productive open-water season for reproduction and survival. Evidence of ringed seal sensitivity to environmental variations has been reported, but mechanisms involved were poorly understood. In western Hudson Bay, density, life-history traits, and diet of ringed seals were monitored over two decades, providing an opportunity to understand the effects of climatic variations on the population dynamics of this long-lived carnivore. Ringed seal density was estimated through strip-transect analyses after aerial surveys were flown in western Hudson Bay in late spring during the annual moult in the 1990s and 2000s. During these periods, ringed seals were also sampled from Inuit subsistence fall harvests In Arviat, NU, and ages, reproductive status, percentage of pups in the harvest, body condition, and diet were assessed. Strong inter-annual variations in these parameters were observed, and a decadal cycle was suggested and related to variations in the sea-ice regime. The cold and heavy ice conditions that prevailed in western Hudson Bay in 1991-92 likely induced a decrease in pelagic productivity, reducing the availability to ringed seals of sand lances (Ammodytes sp.), their major prey. The nutritional stress endured, combined with a strong predation pressure, led to a decrease in ringed seal reproductive performances, pup survival, and density during the 1990s. The recovery of ringed seal demographic parameters and number in the 2000s was associated with the immigration of pups, juveniles, and young adults into western Hudson Bay. Impact of current climatic trends on ringed seal population dynamics was not apparent, but considering the limited range of environmental variations tolerated by ringed seals, the response of this species to climate warming might be of a catastrophic type. Ringed seals were found to be good indicators of ecosystem changes, and long-term monitoring of the species in Hudson Bay should be a priority.

A return-period analysis of annual peak spring break-up and open-water levels for 136 Water Survey of Canada hydrometric stations was used to classify rivers across Canada and to assess the physical controls on peak break-up water-levels. According to the peak water-level river-regime classification and subsequent analysis, 32% of rivers were classified as spring break-up dominated, characterized by low elevations and slopes and large basin sizes while 45% were open-water dominated and associated with alpine environments of high elevations and channel slopes, and smaller basin sizes. The remaining 23% of rivers were classified as a mixed regime. A spatial and temporal analysis (1969-2006) of the river ice break-up season using hydrometric variables of timing and water levels, never before assessed at the northern Canada-wide scale, revealed significant declines in break-up water levels and significant trends towards earlier and prolonged break-up in western and central Canada. The spatial and temporal influence of air temperature on break-up timing was assessed using the spring 0°C isotherm, which revealed a significant positive relationship but no spatial patterns. In the case of major ocean/atmosphere oscillations, significant negative (positive) correlations indicate that break-up occurs earlier (later) during the positive phases of the Pacific North American Pattern (El Niño Southern Oscillation) over most of western Canada. Fewer significant positive correlations show that break-up occurs later during the positive phases of the Arctic Oscillation and North Atlantic Oscillation in eastern Canada. / Graduate

Les cassures Double-brin de l'ADN (DSBs) sont une menace majeure pour la stabilité du génome. Afin de se protéger des effets délétères de ces dommages, les cellules activent une voie de réponse aux cassures double-brins (DDR) qui comprend des évènements qui conduisent à la reconnaissance et à la réparation de ces cassures ainsi qu'à un délai du cycle cellulaire. Cette DDR repose largement sur 2 membres de la famille des PI3K-like kinase, ataxia telangiectasia mutated (ATM) et DNA Protein Kinase (DNAPK) dont les fonctions respectives lors de la réparation restent controversées. Grâce à l'utilisation d'une lignée cellulaire contenant l'enzyme de restriction AsiSI combinée à de la cartographie par ChIP-chip, de l'analyse de la réparation de cassures séquence-spécifique ainsi qu'à de la microscopie haute résolution, j'ai pu, au cours de ma thèse mettre en évidence que aussi bien ATM que DNAPK sont recrutées sur une région confinée autour des DSBs. Cependant, une fois recrutées, elles présentent des fonctions non-redondantes que ce soit pour la ligation des cassures ou pour l'établissement des domaines yH2AX. Concernant la réparation, DNAPK est absolument requise pour la ligation des extrémités de la cassure alors que ATM est dispensable mais promeut la fidélité. En revanche, ATM est la principale kinase requise pour l'établissement des domaines yH2AX et ce quelque soit la cassure. J'ai aussi pu mettre en évidence le fait que plusieurs cassures induites par AsiSI sont capables de se regrouper au sein d'un "foyer de réparation" et ce de manière dépendante d'ATM et indépendante de DNAPK. Cette étude éclaircit les rôles respectifs des kinases ATM et DNAPK que ce soit pour la ligation des extrémités ou l'établissement des domaines yH2AX. Enfin elle a permis de mettre en évidence un nouveau rôle d'ATM dans l'organisation spatiale de la réparation et plus précisemment dans le regroupement de plusieurs DSBs au sein de "foyers de réparation" afin d'être réparées. / DNA Double Strand Breaks (DSBs) form a major threat to the genome stability. To circumvent the deleterious effects of DSBs, cells activate the DNA damage response (DDR), which comprises events that lead to detection and repair of these lesions, as well as a delay in cell cycle progression. This DDR largely rely on two members of the PI3K-like kinase family : ataxia telangiectasia mutated (ATM) and DNA Protein Kinase (DNAPK), whose respective functions during the DDR remains controversial. Using a cell line, expressing the AsiSI restriction enzyme, combined with high resolution ChIP-chip mapping, sequence-specific DSB repair kinetics analysis and advanced high resolution microscopy, we uncovered that both ATM and DNA-PK are recruited to a confined region surrounding DSBs. However, once present at the DSB site, they exhibit non-overlapping functions on end-joining and yH2AX domain establishment. At the repair level, DNAPK is absolutely required for end-joining while ATM is dispensable although promoting repair fidelity. By contrast, ATM is the main kinase required for the establishment of the histone mark yH2AX at all breaks. We also clearly demonstrated that multiple AsiSI-induced DSBs are able to associate within "repair foci", in a manner that strictly depends on ATM, but not DNAPK, activity. Our study shed light on the respective roles of ATM and DNAPK regarding end joining and yH2AX domain establishment. Lastly it allowed us to uncover a function of ATM in the spatial organisation of the repair, more precisely in the clustering of multiple breaks within "repair foci" in order to be repaired.