823 research outputs found

    Simulation model for self-adaptive applications in pervasive computing

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    A learning model for trustworthiness of context-awareness services

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    Using real-time dependability in adaptive service selection

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    Rectifiability of Optimal Transportation Plans

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    The purpose of this note is to show that the solution to the Kantorovich optimal transportation problem is supported on a Lipschitz manifold, provided the cost is C2C^{2} with non-singular mixed second derivative. We use this result to provide a simple proof that solutions to Monge's optimal transportation problem satisfy a change of variables equation almost everywhere

    Local association of Trypanosoma cruzi chronic infection foci and enteric neuropathic lesions at the tissue micro-domain scale

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    Chagas disease (American trypanosomiasis) is caused by the protozoan parasite Trypanosoma cruzi. Chagas disease has two types, the cardiac form and the digestive form; some patients have symptoms of both. How the parasite causes digestive disease is poorly understood. It is known that damage to the gut’s nervous system is an important factor, but it has been unclear exactly where and when this damage occurs during the course of an infection and also why only a subset of infected people suffer from this outcome. We studied infections in mice and found certain combinations of strains of parasites and mice that exhibited symptoms similar to human digestive Chagas patients, including a problem with peristalsis that localised specifically to the colon. Using parasites that were genetically engineered to emit both bioluminescent and fluorescent light, we tracked infections over time and were able to analyse rare infected cells deep within the muscle tissue of the wall of the colon. We found evidence of damaged neurons in the same location as these infection foci over 6 months after initial infection. Our results show that digestive Chagas disease probably develops as a result of chronic infection and inflammation, which potentially changes approaches to treatment

    In Vivo Analysis of Trypanosoma cruzi Persistence Foci at Single-Cell Resolution

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    Infections with Trypanosoma cruzi are usually lifelong despite generating a strong adaptive immune response. Identifying the sites of parasite persistence is therefore crucial to understanding how T. cruzi avoids immune-mediated destruction. However, this is a major technical challenge, because the parasite burden during chronic infections is extremely low. Here, we describe an integrated approach involving comprehensive tissue processing, ex vivo imaging, and confocal microscopy, which allowed us to visualize infected host cells in murine tissue with exquisite sensitivity. Using bioluminescence-guided tissue sampling, with a detection level of 200 parasites, which we term mega-nests. In contrast, during the acute stage, when the total parasite burden is considerably higher and many cells are infected, nests containing >50 parasites are rarely found. In C3H/HeN mice, but not BALB/c mice, we identified skeletal muscle as a major site of persistence during the chronic stage, with most parasites being found in large mega-nests within the muscle fibers. Finally, we report that parasites are also frequently found in the skin during chronic murine infections, often in multiple infection foci. In addition to being a site of parasite persistence, this anatomical reservoir could play an important role in insect-mediated transmission and have implications for drug development.IMPORTANCETrypanosoma cruzi causes Chagas disease, the most important parasitic infection in Latin America. Major pathologies include severe damage to the heart and digestive tract, although symptoms do not usually appear until decades after infection. Research has been hampered by the complex nature of the disease and technical difficulties in locating the extremely low number of parasites. Here, using highly sensitive imaging technology, we reveal the sites of parasite persistence during chronic-stage infections of experimental mice at single-cell resolution. We show that parasites are frequently located in smooth muscle cells in the circular muscle layer of the colon and that skeletal muscle cells and the skin can also be important reservoirs. This information provides a framework for investigating how the parasite is able to survive as a lifelong infection, despite a vigorous immune response. It also informs drug development strategies by identifying tissue sites that must be accessed to achieve a curative outcome

    Alterations in Team Physical Performance and Possession in Elite Gaelic Football Competition

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    Differences in performance between winning and losing were examined in 1 elite Gaelic football team in 20 games across 2 complete competitive seasons. Possession was codified using Dartfish TeamPro software and distance covered; walking, jogging, running, and running at high and maximum speeds, was evaluated using Catapult Optimeye S5 player tracking devices. Distance covered in low intensity activity (LIA, ˂4.0 m.s-1 ), high intensity running (HIR, ≄4.0 m·s-1 ) and very high intensity running (VHIR, ≄5.5 m·s-1 ) was also examined along with PlayerLoadℱ, which represented a composite of all accelerations. Data from 53 players (n=405 files) was collated into specific match periods to facilitate a temporal analysis between the first and second halves and from quarter 1 (Q1) to quarter 4 (Q4), with significance accepted at p ≀ 0.05. Total distance and running was higher in games lost, whereas total distance, walking and LIA was higher in halves lost. Only walking was higher in quarters lost. The percentage of possession declined in halves and quarters lost. In games lost, high speed running declined in the second half. From Q1 to Q4; PlayerLoadℱ, total distance, jogging, high speed running, HIR and VHIR, decreased in all games combined and in games lost. Possession frequency declined in Q4 in all games and in games won. Overall, total distance was higher in games lost and physical performance declines were more pronounced when examined by match quarter compared to half and were only apparent in games lost. Similarly, reductions in possession frequency and percentage were more evident when examined by quarter or period lost, respectively. These findings can inform the prescription of conditioning and field-training strategies to mitigate the reductions in performance observed in losing and towards the end of games

    Antifungal Potential of Copper(II), Manganese(II) and Silver(I) 1,10-Phenanthroline Chelates Against Multidrug-Resistant Fungal Species Forming the Candida haemulonii Complex: Impact on the Planktonic and Biofilm Lifestyles

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    Candida haemulonii, Candida haemulonii var. vulnera and Candida duobushaemulonii, which form the C. haemulonii complex, are emerging etiologic agents of fungal infections known to be resistant to the most commonly used antifungals. The well-established anti-Candida potential ofmetal complexes containing 1,10-phenanthroline (phen) ligands encouraged us to evaluate different copper(II), manganese(II), and silver(I) phen chelates for their ability to inhibit planktonic growth and biofilm of C. haemulonii species complex. Two novel coordination complexes, {[Cu(3,6,9-tdda)(phen)2].3H2O.EtOH}n and [Ag2(3,6,9-tdda)(phen)4].EtOH (3,6,9-tddaH2 = 3,6,9-trioxaundecanedioic acid), were synthesized in a similar fashion to the other, previously documented, sixteen copper(II), manganese(II), and silver(I) chelates employed herein. Three isolates of each C. haemulonii species complex were used and the effect of the metal chelates on viability was determined utilizing the CLSI standard protocol and on biofilm-growing cells using the XTT assay. Cytotoxicity of the chelates was evaluated by the MTT assay, employing lung epithelial cells. The majority of the metal chelates were capable of interfering with the viability of planktonic-growing cells of all the fungal isolates
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