12 resultados para special functions
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Due to usage conditions, hazardous environments or intentional causes, physical and virtual systems are subject to faults in their components, which may affect their overall behaviour. In a black-box agent modelled by a set of propositional logic rules, in which just a subset of components is externally visible, such faults may only be recognised by examining some output function of the agent. A (fault-free) model of the agents system provides the expected output given some input. If the real output differs from that predicted output, then the system is faulty. However, some faults may only become apparent in the system output when appropriate inputs are given. A number of problems regarding both testing and diagnosis thus arise, such as testing a fault, testing the whole system, finding possible faults and differentiating them to locate the correct one. The corresponding optimisation problems of finding solutions that require minimum resources are also very relevant in industry, as is minimal diagnosis. In this dissertation we use a well established set of benchmark circuits to address such diagnostic related problems and propose and develop models with different logics that we formalise and generalise as much as possible. We also prove that all techniques generalise to agents and to multiple faults. The developed multi-valued logics extend the usual Boolean logic (suitable for faultfree models) by encoding values with some dependency (usually on faults). Such logics thus allow modelling an arbitrary number of diagnostic theories. Each problem is subsequently solved with CLP solvers that we implement and discuss, together with a new efficient search technique that we present. We compare our results with other approaches such as SAT (that require substantial duplication of circuits), showing the effectiveness of constraints over multi-valued logics, and also the adequacy of a general set constraint solver (with special inferences over set functions such as cardinality) on other problems. In addition, for an optimisation problem, we integrate local search with a constructive approach (branch-and-bound) using a variety of logics to improve an existing efficient tool based on SAT and ILP.
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The extensional process affecting Iberia during the Triassic and Jurassic times change from the end of the Cretaceous and, throughout the Palaeocene, the displacement between the African and European plates was clearly convergent and part of the future Internal Zone of the Betic Cordillera was affected. To the west, the Atlantic continued to open as a passive margin and, to the north, no significant deformation occurred. During the Eocene, the entire Iberian plate was subjected to compression. which caused major deformations in the Pyrenees and also in the Alpujarride and Nevado-Filabride, Internal Betic, complexes. In the Oligocene continued this situation, but in addition, the new extensional process ocurring in the western Mediterranean area, together with the constant eastward drift of Iberia due to Atlantic opening, compressed the eastern sector of Iberia, giving rise to the structuring of the Iberian Cordillera. The Neogene was the time when the Betic Cordillera reached its fundamental features with the westward displacement of the Betic-Rif Internal Zone, expelled by the progressive opening of the Algerian Basin, opening prolonged till the Alboran Sea. From the late Miocene onwards, all Iberia was affected by a N-S to NNW-SSE compression, combined in many points by a near perpendicular extension. Specially in eastern and southern Iberia a radial extension superposed these compression and extension.
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Dissertation presented at Universidade Nova de Lisboa, Faculdade de Cincias e Tecnologia in fulfilment of the requirements for the Masters degree in Mathematics and Applications, specialization in Actuarial Sciences, Statistics and Operations Research
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Dissertation presented to obtain the Ph.D degree in Biochemisry, Biotechnology
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Dissertation presented to obtain the Ph.D degree in Biology.
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RESUMO: A estrutura demogrfica portuguesa marcada por baixas taxas de natalidade e mortalidade, onde a populao idosa representa uma fatia cada vez mais representativa, fruto de uma maior longevidade. A incidncia do cancro, na sua generalidade, maior precisamente nessa classe etria. A par de outras doenas igualmente lesivas (e.g. cardiovasculares, degenerativas) cuja incidncia aumenta com a idade, o cancro merece relevo. Estudos epidemiolgicos apresentam o cancro como lder mundial na mortalidade. Em pases desenvolvidos, o seu peso representa 25% do nmero total de bitos, percentagem essa que mais que duplica noutros pases. A obesidade, a baixa ingesto de frutas e vegetais, o sedentarismo, o consumo de tabaco e a ingesto de lcool, configuram-se como cinco dos fatores de risco presentes em 30% das mortes diagnosticadas por cancro. A nvel mundial e, em particular no Sul de Portugal, os cancros do estmago, recto e clon apresentam elevadas taxas de incidncia e de mortalidade. Do ponto de vista estritamente econmico, o cancro a doena que mais recursos consome enquanto que do ponto de vista fsico e psicolgico uma doena que no limita o seu raio de ao ao doente. O cancro , portanto, uma doena sempre atual e cada vez mais presente, pois reflete os hbitos e o ambiente de uma sociedade, no obstante as caractersticas intrnsecas a cada indivduo. A adoo de metodologia estatstica aplicada modelao de dados oncolgicos , sobretudo, valiosa e pertinente quando a informao oriunda de Registos de Cancro de Base Populacional (RCBP). A pertinncia justificada pelo fato destes registos permitirem aferir numa populao especfica, o risco desta sofrer e/ou vir a sofrer de uma dada neoplasia. O peso que as neoplasias do estmago, clon e recto assumem foi um dos elementos que motivou o presente estudo que tem por objetivo analisar tendncias, projees, sobrevivncias relativas e a distribuio espacial destas neoplasias. Foram considerados neste estudo todos os casos diagnosticados no perodo 1998-2006, pelo RCBP da regio sul de Portugal (ROR-Sul). O estudo descritivo inicial das taxas de incidncia e da tendncia em cada uma das referidas neoplasias teve como base uma nica varivel temporal - o ano de diagnstico - tambm designada por perodo. Todavia, uma metodologia que contemple apenas uma nica varivel temporal limitativa. No cancro, para alm do perodo, a idade data do diagnstico e a coorte de nascimento, so variveis temporais que podero prestar um contributo adicional na caracterizao das taxas de incidncia. A relevncia assumida por estas variveis temporais justificou a sua incluso numaclasse de modelos designada por modelos Idade-Perodo-Coorte (Age-Period-Cohort models - APC), utilizada na modelao das taxas de incidncia para as neoplasias em estudo. Os referidos modelos permitem ultrapassar o problema de relaes no lineares e/ou de mudanas sbitas na tendncia linear das taxas. Nos modelos APC foram consideradas a abordagem clssica e a abordagem com recurso a funes suavizadoras. A modelao das taxas foi estratificada por sexo. Foram ainda estudados os respectivos submodelos (apenas com uma ou duas variveis temporais). Conhecido o comportamento das taxas de incidncia, uma questo subsequente prende-se com a sua projeo em perodos futuros. Porm, o efeito de mudanas estruturais na populao, ao qual Portugal no alheio, altera substancialmente o nmero esperado de casos futuros com cancro. Estimativas da incidncia de cancro a nvel mundial obtidas a partir de projees demogrficas apontam para um aumento de 25% dos casos de cancro nas prximas duas dcadas. Embora a projeo da incidncia esteja associada a alguma incerteza, as projees auxiliam no planeamento de polticas de sade para a afetao de recursos e permitem a avaliao de cenrios e de intervenes que tenham como objetivo a reduo do impacto do cancro. O desconhecimento de projees da taxa de incidncia destas neoplasias na rea abrangida pelo ROR-Sul, levou utilizao de modelos de projeo que diferem entre si quanto sua estrutura, linearidade (ou no) dos seus coeficientes e comportamento das taxas na srie histrica de dados (e.g. crescente, decrescente ou estvel). Os referidos modelos pautaram-se por duas abordagens: (i)modelos lineares no que concerne ao tempo e (ii) extrapolao de efeitos temporais identificados pelos modelos APC para perodos futuros. Foi feita a projeo das taxas de incidncia para os anos de 2007 a 2010 tendo em conta o gnero, idade e neoplasia. ainda apresentada uma estimativa do impacto econmico destas neoplasias no perodo de projeo. Uma questo pertinente e habitual no contexto clnico e a que o presente estudo pretende dar resposta, reside em saber qual a contribuio da neoplasia em si para a sobrevivncia do doente. Nesse sentido, a mortalidade por causa especfica habitualmente utilizada para estimar a mortalidade atribuvel apenas ao cancro em estudo. Porm, existem muitas situaes em que a causa de morte desconhecida e, mesmo que esta informao esteja disponvel atravs dos certificados de bito, no fcil distinguir os casos em que a principal causa de morte devida ao cancro. A sobrevivncia relativa surge como uma medida objetiva que no necessita do conhecimento da causa especfica da morte para o seu clculo e dar-nos- uma estimativa da probabilidade de sobrevivncia caso o cancro em anlise, num cenrio hipottico, seja a nica causa de morte. Desconhecida a principal causa de morte nos casos diagnosticados com cancro no registo ROR-Sul, foi determinada a sobrevivncia relativa para cada uma das neoplasias em estudo, para um perodo de follow-up de 5 anos, tendo em conta o sexo, a idade e cada uma das regies que constituem o registo. Foi adotada uma anlise por perodo e as abordagens convencional e por modelos. No eplogo deste estudo, analisada a influncia da variabilidade espao-temporal nas taxas de incidncia. O longo perodo de latncia das doenas oncolgicas, a dificuldade em identificar mudanas sbitas no comportamento das taxas, populaes com dimenso e riscos reduzidos, so alguns dos elementos que dificultam a anlise da variao temporal das taxas. Nalguns casos, estas variaes podem ser reflexo de flutuaes aleatrias. O efeito da componente temporal aferida pelos modelos APC d-nos um retrato incompleto da incidncia do cancro. A etiologia desta doena, quando conhecida, est associada com alguma frequncia a fatores de risco tais como condies socioeconmicas, hbitos alimentares e estilo de vida, atividade profissional, localizao geogrfica e componente gentica. O contributo, dos fatores de risco , por vezes, determinante e no deve ser ignorado. Surge, assim, a necessidade em complementar o estudo temporal das taxas com uma abordagem de cariz espacial. Assim, procurar-se- aferir se as variaes nas taxas de incidncia observadas entre os concelhos inseridos na rea do registo ROR-Sul poderiam ser explicadas quer pela variabilidade temporal e geogrfica quer por fatores socioeconmicos ou, ainda, pelos desiguais estilos de vida. Foram utilizados os Modelos Bayesianos Hierrquicos Espao-Temporais com o objetivo de identificar tendncias espao-temporais nas taxas de incidncia bem como quantificar alguns fatores de risco ajustados influncia simultnea da regio e do tempo. Os resultados obtidos pela implementao de todas estas metodologias considera-se ser uma mais valia para o conhecimento destas neoplasias em Portugal.------------ABSTRACT: mortality rates, with the elderly being an increasingly representative sector of the population, mainly due to greater longevity. The incidence of cancer, in general, is greater precisely in that age group. Alongside with other equally damaging diseases (e.g. cardiovascular,degenerative), whose incidence rates increases with age, cancer is of special note. In epidemiological studies, cancer is the global leader in mortality. In developed countries its weight represents 25% of the total number of deaths, with this percentage being doubled in other countries. Obesity, a reduce consumption of fruit and vegetables, physical inactivity, smoking and alcohol consumption, are the five risk factors present in 30% of deaths due to cancer. Globally, and in particular in the South of Portugal, the stomach, rectum and colon cancer have high incidence and mortality rates. From a strictly economic perspective, cancer is the disease that consumes more resources, while from a physical and psychological point of view, it is a disease that is not limited to the patient. Cancer is therefore na up to date disease and one of increased importance, since it reflects the habits and the environment of a society, regardless the intrinsic characteristics of each individual. The adoption of statistical methodology applied to cancer data modelling is especially valuable and relevant when the information comes from population-based cancer registries (PBCR). In such cases, these registries allow for the assessment of the risk and the suffering associated to a given neoplasm in a specific population. The weight that stomach, colon and rectum cancers assume in Portugal was one of the motivations of the present study, that focus on analyzing trends, projections, relative survival and spatial distribution of these neoplasms. The data considered in this study, are all cases diagnosed between 1998 and 2006, by the PBCR of Portugal, ROR-Sul.Only year of diagnosis, also called period, was the only time variable considered in the initial descriptive analysis of the incidence rates and trends for each of the three neoplasms considered. However, a methodology that only considers one single time variable will probably fall short on the conclusions that could be drawn from the data under study. In cancer, apart from the variable period, the age at diagnosis and the birth cohort are also temporal variables and may provide an additional contribution to the characterization of the incidence. The relevance assumed by these temporal variables justified its inclusion in a class of models called Age-Period-Cohort models (APC). This class of models was used for the analysis of the incidence rates of the three cancers under study. APC models allow to model nonlinearity and/or sudden changes in linear relationships of rate trends. Two approaches of APC models were considered: the classical and the one using smoothing functions. The models were stratified by gender and, when justified, further studies explored other sub-models where only one or two temporal variables were considered. After the analysis of the incidence rates, a subsequent goal is related to their projections in future periods. Although the effect of structural changes in the population, of which Portugal is not oblivious, may substantially change the expected number of future cancer cases, the results of these projections could help planning health policies with the proper allocation of resources, allowing for the evaluation of scenarios and interventions that aim to reduce the impact of cancer in a population. Worth noting that cancer incidence worldwide obtained from demographic projections point out to an increase of 25% of cancer cases in the next two decades. The lack of projections of incidence rates of the three cancers under study in the area covered by ROR-Sul, led us to use a variety of forecasting models that differ in the nature and structure. For example, linearity or nonlinearity in their coefficients and the trend of the incidence rates in historical data series (e.g. increasing, decreasing or stable).The models followed two approaches: (i) linear models regarding time and (ii) extrapolation of temporal effects identified by the APC models for future periods. The study provide incidence rates projections and the numbers of newly diagnosed cases for the year, 2007 to 2010, taking into account gender, age and the type of cancer. In addition, an estimate of the economic impact of these neoplasms is presented for the projection period considered. This research also try to address a relevant and common clinical question in these type of studies, regarding the contribution of the type of cancer to the patient survival. In such studies, the primary cause of death is commonly used to estimate the mortality specifically due to the cancer. However, there are many situations in which the cause of death is unknown, or, even if this information is available through the death certificates, it is not easy to distinguish the cases where the primary cause of death is the cancer. With this in mind, the relative survival is an alternative measure that does not need the knowledge of the specific cause of death to be calculated. This estimate will represent the survival probability in the hypothetical scenario of a certain cancer be the only cause of death. For the patients with unknown cause of death that were diagnosed with cancer in the ROR-Sul, the relative survival was calculated for each of the cancers under study, for a follow-up period of 5 years, considering gender, age and each one of the regions that are part the registry. A period analysis was undertaken, considering both the conventional and the model approaches. In final part of this study, we analyzed the influence of space-time variability in the incidence rates. The long latency period of oncologic diseases, the difficulty in identifying subtle changes in the rates behavior, populations of reduced size and low risk are some of the elements that can be a challenge in the analysis of temporal variations in rates, that, in some cases, can reflect simple random fluctuations. The effect of the temporal component measured by the APC models gives an incomplete picture of the cancer incidence. The etiology of this disease, when known, is frequently associated to risk factors such as socioeconomic conditions, eating habits and lifestyle, occupation, geographic location and genetic component. The "contribution"of such risk factors is sometimes decisive in the evolution of the disease and should not be ignored. Therefore, there was the need to consider an additional approach in this study, one of spatial nature, addressing the fact that changes in incidence rates observed in the ROR-Sul area, could be explained either by temporal and geographical variability or by unequal socio-economic or lifestyle factors. Thus, Bayesian hierarchical space-time models were used with the purpose of identifying space-time trends in incidence rates together with the the analysis of the effect of the risk factors considered in the study. The results obtained and the implementation of all these methodologies are considered to be an added value to the knowledge of these neoplasms in Portugal.
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The purpose of this work is to create a case to reflect about the leadership role of Jos Mourinho in Real Madrid CF, considering his successful background experiences in FC Porto, Chelsea FC and FC Inter. The case is based on the failure of the Special One in Real Madrid CF. This paper is mainly focused in the leadership process, charismatic leadership and contingency theory of leadership. Moreover it is intended to introduce concepts about the influence of leaders in the organizational culture, the management of human resources, and the role of a leader adapting to a different context.
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Salmonella enterica serovars are Gram-negative facultative intracellular bacterial pathogens that infect a wide variety of animals. Salmonella infections are common in humans, causing usually typhoid fever and gastrointestinal diseases. Salmonella enterica serovar Typhimurium (S. Typhimurium), which is a leading cause of human gastroenteritis, has been extensively used to study the molecular pathogenesis of Salmonella, because of the availability of sophisticated genetic tools, and of suitable animal and tissue culture models mimicking different aspects of Salmonella infections.(...)
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RESUMO: As clulas dendrticas (CDs) so fundamentais na imunomodulao e iniciao de respostas imunes adaptativas, enquanto os cidos silicos (Sias) so potenciais imunomoduladores. Estas clulas expressam nveis elevados da sialiltransferase ST6Gal-1, que transfere Sias para a posio terminal de oligossacridos. De facto, a maturao de CDs est associada a uma diminuio da sialilao na sua superfcie celular. Apesar de ter funo biolgica desconhecida, a forma solvel, extracelular de ST6Gal-1 aumenta em cancros e inflamao. Ainda assim, esta foi recentemente identificada como moduladora da hematopoiese. Considerando o importante papel das CDs na iniciao de respostas anticancergenas, uma ligao entre a sialilao extrnseca induzida por ST6Gal-1 extracelular e o seu papel na modulao de CDs deve ser identificada. Neste trabalho hipotetizou-se que a sialilao 2,6 extrnseca de CDs diminui o seu perfil de maturao mediante ativao por lipopolissacardeo (LPS). O objetivo principal foi sialilar extrinsecamente em 2,6 CDs da medula ssea de murganhos, avaliando os seus perfis de maturao e de libertao de citocinas, aps estimulao com LPS (por Citometria de Fluxo e ELISA, respetivamente). Ao contrrio da hiptese, o perfil celular no foi modulado, usando vrias abordagens. Por outro lado, a consequncia da falta de 2,6 Sias na maturao de CDs foi avaliada analisando: 1) CDs da medula ssea de murganhos tratadas com sialidase, 2) CDs da medula ssea e 3) CDs das vias areas, ambas de murganhos deficientes em ST6Gal-1, comparando com a estirpe selvagem. Estes resultados sugerem que a perta total de 2,6 Sias se relaciona com o aumento da expresso do complexo de histocompatibilidade principal de classe II. Apesar de controverso, provvel existirem mecanismos inerentes ativao por LPS, reduzindo a eficcia de ST6Gal-1 extracelular. Por outro lado, a modificao no perfil de CDs de murganhos deficientes em ST6Gal-1 poder relacionar-se com uma predisposio para um estado inflamatrio severo. Com isto, o trabalho desenvolvido abriu futuras linhas de investigao, nomeadamente explorar outros fatores envolvidos na (de)sialilao 2,6 de CDs, podendo ter impacto em imunoterapia com uso de CDs.--------------------------ABSTRACT: Dendritic cells (DCs) are vital for immunomodulation and the initiation of adaptive immune responses, whereas sialic acids (Sias) are potential immunomodulators. These cells express high levels of sialyltransferase ST6Gal-1, responsible for transferring Sias to the terminal position of oligosaccharide chains. Indeed, DCs maturation is associated with decreased cell surface sialylation. Although its biological significance is unknown, the soluble, extracellular form of ST6Gal-1 increases in cancers and inflammation. However, extracellular ST6Gal-1 was recently identified as modulator of hematopoiesis. Considering that DCs play a crucial role in the initiation of a productive anti-cancer immune response, a link between extrinsic sialylation by the extracellular ST6Gal-1 on DC function needs to be investigated. We hypothesize that extrinsic 2,6 sialylation of DCs diminishes their maturation features upon lipopolysaccharide (LPS) stimulation. The main goal was to extrinsically 2,6 sialylate mice bone marrow derived DCs (BMDCs) and to evaluate their maturation and cytokine profiles upon LPS stimulation (by Flow Cytometry and ELISA, respectively). Unlike the hypothesis, we observed that BMDCs profile is not modulated, even using several approaches. In contrast, the consequence of lacking cell surface 2,6 Sias in DC maturation was assessed by analysing: 1) sialidase treated BMDCs, 2) BMDCs from mice lacking ST6Gal-1 and 3) DCs from mice airways, comparing wild type with ST6Gal-1 knockout mice. These results suggest that overall lack in 2,6 Sias is related with increased expression of major histocompatibility class II (MHC-II). Although appearing to be controversial findings, other intracellular mechanisms might be occurring upon LPS-induced BMDC activation, probably reducing extracellular ST6Gal-1 effect. In opposite, the modification observed in DC profile of ST6Gal-1 knockout mice might be related to its predisposition to a more severe inflammatory status. With this, the developed work opened future lines of investigation, namely exploring other factors involved in 2,6 (de)sialylation of DC, which might have influence in immunotherapy using DCs.
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One cannot analyse a legal concept outside the economic and socio-cultural context in which it was applied such is the longstanding thesis of Antnio Manuel Hespanha. I argue that Hespanhas line of argument relative to legal concepts is also applicable, mutatis mutandis, to legal agents: the magistrates, advocates, notaries, solicitors and clerks who lived and exercised their professions in a given time and place. The question, then, is how to understand the actions of these individuals in particular contexts more specifically in late 18th century and 19th century Goa. The main goal of the present thesis was to comprehend how westernized and Catholic Goan elite of Brahman and Chard origin who provided the majority of Goan legal agents used Portuguese law to their own advantage. It can be divided into five key points. The first one is the importance of the Constitutional liberalism regime (with all the juridical, judicial, administrative and political changes that it has brought, namely the parliamentary representation) and its relations with the perismo a local political and ideological tendency nurtured by Goan native Catholic elite. It was explored in the chapter 2 of this thesis. The second key point is the repeated attempts made by Goan native Catholic elite to implement the jury system in local courts. It was studied in the chapter 3. Chapter 4 aims to understand the participation of the native Catholic elite in the codification process of the uses and traditions of the indigenous peoples in New Conquests territory. The fourth key point is the involvement of those elites not only in the conflict of civil and ecclesiastical jurisdictions but also in the succession of the Royal House of Sunda. It was analyzed in the chapter 5. The functions of an advocate could be delegated to someone who, though lacking a law degree, possessed sufficient knowledge to perform this role satisfactorily. Those who held a special licence to practice law were known as provisionrios (from proviso, or licence, as opposed to the letrados, or lettered). In the Goa of the second half of the 18th century and the 19th century, such provisionrios were abundant, the vast majority coming from the native Catholic elite. The characteristics of those provisionrios, the role played by the Portuguese letrados in Goa and the difficult relations between both groups were studied in the chapter 6.
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A permanently changing occidental society framework, simultaneously, to a world Globalization and a market liberalization, requires to know how important and which role the agents plays, in Estates representation, to guarantee their own intern security. Portugal is an example of that since has been integrated in European and world politics that allowed the borders opening, with all the negative consequences of that kind of measures. In way to struggle with those debilities emerge, in our Juridical Order, several security forces such as Prison Guards Corporation, whose contribute to intern security seems undefined and confuse, being urgent legislation in way to describe and clearly define their goals and functions. We begin with a brief history view to understand the evolution, focusing on the present moment, correlate several laws in way to clarify their juridical situation. Using a own critical sense, it draws attention to legislation lack problem in opposition to the conclusion that, Prison Guards Corporation is a security force with specialized expertise in matter and territory fields. Their activity occurs, generally, in penitentiaries where people see themselves without their freedom, legally determinated and confined to places as other individuals with deviant behaviors that deserve society refutation, establishing a separation period having rehabilitation as a goal it is called general and special prevention. Penitentiaries specificities requires specially police force because penitentiaries are places where tensions are often, both between inmates and against employees, above all prison guards, the first to struggle inmates daily frustrations. In way that institutions achieve their purpose, it is necessary that citizens respect all the rules, although, to their efficacy is necessary to inflict punishment to those who did not respect the rules. Furthermore, it will be indispensable to act immediately in situations as impeding runaway helping, illegally standing in jail and to avoid violent acts against personal and patrimonial belongings. Juridical Order has a few security tools that are available to administration, in which is included coercive methods, that as damaging to citizens in whom they are use, are restricted, unavoidably, to inflexible control rules. Concluding, Prison Guards and Penitentiaries General Direction last goal is to give back recovered inmates to society, in a way to conduct their lives responsibly, without committing crimes.
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Double Degree