Regulation of cell growth, death, and polarization by ERBB4

Regulation of cell growth, death, and polarization by ERBB4 ErbB4 is a member of the epidermal growth factor receptor (EGFR, ErbB) family. The other members are EGFR, ErbB2 and ErbB3. ErbB receptors are important regulators for example in cardiovascular, neural and breast development but control key cellular functions also in many adult tissues. Abnormal ErbB signaling has been shown to be involved in various illnesses such as cancers and heart diseases. Among the ErbBs, ErbB4 has been shown to have unique signaling characteristics. ErbB4 exists in four alternatively spliced isoforms that are expressed in a tissue-specific manner. Two of the isoforms can be cleaved by membrane proteases, resulting in release of soluble intracellular domains (ICD). Once released into the cytosol, the ICD is capable of translocating into the nucleus and participating in regulation of transcription. The functional differences and the tissue-specific expression patterns suggest isoformspecific roles for ErbB4 isoforms. However, the abilities of ErbB4 isoforms to differently regulate cellular functions were discovered only recently and are not well understood. This study aimed to determine the expression patterns of ErbB4 in normal and diseased tissue, and to define whether the cleavable and non-cleavable isoforms could regulate different target genes and therefore, cellular functions. In this study, a comprehensive ErbB4 expression pattern in several normal tissues, various cancers and non-neoplastic diseases was determined. In addition, the data demonstrated that the cleavable and non-cleavable ErbB4 isoforms could regulate different cellular functions and target genes. Finally, this study defined the cellular responses regulated by ErbB4 during kidney development.

Possibilities and challenges of longitudinal studies in operations management

Longitudinal studies are quite rare in the area of Operations Management. One reason might be the time needed to conduct such studies, and then the lack of experience and real-life examples and results. The aim of the thesis is to examine longitudinal studies in the area of OM and the possible advantages, challenges and pitfalls of such studies. A longitudinal benchmarking study, Made in Finland, was analyzed in terms of the study methodology and its outcomes. The timeline of this longitudinal study is interesting. The first study was made in 1993, the second in 2004 and the third in 2010. Between these studies some major changes occurred in the Finnish business environment. Between the first and second studies, Finland joined the ETA and the EU, and globalization started with the rise of the Internet era, while between the second and third studies financial turmoil started in 2007. The sample and cases used in this study were originally 23 manufacturing sites in Finland. These sites were interviewed in 1993, in 2004 and 2010. One important and interesting aspect is that all the original sites participated in 2004, and 19 sites were still able to participate in 2010. Four sites had been closed and/or moved abroad. All of this gave a good opportunity to study the changes that occurred in the Finnish manufacturing sites and their environment, and how they reacted to these changes, and the effects on their performance. It is very seldom, if ever, that the same manufacturing sites have been studied in a longitudinal setting by using three data points. The results of this study are thus unique, and the experience gained is valuable for practitioners.

ANÁLISE DA DEFORMAÇÃO RESIDUAL LONGITUDINAL E SUA RELAÇÃO COM PROPRIEDADES TECNOLÓGICAS DA MADEIRA DE ACÁCIA-NEGRA

RESUMOA madeira de acácia-negra tem sido utilizada em nichos que conferem pouco valor agregado à esse material. Diante disso, este trabalho teve como objetivo analisar as deformações residuais longitudinais (DRL) e suas relações com propriedades da madeira de Acacia mearnsii. Para tanto, foram selecionadas 60 árvores em plantios com idades distintas (4 e 7 anos) no Município de Piratini, RS. As características de crescimento avaliadas consistiram em diâmetro à altura do peito (1,3 m; DAP), espessura de casca (EP) e altura comercial (h). As propriedades físicas avaliadas massa específica básica (ρ) e teorde umidade à base seca (Tu). Já o tempo de propagação de onda ultrassonora foi determinado em conformidade com o procedimento NBR 15521. As propriedades mecânicas foram o módulo de elasticidade dinâmico (Ed), bem como as propriedades descritas no procedimento normativo D143-94, através dos ensaios de flexão estática, compressão paralela às fibras e Dureza Janka. ADRLesuas relações com as propriedades da madeira mostraram-se semelhantes aos resultados encontrados na literatura para a madeira de espécies do gênero Eucalyptus. No entanto, em magnitude, tais níveis se mostraram sensivelmente menores, conferindo à madeira de acácia-negra no que se refere a esse parâmetro de qualidade, indicação para a confecção de produtos sólidos.

Distribuição longitudinal e germinação de sementes de milho com emprego de tratamento fitossanitário e grafite

Teve-se o objetivo de avaliar as formas de se misturar o lubrificante sólido grafite nas sementes de milho, as dosagens e a influência desse na distribuição longitudinal e na germinação, em sementes sem e com tratamento fitossanitário, em mecanismo dosador com disco perfurado horizontal. Os fatores analisados foram: distribuição longitudinal das sementes (espaçamentos falhos, múltiplos e aceitáveis) e a porcentagem de germinação aos 7 e aos 14 dias após a instalação no germinador. Concluiu-se que o tratamento fitossanitário aumentou os espaçamentos falhos e múltiplos e reduziu os espaçamentos aceitáveis. O emprego de grafite reduziu os espaçamentos falhos e múltiplos e elevou os espaçamentos aceitáveis. A melhor forma de mistura do grafite ocorreu na máquina de tratamento fitossanitário de sementes. A distribuição longitudinal alcançou seu ponto ótimo com a dosagem de grafite de 3,37 g kg-1 de semente. As variáveis tratamento fitossanitário, mecanismo dosador e grafite não influíram na germinação das sementes de milho.

Distribuição longitudinal de sementes de soja e características físicas do solo no plantio direto

As técnicas do plantio direto são complementares às atuais técnicas de conservação do solo, que envolvem menor mobilização e permanência de cobertura vegetal na superfície do solo. O trabalho foi realizado na UNESP - Jaboticabal, de novembro de 2003 a março de 2004, e teve como objetivo avaliar o efeito de culturas, manejos e marchas do trator na semeadura da soja no plantio direto. O delineamento utilizado para instalação do experimento foi em blocos ao acaso, no esquema de parcelas subsubdivididas, com quatro repetições. Foram analisados: estande inicial, distribuição longitudinal de plantas, resistência mecânica à penetração, densidade e teor de água no solo. O estande inicial não foi influenciado pelos tratamentos. A distribuição longitudinal das plantas foi afetada pela marcha do trator. A resistência do solo à penetração sofreu efeito apenas na camada de 0,20 a 0,25 m na interação culturas, manejos e marchas do trator. A interação culturas e manejos na camada de 0,10 a 0,20 m para densidade indicou a presença de resistência maior do que 0 a 0,10 m e de 0,20 a 0,30 m. O teor de água no solo foi menor nas camadas superficiais do solo, influenciado pelos manejos.

Numerical evaluation of the modulus of longitudinal elasticity in structural round timber elements of the Eucalyptus genus

Currently, the standards that deal with the determination of the properties of rigidity and strength for structural round timber elements do not take in consideration in their calculations and mathematical models the influence of the existing irregularities in the geometry of these elements. This study has as objective to determine the effective value of the modulus of longitudinal elasticity for structural round timber pieces of the Eucalyptus citriodora genus by a technique of optimization allied to the Inverse Analysis Method, to the Finite Element Method and the Least Square Method.

Longitudinal distribution of bean seeds in horizontal plate meter operating with one or two seed outlets

This study aimed to evaluate the effect of horizontal plate meter with oblong holes operating with one or two seed outlets at different speeds over the accuracy of longitudinal distribution of common bean seeds (Phaseolus vulgaris L.). The experiment was performed in laboratory using the meter with one and two seed outlet points in relation to ten tangential disk plate speeds (0.03 to 0.30 m s-1). It was used a complete randomized design with four replications, summing up 80 experimental treatments. Tangential speed quantitative factor was estimated through a 2nd order polynomial regression. There was no significant difference in the behavior of the seed meter operating with one or two outlets in the metering of bean seeds in all tested speeds, with percentage of single seeds spacing over 60% in tangential speeds below of 0.24 m s-1.

Abdominoplastia por plicatura anterior longitudinal na síndrome de prune belly: experiência inicial do hospital municipal Jesus

OBJETIVO: Apresentar os resultados iniciais com o uso da técnica de abdominoplastia longitudinal anterior por plicatura parietal descrita por Furness et al (1998) no Hospital Municipal Jesus. MÉTODO: Descrevemos as características e resultados dos primeiros pacientes tratados em nosso serviço, inclusive duas modificações adotadas com relação à técnica descrita, a saber, a exploração retroperitoneal sistemática para cura da criptorquia bilateral simultânea à abdominoplastia e a celiotomia "de segurança" para todos os pacientes operados. RESULTADOS: O seguimento dos pacientes foi de 1,5 ano, 15 meses e 10 meses, respectivamente. Foi possível demonstrar que a técnica adotada foi de fácil execução e pequena morbidade, com resultados estéticos satisfatórios, grande melhora das condições psicológicas e do convívio social para os pacientes desde o pós-operatório imediato, melhora da constipação crônica, capacidade aeróbica e postura. Quanto às repercussões urodinâmicas, aguardamos reavaliação a longo prazo, para conclusões mais efetivas. CONCLUSÃO: A abdominoplastia longitudinal anterior é uma técnica de fácil execução e segura para o tratamento da síndrome de prune belly e melhora a capacidade funcional muscular abdominal. Tem conseqüências urodinâmicas, que necessitam de avaliação após longo prazo.

Alterações morfométricas da musculatura dos músculos longitudinal e circular de ratos submetidos à criação de piloros no intestino delgado

OBJETIVO: Realizar um estudo morfométrico comparativo da musculatura longitudinal e circular do intestino delgado de ratos submetidos à construção cirúrgica de um e de dois piloros no intestino delgado utilizando-se da técnica de criação de piloros proposta por Rena et al. MÉTODO: Foram utilizados 52 ratos Wistar machos divididos em três grupos. O Grupo A, destacado como controle, composto de 10 animas, cada um forneceu 20mm de segmento de intestino para o estudo. Os animais do Grupo B, composto de 32 animais, foram submetidos à construção de dois piloros, um a 100mm e outro a 150mm da válvula ileocecal e os animais do grupo C, composto de 10 animais, foram submetidos à construção de um piloro a 100mm da mesma. A eutanásia ocorreu no décimo dia. A morfometria das camadas musculares longitudinal e circular acima e abaixo dos piloros foi estudada com utilização do microscópico modelo "Axiostar plus" conectado à câmera "Axioncam Version 5.05.10" com objetiva X5 / 0,12 no o programa "AxioVision 3.1.2.1". RESULTADOS: As alças apresentaram aumento da espessura da camada muscular acima e abaixo do ponto da operação. O estudo morfométrico comparativo das camadas musculares longitudinal e circular mostrou aumento significativo em comparação ao controle, não demonstrando significância entre os grupos B e C. CONCLUSÃO: Os resultados deste estudo revelaram importante aumento de espessura das camadas musculares, porém, menos acentuados que aqueles descritos na literatura quando foram realizados em animais submetidos à estenose fixa. Esses dados indicam que a construção operatória de piloros pela técnica utilizada promove alterações musculares de menor monta, possivelmente, pela função valvular do piloro.

Morfologia e resistência cicatriciais da parede abdominal após laparotomias longitudinal e transversal em coelhos

OBJETIVO: Foram estudadas comparativamente as laparotomias longitudinais paramediana e transversal avaliando-se a resistência cicatricial da parede abdominal e seu aspecto histológico, com peritônio suturado ou não. MÉTODO: 30 coelhos foram distribuídos em dois grupos: Grupo 1 (n = 10) - laparotomia longitudinal, Subgrupo 1A (n = 5) sutura das bainhas anterior e posterior do músculo reto abdominal, bem como do peritônio, Subgrupo 1B (n = 5) sutura da bainha anterior do músculo reto abdominal. Grupo 2 (n = 20) - laparotomia transversa, Subgrupo 2A (n = 5) sutura das bainhas anterior e posterior do músculo reto abdominal, bem como do peritônio, Subgrupo 2B (n = 5) sutura apenas da bainha anterior do músculo reto abdominal, Subgrupo 2C (n = 5) sutura, em plano único, do músculo reto abdominal e de sua bainha anterior, Subgrupo 2D (n = 5) síntese, da bainha posterior do músculo reto abdominal junto com o peritônio e, em seguida, sutura do músculo reto abdominal, complementada por sutura da bainha anterior desse músculo. Após 17 dias, foram retirados dois segmentos peritonio-aponeurotico-musculares da cicatriz para avaliação da resistência e de seus aspectos histológicos. RESULTADOS: O valor da resistência para cada um dos grupos avaliados mostrou 1A > 1B, 1A > 2A e 1B > 2B, e 2B > 2C > 2D > 2A (p = 0,014). Deiscência, infecção e aderências foram mais freqüentes no Grupo 2. A histologia mostrou degeneração e necrose muscular, com sua substituição por tecido conjuntivo fibroso maduro cicatricial. CONCLUSÃO: Esses dados indicam que o corte muscular transversal provoca maior enfraquecimento muscular e que o peritônio deixado aberto não altera a resistência cicatricial.

Searching for keys to successful post-merger integration : a longitudinal case-study following a public sector merger

Unsuccessful mergers are unfortunately the rule rather than the exception. Therefore it is necessary to gain an enhanced understanding of mergers and post-merger integrations (PMI) as well as learning more about how mergers and PMIs of information systems (IS) and people can be facilitated. Studies on PMI of IS are scarce and public sector mergers are even less studied. There is nothing however to indicate that public sector mergers are any more successful than those in the private sector. This thesis covers five studies carried out between 2008 and 2011 in two organizations in higher education that merged in January 2010. The most recent study was carried out two years after the new university was established. The longitudinal case-study focused on the administrators and their opinions of the IS, the work situation and the merger in general. These issues were investigated before, during and after the merger. Both surveys and interviews were used to collect data, to which were added documents that both describe and guide the merger process; in this way we aimed at a triangulation of findings. Administrators were chosen as the focus of the study since public organizations are highly dependent on this staff category, forming the backbone of the organization and whose performance is a key success factor for the organization. Reliable and effective IS are also critical for maintaining a functional and effective organization, and this makes administrators highly dependent on their organizations’ IS for the ability to carry out their duties as intended. The case-study has confirmed the administrators’ dependency on IS that work well. A merger is likely to lead to changes in the IS and the routines associated with the administrators’ work. Hence it was especially interesting to study how the administrators viewed the merger and its consequences for IS and the work situation. The overall research objective is to find key issues for successful mergers and PMIs. The first explorative study in 2008 showed that the administrators were confident of their skills and knowledge of IS and had no fear of having to learn new IS due to the merger. Most administrators had an academic background and were not anxious about whether IS training would be given or not. Before the merger the administrators were positive and enthusiastic towards the merger and also to the changes that they expected. The studies carried out before the merger showed that these administrators were very satisfied with the information provided about the merger. This information was disseminated through various channels and even negative information and postponed decisions were quickly distributed. The study conflicts with the theories that have found that resistance to change is inevitable in a merger. Shortly after the merger the (third) study showed disappointment with the fact that fewer changes than expected had been implemented even if the changes that actually were carried out sometimes led to a more problematic work situation. This was seen to be more prominent for routine changes than IS changes. Still the administrators showed a clear willingness to change and to share their knowledge with new colleagues. This knowledge sharing (also tacit) worked well in the merger and the PMI. The majority reported that the most common way to learn to use new ISs and to apply new routines was by asking help from colleagues. They also needed to take responsibility for their own training and development. Five months after the merger (the fourth study) the administrators had become worried about the changes in communication strategy that had been implemented in the new university. This was perceived as being more anonymous. Furthermore, it was harder to get to know what was happening and to contact the new decision makers. The administrators found that decisions, and the authority to make decisions, had been moved to a higher administrative level than they were accustomed to. A directive management style is recommended in mergers in order to achieve a quick transition without distracting from the core business. A merger process may be tiresome and require considerable effort from the participants. In addition, not everyone can make their voice heard during a merger and consensus is not possible in every question. It is important to find out what is best for the new organization instead of simply claiming that the tried and tested methods of doing things should be implemented. A major problem turned out to be the lack of management continuity during the merger process. Especially problematic was the situation in the IS-department with many substitute managers during the whole merger process (even after the merger was carried out). This meant that no one was in charge of IS-issues and the PMI of IS. Moreover, the top managers were appointed very late in the process; in some cases after the merger was carried out. This led to missed opportunities for building trust and management credibility was heavily affected. The administrators felt neglected and that their competences and knowledge no longer counted. This, together with a reduced and altered information flow, led to rumours and distrust. Before the merger the administrators were convinced that their achievements contributed value to their organizations and that they worked effectively. After the merger they were less sure of their value contribution and effectiveness even if these factors were not totally discounted. The fifth study in November 2011 found that the administrators were still satisfied with their IS as they had been throughout the whole study. Furthermore, they believed that the IS department had done a good job despite challenging circumstances. Both the former organizations lacked IS strategies, which badly affected the IS strategizing during the merger and the PMI. IS strategies deal with issues like system ownership; namely who should pay and who is responsible for maintenance and system development, for organizing system training for new IS, and for effectively run IS even during changing circumstances (e.g. more users). A proactive approach is recommended for IS strategizing to work. This is particularly true during a merger and PMI for handling issues about what ISs should be adopted and implemented in the new organization, issues of integration and reengineering of IS-related processes. In the new university an ITstrategy had still not been decided 26 months after the new university was established. The study shows the importance of the decisive management of IS in a merger requiring that IS issues are addressed in the merger process and that IS decisions are made early. Moreover, the new management needs to be appointed early in order to work actively with the IS-strategizing. It is also necessary to build trust and to plan and make decisions about integration of IS and people.

Estudo Longitudinal, Bioquímico e Histoquímico, de Placentas de Ratas Diabéticas: Relação com a Macrossomia e o Retardo de Crescimento Intra-uterino

Objetivo: o estudo longitudinal, entre o 18º e o 21º dias de prenhez, das alterações bioquímicas e histoquímicas das placentas de ratas diabéticas, cujos fetos tiveram macrossomia e retardo de crescimento intra-uterino (CIUR). Material e Método: usando modelo experimental em ratas, foram estudados 3 grupos: controle, diabete moderado e grave. A prenhez foi resolvida por cesárea no 18º ou no 21º dia. Compararam-se as glicemias materna e fetal; a incidência de recém-nascidos (RN) de peso pequeno (PIP), adequado (AIP) e grande (GIP) para tempo de prenhez; peso, índice e conteúdo de DNA, RNA e proteínas placentários e quantidade de glicogênio na superfície de trocas materno-fetais. Resultados: no diabete moderado houve maior proporção de RN-GIP com placentas ricas em DNA e diminuição progressiva de glicogênio em suas membranas no final da prenhez. No diabete grave houve predomínio de RN-GIP e as placentas exibiram menor conteúdo de DNA, síntese aumentada de RNA e tendência a maior produção protéica, com manutenção dos depósitos de glicogênio. Conclusões: concluiu-se que, entre o 18º e o 21º dias, os desvios do crescimento fetal no diabete materno, moderado e grave relacionam-se a alterações placentárias distintas. No moderado há apenas hiperplasia celular, com desaparecimento do glicogênio no final da prenhez. No grave, a superfície de trocas materno-fetais é mais espessada e, além de hiperplasia, há hipertrofia das células, com manutenção dos estoques placentários de glicogênio.

Pregnancy and periodontium. A clinical, microbiological, and enzymological approach via a longitudinal study

The mechanisms leading to an enhanced susceptibility to gingivitis in pregnant women have not yet been completely described. Therefore, the current study series were performed to investigate longitudinally the influence of pregnancy on periodontal tissues, and to evaluate microbial and host response factors related to pregnancy gingivitis formation. Pregnancy-related periodontal changes were analysed in 30 generally healthy women (24- 35 years old) once per trimester, till the end of lactation. Matched non-pregnant women (n=24) served as the controls, and were examined three times, once per following month. Pregnancy-related gingival inflammation was observed as enhanced tendency towards gingival bleeding and pseudopocket formation with a concomitant decrease in plaque levels. Gingivitis reached its peak during mid-pregnancy and then decreased transiently visit by visit. After lactation, no differences in periodontal status were seen between the study and control populations. In contrast to previous studies reporting increased levels of Prevotella intermedia, a specific aim was to analyse phenotypically two identical species, P. intermedia and Prevotella nigrescens, separately using a 16S ribosomal DNA-based PCR. As a result, the increased levels of P. nigrescens were related to pregnancy gingivitis. Matrix metalloproteinases (MMPs) are involved in periodontal destruction. However, their role in pregnancy gingivitis is not well studied. Therefore, neutrophilic enzymes and proteinases, such as MMP and myeloperoxidase (MPO) levels were analysed from saliva and gingival crevicular fluid (GCF) samples during the follow-up. Despite increased inflammation and microbial shift towards anaerobes, the host response did not activate the MMP, elastase and MPO secretion during pregnancy. These results demonstrate that during pregnancy gingival inflammation is enhanced especially during the second trimester, when P. nigrescens levels in subgingival plaque were increased, whereas the neutrophilic enzymes and proteinase levels in both saliva and GCF remained low. These findings could explain, at least in part, why pregnancy gingivitis itself does not predispose or proceed to periodontitis.