846 resultados para Naïve


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Num contexto de urbanização, de acesa competitividade e desertificação do interior, assiste-se cada vez mais a cenários de concorrência entre territórios pela captação de recursos, investimentos, negócios e até visitantes e turistas, capazes de gerar dinâmicas positivas no território, palco deste movimento. Algumas projeções indiciam que o interior de Portugal terá, em 2040, cerca de um terço da população atual e, se a tendência de declínio demográfico se mantiver, em 90 anos o interior perderá 75 por cento da população. Neste contexto, o presente estudo tem por finalidade alertar os decisores políticos para o desenvolvimento de estratégias que possam atrair pessoas para o interior do país e estancar a sua desertificação. Para o efeito, o projeto que se apresenta vai procurar definir uma estratégia de marketing territorial para o concelho de Moimenta da Beira, tendo por base os seus produtos endógenos, como a maçã, o vinho, o mel, os enchidos, os granitos, o património religioso e cultural e, por fim, o património natural, como a Albufeira do Vilar e a Serra da Nave. Para a realização do referido estudo, foi seguida uma metodologia que teve por base uma revisão de literatura na área do marketing territorial, a análise de dados secundários e a realização de entrevistas aos principais Stakeholders da região. Os resultados deste estudo permitirão definir orientações para reforçar a atratividade e competitividade da oferta territorial junto dos segmentos alvo, ou seja, dos atuais e potenciais utilizadores do território.

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Hebb proposed that synapses between neurons that fire synchronously are strengthened, forming cell assemblies and phase sequences. The former, on a shorter scale, are ensembles of synchronized cells that function transiently as a closed processing system; the latter, on a larger scale, correspond to the sequential activation of cell assemblies able to represent percepts and behaviors. Nowadays, the recording of large neuronal populations allows for the detection of multiple cell assemblies. Within Hebb's theory, the next logical step is the analysis of phase sequences. Here we detected phase sequences as consecutive assembly activation patterns, and then analyzed their graph attributes in relation to behavior. We investigated action potentials recorded from the adult rat hippocampus and neocortex before, during and after novel object exploration (experimental periods). Within assembly graphs, each assembly corresponded to a node, and each edge corresponded to the temporal sequence of consecutive node activations. The sum of all assembly activations was proportional to firing rates, but the activity of individual assemblies was not. Assembly repertoire was stable across experimental periods, suggesting that novel experience does not create new assemblies in the adult rat. Assembly graph attributes, on the other hand, varied significantly across behavioral states and experimental periods, and were separable enough to correctly classify experimental periods (Naïve Bayes classifier; maximum AUROCs ranging from 0.55 to 0.99) and behavioral states (waking, slow wave sleep, and rapid eye movement sleep; maximum AUROCs ranging from 0.64 to 0.98). Our findings agree with Hebb's view that assemblies correspond to primitive building blocks of representation, nearly unchanged in the adult, while phase sequences are labile across behavioral states and change after novel experience. The results are compatible with a role for phase sequences in behavior and cognition.

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The intestinal tract is exposed to a large variety of antigens such as food proteins, commensal bacteria and pathogens and contains one of the largest arms of the immune system. The intestinal immune system has to discriminate between harmless and harmful antigens, inducing tolerance to harmless antigens and active immunity towards pathogens and other harmful materials. Dendritic cells (DC) in the mucosal lamina propria (LP) are central to this process, as they sample bacteria from the local environment and constitutively migrate to the draining mesenteric lymph nodes (MLN), where they present antigen to naïve T cells in order to direct an appropriate immune response. Despite their crucial role, understanding the function and phenotype of LP DC has been hampered by the fact that they share phenotypic markers with macrophages (mφ), which are the dominant population of mononuclear phagocyte (MP) in the LP. Recent work in our own and other laboratories has established gating strategies and phenotyping panels that allow precise discrimination between intestinal DC and mφ using the mφ specific markers CD64 and F4/80. In this way four bona fide DC subsets with distinct functions have been identified in adult LP based on their expression of CD11b and CD103 and a major aim of my project was to understand how these subsets might develop in the neonatal intestine. At the beginning of my PhD, the laboratory had used these new methods to show that signal regulatory protein α (SIRPα), an inhibitory receptor expressed by myeloid cells, was expressed by mφ and most DC in the intestine, except for those expressing CD103 alone. In addition, mice carrying a non-signalling mutation in SIRPα (SIRPα mt) had a selective reduction in CD103+CD11b+ DC, a subset which is unique to the intestinal LP. This was the basis for the initial experiments of my project, described in Chapter 3, where I investigated if the phenotype in SIRPα mt mice was intrinsic to haematopoietic cells or not. To explore this, I generated bone marrow (BM) chimeric mice by reconstituting irradiated WT mice with SIRPα mt BM, or SIRPα mt animals with WT BM. These experiments suggested that the defect in CD103+CD11b+ DC was not replicated in DC derived from BM of SIRPα origin. However as this seemed inconsistent with other data, I considered the possibility that 18 the phenotype may have been lost with age, as the BM chimeric mice were considerably older than those used in the original studies of SIRPα function. However a comparison of DC subsets in the intestine of WT and SIRPα mt mice as they aged provided no conclusive evidence to support this idea. As these experiments did show age-dependent effects on DC subsets, in Chapter 4, I went on to investigate how the DC populations appeared in the intestine and other tissues in the neonatal period. These experiments showed there were few CD103+CD11b+ DC present in the LP and migratory DC compartment of the MLN in the neonate and that as this population gradually increased in proportion with age, there was a reciprocal decrease in the relative proportion of CD103-CD11b+ DC. Interestingly, most of the changes in DC numbers in the intestine were found during the second or third week of life when the weaning process began. To validate my findings that there were few CD103+CD11b+ DC in the neonate and that this was not merely an absence of CD103 upregulation, I examined the expression of CD101 and Trem-1, markers that other work in the laboratory had suggested were specific to the CD103+CD11b+ DC lineage. My work showed that CD101 and Trem-1 were co- expressed by most CD103+CD11b+ DC in small intestine (SI) LP, as well as a small subset of CD103-CD11b+ DC in this tissue. Interestingly, Trem-1 was highly specific to the SI LP and migratory DC in the MLN, but absent from the colon and other tissues. CD101 expression was also only found on CD11b+ DC, but showed a less restricted pattern of distribution, being found in several tissues as well as the SI LP. The relative timing of their development suggested there might be a relationship between CD103+CD11b+ and CD103-CD11b+ DC and this was supported by microarray analysis. I hypothesised that the CD103-CD11b+ DC that co-expressed CD101 and Trem-1 may be the cells that developed into CD103+CD11b+ DC. To investigate this I analysed how CD101 and Trem-1 expression changed with age amongst the DC subsets in SI LP, colonic LP (CLP) and MLN. The proportion of CD101+Trem-1+ cells increased amongst CD103+CD11b+ DC in the SI LP and MLN with age, while amongst CD103+CD11b+ DC in the CLP this decreased. This was not the same in CD103-CD11b+ DC, where CD101 and Trem-1 expression was more varied with age in all tissues. CD101 and Trem-1 were not expressed to any great extent on CD103+CD11b- or CD103-CD11b- DC. The phenotypic development of the 19 intestinal DC subsets was paralleled by the gradual upregulation of CD103 expression, while the production of retinoic acid (RA), as assessed by the AldefluorTM assay, was low early in life and did not attain adult levels until after weaning. Thus DC in the neonatal intestine take some time to acquire the adult pattern of phenotypic subsets and are functionally immature compared with their adult counterparts. In Chapter 5, I used CD101 and Trem-1 to explore the ontogeny of intestinal DC subsets in CCR2-/- and SIRPα mt mice, both of which have selective defects in one particular group of DC. The selective defect seen amongst CD103+CD11b+ DC in adult SIRPα mt mice was more profound in mice at D7 and D14 of age, indicating that it may be intrinsic to this population and not highly dependent on environmental factors that change after birth. The expression of CD101 and Trem-1 by both CD103+CD11b+ and CD103-CD11b+ DC was reduced in SIRPα mt mice, again indicating that this entire lineage was affected by the lack of SIRPα signalling. However there was also a generalised defect in the numbers of all DC subsets in many tissues from early in life, suggesting there was compromised development, recruitment or survival of DC in the absence of SIRPα signalling. In contrast to the findings in SIRPα mt mice, more CD103+CD11b+ DC co-expressed CD101 and Trem-1 in CCR2-/- mice, while there were no differences in the expression of these molecules amongst CD103-CD11b+ DC. This may suggest that CCR2+ CD103-CD11b+ DC are not the cells that express CD101 and Trem-1 that are predicted to be the direct precursors of CD103+CD11b+ DC. I also examined the expression of DC growth factor receptors on DC subsets from mice of different ages, but no clear age or subset- related patterns of the expression of mRNA for Csf2ra, Irf4, Tgfbr1 and Rara could be observed. Next, I investigated whether Trem-1 played any role in DC development. Preliminary experiments in Trem-1-/- mice show no differences between any of the DC subsets, nor were there any selective effects on individual subsets when DC development from Trem-1-/- KO and WT BM was compared in competitive chimeras. However these experiments were difficult to interpret due to viability problems and because I found an unexpected defect in the ability of Trem-1-/- BM to generate all DC, irrespective of whether they expressed Trem-1 or not. 20 The final experiments I carried out were to examine the role of the microbiota in driving the differentiation of intestinal DC subsets, based on the hypothesis that this could be one of the environmental factors that might influence events in the developing intestine. To this end I performed experiments in both antibiotic treated and germ free adult mice, both of which showed no significant phenotypic differences amongst any of the DC subsets. However the study of germ free mice was compromised by recent contamination of the colony and may not be the conclusive answer. Together the data in this thesis have shown that the population of CD103+CD11b+ DC, which is unique to the intestine, is not present at birth. These cells gradually increase in frequency over time and as this occurs there is a reciprocal decrease in the frequency of CD103-CD11b+ DC. Along with other results, this leads to the idea that there may be a linear developmental pathway from CD103-CD11b+ DC to CD103+CD11b+ DC that is driven by non-microbial factors that are located preferentially in the small intestine. My project indicates that markers such as CD101 and Trem-1 may assist the dissection of this process and highlights the importance of the neonatal period for these events.

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La Compañía Metropolitano Alfonso XIII llevó a cabo, a principios del siglo XX, la empresa de dotar a la capital española de un ferrocarril subterráneo a la altura de otras ciudades europeas: el Metro de Madrid. Del proyecto original de cuatro líneas, la 3 y la 4 se construyeron e inauguraron en plena guerra civil y en los primeros años del franquismo (1936-1945). Esta última fecha es significativa, puesto que poco después de abierta al público la línea 4 (que convertía al metropolitano por fin en una red mallada), murió su primer arquitecto oficial, Antonio Palacios Ramilo, relevante proyectista de la primera mitad del siglo XX, responsable de emblemáticos edificios del centro de la capital (Círculo de Bellas Artes, Palacio de Correos, Banco Español del Río de la Plata...). En su calidad de arquitecto oficial de la Compañía Metropolitano Alfonso XIII, diseñó no sólo las estaciones, bocas y templetes del metro de Madrid, sino también toda una serie de edificios auxiliares entre los que destacan las centrales y subestaciones eléctricas. Explicaremos la evolución de la red de metro en los comienzos del franquismo y analizaremos la arquitectura subterránea que Palacios diseñó para el ferrocarril metropolitano, centrándonos en las llamadas líneas "de los barrios bajos" y "de los bulevares", la planificación de la estación de Sol como centro neurálgico de la red y en cómo los modelos de barandillas, accesos y decoración interior que ideó Antonio Palacios se siguieron utilizando hasta mucho después de su muerte, si bien otros elementos no subsistieron al paso del tiempo y la llamada "modernización" del Metro que se llevó a cabo en los años 60 y 70. También estudiaremos el modo de intervención de Palacios en la arquitectura industrial respecto al resto de su obra y haremos especial hincapié en el estado en que se encuentra actualmente este patrimonio, distinguiendo entre los casos en los que ha habido una intervención restauradora (Nave de Motores en Pacífico, Estación de Chamberí), los que están en desuso (subestaciones de Quevedo y Salamanca...) y los elementos que ya han desaparecido (templetes de Sol y Gran Vía).

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Cálculo y dimensionamiento de una nave industrial para almacenaje destinada al almacenaje para distribución de conductos metálicos y accesorios para la ejecución de sistemas de extracción y chimeneas, con grúa puente de capacidad 4 Tn y una zona de oficinas donde se ubican distintos departamentos de la empresa. Redactado en castellano.

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Dopamine (DA) is known to regulate both sleep and memory formations, while sleep plays a critical role in the consolidation of different types of memories. We believe that pharmacological manipulation of dopaminergic pathways might disrupt the sleep-wake cycle, leading to mnemonic deficits, which can be observed in both behavioral and molecular levels. Therefore, here we investigated how systemic injections of haloperidol (0.3 mg/kg), immediately after training in dark and light periods, affects learning assessed in the novel object preference test (NOPT) in mice. We also investigated the hippocampal levels of the plasticity-related proteins Zif-268, brain-derived neurotrophic factor (BDNF) and phosphorylated Ca2+/calmodulin-dependent protein kinases II (CaMKII-P) in non-exposed (naïve), vehicle-injected controls and haloperidol-treated mice at 3, 6 and 12 hours after training in the light period. Haloperidol administration during the light period led to a subsequent impairment in the NOPT. In contrast, preference was not observed during the dark period neither in mice injected with haloperidol, nor in vehicle-injected animals. A partial increase of CaMKII-P in the hippocampal field CA3 of vehicle-injected mice was detected at 3h. Haloperidol-treated mice showed a significant decrease in the dentate gyrus of CaMKII-P levels at 3, 6 and 12h; of Zif-268 levels at 6h, and of BDNF levels at 12h after training. Since the mnemonic effects of haloperidol were only observed in the light period when animals tend to sleep, we suggest that these effects are related to REM sleep disruption after haloperidol injection

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Tese (doutorado)—Universidade de Brasília, Faculdade de Medicina, Pós-Graduação em Patologia Molecular, 2016.

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La reconnaissance d’un antigène présenté par les cellules présentatrices d’antigène induit la prolifération et la différenciation des lymphocytes T naïfs en lymphocytes T effecteurs et mémoires. Cette reconnaissance se fait par l’interaction du récepteur des cellules T (TCR) des lymphocytes T et le complexe CMH-peptide présent à la surface des DC. Cependant, des signaux additionnels sont requis, une meilleure activation des lymphocytes T implique des corécepteurs présents à la surface de ces deux types cellulaires. Après l’élimination de l’antigène, la plupart des lymphocytes T effecteurs vont mourir. Une petite population de lymphocytes T va persister pour se différencier en lymphocytes T mémoires capables de protéger l’organisme contre une réinfection. Les signaux qui contrôlent le maintien des lymphocytes T mémoires sont encore mal compris. Pour comprendre le rôle de la molécule de costimulation 4-1BB dans le maintien des lymphocytes T CD8 mémoires, nous avons émis l’hypothèse que l’état de phosphorylation de la protéine adaptatrice TRAF1, qui se lie à 4-1BB, module le maintien des lymphocytes T CD8 mémoires. Ainsi, nous avons montré par des expériences de spectrométrie de masse que TRAF1 s’associe préférentiellement à TBK1 lorsqu’elle n’est pas phosphorylée. Nous avons aussi montré que la présence de TRAF1 est requise pour stabiliser TBK1 au récepteur 4-1BB après stimulation des lymphocytes T. Par ailleurs, les lymphocytes T CD8 OT-I TRAF1-/- reconstituées avec un mutant phospho-déficient de TRAF1 (S139A) et ensuite différenciées en lymphocytes T mémoires in vitro induisent une activation de la voie de signalisation NF-ĸB contrairement à ceux exprimant la forme phospho-mimétique de TRAF1 (S139D). Ces premières études démontrent l’importance de l’état de phosphorylation de TRAF1 en aval de 4-1BB dans les cellules T. Dans la seconde partie, nous avons évalué le rôle d’un autre corécepteur; la neuropiline 1, dans la maturation des DC. A cet effet, nous avons émis l’hypothèse que l’interaction de la neuropiline 1 et ses ligands contribuerait à la fonction des DC. Nous avons démontré que l’absence de la neuropiline 1 n’a pas d’effet sur la maturation au LPS des DC. Cependant, la présence du VEGF (un ligand de Nrp-1) inhibe la maturation des DC dérivées de la moelle osseuse. Notre étude a démontré que VEGF inhibe l’expression des molécules de costimulation, la sécrétion des cytokines pro inflammatoires et la signalisation TLR4 principalement les voies MAP Kinase et NF-ĸB. Contrairement aux résultats avec les cellules WT, VEGF n’est pas capable d’affecter la maturation, la sécrétion des cytokines et la signalisation TLR4 des DC Nrp1-Lyz où la neuropiline 1 est délétée. Ainsi, nos résultats ont démontré que VEGF inhibe la maturation des DC de façon Nrp1-dépendante. Enfin, l’analyse des molécules partenaires de la neuropiline 1 montre que Nrp1, VEGF et TLR4 se retrouvent dans le même complexe. Nos résultats démontrent que VEGF, en présence de la neuropiline 1 est capable d’interagir avec TLR4 pour inhiber la maturation des DC. Toutefois, en absence de la neuropiline1, VEGF n’est pas capable de recruter TLR4 pour réduire l’expression des molécules de costimulation. Ces études sur les corécepteurs pourraient être importantes dans l’élaboration de nouvelles approches vaccinales.

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Forecast is the basis for making strategic, tactical and operational business decisions. In financial economics, several techniques have been used to predict the behavior of assets over the past decades.Thus, there are several methods to assist in the task of time series forecasting, however, conventional modeling techniques such as statistical models and those based on theoretical mathematical models have produced unsatisfactory predictions, increasing the number of studies in more advanced methods of prediction. Among these, the Artificial Neural Networks (ANN) are a relatively new and promising method for predicting business that shows a technique that has caused much interest in the financial environment and has been used successfully in a wide variety of financial modeling systems applications, in many cases proving its superiority over the statistical models ARIMA-GARCH. In this context, this study aimed to examine whether the ANNs are a more appropriate method for predicting the behavior of Indices in Capital Markets than the traditional methods of time series analysis. For this purpose we developed an quantitative study, from financial economic indices, and developed two models of RNA-type feedfoward supervised learning, whose structures consisted of 20 data in the input layer, 90 neurons in one hidden layer and one given as the output layer (Ibovespa). These models used backpropagation, an input activation function based on the tangent sigmoid and a linear output function. Since the aim of analyzing the adherence of the Method of Artificial Neural Networks to carry out predictions of the Ibovespa, we chose to perform this analysis by comparing results between this and Time Series Predictive Model GARCH, developing a GARCH model (1.1).Once applied both methods (ANN and GARCH) we conducted the results' analysis by comparing the results of the forecast with the historical data and by studying the forecast errors by the MSE, RMSE, MAE, Standard Deviation, the Theil's U and forecasting encompassing tests. It was found that the models developed by means of ANNs had lower MSE, RMSE and MAE than the GARCH (1,1) model and Theil U test indicated that the three models have smaller errors than those of a naïve forecast. Although the ANN based on returns have lower precision indicator values than those of ANN based on prices, the forecast encompassing test rejected the hypothesis that this model is better than that, indicating that the ANN models have a similar level of accuracy . It was concluded that for the data series studied the ANN models show a more appropriate Ibovespa forecasting than the traditional models of time series, represented by the GARCH model

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Mortality of young Pacific oysters Crassostrea gigas associated with the ostreid herpesvirus 1 (OsHV-1) is occurring worldwide. Here, we examined for the first time the effect of salinity on OsHV-1 transmission and disease-related mortality of C. gigas, as well as salinity-related effects on the pathogen itself. To obtain donors for OsHV-1 transmission, we transferred laboratory-raised oysters to an estuary during a disease outbreak and then back to the laboratory. Oysters that tested OsHV-1 positive were placed in seawater tanks (35‰, 21°C). Water from these tanks was used to infect naïve oysters in 2 experimental setups: (1) oysters acclimated or non-acclimated to a salinity of 10, 15, 25 and 35‰ and (2) oysters acclimated to a salinity of 25‰; the latter were exposed to OsHV-1 water diluted to a salinity of 10 or 25‰. The survival of oysters exposed to OsHV-1 water and acclimated to a salinity of 10‰ was >95%, compared to only 43 to 73% survival in oysters acclimated to higher salinities (Expt 1), reflecting differences in the levels of OsHV-1 DNA and viral gene expression (Expts 1 and 2). However, the survival of their non-acclimated counterparts was only 23% (Expt 2), and the levels of OsHV-1 DNA and the expression of 4 viral genes were low (Expt 1). Thus, OsHV-1 may not have been the ultimate cause of mortality in non-acclimated oysters weakened by a salinity shock. It appears that reducing disease risk by means of low salinity is unlikely in the field.

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Mestrado em Finanças

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Dissertação de Mestrado, Engenharia Biológica, , 2016

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No mundo do trabalho, o êxito depende da capacidade revelada para conhecer e desempenhar o nosso papel. E a carreira docente não foge a esta regra. À semelhança do que acontece com os actores e as actrizes - que são avaliados pela qualidade que imprimem aos papéis representados - também os juízos de valor sobre os docentes assentam na aptidão demonstrada para dominarem todas as subtilezas inerentes ao papel de professores. A sua forma de actuar perante situações melindrosas e excepcionais, de indisciplina e de violência, o seu sentir, constituirão o objecto de análise neste trabalho. Os professores, muitas vezes, actuam com base em conceitos veiculados pelos seus pais e formadores, que poderão ter sido válidos para eles, mas que não o são, decerto, hoje em dia. Podem ter resultado no início das carreiras, mas, em regra, foram perdendo utilidade em fases posteriores. Pela análise das histórias de vida dos professores levantam-se várias hipóteses quanto à construção dessas posturas e aos condimentos que possibilitam uma adesão à mudança necessária. Urge implementar uma alteração da sua maneira de pensar a abordagem às situações de indisciplina e de violência escolares, porque tal é essencial para alterar comportamentos que lhes podem ser prejudiciais. Este trabalho obedeceu a dois propósitos: proporcionar informação enquadrada em bases teóricas sólidas que possa sustentar intervenções ajustadas na sala de aula e suscitar a reflexão dos docentes sobre os seus papéis e as suas práticas. Não temos, contudo, a pretensão de que essa informação seja bastante para a resolução dos problemas de indisciplina, mas alimentamos a esperança de que as pistas de reflexão e de acção, bem como os conceitos mobilizados, possam ajudar a uma acção educativa simultaneamente mais eficaz e satisfatória. Assim, acreditamos que este trabalho estimulará os professores a encarar as situações de indisciplina e violência de um modo mais tranquilo, emocionalmente mais distante, sem o rígido recurso à auto culpabilização ou às hetero-acusações. ABSTRACT: ln the working world, success depends on the way we know and play our roles. And the teaching role is not different. An actor (or actress) is evaluated by the quality of his (or her) role performance; in the same way, the value judgements about teachers are linked with their capacity to dominate all the aspects of their teaching role. Their way to intervene in problematic and special situations, dealing with violence and indiscipline, their feelings, are the main objective of this research project. Many times, teachers act remembering what their parents and old teachers taught them. These old concepts and ideas worked well in the beginning of their careers but are not valid today. Analyzing the life stories of teachers, we can find several answers for their positions when facing these problems. It is necessary to compel them to change their minds, to transform their reactions over problematic situations of indiscipline and violence or they will face more problems in the near future. This research project has two intentions: to give theoretical information helping teachers to act correctly in the classrooms and to show that a time for reflection is necessary, to analyse their roles and procedures. We are not so naïve in thinking that this project is enough to find a solution for all the indiscipline and violence problems in schools, but we really believe that it will help teachers to face those problems in a more peaceful way, not so emotional and with better results.

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2016