A poesia na revista alegretense "Ibirapuitã" (1938/1939)

A revista Ibirapuitã foi criada pelo poeta e jornalista Felisberto Soares Coelho, em Alegrete, interior do Rio Grande do Sul, ao final dos anos trinta. O periódico promoveu a divulgação de autores locais e considerável efervescência cultural no município. No presente trabalho, busca-se o resgate da poesia veiculada pela revista em sua fase inicial, compreendida entre os anos de 1938 e 1939, por se tratar de gênero que se destaca ao longo de seu percurso editorial. Ademais, pretende-se analisar tal produção abarcada em uma organização temática, estabelecendo relações com a história da literatura. Por meio da localização, catalogação e leitura do mensário foram selecionados trinta e nove poemas, obedecendo ao critério de freqüência/ocorrência de publicação de cada colaborador. Como resultado, além da análise da produção poética, pretende-se organizar uma antologia acompanhada de notas biobibliográficas e material iconográfico. Desta forma, pretende-se facilitar o acesso pela comunidade a uma das publicações que possivelmente contribuiu para a formação do sistema literário sul-rio-grandense, proporcionando abertura a novos estudos referentes à história da literatura alegretense.

Functional alkali tantalate 2D structures for microelectronics and related applications

Alkali tantalates and niobates, including K(Ta / Nb)O3, Li(Ta / Nb)O3 and Na(Ta / Nb)O3, are a very promising ferroic family of lead-free compounds with perovskite-like structures. Their versatile properties make them potentially interesting for current and future application in microelectronics, photocatalysis, energy and biomedics. Among them potassium tantalate, KTaO3 (KTO), has been raising interest as an alternative for the well-known strontium titanate, SrTiO3 (STO). KTO is a perovskite oxide with a quantum paraelectric behaviour when electrically stimulated and a highly polarizable lattice, giving opportunity to tailor its properties via external or internal stimuli. However problems related with the fabrication of either bulk or 2D nanostructures makes KTO not yet a viable alternative to STO. Within this context and to contribute scientifically to the leverage tantalate based compounds applications, the main goals of this thesis are: i) to produce and characterise thin films of alkali tantalates by chemical solution deposition on rigid Si based substrates, at reduced temperatures to be compatible with Si technology, ii) to fulfil scientific knowledge gaps in these relevant functional materials related to their energetics and ii) to exploit alternative applications for alkali tantalates, as photocatalysis. In what concerns the synthesis attention was given to the understanding of the phase formation in potassium tantalate synthesized via distinct routes, to control the crystallization of desired perovskite structure and to avoid low temperature pyrochlore or K-deficient phases. The phase formation process in alkali tantalates is far from being deeply analysed, as in the case of Pb-containing perovskites, therefore the work was initially focused on the process-phase relationship to identify the driving forces responsible to regulate the synthesis. Comparison of phase formation paths in conventional solid-state reaction and sol-gel method was conducted. The structural analyses revealed that intermediate pyrochlore K2Ta2O6 structure is not formed at any stage of the reaction using conventional solid-state reaction. On the other hand in the solution based processes, as alkoxide-based route, the crystallization of the perovskite occurs through the intermediate pyrochlore phase; at low temperatures pyrochlore is dominant and it is transformed to perovskite at >800 °C. The kinetic analysis carried out by using Johnson-MehlAvrami-Kolmogorow model and quantitative X-ray diffraction (XRD) demonstrated that in sol-gel derived powders the crystallization occurs in two stages: i) at early stage of the reaction dominated by primary nucleation, the mechanism is phase-boundary controlled, and ii) at the second stage the low value of Avrami exponent, n ~ 0.3, does not follow any reported category, thus not permitting an easy identification of the mechanism. Then, in collaboration with Prof. Alexandra Navrotsky group from the University of California at Davis (USA), thermodynamic studies were conducted, using high temperature oxide melt solution calorimetry. The enthalpies of formation of three structures: pyrochlore, perovskite and tetragonal tungsten bronze K6Ta10.8O30 (TTB) were calculated. The enthalpies of formation from corresponding oxides, ∆Hfox, for KTaO3, KTa2.2O6 and K6Ta10.8O30 are -203.63 ± 2.84 kJ/mol, - 358.02 ± 3.74 kJ/mol, and -1252.34 ± 10.10 kJ/mol, respectively, whereas from elements, ∆Hfel, for KTaO3, KTa2.2O6 and K6Ta10.8O30 are -1408.96 ± 3.73 kJ/mol, -2790.82 ± 6.06 kJ/mol, and -13393.04 ± 31.15 kJ/mol, respectively. The possible decomposition reactions of K-deficient KTa2.2O6 pyrochlore to KTaO3 perovskite and Ta2O5 (reaction 1) or to TTB K6Ta10.8O30 and Ta2O5 (reaction 2) were proposed, and the enthalpies were calculated to be 308.79 ± 4.41 kJ/mol and 895.79 ± 8.64 kJ/mol for reaction 1 and reaction 2, respectively. The reactions are strongly endothermic, indicating that these decompositions are energetically unfavourable, since it is unlikely that any entropy term could override such a large positive enthalpy. The energetic studies prove that pyrochlore is energetically more stable phase than perovskite at low temperature. Thus, the local order of the amorphous precipitates drives the crystallization into the most favourable structure that is the pyrochlore one with similar local organization; the distance between nearest neighbours in the amorphous or short-range ordered phase is very close to that in pyrochlore. Taking into account the stoichiometric deviation in KTO system, the selection of the most appropriate fabrication / deposition technique in thin films technology is a key issue, especially concerning complex ferroelectric oxides. Chemical solution deposition has been widely reported as a processing method to growth KTO thin films, but classical alkoxide route allows to crystallize perovskite phase at temperatures >800 °C, while the temperature endurance of platinized Si wafers is ~700 °C. Therefore, alternative diol-based routes, with distinct potassium carboxylate precursors, was developed aiming to stabilize the precursor solution, to avoid using toxic solvents and to decrease the crystallization temperature of the perovskite phase. Studies on powders revealed that in the case of KTOac (solution based on potassium acetate), a mixture of perovskite and pyrochlore phases is detected at temperature as low as 450 °C, and gradual transformation into monophasic perovskite structure occurs as temperature increases up to 750 °C, however the desired monophasic KTaO3 perovskite phase is not achieved. In the case of KTOacac (solution with potassium acetylacetonate), a broad peak is detected at temperatures <650 °C, characteristic of amorphous structures, while at higher temperatures diffraction lines from pyrochlore and perovskite phases are visible and a monophasic perovskite KTaO3 is formed at >700 °C. Infrared analysis indicated that the differences are due to a strong deformation of the carbonate-based structures upon heating. A series of thin films of alkali tantalates were spin-coated onto Si-based substrates using diol-based routes. Interestingly, monophasic perovskite KTaO3 films deposited using KTOacac solution were obtained at temperature as low as 650 °C; films were annealed in rapid thermal furnace in oxygen atmosphere for 5 min with heating rate 30 °C/sec. Other compositions of the tantalum based system as LiTaO3 (LTO) and NaTaO3 (NTO), were successfully derived as well, onto Si substrates at 650 °C as well. The ferroelectric character of LTO at room temperature was proved. Some of dielectric properties of KTO could not be measured in parallel capacitor configuration due to either substrate-film or filmelectrode interfaces. Thus, further studies have to be conducted to overcome this issue. Application-oriented studies have also been conducted; two case studies: i) photocatalytic activity of alkali tantalates and niobates for decomposition of pollutant, and ii) bioactivity of alkali tantalate ferroelectric films as functional coatings for bone regeneration. Much attention has been recently paid to develop new type of photocatalytic materials, and tantalum and niobium oxide based compositions have demonstrated to be active photocatalysts for water splitting due to high potential of the conduction bands. Thus, various powders of alkali tantalates and niobates families were tested as catalysts for methylene blue degradation. Results showed promising activities for some of the tested compounds, and KNbO3 is the most active among them, reaching over 50 % degradation of the dye after 7 h under UVA exposure. However further modifications of powders can improve the performance. In the context of bone regeneration, it is important to have platforms that with appropriate stimuli can support the attachment and direct the growth, proliferation and differentiation of the cells. In lieu of this here we exploited an alternative strategy for bone implants or repairs, based on charged mediating signals for bone regeneration. This strategy includes coating metallic 316L-type stainless steel (316L-SST) substrates with charged, functionalized via electrical charging or UV-light irradiation, ferroelectric LiTaO3 layers. It was demonstrated that the formation of surface calcium phosphates and protein adsorption is considerably enhanced for 316L-SST functionalized ferroelectric coatings. Our approach can be viewed as a set of guidelines for the development of platforms electrically functionalized that can stimulate tissue regeneration promoting direct integration of the implant in the host tissue by bone ingrowth and, hence contributing ultimately to reduce implant failure.

Remoção de instrumentos fraturados em Endodontia

A área da Endodontia está em constante progresso. Os materiais utilizados nos instrumentos Endodônticos, primordialmente, eram construídos com base em cordas de piano. Seguiu-se uma fase em que estes eram de aço de carbono, mas sofriam corrosão significativa devido ao cloro presente no hipoclorito de sódio, bem como aos processos de esterilização a vapor. Foi necessário evoluir novamente e foram introduzidos os instrumentos de aço inoxidável. Estes apresentavam alta resistência e dureza, mas algumas desvantagens devido à falta de flexibilidade. Atualmente, os instrumentos de NiTi proporcionam uma melhor flexibilidade e efeito de memória de forma. A fratura de instrumentos em Endodontia pode ocorrer por dois grandes fatores: a torção e a flexão por fadiga cíclica, podendo também ser a conjugação de ambos. Fatores anatômicos, como a curvatura e a largura do canal ou outros fatores como ciclos de esterilização, número de usos, etc., podem influenciar uma fratura mais precoce dos instrumentos. A incidência da fratura de instrumentos, embora seja pouco frequente, pode ser reduzida a um mínimo absoluto se os clínicos usarem as características de torque e de stress adequadas. Um bom conhecimento dos procedimentos clínicos, da anatomia, dos materiais e a utilização de instrumentos como o microscópio podem ajudar a prevenir ou a resolver a fratura dos instrumentos. No entanto, a melhor forma de prevenir a fratura é a sua prevenção. A desinfeção é o procedimento mais importante para o sucesso de um tratamento Endodôntico, portanto para que isto seja possível, é necessária uma boa conformação canalar. A presença de um instrumento no interior do canal pode comprometer a desinfecção, especialmente caso tenha ocorrido numa fase precoce da preparação canalar. Aquando da fratura de um instrumento, deve-se refletir sobre os procedimentos a seguir, podendo-se optar por várias abordagens, nomeadamente pela manutenção do instrumento no canal e obturação incorporando o fragmento, pela remoção do segmento através de diversas técnicas (ultrassons ou técnicas de microtubos, etc.), e ainda pela realização do bypass ou pela cirurgia Endodôntica. Em última instância pode ser realizada a extração do elemento dentário.

Síndrome de Sjögren Primário

A Síndrome de Sjögren (SS) é uma das três patologias autoimunes mais frequentes na população mundial, ainda assim frequentemente infradiagnosticada. Esta síndrome é uma doença autoimune crónica que afeta as glândulas exócrinas, particularmente as glândulas salivares e lacrimais. A SS primária (SSp) afeta especificamente as glândulas exócrinas, enquanto que a SS secundária (SSs) aparece associada a outras patologias autoimunes sistémicas. A SS é caracterizada, histopatologicamente, por um infiltrado inflamatório linfocitário que interfere com a função glandular normal. Afeta 0,5% da população mundial, sendo claramente mais predominante em mulheres (9:1 versus homens), principalmente por volta dos 50 anos (após a menopausa), ainda que também possa aparecer depois da menarca (entre os 20 e os 30 anos). Considera se que a etiologia da SS é multifatorial. Fatores genéticos, ambientais, hormonais e virais estão implicados na sua etiopatogénese. É muito importante o papel dos Médicos Dentistas no diagnóstico da SSp, uma vez que na maior parte dos casos são eles quem detetam os primeiros sintomas, mais propriamente a boca seca. Diversos testes auxiliares são utilizados para o diagnóstico desta doença, tais como: o teste de Schimer, o teste de Rosa Bengala, a Sialometria, a Sialografia, a Biópsia das glândulas salivares, entre outros. A SSp, regra geral, tem um curso não doloroso, sendo a boca seca e a secura ocular as suas duas características clínicas mais salientes. A maior parte das manifestações orais que se apresentam nestes pacientes são resultado de hipofunção das glândulas salivares (da boca seca), tais como: a cárie dentária, a doença periodontal, as infeções fúngicas, entre outras. Esta doença também se pode associar a problemas a nível sistémico, que podem ser subdivididos em não viscerais (pele, artralgia, mialgia) e viscerais (pulmão, coração, rim, sistema gastrointestinal, sistema endócrino e sistema nervoso central e periférico). O tratamento é empírico, sintomático e direcionado a tratar as complicações da doença mais inicial, que consiste em limitar os danos da xerostomia e da queratoconjuntivite. A prevenção dos sintomas a nível oral e ocular é fundamental em pacientes com SSp, para assim terem maior qualidade de vida.

Tumores do espaço parafaríngeo: experiência de 10 anos do IPO-LFG

Introdução: As neoplasias do espaço parafaríngeo são raras, representando apenas 0,5% dos tumores da cabeça e pescoço. A maioria são benignas, mas uma ampla variedade de patologias benignas e malignas podem ser encontradas neste espaço, o que cria desafios complexos de diagnóstico e tratamento. Objetivo: Descrever e analisar uma série de casos de neoplasias primárias do espaço parafaríngeo tratadas no Instituto Português de Oncologia de Lisboa Francisco Gentil (IPOLFG). Material e métodos: Estudo retrospetivo, com recolha e análise dos dados dos processos clínicos de tumores primários do espaço parafaríngeo, que foram diagnosticados ou referenciados ao IPOLFG entre 1 de Janeiro de 2003 e 31 de Dezembro de 2013. Resultados: Foram incluídos 38 doentes. A idade mediana foi de 52 anos (Âmbito Interquartil: 40-63 anos). Dez (26,3%) doentes eram assintomáticos. O sintoma mais comum à apresentação foi a sensação de corpo estranho orofaríngeo (23,7%) e o achado mais frequente foi um abaulamento orofaríngeo (78,4%). Todos os doentes fizeram exames de imagem pré-operatórios: 94,7% tomografia computorizada e 68,4% ressonância magnética. A citologia aspirativa foi realizada em 39,5%. 31 tumores eram benignos (81,6%), sendo os mais frequentes os adenomas pleomórficos (58,1%). 7 eram malignos (18,4%), com os carcinomas exadenomas pleomórficos (28,6%) e os linfomas (28,6%) sendo os mais comuns. 36 doentes (94,7%) foram submetidos a tratamento cirúrgico primário; os outros 2 doentes (5,3%) receberam tratamento não cirúrgico, com quimioterapia e quimioradioterapia, respectivamente. A abordagem cervical foi a mais utilizada (80%). A mandibulotomia foi necessária em apenas 5,7%. A complicação mais frequente foi a neuropatia de pares cranianos de novo, identificada em 22,2%. Destes, 75% foram sequela da resseção de tumores neurogénicos. Todas as neuropatias que resultaram da resseção de tumores não neurogénicos foram transitórias. O follow-up mediano foi de 6,5 anos. A taxa de recorrência foi de 13,5%. Conclusões: Os tumores do espaço parafaríngeo requerem um elevado índice de suspeição para serem diagnosticados num estadio precoce. A resseção cirúrgica completa é o principal tratamento. A abordagem cirúrgica deve ser selecionada caso a caso, mas a cervical fornece um excelente acesso à maioria dos tumores deste espaço

Internacionalização da educação superior: estratégias e ações da Universidade Tecnológica Federal do Paraná

The present dissertation is inserted in the internationalization of the university-level education research field and aimed to analyze the strategies and internationalization actions of the Universidade Tecnológica Federal do Paraná (UTFPR), locus of research. The study sought to establish the current context in which the internationalization is inserted and contextualize the research problematic presenting definitions, concepts, reasons and strategies linked to an international dimension. It also presents a historical context of the internationalization of Brazil and current public policies related to this topic. This research used content analysis to analyze institutional documents (Institutional Development Plans (2004-2017) and Management Reports (2000-2014)); semi-structured interviews (Director of International Relations, Coordinator of programs and actions related to the mobility of students, Head of the Department of Education and Dean of Research and Graduate Studies); information pertaining to the theme from the university’s website and events held in the Campus of the institution. Data were analyzed using the procedures prescribed for this type of analysis with the establishment of three categories: concepts, strategies and actions. Based on the foregoing, in terms of synthesis, could be understood that increasing the participation of UTFPR on the international scene has always been linked to the institution’s policies and goals, yet without an political institutional plan without objectives, strategies and goals established systematically. In the case of the conception of the internationalization of UTFPR it was realized that the theme currently gained more focus and greater coverage in the institution. In this context, Ciência Sem Fronteiras program contributed to, giving greater visibility to UTFPR on the world stage. From then on, specific strategies and actions are being developed in seeking internationalization under institutional perspective, of the servers, the expansion of mobility, and greater visibility of the institution in the international arena, regional integration and promotion of internationalization at the university. Overall, the management of internationalization in the institution does not have a formal project, but has specific strategies and actions seeking their expansion. Thus, the process of internationalization in UTFPR presents itself in an early stage, with strategies and actions seeking to expand the international dimension in the institution who takes singular importance to its expansion and consolidation.

Gestão do conhecimento em contexto de internacionalização: A transferência do conhecimento para as subsidiárias angolanas e a influência dos fatores culturais nesse processo

Mestrado em Gestão e Empreendedorismo

Caraterização e identificação de esquemas Ponzi: Casos Chales Ponzi, Bernard Madoff e Dona Branca

Mestrado em Auditoria

Yrittäjän sosiaalisten verkostojen muodostuminen, niihin vaikuttavat tekijät, niiden rakenne ja merkitys yrittäjälle

Tämän tutkimuksen tavoitteena oli selvittää kuinka yrittäjän verkostot muodostuvat ja minkälainen niiden rakenne on. Tavoitteena oli myös saada tietoa yrittäjän sosiaalisten verkostojen merkityksestä yrittäjälle. Tutkimus toteutettiin laadullisena tutkimuksena. Tutkimusaineisto kerättiin strukturoidulla haastattelulla ja tutkimusaineiston rinnalla käytettiin yrittäjien havainnollistamia piirroksia sekä tieteellisiä julkaisuja ja kirjallisuutta. Haastateltavina oli sekä nais- että miesyrittäjiä eri paikkakunnilta Etelä-Suomen alueelta. Tutkimustulosten mukaan yrittäjien verkostoissa voidaan havaita eri tasoja, jotka rakentuvat eri tavoilla ja ovat yrittäjälle merkitykseltään erilaisia. Verkoston eri tasoille sijoittuu yrittäjälle tärkeitä ihmisiä sen mukaan mitä hyötyä ja arvoa heillä yrittäjälle on. Tulokset osoittavat, että verkostojen rakentamiseen vaikuttavat sekä liiketoiminnan laatu, motiivit sekä yrittäjän persoona. Tulokset ovat linjassa tämän tutkimuksen perustana olevien teorioiden kanssa. Viitteitä löytyy myös siitä, että yrittäjän sukupuolella on myös merkitystä siihen, millaiseksi sosiaaliset verkostot rakentuvat sekä henkilökohtaisessa elämässä että liike-elämän puolella. Sosiaalisista verkostoista saatavat hyödyt ovat moninaisia. Lisätutkimuksia tulisi tehdä tehokkaiden työkalujen kehittämiseksi henkilöstön ja yrittäjän omien resurssien tunnistamiseksi. Tätä kautta myös yrittäjyyskasvatusta ja yrittäjäneuvontaa voitaisiin tehostaa.

A profissionalização em Educação Pré-Escolar e no 1.º Ciclo do Ensino Básico

Relatório de Estágio apresentado à Escola Superior de Educação de Paula Frassinetti para obtenção de grau de Mestre em Educação Pré-Escolar e Ensino do 1º Ciclo do Ensino Básico

Financing local development through crowdfunding: An empirical analysis of social projects in Portugal

Crowdfunding (CF) is an increasingly attractive source to fund social projects. However, to our best knowledge, the study of CF for social purposes has remained largely unexplored in the literature. This research envisages a detailed examination of the role of CF on the early-stage of the social projects at regional level. By comparing the characteristics of the projects available in the Portuguese Social Stock Exchange (PSSE) platform with others that did not use this source of financial support, we explore its role on regional development. The results we got show that, in most cases, both PSSE and Non-Governmental Organizations projects complemented the services offered by the State or by the private sector. Furthermore, about a quarter of the projects present in PSSE operated in areas that were not being addressed neither by the services offered by the State nor by the ones of the private sector. The results attained show that more recent social ventures have a greater propensity to use PSSE. The same is find in those organizations which work closely with the target audience. We also observed that the use of PSSE was correlated with the geographical scope of the Social Venture. The circumstance of having the social organization acting at a local or regional level seems to be strongly associated with the possibility of using social crowdfunding for financing social projects.

A Gestão da dualidade Afetos/Limites, numa sala de 4 anos

Relatório de estágio para a obtenção do grau Mestre em Educação Pré-Escolar

Using Intelligent Agents to Understand Management Practices and Retail Productivity

Intelligent agents offer a new and exciting way of understanding the world of work. In this paper we apply agent-based modeling and simulation to investigate a set of problems in a retail context. Specifically, we are working to understand the relationship between human resource management practices and retail productivity. Despite the fact we are working within a relatively novel and complex domain, it is clear that intelligent agents could offer potential for fostering sustainable organizational capabilities in the future. The project is still at an early stage. So far we have conducted a case study in a UK department store to collect data and capture impressions about operations and actors within departments. Furthermore, based on our case study we have built and tested our first version of a retail branch simulator which we will present in this paper.

TRIB2 in human AML: a biological and clinical investigation

Acute myeloid leukemia (AML) involves the proliferation, abnormal survival and arrest of cells at a very early stage of myeloid cell differentiation. The biological and clinical heterogeneity of this disease complicates treatment and highlights the significance of understanding the underlying causes of AML, which may constitute potential therapeutic targets, as well as offer prognostic information. Tribbles homolog 2 (Trib2) is a potent murine oncogene capable of inducing transplantable AML with complete penetrance. The pathogenicity of Trib2 is attributed to its ability to induce proteasomal degradation of the full length isoform of the transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα p42). The role of TRIB2 in human AML cells, however, has not been systematically investigated or targeted. Across human cancers, TRIB2 oncogenic activity was found to be associated with its elevated expression. In the context of AML, TRIB2 overexpression was suggested to be associated with the large and heterogeneous subset of cytogenetically normal AML patients. Based upon the observation that overexpression of TRIB2 has a role in cellular transformation, the effect of modulating its expression in human AML was examined in a human AML cell line that expresses high levels of TRIB2, U937 cells. Specific suppression of TRIB2 led to impaired cell growth, as a consequence of both an increase in apoptosis and a decrease in cell proliferation. Consistent with these in vitro results, TRIB2 silencing strongly reduced progression of the U937 in vivo xenografts, accompanied by detection of a lower spleen weight when compared with mice transplanted with TRIB2- expressing control cells. Gene expression analysis suggested that TRIB2 modulates apoptosis and cell-cycle sensitivity by influencing the expression of a subset of genes known to have implications on these phenotypes. Furthermore, TRIB2 was found to be expressed in a significant subset of AML patient samples analysed. To investigate whether increased expression of this gene could be afforded prognostic significance, primary AML cells with dichotomized levels of TRIB2 transcripts were evaluated in terms of their xenoengraftment potential, an assay reported to correlate with disease aggressiveness observed in humans. A small cohort of analysed samples with higher TRIB2 expression did not associate with preferential leukaemic cell engraftment in highly immune-deficient mice, hence, not predicting for an adverse prognosis. However, further experiments including a larger cohort of well characterized AML patients would be needed to clarify TRIB2 significance in the diagnostic setting. Collectively, these data support a functional role for TRIB2 in the maintenance of the oncogenic properties of human AML cells and suggest TRIB2 can be considered a rational therapeutic target. Proteasome inhibition has emerged as an attractive target for the development of novel anti-cancer therapies and results from translational research and clinical trials support the idea that proteasome inhibitors should be considered in the treatment of AML. The present study argued that proteasome inhibition would effectively inhibit the function of TRIB2 by abrogating C/EBPα p42 protein degradation and that it would be an effective pharmacological targeting strategy in TRIB2-positive AMLs. Here, a number of cell models expressing high levels of TRIB2 were successfully targeted by treatment with proteasome inhibitors, as demonstrated by multiple measurements that included increased cytotoxicity, inhibition of clonogenic growth and anti-AML activity in vivo. Mechanistically, it was shown that block of the TRIB2 degradative function led to an increase of C/EBPα p42 and that response was specific to the TRIB2-C/EBPα axis. Specificity was addressed by a panel of experiments showing that U937 cells (express detectable levels of endogenous TRIB2 and C/EBPα) treated with the proteasome inhibitor bortezomib (Brtz) displayed a higher cytotoxic response upon TRIB2 overexpression and that ectopic expression of C/EBPα rescued cell death. Additionally, in C/EBPα-negative leukaemia cells, K562 and Kasumi 1, Brtz-induced toxicity was not increased following TRIB2 overexpression supporting the specificity of the compound on the TRIB2-C/EBPα axis. Together these findings provide pre-clinical evidence that TRIB2- expressing AML cells can be pharmacologically targeted with proteasome inhibition due, in part, to blockage of the TRIB2 proteolytic function on C/EBPα p42. A large body of evidence indicates that AML arises through the stepwise acquisition of genetic and epigenetic changes. Mass spectrometry data has identified an interaction between TRIB2 and the epigenetic regulator Protein Arginine Methyltransferase 5 (PRMT5). Following assessment of TRIB2‟s role in AML cell survival and effective targeting of the TRIB2-C/EBPα degradation pathway, a putative TRIB2/PRMT5 cooperation was investigated in order to gain a deeper understanding of the molecular network in which TRIB2 acts as a potent myeloid oncogene. First, a microarray data set was interrogated for PRMT5 expression levels and the primary enzyme responsible for symmetric dimethylation was found to be transcribed at significantly higher levels in AML patients when compared to healthy controls. Next, depletion of PRMT5 in the U937 cell line was shown to reduce the transformative phenotype in the high expressing TRIB2 AML cells, which suggests that PRMT5 and TRIB2 may cooperate to maintain the leukaemogenic potential. Importantly, PRMT5 was identified as a TRIB2-interacting protein by means of a protein tagging approach to purify TRIB2 complexes from 293T cells. These findings trigger further research aimed at understanding the underlying mechanism and the functional significance of this interplay. In summary, the present study provides experimental evidence that TRIB2 has an important oncogenic role in human AML maintenance and, importantly in such a molecularly heterogeneous disease, provides the rational basis to consider proteasome inhibition as an effective targeting strategy for AML patients with high TRIB2 expression. Finally, the identification of PRMT5 as a TRIB2-interacting protein opens a new level of regulation to consider in AML. This work may contribute to our further understanding and therapeutic strategies in acute leukaemias.

Tissue and cell's trafficking: a byproduct of transplant activity's trash. The future is now. A Public Health problem

Transplantation is one of the most beautiful achievements for humanity in the last century and became the last hope to many patients. As other beautiful achievements, it has been used by criminals. The future of transplantation will be focused on tissue and cells transplantation. Trafficking of human beings to organ removal and trafficking of human organs are an early stage of trafficking on tissues and cells comparable with slaves trafficking in the 17th and 18th century. As 400 years ago, the motive for the crime is development, economy and profit. Transplant surgery is the modern “cotton gin” to this new commerce. Poverty exploitation, unprotected people, are always the victims. Even so, there are some differences since then. The paying buyers are the patients themselves and the “cotton” transplanted is not so harmless. Unsafe tissues and cells inappropriately collected and allocated can be so dangerous to the recipient and his family, that the dreamed transplant/implant becomes a nightmare. Beyond the trafficking crime, there is a most dangerous associated crime that is the crime of spreading dangerous infectious diseases.