332 research outputs found

    Dual-modality, fluorescent, PLGA encapsulated bismuth nanoparticles for molecular and cellular fluorescence imaging and computed tomography

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    Reports of molecular and cellular imaging using computed tomography (CT) are rapidly increasing. Many of these reports use gold nanoparticles. Bismuth has similar CT contrast properties to gold while being approximately 1000-fold less expensive. Herein we report the design, fabrication, characterization, and CT and fluorescence imaging properties of a novel, dual modality, fluorescent, polymer encapsulated bismuth nanoparticle construct for computed tomography and fluorescence imaging. We also report on cellular internalization and preliminary in vitro and in vivo toxicity effects of these constructs. 40 nm bismuth(0) nanocrystals were synthesized and encapsulated within 120 nm Poly(DL-lactic-co-glycolic acid) (PLGA) nanoparticles by oil-in-water emulsion methodologies. Coumarin-6 was co-encapsulated to impart fluorescence. High encapsulation efficiency was achieved ∼ 70% bismuth w/w. Particles were shown to internalize within cells following incubation in culture. Bismuth nanocrystals and PLGA encapsulated bismuth nanoparticles exhibited >90% and >70% degradation, respectively, within 24 hours in acidic, lysosomal environment mimicking media and both remained nearly 100% stable in cytosolic/extracellular fluid mimicking media. μCT and clinical CT imaging was performed at multiple X-ray tube voltages to measure concentration dependent attenuation rates as well as to establish the ability to detect the nanoparticles in an ex vivo biological sample. Dual fluorescence and CT imaging is demonstrated as well. In vivo toxicity studies in rats revealed neither clinically apparent side effects nor major alterations in serum chemistry and hematology parameters. Calculations on minimal detection requirements for in vivo targeted imaging using these nanoparticles are presented. Indeed, our results indicate that these nanoparticles may serve as a platform for sensitive and specific targeted molecular CT and fluorescence imaging

    Evidence for the Sialylation of PilA, the PI-2a Pilus-Associated Adhesin of Streptococcus agalactiae Strain NEM316.

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    International audienceStreptococcus agalactiae (or Group B Streptococcus, GBS) is a commensal bacterium present in the intestinal and urinary tracts of approximately 30% of humans. We and others previously showed that the PI-2a pilus polymers, made of the backbone pilin PilB, the tip adhesin PilA and the cell wall anchor protein PilC, promote adhesion to host epithelia and biofilm formation. Affinity-purified PI-2a pili from GBS strain NEM316 were recognized by N-acetylneuraminic acid (NeuNAc, also known as sialic acid) specific lectins such as Elderberry Bark Lectin (EBL) suggesting that pili are sialylated. Glycan profiling with twenty different lectins combined with monosaccharide composition by HPLC suggested that affinity-purified PI-2a pili are modified by N-glycosylation and decorated with sialic acid attached to terminal galactose. Analysis of various relevant mutants in the PI-2a pilus operon by flow-cytometry and electron microscopy analyses pointed to PilA as the pilus subunit modified by glycosylation. Double labeling using PilB antibody and EBL lectin, which specifically recognizes N-acetylneuraminic acid attached to galactose in α-2, 6, revealed a characteristic binding of EBL at the tip of the pilus structures, highly reminiscent of PilA localization. Expression of a secreted form of PilA using an inducible promoter showed that this recombinant PilA binds specifically to EBL lectin when produced in the native GBS context. In silico search for potentially glycosylated asparagine residues in PilA sequence pointed to N427 and N597, which appear conserved and exposed in the close homolog RrgA from S. pneumoniae, as likely candidates. Conversion of these two asparagyl residues to glutamyl resulted in a higher instability of PilA. Our results provide the first evidence that the tip PilA adhesin can be glycosylated, and suggest that this modification is critical for PilA stability and may potentially influence interactions with the host

    Liver fibrosis staging using supersonic shear imaging : a clinical study on 142 patients

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    International audienceI. Background, Motivation and ObjectiveFibrosis staging can be assessed by a rough estimation of the liver stiffness averaged along an ultrasonic A-line. Providing a complete 2D map of liver stiffness would thus be of great clinical interest for the diagnosis of hepatic fibrosis and help prevent upcoming cirrhosis. However, such measurement requires both a quantitative value of shear elasticity and a great precision to discriminate between different fibrosis levels. Beyond the scope of non-invasive fibrosis quantification, it is also envisioned that quantitative elasticity imaging of liver will have potential interest for liver cancer diagnosis. In this work, the Supersonic Shear Imaging technique (SSI) is proposed to map the in vivo viscoelastic parameters of liver on patients with hepatitis C and derive a mean elasticity of liver tissues. The results are compared to biological tests (Fib4, Apri, Forns) and Fibroscan® measurements. II. Statement of Contribution / MethodsThe SSI technique is based on the radiation force induced by a conventional ultrasonic probe to generate a planar shear wave deep into tissues. The shear wave propagation throughout the medium is caught in real time thanks to an ultrafast ultrasound scanner (up to 5000 frames/s). Using modified sequences and post-processing, this technique is implemented on curved arrays in order to get a larger field of view of liver tissues. A study on 150 HCV patients with different fibrosis stages F has been conducted in order to investigate the accuracy of the technique (F ϵ [0;4]). Quantitative maps of liver elasticity are produced for each volunteer with a linear and a curved array. III. ResultsB-mode images of 120x75 mm² and corresponding elasticity maps are obtained using a 2.5 MHz curved ultrasonic probe with a good reproducibility and accuracy. The shear wave phase velocity dispersion is also calculated. This study shows a good correlation between the values obtained by SSI and the fibrosis levels diagnosed by biological tests (p-index 0.9 for F>3 and Y> 0.8 for F>2). Results are also compared (r2 > 0.92) to the Fibroscan® elasticity measurement by fitting the velocity dispersion curves obtained by SSI at 50 Hz.IV. Discussion and ConclusionsThis real-time elasticity mapping using an ultrasonic curved probe offers better signal to noise ratio than linear arrays and a larger area in the patient's liver (13.3±2.8 cm² estimation area). This gives more confidence on the accuracy of the diagnosis of the fibrosis stage. Furthermore, the elasticity parameters obtained with SSI give access to the shear wave group velocity and the phase velocity. As a consequence, the SSI assessment of liver stiffness could potentially give more information on the viscoelasticity properties of the liver

    Screening Of Alternatives To Decrease Copper Dependency For Plasmopara Viticola Control In Organic Grape Production

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    Downy mildew caused by Plasmopara viticola is a major pest in viticulture worldwide. Organic viticulture is highly dependent of copper-based product to control this disease. Because copper has negative environmental impact, strategies to decrease dependency to copper-based products are needed. In that context, during 2005-2017 period, we have assessed the efficacy of 35 compounds to control downy mildew on-farm. This study present a selection of our results. The screening showed that several formulated products and compounds have an efficacy to control the downy mildew when they are compared with the untreated control, but none at an efficiency similar to copper. When alternatives compounds are associated with a low copper dose, significant additional effect are rarely observed over the whole season

    Computing the smallest fixed point of order-preserving nonexpansive mappings arising in positive stochastic games and static analysis of programs

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    The problem of computing the smallest fixed point of an order-preserving map arises in the study of zero-sum positive stochastic games. It also arises in static analysis of programs by abstract interpretation. In this context, the discount rate may be negative. We characterize the minimality of a fixed point in terms of the nonlinear spectral radius of a certain semidifferential. We apply this characterization to design a policy iteration algorithm, which applies to the case of finite state and action spaces. The algorithm returns a locally minimal fixed point, which turns out to be globally minimal when the discount rate is nonnegative.Comment: 26 pages, 3 figures. We add new results, improvements and two examples of positive stochastic games. Note that an initial version of the paper has appeared in the proceedings of the Eighteenth International Symposium on Mathematical Theory of Networks and Systems (MTNS2008), Blacksburg, Virginia, July 200

    Secondary contact and admixture between independently invading populations of the Western corn rootworm, diabrotica virgifera virgifera in Europe

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    The western corn rootworm, Diabrotica virgifera virgifera (Coleoptera: Chrysomelidae), is one of the most destructive pests of corn in North America and is currently invading Europe. The two major invasive outbreaks of rootworm in Europe have occurred, in North-West Italy and in Central and South-Eastern Europe. These two outbreaks originated from independent introductions from North America. Secondary contact probably occurred in North Italy between these two outbreaks, in 2008. We used 13 microsatellite markers to conduct a population genetics study, to demonstrate that this geographic contact resulted in a zone of admixture in the Italian region of Veneto. We show that i) genetic variation is greater in the contact zone than in the parental outbreaks; ii) several signs of admixture were detected in some Venetian samples, in a Bayesian analysis of the population structure and in an approximate Bayesian computation analysis of historical scenarios and, finally, iii) allelic frequency clines were observed at microsatellite loci. The contact between the invasive outbreaks in North-West Italy and Central and South-Eastern Europe resulted in a zone of admixture, with particular characteristics. The evolutionary implications of the existence of a zone of admixture in Northern Italy and their possible impact on the invasion success of the western corn rootworm are discussed

    The Group of Responsables "Aerodynamics (GoR AD)" - An Overview of Activities and Success Stories

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    The GARTEUR Group of Responsables Aerodynamics (GoR AD) is initiating and organizing basic and applied research in aerodynamics and aerothermodynamics. The activities aim to advance the collaborative aerodynamic research in Europe, combining both numerical and experimental research. This paper gives an overview of past and recent acitivites and some success stories

    Sympatric Speciation: When Is It Possible in Bacteria?

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    This study investigated a potential auditory illusion in duration perception induced by rhythmic temporal contexts. Listeners with or without musical training performed a duration discrimination task for a silent period in a rhythmic auditory sequence. The critical temporal interval was presented either within a perceptual group or between two perceptual groups. We report the just-noticeable difference (difference limen, DL) for temporal intervals and the point of subjective equality (PSE) derived from individual psychometric functions based on performance of a two-alternative forced choice task. In musically untrained individuals, equal temporal intervals were perceived as significantly longer when presented between perceptual groups than within a perceptual group (109.25% versus 102.5% of the standard duration). Only the perceived duration of the between-group interval was significantly longer than its objective duration. Musically trained individuals did not show this effect. However, in both musically trained and untrained individuals, the relative difference limens for discriminating the comparison interval from the standard interval were larger in the between-groups condition than in the within-group condition (7.3% vs. 5.6% of the standard duration). Thus, rhythmic grouping affected sensitivity to duration changes in all listeners, with duration differences being harder to detect at boundaries of rhythm groups than within rhythm groups. Our results show for the first time that temporal Gestalt induces auditory duration illusions in typical listeners, but that musical experts are not susceptible to this effect of rhythmic grouping.Ellison Medical FoundationSwiss National Science Foundation (PA00P1_131448/1
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