An efficient total variation algorithm for super-resolution in fetal brain MRI with adaptive regularization.

Although fetal anatomy can be adequately viewed in new multi-slice MR images, many critical limitations remain for quantitative data analysis. To this end, several research groups have recently developed advanced image processing methods, often denoted by super-resolution (SR) techniques, to reconstruct from a set of clinical low-resolution (LR) images, a high-resolution (HR) motion-free volume. It is usually modeled as an inverse problem where the regularization term plays a central role in the reconstruction quality. Literature has been quite attracted by Total Variation energies because of their ability in edge preserving but only standard explicit steepest gradient techniques have been applied for optimization. In a preliminary work, it has been shown that novel fast convex optimization techniques could be successfully applied to design an efficient Total Variation optimization algorithm for the super-resolution problem. In this work, two major contributions are presented. Firstly, we will briefly review the Bayesian and Variational dual formulations of current state-of-the-art methods dedicated to fetal MRI reconstruction. Secondly, we present an extensive quantitative evaluation of our SR algorithm previously introduced on both simulated fetal and real clinical data (with both normal and pathological subjects). Specifically, we study the robustness of regularization terms in front of residual registration errors and we also present a novel strategy for automatically select the weight of the regularization as regards the data fidelity term. Our results show that our TV implementation is highly robust in front of motion artifacts and that it offers the best trade-off between speed and accuracy for fetal MRI recovery as in comparison with state-of-the art methods.

Activity of daptomycin- and vancomycin-loaded poly-epsilon-caprolactone microparticles against mature staphylococcal biofilms.

The aim of the present study was to develop novel daptomycin-loaded poly-epsilon-caprolactone (PCL) microparticles with enhanced antibiofilm activity against mature biofilms of clinically relevant bacteria, methicillin-resistant Staphylococcus aureus (MRSA) and polysaccharide intercellular adhesin-positive Staphylococcus epidermidis. Daptomycin was encapsulated into PCL microparticles by a double emulsion-solvent evaporation method. For comparison purposes, formulations containing vancomycin were also prepared. Particle morphology, size distribution, encapsulation efficiency, surface charge, thermal behavior, and in vitro release were assessed. All formulations exhibited a spherical morphology, micrometer size, and negative surface charge. From a very early time stage, the released concentrations of daptomycin and vancomycin were higher than the minimal inhibitory concentration and continued so up to 72 hours. Daptomycin presented a sustained release profile with increasing concentrations of the drug being released up to 72 hours, whereas the release of vancomycin stabilized at 24 hours. The antibacterial activity of the microparticles was assessed by isothermal microcalorimetry against planktonic and sessile MRSA and S. epidermidis. Regarding planktonic bacteria, daptomycin-loaded PCL microparticles presented the highest antibacterial activity against both strains. Isothermal microcalorimetry also revealed that lower concentrations of daptomycin-loaded microparticles were required to completely inhibit the recovery of mature MRSA and S. epidermidis biofilms. Further characterization of the effect of daptomycin-loaded PCL microparticles on mature biofilms was performed by fluorescence in situ hybridization. Fluorescence in situ hybridization showed an important reduction in MRSA biofilm, whereas S. epidermidis biofilms, although inhibited, were not eradicated. In addition, an important attachment of the microparticles to MRSA and S. epidermidis biofilms was observed. Finally, all formulations proved to be biocompatible with both ISO compliant L929 fibroblasts and human MG63 osteoblast-like cells.

Unidirectional quantum walks: Evolution and exit times

In this paper we focus our attention on a particle that follows a unidirectional quantum walk, an alternative version of the currently widespread discrete-time quantum walk on a line. Here the walker at each time step can either remain in place or move in a fixed direction, e.g., rightward or upward. While both formulations are essentially equivalent, the present approach leads us to consider discrete Fourier transforms, which eventually results in obtaining explicit expressions for the wave functions in terms of finite sums and allows the use of efficient algorithms based on the fast Fourier transform. The wave functions here obtained govern the probability of finding the particle at any given location but determine as well the exit-time probability of the walker from a fixed interval, which is also analyzed.

New cationic nanovesicular systems containing lysine-based surfactants for topical administration: Toxicity assessment using representative skin cell lines

Many strategies for treating diseases require the delivery of drugs into the cell cytoplasm following internalization within endosomal vesicles. Thus, compounds triggered by low pH to disrupt membranes and release endosomal contents into the cytosol are of particular interest. Cationic nanovesicles have attracted considerable interest as effective carriers to improve the delivery of biologically active molecules into and through the skin. In this study, lipid-based nanovesicles containing three different cationic lysine-based surfactants were designed for topical administration. We used representative skin cell lines and in vitro assays to assess whether the cationic compounds modulate the toxic responses of these nanocarriers. The nanovesicles were characterized in both water and cell culture medium. In general, significant agglomeration occurred after 24 h incubation under cell culture conditions. We found different cytotoxic responses among the formulations, which depended on the surfactant,cell line (3T3, HaCaT, and THP-1) and endpoint assayed (MTT, NRU, and LDH). Moreover, no potential phototoxicity was detected in fibroblast or keratinocyte cells, whereas only a slight inflammatory response was induced, as detected by IL-1a and IL-8 production in HaCaT and THP-1 cell lines, respectively. A key finding of our research was that the cationic charge position and the alkyl chain length of the surfactants determine the nanovesicles resulting toxicity. The charge on the a-amino group of lysine increased the depletion of cell metabolic activity, as determined by the MTT assay, while a higher hydrophobicity tends to enhance the toxic responses of the nanovesicles. The insights provided here using different cell lines and assays offer a comprehensive toxicological evaluation of this group of new nanomaterials.

Nanocarriers for DNA Vaccines: Co-Delivery of TLR-9 and NLR-2 Ligands Leads to Synergistic Enhancement of Proinflammatory Cytokine Release

Adjuvants enhance immunogenicity of vaccines through either targeted antigen delivery or stimulation of immune receptors. Three cationic nanoparticle formulations were evaluated for their potential as carriers for a DNA vaccine, and muramyl dipeptide (MDP) as immunostimulatory agent, to induce and increase immunogenicity of Mycobacterium tuberculosis antigen encoding plasmid DNA (pDNA). The formulations included (1) trimethyl chitosan (TMC) nanoparticles, (2) a squalene-in-water nanoemulsion, and (3) a mineral oil-in-water nanoemulsion. The adjuvant effect of the pDNA-nanocomplexes was evaluated by serum antibody analysis in immunized mice. All three carriers display a strong adjuvant effect, however, only TMC nanoparticles were capable to bias immune responses towards Th1. pDNA naturally contains immunostimulatory unmethylated CpG motifs that are recognized by Toll-like receptor 9 (TLR-9). In mechanistic in vitro studies, activation of TLR-9 and the ability to enhance immunogenicity by simultaneously targeting TLR-9 and NOD-like receptor 2 (NLR-2) was determined by proinflammatory cytokine release in RAW264.7 macrophages. pDNA in combination with MDP was shown to significantly increase proinflammatory cytokine release in a synergistic manner, dependent on NLR-2 activation. In summary, novel pDNA-Ag85A loaded nanoparticle formulations, which induce antigen specific immune responses in mice were developed, taking advantage of the synergistic combinations of TLR and NLR agonists to increase the adjuvanticity of the carriers used.

Long-term persistence of immunity induced by OVA-coupled gas-filled microbubble vaccination partially protects mice against infection by OVA-expressing Listeria.

Vaccination aims at generating memory immune responses able to protect individuals against pathogenic challenges over long periods of time. Subunit vaccine formulations based on safe, but poorly immunogenic, antigenic entities must be combined with adjuvant molecules to make them efficient against infections. We have previously shown that gas-filled microbubbles (MB) are potent antigen-delivery systems. This study compares the ability of various ovalbumin-associated MB (OVA-MB) formulations to induce antigen-specific memory immune responses and evaluates long-term protection toward bacterial infections. When initially testing dendritic cells reactivity to MB constituents, palmitic acid exhibited the highest degree of activation. Subcutaneous immunization of naïve wild-type mice with the OVA-MB formulation comprising the highest palmitic acid content and devoid of PEG2000 was found to trigger the more pronounced Th1-type response, as reflected by robust IFN-γ and IL-2 production. Both T cell and antibody responses persisted for at least 6 months after immunization. At that time, systemic infection with OVA-expressing Listeria monocytgenes was performed. Partial protection of vaccinated mice was demonstrated by reduction of the bacterial load in both the spleen and liver. We conclude that antigen-bound MB exhibit promising properties as a vaccine candidate ensuring prolonged maintenance of protective immunity.

Immunogenicity of dimorphic and C-terminal fragments of Plasmodium falciparum MSP2 formulated with different adjuvants in mice.

BACKGROUND: Plasmodium falciparum MSP2 is a blood stage protein that is associated with protection against malaria. It was shown that the MSP2 dimorphic (D) and constant (C) regions were well recognized by immune human antibodies, and were characterized by major conserved epitopes in different endemic areas and age groups. These Abs recognized merozoite-derived proteins in WB and IFA. Here, the goal was to determine in mice the immunogenicity of the two allelic MSP2 D and C domains formulated with different adjuvants, for their possible use in future clinical studies. METHOD: Female A/J, C3H, and ICR mice were immunized subcutaneously 3 times at 3-week interval with a mixture of allelic and conserved MSP2 long synthetic peptides formulated with different adjuvants. One week after the third injection, sera from each group were obtained and stored at -20°C for subsequent testing. RESULTS: Both domains of the two MSP2 families are immunogenic and the fine specificity and intensity of the Ab responses are dependent on mouse strains and adjuvants. The major epitopes were restricted to the 20-mer peptide sequences comprising the last 8aa of D and first 12aa of C of the two allelic families and the first 20aa of the C region, this for most strains and adjuvants. Strong immune responses were associated with GLA-SE adjuvant and its combination with other TLR agonists (CpG or GDQ) compared to alhydrogel and Montanide. Further, the elicited Abs were also capable of recognizing Plasmodium-derived MSP2 and inhibiting parasite growth in ADCI. CONCLUSION: The data provide a valuable opportunity to evaluate in mice different adjuvant and antigen formulations of a candidate vaccine containing both MSP2 D and C fragments. The formulations with GLA-SE seem to be a promising option to be compared with the alhydrogel one in human clinical trials.

La Incidencia de las nuevas tecnologías en los hábitos formativos de los estudiantes de magisterio = The Impact of new technologies in the learning habits of teacher students

Este trabajo persigue dos objetivos: el primero es analizar el uso de las TIC en un grupo de estudiantes de segundo curso de Magisterio de la Universidad de Girona; el segundo es analizar los documentos normativos legales que establecen el currículum de educación primaria en Cataluña para observar qué tipo de papel juegan las TIC en las nuevas programaciones educativas. La primera parte se ha llevado a cabo mediante una encuesta, cuyos resultados permiten observar tres aspectos distintos: el primero, que una parte considerable del grupo considera las TIC más como un complemento para el aprendizaje que como una forma de aprendizaje; el segundo, que a pesar de hacer un uso considerable de las TIC, el conocimiento que tienen de ellas es muy básico y utilizan aplicaciones muy genéricas; y el tercero es que una parte de sus propuestas didácticas para el uso de las TIC son propuestas tradicionales simplemente adaptadas a un nuevo instrumento, sin buscar realmente la innovación que puede suponer la incorporación de las TIC. En la segunda parte del artículo, a partir del análisis e interpretación de los documentos legales que establecen el currículum de Educación Primaria, se observa que en un mismo documento conviven aserciones sobre las TIC como complemento al aprendizaje de contenidos con otras formulaciones que consideran las TIC como constructoras de conocimiento. A partir del perfil de los estudiantes y del estado de los documentos legales, al final del artículo se hacen propuestas para formar al futuro maestro teniendo en cuenta las TIC como herramientas básicas de conocimiento

Alcatrão ou creosoto de eucalipto na produção de adesivos fenólicos para colagem de madeira

This study has shown that Eucalyptus tar and creosote can be used in phenolic adhesive formulations (resols) for wood products bonding. Some adhesives were prepared substituting 0; 17.7; 35.0 and 67.0% of the phenol by anhydrous tar and 0; 15.0 e 28.5% by creosote. In gluing Brazilian pine veneers, eucalypt tar and creosote based adhesives required longer pressing times for curing than conventional phenol-formaldehyde adhesives. By using 13C NMR, the number of carbons in side chains and hydroxyl, carbonyl, carboxyl and methoxyl groups related to 100 aromatic rings could be estimated in tar and creosote. In creosote, after reaction with excess formaldehyde in alkaline medium, only 0,28 hydroxymethyl groups was detected per phenolic ring. This low amount of hydroxymethylation explains the lack of reactivity in curing observed when creosote was introduced in a standard adhesive formulation.

Controle de autenticidade de óleos de copaíba comerciais por cromatografia gasosa de alta resolução

Copaiba oil is a resin extracted from the trunk of trees of Copaifera species which grow in Brazil where it is widely used in popular medicine as an anti-inflammatory, antiseptic anti-bactericidal, diuretic, dermatological, expectorant, and anti-infective. The comparative study of the composition of commercial copaiba oils was carried out by high resolution gas chromatography (HRGC) and high resolution gas chromatography-mass spectrometry (HRGC-MS) analysis. The commercial oils were compared with authentic oils, collected from the southeast and northern regions of Brazil. Sixteen commercial oils were analysed and two of them revealed adulterations with fatty acids. Using the chromatographic profile of authentic copaiba species oils, it is possible to analyse commercial oils and determine the authenticity of these materials.

Spectrophotometric determination of cefaclor in pharmaceutical preparations

A simple spectrophotometric method is proposed for the determination of cefaclor. The method involves alkaline hydrolysis of the drug in ammonia buffer solution at pH 10 to yield diketopiperazine-2,5-dione derivative and subsequent measurement at 340 nm. Beer's law is obeyed in the concentration range 1.8 - 55 mg/mL. The proposed method was successfully applied to the determination of cefaclor in pharmaceutical formulations.

Drug loading of mesoporous silicon particles

Porous silicon (PSi) is a promising material to be utilized in drug delivery formulations. The release rate of the drug compound can be controlled by changing the pore properties and surface chemistry of PSi. The loading of a poorly soluble drug into mesoporous silicon particles enhances its dissolution in the body. The drug loading is based on adsorption. The attainable maximum loaded amount depends on the properties of the drug compound and the PSi material, and on the process conditions. The loading solvent also essentially affects the adsorption process. The loading of indomethacin into PSi particles with varying surface modification was studied. Solvent mixtures were applied in the loading, and the loaded samples were analyzed with thermal analysis methods. The best degree of loading was obtained using a mixture of dichloromethane and methanol. The drug loads varied from 7.7 w-% to 26.8 w-%. A disturbing factor in the loading experiments was the tendency of indomethacin to form solvates with the solvents applied. In addition, the physical form and stability of indomethacin loaded in PSi and silica particles were studied using Raman spectroscopy. In the case of silica, the presence of crystalline drug as well as the polymorph form can be detected, but the method proved to be not applicable for PSi particles.

Determinação espectrofotométrica por injeção em fluxo de vitamina B6 (piridoxina) em formulações farmacêuticas

A flow injection (FI) spectrophotometric procedure is proposed for the determination of vitamin B6 (pyridoxine hydrochloride) in pharmaceutical preparations. Powdered samples containing from 2.5 to 4.5 mg, were previously dissolved in 0.1 mol L-1 phosphate buffer solution (pH 7.0) and a volume of 500 muL was injected directly into a carrier stream consisting of this same phosphate buffer solution, flowing at 4.4 mL min-1. The stable blue indophenol dye produced in the oxidation of pyridoxine hydrochloride by potassium hexacyanoferrate(III) and N,N-diethyl-p-phenylenediamine solution was directly measured at 684 nm. Vitamin B6 was determined in five pharmaceutical preparations in the 0.5 to 6.0 mg L-1 concentration range (calibration graph: A= -0.00499 + 0.11963 C; r= 0.9991, where A is the absorbance and C is the vitamin B6 concentration in mg L-1), with a detection limit of 0.02 mg L-1 (3 Sblank/slope). The recovery of this vitamin from three samples ranged from 97.5 to 103.3 %. The analytical frequency was 62 h-1 and r.s.d. were less than 2% for solutions containing 1.0 and 3.0 mg L-1 vitamin B6 (n= 10). The results obtained for the determination of vitamin B6 in commercial formulations were in good agreement with those obtained by a spectrophotometric procedure (r=0.9997) and also with the label values (r= 0.9998).

Estudo da influência do diluente reativo PGE na cinética de cura de resina epóxi utilizada em compósitos estruturais

Phenil glycidyl ether (PGE), a monofunctional diluent, has been used in epoxy resins formulations in order to increase the toughness of the epoxy molded composite. In a systematic study concerning its influence in the cure kinetics of the epoxy resin, it was used in concentrations of 2,5; 5,0; 10 and 20% in relation to a diglycidyl ether bisphenol-A (DGEBA)/diamino diphenil-sulfone (DDS) base matrix. Dynamic and isothermal scanning analysis were carried out using a differential scanning calorimety (DSC) equipment. For all the concentrations of PGE, a n order kinetics was observed, with n varing between 0,35 -- 0,91 as a function of the increase in the PGE concentration.

Determinação espectrofotométrica de vitamina B2 (riboflavina) em formulações farmacêuticas empregando sistema de análises por injeção em fluxo

A flow injection spectrophotometric procedure exploiting merging zones is proposed for determining vitamin B2 (riboflavin) in pharmaceutical preparations. The determination is based on the red-colored complex formation between vitamin B2 and silver(I) which was measured at 520 nm. Vitamin B2 was determined in four pharmaceutical preparations in the 1.0 to 50.0 mg L-1 concentration range, with a detection limit of 0.5 mg L-1. The recovery from three samples ranged from 98.0 to 104.0 %. The analytical frequency was 42 h-1 and r.s.d. were lower than 1% for solutions containing 10.0, 30.0 and 50.0 mg L-1 vitamin B2 (n= 10). The results obtained in commercial formulations using the FIA procedure were in good agreement with those obtained by using a conventional fluorimetric procedure (r=0.9998) and also with the label values (r= 0.9997).