Sp1 phosphorylation regulates inducible expression of platelet-derived growth factor B-chain gene via atypical protein kinase C-ζ

Platelet-derived growth factor (PDGF) is a broadly expressed mitogenic and chemotactic factor with diverse roles in a number of physiologic and pathologic settings. The zinc finger transcription factors Sp1, Sp3 and Egr-1 bind to overlapping elements in the proximal PDGF B-chain promoter and activate transcription of this gene. The anthracycline nogalamycin has previously been reported to inhibit the capacity of Egr-1 to bind DNA in vitro. Here we used electrophoretic mobility shift assays to show that nogalamycin added to cells in culture did not alter the interaction of Egr-1 with the PDGF-B promoter. Instead, it enhanced the capacity of Sp1 to bind DNA. Nogalamycin increased PDGF-B mRNA expression at the level of transcription, which was abrogated by mutation of the Sp1 binding site in the PDGF-B promoter or overexpression of mutant Sp1. Rather than increasing total levels of Sp1, nogalamycin altered the phosphorylation state of the transcription factor. Overexpression of dominant-negative PKC-ζ blocked nogalamycin-inducible Sp1 phosphorylation and PDGF-B promoter-dependent expression. Nogalamycin stimulated the phosphorylation of PKC-ζ (on residue Thr410). These findings demonstrate for the first time that PKC-ζ and Sp1 phosphorylation mediate the inducible expression of this growth factor.

Adenoviral gene transfer of Caenorhabditis elegans n−3 fatty acid desaturase optimizes fatty acid composition in mammalian cells

Omega−3 polyunsaturated fatty acids (PUFAs) are essential components required for normal cellular function and have been shown to exert many preventive and therapeutic actions. The amount of n−3 PUFAs is insufficient in most Western people, whereas the level of n−6 PUFAs is relatively too high, with an n−6/n−3 ratio of >18. These two classes of PUFAs are metabolically and functionally distinct and often have important opposing physiological functions; their balance is important for homeostasis and normal development. Elevating tissue concentrations of n−3 PUFAs in mammals relies on chronic dietary intake of fat rich in n−3 PUFAs, because mammalian cells lack enzymatic activities necessary either to synthesize the precursor of n−3 PUFAs or to convert n−6 to n−3 PUFAs. Here we report that adenovirus-mediated introduction of the Caenorhabditis elegans fat-1 gene encoding an n−3 fatty acid desaturase into mammalian cells can quickly and effectively elevate the cellular n−3 PUFA contents and dramatically balance the ratio of n−6/n−3 PUFAs. Heterologous expression of the fat-1 gene in rat cardiac myocytes rendered cells capable of converting various n−6 PUFAs to the corresponding n−3 PUFAs, and changed the n−6/n−3 ratio from about 15:1 to 1:1. In addition, an eicosanoid derived from n−6 PUFA (i.e., arachidonic acid) was reduced significantly in the transgenic cells. This study demonstrates an effective approach to modifying fatty acid composition of mammalian cells and also provides a basis for potential applications of this gene transfer in experimental and clinical settings.

Métodos de adequação e diagnóstico em modelos de sobrevivência dinâmicos

A análise de dados de sobrevivência tem sido tradicionalmente baseada no modelo de regressão de Cox (COX, 1972). No entanto, a suposição de taxas de falha proporcionais assumida para esse modelo pode não ser atendida em diversas situações práticas. Essa restrição do modelo de Cox tem gerado interesse em abordagens alternativas, dentre elas os modelos dinâmicos que permitem efeito das covariáveis variando no tempo. Neste trabalho, foram revisados os principais modelos de sobrevivência dinâmicos com estrutura aditiva e multiplicativa nos contextos não paramétrico e semiparamétrico. Métodos gráficos baseados em resíduos foram apresentados com a finalidade de avaliar a qualidade de ajuste desses modelos. Uma versão tempo-dependente da área sob a curva ROC, denotada por AUC(t), foi proposta com a finalidade de avaliar e comparar a qualidade de predição entre modelos de sobrevivência com estruturas aditiva e multiplicativa. O desempenho da AUC(t) foi avaliado por meio de um estudo de simulação. Dados de três estudos descritos na literatura foram também analisados para ilustrar ou complementar os cenários que foram considerados no estudo de simulação. De modo geral, os resultados obtidos indicaram que os métodos gráficos apresentados para avaliar a adequação dos modelos em conjunto com a AUC(t) se constituem em um conjunto de ferramentas estatísticas úteis para o próposito de avaliar modelos de sobrevivência dinâmicos nos contextos não paramétrico e semiparamétrico. Além disso, a aplicação desse conjunto de ferramentas em alguns conjuntos de dados evidenciou que se, por um lado, os modelos dinâmicos são atrativos por permitirem covariáveis tempo-dependentes, por outro lado podem não ser apropriados para todos os conjuntos de dados, tendo em vista que estimação pode apresentar restrições para alguns deles.

A integralidade no cuidado das pessoas vivendo com HIV e AIDS: a experiência do Centro de Referência e Treinamento em DST/AIDS da SES-SP

Ao assumir o compromisso com a prevenção e tratamento, baseada no princípio da integralidade, a estratégia brasileira, fez a diferença na resposta nacional à aids nas décadas de 1980/90 e criou um novo paradigma que mostrou-se avançado do ponto de vista técnico, ético e político, contribuindo para a mudança nas recomendações das agências internacionais (OMS\\Banco Mundial) - do \"não tratar e só prevenir\" do início dos anos 1990, para o \"Tratamento como Prevenção\", base da atual proposta dos 90/90/90. Essa estratégia de controle da epidemia concentra responsabilidade na Rede de Serviços, em um período de discussão sobre mudanças no modelo de atenção a ser priorizado no país. Características relevantes dos contextos político e programáticos permitiram uma maior efetivação do cuidado às PVHA no Estado de São Paulo. O objetivo do presente estudo é recuperar a história do Centro de Referência e Treinamento em DST/Aids (CRT) na gestão e organização programática do cuidado em HIV/Aids no Estado de São Paulo, no período de 1988 a 2015, interpretando-a sob a perspectiva dos aspectos facilitadores e limitadores da incorporação prática do princípio da integralidade às ações de saúde. Realizou-se, nesse sentido, uma revisão narrativa da literatura sobre o tema da integralidade no campo da Saúde Coletiva Brasileira nas últimas cinco décadas. Tomando por base o cotejamento com esse desenvolvimento conceitual, a trajetória do CRT foi analisada por meio de entrevistas com atores-chaves no processo da gestão e organização programática do cuidado das PVHA no Estado de São Paulo, e análise dos documentos produzidos no processo. Esta análise foi organizada em torno de dois grandes eixos temáticos: (1) a criação e estruturação do CRT, e (2) as relações entre o CRT, os Programas Municipais de DST/aids e a rede de serviços assistenciais no Estado de São Paulo. Entre os resultados do estudo, destacam-se o resgate e reflexão crítica sobre o desenvolvimento dos discursos tecnocientíficos sobre integralidade no contexto das propostas de reforma da saúde no Brasil; a incorporação desses construtos às propostas desenvolvidas pelo CRT, especialmente em torno aos conceitos de vulnerabilidade, cuidado, clínica ampliada e direitos humanos em saúde; e a identificação de arranjos institucionais, estratégias técnicas e configurações políticas que permitiram ao CRT o exercício articulado de três níveis de gestão do cuidado (das PVHA, dos serviços e da Rede) numa mesma plataforma. Conclui-se apontando alcances e limites na efetivação da integralidade, que se mostraram desiguais nos três níveis de gestão do cuidado. Aponta-se maiores avanços na dimensão gerencial da rede e as maiores dificuldades na efetivação da integralidade no cuidado das PVHA e na gestão dos serviços de saúde

Análisis traductológico de la obra paremiográfica de Charles Cahier, (francés-español)

This thesis contains a translatological analysis of the Spanish proverbs collected by Charles Cahier in Quelque six mille proverbes et aphorismes usuels empruntés à notre âge et aux siècles derniers. Proverbs and other sententious sayings are part of our day-to-day life, and are more or less intensely used according to cultures and their types of speech. They have always existed in every single civilisation. There is, indeed, no denying that the purpose of proverbs is to convey an old experience. They are quoted by major philosophers and writers of all times. As a result of the interest they have raised, books of proverbs have been published for many centuries in a high number of countries. Proverbs can be found everywhere, both in professional and personal settings, or in a conversation between friends. In France, these sayings are more commonly used in literature than in spoken language, whereas in Spain proverbs can be found at all levels of communication. In this regard, it is interesting to compare the translations of international works to detect a number of misunderstandings regarding the interpretation of paremiological elements. This is why translating proverbs is a genuine, complex issue. This thesis, which is aimed at Spanish and French speakers (including native and foreign speakers), has a double application (translatological and linguistic) and falls within the context of translatological and comparative paremiology...

Estado actual de la investigación sobre la teoría tridimensional de la ansiedad de Lang

Este estudio ofrece una revisión de la teoría tridimensional propuesta por Lang (1968), quien mantiene que la ansiedad se manifiesta según un triple sistema de respuesta (cognitivo, fisiológico y motor o conductual) que pueden ser discordantes. Estos tres sistemas, regulados por normas diferentes, dan lugar a perfiles de respuesta diferenciales, los cuales será necesario evaluar por separado para, posteriormente, elegir el método de tratamiento más adecuado. En esta línea, el presente estudio ofrece una revisión de investigaciones que, hasta el día de hoy, han apoyado la teoría propuesta por Lang. Finalmente, este estudio revisa diferentes cuestionarios, inventarios y escalas construidos desde la teoría propuesta por Lang, revelando que, en la actualidad, la teoría tridimensional de la ansiedad continúa siendo aplicada en el ámbito clínico, de la salud y el escolar, lo que denota su actualidad, relevancia y practicidad.

THE DESIGN OF A POWER SYSTEM FOR A WIRELESS SENSOR NETWORK FOR LONG-TERM OPERATION

Wireless sensor networks (WSNs) have shown wide applicability to many fields including monitoring of environmental, civil, and industrial settings. WSNs however are resource constrained by many competing factors that span their hardware, software, and networking. One of the central resource constrains is the charge consumption of WSN nodes. With finite energy supplies, low charge consumption is needed to ensure long lifetimes and success of WSNs. This thesis details the design of a power system to support long-term operation of WSNs. The power system’s development occurs in parallel with a custom WSN from the Queen’s MEMS Lab (QML-WSN), with the goal of supporting a 1+ year lifetime without sacrificing functionality. The final power system design utilizes a TPS62740 DC-DC converter with AA alkaline batteries to efficiently supply the nodes while providing battery monitoring functionality and an expansion slot for future development. Testing tools for measuring current draw and charge consumption were created along with analysis and processing software. Through their use charge consumption of the power system was drastically lowered and issues in QML-WSN were identified and resolved including the proper shutdown of accelerometers, and incorrect microcontroller unit (MCU) power pin connection. Controlled current profiling revealed unexpected behaviour of nodes and detailed current-voltage relationships. These relationships were utilized with a lifetime projection model to estimate a lifetime between 521-551 days, depending on the mode of operation. The power system and QML-WSN were tested over a long term trial lasting 272+ days in an industrial testbed to monitor an air compressor pump. Environmental factors were found to influence the behaviour of nodes leading to increased charge consumption, while a node in an office setting was still operating at the conclusion of the trail. This agrees with the lifetime projection and gives a strong indication that a 1+ year lifetime is achievable. Additionally, a light-weight charge consumption model was developed which allows charge consumption information of nodes in a distributed WSN to be monitored. This model was tested in a laboratory setting demonstrating +95% accuracy for high packet reception rate WSNs across varying data rates, battery supply capacities, and runtimes up to full battery depletion.

Exploring several nonconventional interactions of ice-binding proteins

Traditionally, ice-binding proteins (IBPs), also known as antifreeze proteins (AFPs), have been defined by two universal activities: ice recrystallization inhibition and thermal hysteresis. However, there remains the possibility IBPs have other complementary functions given the diversity found within this protein group. This thesis explores some of these in both natural and applied settings, in the hopes of furthering our understanding of this remarkable group of proteins. Plant IBPs could function as part of a defensive strategy against ice nucleators produced by certain pathogens. To assess this hypothesis, recombinant IBPs from perennial ryegrass and purple false brome were combined with the ice nucleation protein (INP) from the plant pathogen, Pseudomonas syringae. Strikingly, the plant proteins depressed the freezing point of the bacterial INP, while a fish AFP could not, nor did the INPs have any effect on IBP activity. Thus, the interaction between these two different proteins suggests a role in plant defensive strategies against pathogenic bacteria as another IBP function. In addition, the potential use of hyperactive insect IBPs in organ preservation was investigated. Current kidney preservation techniques involve storing the organ at 4 °C for a maximum of 24 h prior to transplantation. Extending this “safe” time would have profound effects on renal transplants, however, ischemic injury is prevalent when storage periods are prolonged. Experiments described here allowed subzero preservation for 72 h with the addition of a beetle IBP to CryoStasis® solution. Kidneys stored using the traditional technique for 24 h and the method developed here for 72 h showed similar levels of biomarker enzymes, underscoring the potential utility of insect IBPs for future transplant purposes. Finally, IBP function in the freeze-tolerant gall fly, Eurosta solidaginis, was examined. Larvae representing the mid-autumn stage displayed ice-binding activity, suggesting an IBP is being expressed, possibly as a protective measure against freezing damage when fall temperatures can unpredictably drop. IBP activity was also observed in the larvae’s host plant, Solidago spp. Mass spectrometry analysis of ice-affinity purified plant extracts provided three candidate pathogenesis-related proteins that could be responsible for the detected activity, further demonstrating additional functions of IBPs.

The Danish Flexicurity Model - a Lesson for the US? ACES Working Paper No. 2, May 2007

Within recent years, increasing international competition has caused an increase in job transitions worldwide. Many countries find it difficult to manage these transitions in a way that ensures a match between labour and demand. One of the countries that seem to manage the transitions in a successful way is Denmark, where unemployment has been dropping dramatically over the last decade without a drop in job quality. This success is ascribed the so-called Danish flexicurity model, where an easy access to hiring and firing employees (flexibility) is combined with extensive active and passive labour market policies (security). The Danish results have gained interest not only among other European countries, where unemployment rates remain high, but also in the US, where job loss is often related to lower job quality. It has, however, been subject to much debate both in Europe and in the US, whether or not countries with distinctively different political-economic settings can learn from one another. Some have argued that cultural differences impose barriers to successful policy transfer, whereas others see it as a perfectly rational calculus to introduce 'best practices' from elsewhere. This paper presents a third strategy. Recent literature on policy transfer suggests that successful cross national policy transfer is possible, even across the Atlantic, but that one must be cautious in choosing the form, content and level of the learning process. By analysing and comparing the labour market policies and their settings in Denmark and the US in detail, this paper addresses the question, what and how the US can learn from the Danish model. Where the US and Denmark share a high degree of flexibility, they differ significantly on the level of security. This also means that the Danish budget for active and passive labour market policies is significantly higher than the American, and it seems unlikely that political support for the introduction of Danish levels of security in the US can be established. However, the paper concludes that there is a learning potential between the US and Demnark in the different local level efficiency of the money already spent. A major reason for the Danish success has been the introduction of tailor made initiatives to the single displaced worker and a stronger coordination between local level actors. Both of which are issues, where a lack of efficiency in the implementation of American active labour market policies has been reported.

Attitudes of the autism community to early autism research

Investigation into the earliest signs of autism in infants has become a significant sub-field of autism research. This work invokes specific ethical concerns such as use of 'at-risk' language, communicating study findings to parents and the future perspective of enrolled infants when they reach adulthood. This study aimed to ground this research field in an understanding of the perspectives of members of the autism community. Following focus groups to identify topics, an online survey was distributed to autistic adults, parents of children with autism and practitioners in health and education settings across 11 European countries. Survey respondents (n = 2317) were positively disposed towards early autism research, and there was significant overlap in their priorities for the field and preferred language to describe infant research participants. However, there were also differences including overall less favourable endorsement of early autism research by autistic adults relative to other groups and a dislike of the phrase 'at-risk' to describe infant participants, in all groups except healthcare practitioners. The findings overall indicate that the autism community in Europe is supportive of early autism research. Researchers should endeavour to maintain this by continuing to take community perspectives into account.

Analysis of analogue models by helical X-ray computed tomography

The aim of analogue model experiments in geology is to simulate structures in nature under specific imposed boundary conditions using materials whose rheological properties are similar to those of rocks in nature. In the late 1980s, X-ray computed tomography (CT) was first applied to the analysis of such models. In early studies only a limited number of cross-sectional slices could be recorded because of the time involved in CT data acquisition, the long cooling periods for the X-ray source and computational capacity. Technological improvements presently allow an almost unlimited number of closely spaced serial cross-sections to be acquired and calculated. Computer visualization software allows a full 3D analysis of every recorded stage. Such analyses are especially valuable when trying to understand complex geological structures, commonly with lateral changes in 3D geometry. Periodic acquisition of volumetric data sets in the course of the experiment makes it possible to carry out a 4D analysis of the model, i.e. 3D analysis through time. Examples are shown of 4D analysis of analogue models that tested the influence of lateral rheological changes on the structures obtained in contractional and extensional settings.

(Table 1) Argon dating of ash layers from DSDP Hole 18-178

Ash layers from Deep Sea Drilling Project site 178 in the northeast Pacific Ocean have been dated by the 40Ar-39Ar stepwise heating technique to resolve published discrepancies concerning the length of time explosive volcanism has affected the eastern Aleutian arc and Alaskan Peninsula. The results of the investigation indicate that the record of ash-fall deposition at site 178 extends back at least 6.5 m.y. Assuming that 6.5 m.y. ago marks the onset of renewed calc-alkalic volcanism of the volcanic arc, proposed models of continuous and discontinuous motion between the Pacific and North American lithospheric plates can be evaluated. If appreciable time elapsed between the onset of subduction and the onset of arc volcanism, the 6.5-m.y. record of ash-fall deposition in the north-east Pacific is most compatible with models of continuous plate motion throughout late Cenozoic time.

Element concentrations of aluminosilicate components from ODP sites in the Pacific Ocean

We measured major and trace element concentrations in the operationally defined, chemically extracted, residual aluminosilicate component of sediment from Ocean Drilling Program Sites 1215 and 1256 in the central and eastern equatorial Pacific Ocean and found that this residual component contains volcanogenic and authigenic aluminosilicates in addition to inferred eolian material. While the residual component younger than 20 Ma from the central Pacific (ODP Site 1215) is similar compositionally to upper continental crust and suggests an increase in the delivery of Asian dust material since 20 Ma, the residual in sediment older than 20 Ma indicates significant amounts of volcanogenic and authigenic materials. Volcanogenic debris comprises as much as ~ 40% of the residual between 23-40 Ma, which coincides with the mid-Tertiary "ignimbrite flare-up" that occurred in much of western North America. The residual component extracted from the 50 Ma biogenic sediment reflects authigenic signatures (seawater-like negative cerium anomalies and elevated Fe/Si ratios). The previously interpreted increase in an andesitic detrital source in North Pacific locations may instead be authigenic material, presenting significant challenges for many paleoclimate proxies. Additionally, in the eastern Pacific (ODP Site 1256), the residual component contains ~70% of volcanogenic material, most likely originating from Central America, and also includes refractory barite. The ability to separately identify eolian, volcanogenic, and authigenic materials in the aluminosilicate component of pelagic sediment allows resolution, respectively, of the climatic, geologic, and chemical processes contributing to the paleoceanographic archive in this critical oceanic region.

El uso del valenciano, la actitud hacia la lengua y la destreza escrita : Un estudio sociolingüístico sobre el dominio del valenciano de jóvenes alicantinos

Los jóvenes de Alicante viven en una sociedad donde coexisten dos lenguas, el castellano y el valenciano. La lengua valenciana es utilizada por jóvenes de Alicante tanto en ámbitos formales como informales. Los jóvenes hablantes de valenciano sienten un lazo identificativo con la lengua que se rige por las actitudes de éstos. La actitud lingüística conlleva a una identificación lingüística del hablante, la cual es una construcción social que se rige por las normas que rodean al hablante. La identificación bilingüe podría, por lo tanto, ser influenciada e influenciar a su vez a la competencia lingüística. El propósito del presente estudio es investigar en qué situaciones y contextos es usado el valenciano; con el objetivo de estudiar la relación entre el grado de bilingüismo, la actitud lingüística y el nivel de complejidad, corrección y fluidez (CAF) en la expresión escrita del valenciano. Partimos de la hipótesis de que el valenciano tiene, para la generación joven de Alicante, una función social y que la actitud hacia la lengua es positiva, lo que a su vez se refleja en la destreza escrita. Para comprobar nuestra hipótesis nos hemos basado en un cuestionario de hábitos sociales, un test de nivel de valenciano y dos redacciones, una escrita en castellano y una en valenciano. Con la participación de 59 jóvenes alicantinos, llegamos a la conclusión de que el valenciano es usado tanto en ámbitos formales como informales y que la actitud hacia la lengua es positiva, y que consideran importante dominar y preservar el valenciano. Además, los participantes han presentado un nivel alto de destreza en el valenciano escrito, mostrando complejidad y fluidez en la expresión escrita. Por otro lado, la corrección es más elevada en el castellano. También se ha podido ver que la identificación de los participantes está relativamente correlacionada con la competencia lingüística.