186 research outputs found

    Multivariate Analysis, Retrieval, and Storage System (MARS). Volume 1: MARS System and Analysis Techniques

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    A method for rapidly examining the probable applicability of weight estimating formulae to a specific aerospace vehicle design is presented. The Multivariate Analysis Retrieval and Storage System (MARS) is comprised of three computer programs which sequentially operate on the weight and geometry characteristics of past aerospace vehicles designs. Weight and geometric characteristics are stored in a set of data bases which are fully computerized. Additional data bases are readily added to the MARS system and/or the existing data bases may be easily expanded to include additional vehicles or vehicle characteristics

    Multivariate Analysis, Retrieval, and Storage System (MARS). Volume 4: Turbojet and Turbofan Data Base (By Engine)

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    A partial listing of turbojet and turbofan engine specifications data, as provided by the MARS (Multivariable Data Analysis, Retrieval, and Storage) system, was given for a number of engines

    Migration of Apicomplexa Across Biological Barriers: The Toxoplasma and Plasmodium Rides

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    The invasive stages of Apicomplexa parasites, called zoites, have been largely studied in in vitro systems, with a special emphasis on their unique gliding and host cell invasive capacities. In contrast, the means by which these parasites reach their destination in their hosts are still poorly understood. We summarize here our current understanding of the cellular basis of in vivo parasitism by two well-studied Apicomplexa zoites, the Toxoplasma tachyzoite and the Plasmodium sporozoite. Despite being close relatives, these two zoites use different strategies to reach their goal and establish infection

    Comparison of Plasmodium berghei challenge models for the evaluation of pre-erythrocytic malaria vaccines and their effect on perceived vaccine efficacy

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    <p>Abstract</p> <p>Background</p> <p>The immunological mechanisms responsible for protection against malaria infection vary among <it>Plasmodium </it>species, host species and the developmental stage of parasite, and are poorly understood. A challenge with live parasites is the most relevant approach to testing the efficacy of experimental malaria vaccines. Nevertheless, in the mouse models of <it>Plasmodium berghei </it>and <it>Plasmodium yoelii</it>, parasites are usually delivered by intravenous injection. This route is highly artificial and particularly in the <it>P. berghei </it>model produces inconsistent challenge results. The initial objective of this study was to compare an optimized intravenous (IV) delivery challenge model with an optimized single infectious mosquito bite challenge model. Finding shortcomings of both approaches, an alternative approach was explored, <it>i.e</it>., the subcutaneous challenge.</p> <p>Methods</p> <p>Mice were infected with <it>P. berghei </it>sporozoites by intravenous (tail vein) injection, single mosquito bite, or subcutaneous injection of isolated parasites into the subcutaneous pouch at the base of the hind leg. Infection was determined in blood smears 7 and 14 days later. To determine the usefulness of challenge models for vaccine testing, mice were immunized with circumsporozoite-based DNA vaccines by gene gun.</p> <p>Results</p> <p>Despite modifications that allowed infection with a much smaller than reported number of parasites, the IV challenge remained insufficiently reliable and reproducible. Variations in the virulence of the inoculum, if not properly monitored by the rigorous inclusion of sporozoite titration curves in each experiment, can lead to unacceptable variations in reported vaccine efficacies. In contrast, mice with different genetic backgrounds were consistently infected by a single mosquito bite, without overwhelming vaccine-induced protective immune responses. Because of the logistical challenges associated with the mosquito bite model, the subcutaneous challenge route was optimized. This approach, too, yields reliable challenge results, albeit requiring a relatively large inoculum.</p> <p>Conclusions</p> <p>Although a single bite by <it>P. berghei </it>infected <it>Anopheles </it>mosquitoes was superior to the IV challenge route, it is laborious. However, any conclusive evaluation of a pre-erythrocytic malaria vaccine candidate should require challenge through the natural anatomic target site of the parasite, the skin. The subcutaneous injection of isolated parasites represents an attractive compromise. Similar to the mosquito bite model, it allows vaccine-induced antibodies to exert their effect and is, therefore not as prone to the artifacts of the IV challenge.</p

    The <i>Plasmodium</i> eukaryotic initiation factor-2α kinase IK2 controls the latency of sporozoites in the mosquito salivary glands

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    Sporozoites, the invasive form of malaria parasites transmitted by mosquitoes, are quiescent while in the insect salivary glands. Sporozoites only differentiate inside of the hepatocytes of the mammalian host. We show that sporozoite latency is an active process controlled by a eukaryotic initiation factor-2α (eIF2α) kinase (IK2) and a phosphatase. IK2 activity is dominant in salivary gland sporozoites, leading to an inhibition of translation and accumulation of stalled mRNAs into granules. When sporozoites are injected into the mammalian host, an eIF2α phosphatase removes the PO4 from eIF2α-P, and the repression of translation is alleviated to permit their transformation into liver stages. In IK2 knockout sporozoites, eIF2α is not phosphorylated and the parasites transform prematurely into liver stages and lose their infectivity. Thus, to complete their life cycle, Plasmodium sporozoites exploit the mechanism that regulates stress responses in eukaryotic cells

    Virtual Blocks: a serious game for spatial ability improvement on mobile devices

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    This paper presents a novel spatial instruction system for improving spatial abilities of engineering students. A 3D mobile game application called Virtual Blocks has been designed to provide a 3D virtual environment to build models with cubes that help students to perform visualization tasks to promote the development of their spatial ability during a short remedial course. A validation study with 26 freshman engineering students at La Laguna University (Spain) has concluded that the training had a measurable and positive impact on students spatial ability. In addition, the results obtained using a satisfaction questionnaire show that Virtual Blocks is considered an easy to use and stimulating application.This work has been partially supported by the (Spanish) National Program for Studies and Analysis project "Evaluation and development of competencies associated to the spatial ability in the new engineering undergraduate courses" (Ref. EA2009-0025) and the (Spanish) National Science Project "Enhancing Spatial REasoning and VIsual Cognition with advanced technological tools (ESREVIC)" (Ref TIN2010-21296-C02-02)Martín Dorta, NN.; Sanchez Berriel, I.; Bravo, M.; Hernández, J.; Saorin, JL.; Contero, M. (2014). Virtual Blocks: a serious game for spatial ability improvement on mobile devices. Multimedia Tools and Applications. 73(3):1575-1595. https://doi.org/10.1007/s11042-013-1652-0S15751595733Baartmans BG, Sorby SA (1996) Introduction to 3-D spatial visualization. Prentice Hall, Englewood CliffsClements D, Battista M (1992) Geometry and spatial reasoning. In: Grouws DA (ed) Handbook of research on mathematics teaching and learning. New York, pp 420–464Cohen J (1988) Statistical power analysis for the behavioral sciences, 2nd edn. Erlbaum, HillsdaleDe Lisi R, Cammarano DM (1996) Computer experience and gender differences in undergraduate mental rotation performance. 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ACM Press, New York pp 271–280Linn MC, Petersen AC (1985) Emergence and characterization of gender differences in spatial abilities: a meta-analysis. Child Dev 56:1479–1498Martin-Dorta N, Sanchez-Berriel I, Bravo M, Hernandez J, Saorin JL, Contero M (2010) A 3D educational mobile game to enhance student’s spatial skills, ICALT, pp.6–10, 2010 10th IEEE International Conference on Advanced Learning TechnologiesMartin-Dorta N, Saorin J, Contero M (2008) Development of a fast remedial course to improve the spatial abilities of engineering students. J Eng Educ 27(4):505–514Martin-Dorta N, Saorin JL, Contero M (2011) Web-based spatial training using handheld touch screen devices. Educ Technol Soc 14(3):163–177McGee MG (1979) Human spatial abilities: psychometric studies and environmental, genetic, hormonal, and neurological influences. Psychol Bull 86:889–918Noguera JM, Segura RJ, Ogayar CJ, Joan-Arinyo R (2011) Navigating large terrains using commodity mobile devices. 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    Gliding Motility of Babesia bovis Merozoites Visualized by Time-Lapse Video Microscopy

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    BACKGROUND: Babesia bovis is an apicomplexan intraerythrocytic protozoan parasite that induces babesiosis in cattle after transmission by ticks. During specific stages of the apicomplexan parasite lifecycle, such as the sporozoites of Plasmodium falciparum and tachyzoites of Toxoplasma gondii, host cells are targeted for invasion using a unique, active process termed "gliding motility". However, it is not thoroughly understood how the merozoites of B. bovis target and invade host red blood cells (RBCs), and gliding motility has so far not been observed in the parasite. METHODOLOGY/PRINCIPAL FINDINGS: Gliding motility of B. bovis merozoites was revealed by time-lapse video microscopy. The recorded images revealed that the process included egress of the merozoites from the infected RBC, gliding motility, and subsequent invasion into new RBCs. The gliding motility of B. bovis merozoites was similar to the helical gliding of Toxoplasma tachyzoites. The trails left by the merozoites were detected by indirect immunofluorescence assay using antiserum against B. bovis merozoite surface antigen 1. Inhibition of gliding motility by actin filament polymerization or depolymerization indicated that the gliding motility was driven by actomyosin dependent process. In addition, we revealed the timing of breakdown of the parasitophorous vacuole. Time-lapse image analysis of membrane-stained bovine RBCs showed formation and breakdown of the parasitophorous vacuole within ten minutes of invasion. CONCLUSIONS/SIGNIFICANCE: This is the first report of the gliding motility of B. bovis. Since merozoites of Plasmodium parasites do not glide on a substrate, the gliding motility of B. bovis merozoites is a notable finding

    Environmental Constraints Guide Migration of Malaria Parasites during Transmission

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    Migrating cells are guided in complex environments mainly by chemotaxis or structural cues presented by the surrounding tissue. During transmission of malaria, parasite motility in the skin is important for Plasmodium sporozoites to reach the blood circulation. Here we show that sporozoite migration varies in different skin environments the parasite encounters at the arbitrary sites of the mosquito bite. In order to systematically examine how sporozoite migration depends on the structure of the environment, we studied it in micro-fabricated obstacle arrays. The trajectories observed in vivo and in vitro closely resemble each other suggesting that structural constraints can be sufficient to guide Plasmodium sporozoites in complex environments. Sporozoite speed in different environments is optimized for migration and correlates with persistence length and dispersal. However, this correlation breaks down in mutant sporozoites that show adhesion impairment due to the lack of TRAP-like protein (TLP) on their surfaces. This may explain their delay in infecting the host. The flexibility of sporozoite adaption to different environments and a favorable speed for optimal dispersal ensures efficient host switching during malaria transmission

    Temperature Shift and Host Cell Contact Up-Regulate Sporozoite Expression of Plasmodium falciparum Genes Involved in Hepatocyte Infection

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    Plasmodium sporozoites are deposited in the skin by Anopheles mosquitoes. They then find their way to the liver, where they specifically invade hepatocytes in which they develop to yield merozoites infective to red blood cells. Relatively little is known of the molecular interactions during these initial obligatory phases of the infection. Recent data suggested that many of the inoculated sporozoites invade hepatocytes an hour or more after the infective bite. We hypothesised that this pre-invasive period in the mammalian host prepares sporozoites for successful hepatocyte infection. Therefore, the genes whose expression becomes modified prior to hepatocyte invasion would be those likely to code for proteins implicated in the subsequent events of invasion and development. We have used P. falciparum sporozoites and their natural host cells, primary human hepatocytes, in in vitro co-culture system as a model for the pre-invasive period. We first established that under co-culture conditions, sporozoites maintain infectivity for an hour or more, in contrast to a drastic loss in infectivity when hepatocytes were not included. Thus, a differential transcriptome of salivary gland sporozoites versus sporozoites co-cultured with hepatocytes was established using a pan-genomic P. falciparum microarray. The expression of 532 genes was found to have been up-regulated following co-culture. A fifth of these genes had no orthologues in the genomes of Plasmodium species used in rodent models of malaria. Quantitative RT-PCR analysis of a selection of 21 genes confirmed the reliability of the microarray data. Time-course analysis further indicated two patterns of up-regulation following sporozoite co-culture, one transient and the other sustained, suggesting roles in hepatocyte invasion and liver stage development, respectively. This was supported by functional studies of four hitherto uncharacterized proteins of which two were shown to be sporozoite surface proteins involved in hepatocyte invasion, while the other two were predominantly expressed during hepatic parasite development. The genome-wide up-regulation of expression observed supports the hypothesis that the shift from the mosquito to the mammalian host contributes to activate quiescent salivary gland sporozoites into a state of readiness for the hepatic stages. Functional studies on four of the up-regulated genes validated our approach as one means to determine the repertoire of proteins implicated during the early events of the Plasmodium infection, and in this case that of P. falciparum, the species responsible for the severest forms of malaria
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