Chronic systemic therapy with low-dose morpholino oligomers ameliorates the pathology and normalizes locomotor behavior in mdx Mice

The administration of antisense oligonucleotides (AOs) to skip one or more exons in mutated forms of the DMD gene and so restore the reading frame of the transcript is one of the most promising approaches to treat Duchenne muscular dystrophy (DMD). At present, preclinical studies demonstrating the efficacy and safety of long-term AO administration have not been conducted. Furthermore, it is essential to determine the minimal effective dose and frequency of administration. In this study, two different low doses (LDs) of phosphorodiamidate morpholino oligomer (PMO) designed to skip the mutated exon 23 in the mdx dystrophic mouse were administered for up to 12 months. Mice treated for 50 weeks showed a substantial dose-related amelioration of the pathology, particularly in the diaphragm. Moreover, the generalized physical activity was profoundly enhanced compared to untreated mdx mice showing that widespread, albeit partial, dystrophin expression restores the normal activity in mdx mice. Our results show for the first time that a chronic long-term administration of LDs of unmodified PMO, equivalent to doses in use in DMD boys, is safe, significantly ameliorates the muscular dystrophic phenotype and improves the activity of dystrophin-deficient mice, thus encouraging the further clinical translation of this approach in humans.

Immobilisation of phenanthroline-bis triazine(c1-btphen) on magnetic nanoparticles for co-extraction of americium(III) and europium(III)

The present work reports a convenient route for the immobilisation of a phenanthroline-bis triazine (C1-BTPhen) group on the surface of zirconia-coated maghemite (γ-Fe2O3) magnetic nanoparticles. The magnetic nanoparticles functionalized with C1-BTPhen were able to co-extract Am(III) and Eu(III) from nitric acid (HNO3). The extraction efficiency of these C1-BTPhen-functionalized magnetic nanoparticles for both Am(III) and Eu(III) was 20% at 4M HNO3. The interaction between C1-BTPhen and metal cations is reversible. These functionalized magnetic nanoparticles can be used for the co-extraction of traces of Am(III) and Eu(III).

Utilizing electronic effects in the modulation of BTPhen ligands with respect to the partitioning of minor actinides from lanthanides

Effects of bromine substitution at the 5 and 5,6-positions of the 1,10-phenanthroline nucleus of BTPhen ligand on their extraction properties for Ln(III) andAn(III) cations have been studied. Compared to C5-BTPhen, electronic modulation in BrC5-BTPhen and Br2C5-BTPhen enabled these ligands to be fine-tuned in order to enhance the separation selectivity of Am(III) from Eu(III)

The effect of alkyl substitution on the extraction properties of BTPhen ligands for the partitioning of trivalent minor actinides and lanthanides in spent nuclear fuels

Bis-triazinylphenanthroline ligands (BTPhens), which contain additional alkyl (n-butyl and sec-butyl) groups attached to the triazine rings, have been synthesized, and the effects of this alkyl substitution on their extraction properties with Ln(III) and An(III) cations in simulated nuclear waste solutions have been studied. The speciation of n-butyl-substituted ligand (C4- BTPhen) with some trivalent lanthanide nitrates was elucidated by 1 H-NMR spectroscopic titrations. These experiments have shown that the dominant species in solution were the 1:2 complexes [Ln(III)(BTPhen)2], even at higher Ln(III) concentrations, and the relative stability of 2:1 to 1:1 BTPhen-Ln(III) complexes varied with different lanthanides. As expected, sec-butylsubstituted ligand (sec-C4 BTPhen) showed higher solubility than C4-BTPhen in certain diluents. A greater separation factor (SFAm/Eu = ca. 210) was observed for sec-C4-BTPhen compared to C4-BTPhen (SFAm/Eu = ca. 125) in 1-octanol at 4 M HNO3 solutions. The greater separation factor may be due to the higher solubility of the 2:1 complex for sec-C4-BTPhen at the interface than the 1:1 complex of C4-BTPhen.

Firms in international trade: importers’ and exporters’ heterogeneity in Italian manufacturing industry

Combining data on structural characteristics and economic performance for a large sample of Italian firms with data on exporting and importing activity, we uncover evidence supporting recent theories on firm heterogeneity and international trade, together with some new facts. In particular, we find that importing is associated with substantial firm heterogeneity. First, we document that trade is more concentrated than employment and sales, and show that importing is even more concentrated than exporting both within sectors and along the sector- and country-extensive margins. Second, while supporting the fact that firms involved in both are the best performers, we also find that firms involved only in importing activities perform better than those involved only in exporting. Our evidence suggests there is a strong self-selection effect in the case of importers and the performance premia of internationalised firms correlate relatively more with the degree of geographical and sectoral diversification of imports.

Supporting local diversity of habitats and species on farmland: a comparison of three wildlife-friendly schemes

Restoration and maintenance of habitat diversity have been suggested as conservation priorities in farmed landscapes, but how this should be achieved and at what scale are unclear. This study makes a novel comparison of the effectiveness of three wildlife-friendly farming schemes for supporting local habitat diversity and species richness on 12 farms in England. The schemes were: (i) Conservation Grade (Conservation Grade: a prescriptive, non-organic, biodiversity-focused scheme), (ii) organic agriculture and (iii) a baseline of Entry Level Stewardship (Entry Level Stewardship: a flexible widespread government scheme). Conservation Grade farms supported a quarter higher habitat diversity at the 100-m radius scale compared to Entry Level Stewardship farms. Conservation Grade and organic farms both supported a fifth higher habitat diversity at the 250-m radius scale compared to Entry Level Stewardship farms. Habitat diversity at the 100-m and 250-m scales significantly predicted species richness of butterflies and plants. Habitat diversity at the 100-m scale also significantly predicted species richness of birds in winter and solitary bees. There were no significant relationships between habitat diversity and species richness for bumblebees or birds in summer. Butterfly species richness was significantly higher on organic farms (50% higher) and marginally higher on Conservation Grade farms (20% higher), compared with farms in Entry Level Stewardship. Organic farms supported significantly more plant species than Entry Level Stewardship farms (70% higher) but Conservation Grade farms did not (10% higher). There were no significant differences between the three schemes for species richness of bumblebees, solitary bees or birds. Policy implications. The wildlife-friendly farming schemes which included compulsory changes in management, Conservation Grade and organic, were more effective at increasing local habitat diversity and species richness compared with the less prescriptive Entry Level Stewardship scheme. We recommend that wildlife-friendly farming schemes should aim to enhance and maintain high local habitat diversity, through mechanisms such as option packages, where farmers are required to deliver a combination of several habitats.

SEM, EPR and ToF-SIMS analyses applied to unravel the technology employed for pottery-making by pre-colonial Indian tribes from Pantanal, Brazil

The present work aims at elucidating the technology applied in the fabrication of ceramic objects by the ancient ceramists that inhabited the western border of Pantanal, Mato-Grosso do Sul, with the help of a multidisciplinary approach making use of chemical and physical methods of analysis. The potshards under study show the presence of different types of additives, as determined by scanning electron microscopy (SEM) and time of flight secondary ion mass spectrometry (ToF-SIMS). The dispersion of the additives within the ceramic matrix was also addressed by SEM, which shed light on the mounting technique used by the potters to assemble the ceramic vessels. Moreover, the tensile strength conferred to the pottery by the use of a specific type of additive was evaluated by applying a mechanical test. These results were correlated with the firing temperature of the potshards, determined by means of electron paramagnetic resonance (EPR). (C) 2010 Elsevier Ltd. All rights reserved.

The First Provenance Challenge

The first Provenance Challenge was set up in order to provide a forum for the community to understand the capabilities of different provenance systems and the expressiveness of their provenance representations. To this end, a Functional Magnetic Resonance Imaging workflow was defined, which participants had to either simulate or run in order to produce some provenance representation, from which a set of identified queries had to be implemented and executed. Sixteen teams responded to the challenge, and submitted their inputs. In this paper, we present the challenge workflow and queries, and summarise the participants contributions.

Localization strategies of multinationals in Brazil which characteristics of the Brazilian market force multinational companies to localize their marketing activities?

Uma vez que as perspectivas de crescimento económico nos países mais desenvolvidos, como a Europa, os EUA eo Japão estão diminuindo, os mercados emergentes têm se tornado cada vez mais importante para muitas empresas multinacionais. Brasil, Rússia, Índia e China (BRICs) são agora os principais mercados em crescimento em todo o mundo e as empresas estão buscando estratégias para explorar ao máximo o potencial de consumo promissor nessas regiões. Um dos modos mais elaborados de prosseguir essa estratégia é conhecida como "localização" - uma adaptação das práticas de negócios (ao longo de toda a cadeia de suprimentos) com as preferências e condições locais. Este artigo é projetado para analisar as atividades de localização de empresas multinacionais no Brasil. O foco da análise é o de investigar as características do mercado brasileiro, que induzem as multinacionais a localizar o seu marketing mix (composto de produto, preço, colocação e promoção). Em dois estudos de casos com a empresa Suiça Nestlé e a empresa Alemã Volkswagen vários padrões de localização foram no mercado consumidor brasileiro. Os quatro resultados mais significativos da análise são os diferentes padrões sociais o Brasil, que forçar as empresas a reformular certas funções do seu mix de marketing (por exemplo, a colocação no caso da Nestlé), a aceitação dos consumidores brasileiros a pagar preços relativamente elevados (por exemplo, taxas de Volkswagen até 100% mais por seus produtos em relação à Alemanha); o enorme tamanho do Brasil ea infra-estrutura deficiente, que exigem uma abordagem de distribuição localizada; eo caráter atualmente ainda menos exigente dos estratos de consumidores brasileiros emergentes, que permitem às empresas oferecer produtos menos sofisticados em comparação aos mercados europeus.

Como se chega ou como nos tornamos docentes no Ensino Superior

The Thesis weaved in the (auto) biographical boarding studies the existence of existential teaching, in the scope of Superior Teaching, guided in the experience and the (auto) formative scope as a theoreticianmethodological support present in the classrooms, being three the essential questions: Which the way of (auto) formation traveled by professors of Superior Teaching, what is, for these citizens, the teaching in Superior Teaching and what they understand from existential teaching according to their narratives. The epistemology of this work, based on Program of After-Graduation in Education of Universidade Federal do Rio Grande do Norte, Support of Research: Professionalization and Formation Lecturing emerges, especially, of the studies and research realized by Ramalho and Nuñez (2005, 2006), Morosini (2001), Pimenta and Anastasiou (2002), Nóvoa (2000), Josso (2004), Dominicé (1988), Catani (2002), and Souza (2004), among other authors, yonder the educational practice exercised by researcher and involved citizens in inquiryformation, what it is confirmed from the three methodological tools that given support to the covered way: Eight topic narratives, a participantcomment and seven laboratories or parallel meeting of formation (EPF's) experimented with licensed teachers that actuate in superior teaching institutions (IES), public and private, localized in the city of Natal/RN. The Thesis points out, in this way, existential education in the guideline of viable and concrete methodological alternatives amongst the problematic of the (auto) formation faced for the professors in Superior Teaching

Improvement of heart rate variability after exercise training and its predictors in COPD

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Food restriction promotes downregulation of myocardial L-type Ca2+ channels

Food restriction (FR) has been shown to impair myocardial performance. However, the mechanisms behind these changes in myocardial function due to FR remain unknown. Since myocardial L-type Ca2+ channels may contribute to the cardiac dysfunction, we examined the influence of FR on L-type Ca2+ channels. Male 60-day-old Wistar rats were fed a control or a restricted diet (daily intake reduced to 50% of the amount of food consumed by the control group) for 90 days. Myocardial performance was evaluated in isolated left ventricular papillary muscles. The function of myocardial L-type Ca2+ channels was determined by using a pharmacological Ca2+ channel blocker, and changes in the number of channels were evaluated by mRNA and protein expression. FR decreased final body weights, as well as weights of the left and right ventricles. The Ca2+ channel blocker diltiazem promoted a higher blockade on developed tension in FR groups than in controls. The protein content of L-type Ca2+ channels was significantly diminished in FR rats, whereas the mRNA expression was similar between groups. These results suggest that the myocardial dysfunction observed in previous studies with FR animals could be caused by downregulation of L-type Ca2+ channels.

Compósitos de Al2O3/ZrO2 recobertos com hidroxiapatita dopada com íons Ag

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)