Alterations in gene expression and activity during squamous cell carcinoma development

This study focuses on characterizing the genetic and biological alterations associated with squamous cell carcinoma development. Normal human epidermal keratinocytes (HEKs), cells isolated from a preneoplastic lesion (IEC-1), and two neoplastic cell lines, SCC-25 and COLD-16, were grown as raft cultures, and their gene expression profiles were screened using cDNA arrays. Our data indicated that the expression levels of at least 37 genes were significantly (P less than or equal to 0.05; 1.9% of genes screened) altered in neoplastic cells compared with normal cells. Of these genes, 10 genes were up-regulated and 27 genes were down-regulated in the neoplastic cells. In addition, 51% of the genes altered in the neoplastic cells were already altered in the preneoplastic IEC-1 cells. Immunohistochemical staining of patient tumors was used to verify the cDNA array analysis. Our analysis indicated that alterations in genes associated with extracellular matrix production and apoptosis are disrupted in preneoplastic cells, whereas later stages of neoplasia are associated with alterations in gene expression for genes involved in DNA repair or epidermal growth factor (EGF) receptor/mitogen-activated protein kinase kinase (MAPKK)/MAPK/activator protein-1 (AP-1) signaling. Subsequent functional analysis of the alterations in expression of the EGF receptor/MAPKK/MAPK/AP-1 genes suggested they did not contribute to the neoplastic phenotype.

Gas permeation in silicon-oxide/polymer (SiOx/PET) barrier films: role of the oxide lattice, nano-defects and macro-defects

We propose a model for permeation in oxide coated gas barrier films. The model accounts for diffusion through the amorphous oxide lattice, nano-defects within the lattice, and macro-defects. The presence of nano-defects indicate the oxide layer is more similar to a nano-porous solid (such as zeolite) than silica glass with respect to permeation properties. This explains why the permeability of oxide coated polymers is much greater, and the activation energy of permeation much lower, than values expected for polymers coated with glass. We have used the model to interpret permeability and activation energies measured for the inert gases (He, Ne and Ar) in evaporated SiOx films of varying thickness (13-70 nm) coated on a polymer substrate. Atomic force and scanning electron microscopy were used to study the structure of the oxide layer. Although no defects could be detected by microscopy, the permeation data indicate that macro-defects (>1 nm), nano-defects (0.3-0.4 nm) and the lattice interstices (<0.3 nm) all contribute to the total permeation. (C) 2002 Elsevier Science B.V. All rights reserved.

Computation of the linear elastic properties of random porous materials with a wide variety of microstructure

A finite-element method is used to study the elastic properties of random three-dimensional porous materials with highly interconnected pores. We show that Young's modulus, E, is practically independent of Poisson's ratio of the solid phase, nu(s), over the entire solid fraction range, and Poisson's ratio, nu, becomes independent of nu(s) as the percolation threshold is approached. We represent this behaviour of nu in a flow diagram. This interesting but approximate behaviour is very similar to the exactly known behaviour in two-dimensional porous materials. In addition, the behaviour of nu versus nu(s) appears to imply that information in the dilute porosity limit can affect behaviour in the percolation threshold limit. We summarize the finite-element results in terms of simple structure-property relations, instead of tables of data, to make it easier to apply the computational results. Without using accurate numerical computations, one is limited to various effective medium theories and rigorous approximations like bounds and expansions. The accuracy of these equations is unknown for general porous media. To verify a particular theory it is important to check that it predicts both isotropic elastic moduli, i.e. prediction of Young's modulus alone is necessary but not sufficient. The subtleties of Poisson's ratio behaviour actually provide a very effective method for showing differences between the theories and demonstrating their ranges of validity. We find that for moderate- to high-porosity materials, none of the analytical theories is accurate and, at present, numerical techniques must be relied upon.

Analysis of the wind field and heat budget in an alpine lake basin during summertime fair weather conditions

Observational data collected in the Lake Tekapo hydro catchment of the Southern Alps in New Zealand are used to analyse the wind and temperature fields in the alpine lake basin during summertime fair weather conditions. Measurements from surface stations, pilot balloon and tethersonde soundings, Doppler sodar and an instrumented light aircraft provide evidence of multi-scale interacting wind systems, ranging from microscale slope winds to mesoscale coast-to-basin flows. Thermal forcing of the winds occurred due to differential heating as a consequence of orography and heterogeneous surface features, which is quantified by heat budget and pressure field analysis. The daytime vertical temperature structure was characterised by distinct layering. Features of particular interest are the formation of thermal internal boundary layers due to the lake-land discontinuity and the development of elevated mixed layers. The latter were generated by advective heating from the basin and valley sidewalls by slope winds and by a superimposed valley wind blowing from the basin over Lake Tekapo and up the tributary Godley Valley. Daytime heating in the basin and its tributary valleys caused the development of a strong horizontal temperature gradient between the basin atmosphere and that over the surrounding landscape, and hence the development of a mesoscale heat low over the basin. After noon, air from outside the basin started flowing over mountain saddles into the basin causing cooling in the lowest layers, whereas at ridge top height the horizontal air temperature gradient between inside and outside the basin continued to increase. In the early evening, a more massive intrusion of cold air caused rapid cooling and a transition to a rather uniform slightly stable stratification up to about 2000 m agl. The onset time of this rapid cooling varied about 1-2 h between observation sites and was probably triggered by the decay of up-slope winds inside the basin, which previously countered the intrusion of air over the surrounding ridges. The intrusion of air from outside the basin continued until about mid-night, when a northerly mountain wind from the Godley Valley became dominant. The results illustrate the extreme complexity that can be caused by the operation of thermal forcing processes at a wide range of spatial scales.

N4WBP5, a potential target for ubiquitination by the Nedd4 family of proteins, is a novel golgi-associated protein

Nedd4 belongs to a family of ubiquitin-protein ligases that is characterized by 2-4 WW domains, a carboxyl-terminal Hect ((h) under bar omologous to (E) under bar6-AP (C) under bar arboxyl (t) under bar erminus)-domain and in most cases an amino-terminal C2 domain. We had previously identified a series of proteins that associates with the WW domains of Nedd4. In this paper, we demonstrate that one of the Nedd4-binding proteins, N4WBP5, belongs to a small group of evolutionarily conserved proteins with three transmembrane domains. N4WBP5 binds Nedd4 WW domains via the two PPXY motifs present in the amino terminus of the protein. In addition to Nedd4, N4WBP5 can interact with the WW domains of a number of Nedd4 family members and is ubiquitinated. Endogenous N4WBP5 localizes to the Golgi complex. Ectopic expression of the protein disrupts the structure of the Golgi, suggesting that N4WBP5 forms part of a family of integral Golgi membrane proteins. Based on previous observations in yeast, we propose that N4WBP5 may act as an adaptor for Nedd4-like proteins and their putative targets to control ubiquitin-dependent protein sorting and trafficking.

Tyrosinase-Cre mice for tissue-specific gene ablation in neural crest and neuroepithelial-derived tissues

This study describes the derivation of two new lines of transgenic mice that express Cre recombinase under the control of tyrosinase transcriptional elements. To determine the suitability of the Tyrosinase-Cre transgene for tissue-specific gene ablation studies, a fate map of Cre expression domains was determined using the Z/AP reporter strain. It was shown that Cre-expressing cells contribute to a wide array of neural crest and neuroepithelial-derived lineages. The melanocytes of the harderian gland and eye choroid, sympathetic cephalic ganglia, leptomeninges of the telencephalon, as well as cranial nerves (V), (VII), and (IX) are derived either fully or partly from Cre-expressing cephalic crest. The cells contributing to the cranial nerves were the first to exhibit Cre expression at E10.5 as they were migrating into the branchial arches. The melanocytes, chromaffin cells of the adrenal medulla, and dorsal root ganglia are derived from trunk neural crest that either express Cre or were derived from Cre-expressing precursors. An array of brain tissue including the basal forebrain, hippocampus, olfactory bulb, and the granule cell layer of the lateral cerebellum, as well as the retinal pigmented epithelium and glia of the optic nerve originate from Cre-expressing neuroepithelial cells. (C) 2003 Wiley-Liss, Inc.

Distribution of Sugarcane mosaic virus in sugarcane plants

Variation in the concentration of virus in different parts of the plant has implications for virus-indexing programs. To allow more reliable detection of Sugarcane mosaic virus (SCMV), the distribution of the virus in sugarcane plants after artificial inoculation was studied using a reverse transcription polymerase chain reaction (RT-PCR) assay. Leaves of susceptible and moderately resistant sugarcane were mechanically inoculated with SCMV 6 weeks after planting. Weekly for 8 weeks after inoculation, plants were examined for mosaic symptoms and samples of leaves, roots and tillers were tested by RT-PCR to detect virus. SCMV moved from the point of inoculation to younger leaves, roots and tillers and eventually to leaves that emerged prior to inoculation. The pattern of SCMV distribution in moderately resistant and susceptible cultivars was not substantially different. However, the virus moved more slowly in the moderately resistant than in the susceptible cultivar. Young leaves proved to be the most suitable tissue for testing.

Compromisso nacional para aperfei??oar as condi????es de trabalho na cana-de-a????car

O Compromisso Nacional para Aperfei??oar as Condi????es de Trabalho na Cana-de-A????car, firmado pelo Governo Federal e entidades de trabalhadores e empres??rios do setor sucroenerg??tico, ?? resultado de uma experi??ncia in??dita no pa??s de negocia????o tripartite para enfrentar o desafio de melhorar as condi????es de vida e trabalho no cultivo manual da cana-de-a????car. Por meio de uma Mesa de Di??logo, sob a coordena????o da Secretaria-Geral da Presid??ncia da Rep??blica, foi constru??do um acordo hist??rico para valorizar e disseminar as melhores pr??ticas trabalhistas na lavoura da cana, evidenciando a import??ncia do di??logo social na elabora????o das Pol??ticas P??blicas. Atrav??s da ades??o volunt??ria das empresas ao Compromisso, da divulga????o das boas pr??ticas empresariais e do cadastro positivo formado pelo selo ???Empresa Compromissada???, conferido ap??s verifica????o in loco de auditoria independente, a iniciativa induz os demais atores do setor a aderir ao Compromisso e adotar as boas pr??ticas trabalhistas

A trag??dia da regi??o serrana do Rio de Janeiro em 2011: procurando respostas

O estudo de caso trata do desastre natural ocorrido na regi??o serrana do Rio de Janeiro nos dias 11 e 12 de janeiro de 2011, considerado a maior cat??strofe clim??tica e geot??cnica do pa??s, causado por fortes chuvas que provocaram enchentes e deslizamentos em sete munic??pios. O caso tem por finalidade despertar a discuss??o sobre as vari??veis e atores que influenciaram o processo de gest??o da crise, contextualizando o desastre no cen??rio da regi??o e reconstituindo, especialmente, o processo de resposta imediata dada ?? trag??dia pelos ??rg??os envolvidos. O estudo pode ser utilizado em cursos que abordem, entre outros, os seguintes t??picos: gest??o de crise e gest??o de riscos, negocia????o, comunica????o e planejamento estrat??gico

Atividade pioneira na Pol??cia Rodovi??ria Federal e no Brasil: fiscaliza????o de excesso de peso

Anteriormente ?? implementa????o da iniciativa, a situa????o encontrada no trabalho de fiscaliza????o ao excesso de peso nos ve??culos que transitam nas rodovias federais era a de que as multas aplicadas n??o surtiam o efeito de inibir tal pr??tica, uma vez que destinavam-se somente aos propriet??rios dos ve??culos. Atualmente, ap??s a detec????o e autua????o do excesso de peso, confecciona-se um Boletim de Ocorr??ncia Policial que ?? encaminhado ao Minist??rio P??blico Federal, visando ?? responsabiliza????o das empresas que embarcaram as cargas. A partir da??, os envolvidos s??o acionados judicialmente e ?? apresentado o Termo de Ajuste de Conduta. Ap??s o acionamento judicial, as empresas se comprometem a n??o mais transitarem com excesso de peso e assim o fazem. Todo esse servi??o ?? divulgado pela m??dia (emissoras de TV, r??dios e jornais) e por meio da Assessoria de Comunica????o Social do Minist??rio P??blico Federal de Minas Gerais. Sempre acompanhada pelo Poder Judici??rio, essa inova????o j?? ?? vivenciada em algumas cidades e, em outras, est?? em fase de estudos

Aposentadoria em at?? 30 minutos

A procura pela qualidade e resolutividade do reconhecimento do direito previdenci??rio em menor tempo ?? uma busca incessante do Instituto Nacional do Seguro Social (INSS). Da forma conceituada anteriormente, o servi??o n??o atendia a necessidade da sociedade, pois havia demora significativa na resolu????o dos processos de benef??cios. Isso se devia ao fato de que cabia ao segurado a apresenta????o e comprova????o da documenta????o necess??ria ao direito previdenci??rio. Ap??s v??rios debates promovidos pelo INSS e a mudan??a no fluxo do reconhecimento do direito, o instituto p??de garantir que maior n??mero de segurados tenha acesso ao reconhecimento do direito em at?? 30 minutos, considerando a invers??o do ??nus da prova, dispensando a apresenta????o de documentos pelo segurado. A internaliza????o do novo conceito e da fixa????o de metas garantiu o reconhecimento do direito em at?? 30 minutos e a redu????o no tempo m??dio de atendimento do cidad??o.

Sistema de registro eletr??nico de ponto

O Sistema de Registro Eletr??nico de Ponto (SREP) representou um importante avan??o nos instrumentos de prote????o e seguran??a dos trabalhadores e empresas que utilizam o ponto eletr??nico, por coibir fraudes de altera????o dos hor??rios efetivamente registrados, de supress??o ou de impedimento na marca????o de horas extras. Ap??s investiga????o das modalidades de fraudes e dos sistemas que propiciavam as adultera????es, a equipe t??cnica do Minist??rio do Trabalho e Emprego (MTE) desenvolveu o modelo de regulamenta????o, consolidado na Portaria n?? 1.510/2009, que garante as marca????es dos hor??rios de jornada de trabalho sem possibilidade de adultera????o. O SREP ?? composto de um hardware e um software. O hardware, Registrador Eletr??nico de Ponto (REP), preserva as marca????es de ponto e fornece ao trabalhador o seu comprovante. O software opera nos computadores das empresas, permitindo o tratamento seguro dos dados para pagamento das horas trabalhadas. S?? em 2010, o SREP recuperou uma sonega????o de R$ 1,5 bilh??o em sal??rios e R$ 446,6 milh??es em contribui????es previdenci??rias e Fundo de Garantia do Tempo de Servi??o (FGTS)

Um (Des)caso do planejamento estrat??gico em ??rg??o da Administra????o P??blica

O estudo de caso descreve o processo de planejamento estrat??gico ocorrido em uma organiza????o p??blica e os resultados alcan??ados ap??s a sua implanta????o. A organiza????o, com o nome fict??cio de Companhia de Defesa, desenvolveu seu planejamento estrat??gico com inten????o de aderir ?? administra????o estrat??gica. Os principais problemas reconhecidos pela organiza????o s??o a morosidade, a falta de transpar??ncia e a inefici??ncia de suas a????es. Atuaram no planejamento estrat??gico a alta administra????o, coordenadores nomeados e representantes regionais e uma consultoria especializada. O ambiente organizacional existente ?? ??poca n??o foi prop??cio ao planejamento estrat??gico: mudan??as de dire????o, pouca capacita????o funcional, capilaridade da institui????o e dificuldade de consenso entre planejadores e executores. ?? poss??vel, ??queles que estudarem o caso, contrapor a teoria e a pr??tica do planejamento estrat??gico, identificando boas a????es realizadas e erros cometidos

Revis??o dos Procedimentos de P??s-Registro de Medicamentos

O Grupo de Trabalho (GT) de revis??o do regulamento t??cnico para p??s-registro de -medicamentos da Anvisa vem trabalhando na desburocratiza????o e celeridade dos procedimentos regulat??rios referentes ?? atualiza????o de dados do medicamento ap??s a obten????o de seu registro. Esses s??o itens de fundamental import??ncia para o est??mulo da produ????o e da qualidade dos medicamentos comercializados no pa??s. Foi feita uma classifica????o das modifica????es p??s-registro de medicamentos conforme o risco sanit??rio, a complexidade de an??lise e testes farmacot??cnicos. A abordagem permitiu efici??ncia da an??lise t??cnica e, uma vez que esses procedimentos tornaram-se mais c??leres, houve maior previsibilidade nas a????es de p??s-registro com a ado????o dos novos fluxos e prazos de an??lise