The development of a "good" information system relies heavily on the designer's (or project leader's) understanding of the system's boundaries and environment within the organization, and the ability to derive an appropriate model of the system. This report presents an overview of the systems appproach to organizational theory and information systems development, and examines one computer supported analysis and documentation tool, PSL/PSA. The report also shows that this tool, PSL/PSA, is not only able to represent such a systems view, but that it is also valuable as an aid, in terms of modeling, to other techniques which try to reach these goals. The examination of PSL/PSA is followed with two examples showing how it is applied to the BIAIT BICMX and Structured Analysis. / Thesis / Master of Science (MSc)

Safety and risk assessment are key priorities for nuclear power plants. Probabilistic risk assessment (PRA) is a method for quantitative evaluation of accident risk, in particular severe nuclear core damage and the associated release of radioactive materials into the environment. The reliability and certainty of PRA have at times been questioned, especially when real-world observations have indicated that the frequency of nuclear accidents is higher than the probabilities predicted by PRA. This thesis provides a philosophical review of the epistemic uncertainties in PRA, using the Fukushima Daiichi accident of March 2011 as a case study. The thesis provides an overview of the PRA model structure, its key elements, and possible sources of uncertainty, in an attempt to understand the deviation between the real frequency of nuclear core-melt accidents and the probabilities predicted by PRA.The analyses in this thesis address several sources of epistemic uncertainty in PRA. Analyses of the PRA approach reveal the difficulty involved in covering all possible initiating events, all component and system failures, as well as their possible combinations in the risk evaluations. This difficulty represents the source of a characteristic epistemic uncertainty, referred to as completeness uncertainty. Analyses from the case study (the Fukushima Daiichi accident) illustrate this difficulty, as the PRA failed to identify a combined earthquake and tsunami, with the resultant flooding and consequent power failure and total blackout, as an initiating causal event in its logic structure.The analyses further demonstrate how insufficient experience and knowledge, as well as a lack of empirical data, lead to incorrect assumptions, which are used by the model as input parameters to estimate the probabilities of accidents. With limited availability of input data, decision-makers rely upon the subjective judgements and individual experiences of experts, which adds a further source of epistemic uncertainty to the PRA, usually referred to as input parameter uncertainty. As a typical example from the case study, the Fukushima Daiichi accident revealed that the PRA had underestimated the height of a possible tsunami. Consequently, the risk mitigation systems (e.g. the barrier seawalls) built to protect the power plant were inadequate due to incorrect input data.Poor assumptions may also result in improper modeling of failure modes and sequences in the PRA logic structure, which makes room for an additional source of epistemic uncertainty referred to as model uncertainty. For instance, the Fukushima Daiichi accident indicated insufficient backup of the power supply, because the possibility of simultaneous failure of several emergency diesel generators was assumed to be negligibly small. However, that was exactly what happened when 12 out of the 13 generators failed at the same time as a result of flooding.Furthermore, the analyses highlight the difficulty of modeling the human interventions and actions, in particular during the course of unexpected accidents, taking into account the physiological and psychological effects on the cognitive performance of humans, which result in uncertain operator interventions. This represents an additional source of epistemic uncertainty, usually referred to as uncertainty in modeling human interventions. As a result, there may be an increase in the probability of human error, characterized by a delay in making a diagnosis, formulating a response and taking action. Even this statement confirms the complexity of modelling human errors. In the case of the Fukushima Daiichi accident, lack ofvsufficient instructions for dealing with this "unexpected" accident made the coordination of operators' interventions almost impossible.Given the existence of all these sources of epistemic uncertainty, it would be reasonable to expect such a detected deviation between the real frequency of nuclear core-melt accidents and the probabilities predicted by PRA.It is, however, important to highlight that the occurrence of the Fukushima Daiichi accident could lie within the uncertainty distribution that the PRA model predicted prior to the accident. Hence, from the probabilistic point of view, the occurrence of a single unexpected accident should be interpreted with care, especially in political and commercial debates. Despite the limitations that have been highlighted in this thesis, the model still can provide valuable insights for systematic examination of safety systems, risk mitigation approaches, and strategic plans aimed at protecting the nuclear power plants against failures. Nevertheless, the PRA model does have development potentials, which deserves serious attention. The validity of calculated frequencies in PRA is restricted to the parameter under study. This validity can be improved by adding further relevant scenarios to the PRA, improving the screening approaches and collecting more input data through better collaboration between nuclear power plants world-wide. Lessons learned from the Fukushima Daiichi accident have initiated further studies aimed at covering additional scenarios. In subsequent IAEA safety report series, external hazards in multi-unit nuclear power plants have been considered. Such an action shows that PRA is a dynamic approach that needs continuous improvement toward better reliability.

No description available.

No description available.

No description available.

Nuclear power is an important part of Sweden's energy system and contributes with about 30 % of the supplied electric energy. Interest in new construction is currently high and one type of reactor that may be built is small modular reactors, SMRs. A method that is used to evaluate the safety of a traditional nuclear power plant is the so called probabilistic safety assessment (PSA). An important question is if PSA is applicable to SMRs. This thesis examines differences between a BWRX-300 type SMR and a generic boiling water reactor to investigate if the traditional PSA method is applicable to SMRs and what characteristics that may affect the results.  To investigate the topic, a simplified PSA analysis is carried out at level 1 for five different initiating events: extreme snowfall, loss of cooling accident, loss of main feedwater, loss of offsite power supply and transient. These are then compared to a model of a generic BWR reactor.  The conclusions that emerge from the analysis are that the traditional PSA method can be applied for SMRs of the BWRX-300 type. The features that distinguish the BWRX-300 compared to a generic BWR are mainly that the SMR is smaller in size and power and the influence of the passive safety systems. This results in a lower core damage frequency. Some the areas where the PSA method could be developed for SMRs are the analysis of passive components and passive functions.

Plusieurs cancers sont associés à des concentrations sériques anormales de marqueurs tumoraux, tels que le prostate specific antigen (PSA) dans le cancer de prostate, l’alfafoetoproteine (AFP) ou l’human chorionic gonadotrophin (hCG) dans les tumeurs germinales ou les maladies trophoblastiques gestationnelles (MTG). Le traitement du cancer doit s’accompagner d’une chute de leurs concentrations. Les valeurs prédictives de nombreux paramètres cinétiques censés caractériser la décroissance des marqueurs ont été publiées dans la littérature (nadir, valeur seuil, demi-vie, temps à normalisation etc…) Cependant très peu de ces paramètres sont utilisés en pratique par manque de reproductibilité. La modélisation en approche de cinétique de population, déjà utilisée dans les études pharmacocinétiques, permettrait de caractériser de façon dynamique la décroissance des marqueurs tumoraux sériques et de compenser les limites des autres méthodes. Nous avons étudié la faisabilité et l’intérêt de cette approche dans 4 études portant sur le PSA après chirurgie d’adénome ou de cancer de la prostate, l’hCG-AFP dans les tumeurs germinales non-séminomateuses traitées par polychimiothérapie de type Bléomycine-Etoposide- Cisplatine (BEP) et l’hCG dans les MTG traitées par méthotrexate. La modélisation de la décroissance des marqueurs tumoraux a été possible dans toutes les études en adaptant la méthodologie aux spécificités de chaque marqueur. Il apparaît que les clairances apparentes du PSA et de l’hCG permettraient d’identifier les patients ayant des profils cinétiques défavorables et donc à haut risque de rechute. Des études de validation sur des cohortes indépendantes sont nécessaires / Several cancers are associated with abnormal serum concentrations of tumor markers such as prostate specific antigen (PSA) in prostate tumor diseases, alfa-fetoprotein (AFP) or human chorionic gonadotrophin (hCG) in germ cell tumors or persistent gestational trophoblastic diseases (GTD). Cancer treatment should induce decline of serum tumor marker concentrations. The predictive values of many kinetic parameters supposed to characterize tumor marker declines such as nadir, time-point cutoff, half-life, time to normalization etc…, have been reported in previous studies. However very few of them have been used in routine due to the lack of outcome reproducibility. Population pharmacokinetic approach-based modeling is already used in pharmacokinetic studies. It might be helpful to characterize tumor marker decline equations dynamically and overcome limitations of previous studies. The feasibility and the relevance of this approach were assessed in 4 studies involving: PSA titers in patients with prostate adenoma or cancer treated with surgery; hCG-AFP in non-seminomatous germ cell tumor patients treated with BEP regimen (Bleomycin-Etoposide-Cisplatin) and hCG in GTD patients treated with methotrexate. Tumor marker decline modeling was feasible in all studies provided the methodology was adjusted to marker specificities. Apparent clearance of hCG and PSA might enable identification of patients with unfavorable decline profiles and thereby with high risk of relapse. Confirmatory studies with independent cohorts of patients are warranted

Within the safety analysis industry there are a variety of tools used to ensure reliability and security of systems, ranging from mostly qualitative approaches to mostly quantitative. One safety analysis method that lies in between these two is called Layers Of Protection Analysis (LOPA). LOPA is known as a “semi-quantitative” approach that uses a mix of quantitative and qualitative approaches to draw conclusions. In this masters thesis the LOPA approach is demonstrated, in addition to being developed into two alternate LOPA approaches, known as MarkovLOPA and RBDLOPA. These two developed approaches use the concept of Markov chains and Reliability block diagram (RBD) respectively, to extend the applicability of the traditional LOPA methodology. Furthermore, a conventional hydraulic braking system (CHB), which includes ABS/TCS- and ESP functionality was analysed by these three methodologies. The results of the analysis show that in the analysis by LOPA and RBDLOPA 4- and 3 out of 10 scenarios need slight improvements and only 1 scenario for MarkovLOPA. Additionally, the validity of the alternative approaches are analysed by a sensitivity analysis, showing irregularities in the results, leading to the conclusion that further research and development is required prior to industrial applications of the approaches.

Made available in DSpace on 2014-08-20T14:25:48Z (GMT). No. of bitstreams: 1 capa_gustavo_silva.pdf: 18556 bytes, checksum: 0dbba1e8aa0d3a9e07f94e8b68dc1b9f (MD5) Previous issue date: 2009-06-24 / On certain occasions the State of Rio Grande do Sul is affected by atypical weather systems events which are among the category of mesoscale phenomena. The inability of large scale numerical models to appropriately simulate several localized effects, which occurs over the most varied regions, associated to the fast increase of computational resources, it is facilitating and increasingly inducing the use of mesoscale models to improve the knowledge on those anomalous and severe events and even for use as a necessary and indispensable operational tool. The skill of mesoescala model to proceed in providing precipitation forecasts, in space and time scale compatible with to those of a Doppler meteorological radar, it is implemented the whole system of mesoscale modeling that constitutes the MM5. The occurrence of the relatively severe precipitation event, in the area close to the city of Canguçu / RS, on January 11, 2008 was arbitrarily selected to evaluate the model skill - in inferring the reflectivity of the meteorological radar, installed in Canguçu / RS proceeding with conventional data assimilations, PCA (Processing With Assimilation) and PSA (Processing Without Assimilation), as well an approach to the analysis of the thermo-hydrodynamics and synoptic conditions. / Em certas ocasiões o Estado do Rio Grande do Sul é assolado por sistemas meteorológico com manifestações atmosféricas atípicas e que se enquadram entre os fenômenos de mesoescala. A impossibilidade de modelos numéricos de grande escala simularem adequadamente diversos efeitos localizados, que ocorrem nas mais variadas regiões, associada ao rápido aumento dos recursos computacionais, vem facilitando e crescentemente induzindo o emprego de modelos de mesoescala para melhorar os conhecimentos sobre esses eventos anômalos e severos e até mesmo para utilização como uma ferramenta operacional necessária e imprescindível. Para se proceder a destreza de um modelo de mesoescala em prover previsões de precipitação, em escala espacial e temporal compatível com àquelas de um radar meteorológico Doppler, é implantado todo o sistema de modelagem de mesoescala que constitui o MM5. A ocorrência do evento relativamente severo de precipitação, na região próxima da cidade de Canguçu/RS, do dia 11 de janeiro de 2008 foi arbitrariamente selecionada para avaliação do modelo - em inferir a refletividade do radar meteorológico instalado na cidade de Canguçu/RS - com os processamentos PCA (Processamento Com Assimilação) e PSA (Processamento Sem Assimilação) de dados convencionais e abordagem da análise da situação termo-hidrodinâmica e sinótica.

The inhibitor of DNA binding protein 4 (ID4) is a dominant negative regulator of basic helix loop helix (bHLH) family of transcription factors.1 Recently, Patel et al., demonstrated that inhibitor of differentiation 4 (ID4) acts as a tumor suppressor and its loss, frequently observed in prostate cancer, promotes castration-resistant prostate cancer (CRPC) through constitutive androgen receptor (AR) activation.2 However, the mechanism by which loss of ID4 promotes constitutively active AR signaling in the CRPC conditions is unknown. The rationale of the present study was to unravel the underlying molecular mechanisms through which loss of ID4 potentiates AR signaling in this setting. Initially, chromatin immunoprecipitation (ChIP) assay results demonstrated a significant increase in binding of AR to its respective response elements on PSA, FKBP51, TMPRSS2, and ETV1 promoters in L(-)ID4 cells, further implicating constitutive AR activity. Among the notable findings, proteomic profiling between prostate cancer cell line LNCaP (L+ns) and LNCaP lacking ID4 (L(-)ID4) revealed elevated protein levels of Heat shock protein 27 (Hsp27) and the 52-kDa FK506-binding protein (FKBP52), suggesting a role for these AR-associated co-chaperones in promoting constitutively active AR signaling in L(-)ID4 cells. Interestingly, protein interaction studies further confirmed a direct interaction between ID4 and FKBP52 in vitro but not with AR. Recent evidences suggest that FKBP52 is a positive regulator of AR signaling in cellular and whole animal models.3-6 Thus, we hypothesized that ID4 acts as a tumor suppressor by selectively regulating AR activity through interaction with FKBP52. To address the underlying mechanism, we blocked the FKBP52-AR signaling using a specific inhibitory compound known as MJC13.4, 6-7 The results demonstrated that MJC13 effectively inhibited AR-dependent expression and activity in a dose-dependent manner. In addition, xenograft studies further confirmed that inhibiting FKBP52-regulated AR activity via MJC13 significantly attenuated the growth of subcutaneous L(-)ID4 xenografts in vivo. Collectively, our results suggested that ID4 selectively regulates AR activity through direct interaction with FKBP52 in vitro, and, its loss promotes CRPC through FKBP52-mediated AR signaling. Increased AR signaling along with a subsequent decrease in ID4 expression levels in prostate cancer strongly supports this model.