[pt] Entender como características culturais interferem no desempenho de uma empresa, é extremamente relevante em mercados cada vez mais competitivos e dinâmicos. Assim sendo, o objetivo deste trabalho é analisar a relação da Cultura e o Desempenho Organizacional. A partir da revisão da literatura foi realizado um estudo de caso em uma empresa privada do setor de seguros, que se destaca no mercado em que atua, estando entre as maiores seguradoras independentes do Brasil em Vida, Previdência e Capitalização e ao longo dos anos, recebeu prêmios e participou dos mais importantes rankings financeiros nacionais, reunindo certificações que reforçam a credibilidade, o desempenho e a excelência em sua gestão. A pesquisa coletou dados referentes ao resultado do desempenho organizacional, mais especificamente o resultado dos indicadores financeiros - Return on Sales (ROS), Return on Asset (ROA) e Retorno sobre Patrimônio Líquido (ROE) e, pela aplicação do questionário do modelo de Cultura Organizacional de Denison - DOCS (1990) no seu quadro gerencial, foi possível avaliar as características chaves da cultura organizacional, sob as dimensões de Missão, Consistência, Envolvimento e Adaptabilidade. A análise qualitativa dos dados coletados evidenciou que existe relação entre o resultado das dimensões culturais e os indicadores de rentabilidade, e sugere a importância do aprofundamento desta linha de pesquisa em outras organizações. / [en] Understanding how organizational cultures interfere with a company s performance, and what are the important cultural characteristics to leverage this performance, is extremely relevant in increasingly competitive and dynamic markets. Therefore, the objective of this work is to analyze the relationship between Culture and Organizational Performance. From the literature review, a case study was conducted in a private insurance company, which stands out in the market in which it operates, being among the largest independent insurers in Brazil in Life, Private Pension and Savings Bonds and over the years, received awards and participated in the most important national financial rankings, gathering certifications that reinforce the credibility, the performance and the excellence in its management. The survey collected data on the results of organizational performance, more specifically the result of the financial indicators - Return on Sales (ROS), Return on Asset (ROA) and Return on Equity (ROE) and, by applying the Denison Organizational Culture Model - DOCS questionnaire to managers, it was possible to evaluate the key characteristics of the organizational culture, under the dimensions of Mission, Consistency, Involvement and Adaptability. The qualitative analysis of the data collected showed that there is a relationship between the results of the cultural dimensions and the indicators of profitability and suggests the importance of future research on this subject in other organizations.

This thesis describes the influences of organizational culture on the success of Alibaba company. In this thesis the influence of organizational culture on the success of Alibaba is explored from 4 aspects. These four aspects include: a) the definition of organizational culture, b) the characteristics of organizational culture, c) the effect of organizational culture on employees, d) the organizational culture model. This thesis uses the case study and interview to explore the relationship between the organizational culture and the success of Alibaba company. The result of the thesis is basic on the answer to the interview from the employees of Alibaba company. The author found that the reason of Alibaba becoming a successful company is its' established organizational culture based on the value of all employees. All the employees believe and trust the organizational culture and they use organizational culture to demand oneself whatever in the company or life. The organizational culture pushes the company and employees' development and growth, which is the main reason for Alibaba company to be a success.

Chlamydia trachomatis infections represent the predominant cause of bacterial sexually transmitted infections. As an obligate intracellular bacterium, C. trachomatis is dependent on the host cell for survival, propagation, and transmission. Thus, factors that affect the host cell, including nutrition, cell cycle, and environmental signals, have the potential to impact chlamydial development. Previous studies have demonstrated that activation of Wnt/β-catenin signaling benefits C. trachomatis infections in fallopian tube epithelia. In cervical epithelial cells chlamydiae sequester β-catenin within the inclusion. These data indicate that chlamydiae interact with the Wnt signaling pathway in both the upper and lower female genital tract (FGT). However, hormonal activation of canonical and non-canonical Wnt signaling pathways is an essential component of cyclic remodeling in another prominent area of the FGT, the endometrium. Given this information, we hypothesized that Wnt signaling would impact chlamydial infection in endometrial epithelial cells. To investigate this hypothesis, we analyzed the effect of Wnt inhibition on chlamydial inclusion development and elementary body (EB) production in two endometrial cell lines, Ishikawa (IK) and Hec-1B, in nonpolarized cell culture and in a polarized endometrial epithelial (IK)/stromal (SHT-290) cell co-culture model. Inhibition of Wnt by the small molecule inhibitor (IWP2) significantly decreased inclusion size in IK and IK/SHT-290 cultures (p < 0.005) and chlamydial infectivity (p ≤ 0.01) in both IK and Hec-1B cells. Confocal and electron microscopy analysis of chlamydial inclusions revealed that Wnt inhibition caused chlamydiae to become aberrant in morphology. EB formation was also impaired in IK, Hec-1B and IK/SHT-290 cultures regardless of whether Wnt inhibition occurred throughout, in the middle (24 hpi) or late (36 hpi) during the development cycle. Overall, these data lead us to conclude that Wnt signaling in the endometrium is a key host pathway for the proper development of C. trachomatis.

Les lymphomes B non-Hodgkiniens (LNHB) représentent le type d’hémopathie maligne le plus fréquent. Ces pathologies sont traitées par l’association de chimiothérapies conventionnelles et d’immunothérapies dirigées contre le CD20. Bien qu’efficace, 40% des patients résistent ou rechutent après le traitement. Deux raisons peuvent expliquer ces échecs thérapeutiques : 1) l’absence de cibles thérapeutiques impliquées dans plusieurs processus oncogéniques et 2) l’absence de modèles pré-cliniques de LNHB pertinents pour le test de molécules thérapeutiques et la compréhension de la lymphomagenèse. Le calcium est un messager ubiquitaire qui est impliqué dans de nombreux processus cellulaires en condition physiologique et pathologique. La principale voie d’entrée de calcium dans les lymphocytes B est l’entrée capacitive de calcium médiée par Orai1 et STIM1. Ces deux protéines ont été largement décrites pour être impliquées dans les processus tumoraux de nombreux cancers, cependant leurs rôles dans la lymphomagenèse restait à élucider. Nos travaux ont révélé l'implication de la signalisation calcique dans la mort induite par le GA101, un anti CD20 de nouvelle génération actuellement en essai clinique. De plus, nous avons mis en évidence l’implication des protéines Orai1 et STIM1 dans la migration des cellules cancéreuses de LNHB. De manière intéressante, l’implication de ces deux protéines dans la migration cellulaire est calcium indépendante, suggérant donc un nouveau rôle de ces protéines. Enfin, grâce à la technologie des capsules cellulaires nous avons établi un nouveau modèle 3D de lymphome mimant la niche tumorale en incluant des cellules du microenvironnement et de la matrice extracellulaire. Ce modèle semble particulièrement pertinent pour le screening de molécules et la compréhension des mécanismes de la lymphomagenèse. Ce travail de thèse révèle ainsi le ciblage de Orai1 et STIM1 comme potentiellement intéressant dans le traitement du LNHB. / B-cell non-Hodgkin lymphomas (BNHL) are the most common hematological malignancies, usually treated with a combination of chemotherapy and anti CD20 immunothérapie. However, 40% of patients are resistant or relapse after treatment. These therapeutic failures could be due to 1) lack of therapeutic targets implicated in several oncogenic processes, 2) lack of relevant preclinical BNHL models for drug screening and lymphomagenesis studies. Calcium is an essential second messenger involved in various cell functions. In B cells, calcium entry is mainly due to Orai1 and STIM1 proteins, both of which have been associated with oncogenesis on solid tumors. However, their role in lymphomagenesis still remains to be elucidated. Our work shows that calcium signaling in BNHL cells participates in cell death induced by GA101, a novel anti-CD20 monoclonal antibody. We also demonstrate that Orai1 and STIM1 play a role in BNHL cell migration. Interestingly, both proteins controlled cell migration in a calcium-independent manner, suggesting a new role for these proteins. Finally, using cellular capsule technology, we established a new BNHL 3D model mimicking tumoral niche by including extracellular matrix and stromal cells. This new model could be used for drug screening and understanding lymphomagenesis. In summary, this work suggests that targeting of Orai1 and STIM1 is promising for BNHL treatment.

Submitted by Cássia Santos (cassia.bcufg@gmail.com) on 2016-08-05T11:42:52Z No. of bitstreams: 2 Tese - Darliane de Castro Santos - 2016.pdf: 2196832 bytes, checksum: 3914f15d046c5d2c2bd24d888cb44fab (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2016-08-05T13:59:40Z (GMT) No. of bitstreams: 2 Tese - Darliane de Castro Santos - 2016.pdf: 2196832 bytes, checksum: 3914f15d046c5d2c2bd24d888cb44fab (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2016-08-05T13:59:40Z (GMT). No. of bitstreams: 2 Tese - Darliane de Castro Santos - 2016.pdf: 2196832 bytes, checksum: 3914f15d046c5d2c2bd24d888cb44fab (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-03-23 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The presence of trees in silvopastoral systems (SSP) can influence the forage dry mass, the structural and chemical characteristics as well as animal performance in these systems. Modeling is a tool that can help to understand the dynamics of forage growth in SSP. The research objective was to evaluate the cumulative dry matter, availability, structural characteristics and chemical composition of Brachiaria brizantha cv. BRS Piatã (Piatã grass) and animal performance in two densities of trees in silvopastoral system, in contrast to area without trees, in the rainy and dry periods in the Brazilian Cerrado. Concomitantly, the study tested the ability of the STICS crop model to simulate forage dry mass production and leaf area index of Piatã grass. The forage was the Piatã grass and the tree species the eucalyptus urograndis (Eucalyptus grandis x E. urophylla) planted on the North-South direction, with the treatments: forage in area without eucalyptus (control); forage grown on eucalyptus understory with spacing between rows of 22 m (SSP22); forage grown on eucalyptus understory with spacing between rows of 12 m (SSP12). The experimental design was a randomized complete block with three replications and evaluations were conducted from April 2013 to April 2014. There was a reduction in cumulative dry mass and in the accumulation rate of Piatã grass in SSP in the rainy period and the Western side suffered greater interference from trees during this period. For every 1% reduction of photosynthetically active radiation occurred a decrease of 1.35% in the forage dry mass, corresponding to 42.8 kg ha-1. The structural traits of Piatã grass were changed in both periods in SSP. There was a higher availability of dry mass in the treatment without trees in both periods and the SSP22 treatment was higher than SSP12 only in the rainy season. In SSP12 and SSP22 treatments higher levels of crude protein, but lower density of forage were observed. The stem-leaf ratio and in vitro digestibility of dry matter were higher in control compared to SSP12. The treatments did not affect cell wall components, but the period of the year did. The stocking rate was higher in control and the animal average daily gain did not differ between treatments. The live weight gain per hectare was higher in SSP22 compared to SSP12 and both were lower than control. The low values for all statistical criteria showed the good performance of the STICS model in the simulation of dry mass, forage accumulation and leaf area index, and it is a promising model for the simulation of these variables. From this study, new simulations may be conducted to calibrate this model to help to define spacing between alleys potential for SSP. To adopt the SSP, with eucalyptus trees planted on North-South direction and with the main objective of producing animals, spacing between alleys not less than 22 m is recommended. / A presença de árvores em sistemas silvipastoris (SSP) pode influenciar a massa seca de forragem, as características estruturais, bromatológicas e o desempenho animal nestes sistemas. Uma ferramenta que pode ajudar a compreender a dinâmica do crescimento de forragem em SSP é a modelagem. Diante disso, objetivou-se avaliar o acúmulo de massa seca, a disponibilidade, as características estruturais e a composição bromatológica da Brachiaria brizantha cv. BRS Piatã (capim-Piatã), bem como o desempenho animal em duas densidades de árvores em sistema silvipastoril, em contraste com área sem a presença de árvores nos períodos chuvoso e seco do Cerrado brasileiro. Concomitantemente, foi testada a capacidade do modelo de cultura STICS na simulação da produção de massa seca de forragem e do índice de área foliar do capim-Piatã. A forrageira foi o capim-Piatã e a espécie arbórea o eucalipto urograndis (Eucalyptus grandis x E. urophylla) plantado na orientação norte-sul, sendo os tratamentos: forrageira cultivada em área sem árvores (controle); forrageira cultivada em sub-bosque de eucalipto com espaçamento entre renques de 22 m (SSP22); forrageira cultivada em sub-bosque de eucalipto com espaçamento entre renques de 12 m (SSP12). O delineamento experimental foi em blocos completos ao acaso com três repetições e as avaliações conduzidas de abril de 2013 a abril de 2014. Houve redução na massa seca acumulada e na taxa de acúmulo do capim-Piatã em SSP no período chuvoso e a face Oeste foi a que sofreu maior interferência das árvores neste período. Para cada 1% de redução de radiação fotossinteticamente ativa ocorreu diminuição de 1,35% na massa seca de forragem, o que correspondeu a 42,8 kg ha-1. As características estruturais do capim-Piatã foram alteradas nos dois períodos em SSP. Houve maior disponibilidade de massa seca de forragem no tratamento sem árvores nos dois períodos e o tratamento SSP22 foi superior ao SSP12 somente no período chuvoso. Nos tratamentos SSP12 e SSP22 observou-se maiores teores de proteína bruta, porém menor densidade de forragem. Já a relação folha-colmo e a digestibilidade in vitro da matéria seca foram superiores no controle quando comparado ao SSP12. Os componentes da parede celular não foram afetados pelos tratamentos, mas somente pelo período do ano. A taxa de lotação foi maior no controle e o ganho animal médio diário não se diferiu entre os tratamentos. O ganho de peso vivo por hectare foi superior no SSP22 quando comparado ao SSP12 e os dois foram inferiores ao controle. Os baixos valores para todos os critérios estatísticos mostram a boa performance do modelo STICS na simulação das variáveis massa seca de forragem, acúmulo de forragem e índice de área foliar sendo um modelo promissor para a simulação dessas variáveis. A partir desse estudo, novas simulações poderão ser conduzidas visando a calibração desse modelo para auxiliar na definição de espaçamentos entre renques potenciais para SSP. Quando se desejar adotar o SSP, com árvores de eucalipto em sentido de plantio Norte-Sul, com objetivo principal a produção animal recomenda-se, espaçamentos entre os renques não inferiores a 22 m

No description available.

Biomaterials are designed to improve impaired healing of injured tissue. To accomplish better cell integration, we suggest to coat biomaterial surfaces with bio-functional proteins. Here, a mussel-derived surface-binding peptide is used and coupled to CXCL12 (stromal cell-derived factor 1α), a chemokine that activates CXCR4 and consequently recruits tissue-specific stem and progenitor cells. CXCL12 variants with either non-releasable or protease-mediated-release properties were designed and compared. Whereas CXCL12 was stabilized at the N-terminus for protease resistance, a C-terminal linker was designed that allowed for specific cleavage-mediated release by matrix metalloproteinase 9 and 2, since both enzymes are frequently found in wound fluid. These surface adhesive CXCL12 derivatives were produced by expressed protein ligation. Functionality of the modified chemokines was assessed by inositol phosphate accumulation and cell migration assays. Increased migration of keratinocytes and primary mesenchymal stem cells was demonstrated. Immobilization and release were studied for bioresorbable PCL-co-LC scaffolds, and accelerated wound closure was demonstrated in an ex vivo wound healing assay on porcine skin grafts. After 24 h, a significantly improved CXCL12-specific growth stimulation of the epithelial tips was already observed. The presented data display a successful application of protein-coated biomaterials for skin regeneration.

O carcinoma epidermóide representa mais de 90% das neoplasias malignas de cabeça e pescoço, apresentando taxas elevadas de morbi-mortalidade, porém pouco se sabe sobre as vias de sinalização que estão envolvidas na progressão tumoral. Têm sido relatado na literatura, que alguns estímulos podem ativar a holoenzima PI3K que, por sua vez, desencadeia um processo que induz a fosforilação da proteína Akt (pAkt) que leva a ativação e a translocação do NF-B do citoplasma para o núcleo, onde ocorre a transcrição de genes envolvidos na proliferação e invasão celular. Assim, esse estudo analisou, através dos métodos de Imunofluorescência e Western Blot, a expressão das proteínas pAkt, NF-B e Ciclina D1 em três linhagens de células de carcinoma epidermóide de cabeça e pescoço (HN6, HN30 e HN31) submetidas a cultivo tridimensional e ensaio de invasão (gerando clones invasivos HN6.1, HN30.1 e HN31.1), ambos realizados com Matrigel®. O pAkt apresentou marcação citoplasmática e nuclear nas linhagens celulares HN6, HN30, HN6.1 e na HN30 submetida ao cultivo tridimensional, todavia, as linhagens celulares HN31, HN30.1, HN31.1 e HN6/HN31 cultivadas tridimensionalmente, apresentaram positividade predominantemente nuclear. No caso do NF-B, a localização foi marcadamente citoplasmática em todas as linhagens celulares cultivadas bi ou tridimensionalmente, porém, com exceção da HN31.1, o padrão de marcação foi citoplasmático e nuclear nos clones invasivos. Por fim, a Ciclina D1 exibiu imunopositividade apenas nuclear. A técnica de Western Blot mostrou diminuição nos níveis de expressão das proteínas analisadas quando as células foram cultivadas em Matrigel®, sendo, na maioria das vezes, essa redução estatisticamente significante, exceto no caso da linhagem celular HN6, que apresentou um aumento significativo de Ciclina D1. Os clones invasivos HN6.1 e HN30.1 exibiram elevação significativa dos níveis de expressão de pAkt e NF-B porém, a HN31.1 apresentou aumento de pAkt e discreta diminuição de NF-B, mas ambos os valores não estatisticamente significantes. Em relação à Ciclina D1, houve um aumento dos seus níveis em todas as linhagens invasivas, sendo que apenas na HN6.1 foi estatisticamente significante. Esses resultados mostraram que, nas linhagens celulares avaliadas, quando cultivadas em ambiente tridimensional, a significativa redução dos níveis de expressão de proteínas da via de sinalização PI3K ocorreu devido a uma possível fase adaptativa dessas células ao Matrigel® que seria seguida provavelmente por uma etapa de aumento do potencial proliferativo e posterior transdiferenciação de algumas células para ganho de fenótipo mais agressivo. Além disso, este estudo mostrou a participação da via de sinalização Akt/NF-B/Ciclina D1 no processo de invasão das células de carcinoma epidermóide de cabeça e pescoço (HN6.1 e HN30.1). / Squamous cell carcinoma represents more than 90% of the head and neck malignant tumors, with high mortality rates. Nevertheless, the knowledge about signaling pathways involved in tumor progression remains unclear. The relationship between pAkt and NF-B is well established in carcinogenesis. It is known that the activation of PI3K can be induced by some factors what leads to Akt phosphorilation (pAkt). This further event starts an activation cascade that induces NF-B translocation from the cytoplasm into the nucleus where the transcription of genes enrolled in cellular proliferation and invasion will be done. Therefore, this study analyzed the status of pAkt, NF-B and Cyclin D1 proteins by Immunofluorescence and Western Blot methods in three head and neck squamous cell carcinoma cell lines (HN6, HN30 and HN31) submitted to three-dimensional culture model and an in vitro invasion assay (invasive clones HN6.1, HN30.1 e HN31.1), both with Matrigel®. pAkt expression was detected in cytoplasm and nucleus in HN6, HN30, HN6.1 and HN30 cultured with Matrigel®, however, HN31, HN30.1, HN31.1 cell lines and HN6/HN31 submitted to three-dimensional culture model showed nuclear expression. NF-B localization was strongly cytoplasmatic in all cell lines cultured with or without Matrigel®, but, regarding HN31.1, NF-B protein expression was nuclear and cytoplasmatic in the invasive clones. Cyclin D1 was nuclear in all cell lines analyzed. Western blot assays showed a decrease in pAkt, NF-B and Cyclin D1 expression levels in all cells lines in three-dimensional culture model, most of them statistically significant, but It was detected a considerable increase in Cyclin D1 expression in HN6 cultured in threedimensional model. Moreover, HN6.1 and HN30.1 showed a significant enhance in pAkt and NF-B levels but, HN31.1 demonstrated a raise in pAkt and a slight decline in NF-B, both were not statistically significant. Finally, an increase in Cyclin D1 expression levels was illustrated in all cell lines but, only HN6.1 showed a statistic signal. These results suggest that, in the cell lines studied, when cultured in threedimensional model, a noteworthy reduction in expression levels of PI3K signaling pathway proteins happened for the reason that a possibly adaptation phase of these cells to Matrigel® was occurring, in the first moment, but it would be probably followed by an increase proliferative potential stage and subsequent transdifferentiation of some cells that could show, consequently, a more aggressive phenotype. At last, this study revealed the participation of Akt/NF-B/Cyclin D1 signaling pathway in invasion process of head and neck squamous cell carcinoma (HN6.1 and HN30.1).

O carcinoma epidermóide representa mais de 90% das neoplasias malignas de cabeça e pescoço, apresentando taxas elevadas de morbi-mortalidade, porém pouco se sabe sobre as vias de sinalização que estão envolvidas na progressão tumoral. Têm sido relatado na literatura, que alguns estímulos podem ativar a holoenzima PI3K que, por sua vez, desencadeia um processo que induz a fosforilação da proteína Akt (pAkt) que leva a ativação e a translocação do NF-B do citoplasma para o núcleo, onde ocorre a transcrição de genes envolvidos na proliferação e invasão celular. Assim, esse estudo analisou, através dos métodos de Imunofluorescência e Western Blot, a expressão das proteínas pAkt, NF-B e Ciclina D1 em três linhagens de células de carcinoma epidermóide de cabeça e pescoço (HN6, HN30 e HN31) submetidas a cultivo tridimensional e ensaio de invasão (gerando clones invasivos HN6.1, HN30.1 e HN31.1), ambos realizados com Matrigel®. O pAkt apresentou marcação citoplasmática e nuclear nas linhagens celulares HN6, HN30, HN6.1 e na HN30 submetida ao cultivo tridimensional, todavia, as linhagens celulares HN31, HN30.1, HN31.1 e HN6/HN31 cultivadas tridimensionalmente, apresentaram positividade predominantemente nuclear. No caso do NF-B, a localização foi marcadamente citoplasmática em todas as linhagens celulares cultivadas bi ou tridimensionalmente, porém, com exceção da HN31.1, o padrão de marcação foi citoplasmático e nuclear nos clones invasivos. Por fim, a Ciclina D1 exibiu imunopositividade apenas nuclear. A técnica de Western Blot mostrou diminuição nos níveis de expressão das proteínas analisadas quando as células foram cultivadas em Matrigel®, sendo, na maioria das vezes, essa redução estatisticamente significante, exceto no caso da linhagem celular HN6, que apresentou um aumento significativo de Ciclina D1. Os clones invasivos HN6.1 e HN30.1 exibiram elevação significativa dos níveis de expressão de pAkt e NF-B porém, a HN31.1 apresentou aumento de pAkt e discreta diminuição de NF-B, mas ambos os valores não estatisticamente significantes. Em relação à Ciclina D1, houve um aumento dos seus níveis em todas as linhagens invasivas, sendo que apenas na HN6.1 foi estatisticamente significante. Esses resultados mostraram que, nas linhagens celulares avaliadas, quando cultivadas em ambiente tridimensional, a significativa redução dos níveis de expressão de proteínas da via de sinalização PI3K ocorreu devido a uma possível fase adaptativa dessas células ao Matrigel® que seria seguida provavelmente por uma etapa de aumento do potencial proliferativo e posterior transdiferenciação de algumas células para ganho de fenótipo mais agressivo. Além disso, este estudo mostrou a participação da via de sinalização Akt/NF-B/Ciclina D1 no processo de invasão das células de carcinoma epidermóide de cabeça e pescoço (HN6.1 e HN30.1). / Squamous cell carcinoma represents more than 90% of the head and neck malignant tumors, with high mortality rates. Nevertheless, the knowledge about signaling pathways involved in tumor progression remains unclear. The relationship between pAkt and NF-B is well established in carcinogenesis. It is known that the activation of PI3K can be induced by some factors what leads to Akt phosphorilation (pAkt). This further event starts an activation cascade that induces NF-B translocation from the cytoplasm into the nucleus where the transcription of genes enrolled in cellular proliferation and invasion will be done. Therefore, this study analyzed the status of pAkt, NF-B and Cyclin D1 proteins by Immunofluorescence and Western Blot methods in three head and neck squamous cell carcinoma cell lines (HN6, HN30 and HN31) submitted to three-dimensional culture model and an in vitro invasion assay (invasive clones HN6.1, HN30.1 e HN31.1), both with Matrigel®. pAkt expression was detected in cytoplasm and nucleus in HN6, HN30, HN6.1 and HN30 cultured with Matrigel®, however, HN31, HN30.1, HN31.1 cell lines and HN6/HN31 submitted to three-dimensional culture model showed nuclear expression. NF-B localization was strongly cytoplasmatic in all cell lines cultured with or without Matrigel®, but, regarding HN31.1, NF-B protein expression was nuclear and cytoplasmatic in the invasive clones. Cyclin D1 was nuclear in all cell lines analyzed. Western blot assays showed a decrease in pAkt, NF-B and Cyclin D1 expression levels in all cells lines in three-dimensional culture model, most of them statistically significant, but It was detected a considerable increase in Cyclin D1 expression in HN6 cultured in threedimensional model. Moreover, HN6.1 and HN30.1 showed a significant enhance in pAkt and NF-B levels but, HN31.1 demonstrated a raise in pAkt and a slight decline in NF-B, both were not statistically significant. Finally, an increase in Cyclin D1 expression levels was illustrated in all cell lines but, only HN6.1 showed a statistic signal. These results suggest that, in the cell lines studied, when cultured in threedimensional model, a noteworthy reduction in expression levels of PI3K signaling pathway proteins happened for the reason that a possibly adaptation phase of these cells to Matrigel® was occurring, in the first moment, but it would be probably followed by an increase proliferative potential stage and subsequent transdifferentiation of some cells that could show, consequently, a more aggressive phenotype. At last, this study revealed the participation of Akt/NF-B/Cyclin D1 signaling pathway in invasion process of head and neck squamous cell carcinoma (HN6.1 and HN30.1).

To safeguard the health and well-being of faculty, students, staff, and the community is of moral imperative for higher education institutions. Likewise, protecting the environment is a socially sound practice. Furthermore, building and maintaining a positive safety culture is believed to contribute to productive environmental health and safety (EH&S) outcomes. Higher education EH&S leaders are at the center of universities’ efforts in maintaining a positive safety culture. The purpose of this inquiry was to study higher education EH&S leaders’ perspectives on safety culture and contribute to closing the academic literature gap in the higher education setting. Interviews and a survey were the data collection techniques. EH&S leaders of U.S. higher education institutions participated in the study. I used Cooper’s (2000, 2016) reciprocal safety culture model as a theoretical framework and a mixed methods research design to find answers to the research questions. The survey results revealed how EH&S leaders viewed different aspects of their operations, and findings from the interviews revealed the leaders’ lived experiences. For example, the quantitative study showed 100% of the participants strongly agree or agree that shaping the safety culture of their campus is part of their role. In addition, the qualitative data identified distinct strategies employed by leaders to shape the safety culture of their campuses. Four major themes were identified in the qualitative data. In the first theme, The Higher Education Safety Culture, the EH&S leaders reflected on their lived experiences and the importance of positive safety culture in accomplishing their goals. They mobilize their campus communities in a collective effort to achieve a healthy and safe working environment, minimize the impact on the environment, and remain compliant with regulatory requirements. The second theme, Higher Education Environmental Health and Safety Programs, stressed the plans and procedures the leaders and their departments engage in their daily operations. The third theme, Higher Education Management’s Role in Environmental Health and Safety Operations, manifested the leaders’ equivocal voice on the necessity of the higher education leadership and upper management support to fulfill their missions. The last theme, Modus Operandi of Higher Education Environmental Health and Safety Leaders, is about a range of strategies and tactics the EH&S leaders employed to succeed in a structured, bureaucratic, and challenging environment. The findings have direct implications for both higher education EH&S professionals and higher education senior leadership. The study findings implied EH&S leaders should focus their effort where it generates the best outcome, namely: (a) orchestrate the campus community toward a positive safety; (b) build and implement effective EH&S programs; (c) bring upper management and leadership aboard; (d) apply effective communication; (e) build trust; (f) define their role as a consultant; (g) stand out; and (h) create a brand, motto, and slogan where possible. For higher education senior leadership, participants emphasized the necessity of upper management and leadership support to build and maintain a positive safety culture on the campus, agreeing with Cooper (2000, 2016). This work helps contribute to making higher education senior leadership and upper management understand their role in their campuses’ safety culture and provide due support and actively participate. This study served as an initial exploration in understanding higher education EH&S leaders’ perspectives on safety culture and contributing to closing the literature gap. It also opened a door for future research. Broadening the audience to students, faculty, and staff are reasonable candidates for further research for a more comprehensive understanding of the safety culture in higher education. In addition, expanding the survey to include more EH&S leaders of higher education will elaborate on the EH&S operations, challenges, and sentiment.