Cholesterol 24S-Hydroxylase overexpression inhibits the liver X receptor (LXR) pathway by activating small guanosine triphosphate-binding proteins (sGTPases) in neuronal cells

The neuronal-specific cholesterol 24S-hydroxylase (CYP46A1) is important for brain cholesterol elimination. Cyp46a1 null mice exhibit severe deficiencies in learning and hippocampal long-term potentiation, suggested to be caused by a decrease in isoprenoid intermediates of the mevalonate pathway. Conversely, transgenic mice overexpressing CYP46A1 show an improved cognitive function. These results raised the question of whether CYP46A1 expression can modulate the activity of proteins that are crucial for neuronal function, namely of isoprenylated small guanosine triphosphate-binding proteins (sGTPases). Our results show that CYP46A1 overexpression in SH-SY5Y neuroblastoma cells and in primary cultures of rat cortical neurons leads to an increase in 3-hydroxy-3-methyl-glutaryl-CoA reductase activity and to an overall increase in membrane levels of RhoA, Rac1, Cdc42 and Rab8. This increase is accompanied by a specific increase in RhoA activation. Interestingly, treatment with lovastatin or a geranylgeranyltransferase-I inhibitor abolished the CYP46A1 effect. The CYP46A1-mediated increase in sGTPases membrane abundance was confirmed in vivo, in membrane fractions obtained from transgenic mice overexpressing this enzyme. Moreover, CYP46A1 overexpression leads to a decrease in the liver X receptor (LXR) transcriptional activity and in the mRNA levels of ATP-binding cassette transporter 1, sub-family A, member 1 and apolipoprotein E. This effect was abolished by inhibition of prenylation or by co-transfection of a RhoA dominant-negative mutant. Our results suggest a novel regulatory axis in neurons; under conditions of membrane cholesterol reduction by increased CYP46A1 expression, neurons increase isoprenoid synthesis and sGTPase prenylation. This leads to a reduction in LXR activity, and consequently to a decrease in the expression of LXR target genes.

Groundwater from infiltration galleries used for small public water supply systems: contamination with pesticides and endocrine disruptors

Infiltration galleries are among the oldest known means used for small public water fountains. Owing to its ancestral origin they are usually associated with high quality water. Thirty-one compounds, including pesticides and estrogens from different chemical families, were analysed in waters from infiltration galleries collected in Alto Douro Demarcated Wine region (North of Portugal). A total of twelve compounds were detected in the water samples. Nine of these compounds are described as presenting evidence or potential evidence of interfering with the hormone system of humans and wildlife. Although concentrations of the target analytes were relatively low, many of them below their limit of quantification, four compounds were above quantification limit and two of them even above the legal limit of 0.1 lg/L: dimethoate (30.38 ng/L), folpet (64.35 ng/L), terbuthylazine-desethyl (22.28 to 292.36 ng/L) and terbuthylazine (22.49 to 369.33 ng/L).

Broad-temperature range spectroscopy of the two-centre modular redox metalloprotein Desulfovibrio desulfuricans desulfoferrodoxin

Dalton Trans., 2003, 3328-3338

Electrochemical studies on small electron transfer proteins using membrane electrodes

Journal of Electroanalytical Chemistry 541 (2003) 153-162

Modular high-current generator for electromagnetic forming with energy recovery

A 10 kJ electromagnetic forming (EMF) modulator with energy recovery based on two resonant power modules, each containing a 4.5 kV/30-kA silicon controlled rectifier, a 1.11-mF capacitor bank and an energy recovery circuit, working in parallel to allow a maximum actuator discharge current amplitude and rate of 50 kA and 2 kA/mu s was successfully developed and tested. It can be plugged in standard single phase 230 V/16 A mains socket and the circuit is able to recover up to 32% of its initial energy, reducing the charging time of conventional EMF systems by up to 68%.

Multilevel high-voltage pulse generation based on a new modular solid-state switch

This paper describes a modular solid-state switching cell derived from the Marx generator concept to be used in topologies for generating multilevel unipolar and bipolar high-voltage (HV) pulses into resistive loads. The switching modular cell comprises two ON/OFF semiconductors, a diode, and a capacitor. This cell can be stacked, being the capacitors charged in series and their voltages balanced in parallel. To balance each capacitor voltage without needing any parameter measurement, a vector decision diode algorithm is used in each cell to drive the two switches. Simulation and experimental results, for generating multilevel unipolar and bipolar HV pulses into resistive loads are presented.

Invariant integrals applied to nematic liquid crystals with small Ericksen number and topological defects

Invariant integrals are derived for nematic liquid crystals and applied to materials with small Ericksen number and topological defects. The nematic material is confined between two infinite plates located at y = -h and y = h (h is an element of R+) with a semi-infinite plate at y = 0 and x < 0. Planar and homeotropic strong anchoring boundary conditions to the director field are assumed at these two infinite and semi-infinite plates, respectively. Thus, a line disclination appears in the system which coincides with the z-axis. Analytical solutions to the director field in the neighbourhood of the singularity are obtained. However, these solutions depend on an arbitrary parameter. The nematic elastic force is thus evaluated from an invariant integral of the energy-momentum tensor around a closed surface which does not contain the singularity. This allows one to determine this parameter which is a function of the nematic cell thickness and the strength of the disclination. Analytical solutions are also deduced for the director field in the whole region using the conformal mapping method. (C) 2013 Elsevier Ltd. All rights reserved.

Reactivity of bulky tris(Phenylpyrazolyl) methanesulfonate copper(I) complexes towards small unsaturated molecules

Reaction of the tris(3-phenylpyrazolyl)methane sulfonate species (Tpms(Ph))Li with the copper(I) complex [Cu(MeCN)(4)][PF6] affords [Cu(Tpms(Ph))(MeCN)] 1. The latter, upon reaction with equimolar amounts of cyclohexyl-(CyNC) or 2,6-dimethylphenyl (XylNC) isocyanides, or excess CO, furnishes the corresponding Cu(I)complexes [Cu(Tpms(Ph))(CNR)] (R = Cy 2, Xyl 3) or [Cu(Tpms(Ph))(CO)] 4. The ligated isocyanide in 2 or 3 (or the acetonitrile ligand in 1)is displaced by 3-iminoisoindolin-1-one to afford 5, the first copper(I) complex containing an 3-iminoisoindolin-1-one ligand. The ligated acetonitrile in 1 undergoes nucleophilic attack by methylamine to give the amidine complex [Cu(Tpms(Ph)){MeC(NH)NHMe}] 6, whereas only the starting materials were recovered from the attempted corresponding reactions of 2 and 3 with methylamine. Complexes 1 or 6 form the trinuclear hydroxo-copper(II)species [(mu-Cu){Cu(mu-OH) (2)(Tpms(Ph))}(2)] 7 upon air oxidation in moist methanol. In all the complexes the scorpionate ligand facially caps the metal in the N,N,O-coordination mode.

An overview of the higher level classification of Pucciniomycotina based on combined analyses of nuclear large and small subunit rDNA sequences

Mycologia, Vol. 98, nº6

Habitação modular evolutiva

Da necessidade de criação de habitações que se adaptem ao constante dinamismo do ser humano, surgiu a ideia da concepção de um edifício evolutivo com base na construção modular. A construção modular poderá ser entendida como sendo a principal resposta ao combate da construção de estruturas físicas e imóveis, com características inalteráveis ao longo do tempo. Com este trabalho idealizou-se uma habitação evolutiva, baseado nos conceitos da Coordenação Modular, identificando-se as suas especificações, exigências de desempenho e características funcionais. Foi considerada como medida modular base 0,10m. Os módulos foram pensados com o intuito de que o seu desempenho prático seja satisfatório. A sua base estrutural foi executada a partir do rearranjo de contentores marítimos. Previu-se ainda, o uso de coberturas verdes por serem uma solução comprovada de minorar notoriamente o efeito pernicioso que a construção tem sobre o meio ambiente, ao mesmo tempo que apresentam vantagens térmicas e acústicas. A questão do incentivo do uso da pré-fabricação em Portugal a uma maior escala, não poderia ser descurada. A apresentação de eventuais desenvolvimentos futuros é também relevante, dada a importância que é inerente ao âmbito da industrialização da construção. Do estudo realizado ficaram ainda, bem patentes, os benefícios da racionalização e da industrialização, tanto em termos económicos como em termos ambientais. É possível executar um projecto com níveis de perdas mais baixos e com índices de qualidade superiores a um menor preço.

Functional domains of Bacillus subtilis transcription factor AraR and identification of aminoacids important for nucleoprotein complex assembly and effector-binding.

Journal of Bacteriology (Apr 2006) 3024-3036

Integrated Management of IaaS Resources

This paper proposes and reports the development of an open source solution for the integrated management of Infrastructure as a Service (IaaS) cloud computing resources, through the use of a common API taxonomy, to incorporate open source and proprietary platforms. This research included two surveys on open source IaaS platforms (OpenNebula, OpenStack and CloudStack) and a proprietary platform (Parallels Automation for Cloud Infrastructure - PACI) as well as on IaaS abstraction solutions (jClouds, Libcloud and Deltacloud), followed by a thorough comparison to determine the best approach. The adopted implementation reuses the Apache Deltacloud open source abstraction framework, which relies on the development of software driver modules to interface with different IaaS platforms, and involved the development of a new Deltacloud driver for PACI. The resulting interoperable solution successfully incorporates OpenNebula, OpenStack (reuses pre-existing drivers) and PACI (includes the developed Deltacloud PACI driver) nodes and provides a Web dashboard and a Representational State Transfer (REST) interface library. The results of the exchanged data payload and time response tests performed are presented and discussed. The conclusions show that open source abstraction tools like Deltacloud allow the modular and integrated management of IaaS platforms (open source and proprietary), introduce relevant time and negligible data overheads and, as a result, can be adopted by Small and Medium-sized Enterprise (SME) cloud providers to circumvent the vendor lock-in problem whenever service response time is not critical.

Six sigma methodologies: implementation and impacts on Portuguese small and medium companies (SMES)

Artigo elaborador no âmbito dos trabalhos decorrentes à dissertação de Mestrado do Aluno David Leite, no Mestrado em Gestão Integrada Qualidade, Ambiente e Segurança, ESTGF-IPP, Oreintados pelos Professores Luís Fonseca (ISEP-IPP) e Vanda Lima (ESTGF-IPP).

Rotavírus, adenovírus, astrovírus, calicivírus e "Small Round Virus Particles" em fezes de crianças, com e sem diarréia aguda, no período de 1987 a 1988, na Grande São Paulo

No período de agosto de 1987 a setembro de 1988, 193 amostras de fezes de crianças, com e sem sintomatologia diarréica aguda, foram submetidas às provas diagnósticas do ensaio imunoenzimático (EIE), eletroforese em gel de poliacrilamida (EGPA) e microscopia eletrônica (ME) para a detecção de vírus. A positividade para Rotavírus, Adenovírus, Astrovírus, Calicivírus e "Small Round Virus Particles" (SRVP) foi encontrada nas 97 crianças com diarréia aguda em 11,3%, 3,1%, 2,1%, l,0%e4,l%, respectivamente. Das 96 crianças sem diarréia, 4,2% foram positivas para Rotavírus, 1,0% para Calicivírus e 7,3% para SRVP. Das 15 amostras positivas para Rotavírus, 14 apresentaram perfil eletroforético característico do Grupo A e 1 amostra do Grupo C. A análise dos eletroforotipos demonstrou a grande heterogeneidade de perfis e a predominância do perfil "longo". A associação de vírus, bactéria e parasita foi encontrada tanto em crianças com diarréia como em crianças sem diarréia.

Medir e modular

A necessidade de construir que se manifesta em todos os sectores, desde o da habitação, em que o homem recupera da fadiga física e intelectual, consequência da sua actividade diária, até àquele em que exerce a sua actividade de produção ou onde realiza as suas ocupações sociais dos tempos livres, obriga a procurar soluções, para a limitação de espaços - cada vez mais económicos em tempo, dinheiro, materiais e mão de obra. Este objectivo levou ao desenvolvimento de técnicas de pré-fabricação,e bem assim a industrializar a construção, por elementos cada vez maiores - de acordo com os meios mecânicos de que se pode dispor na zona industrial, nos transportes e no estaleiro. Assim, conforme os elementos de construção a colocar em obra são manuseáveis ou, pelas suas dimensões e peso, careçam de meios mecânicos para poderem ser utilizados, a pré fabricação está diferenciada em: a) Pré fabricação ligeira b) Pré fabricação pesada Por outro lado, os diversos materiais que se utilizam na construção permitem a pré fabricação industrial de elementos de construção: metálicos, de madeira, de betão, de pedra, de argila cozida, de vidro, etc.