Highly potent delivery method of gp160 envelope vaccine combining lentivirus-like particles and DNA electrotransfer

Particulate antigen assemblies in the nanometer range and DNA plasmids are particularly interesting for designing vaccines. We hypothesised that a combination of these approaches could result in a new delivery method of gp160 envelope HIV-1 vaccine which could combine the potency of virus-like particles (VLPs) and the simplicity of use of DNA vaccines. Characterisation of lentivirus-like particles (lentiVLPs) by western blot, dynamic light scattering and electron microscopy revealed that their protein pattern, size and structure make them promising candidates for HIV-1 vaccines. Although all particles were similar with regard to size and distribution, they clearly differed in p24 capsid protein content suggesting that Rev may be required for particle maturation and Gag processing. In vivo, lentiVLP pseudotyping with the gp160 envelope or with a combination of gp160 and VSV-G envelopes did not influence the magnitude of the immune response but the combination of lentiVLPs with Alum adjuvant resulted in a more potent response. Interestingly, the strongest immune response was obtained when plasmids encoding lentiVLPs were co-delivered to mice muscles by electrotransfer, suggesting that lentiVLPs were efficiently produced in vivo or the packaging genes mediate an adjuvant effect. DNA electrotransfer of plasmids encoding lentivirus-like particles offers many advantages and appears therefore as a promising delivery method of HIV-1 vaccines. Keywords:VLP, Electroporation, Electrotransfer, HIV vaccine, DNA vaccine

Diurnal warm-layer events in the western Mediterranean and European shelf seas

We characterize near-surface ocean diurnal warm-layer events, using satellite observations and fields from numerical weather forecasting. The study covers April to September, 2006, over the area 11°W to 17°E and 35°N to 57°N, with 0.1° cells. We use hourly satellite SSTs from which peak amplitudes of diurnal cycles in SST (dSSTs) can be estimated with error ∼0.3 K. The diurnal excursions of SST observed are spatially and temporally coherent. The largest dSSTs exceed 6 K, affect 0.01% of the surface, and are seen in the Mediterranean, North and Irish Seas. There is an anti-correlation between the magnitude and the horizontal length scale of dSST events. Events wherein dSST exceeds 4 K have length scales of ≤40 km. From the frequency distribution of different measures of wind-speed minima, we infer that extreme dSST maxima arise where conditions of low wind speed are sustained from early morning to mid afternoon.

Estimating Lorenz's reference state in an ocean with a nonlinear equation of state for seawater

The study of the mechanical energy budget of the oceans using Lorenz available potential energy (APE) theory is based on knowledge of the adiabatically re-arranged Lorenz reference state of minimum potential energy. The compressible and nonlinear character of the equation of state for seawater has been thought to cause the reference state to be ill-defined, casting doubt on the usefulness of APE theory for investigating ocean energetics under realistic conditions. Using a method based on the volume frequency distribution of parcels as a function of temperature and salinity in the context of the seawater Boussinesq approximation, which we illustrate using climatological data, we show that compressibility effects are in fact minor. The reference state can be regarded as a well defined one-dimensional function of depth, which forms a surface in temperature, salinity and density space between the surface and the bottom of the ocean. For a very small proportion of water masses, this surface can be multivalued and water parcels can have up to two statically stable levels in the reference density profile, of which the shallowest is energetically more accessible. Classifying parcels from the surface to the bottom gives a different reference density profile than classifying in the opposite direction. However, this difference is negligible. We show that the reference state obtained by standard sorting methods is equivalent, though computationally more expensive, to the volume frequency distribution approach. The approach we present can be applied systematically and in a computationally efficient manner to investigate the APE budget of the ocean circulation using models or climatological data.

Mapping power law distributions in digital health social networks: methods, interpretations, and practical implications

BACKGROUND: Social networks are common in digital health. A new stream of research is beginning to investigate the mechanisms of digital health social networks (DHSNs), how they are structured, how they function, and how their growth can be nurtured and managed. DHSNs increase in value when additional content is added, and the structure of networks may resemble the characteristics of power laws. Power laws are contrary to traditional Gaussian averages in that they demonstrate correlated phenomena. OBJECTIVES: The objective of this study is to investigate whether the distribution frequency in four DHSNs can be characterized as following a power law. A second objective is to describe the method used to determine the comparison. METHODS: Data from four DHSNs—Alcohol Help Center (AHC), Depression Center (DC), Panic Center (PC), and Stop Smoking Center (SSC)—were compared to power law distributions. To assist future researchers and managers, the 5-step methodology used to analyze and compare datasets is described. RESULTS: All four DHSNs were found to have right-skewed distributions, indicating the data were not normally distributed. When power trend lines were added to each frequency distribution, R(2) values indicated that, to a very high degree, the variance in post frequencies can be explained by actor rank (AHC .962, DC .975, PC .969, SSC .95). Spearman correlations provided further indication of the strength and statistical significance of the relationship (AHC .987. DC .967, PC .983, SSC .993, P<.001). CONCLUSIONS: This is the first study to investigate power distributions across multiple DHSNs, each addressing a unique condition. Results indicate that despite vast differences in theme, content, and length of existence, DHSNs follow properties of power laws. The structure of DHSNs is important as it gives insight to researchers and managers into the nature and mechanisms of network functionality. The 5-step process undertaken to compare actor contribution patterns can be replicated in networks that are managed by other organizations, and we conjecture that patterns observed in this study could be found in other DHSNs. Future research should analyze network growth over time and examine the characteristics and survival rates of superusers.

Improving the estimation of probability of bidder participation in procurement auctions

Anticipating the number and identity of bidders has significant influence in many theoretical results of the auction itself and bidders' bidding behaviour. This is because when a bidder knows in advance which specific bidders are likely competitors, this knowledge gives a company a head start when setting the bid price. However, despite these competitive implications, most previous studies have focused almost entirely on forecasting the number of bidders and only a few authors have dealt with the identity dimension qualitatively. Using a case study with immediate real-life applications, this paper develops a method for estimating every potential bidder's probability of participating in a future auction as a function of the tender economic size removing the bias caused by the contract size opportunities distribution. This way, a bidder or auctioner will be able to estimate the likelihood of a specific group of key, previously identified bidders in a future tender.

Changes of a mutualistic network over time: reanalysis over a 10-year period

We analyzed the structure of a multispecific network or interacting ants and plants bearing extrafloral nectaries recorded in 1990 and again in 2000 in La Mancha, Veracruz, Mexico. We assessed the replicability of the number of interactions found among species and also whether there had been changes in the network structure associated with appearance of new ant and plant species during. that 10-year period. Our results show that the nested topology of the network was similar between sampling dates, group dissimilarity increased, mean number of interactions for ant species increased, the frequency distribution of standardized degrees reached higher values for plant species, more ant species and fewer plant species constituted the core of the more recent network, and the presence of new ant and plant species increased while their contribution to nestedness remained the same. Generalist species (i.e., those with the most links or interactions) appeared to maintain the stability of the network because the new species incorporated into the communities were linked to this core of generalists. Camponotus planatus was the most extreme generalist ant species (the one with the most links) in both networks, followed by four other ant species; but other species changed either their position along the continuum of generalists relative to specialists or their presence or absence within the network. Even though new species moved into the area during the decade between the surveys, the overall network structure remained unmodified.

A WAVELET-BASED SPEAKER VERIFICATION ALGORITHM

This paper presents a study on wavelets and their characteristics for the specific purpose of serving as a feature extraction tool for speaker verification (SV), considering a Radial Basis Function (RBF) classifier, which is a particular type of Artificial Neural Network (ANN). Examining characteristics such as support-size, frequency and phase responses, amongst others, we show how Discrete Wavelet Transforms (DWTs), particularly the ones which derive from Finite Impulse Response (FIR) filters, can be used to extract important features from a speech signal which are useful for SV. Lastly, an SV algorithm based on the concepts presented is described.

Características de personalidade e preferências de aprendizagens: um estudo exploratório

O presente trabalho descreve um estudo exploratório de características de personalidade e preferências de aprendizagem em estudantes universitários de quatro cursos da área da Saúde: Medicina, Odontologia, Enfermagem e Nutrição. Para este estudo utilizou-se como fonte de dados dois instrumentos de medida, as Escalas de personalidade de Comrey e o Inventário de Pre2erências de Aprendizagem. O tratamento dos dados foi feito através das estatísticas distribuição de frequência, correlação e análise da regressão. Os resultados do tratamento estatístico não nos possibilitou. alcançar nenhuma conclusão objetiva das relações entre as variáveis de personalidade e preferências de aprendizagem, no entanto, forneceu-nos dados para posteriores estudos.

Estudo exploratório das dificuldades do desenvolvimento de pesquisas científicas financiadas com recursos não reembolsáveis na modalidade convênio, com foco na FINEP

O Objetivo desta pesquisa é conhecer, a partir da percepção de pesquisadores e de analistas da Financiadora de Estudos e Projetos (Finep), os principais entraves que impactam o desenvolvimento de projetos de pesquisas científicas e tecnológicas financiados por recursos públicos não reembolsáveis no âmbito de convênios, com ênfase naqueles contratados junto a esta Financiadora. Este trabalho tem relevância a partir da constatação de que os recursos públicos para pesquisa e desenvolvimento vêm sofrendo redução de volume. O Fundo Nacional de Desenvolvimento Científico e Tecnológico (FNDCT), maior financiador público do país para Ciência, Tecnologia e Inovação, há alguns anos tem tido seu orçamento contingenciado e recentemente perdeu 40% do seu orçamento anual por conta da transferência de destinação dos recursos do Fundo Setorial de Petróleo e Gás Natural (CT-Petro). Neste contexto, a oferta de recursos públicos para pesquisas científicas e tecnológicas das universidades e outros centros de pesquisa ficou mais escassa. Esta circunstância exige que as instituições de pesquisa, por um lado elaborem projetos mais consistentes e bem estruturados, de forma a aumentar as chances de conquistar verbas junto às financiadoras públicas e, por outro lado, apliquem os recursos com eficiência para potencializar os resultados das pesquisas. A Finep, como secretaria executiva do FNDCT, tem papel destacado no apoio a projetos de pesquisa no país. Neste sentido, a proposição de um estudo para conhecer as dificuldades do desenvolvimento de pesquisas em projetos com a Finep assume destaque. A partir da discussão do tema, podem surgir novos caminhos e alternativas para melhoria da gestão dos projetos de pesquisa e com isso um melhor aproveitamento dos recursos em prol da Ciência.

Prestação de contas de convênios com recursos do FNDCT na FINEP: proposta de orientações aos convenentes

O objetivo desta pesquisa é fornecer informações que propiciem ao gestor de convênios, condição necessária para apresentar uma prestação de contas com maior probabilidade de aceitação por parte da FINEP. Foram pesquisadas as causas dos erros mais frequentes detectados na execução financeira dos projetos que impedem a aprovação da prestação de contas no momento da análise. A pesquisa foi realizada em duas etapas: pesquisa documental e tratamento dos dados. A primeira etapa foi qualitativa constando de coleta de dados e análise documental. O período analisado foi de 01/01/2013 a 30/11/2013, por serem as mais recentes, abrangendo convênios assinados entre 2001 e 2012. Nesta pesquisa foram considerados todos os convênios analisados no período acima referido, apoiados com recursos FNDCT para desenvolvimento de estudos e pesquisas, analisados pela FINEP, e com ao menos uma impropriedade. A pesquisa documental foi realizada no Departamento de Prestação de Contas de Convênio, Termos e Acordos de Cooperação - DPC1, responsável pelo acompanhamento da execução financeira dos convênios na FINEP. Cabe informar que foram analisados 2.476 convênios ao todo no ano de 2013, sendo 1.248 aprovados e 1.228 com alguma impropriedade. A segunda etapa da pesquisa foi quantitativa, e a técnica por saturação, utilizando estatística descritiva com análise exploratória dos dados. O tratamento dos dados foi realizado a partir da distribuição de frequência observada. Como resultado da pesquisa, observa-se que as dez impropriedades mais recorrentes correspondem a 90% de todas as impropriedades do período analisado. Diante disto, cabe a proposta de orientação ao convenente, através de um FAQ no site da FINEP, abordando assuntos afetos a convênios assinados com recursos FNDCT, de fácil entendimento e acesso.

Caracterização de compósitos Nb-20%cu obtidos por moagem de alta energia e sinterizados por fase líquida

In this work, was studied the formation of a composite of the refractory metal niobium with copper, through the process of high-energy milling and liquid phase sintering. The HEM can be used to synthesize composite powders with high homogeneity and fine size particle distribution. It may also produce the solid solubility in immiscible systems such as Nb-Cu, or extend the solubility of systems with limited solubility. Therefore, in the immiscible system Cu-Nb, the high-energy milling was successfully used to obtain the composite powder particles. Initially, the formation of composite particles during the HEM and the effect of preparation technique on the microstructure of the material was evaluated. Four loads of Nb and Cu powders containing 20%wt Cu were synthesized by MAE in a planetary type ball mill under different periods of grinding. The influence of grinding time on the metal particles is evaluated during the process by the withdrawal of samples at intermediate times of milling. After compaction under different forces, the samples were sintered in a vacuum furnace. The liquid phase sintering of these samples prepared by HEM produced a homogeneous and fine grained. The composite particles forming the sintered samples are the addition of a hard phase (Nb) with a high melting point, and a ductile phase (Cu) with low melting point and high thermal and electrical conductivities. Based on these properties, the Nb-Cu system is a potential material for many applications, such as electrical contacts, welding electrodes, coils for generating high magnetic fields, heat sinks and microwave absorbers, which are coupled to electronic devices. The characterization techniques used in this study, were laser granulometry, used to evaluate the homogeneity and particle size, and the X-ray diffraction, in the phase identification and to analyze the crystalline structure of the powders during milling. The morphology and dispersion of the phases in the composite powder particles, as well the microstructures of the sintered samples, were observed by scanning electron microscopy (SEM). Subsequently, the sintered samples are evaluated for density and densification. And finally, they were characterized by techniques of measuring the electrical conductivity and microhardness, whose properties are analyzed as a function of the parameters for obtaining the composite

A rede de marcação e recaptura: o caso de borboletas do gênero heliconius

(The Mark and Recapture Network: a Heliconius case study). The current pace of habitat destruction, especially in tropical landscapes, has increased the need for understanding minimum patch requirements and patch distance as tools for conserving species in forest remnants. Mark recapture and tagging studies have been instrumental in providing parameters for functional models. Because of their popularity, ease of manipulation and well known biology, butterflies have become model in studies of spatial structure. Yet, most studies on butterflies movement have focused on temperate species that live in open habitats, in which forest patches are barrier to movement. This study aimed to view and review data from mark-recapture as a network in two species of butterfly (Heliconius erato and Heliconius melpomene). A work of marking and recapture of the species was carried out in an Atlantic forest reserve located about 20km from the city of Natal (RN). Mark recapture studies were conducted in 3 weekly visits during January-February and July-August in 2007 and 2008. Captures were more common in two sections of the dirt road, with minimal collection in the forest trail. The spatial spread of captures was similar in the two species. Yet, distances between recaptures seem to be greater for Heliconius erato than for Heliconius melpomene. In addition, the erato network is more disconnected, suggesting that this specie has shorter traveling patches. Moving on to the network, both species have similar number of links (N) and unweighed vertices (L). However, melpomene has a weighed network 50% more connections than erato. These network metrics suggest that erato has more compartmentalized network and restricted movement than melpomene. Thus, erato has a larger number of disconnected components, nC, in the network, and a smaller network diameter. The frequency distribution of network connectivity for both species was better explained by a Power-law than by a random, Poissom distribution, showing that the Power-law provides a better fit than the Poisson for both species. Moreover, the Powerlaw erato is much better adjusted than in melpomene, which should be linked to the small movements that erato makes in the network

Nanotechnological delivery systems for the oral administration of active molecules: Polymeric microparticles and microemulsions applied to anti-inflammatory and anti-infectious drugs

This thesis was devoted to the development of innovative oral delivery systems for two different molecules. In the first part, microparticles (MPs) based on xylan and Eudragit® S- 100 were produced and used to encapsulate 5-aminosalicylic acid for colon delivery. Xylan was extracted from corn cobs and characterized in terms of its physicochemical, rheological and toxicological properties. The polymeric MPs were prepared by interfacial cross-linking polymerization and spray-drying and characterized for their morphology, mean size and distribution, thermal stability, crystallinity, entrapment efficiency and in vitro drug release. MPs with suitable physical characteristics and satisfactory yields were prepared by both methods, although the spray-dried systems showed higher thermal stability. In general, spraydried MPs would be preferable systems due to their thermal stability and absence of toxic agents used in their preparation. However, drug loading and release need to be optimized. In the second part of this thesis, oil-in-water microemulsions (O/W MEs) based on mediumchain triglycerides were formulated as drug carriers and solubility enhancers for amphotericin B (AmB). Phase diagrams were constructed using surfactant blends with hydrophiliclipophilic balance values between 9.7 and 14.4. The drug-free and drug-loaded MEs presented spherical non-aggregated droplets around 80 and 120 nm, respectively, and a low polydispersity index. The incorporation of AmB was high and depended on the volume fraction of the disperse phase. These MEs did not reduce the viability of J774.A1 macrophage-like cells for concentrations up to 25 μg/mL of AmB. Therefore, O/W MEs based on propylene glycol esters of caprylic acid may be considered as suitable delivery systems for AmB

Estudo de pré-formulação para dose fixa combinada dos tuberculostáticos rifampicina, isoniazida, pirazinamida e etambutol (4 em 1)

According to the global framework regarding new cases of tuberculosis, Brazil appears at the 18th place. Thus, the Ministry of Health has defined this disease as a priority in the governmental policies. As a consequence, studies concerning treatment and prevention have increased. Fixed-dose combination formulations (FDC) are recognized as beneficial and are recommended by WHO, but they present instability and loss on rifampicin bioavailability. The main purpose of this work was to carry out a pre-formulation study with the schedule 1 tuberculosis treatment drugs: rifampicin, isoniazid, pyrazinamide and ethambutol and pharmaceutical excipients (lactose, cellulose, magnesium stearate and talc), in order to develop an FDC product (150 mg of rifampicin + 75 mg of isoniazid + 400 mg of pyrazinamide + 250 mg of ethambutol). The studies consisted of the determination of particle size and distribution (Ferret s diameter) and shape through optical microscopy, as well as rheological and technological properties (bulk and tapped densities, Hausner Factor, Carr s Index, repose angle and flux rate) and interactions among drugs and drug excipient through thermal analysis (DSC, DTA, TG and your derivate). The results showed that, except isoniazid, the other drugs presented poor rheological properties, determined by the physical characteristics of the particles: small size and rod like particles shape for rifampicin; rectangular shape for pyrazinamide and ethambutol, beyond its low density. The 4 drug mixture also not presented flowability, particularly that one containing drug quantity indicated for the formulation of FDC products. In this mixture, isoniazid, that has the best flowability, was added in a lower concentration. The addition of microcrystalline cellulose, magnesium stearate and talc to the drug mixtures improved flowability properties. In DSC analysis probable interactions among drugs were found, supporting the hypothesis of ethambutol and pyrazinamide catalysis of the rifampicin-isoniazid reaction resulting in 3- formylrifamycin isonicotinyl hydrazone (HYD) as a degradation product. In the mixtures containing lactose Supertab® DSC curves evidenced incompatibility among drugs and excipient. In the DSC curves of mixtures containing cellulose MC101®, magnesium stearate and talc, no alterations were observed comparing to the drug profiles. The TG/DTG of the binary and ternary mixtures curves showed different thermogravimetrics profiles relating that observed to the drug isolated, with the thermal decomposition early supporting the evidences of incompatibilities showed in the DSC and DTA curves

Distribuição de probabilidade de ocorrência de Orthezia praelonga Douglas (Hemiptera: Sternorrhyncha: Ortheziidae) na cultura de citros

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)