Improvement of theoretical storm characterization for different climate conditions

The different theoretical models related with storm wave characterization focus on determining the significant wave height of the peak storm, the mean period and, usually assuming a triangle storm shape, their duration. In some cases, the main direction is also considered. Nevertheless, definition of the whole storm history, including the variation of the main random variables during the storm cycle is not taken into consideration. The representativeness of the proposed storm models, analysed in a recent study using an empirical maximum energy flux time dependent function shows that the behaviour of the different storm models is extremely dependent on the climatic characteristics of the project area. Moreover, there are no theoretical models able to adequately reproduce storm history evolution of the sea states characterized by important swell components. To overcome this shortcoming, several theoretical storm shapes are investigated taking into consideration the bases of the three best theoretical storm models, the Equivalent Magnitude Storm (EMS), the Equivalent Number of Waves Storm (ENWS) and the Equivalent Duration Storm (EDS) models. To analyse the representativeness of the new storm shape, the aforementioned maximum energy flux formulation and a wave overtopping discharge structure function are used. With the empirical energy flux formulation, correctness of the different approaches is focussed on the progressive hydraulic stability loss of the main armour layer caused by real and theoretical storms. For the overtopping structure equation, the total volume of discharge is considered. In all cases, the results obtained highlight the greater representativeness of the triangular EMS model for sea waves and the trapezoidal (nonparallel sides) EMS model for waves with a higher degree of wave development. Taking into account the increase in offshore and shallow water wind turbines, maritime transport and deep vertical breakwaters, the maximum wave height of the whole storm history and that corresponding to each sea state belonging to its cycle's evolution is also considered. The procedure considers the information usually available for extreme waves' characterization. Extrapolations of the maximum wave height of the selected storms have also been considered. The 4th order statistics of the sea state belonging to the real and theoretical storm have been estimated to complete the statistical analysis of individual wave height

Resistance to DNA fragmentation and chromatin condensation in mice lacking the DNA fragmentation factor 45

The DNA fragmentation factor 45 (DFF45) is a subunit of a heterodimeric nuclease complex critical for the induction of DNA fragmentation in vitro. To understand the in vivo role of DFF45 in programmed cell death, we generated DFF45 mutant mice. DNA fragmentation activity is completely abolished in cell extracts from DFF45 mutant tissues. In response to apoptotic stimuli, splenocytes, thymocytes, and granulocytes from DFF45 mutant mice are resistant to DNA fragmentation, and splenocytes and thymocytes are also resistant to chromatin condensation. Nevertheless, development of the immune system in the DFF45 mutant mice is normal. These results demonstrate that DFF45 is critical for the induction of DNA fragmentation and chromatin condensation in vivo, but is not required for normal immune system development.

Essential role of POU–domain factor Brn-3c in auditory and vestibular hair cell development

The Brn-3 subfamily of POU–domain transcription factor genes consists of three highly homologous members—Brn-3a, Brn-3b, and Brn-3c—that are expressed in sensory neurons and in a small number of brainstem nuclei. This paper describes the role of Brn-3c in auditory and vestibular system development. In the inner ear, the Brn-3c protein is found only in auditory and vestibular hair cells, and the Brn-3a and Brn-3b proteins are found only in subsets of spiral and vestibular ganglion neurons. Mice carrying a targeted deletion of the Brn-3c gene are deaf and have impaired balance. These defects reflect a complete loss of auditory and vestibular hair cells during the late embryonic and early postnatal period and a secondary loss of spiral and vestibular ganglion neurons. Together with earlier work demonstrating a loss of trigeminal ganglion neurons and retinal ganglion cells in mice carrying targeted disruptions in the Brn-3a and Brn-3b genes, respectively, the Brn-3c phenotype reported here demonstrates that each of the Brn-3 genes plays distinctive roles in the somatosensory, visual, and auditory/vestibular systems.

Evolution of paired domains: Isolation and sequencing of jellyfish and hydra Pax genes related to Pax-5 and Pax-6

Pax proteins are a family of transcription factors with a highly conserved paired domain; many members also contain a paired-type homeodomain and/or an octapeptide. Nine mammalian Pax genes are known and classified into four subgroups: Pax-1/9, Pax-2/5/8, Pax-3/7, and Pax-4/6. Most of these genes are involved in nervous system development. In particular, Pax-6 is a key regulator that controls eye development in vertebrates and Drosophila. Although the Pax-4/6 subgroup seems to be more closely related to Pax-2/5/8 than to Pax-3/7 or Pax-1/9, its evolutionary origin is unknown. We therefore searched for a Pax-6 homolog and related genes in Cnidaria, which is the lowest phylum of animals that possess a nervous system and eyes. A sea nettle (a jellyfish) genomic library was constructed and two pax genes (Pax-A and -B) were isolated and partially sequenced. Surprisingly, unlike most known Pax genes, the paired box in these two genes contains no intron. In addition, the complete cDNA sequences of hydra Pax-A and -B were obtained. Hydra Pax-B contains both the homeodomain and the octapeptide, whereas hydra Pax-A contains neither. DNA binding assays showed that sea nettle Pax-A and -B and hydra Pax-A paired domains bound to a Pax-5/6 site and a Pax-5 site, although hydra Pax-B paired domain bound neither. An alignment of all available paired domain sequences revealed two highly conserved regions, which cover the DNA binding contact positions. Phylogenetic analysis showed that Pax-A and especially Pax-B were more closely related to Pax-2/5/8 and Pax-4/6 than to Pax-1/9 or Pax-3/7 and that the Pax genes can be classified into two supergroups: Pax-A/Pax-B/Pax-2/5/8/4/6 and Pax-1/9/3/7. From this analysis and the gene structure, we propose that modern Pax-4/6 and Pax-2/5/8 genes evolved from an ancestral gene similar to cnidarian Pax-B, having both the homeodomain and the octapeptide.

Conservation of the Drosophila lateral inhibition pathway in human lung cancer: A hairy-related protein (HES-1) directly represses achaete-scute homolog-1 expression

The achaete-scute genes encode essential transcription factors in normal Drosophila and vertebrate nervous system development. Human achaete-scute homolog-1 (hASH1) is constitutively expressed in a human lung cancer with neuroendocrine (NE) features, small cell lung cancer (SCLC), and is essential for development of the normal pulmonary NE cells that most resemble this neoplasm. Mechanisms regulating achaete-scute homolog expression outside of Drosophila are presently unclear, either in the context of the developing nervous system or in normal or neoplastic cells with NE features. We now provide evidence that the protein hairy-enhancer-of-split-1 (HES-1) acts in a similar manner as its Drosophila homolog, hairy, to transcriptionally repress achaete-scute expression. HES-1 protein is detected at abundant levels in most non-NE human lung cancer cell lines which lack hASH1 but is virtually absent in hASH1-expressing lung cancer cells. Moreover, induction of HES-1 in a SCLC cell line down-regulates endogenous hASH1 gene expression. The repressive effect of HES-1 is directly mediated by binding of the protein to a class C site in the hASH1 promoter. Thus, a key part of the process that determines neural fate in Drosophila is conserved in human lung cancer cells. Furthermore, modulation of this pathway may underlie the constitutive hASH1 expression seen in NE tumors such as SCLC, the most virulent human lung cancer.

Altered thymic positive selection and intracellular signals in Cbl-deficient mice

Cbl is the product of the protooncogene c-cbl and is involved in T cell antigen receptor (TCR)-mediated signaling. To understand the role of Cbl for immune system development and function, we generated a Cbl-deficient mouse strain. In Cbl-deficient mice, positive selection of the thymocytes expressing major histocompatibility complex class II-restricted transgenic TCR was significantly enhanced. Two factors may have contributed to the altered thymic selection. First, Cbl deficiency markedly up-regulated the activity of ZAP-70 and mitogen-activated protein kinases. The mitogen-activated protein kinase pathway was shown previously to be involved in thymic positive selection. Second, Cbl-deficient thymocytes expressed CD3 and CD4 molecules at higher levels, which consequently may increase the avidity of TCR/major histocompatibility complex/coreceptor interaction. Thus, Cbl plays a novel role in modulating TCR-mediated multiple signaling pathways and fine-tunes the signaling threshold for thymic selection.

Reduction of atherosclerosis in apolipoprotein E knockout mice by activation of the retinoid X receptor

A common feature of many metabolic pathways is their control by retinoid X receptor (RXR) heterodimers. Dysregulation of such metabolic pathways can lead to the development of atherosclerosis, a disease influenced by both systemic and local factors. Here we analyzed the effects of activation of RXR and some of its heterodimers in apolipoprotein E −/− mice, a well established animal model of atherosclerosis. An RXR agonist drastically reduced the development of atherosclerosis. In addition, a ligand for the peroxisome proliferator-activated receptor (PPAR)γ and a dual agonist of both PPARα and PPARγ had moderate inhibitory effects. Both RXR and liver X receptor (LXR) agonists induced ATP-binding cassette protein 1 (ABC-1) expression and stimulated ABC-1-mediated cholesterol efflux from macrophages from wild-type, but not from LXRα and β double −/−, mice. Hence, activation of ABC-1-mediated cholesterol efflux by the RXR/LXR heterodimer might contribute to the beneficial effects of rexinoids on atherosclerosis and warrant further evaluation of RXR/LXR agonists in prevention and treatment of atherosclerosis.

Human CD100, a novel leukocyte semaphorin that promotes B-cell aggregation and differentiation.

Herein we describe the molecular characterization of the human leukocyte activation antigen CD100 and identify it as the first semaphorin, to our knowledge, in the immune system. Semaphorins have recently been described as neuronal chemorepellants that direct pioneering neurons during nervous system development. In this study we demonstrate that CD100 induces B cells to aggregate and improves their viability in vitro. We show that CD100 modifies CD40-CD40L B-cell signaling by augmenting B-cell aggregation and survival and down-regulating CD23 expression. Thus, these results suggest that semaphorins as exemplified by CD100 also play a functional role in the immune system.

Retinal engineering: engrafted neural cell lines locate in appropriate layers.

A major question in central nervous system development, including the neuroretina, is whether migrating cells express cues to find their way and settle at specific locations. We have transplanted quail neuroretinal cell lines QNR/D, a putative amacrine or ganglion cell, and QNR/K2, a putative Müller cell into chicken embryo eyes. Implanted QNR/D cells migrate only to the retinal ganglion and amacrine cell layers and project neurites in the plane of retina; in contrast, QNR/K2 cells migrate through the ganglion and amacrine layers, locate in the inner nuclear layer, and project processes across the retina. These data show that QNR/D and QNR/K2 cell lines represent distinct neural cell types, suggesting that migrating neural cells express distinct address cues. Furthermore, our results raise the possibility that immortalized cell lines can be used for replacement of specific cell types and for the transport of genes to given locations in neuroretina.

Isolation of a Pax-6 homolog from the ribbonworm Lineus sanguineus.

The Pax-6 genes of vertebrates and Drosophila encode transcription factors with highly conserved paired- and homeodomains. They are expressed in the nervous system and the developing eyes. Loss-of-function mutations in mammals and flies lead to a reduction or absence of the eyes. By ectopic expression of Pax-6 in Drosophila ectopic eyes can be induced, indicating a determinative role in eye morphogenesis. We have isolated a Pax-6 homolog of the ribbonworm Lineus sanguineus. This gene shares extensive sequence identity and several conserved splice sites with the mammalian and Drosophila genes. During head regeneration the L. sanguineus Pax-6 homolog is expressed in the central nervous system, in the cerebral organ, and in the eye region. These findings support the hypothesis that Pax-6 was present in primitive metazoa before the evolutionary separation of vertebrates and arthropods and suggest a fundamental role in eye and central nervous system development.

Reduced sympathetic innervation after alteration of target cell neurotransmitter phenotype in transgenic mice.

Neurotransmitters play a variety of important roles during nervous system development. In the present study, we hypothesized that neurotransmitter phenotype of both projecting and target cells is an important factor for the final synaptic linkage and its specificity. To test this hypothesis, we used transgenic techniques to convert serotonin/melatonin-producing cells of the pineal gland into cells that also produce dopamine and investigated the innervation of the phenotypically altered target cells. This phenotypic alteration markedly reduced the noradrenergic innervation originating from the superior cervical ganglia. Although the mechanism by which the reduction occurs is presently unknown, quantitative enzyme-linked immunoassay showed the presence of the equivalent amounts of nerve growth factor (NGF) in the control and transgenic pineal glands, suggesting that it occurred in a NGF-independent manner. The results suggest that target neurotransmitter phenotype influences the formation of afferent connections during development.

As entidades fechadas de previdência complementar enquanto instrumentos de atuação do Estado na economia

Com as transformações ocorridas nas últimas décadas do século XX, notadamente a expansão financeira pela qual passou o capitalismo, o enfraquecimento fiscal dos Estados nacionais e o questionamento aos sistemas de previdência pública por repartição, ganham importância em todo o mundo os fundos de pensão. Estes fundos, ao lado de outros investidores institucionais, como seguradoras e fundos de investimentos, passam a cumprir papel central no mercado acionário e também no mercado de títulos públicos e privados. Com o objetivo de realizar lucros para pagar benefícios de aposentadoria para os seus participantes, os fundos de pensão arrecadam e concentram poupança privada pulverizada, transformando-a em um ativo poderoso. No Brasil, as Entidades Fechadas de Previdência Complementar nomenclatura jurídica dos fundos de pensão possuem um total de 702 bilhões de reais em ativos, que se concentram nas três maiores entidades do país: Previ, Petros e Funcef. Em comum, estes três fundos têm o fato de serem patrocinados por empresas estatais, o que, pela legislação vigente, dá ao Poder Executivo a competência de indicar metade de seus dirigentes, incluindo o seu presidente que possui voto de desempate. O presente trabalho pesquisou o papel que estas três EFPCs cumprem enquanto instrumento de atuação do Estado no domínio econômico, especialmente para o provimento de fundos para o desenvolvimento. Para isso, primeiramente, o estudo explora o movimento de expansão financeira do capitalismo e a crise no padrão de desenvolvimento brasileiro. Depois, investiga de maneira sistemática o arcabouço jurídico que regula os fundos de pensão; e, por fim, analisa a alocação dos seus investimentos e o perfil dos seus dirigentes.

Controle epigenético do gene imprinted SNRPN durante o desenvolvimento e reprogramação nuclear em equídeos

A tranferência nuclear de células somáticas (TNCS) está sendo utilizada para produzir cavalos de elite. No entanto, durante este procedimento pode ocorrer a perfuração da zona pelúcida, levando, ocasionalmente, à secção da massa celular interna, e conseqüente derivação de gêmeos monozigóticos. Além de serem relatadas alterações no processo de imprinting genômico, que conduzem ao desenvolvimento de doenças. Com a descoberta da possibilidade de reprogramar as células somáticas a um estado de pluripotência (iPSCs), estas células passaram a ser muito utilizadas em pesquisas de neurociência. Contudo, também ocorrem modificações epigenéticas durante esta reprogramação celular. Portanto, nossas hipóteses são que os gêmeos eqüinos gerados pela TNCS podem levar às irregularidades no desenvolvimento do sistema nervoso. O padrão de metilação do SNRPN nas estruturas dos fetos muares clonados, e as células iPSCs são diferentes dos padrões encontrados nos muares analisados. A expressão dos genes SNRPN, Necdin e UBE3A são maiores no cérebro, enquanto a expressão do H19 é maior nas membranas extra-embrionárias. Em nosso estudo, obtivemos duas gestações gemelares equinas derivadas da TNCS, que foram interrompidas com 40 e 60 dias de gestação, e comparados com gestações eqüinas únicas de idade similar. Diferenças no comprimento entre os embriões gêmeos foram observadas aos 40 (2.0 e 2.2 cm 10%) e aos 60 (6,5 e 8,5 cm 24%) dias de gestação. Somente o plexo coróide do quarto ventrículo apresentou-se mais desenvolvido nos fetos com maior comprimento. Ao analisarmos fetos muares clonados em diferentes idades gestacionais e compará-los com muares, nos períodos embrionário, fetal e adulto, não foi observada diferença no padrão de metilação do gene SNRPN. No entanto, na décima passagem das células iPSC o padrão de metilação alterou, em relação aos muares estudados e ao padrão observado nos fibroblastos. Ao analisarmos os fetos clonados nas diferentes idades gestacionais observou-se no cérebro menor expressão dos gene H19 e UBE3A, e maior expressão do gene SNRPN. Contudo, a expressão do gene Necdin variou entre as estruturas estudadas. Em conclusão, apesar dos gêmeos eqüinos provenientes de TNCS diferirem quanto ao tamanho, morfologicamente são iguais. Dentre as estruturas cerebrais o plexo coróide se apresentou mais desenvolvido nos fetos de maior comprimento. Os fetos muares clonados não apresentaram diferença no padrão de metilação do gene SNRPN. No entanto, as iPSCs apresentaram alteração no padrão de metilação deste gene na décima passagem. Embora os genes SNRPN, Necdin e UBE3A sejam expressos no cérebro, o SNRPN apresentou-se prevalente nessa estrutura

As concepções de professores de química sobre a utilização de elementos da história e filosofia da ciência no ensino

Nas últimas décadas, investigações têm destacado o papel da história e filosofia da ciência (HFC) na educação científica. O reconhecimento da pluralidade e complexidade da ciência tem originado estudos, os quais apontam que o ensino sobre ciências deve levar em conta as diferenças entre as disciplinas científicas. Assim, tem-se discutido a importância da consideração de elementos da história e da filosofia da química no aprimoramento do processo de ensino e aprendizagem dessa ciência. Apesar disso, investigações têm constatado que pouco ou nada se discute acerca desses assuntos nas aulas de ciências. Diante disso, esta dissertação tem como intuito investigar a concepção de professores de química sobre a inclusão de elementos da HFC no ensino, com foco nas características inerentes às práticas e aos conhecimentos químicos. Foram investigadas as concepções de cinco professores de química, que atuam em diferentes escolas públicas da região metropolitana de São Paulo, acerca de cinco temas, elaborados com base em estudos da área de ensino de ciências e em diretrizes curriculares oficiais: relações com a sociedade, modelos e modelagem, experimentação, desenvolvimento histórico e reducionismo. Por meio da análise qualitativa dos dados, as concepções docentes, para cada tema, foram classificadas em dois subeixos temáticos: prática docente e relevância. Ademais, foram identificados fatores externos e internos que influenciam as práticas e concepções dos sujeitos concernentes a considerações filosóficas, históricas e sociológicas sobre a química. Os resultados evidenciam que, de modo geral, os sujeitos consideram relevantes determinados assuntos relacionados à natureza da química e, em certa medida, buscam inseri-los em suas práticas cotidianas. Contudo, mostraram também que os motivos pelos quais os docentes conferem importância a algumas discussões, e o modo como as desenvolvem, podem limitar a compreensão dos estudantes sobre a complexidade da construção do conhecimento científico. Além disso, foram raras as referências a aspectos específicos da química, à importância de evidenciar e discutir esses aspectos com os estudantes, assim como à preparação de situações didáticas próximas à prática química autêntica.

La Universidad de Alicante Universidad promotora de salud/Universidad Saludable. Un reto y una oportunidad

Justificación: Dentro de la estrategia de Universidades Saludables, la Universidad de Alicante (UA) inicia un proyecto para conocer, difundir y potenciar los activos para la salud. Se plantea dotar de contenido empírico la propuesta de Morgan y Ziglio de usar el modelo de activos para la salud pública identificados por la comunidad universitaria. Objetivos: explorar la factibilidad y los retos de la aplicación de mapeos de activos para la salud en la UA con el fin de que la comunidad universitaria pueda ganar salud, calidad de vida y bienestar. Desarrollo de la experiencia: Formación de promotores de salud: • La promoción de la salud y la teoría salutogénica. • Aproximación al modelo y la estrategia de activos en salud. Enfoque Asset-Based Community Development (ABCD). • Diferencia entre recursos y activos. • Técnicas de observación y diálogo. • Técnicas mixtas: open space, TICs y mapping... • Competencias profesionales, entorno facilitador y apoyo para obtener resultados. Metodología: Lograr el mapeo de los activos en salud, sus entornos y sus estudiantes siguiendo el enfoque de John McKnight. Aplicación de “lo aprendido” en el contexto de la UA: Planificación del proyecto para el año 2014. Resultados: construcción de un mapa de activos para la salud, geolocalizado en la Universidad de Alicante. Dinamización del mapa de activos, estudiando conexiones entre activos y necesidades de la comunidad universitaria con las personas participantes, para realizar propuestas de acción futura. Difusión del mismo a través de tecnologías de la información.