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Sample records for concurrent plasmodium yoelii

  1. Comparative histopathology of mice infected with the 17XL and 17XNL strains of Plasmodium yoelii.

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    Fu, Yong; Ding, Yan; Zhou, Tao-li; Ou, Qian-yi; Xu, Wen-yue

    2012-04-01

    Plasmodium yoelii 17XL was used to investigate the mechanism of Plasmodium falciparum-caused cerebral malaria, although its histological effect on other mouse organs is still unclear. Here, histological examination was performed on mice infected with P. yoelii 17XL; the effect of P. yoelii 17XL infection on anemia and body weight loss, as well as its lesions in the brain, liver, kidney, lung, and spleen, also was investigated. Plasmodium yoelii 17XL-infected red blood cells were sequestered in the microcirculation of the brain and in the kidney. Compared with the nonlethal P. yoelii 17XNL strain, infection by P. yoelii 17XL caused substantial pulmonary edema, severe anemia, and significant body weight loss. Although P. yoelii 17XNL and 17XL produced a similar focal necrosis in the mouse liver, infection of P. yoelii 17XL induced coalescing of red and white pulp. Mortality caused by P. yoelii 17XL may be due to cerebral malaria, as well as respiratory distress syndrome and severe anemia. Plasmodium yoelii 17XL-infected rodent malaria seems to be a useful model for investigating severe malaria caused by P. falciparum.

  2. Plasmodium yoelii: induction of attenuated mutants by irradiation

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    Waki, S.; Yonome, I.; Suzuki, M.

    1986-12-01

    When erythrocytic forms of Plasmodium yoelii nigeriensis, which is invariably fatal in mice, were exposed to X rays, the dose to reduce surviving parasites to one millionth was 100 gray (10 Krad). A suspension of 5 X 10(6) per ml of parasitized erythrocyte was irradiated at 100 gray, and 0.2 ml aliquots were inoculated into 22 mice. Eleven mice showed patent parasitemia, and in these the growth curves were less steep than that found in nonirradiated parasites. The infections of 8 mice of the 11 were self-resolving, and the attenuated feature of the parasites maintained following a limited number of blood passages. The parasites were slowly growing even in nude mice and cause self-resolving infections in intact mice. BALB/c mice immunized with the attenuated parasites were protected against subsequent challenge infections with the original virulent erythrocytic and sporogonic forms. These findings indicate that attenuated mutants of malaria parasites can be readily induced by this method.

  3. Release of hepatic Plasmodium yoelii merozoites into the pulmonary microvasculature.

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    Kerstin Baer

    2007-11-01

    Full Text Available Plasmodium undergoes one round of multiplication in the liver prior to invading erythrocytes and initiating the symptomatic blood phase of the malaria infection. Productive hepatocyte infection by sporozoites leads to the generation of thousands of merozoites capable of erythrocyte invasion. Merozoites are released from infected hepatocytes as merosomes, packets of hundreds of parasites surrounded by host cell membrane. Intravital microscopy of green fluorescent protein-expressing P. yoelii parasites showed that the majority of merosomes exit the liver intact, adapt a relatively uniform size of 12-18 microm, and contain 100-200 merozoites. Merosomes survived the subsequent passage through the right heart undamaged and accumulated in the lungs. Merosomes were absent from blood harvested from the left ventricle and from tail vein blood, indicating that the lungs effectively cleared the blood from all large parasite aggregates. Accordingly, merosomes were not detectable in major organs such as brain, kidney, and spleen. The failure of annexin V to label merosomes collected from hepatic effluent indicates that phosphatidylserine is not exposed on the surface of the merosome membrane suggesting the infected hepatocyte did not undergo apoptosis prior to merosome release. Merosomal merozoites continued to express green fluorescent protein and did not incorporate propidium iodide or YO-PRO-1 indicating parasite viability and an intact merosome membrane. Evidence of merosomal merozoite infectivity was provided by hepatic effluent containing merosomes being significantly more infective than blood with an identical low-level parasitemia. Ex vivo analysis showed that merosomes eventually disintegrate inside pulmonary capillaries, thus liberating merozoites into the bloodstream. We conclude that merosome packaging protects hepatic merozoites from phagocytic attack by sinusoidal Kupffer cells, and that release into the lung microvasculature enhances the

  4. Etiopathogenesis of Burkitt's lymphoma: a lesson from a BL-like in CD1 mouse immune to Plasmodium yoelii yoelii.

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    Malagon, Filiberto; Gonzalez-Angulo, Jorge; Carrasco, Elba; Robert, Lilia

    2011-07-09

    There is a jaw cancer that develops in children five to eight years old in holoendemic malaria regions of Africa, associated to malaria and Epstein Barr virus infections (EBV). This malignancy is known as endemic Burkitt's lymphoma, and histopatologically is characterized by a starry sky appearance. To date, no histopathologic expression of Burkitt's lymphoma has been reported in non-genetically manipulated experimental animals. The purpose of the study is to describe the case of a mouse immune to Plasmodium yoelii yoelii (Pyy) that developed a Burkitt's lymphoma-like neoplasm after repeated malaria infections. Immune mouse 10 (IM-10) developed neoplasms at eight months of age, after receiving three Pyy inoculations. At autopsy eight subcutaneous tumors were found of which the right iliac fosse tumor perforated the abdominal wall and invaded the colon. The histopathologic study showed that all neoplasms were malignant lymphomas of large non-cleaved cells also compatible with variants or previous states of development of a Burkitt's lymphoma-like. The thymus, however, showed a typical starry sky Burkitt's lymphoma-like neoplasm. Neoplasm development in CD1 mouse is associated to both, immunity against malaria and continuous antigenic stimulation with living parasites.It is the first observation of a histopathologically expressed Human Burkitt's lymphoma-like neoplasm in a non-genetically manipulated mouse.Chronic immune response associated to neoplasms development could probably be not an exclusive expression of malaria-host interaction but, it could be a pattern that can bee applied also to other agent-host interactions such as host-bacteria, fungus, virus and other parasites.

  5. Etiopathogenesis of Burkitt's lymphoma: a lesson from a BL-like in CD1 mouse immune to Plasmodium yoelii yoelii

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    Robert Lilia

    2011-07-01

    Full Text Available Abstract Introduction There is a jaw cancer that develops in children five to eight years old in holoendemic malaria regions of Africa, associated to malaria and Epstein Barr virus infections (EBV. This malignancy is known as endemic Burkitt's lymphoma, and histopatologically is characterized by a starry sky appearance. To date, no histopathologic expression of Burkitt's lymphoma has been reported in non-genetically manipulated experimental animals. The purpose of the study is to describe the case of a mouse immune to Plasmodium yoelii yoelii (Pyy that developed a Burkitt's lymphoma-like neoplasm after repeated malaria infections. Results Immune mouse 10 (IM-10 developed neoplasms at eight months of age, after receiving three Pyy inoculations. At autopsy eight subcutaneous tumors were found of which the right iliac fosse tumor perforated the abdominal wall and invaded the colon. The histopathologic study showed that all neoplasms were malignant lymphomas of large non-cleaved cells also compatible with variants or previous states of development of a Burkitt's lymphoma-like. The thymus, however, showed a typical starry sky Burkitt's lymphoma-like neoplasm. Conclusions Neoplasm development in CD1 mouse is associated to both, immunity against malaria and continuous antigenic stimulation with living parasites. It is the first observation of a histopathologically expressed Human Burkitt's lymphoma-like neoplasm in a non-genetically manipulated mouse. Chronic immune response associated to neoplasms development could probably be not an exclusive expression of malaria-host interaction but, it could be a pattern that can bee applied also to other agent-host interactions such as host-bacteria, fungus, virus and other parasites.

  6. In vivo antimalarial activity of leaves of Plectranthus amboinicus (lour) spreng on Plasmodium berghei yoelii.

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    Periyanayagam, K; Nirmala Devi, K; Suseela, L; Uma, A; Ismail, M

    2008-06-01

    An invivo study of aqueous extract of the leaves of Plectranthus amboinicus on Plasmodium berghei yoelii was conducted on laboratory infected albino mice and compared with standard drug chloroquine. Reduction of parasitemia at 250 mg/kg and 500 mg/kg of aqueous extract for 24 hrs, 48 hrs, 72 hrs and 96 hrs were determined. The reduction of parasitemia after 96 hrs was 100%, 67.9% and 76.2% for standard, 250 mg/kg and 500 mg/kg of aqueous extract respectively. The isolation of active principle responsible for the reduction of parasitemia may give a promising drug molecule.

  7. An efficient strategy for gene targeting and phenotypic assessment in the Plasmodium yoelii rodent malaria model.

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    Mikolajczak, Sebastian A; Aly, Ahmed S I; Dumpit, Ronald F; Vaughan, Ashley M; Kappe, Stefan H I

    2008-04-01

    In this report, we describe a cloning procedure for gene replacement by double homologous recombination in Plasmodium yoelii, which requires only one digestion and ligation step. This significantly shortens the time required to complete the production of the targeting vector. Furthermore, for more efficient phenotypic evaluation of the gene knockout parasites, we have also introduced a fluorescent protein cassette into the targeting vector. This allows for a more rapid assessment of parasite growth in all of its developmental stages. In addition, the introduction of the fluorescent marker via the replacement strategy confers the stable integration of the marker.

  8. Identification of a new export signal in Plasmodium yoelii: identification of a new exportome.

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    Siau, Anthony; Huang, Ximei; Yam, Xue Yan; Bob, Ndeye Sakha; Sun, Hequan; Rajapakse, Jagath C; Renia, Laurent; Preiser, Peter R

    2014-05-01

    Development of the erythrocytic malaria parasite requires targeting of parasite proteins into multiple compartments located within and beyond the parasite confine. Beyond the PEXEL/VTS pathway and its characterized players, increasing amount of evidence has highlighted the existence of proteins exported using alternative export-signal(s)/pathway(s); hence, the exportomes currently predicted are incomplete. The nature of these exported proteins which could have a prominent role in most of the Plasmodium species remains elusive. Using P.  yoelii variant proteins, we identified a signal associated to lipophilic region that mediates export of P.  yoelii proteins. This non-PEXEL signal termed PLASMED is defined by semi-conserved residues and possibly a secondary structure. In vivo characterization of exported-proteins indicated that PLASMED is a bona fide export-signal that allowed us to identify an unseen P.  yoelii exportome. The repertoire of the newly predicted exported proteins opens up perspectives for unravelling the remodelling of the host-cell by the parasite, against which new therapies could be elaborated.

  9. Differential gene expression in Anopheles stephensi following infection with drug-resistant Plasmodium yoelii.

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    Zhang, Jingru; Huang, Jiacheng; Zhu, Feng; Zhang, Jian

    2017-08-29

    The transmission of drug-resistant parasites by the mosquito may be influenced by the altered biological fitness of drug-resistant parasites and different immune reactions or metabolic change in the mosquito. At this point, little is known about the variations in mosquito immunity and metabolism when mosquitoes are infected with drug-resistant parasites. To understand the differential gene expression in Anopheles following infection with drug-resistant Plasmodium, we conducted a genome-wide transcriptomic profiling analysis of Anopheles stephensi following feeding on mice with drug-resistant or drug-sensitive P. yoelii, observed changes in gene expression profiles and identified transcripts affected by the drug-resistant parasite. To study the impact of drug-resistant Plasmodium infections on An. stephensi gene transcription, we analyzed the three major transition stages of Plasmodium infections: at 24 h and 13 and 19 days after blood-feeding. Six cDNA libraries (R-As24h, R-As13d, R-As19d,S-As24h, S-As13dand S-As19d) were constructed, and RNA sequencing was subsequently performed. In total, approximately 50.1 million raw reads, 47.9 million clean reads and 7.18G clean bases were obtained. Following differentially expressed gene (DEG) analysis, GO enrichment analysis of DEGs, and functional classification by KEGG, we showed that the variations in gene expression in An. stephensi infected by the drug-resistant P. yoelii NSM occurred mainly at 13 days after blood meal during sporozoite migration through the hemolymph. The differentially expressed genes included those functioning in some important immune reaction and iron metabolism pathways, such as pattern recognition receptors, regulators of the JNK pathway, components of the phagosome pathway, regulators of the melanization response, activators of complement reactions, insulin signaling cascade members, oxidative stress and detoxification proteins. Our study shows that drug-resistant P. yoelii NSM has an

  10. The novel oxygenated chalcone, 2,4-dimethoxy-4'-butoxychalcone, exhibits potent activity against human malaria parasite Plasmodium falciparum in vitro and rodent parasites Plasmodium berghei and Plasmodium yoelii in vivo

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    Chen, M; Brøgger Christensen, S; Zhai, L

    1997-01-01

    growth of both a chloroquine-susceptible (3D7) and a chloroquine-resistant (Dd2) strain of Plasmodium falciparum in a [3H]hypoxanthine uptake assay. The in vivo activity of 2,4mbc was tested in mice infected with Plasmodium berghei or Plasmodium yoelii and in rats infected with P. berghei. 2,4mbc...

  11. Status of ammonia, glutamate, lactate and pyruvate during Plasmodium yoelii infection and pyrimethamine treatment in mice.

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    Agarwal, A; Tripathi, L M; Pandey, V C

    1997-09-01

    Ammonia, lactate, glutamate and pyruvate levels in blood, liver, brain, spleen and kidney were determined during Plasmodium yoelii infection and pyrimethamine treatment in mice. Ammonia and lactate levels showed significant increase with rise in parasitaemia except in spleen where decrease in the lactate levels was observed. The glutamate level displayed a marked decrease in blood, liver and splenic tissues, whereas, significant increase in glutamate level in kidney was observed, although its level in cerebral tissue remained unaltered. The pyruvate level in blood and liver showed a noticeable decrease but brain, spleen and kidney registered an elevation of the same due to the parasitic infection. Pyrimethamine (oral) treatment (10 mg/kg body weight) to infected mice (5-10%) for four days brought back the altered levels of the above cellular constituents in different tissues to normal, a week after cessation of drug treatment.

  12. Within-host competition does not select for virulence in malaria parasites; studies with Plasmodium yoelii.

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    Hussein M Abkallo

    2015-02-01

    Full Text Available In endemic areas with high transmission intensities, malaria infections are very often composed of multiple genetically distinct strains of malaria parasites. It has been hypothesised that this leads to intra-host competition, in which parasite strains compete for resources such as space and nutrients. This competition may have repercussions for the host, the parasite, and the vector in terms of disease severity, vector fitness, and parasite transmission potential and fitness. It has also been argued that within-host competition could lead to selection for more virulent parasites. Here we use the rodent malaria parasite Plasmodium yoelii to assess the consequences of mixed strain infections on disease severity and parasite fitness. Three isogenic strains with dramatically different growth rates (and hence virulence were maintained in mice in single infections or in mixed strain infections with a genetically distinct strain. We compared the virulence (defined as harm to the mammalian host of mixed strain infections with that of single infections, and assessed whether competition impacted on parasite fitness, assessed by transmission potential. We found that mixed infections were associated with a higher degree of disease severity and a prolonged infection time. In the mixed infections, the strain with the slower growth rate was often responsible for the competitive exclusion of the faster growing strain, presumably through host immune-mediated mechanisms. Importantly, and in contrast to previous work conducted with Plasmodium chabaudi, we found no correlation between parasite virulence and transmission potential to mosquitoes, suggesting that within-host competition would not drive the evolution of parasite virulence in P. yoelii.

  13. Plasmodium yoelii vitamin B5 pantothenate transporter candidate is essential for parasite transmission to the mosquito.

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    Hart, Robert J; Lawres, Lauren; Fritzen, Emma; Ben Mamoun, Choukri; Aly, Ahmed S I

    2014-07-11

    In nearly all non-photosynthetic cells, pantothenate (vitamin B5) transport and utilization are prerequisites for the synthesis of the universal essential cofactor Coenzyme A (CoA). Early studies showed that human malaria parasites rely on the uptake of pantothenate across the parasite plasma membrane for survival within erythrocytes. Recently, a P. falciparum candidate pantothenate transporter (PAT) was characterized by functional complementation in yeast. These studies revealed that PfPAT mediated survival of yeast cells in low pantothenate concentrations and restored sensitivity of yeast cells lacking pantothenate uptake to fenpropimorph. In addition, PfPAT was refractory to deletion in P. falciparum in vitro, but nothing is known about the in vivo functions of PAT in Plasmodium life cycle stages. Herein, we used gene-targeting techniques to delete PAT in Plasmodium yoelii. Parasites lacking PAT displayed normal asexual and sexual blood stage development compared to wild-type (WT) and WT-like p230p(-) parasites. However, progression from the ookinete to the oocyst stage and sporozoite formation were completely abolished in pat(-) parasites. These studies provide the first evidence for an essential role of a candidate pantothenate transport in malaria transmission to Anopheles mosquitoes. This will set the stage for the development of PAT inhibitors against multiple parasite life cycle stages.

  14. Multivariable analysis of host amino acids in plasma and liver during infection of malaria parasite Plasmodium yoelii

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    Saiki Erisha

    2013-01-01

    Full Text Available Abstract Background Malaria is the most significant human parasitic disease, and yet understanding of the energy metabolism of the principle pathogen, Plasmodium falciparum, remains to be fully elucidated. Amino acids were shown to be essential nutritional requirements since early times and much of the current knowledge of Plasmodium energy metabolism is based on early biochemical work, performed using basic analytical techniques, carried out almost exclusively on human plasma with considerable inter-individual variability. Methods In order to further characterize the fate of amino acid metabolism in malaria parasite, multivariate analysis using statistical modelling of amino acid concentrations (aminogram of plasma and liver were determined in host infected with rodent malaria parasite, Plasmodium yoelii. Results and conclusion Comprehensive and statistical aminogram analysis revealed that P. yoelii infection caused drastic change of plasma and liver aminogram, and altered intra- and inter-correlation of amino acid concentration in plasma and liver. These findings of the interactions between amino acids and Plasmodium infection may provide insight to reveal the interaction between nutrients and parasites.

  15. The antiplasmodial effect of the extracts and formulated capsules of Phyllanthus amarus onPlasmodium yoelii infection in mice

    Institute of Scientific and Technical Information of China (English)

    Tolulope O Ajala; Cecilia I Igwilo; Ibrahim A Oreagba; Oluwatoyin A Odeku

    2011-01-01

    Objective:To investigate the antiplasmodial activity of the extracts ofPhyllanthus amarus (P. amarus) onPlasmodium yoelii (P. yoelii) (a resistant malaria parasite strain used in animal studies) infection in mice.Methods: The aqueous and ethanol extracts of the whole plant of Phyllanthus amarus was administered to Swiss albino mice at doses of200 mg/kg/day,400 mg/kg/day,800 mg/kg/day and1 600 mg/kg/day and the prophylactic and chemotherapeutic effect of the extracts againstP. yoelii infection in mice was investigated and compared with those of standard antimalaria drugs used in the treatment of malaria parasite infection. Acute toxicity test was carried out in mice to determine the safety of the plant extract when administered orally. Results: The results showed that the extracts demonstrated a dose-dependent prophylactic and chemotherapeutic activity with the aqueous extracts showing slightly higher effect than the ethanol extract. The antiplasmodial effects of the extracts were comparable to the standard prophylactic and chemotherapeutic drugs used in chloroquine resistantPlasmodium infection although the activity depended on the dose of the extract administered. The extracts showed prophylactic effect by significantly delaying the onset of infection with the suppression of79%at a dose of 1 600mg/kg/day.Conclusions: The results obtained indicate that the extracts of the whole plant ofP. amaruspossess repository and chemotherapeutic effects against resistant strains ofP. yoelii in Swiss albino mice. The findings justify the use of the extract ofP. amarus in traditional medicine practice, for the treatment of malaria infections.

  16. Kinetics of antigen specific and non-specific polyclonal B-cell responses during lethal Plasmodium yoelii malaria

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    Laurence Rolland

    1992-06-01

    Full Text Available In order to study the kinetics and composition of the polyclonal B-cell activation associated to malaria infection, antigen-specific and non-specific B-cell responses were evaluated in the spleens of mice infected with Plasmodium yoelii 17 XL or injected with lysed erythrocytes or plasma from P. yoelii infected mice or with P. falciparum culture supernatants. Spleen/body weigth ratio, numbers of nucleated spleen cells and Immunoglobulin-containing and Immunoglobulin-secreting cells increased progressively during the course of infection,in parallel to the parasitemia. A different pattern of kinetics was observed when anti-sheep red blood cell and anti-trinitrophenylated-sheep red blood cell plaque forming cells response were studied: maximum values were observed at early stages of infection, whereas the number of total Immunoglobulin-containing and Immunoglobulin-secreting cells were not yet altered. Conversely, at the end of infection, when these latter values reached their maximum, the anti-sheep red blood cell and anti-trinitrophenylated-sheep red blood cell specific responses were normal or even infranormal. In mice injected with Plasmodium-derived material, a higher increase in antigen-specific PFC was observed, as compared to the increase of Immunoglobulin-containing and Immunoglobulin-secreting cell numbers. This suggested a "preferential" (antigen-plus mitogen-induced stimulation of antigen-specific cells rather than a generalized non-specific (mitogen-induced triggering of B-lymphocytes. On the basis of these and previous results, it is suggested that polyclonal B-cell activation that takes place during the course of infection appears as a result of successive waves of antigen-specific B-cell activation.

  17. Nonobese Diabetic (NOD Mice Lack a Protective B-Cell Response against the “Nonlethal” Plasmodium yoelii 17XNL Malaria Protozoan

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    Mirian Mendoza

    2016-01-01

    Full Text Available Background. Plasmodium yoelii 17XNL is a nonlethal malaria strain in mice of different genetic backgrounds including the C57BL/6 mice (I-Ab/I-Enull used in this study as a control strain. We have compared the trends of blood stage infection with the nonlethal murine strain of P. yoelii 17XNL malaria protozoan in immunocompetent Nonobese Diabetic (NOD mice prone to type 1 diabetes (T1D and C57BL/6 mice (control mice that are not prone to T1D and self-cure the P. yoelii 17XNL infection. Prediabetic NOD mice could not mount a protective antibody response to the P. yoelii 17XNL-infected red blood cells (iRBCs, and they all succumbed shortly after infection. Our data suggest that the lack of anti-P. yoelii 17XNL-iRBCs protective antibodies in NOD mice is a result of parasite-induced, Foxp3+ T regulatory (Treg cells able to suppress the parasite-specific antibody secretion. Conclusions. The NOD mouse model may help in identifying new mechanisms of B-cell evasion by malaria parasites. It may also serve as a more accurate tool for testing antimalaria therapeutics due to the lack of interference with a preexistent self-curing mechanism present in other mouse strains.

  18. Effect of Plasmodium yoelii YM Infection on Vaccination with 19 kDa Carboxylterminus of the Merozoite Surface Protein 1 (MSP1 19)

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    徐沪济; JiraprapaWIPASA; 刘雪琴; AnthonySTOWERS; 杨晓平; MichaelFGOOD

    2004-01-01

    We have previously demonstrated the ability of malaria parasites to interfere with specific immune responses. CD4 T cells specific to parasite antigens, but not CD4 T cells specific to an irrelevant antigen, ovalbumin (OVA), are deleted via apoptosis during malaria infection. It is of interest, therefore, to investigate the immune responses that developed following vaccination with the 19 kDa carboxylterminus of the merozoite surface protein 1 (MSP1 19) in mice that had previously experienced malaria infection. In this study, pre-exposure of mice to Plasmodium yoelii elicited native anti-MSP1 19 antibody responses, which could be boosted by vaccination with recombinant MSP1 19 ,Likewise, infection of MSP1 19-primed mice with Plasmodium yoelii (P. yoelii) led to an increase of anti-MSP1 19 antibodies. MSP1 19 vaccination of malaria preexposed mice or immunization by infection/cure of MSP1 19-primed mice enabled the mice to survive challenge infection, with the former group having slightly lower parasitaemia. The data suggest that exposure to malaria infection primes a natural immune response which can be boosted by vaccination. This information is relevant to the development of a vaccine for use in individuals living in malaria-endemic areas.

  19. Differential immune response associated to malaria outcome is detectable in peripheral blood following Plasmodium yoelii infection in mice.

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    Isabel G Azcárate

    Full Text Available Malaria infection in humans elicits a wide range of immune responses that can be detected in peripheral blood, but we lack detailed long-term follow-up data on the primary and subsequent infections that lead to naturally acquired immunity. Studies on antimalarial immune responses in mice have been based on models yielding homogenous infection profiles. Here, we present a mouse model in which a heterogeneous course of Plasmodium yoelii lethal malaria infection is produced in a non-congenic ICR strain to allow comparison among different immunological and clinical outcomes. Three different disease courses were observed ranging from a fatal outcome, either early or late, to a self-resolved infection that conferred long-term immunity against re-infection. Qualitative and quantitative changes produced in leukocyte subpopulations and cytokine profiles detected in peripheral blood during the first week of infection revealed that monocytes, dendritic cells and immature B cells were the main cell subsets present in highly-parasitized mice dying in the first week after infection. Besides, CD4(+CD25(high T cells expanded at an earlier time point in early deceased mice than in surviving mice and expressed higher levels of intracellular Foxp3 protein. In contrast, survivors showed a limited increase of cytokines release and stable circulating innate cells. From the second week of infection, mice that would die or survive showed similar immune profiles, although CD4(+CD25(high T cells number increased earlier in mice with the worst prognosis. In surviving mice the expansion of activated circulating T cell and switched-class B cells with a long-term protective humoral response from the second infection week is remarkable. Our results demonstrate that the follow-up studies of immunological blood parameters during a malaria infection can offer information about the course of the pathological process and the immune response.

  20. Dynamic Balance of pSTAT1 and pSTAT3 in C57BL/6 Mice Infected with Lethal or Nonlethal Plasmodium yoelii

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    Xibao Shi; Li Qin; Guangjie Liu; Siting Zhao; Nanzheng Peng; Xiaoping Chen

    2008-01-01

    Signal transducer and activator of transcription(STAT)proteins play an important role in cytokine signaling pathways and regulation of immune responses.The balance of the phosphorylated(activated)STAT1(pSTAT1) and STAT3 (pSTAT3)has been documented in cancer immunology.In this study,we investigated the dynamic balance of pSTAT1 and pSTAT3 in C57BL/6 mice infected with either a nonlethal(py17XNL)or lethal(ey17XL) strain of Plasmodium yoelii.Both pylNL and ey17XL infections induced a maximum activation of STAT1 and STAT3 On the first day after parasite inoculation.Additionally,the py17XNL infection induced a pSTAT1- dominant response in mice during the early stage of infection,with the resolution of parasitemia.In contrast, Py17XL infection induced a pSTAT3-dominant response during the early phase of infection,with the death of the animals.Our results indicated that maximum activation of STAT1 and STAT3 occurred much earlier than the peak levels of cytokines induced by Plasmodium yoelii infection based on previous reports and that infection with Py17XNL-and py17XL induced different dynamic patterns of pSTAT1 and pSTAT3 balance.

  1. Clarithromycin, a cytochrome P450 inhibitor, can reverse mefloquine resistance in Plasmodium yoelii nigeriensis- infected Swiss mice.

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    Tripathi, Renu; Pandey, Swaroop Kumar; Rizvi, Amber

    2011-08-01

    During the last 2 decades there have been numerous reports of the emergence of mefloquine resistance in Southeast Asia and nearly 50% resistance is reported in Thailand. A World Health Organization report (2001) considers mefloquine as an important component of ACT (artesunate+mefloquine) which is the first line of treatment for the control of uncomplicated/multi-drug resistant (MDR) Plasmodium falciparum malaria. In view of the emergence of resistance towards this drug, it is proposed to develop new drug combinations to prolong the protective life of this drug. Prior studies have suggested that mefloquine resistance can be overcome by a variety of agents such as ketoconazole, cyproheptadine, penfluridol, Icajine and NP30. The present investigation reports that clarithromycin (CLTR), a new macrolide, being a potent inhibitor of Cyt. P450 3A4, can exert significant resistance reversal action against mefloquine resistance of plasmodia. Experiments were carried out to find out the curative dose of CLTR against multi-drug resistant P. yoelii nigeriensis. Mefloquine (MFQ) and clarithromycin (CLTR) combinations have been used for the treatment of this MDR parasite. Different dose combinations of these two drugs were given to the infected mice on day 0 (prophylactic) and day 1 with established infection (therapeutic) to see the combined effect of these combinations against the MDR malaria infection. With a dose of 32 mg/kg MFQ and 225 mg/kg CLTR, 100% cure was observed, while in single drug groups, treated with MFQ or CLTR, the cure was zero and 40% respectively. Therapeutically, MFQ and CLTR combinations 32+300 mg/kg doses cleared the established parasitaemia on day 10. Single treatment with MFQ or CLTR showed considerable suppression of parasitaemia on day 14 but neither was curative. Follow-up of therapeutically treated mice showed enhanced anti-malarial action as reflected by their 100% clearance of parasitaemia. The present study reveals that CLTR is a useful

  2. Unlike the synchronous Plasmodium falciparum and P. chabaudi infection, the P. berghei and P. yoelii asynchronous infections are not affected by melatonin

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    Piero Bagnaresi

    2009-04-01

    Full Text Available Piero Bagnaresi1, Eduardo Alves1, Henrique Borges da Silva1, Sabrina Epiphanio2, Maria M Mota2, Célia RS Garcia11Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil; 2Unidade de Malária, Instituto de Medicina Molecular, Universidade de Lisboa, Lisboa, PortugalAbstract: We have previously reported that Plasmodium chabaudi and P. falciparum sense the hormone melatonin and this could be responsible for the synchrony of malaria infection. In P. chabaudi and P. falciparum, melatonin induces calcium release from internal stores, and this response is abolished by U73122, a phospholipase C inhibitor, and luzindole, a melatoninreceptor competitive antagonist. Here we show that, in vitro, melatonin is not able to modulate cell cycle, nor to elicit an elevation in intracellular calcium concentration of the intraerythrocytic forms of P. berghei or P. yoelii, two rodent parasites that show an asynchrononous development in vivo. Interestingly, melatonin and its receptor do not seem to play a role during hepatic infection by P. berghei sporozoites either. These data strengthen the hypothesis that hostderived melatonin does not synchronize malaria infection caused by P. berghei and P. yoelii. Moreover, these data explain why infections by these parasites are asynchronous, contrary to what is observed in P. falciparum and P. chabaudi infections.Keywords: malaria, calcium, melatonin, cell cycle, rhythm, sporozoite

  3. Plasmodium yoelii 17XL infection up-regulates RANTES, CCR1, CCR3 and CCR5 expression, and induces ultrastructural changes in the cerebellum

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    Singh Shailesh

    2005-12-01

    Full Text Available Abstract Background Malaria afflicts 300–500 million people causing over 1 million deaths globally per year. The immunopathogenesis of malaria is mediated partly by co mplex cellular and immunomodulator interactions involving co-regulators such as cytokines and adhesion molecules. However, the role of chemokines and their receptors in malaria immunopathology remains unclear. RANTES (Regulated on Activation Normal T-Cell Expressed and Secreted is a chemokine involved in the generation of inflammatory infiltrates. Recent studies indicate that the degradation of cell-cell junctions, blood-brain barrier dysfunction, recruitment of leukocytes and Plasmodium-infected erythrocytes into and occlusion of microvessels relevant to malaria pathogenesis are associated with RANTES expression. Additionally, activated lymphocytes, platelets and endothelial cells release large quantities of RANTES, thus suggesting a unique role for RANTES in the generation and maintenance of the malaria-induced inflammatory response. The hypothesis of this study is that RANTES and its corresponding receptors (CCR1, CCR3 and CCR5 modulate malaria immunopathogenesis. A murine malaria model was utilized to evaluate the role of this chemokine and its receptors in malaria. Methods The alterations in immunomodulator gene expression in brains of Plasmodium yoelii 17XL-infected mice was analysed using cDNA microarray screening, followed by a temporal comparison of mRNA and protein expression of RANTES and its corresponding receptors by qRT-PCR and Western blot analysis, respectively. Plasma RANTES levels was determined by ELISA and ultrastructural studies of brain sections from infected and uninfected mice was conducted. Results RANTES (p Conclusion The upregulation of RANTES, CCR1, CCR3, and CCR5 mRNA, and RANTES protein mediate inflammation and cellular degradation in the cerebellum during P. yoelii 17XL malaria.

  4. Targeted disruption of py235ebp-1: invasion of erythrocytes by Plasmodium yoelii using an alternative Py235 erythrocyte binding protein.

    Directory of Open Access Journals (Sweden)

    Solabomi A Ogun

    2011-02-01

    Full Text Available Plasmodium yoelii YM asexual blood stage parasites express multiple members of the py235 gene family, part of the super-family of genes including those coding for Plasmodium vivax reticulocyte binding proteins and Plasmodium falciparum RH proteins. We previously identified a Py235 erythrocyte binding protein (Py235EBP-1, encoded by the PY01365 gene that is recognized by protective mAb 25.77. Proteins recognized by a second protective mAb 25.37 have been identified by mass spectrometry and are encoded by two genes, PY01185 and PY05995/PY03534. We deleted the PY01365 gene and examined the phenotype. The expression of the members of the py235 family in both the WT and gene deletion parasites was measured by quantitative RT-PCR and RNA-Seq. py235ebp-1 expression was undetectable in the knockout parasite, but transcription of other members of the family was essentially unaffected. The knockout parasites continued to react with mAb 25.77; and the 25.77-binding proteins in these parasites were the PY01185 and PY05995/PY03534 products. The PY01185 product was also identified as erythrocyte binding. There was no clear change in erythrocyte invasion profile suggesting that the PY01185 gene product (designated PY235EBP-2 is able to fulfill the role of EBP-1 by serving as an invasion ligand although the molecular details of its interaction with erythrocytes have not been examined. The PY01365, PY01185, and PY05995/PY03534 genes are part of a distinct subset of the py235 family. In P. falciparum, the RH protein genes are under epigenetic control and expression correlates with binding to distinct erythrocyte receptors and specific invasion pathways, whereas in P. yoelii YM all the genes are expressed and deletion of one does not result in upregulation of another. We propose that simultaneous expression of multiple Py235 ligands enables invasion of a wide range of host erythrocytes even in the presence of antibodies to one or more of the proteins and that this

  5. Targeted disruption of py235ebp-1: Invasion of erythrocytes by Plasmodium yoelii using an alternative py235 erythrocyte binding protein

    KAUST Repository

    Ogun, Solabomi A.

    2011-02-17

    Plasmodium yoelii YM asexual blood stage parasites express multiple members of the py235 gene family, part of the super-family of genes including those coding for Plasmodium vivax reticulocyte binding proteins and Plasmodium falciparum RH proteins. We previously identified a Py235 erythrocyte binding protein (Py235EBP-1, encoded by the PY01365 gene) that is recognized by protective mAb 25.77. Proteins recognized by a second protective mAb 25.37 have been identified by mass spectrometry and are encoded by two genes, PY01185 and PY05995/PY03534. We deleted the PY01365 gene and examined the phenotype. The expression of the members of the py235 family in both the WT and gene deletion parasites was measured by quantitative RT-PCR and RNA-Seq. py235ebp-1 expression was undetectable in the knockout parasite, but transcription of other members of the family was essentially unaffected. The knockout parasites continued to react with mAb 25.77; and the 25.77-binding proteins in these parasites were the PY01185 and PY05995/PY03534 products. The PY01185 product was also identified as erythrocyte binding. There was no clear change in erythrocyte invasion profile suggesting that the PY01185 gene product (designated PY235EBP-2) is able to fulfill the role of EBP-1 by serving as an invasion ligand although the molecular details of its interaction with erythrocytes have not been examined. The PY01365, PY01185, and PY05995/PY03534 genes are part of a distinct subset of the py235 family. In P. falciparum, the RH protein genes are under epigenetic control and expression correlates with binding to distinct erythrocyte receptors and specific invasion pathways, whereas in P. yoelii YM all the genes are expressed and deletion of one does not result in upregulation of another. We propose that simultaneous expression of multiple Py235 ligands enables invasion of a wide range of host erythrocytes even in the presence of antibodies to one or more of the proteins and that this functional

  6. Targeted disruption of py235ebp-1: invasion of erythrocytes by Plasmodium yoelii using an alternative Py235 erythrocyte binding protein.

    Science.gov (United States)

    Ogun, Solabomi A; Tewari, Rita; Otto, Thomas D; Howell, Steven A; Knuepfer, Ellen; Cunningham, Deirdre A; Xu, Zhengyao; Pain, Arnab; Holder, Anthony A

    2011-02-01

    Plasmodium yoelii YM asexual blood stage parasites express multiple members of the py235 gene family, part of the super-family of genes including those coding for Plasmodium vivax reticulocyte binding proteins and Plasmodium falciparum RH proteins. We previously identified a Py235 erythrocyte binding protein (Py235EBP-1, encoded by the PY01365 gene) that is recognized by protective mAb 25.77. Proteins recognized by a second protective mAb 25.37 have been identified by mass spectrometry and are encoded by two genes, PY01185 and PY05995/PY03534. We deleted the PY01365 gene and examined the phenotype. The expression of the members of the py235 family in both the WT and gene deletion parasites was measured by quantitative RT-PCR and RNA-Seq. py235ebp-1 expression was undetectable in the knockout parasite, but transcription of other members of the family was essentially unaffected. The knockout parasites continued to react with mAb 25.77; and the 25.77-binding proteins in these parasites were the PY01185 and PY05995/PY03534 products. The PY01185 product was also identified as erythrocyte binding. There was no clear change in erythrocyte invasion profile suggesting that the PY01185 gene product (designated PY235EBP-2) is able to fulfill the role of EBP-1 by serving as an invasion ligand although the molecular details of its interaction with erythrocytes have not been examined. The PY01365, PY01185, and PY05995/PY03534 genes are part of a distinct subset of the py235 family. In P. falciparum, the RH protein genes are under epigenetic control and expression correlates with binding to distinct erythrocyte receptors and specific invasion pathways, whereas in P. yoelii YM all the genes are expressed and deletion of one does not result in upregulation of another. We propose that simultaneous expression of multiple Py235 ligands enables invasion of a wide range of host erythrocytes even in the presence of antibodies to one or more of the proteins and that this functional

  7. IL-10在Plasmodium yoelii 17XL和Plasmodium chabaud AS疟原虫混合感染宿主病理损伤中的作用研究%The Role of IL-10 on the Host Pathological Injury in DBA/2 Mice Mixed Infection with Plasmodium yoelii 17XL and Plasmodium chabaudi AS

    Institute of Scientific and Technical Information of China (English)

    陈光; 曹雅明; 刘蕾; 蔡连顺; 毕胜; 苏菊香; 代月

    2013-01-01

    为探讨IL-10在致死型约氏疟原虫(Plasmodium yoelii 17XL,P.y17XL)和夏氏疟原虫(Plasmodium chabaudi AS,P.cAS)混合感染宿主病理损伤中的作用,用P.y17XL、P.cAS和P.y17XL+P.cAS分别感染DBA/2小鼠,计数红细胞感染率;感染后第3、5、8、10、12和19天分别尾静脉取血,肝素抗凝后短暂离心,采用高纯度DNA提取试剂盒抽提DNA,实时定量PCR检测虫负荷水平;感染后第0、1、3、5、8、10、12和15天制备脾细胞悬液,ELISA检测脾细胞培养上清中IL-10水平.实验结果发现,P.y17XL单独感染和混合感染小鼠IL-10水平在感染后第5天和第8天分别达峰值,随后开始下降至正常水平,小鼠虫血症均达中等水平,存活率100%;相比P.cAS感染小鼠IL-10在感染后第3天突然出现高水平升高并且维持时间较长;于感染后第8天达峰值,是同天P.y17XL单独感染和混合感染小鼠IL-10水平的2倍,虫血症水平较高,小鼠全部死亡.同时实时定量PCR结果发现,混合感染小鼠,于感染后3~ 12 d P.y17XL增殖占优势,而感染后15 ~ 19 d则P.cAS增殖处于优势状态.表明以IL-10为核心的免疫调节网络与疟疾感染过程中病理损伤密切相关.同时提示混合感染小鼠应答模式与P.y17XL感染小鼠的应答模式相同.%In order to investigate the role of IL-10 on the host pathological injury mixed infection with lethal Plasmodium yoelii 17XL (P. y17XL) and Plasmodium chabaudi AS (P. cAS) , DBA/2 mice were infected with P. y17XL, P. cAS, or P. y17XL + P. cAS respectively, and counted the infection rate of erythrocytes for each group of mice. Para-sitemia and mortality were monitored daily. Tail blood collected at different time points was anti-coagulated by heparin on day 3, 5, 8, 10, 12 and 19 post infection (PI) and cenlrifuged briefly for DNA extraction using a high pure blood genome DNA extraction kit, real-lime quantitative (RTQ) PCR for determining the level of parasite burden. On day 0, 1

  8. Concurrent infection of Japanese encephalitis and mixed plasmodium infection

    Directory of Open Access Journals (Sweden)

    Girish Chandra Bhatt

    2012-01-01

    Full Text Available Japanese encephalitis (JE and malaria would coexist in the areas where both illnesses are endemic with overlapping clinical pictures, especially in a case of febrile encephalopathy with hepatosplenomegaly. However, there are no published data till date showing concurrent infection of these two agents despite both diseases being coendemic in many areas. We report a case of concurrent infection of JE and mixed plasmodium infection, where the case, initially diagnosed as cerebral malaria did not improve on antimalarials and alternative diagnosis of JEV encephalitis was thought which was confirmed by a serological test. To the best of our knowledge, this is the first case report of concurrent Japanese encephalitis with mixed plasmodium infection. We report a case of 3-year-old male child, who presented with febrile encephalopathy with hepatosplenomegaly. Based on a rapid diagnostic test and peripheral smear examination, a diagnosis of mixed P.Vivax and P.falciparum infection was made and the patient was treated with quinine and doxycycline. However, besides giving antimalarials the patient did not improve and an alternative diagnosis of JE was considered as the patient was from the endemic zone of Japanese encephalitis. Cerebrospinal fluid (CSF of the patient was sent for a virological study which came out to be positive for JE IgM in CSF, which is confirmatory of JE infection. In a patient with febrile encephalopathy with hepatosplenomegaly especially in areas coendemic for JE and malaria, the possibility of mixed infection should be kept in mind.

  9. Assessment of real-time method to detect liver parasite burden under different experimental conditions in mice infected with Plasmodium yoelii sporozoites.

    Science.gov (United States)

    Siddiqui, Arif Jamal; Bhardwaj, Jyoti; Goyal, Manish; Prakash, Kirtika; Soni, Awakash; Tiwari, Vishvanath; Puri, Sunil K

    2015-12-01

    Use of highly specific, sensitive and quantitative Real-Time PCR (qRT-PCR) based methods greatly facilitate the monitoring of experimental drug intervention and vaccination efficacy targeting liver stage malaria parasite. Here, in this study we have used qRT-PCR to detect the growing liver stage parasites following inoculation of Plasmodium yoelii sporozoite. Route of sporozoite administration and size of the sporozoite inoculums are two major determinants that affect the liver stage parasite load and therefore its detection and quantification. Thus, these factors need to be addressed to determine the accuracy of detection and quantification of Real-Time PCR method. Furthermore, applicability of quantitative RT-PCR system needs to be confirmed by analyzing the effect of different antimalarials on liver stage parasite burden. We have observed that parasite burden in mice infected via intravenous route was higher compared to that in subcutaneous, intradermal and intraperitoneal route infected mice. Moreover, this method detected liver stage parasite load with as low as 50 sporozoites. The inhibition studies with primaquine and atovaquone revealed inhibition of liver stage parasite and well correlated with patency and course of blood stage infection. This study characterized the simplicity, accuracy, and quantitative analysis of liver stage parasite development by real time PCR under different experimental conditions. Use of real time PCR method greatly improves the reproducibility and applicability to estimate the efficacy and potency of vaccine or drug candidates targeting liver stage parasite.

  10. Possibility of false-positive detection for sporozoites in mosquitos (Diptera: Culicidae) by nested polymerase chain reaction using Plasmodium yoelii genomic DNA.

    Science.gov (United States)

    Tsuzuki, A; Toma, T; Miyagi, I; Toma, H; Arakawa, T; Sato, Y; Kobayashi, J; Mugissa, M F

    2001-06-01

    Anopheles stephensi Liston and An. saperoi Bohart and Ingram infected with the rodent malaria parasite Plasmodium yoelii nigeriense. They were examined 12 and 19 days after blood feeding for sporozoites in head with anterior thorax (HT) and oocysts in abdomen with posterior thorax (AB) by light microscopy and by the nested polymerase chain reaction (nested PCR-based on the amplification of the sequences of the small subunit ribosomal RNA gene). The detection rate of parasite DNA by nested PCR in HT samples 12 days after blood feeding was similar to that by microscopic method. However, in HT samples 19 days after blood feeding, the rate by the PCR method was higher than that by the microscopic method. The incidence of sporozoites in salivary glands of infected mosquitos for 12 days after blood sucking was examined by the PCR method. Parasite DNA in HT of Aedes albopictus Skuse (a non vector for the rodent malaria) as well as An. stephensi and An. saperoi was detected for up to 4 days after feeding on mouse with the rodent malaria parasites. The results indicate that when the PCR method is used for detection of sporozoites of human malaria in mosquitos collected in the field, there are possibilities of including false-positive data for mosquitos that have just or recently fed on human blood infected with malaria (erythrocytic form).

  11. Structural determination of functional units of the nucleotide binding domain (NBD94 of the reticulocyte binding protein Py235 of Plasmodium yoelii.

    Directory of Open Access Journals (Sweden)

    Ardina Grüber

    Full Text Available BACKGROUND: Invasion of the red blood cells (RBC by the merozoite of malaria parasites involves a large number of receptor ligand interactions. The reticulocyte binding protein homologue family (RH plays an important role in erythrocyte recognition as well as virulence. Recently, it has been shown that members of RH in addition to receptor binding may also have a role as ATP/ADP sensor. A 94 kDa region named Nucleotide-Binding Domain 94 (NBD94 of Plasmodium yoelii YM, representative of the putative nucleotide binding region of RH, has been demonstrated to bind ATP and ADP selectively. Binding of ATP or ADP induced nucleotide-dependent structural changes in the C-terminal hinge-region of NBD94, and directly impacted on the RBC binding ability of RH. METHODOLOGY/PRINCIPAL FINDINGS: In order to find the smallest structural unit, able to bind nucleotides, and its coupling module, the hinge region, three truncated domains of NBD94 have been generated, termed NBD94(444-547, NBD94(566-663 and NBD94(674-793, respectively. Using fluorescence correlation spectroscopy NBD94(444-547 has been identified to form the smallest nucleotide binding segment, sensitive for ATP and ADP, which became inhibited by 4-Chloro-7-nitrobenzofurazan. The shape of NBD94(444-547 in solution was calculated from small-angle X-ray scattering data, revealing an elongated molecule, comprised of two globular domains, connected by a spiral segment of about 73.1 A in length. The high quality of the constructs, forming the hinge-region, NBD94(566-663 and NBD94(674-793 enabled to determine the first crystallographic and solution structure, respectively. The crystal structure of NBD94(566-663 consists of two helices with 97.8 A and 48.6 A in length, linked by a loop. By comparison, the low resolution structure of NBD94(674-793 in solution represents a chair-like shape with three architectural segments. CONCLUSIONS: These structures give the first insight into how nucleotide binding

  12. 鼠疟模型作为恶性疟原虫多表位 疫苗保护性的探索试验%PRELIMINARY STUDIES ON MOUSE PLASMODIUM YOELII MODEL FOR THE EVALUATION OF A MULTI-EPITOPE VACCINE CANDIDATE OF PLASMODIUM FALCIPARUM

    Institute of Scientific and Technical Information of China (English)

    董文其; 毕惠祥; 李明; 曲利芝

    2001-01-01

    To find a suitable animal model for the vaccine assessment of Plasmodium falciparum,Plasmodium yoelii and Plasmodium berghei of mouse were used to evaluate the protection for a multi-epitope vaccine candidate of Plasmodium falciparum. Results showed that mice of the group firstly immunized with the protein expressed in E.coli,then boosted with the recombinant vaccinia virus from the same epitopes survived longer than that of groups immunized with the wild vaccinia virus or the blank control (P<0.01).This indicates that Plasmodium yoelii of mouse could be used as a protective model for the evaluation of multi-epitope vaccine candidate of Plasmodium falciparum.%目的:为寻找恶性疟原虫基因工程多表位疫苗保护性评价的模型动物,利用小鼠约氏疟原虫(Plasmodium yoelii)及小鼠伯氏疟原虫(Plasmodium berghei)模型对本实验室构建的恶性疟原虫(Plasmodium falciparum)多阶段、多表位基因工程候选疫苗进行了体内保护性及免疫模式探索试验。结果在约氏疟原虫模型,先用该疫苗基因的大肠杆菌表达蛋白免疫,后用含同一基因的重组痘苗病毒加强免疫组,与野生型痘苗病毒免疫组及空白对照组相比,小鼠的死亡时间延长(P<0.01)。结果初步显示,约氏疟原虫鼠疟模型可用作该基因工程多表位恶性疟原虫候选疫苗的保护性评价。

  13. Counter-regulatory anti-parasite cytokine responses during concurrent Plasmodium yoelii and intestinal helminth infections in mice

    Science.gov (United States)

    Malaria and helminth infections are two of the most prevalent parasitic diseases in tropical areas. While concomitant infection is common, mechanisms contributing to altered disease outcomes during co-infection remain poorly defined. We have previously reported exacerbation of normally non-lethal ...

  14. 脂多糖对约氏疟原虫感染DBA/2小鼠感染早期的免疫调节作用%Regulatory effect on lipopolysaccharide for lethal Plasmodium yoelii infection in early stage

    Institute of Scientific and Technical Information of China (English)

    李莹; 刘军; 潘艳艳; 王各各; 延娟; 郑丽; 冯辉; 曹雅明

    2011-01-01

    目的 本文主要探讨脂多糖(LPS)在致死型约氏疟原虫(Plasmodium yoelii 17×L,Py17×L)感染早期的调节作用.方法 6~8 w、雌性DBA/2小鼠,随机分为实验组和对照组,经腹腔接种1×106 Py17XL寄生的红细胞.实验组于感染后d2静脉给予LPS(25 μg/只).动态观察两组小鼠的原虫血症水平,小鼠脾脏树突亚群及其表面TLR4和活化T细胞的表达水平.结果 (1)两组小鼠于感染后约d15均自愈,LPS处理组小鼠的原虫血症水平在感染后d5-8显著低于对照组;(2)与对照组相比,在感染后d3和d5,LPS处理组小鼠脾脏DCs亚群表达水平显著升高,在感染后d3,TLR4表达水平显著升高.在感染后d5,LPS处理组小鼠脾脏细胞培养初始活化T表达水平显著升高.结论在Py17×L感染早期,LPS可通过激活TLR4强化DC成熟进一步强化Th1免疫应答反应,降低原虫血症,这将为疫苗的开发提供新的靶点.%This paper discusses the immune regulatory mechanism of the TLR4 agonist-lipopo in 6 to 8 weeks lysaccha-ride (LPS) in the lethal form of Plasmodium yoelii infection in early stage. Female DBA/2 mice were randomly divided into experimental and control groups, intraperitoneally inoculating 1×106 Plasmodium yoelii 17×L(Pyl7×L) parasitized red blood cells. The experimental group was given LPS (25μg/once) intravenously after infection day 2. Parasitemia were dynamicly observed during the whole infection course. In infected day 0, day 3, and day 5, the number of changes of dendritic cell subsets, dendritic cell surface TLR4, and activation on the effect of T cells in the spleen were detected by flow cytometry (FACS). Results demonstrated that the level of parasitemia in LPS treatment mice after infection day 5 to day 8 was significantly lower than that in the control group; on day 3 and day 5 post infection, compared with the control group, the number of CDllc+CDllb+ DCs and CDllc+CD45R/B220"1" DCs subsets in the spleen in LPS treated mouse were

  15. Licochalcone A, a new antimalarial agent, inhibits in vitro growth of the human malaria parasite Plasmodium falciparum and protects mice from em>P. yoelii infection

    DEFF Research Database (Denmark)

    Chen, M; Theander, T G; Christensen, S B;

    1994-01-01

    Licochalcone A, isolated from Chinese licorice roots, inhibited the in vitro growth of both chloroquine-susceptible (3D7) and chloroquine-resistant (Dd2) Plasmodium falciparum strains in a [3H]hypoxanthine uptake assay. The growth inhibition of the chloroquine-resistant strain by licochalcone A w...

  16. Effects of Low Dose of Ketotifen and Chloroquine Combination on the Ultrastructure of Chloroquine Resistant Strain of Plasmodium Yoelii%低剂量氯喹和酮替酚联合作用下疟原虫的超微结构研究

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    46 inbred NIH mice were infected by chloroquine resistant strain of Plasmodium yoelii. The ultrastructure changes were observed under the administration of ketotifen(10mg· kg- 1· d- 1 ) and chloroquine( 10mg. kg-1 · d- 1 ) combination and one after another respectively. The effect of taking ketotifen and chloroquine combination showed that parasites died rapidly with a few of intermittent membranes and vacuoles. The effect of taking two kinds of drugs one after another showed that there were exceedingly rich membranes, concentric arrangement structures similar to rough endo-reticulum and conspiciously blocking of the formation of food vacuoles.

  17. The dangers of accepting a single diagnosis: case report of concurrent Plasmodium knowlesi malaria and dengue infection.

    Science.gov (United States)

    Chong, Soon Eu; Mohamad Zaini, Rhendra Hardy; Suraiya, Siti; Lee, Kok Tong; Lim, Jo Anne

    2017-01-03

    Dengue and malaria are two common, mosquito-borne infections, which may lead to mortality if not managed properly. Concurrent infections of dengue and malaria are rare due to the different habitats of its vectors and activities of different carrier mosquitoes. The first case reported was in 2005. Since then, several concurrent infections have been reported between the dengue virus (DENV) and the malaria protozoans, Plasmodium falciparum and Plasmodium vivax. Symptoms of each infection may be masked by a simultaneous second infection, resulting in late treatment and severe complications. Plasmodium knowlesi is also a common cause of malaria in Malaysia with one of the highest rates of mortality. This report is one of the earliest in literature of concomitant infection between DENV and P. knowlesi in which a delay in diagnosis had placed a patient in a life-threatening situation. A 59-year old man staying near the Belum-Temengor rainforest at the Malaysia-Thailand border was admitted with fever for 6 days, with respiratory distress. His non-structural protein 1 antigen and Anti-DENV Immunoglobulin M tests were positive. He was treated for severe dengue with compensated shock. Treating the dengue had so distracted the clinicians that a blood film for the malaria parasite was not done. Despite aggressive supportive treatment in the intensive care unit (ICU), the patient had unresolved acidosis as well as multi-organ failure involving respiratory, renal, liver, and haematological systems. It was due to the presentation of shivering in the ICU, that a blood film was done on the second day that revealed the presence of P. knowlesi with a parasite count of 520,000/μL. The patient was subsequently treated with artesunate-doxycycline and made a good recovery after nine days in ICU. This case contributes to the body of literature on co-infection between DENV and P. knowlesi and highlights the clinical consequences, which can be severe. Awareness should be raised among

  18. Toll样受体在约氏疟原虫感染早期树突状细胞应答中的作用地位%Role of Toll-like receptor in the dendritic cell response during early Plasmodium yoelii infection

    Institute of Scientific and Technical Information of China (English)

    郑伟; 刘军; 韩路; 冯辉; 孟红蕊; 曹雅明

    2009-01-01

    目的 探讨致死型约氏疟原虫(Plasmodium yoelii 17XL,P.y17XL)感染早期,Toll样受体(Toll like receptor,TLR)在树突状细胞(dendritic cells, DCs)活化中的作用地位.方法 用P.y 17XL感染易感的BALB/c和抵抗的DBA/2小鼠,计数红细胞感染率;制备感染前和感染后第3d、5d小鼠脾细胞悬液,采用流式细胞分析技术检测两种小鼠感染不同时间脾细胞悬液中细胞内表达TLR9(Toll like receptor 9,TLR9)的DCs和细胞表面表达TLR4(Toll like receptor 4,TLR4)的DCs的百分含量.结果 两种小鼠脾DCs细胞内TLR9的表达水平均于感染后第3d开始明显升高(P<0.01),在第5d达到最高水平(P<0.01),但两种小鼠相比无统计学意义.同时,两种小鼠DCs表面TLR4的表达水平均未见明显变化.结论 在P.y 17XL感染早期,TLR9可能是介导DCs活化的模式识别受体.%To investigate the role of Toll like receptor (TLR) in the activation of dendritic cells (DC) during early Plasmodium yoelii infection of the lethal strain 17XL (P.y 17XL), susceptible BALB/c and resistant DBA/2 mice were infected by i.p.injection of the P.y l7XL-parasitized erythrocytes, and the parasitemia of individua1 mice was monitored by the microscopic examination of blood smear stained with Giemsa.Mice from norma1 and infected groups were sacrificed on 0,3 and 5 days post-infection to collect their spleen cells.And the expressions of TLR-9 and TLR-4 on the cell surface of DCs in spenonocytes of these two strains of mice were assayed by applying flow cytometry to quantitatively analyze the percentages of CD11c+TLR9+ DCs and CD11c+TLR4+ DCs. It was found that the population of CD11c+DCs expressing TLR9 was significantly increased on day 3 and peaked on 5 p.i. in BALB/c (P<0.01) and DBA/2 mice(P<0.01). However, there was no statistical significance between these two strains of mice. Meanwhile, there was no change on the population of CD11c+ DCs expressing TLR4 in BALB/c and DBA/2 mice. These results indicate

  19. Concurrence of Plasmodium falciparum dhfr and crt mutations in northern Ghana

    Directory of Open Access Journals (Sweden)

    Otchwemah Rowland N

    2005-09-01

    Full Text Available Abstract Background Both chloroquine (CQ and sulfadoxine-pyrimethamine (SP are failing drugs in much of sub-Saharan Africa. Previous findings suggest an association between resistance to CQ and to SP in vivo, in vitro, and on the molecular level. Methods In 126 Ghanaian children with uncomplicated malaria, associations between mutations conferring resistance in the Plasmodium falciparum dihydrofolate reductase (dhfr; SP and chloroquine resistance transporter (crt; CQ genes, concentrations of residual antimalarial drugs, and gametocyte carriage were examined. Results Mutant dhfr alleles and the CQ-resistance allele crt T76 were strongly associated with each other. Isolates exhibiting the dhfr triple mutation seven times more likely also contained crt T76 parasites as compared to isolates without the dhfr triple variant (P = 0.0001. Moreover, both, isolates with the dhfr triple mutation (adjusted OR, 3.2 (95%CI, 1.0–10.4 and with crt T76 (adjusted OR, 14.5 (1.4–150.8 were associated with an increased likelihood of pre-treatment gametocytaemia. However, crt T76 did not correlate with gametocytaemia following SP treatment and no selection of crt T76 in SP treatment failure isolates was observed. Conclusion These results confirm an association between CQ and SP resistance markers in isolates from northern Ghana. This could indicate accelerated development of resistance to SP if CQ resistance is already present, or vice versa. Considering the enhanced transmission potential as reflected by the increased proportion of isolates containing gametocytes when resistant parasites are present, co-resistance can be expected to spread in this area. However, the underlying mechanism leading to this constellation remains obscure.

  20. Co-infection restrains Litomosoides sigmodontis filarial load and plasmodial P. yoelii but not P. chabaudi parasitaemia in mice

    Directory of Open Access Journals (Sweden)

    Karadjian Gregory

    2014-01-01

    Full Text Available Infection with multiple parasite species is clearly the norm rather than the exception, in animals as well as in humans. Filarial nematodes and Plasmodium spp. are important parasites in human public health and they are often co-endemic. Interactions between these parasites are complex. The mechanisms underlying the modulation of both the course of malaria and the outcome of filarial infection are poorly understood. Despite increasing activity in recent years, studies comparing co- and mono-infections are very much in their infancy and results are contradictory at first sight. In this study we performed controlled and simultaneous co-infections of BALB/c mice with Litomosoides sigmodontis filaria and with Plasmodium spp. (Plasmodium yoelii 17 XNL or Plasmodium chabaudi 864VD. An analysis of pathological lesions in the kidneys and lungs and a parasitological study were conducted at different times of infection. Whatever the plasmodial species, the filarial recovery rate was strongly decreased. The peak of parasitaemia in the plasmodial infection was decreased in the course of P. yoelii infection but not in that of P. chabaudi. Regarding pathological lesions, L. sigmodontis can reverse lesions in the kidneys due to the presence of both Plasmodium species but does not modify the course of pulmonary lesions. The filarial infection induces granulomas in the lungs.

  1. Lentinan treatment of Plasmodium yoelii-infected mice induces ...

    African Journals Online (AJOL)

    Yomi

    2012-01-31

    Jan 31, 2012 ... intraperitoneal (i.p.) injection of 1 × 106 red blood cells containing Py17XL, and the ... through up-regulation of Bax and down-regulation of Bcl-2, and which ... pensions were centrifuged at room temperature at 350 ×g for 10.

  2. HIV nonnucleoside reverse transcriptase inhibitors and trimethoprim-sulfamethoxazole inhibit plasmodium liver stages.

    Science.gov (United States)

    Hobbs, Charlotte V; Voza, Tatiana; De La Vega, Patricia; Vanvliet, Jillian; Conteh, Solomon; Penzak, Scott R; Fay, Michael P; Anders, Nicole; Ilmet, Tiina; Li, Yonghua; Borkowsky, William; Krzych, Urszula; Duffy, Patrick E; Sinnis, Photini

    2012-12-01

    Although nonnucleoside reverse transcriptase inhibitors (NNRTIs) are usually part of first-line treatment regimens for human immunodeficiency virus (HIV), their activity on Plasmodium liver stages remains unexplored. Additionally, trimethoprim-sulfamethoxazole (TMP-SMX), used for opportunistic infection prophylaxis in HIV-exposed infants and HIV-infected patients, reduces clinical episodes of malaria; however, TMP-SMX effect on Plasmodium liver stages requires further study. We characterized NNRTI and TMP-SMX effects on Plasmodium liver stages in vivo using Plasmodium yoelii. On the basis of these results, we conducted in vitro studies assessing TMP-SMX effects on the rodent parasites P. yoelii and Plasmodium berghei and on the human malaria parasite Plasmodium falciparum. Our data showed NNRTI treatment modestly reduced P. yoelii liver stage parasite burden and minimally extended prepatent period. TMP-SMX administration significantly reduced liver stage parasite burden, preventing development of patent parasitemia in vivo. TMP-SMX inhibited development of rodent and P. falciparum liver stage parasites in vitro. NNRTIs modestly affect liver stage Plasmodium parasites, whereas TMP-SMX prevents patent parasitemia. Because drugs that inhibit liver stages target parasites when they are present in lower numbers, these results may have implications for eradication efforts. Understanding HIV drug effects on Plasmodium liver stages will aid in optimizing treatment regimens for HIV-exposed and HIV-infected infected patients in malaria-endemic areas.

  3. Immunization of mice with Plasmodium TCTP delays establishment of Plasmodium infection.

    Science.gov (United States)

    Taylor, K J; Van, T T H; MacDonald, S M; Meshnick, S R; Fernley, R T; Macreadie, I G; Smooker, P M

    2015-01-01

    Translationally controlled tumour protein (TCTP) may play an important role in the establishment or maintenance of parasitemia in a malarial infection. In this study, the potential of TCTP as a malaria vaccine was investigated in two trials. In the initial vaccine trial, Plasmodium falciparum TCTP (PfTCTP) was expressed in Saccharomyces cerevisiae and used to immunize BALB/c mice. Following challenge with Plasmodium yoelii YM, parasitemia was significantly reduced during the early stages of infection. In the second vaccine trial, the TCTP from P. yoelii and P. berghei was expressed in Escherichia coli and used in several mouse malaria models. A significant reduction in parasitemia in the early stages of infection was observed in BALB/c mice challenged with P. yoelii YM. A significantly reduced parasitemia at each day leading up to a delayed and reduced peak parasitemia was also observed in BALB/c mice challenged with the nonlethal Plasmodium chabaudi (P.c.) chabaudi AS. These results suggest that TCTP has an important role for parasite establishment and may be important for pathogenesis. © 2014 John Wiley & Sons Ltd.

  4. High Mobility Group Protein HMGB2 Is a Critical Regulator of Plasmodium Oocyst Development*S⃞

    OpenAIRE

    Gissot, Mathieu; Ting, Li-Min; Daly, Thomas M.; Bergman, Lawrence W.; Sinnis, Photini; Kim, Kami

    2008-01-01

    The sexual cycle of Plasmodium is required for transmission of malaria from mosquitoes to mammals, but how parasites induce the expression of genes required for the sexual stages is not known. We disrupted the Plasmodium yoelii gene encoding high mobility group nuclear factor hmgb2, which encodes a DNA-binding protein potentially implicated in transcriptional regulation of malaria gene expression. We investigated its function in vivo in the vertebrate and invertebrate ...

  5. Identification of a nonameric H-2Kk-restricted CD8+ cytotoxic T lymphocyte epitope on the Plasmodium falciparum circumsporozoite protein

    DEFF Research Database (Denmark)

    Malik, A; Houghten, R; Corradin, G

    1995-01-01

    Class I-restricted CD8+ cytotoxic T lymphocytes (CTL) against the circumsporozoite protein (CSP) protect mice against the rodent malaria parasite, Plasmodium yoelii, and vaccines designed to produce protective CTL against the P. falciparum CSP (PfCSP) are under development. Humans and B10.BR (H-2k...

  6. Evaluation of Purine Salvage as a Chemotherapeutic Target in the Plasmodium yoelii Rodent Model

    Science.gov (United States)

    2008-03-01

    F., Eling, W., Konings, R. N., and Stunnenberg, H. G. (1999) Mol Cell Biol 19, 967-978 13. Gissot, M., Briquet , S., Refour, P., Boschet, C., and...Gutterson, N., and Reuber, T. L. (2004) Curr Opin Plant Biol 7, 465-471 16. Briquet , S., Boschet, C., Gissot, M., Tissandie, E., Sevilla, E., Franetich, J

  7. A Rapid Method for Screening Antibodies to Plasmodium yoelii Liver Stages by Immunofluorescence

    Science.gov (United States)

    1987-12-01

    elements were not generally seen. tigotes (Chapman et al., 1979, Revista do Insti- Rather, toxicity particularly affected the liver, tuto de Medicina...Hamilton, Ontario, Canada L8N 3Z5; nd A. DBefus. University of Calgary, Health Sciences Center. 3330 Hospital Drive, NW, Calgary, Alberta. C ada T2 4N1

  8. 2-Hexadecynoic Acid Inhibits Plasmodial FAS-II Enzymes and Arrest Erythrocytic and Liver Stage Plasmodium Infections

    OpenAIRE

    Tasdemir, Deniz; Sanabria, David; Lauinger, Ina L.; Tarun, Alice; Herman, Rob; Perozzo, Remo; Zloh, Mire; Kappe, Stefan H.; Brun, Reto; Carballeira, Néstor M.

    2010-01-01

    Acetylenic fatty acids are known to display several biological activities, but their antimalarial activity has remained unexplored. In this study, we synthesized the 2-, 5-, 6-, and 9-hexadecynoic acids (HDAs) and evaluated their in vitro activity against erythrocytic (blood) stages of Plasmodium falciparum and liver stages of P. yoelii infections. Since the type II fatty acid biosynthesis pathway (PfFAS-II) has recently been shown to be indispensable for liver stage malaria parasites, the in...

  9. Plasmodium Immunomics

    Science.gov (United States)

    Doolan, Denise L.

    2010-01-01

    The Plasmodium parasite, the causative agent of malaria, is an excellent model for immunomic-based approaches to vaccine development. The Plasmodium parasite has a complex life cycle with multiple stages and stage-specific expression of ~ 5,300 putative proteins. No malaria vaccine has yet been licensed. Many believe that an effective vaccine will need to target several antigens and multiple stages, and will require the generation of both antibody and cellular immune responses. Vaccine efforts to date have been stage-specific and based on only a very limited number of proteins representing Plasmodium parasite life cycle with immune responses implicated in parasite elimination and control. Immunomic approaches which enable the selection of the best possible targets by prioritizing antigens according to clinically relevant criteria may overcome the problem of poorly immunogenic, poorly protective vaccines that has plagued malaria vaccine developers for the past 25 years. Herein, current progress and perspectives regarding Plasmodium immunomics are reviewed. PMID:20816843

  10. Multiplicity of Infection and Disease Severity in Plasmodium vivax

    DEFF Research Database (Denmark)

    Pacheco, M Andreína; Lopez-Perez, Mary; Vallejo, Andrés F

    2016-01-01

    BACKGROUND: Multiplicity of infection (MOI) refers to the average number of distinct parasite genotypes concurrently infecting a patient. Although several studies have reported on MOI and the frequency of multiclonal infections in Plasmodium falciparum, there is limited data on Plasmodium vivax. ...

  11. Marine organism sulfated polysaccharides exhibiting significant antimalarial activity and inhibition of red blood cell invasion by Plasmodium.

    Science.gov (United States)

    Marques, Joana; Vilanova, Eduardo; Mourão, Paulo A S; Fernàndez-Busquets, Xavier

    2016-04-13

    The antimalarial activity of heparin, against which there are no resistances known, has not been therapeutically exploited due to its potent anticoagulating activity. Here, we have explored the antiplasmodial capacity of heparin-like sulfated polysaccharides from the sea cucumbers Ludwigothurea grisea and Isostichopus badionotus, from the red alga Botryocladia occidentalis, and from the marine sponge Desmapsamma anchorata. In vitro experiments demonstrated for most compounds significant inhibition of Plasmodium falciparum growth at low-anticoagulant concentrations. This activity was found to operate through inhibition of erythrocyte invasion by Plasmodium, likely mediated by a coating of the parasite similar to that observed for heparin. In vivo four-day suppressive tests showed that several of the sulfated polysaccharides improved the survival of Plasmodium yoelii-infected mice. In one animal treated with I. badionotus fucan parasitemia was reduced from 10.4% to undetectable levels, and Western blot analysis revealed the presence of antibodies against P. yoelii antigens in its plasma. The retarded invasion mediated by sulfated polysaccharides, and the ensuing prolonged exposure of Plasmodium to the immune system, can be explored for the design of new therapeutic approaches against malaria where heparin-related polysaccharides of low anticoagulating activity could play a dual role as drugs and as potentiators of immune responses.

  12. Marine organism sulfated polysaccharides exhibiting significant antimalarial activity and inhibition of red blood cell invasion by Plasmodium

    Science.gov (United States)

    Marques, Joana; Vilanova, Eduardo; Mourão, Paulo A. S.; Fernàndez-Busquets, Xavier

    2016-01-01

    The antimalarial activity of heparin, against which there are no resistances known, has not been therapeutically exploited due to its potent anticoagulating activity. Here, we have explored the antiplasmodial capacity of heparin-like sulfated polysaccharides from the sea cucumbers Ludwigothurea grisea and Isostichopus badionotus, from the red alga Botryocladia occidentalis, and from the marine sponge Desmapsamma anchorata. In vitro experiments demonstrated for most compounds significant inhibition of Plasmodium falciparum growth at low-anticoagulant concentrations. This activity was found to operate through inhibition of erythrocyte invasion by Plasmodium, likely mediated by a coating of the parasite similar to that observed for heparin. In vivo four-day suppressive tests showed that several of the sulfated polysaccharides improved the survival of Plasmodium yoelii-infected mice. In one animal treated with I. badionotus fucan parasitemia was reduced from 10.4% to undetectable levels, and Western blot analysis revealed the presence of antibodies against P. yoelii antigens in its plasma. The retarded invasion mediated by sulfated polysaccharides, and the ensuing prolonged exposure of Plasmodium to the immune system, can be explored for the design of new therapeutic approaches against malaria where heparin-related polysaccharides of low anticoagulating activity could play a dual role as drugs and as potentiators of immune responses. PMID:27071342

  13. Attempted isolation of the gene encoding the 21 Kd Plasmodium berghei ookinete transmission blocking antigen from Plasmodium yoelli and Plasmodium vivax

    Directory of Open Access Journals (Sweden)

    G. C. Barker

    1994-01-01

    Full Text Available The 21kD ookinete antigen of Plasmodium berghei (Pbs 21 has been shown to elicit an effective and long lasting transmission blocking immune response in mice. Having cloned and sequenced this antigen (Paton et al. 1993 the sequence was compared to the genes of the same family previously identified in P. falciparum, P. gallinaceum (Kaslow et al. 1989 and P. reichenowi (Lal et al. 1990. Four conserved areas were identified in this comparison, to which degenerate oligonucleotides were designed. PCR amplification and screening of genomic libraries was then carried out using these oligonucleotides. The P. yoelii gene was successfully cloned and a number of novel P. vivax genes identified but the P. vivax homologue of Pbs21 remains elusive.

  14. In vitro alterations do not reflect a requirement for host cell cycle progression during Plasmodium liver stage infection.

    Science.gov (United States)

    Hanson, Kirsten K; March, Sandra; Ng, Shengyong; Bhatia, Sangeeta N; Mota, Maria M

    2015-01-01

    Prior to invading nonreplicative erythrocytes, Plasmodium parasites undergo their first obligate step in the mammalian host inside hepatocytes, where each sporozoite replicates to generate thousands of merozoites. While normally quiescent, hepatocytes retain proliferative capacity and can readily reenter the cell cycle in response to diverse stimuli. Many intracellular pathogens, including protozoan parasites, manipulate the cell cycle progression of their host cells for their own benefit, but it is not known whether the hepatocyte cell cycle plays a role during Plasmodium liver stage infection. Here, we show that Plasmodium parasites can be observed in mitotic hepatoma cells throughout liver stage development, where they initially reduce the likelihood of mitosis and ultimately lead to significant acquisition of a binucleate phenotype. However, hepatoma cells pharmacologically arrested in S phase still support robust and complete Plasmodium liver stage development, which thus does not require cell cycle progression in the infected cell in vitro. Furthermore, murine hepatocytes remain quiescent throughout in vivo infection with either Plasmodium berghei or Plasmodium yoelii, as do Plasmodium falciparum-infected primary human hepatocytes, demonstrating that the rapid and prodigious growth of liver stage parasites is accomplished independent of host hepatocyte cell cycle progression during natural infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  15. A rapid and scalable density gradient purification method for Plasmodium sporozoites

    Directory of Open Access Journals (Sweden)

    Kennedy Mark

    2012-12-01

    Full Text Available Abstract Background Malaria remains a major human health problem, with no licensed vaccine currently available. Malaria infections initiate when infectious Plasmodium sporozoites are transmitted by Anopheline mosquitoes during their blood meal. Investigations of the malaria sporozoite are, therefore, of clear medical importance. However, sporozoites can only be produced in and isolated from mosquitoes, and their isolation results in large amounts of accompanying mosquito debris and contaminating microbes. Methods Here is described a discontinuous density gradient purification method for Plasmodium sporozoites that maintains parasite infectivity in vitro and in vivo and greatly reduces mosquito and microbial contaminants. Results This method provides clear advantages over previous approaches: it is rapid, requires no serum components, and can be scaled to purify >107 sporozoites with minimal operator involvement. Moreover, it can be effectively applied to both human (Plasmodium falciparum, Plasmodium vivax and rodent (Plasmodium yoelii infective species with excellent recovery rates. Conclusions This novel method effectively purifies viable malaria sporozoites by greatly reducing contaminating mosquito debris and microbial burdens associated with parasite isolation. Large-scale preparations of purified sporozoites will allow for enhanced in vitro infections, proteomics, and biochemical characterizations. In conjunction with aseptic mosquito rearing techniques, this purification technique will also support production of live attenuated sporozoites for vaccination.

  16. In silico identification of genetically attenuated vaccine candidate genes for Plasmodium liver stage.

    Science.gov (United States)

    Kumar, Hirdesh; Frischknecht, Friedrich; Mair, Gunnar R; Gomes, James

    2015-12-01

    Genetically attenuated parasites (GAPs) that lack genes essential for the liver stage of the malaria parasite, and therefore cause developmental arrest, have been developed as live vaccines in rodent malaria models and recently been tested in humans. The genes targeted for deletion were often identified by trial and error. Here we present a systematic gene - protein and transcript - expression analyses of several Plasmodium species with the aim to identify candidate genes for the generation of novel GAPs. With a lack of liver stage expression data for human malaria parasites, we used data available for liver stage development of Plasmodium yoelii, a rodent malaria model, to identify proteins expressed in the liver stage but absent from blood stage parasites. An orthology-based search was then employed to identify orthologous proteins in the human malaria parasite Plasmodium falciparum resulting in a total of 310 genes expressed in the liver stage but lacking evidence of protein expression in blood stage parasites. Among these 310 possible GAP candidates, we further studied Plasmodium liver stage proteins by phyletic distribution and functional domain analyses and shortlisted twenty GAP-candidates; these are: fabB/F, fabI, arp, 3 genes encoding subunits of the PDH complex, dnaJ, urm1, rS5, ancp, mcp, arh, gk, lisp2, valS, palm, and four conserved Plasmodium proteins of unknown function. Parasites lacking one or several of these genes might yield new attenuated malaria parasites for experimental vaccination studies.

  17. Temperature alters Plasmodium blocking by Wolbachia

    Science.gov (United States)

    Murdock, Courtney C.; Blanford, Simon; Hughes, Grant L.; Rasgon, Jason L.; Thomas, Matthew B.

    2014-02-01

    Very recently, the Asian malaria vector (Anopheles stephensi) was stably transinfected with the wAlbB strain of Wolbachia, inducing refractoriness to the human malaria parasite Plasmodium falciparum. However, conditions in the field can differ substantially from those in the laboratory. We use the rodent malaria P. yoelii, and somatically transinfected An. stephensi as a model system to investigate whether the transmission blocking potential of wAlbB is likely to be robust across different thermal environments. wAlbB reduced malaria parasite prevalence and oocyst intensity at 28°C. At 24°C there was no effect on prevalence but a marked increase in oocyst intensity. At 20°C, wAlbB had no effect on prevalence or intensity. Additionally, we identified a novel effect of wAlbB that resulted in reduced sporozoite development across temperatures, counterbalancing the oocyst enhancement at 24°C. Our results demonstrate complex effects of temperature on the Wolbachia-malaria interaction, and suggest the impacts of transinfection might vary across diverse environments.

  18. Concurrency engineering

    NARCIS (Netherlands)

    Jesshope, C.; Shafarenko, A.

    2008-01-01

    This is a discussion paper on a very important topic that is about to become mainstream. It deals with the issues of software engineering in concurrent systems. It introduces this topic and illustrates the arguments for a change of perspective. It underlines these arguments with two examples, an

  19. Effects of Low Dose of Ketotifen and Chloroquine Combination on the Ultras tructure of Chloroquine Resistant Strain of Plasmodium Yoelii

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    1 Introduction Thewidespreaddevelopmentofchloroquineresis tant (CR)strainofmalariahasresultedinsearchingforneweffectiveanti malariadrugs[1~ 4 ] .Ananti asthmaandanti malariadrugketotifen (K)hasbeenprovedtoshowstronganti malariaactionbyPanetal[5~ 7] .FurthermoreKhadstrongerreverseeffectonP .yoelii (CR)thanVerapmil[8] .TheultrastructurestudyhasrevealedthattheeffectofK ( 10mg·kg- 1·d- 1)onchloroquine sensitive(CS)strainofP .yoeliiandK ( 4 0mg/kg·d)onP .yoelii (CR)isdifferentfromotheranti malariadrugswiththecha...

  20. Use of a Vaccinia Construct Expressing the Circumsporozoite Protein in the Analysis of Protective Immunity to Plasmodium yoelii

    Science.gov (United States)

    1988-01-01

    Sedegah et al Protection After CD8 T Cell Depletion. We knew that a Mab to repeat #2 protected mice in passive transfer experiments, whereas a second Mab...mechanisms in the protective immunity elicited by inmunization with irradiated sporozoites (3,7,8,9). In an attempt to induce a protective cellular immune...challenge. Although IRRspz immunized mice are not protected by antibodies, we have shown that passive transfer of a monoclonal antibody, NYSI directed

  1. Concurrent Collections

    OpenAIRE

    Zoran Budimlić; Michael Burke; Vincent Cavé; Kathleen Knobe; Geoff Lowney; Ryan Newton; Jens Palsberg; David Peixotto; Vivek Sarkar; Frank Schlimbach; Sağnak Taşırlar

    2010-01-01

    We introduce the Concurrent Collections (CnC) programming model. CnC supports flexible combinations of task and data parallelism while retaining determinism. CnC is implicitly parallel, with the user providing high-level operations along with semantic ordering constraints that together form a CnC graph. We formally describe the execution semantics of CnC and prove that the model guarantees deterministic computation. We evaluate the performance of CnC implementations on several applications an...

  2. The MB2 gene family of Plasmodium species has a unique combination of S1 and GTP-binding domains

    Directory of Open Access Journals (Sweden)

    Ogunjumo Oluwasanmi

    2004-06-01

    Full Text Available Abstract Background Identification and characterization of novel Plasmodium gene families is necessary for developing new anti-malarial therapeutics. The products of the Plasmodium falciparum gene, MB2, were shown previously to have a stage-specific pattern of subcellular localization and proteolytic processing. Results Genes homologous to MB2 were identified in five additional parasite species, P. knowlesi, P. gallinaceum, P. berghei, P. yoelii, and P. chabaudi. Sequence comparisons among the MB2 gene products reveal amino acid conservation of structural features, including putative S1 and GTP-binding domains, and putative signal peptides and nuclear localization signals. Conclusions The combination of domains is unique to this gene family and indicates that MB2 genes comprise a novel family and therefore may be a good target for drug development.

  3. Concurrent Collections

    Directory of Open Access Journals (Sweden)

    Zoran Budimlić

    2010-01-01

    Full Text Available We introduce the Concurrent Collections (CnC programming model. CnC supports flexible combinations of task and data parallelism while retaining determinism. CnC is implicitly parallel, with the user providing high-level operations along with semantic ordering constraints that together form a CnC graph. We formally describe the execution semantics of CnC and prove that the model guarantees deterministic computation. We evaluate the performance of CnC implementations on several applications and show that CnC offers performance and scalability equivalent to or better than that offered by lower-level parallel programming models.

  4. Genetic Characterization of Plasmodium Putative Pantothenate Kinase Genes Reveals Their Essential Role in Malaria Parasite Transmission to the Mosquito.

    Science.gov (United States)

    Hart, Robert J; Cornillot, Emmanuel; Abraham, Amanah; Molina, Emily; Nation, Catherine S; Ben Mamoun, Choukri; Aly, Ahmed S I

    2016-09-20

    The metabolic machinery for the biosynthesis of Coenzyme A (CoA) from exogenous pantothenic acid (Vitamin B5) has long been considered as an excellent target for the development of selective antimicrobials. Earlier studies in the human malaria parasite Plasmodium falciparum have shown that pantothenate analogs interfere with pantothenate phosphorylation and block asexual blood stage development. Although two eukaryotic-type putative pantothenate kinase genes (PanK1 and PanK2) have been identified in all malaria parasite species, their role in the development of Plasmodium life cycle stages remains unknown. Here we report on the genetic characterization of PanK1 and PanK2 in P. yoelii. We show that P. yoelii parasites lacking either PanK1 or PanK2 undergo normal asexual stages development and sexual stages differentiation, however they are severely deficient in ookinete, oocyst and sporozoite formation inside the mosquito vector. Quantitative transcriptional analyses in wild-type and knockout parasites demonstrate an important role for these genes in the regulation of expression of other CoA biosynthesis genes. Together, our data provide the first genetic evidence for the importance of the early steps of pantothenate utilization in the regulation of CoA biosynthesis and malaria parasite transmission to Anopheles mosquitoes.

  5. Genetic Characterization of Plasmodium Putative Pantothenate Kinase Genes Reveals Their Essential Role in Malaria Parasite Transmission to the Mosquito

    Science.gov (United States)

    Hart, Robert J.; Cornillot, Emmanuel; Abraham, Amanah; Molina, Emily; Nation, Catherine S.; Ben Mamoun, Choukri; Aly, Ahmed S. I.

    2016-01-01

    The metabolic machinery for the biosynthesis of Coenzyme A (CoA) from exogenous pantothenic acid (Vitamin B5) has long been considered as an excellent target for the development of selective antimicrobials. Earlier studies in the human malaria parasite Plasmodium falciparum have shown that pantothenate analogs interfere with pantothenate phosphorylation and block asexual blood stage development. Although two eukaryotic-type putative pantothenate kinase genes (PanK1 and PanK2) have been identified in all malaria parasite species, their role in the development of Plasmodium life cycle stages remains unknown. Here we report on the genetic characterization of PanK1 and PanK2 in P. yoelii. We show that P. yoelii parasites lacking either PanK1 or PanK2 undergo normal asexual stages development and sexual stages differentiation, however they are severely deficient in ookinete, oocyst and sporozoite formation inside the mosquito vector. Quantitative transcriptional analyses in wild-type and knockout parasites demonstrate an important role for these genes in the regulation of expression of other CoA biosynthesis genes. Together, our data provide the first genetic evidence for the importance of the early steps of pantothenate utilization in the regulation of CoA biosynthesis and malaria parasite transmission to Anopheles mosquitoes. PMID:27644319

  6. Inflammation-associated alterations to the intestinal microbiota reduce colonization resistance against non-typhoidal Salmonella during concurrent malaria parasite infection.

    Science.gov (United States)

    Mooney, Jason P; Lokken, Kristen L; Byndloss, Mariana X; George, Michael D; Velazquez, Eric M; Faber, Franziska; Butler, Brian P; Walker, Gregory T; Ali, Mohamed M; Potts, Rashaun; Tiffany, Caitlin; Ahmer, Brian M M; Luckhart, Shirley; Tsolis, Renée M

    2015-10-05

    Childhood malaria is a risk factor for disseminated infections with non-typhoidal Salmonella (NTS) in sub-Saharan Africa. While hemolytic anemia and an altered cytokine environment have been implicated in increased susceptibility to NTS, it is not known whether malaria affects resistance to intestinal colonization with NTS. To address this question, we utilized a murine model of co-infection. Infection of mice with Plasmodium yoelii elicited infiltration of inflammatory macrophages and T cells into the intestinal mucosa and increased expression of inflammatory cytokines. These mucosal responses were also observed in germ-free mice, showing that they are independent of the resident microbiota. Remarkably, P. yoelii infection reduced colonization resistance of mice against S. enterica serotype Typhimurium. Further, 16S rRNA sequence analysis of the intestinal microbiota revealed marked changes in the community structure. Shifts in the microbiota increased susceptibility to intestinal colonization by S. Typhimurium, as demonstrated by microbiota reconstitution of germ-free mice. These results show that P. yoelii infection, via alterations to the microbial community in the intestine, decreases resistance to intestinal colonization with NTS. Further they raise the possibility that decreased colonization resistance may synergize with effects of malaria on systemic immunity to increase susceptibility to disseminated NTS infections.

  7. Expression of PD-1/LAG-3 and cytokine production by CD4(+) T cells during infection with Plasmodium parasites.

    Science.gov (United States)

    Doe, Henrietta T; Kimura, Daisuke; Miyakoda, Mana; Kimura, Kazumi; Akbari, Masoud; Yui, Katsuyuki

    2016-02-01

    CD4(+) T cells play critical roles in protection against the blood stage of malarial infection; however, their uncontrolled activation can be harmful to the host. In this study, in which rodent models of Plasmodium parasites were used, the expression of inhibitory receptors on activated CD4(+) T cells and their cytokine production was compared with their expression in a bacterial and another protozoan infection. CD4(+) T cells from mice infected with P. yoelii 17XL, P yoelii 17XNL, P. chabaudi, P. vinckei and P. berghei expressed the inhibitory receptors, PD-1 and LAG-3, as early as 6 days after infection, whereas those from either Listeria monocytogenes- or Leishmania major-infected mice did not. In response to T-cell receptor stimulation, CD4(+) T cells from mice infected with all the pathogens under study produced high concentrations of IFN-γ. IL-2 production was reduced in mice infected with Plasmodium species, but not in those infected with Listeria or Leishmania. In vitro blockade of the interaction between PD-1 and its ligands resulted in increased IFN-γ production in response to Plasmodium antigens, implying that PD-1 expressed on activated CD4(+) T cells actively inhibits T cell immune responses. Studies using Myd88(-/-), Trif(-/-) and Irf3(-/-) mice showed that induction of these CD4(+) T cells and their ability to produce cytokines is largely independent of TLR signaling. These studies suggest that expression of the inhibitory receptors PD-1 and LAG-3 on CD4(+) T cells and their reduced IL-2 production are common characteristic features of Plasmodium infection.

  8. Molecular characterization and phylogenetic analysis of Plasmodium vivax, Plasmodium falciparum, Plasmodium ovale, Plasmodium malariae and Plasmodium cynomolgi

    National Research Council Canada - National Science Library

    Chatterjee, Soumendranath; Mukhopadhyay, Priyanka; Bandyopadhyay, Raktima; Dhal, Paltu; Biswal, Debraj; Bandyopadhyay, Prabir Kumar

    18S ribosomal RNA gene sequences of different species of Plasmodium were aligned and analyzed to determine the molecular diversity among different species of Plasmodium. AT content of P. cynomolgi, P. ovale, P. falciparum, P. vivax and P...

  9. Action of adrenalin on the circulation of the murine Plasmodium developing stages, in different blood compartments

    Directory of Open Access Journals (Sweden)

    Bertani S.

    2004-12-01

    Full Text Available Adrenalin was used to investigate in vivo the circulation of the different stages of rodent Plasmodium present in the blood. A single dose of adrenalin injected to mice infected with P. yoelii resulted immediately in i a diminution of the parasitaemia of approximately 50 % in the peripheral large vessels (estimated in tail blood films, as well as in the capillaries (estimated in smears of blood collected from a fed Anopheles, and ii an increased parasitaemia in blood collected by cardiac puncture from the right heart. The numbers of young stages of P. yoelii in the peripheral blood were initially somewhat reduced but, unexpectedly, midterm trophozoites were preferentially expelled from the peripheral blood into major organs like the heart. With P. vinckei, parasitaemia decreased only when midterm trophozoites predominated, and with P. chabaudi no effect was observed at any time. We propose that midterm trophozoites, by their increased surface area, as compared to rings, and their flexibility which contrasts with the rigid schizonts, are particularly susceptible to haemodynamic perturbations.

  10. [Stain hybridization method with pRepHind probe for the diagnosis of Plasmodium falciparum].

    Science.gov (United States)

    Moleón Borodowsky, I

    1992-01-01

    A study was conducted on the parasitemia detection level and the specificity of the pRepHind DNA probe for diagnosing Plasmodium falciparum by the stain hybridization method. The parasitemia detection level was studied by using dilutions of a P. falciparum in vitro culture, adjusted by direct microscopic examination to 1; 0.1; 0.01; 0.001; 0.0001 and 0.00001% of parasited red cells. Specificity was increased by using DNA extractions from P. Yoelii, P. berghei and human leucocytes. The results showed that the method was able to detect 0.0001% of parasitemia starting from DNA extractions of 100 L infected red cells. The pRepHind probe only detected specifically DNA from P. falciparum. It is concluded that the method is suitable for being used in the diagnosis of infection due to P. falciparum.

  11. Plasmodium falciparum MAEBL is a unique member of the ebl family.

    Science.gov (United States)

    Blair, Peter L; Kappe, Stefan H I; Maciel, Jorge E; Balu, Bharath; Adams, John H

    2002-06-01

    Malaria is one of the deadliest human diseases and efforts to control it have been difficult due to the protozoan parasites' complex biology. Malaria merozoite invasion of erythrocytes is an essential part of blood-stage infections. The invasion process is mediated by numerous parasite molecules, such as EBA-175, a member of the ebl family of erythrocyte binding proteins. We have identified maebl, an ebl paralogue, in Plasmodium falciparum and found it highly conserved with its orthologues in P. yoelii and P. berghei, but distinct from other Plasmodium ebl. Importantly, the putative MAEBL ligand domains are highly conserved and are similar to AMA-1, but not the consensus DBL ligand domains present in all other ebl. In mature merozoites, MAEBL localized with rhoptry proteins (RhopH2, RAP-1), including surface localization with RhopH2, but not microneme proteins (EBA-175, BAEBL). MAEBL appears as proteolytically processed fragments in P. falciparum parasites. The amino cysteine-rich ligand domains were present primarily in culture supernatants, while the carboxyl cysteine-rich domain adjacent to the transmembrane domain was preferentially isolated from Triton X-100 extracted fractions. These data indicate that the primary structure of maebl is highly conserved among Plasmodium species, while its characteristics demonstrate a function unique among the ebl proteins.

  12. Human T cell recognition of the blood stage antigen Plasmodium hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT in acute malaria

    Directory of Open Access Journals (Sweden)

    Woodberry Tonia

    2009-06-01

    Full Text Available Abstract Background The Plasmodium purine salvage enzyme, hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT can protect mice against Plasmodium yoelii pRBC challenge in a T cell-dependent manner and has, therefore, been proposed as a novel vaccine candidate. It is not known whether natural exposure to Plasmodium falciparum stimulates HGXPRT T cell reactivity in humans. Methods PBMC and plasma collected from malaria-exposed Indonesians during infection and 7–28 days after anti-malarial therapy, were assessed for HGXPRT recognition using CFSE proliferation, IFNγ ELISPOT assay and ELISA. Results HGXPRT-specific T cell proliferation was found in 44% of patients during acute infection; in 80% of responders both CD4+ and CD8+ T cell subsets proliferated. Antigen-specific T cell proliferation was largely lost within 28 days of parasite clearance. HGXPRT-specific IFN-γ production was more frequent 28 days after treatment than during acute infection. HGXPRT-specific plasma IgG was undetectable even in individuals exposed to malaria for at least two years. Conclusion The prevalence of acute proliferative and convalescent IFNγ responses to HGXPRT demonstrates cellular immunogenicity in humans. Further studies to determine minimal HGXPRT epitopes, the specificity of responses for Plasmodia and associations with protection are required. Frequent and robust T cell proliferation, high sequence conservation among Plasmodium species and absent IgG responses distinguish HGXPRT from other malaria antigens.

  13. Plasmodium genetic loci linked to host cytokine and chemokine responses.

    Science.gov (United States)

    Pattaradilokrat, S; Li, J; Wu, J; Qi, Y; Eastman, R T; Zilversmit, M; Nair, S C; Huaman, M C; Quinones, M; Jiang, H; Li, N; Zhu, J; Zhao, K; Kaneko, O; Long, C A; Su, X-z

    2014-01-01

    Both host and parasite factors contribute to disease severity of malaria infection; however, the molecular mechanisms responsible for the disease and the host-parasite interactions involved remain largely unresolved. To investigate the effects of parasite factors on host immune responses and pathogenesis, we measured levels of plasma cytokines/chemokines (CCs) and growth rates in mice infected with two Plasmodium yoelii strains having different virulence phenotypes and in progeny from a genetic cross of the two parasites. Quantitative trait loci (QTL) analysis linked levels of many CCs, particularly IL-1β, IP-10, IFN-γ, MCP-1 and MIG, and early parasite growth rate to loci on multiple parasite chromosomes, including chromosomes 7, 9, 10, 12 and 13. Comparison of the genome sequences spanning the mapped loci revealed various candidate genes. The loci on chromosomes 7 and 13 had significant (P<0.005) additive effects on IL-1β, IL-5 and IP-10 responses, and the chromosome 9 and 12 loci had significant (P=0.017) interaction. Infection of knockout mice showed critical roles of MCP-1 and IL-10 in parasitemia control and host mortality. These results provide important information for a better understanding of malaria pathogenesis and can be used to examine the role of these factors in human malaria infection.

  14. Basic Concurrency Theory

    DEFF Research Database (Denmark)

    Løvengreen, Hans Henrik

    2002-01-01

    In this set of notes, we present some of the basic theory underlying the discipline of programming with concurrent processes/threads. The notes are intended to supplement a standard textbook on concurrent programming.......In this set of notes, we present some of the basic theory underlying the discipline of programming with concurrent processes/threads. The notes are intended to supplement a standard textbook on concurrent programming....

  15. Identification and bioinformatic characterization of a multidrug resistance associated protein (ABCC) gene in Plasmodium berghei

    Science.gov (United States)

    González-Pons, María; Szeto, Ada C; González-Méndez, Ricardo; Serrano, Adelfa E

    2009-01-01

    the ABCC sub-family. Multiple sequence alignments reveal that this gene is homologous to the Plasmodium y. yoelii and Plasmodium knowlesi mrp, and the Plasmodium vivax and Plasmodium falciparum mrp2 genes. There were no differences in gene organization, copy number, or mRNA expression between N clone and the RC line, but a chromosomal translocation of pbmrp from chromosome 13/14 to chromosome 8 was detected in RC. PMID:19118502

  16. Concurrent weighted logic

    DEFF Research Database (Denmark)

    Xue, Bingtian; Larsen, Kim Guldstrand; Mardare, Radu Iulian

    2015-01-01

    We introduce Concurrent Weighted Logic (CWL), a multimodal logic for concurrent labeled weighted transition systems (LWSs). The synchronization of LWSs is described using dedicated functions that, in various concurrency paradigms, allow us to encode the compositionality of LWSs. To reflect these......-completeness results for this logic. To complete these proofs we involve advanced topological techniques from Model Theory....

  17. Cloning, expression and functional activity of deoxyhypusine synthase from Plasmodium vivax

    Directory of Open Access Journals (Sweden)

    Nassar Marwa

    2006-10-01

    Full Text Available Abstract Background Plasmodium vivax is the most widespread human malaria parasite. However, genetic information about its pathogenesis is limited at present, due to the lack of a reproducible in vitro cultivation method. Sequencing of the Plasmodium vivax genome suggested the presence of a homolog of deoxyhypusine synthase (DHS from P. falciparum, the key regulatory enzyme in the first committed step of hypusine biosynthesis. DHS is involved in cell proliferation, and thus a valuable drug target for the human malaria parasite P. falciparum. A comparison of the enzymatic properties of the DHS enzymes between the benign and severe Plasmodium species should contribute to our understanding of the differences in pathogenicity and phylogeny of both malaria parasites. Results We describe the cloning of a 1368 bp putative deoxyhypusine synthase gene (dhs sequence from genomic DNA of P. vivax PEST strain Salvador I (Accession number AJ549098 after touchdown PCR. The corresponding protein was expressed and functionally characterized as deoxyhypusine synthase by determination of its specific activity and cross-reactivity to human DHS on a Western blot. The putative DHS protein from P. vivax displays a FASTA score of 75 relative to DHS from rodent malaria parasite, P. yoelii, and 74 relative to that from the human parasite, P. falciparum strain 3D7. The ORF encoding 456 amino acids was expressed under control of IPTG-inducible T7 promoter, and expressed as a protein of approximately 50 kDa (theoretically 52.7 kDa in E. coli BL21 DE3 cells. The N-terminal histidine-tagged protein was purified by Nickel-chelate affinity chromatography under denaturing conditions. DHS with a theoretical pI of 6.0 was present in both eluate fractions. The specific enzymatic activity of DHS was determined as 1268 U/mg protein. The inhibitor, N-guanyl-1, 7-diaminoheptane (GC7, suppressed specific activity by 36-fold. Western blot analysis performed with a polyclonal anti

  18. Suppression of Host p53 Is Critical for Plasmodium Liver-Stage Infection

    Directory of Open Access Journals (Sweden)

    Alexis Kaushansky

    2013-03-01

    Full Text Available Plasmodium parasites infect the liver and replicate inside hepatocytes before they invade erythrocytes and trigger clinical malaria. Analysis of host signaling pathways affected by liver-stage infection could provide critical insights into host–pathogen interactions and reveal targets for intervention. Using protein lysate microarrays, we found that Plasmodium yoelii rodent malaria parasites perturb hepatocyte regulatory pathways involved in cell survival, proliferation, and autophagy. Notably, the prodeath protein p53 was substantially decreased in infected hepatocytes, suggesting that it could be targeted by the parasite to foster survival. Indeed, mice that express increased levels of p53 showed reduced liver-stage parasite burden, whereas p53 knockout mice suffered increased liver-stage burden. Furthermore, boosting p53 levels with the use of the small molecule Nutlin-3 dramatically reduced liver-stage burden in vitro and in vivo. We conclude that perturbation of the hepatocyte p53 pathway critically impacts parasite survival. Thus, host pathways might constitute potential targets for host-based antimalarial prophylaxis.

  19. Measuring and modelling concurrency

    Directory of Open Access Journals (Sweden)

    Larry Sawers

    2013-02-01

    Full Text Available This article explores three critical topics discussed in the recent debate over concurrency (overlapping sexual partnerships: measurement of the prevalence of concurrency, mathematical modelling of concurrency and HIV epidemic dynamics, and measuring the correlation between HIV and concurrency. The focus of the article is the concurrency hypothesis – the proposition that presumed high prevalence of concurrency explains sub-Saharan Africa's exceptionally high HIV prevalence. Recent surveys using improved questionnaire design show reported concurrency ranging from 0.8% to 7.6% in the region. Even after adjusting for plausible levels of reporting errors, appropriately parameterized sexual network models of HIV epidemics do not generate sustainable epidemic trajectories (avoid epidemic extinction at levels of concurrency found in recent surveys in sub-Saharan Africa. Efforts to support the concurrency hypothesis with a statistical correlation between HIV incidence and concurrency prevalence are not yet successful. Two decades of efforts to find evidence in support of the concurrency hypothesis have failed to build a convincing case.

  20. Constraints meet concurrency

    CERN Document Server

    Mauro, Jacopo

    2014-01-01

    This book describes the benefits that emerge when the fields of constraint programming and concurrency meet. On the one hand, constraints can be used in concurrency theory to increase the conciseness and the expressive power of concurrent languages from a pragmatic point of view. On the other hand, problems modeled by using constraints can be solved faster and more efficiently using a concurrent system. Both directions are explored providing two separate lines of development. Firstly the expressive power of a concurrent language is studied, namely Constraint Handling Rules, that supports constraints as a primitive construct. The features of this language which make it Turing powerful are shown. Then a framework is proposed to solve constraint problems that is intended to be deployed on a concurrent system. For the development of this framework the concurrent language Jolie following the Service Oriented paradigm is used. Based on this experience, an extension to Service Oriented Languages is also proposed in ...

  1. Towards Composable Concurrency Abstractions

    Directory of Open Access Journals (Sweden)

    Janwillem Swalens

    2014-06-01

    Full Text Available In the past decades, many different programming models for managing concurrency in applications have been proposed, such as the actor model, Communicating Sequential Processes, and Software Transactional Memory. The ubiquity of multi-core processors has made harnessing concurrency even more important. We observe that modern languages, such as Scala, Clojure, or F#, provide not one, but multiple concurrency models that help developers manage concurrency. Large end-user applications are rarely built using just a single concurrency model. Programmers need to manage a responsive UI, deal with file or network I/O, asynchronous workflows, and shared resources. Different concurrency models facilitate different requirements. This raises the issue of how these concurrency models interact, and whether they are composable. After all, combining different concurrency models may lead to subtle bugs or inconsistencies. In this paper, we perform an in-depth study of the concurrency abstractions provided by the Clojure language. We study all pairwise combinations of the abstractions, noting which ones compose without issues, and which do not. We make an attempt to abstract from the specifics of Clojure, identifying the general properties of concurrency models that facilitate or hinder composition.

  2. The novel oxygenated chalcone, 2,4-dimethoxy-4'-butoxychalcone, exhibits potent activity against human malaria parasite Plasmodium falciparum in vitro and rodent parasites Plasmodium berghei and Plasmodium yoelii in vivo

    DEFF Research Database (Denmark)

    Chen, M; Brøgger Christensen, S; Zhai, L;

    1997-01-01

    Previous studies have shown that licochalcone A, an oxygenated chalcone, exhibits antileishmanial and antimalarial activities. The present study was designed to examine the antimalarial activity of an analog of licochalcone A, 2,4-dimethoxy-4'-butoxychalcone (2,4mbc). 2,4mbc inhibited the in vitro...

  3. Plasmodium and mononuclear phagocytes.

    Science.gov (United States)

    Mac-Daniel, Laura; Ménard, Robert

    2015-01-01

    Plasmodium, the causative agent of malaria, initially multiplies inside liver cells and then in successive cycles inside erythrocytes, causing the symptoms of the disease. In this review, we discuss interactions between the extracellular and intracellular forms of the Plasmodium parasite and innate immune cells in the mammalian host, with a special emphasis on mononuclear phagocytes. We overview here what is known about the innate immune cells that interact with parasites, mechanisms used by the parasite to evade them, and the protective or detrimental contribution of these interactions on parasite progression through its life cycle and pathology in the host.

  4. Temporal Concurrent Constraint Programming

    DEFF Research Database (Denmark)

    Nielsen, Mogens; Valencia Posso, Frank Dan

    2002-01-01

    The ntcc calculus is a model of non-deterministic temporal concurrent constraint programming. In this paper we study behavioral notions for this calculus. In the underlying computational model, concurrent constraint processes are executed in discrete time intervals. The behavioral notions studied...... reflect the reactive interactions between concurrent constraint processes and their environment, as well as internal interactions between individual processes. Relationships between the suggested notions are studied, and they are all proved to be decidable for a substantial fragment of the calculus...

  5. Separation Logic and Concurrency

    Science.gov (United States)

    Bornat, Richard

    Concurrent separation logic is a development of Hoare logic adapted to deal with pointers and concurrency. Since its inception, it has been enhanced with a treatment of permissions to enable sharing of data between threads, and a treatment of variables as resource alongside heap cells as resource. An introduction to the logic is given with several examples of proofs, culminating in a treatment of Simpson's 4-slot algorithm, an instance of racy non-blocking concurrency.

  6. Concurrent Software Engineering Project

    Science.gov (United States)

    Stankovic, Nenad; Tillo, Tammam

    2009-01-01

    Concurrent engineering or overlapping activities is a business strategy for schedule compression on large development projects. Design parameters and tasks from every aspect of a product's development process and their interdependencies are overlapped and worked on in parallel. Concurrent engineering suffers from negative effects such as excessive…

  7. Temporal Concurrent Constraint Programming

    DEFF Research Database (Denmark)

    Nielsen, Mogens; Palamidessi, Catuscia; Valencia, Frank Dan

    2002-01-01

    The ntcc calculus is a model of non-deterministic temporal concurrent constraint programming. In this paper we study behavioral notions for this calculus. In the underlying computational model, concurrent constraint processes are executed in discrete time intervals. The behavioral notions studied...

  8. Concurrent Software Engineering Project

    Science.gov (United States)

    Stankovic, Nenad; Tillo, Tammam

    2009-01-01

    Concurrent engineering or overlapping activities is a business strategy for schedule compression on large development projects. Design parameters and tasks from every aspect of a product's development process and their interdependencies are overlapped and worked on in parallel. Concurrent engineering suffers from negative effects such as excessive…

  9. Probabilistic Concurrent Kleene Algebra

    Directory of Open Access Journals (Sweden)

    Annabelle McIver

    2013-06-01

    Full Text Available We provide an extension of concurrent Kleene algebras to account for probabilistic properties. The algebra yields a unified framework containing nondeterminism, concurrency and probability and is sound with respect to the set of probabilistic automata modulo probabilistic simulation. We use the resulting algebra to generalise the algebraic formulation of a variant of Jones' rely/guarantee calculus.

  10. Impredicative concurrent abstract predicates

    DEFF Research Database (Denmark)

    Svendsen, Kasper; Birkedal, Lars

    2014-01-01

    We present impredicative concurrent abstract predicates { iCAP { a program logic for modular reasoning about concurrent, higher- order, reentrant, imperative code. Building on earlier work, iCAP uses protocols to reason about shared mutable state. A key novel feature of iCAP is the ability to dene...

  11. Type II fatty acid biosynthesis is essential for Plasmodium falciparum sporozoite development in the midgut of Anopheles mosquitoes.

    Science.gov (United States)

    van Schaijk, Ben C L; Kumar, T R Santha; Vos, Martijn W; Richman, Adam; van Gemert, Geert-Jan; Li, Tao; Eappen, Abraham G; Williamson, Kim C; Morahan, Belinda J; Fishbaugher, Matt; Kennedy, Mark; Camargo, Nelly; Khan, Shahid M; Janse, Chris J; Sim, Kim Lee; Hoffman, Stephen L; Kappe, Stefan H I; Sauerwein, Robert W; Fidock, David A; Vaughan, Ashley M

    2014-05-01

    The prodigious rate at which malaria parasites proliferate during asexual blood-stage replication, midgut sporozoite production, and intrahepatic development creates a substantial requirement for essential nutrients, including fatty acids that likely are necessary for parasite membrane formation. Plasmodium parasites obtain fatty acids either by scavenging from the vertebrate host and mosquito vector or by producing fatty acids de novo via the type two fatty acid biosynthesis pathway (FAS-II). Here, we study the FAS-II pathway in Plasmodium falciparum, the species responsible for the most lethal form of human malaria. Using antibodies, we find that the FAS-II enzyme FabI is expressed in mosquito midgut oocysts and sporozoites as well as liver-stage parasites but not during the blood stages. As expected, FabI colocalizes with the apicoplast-targeted acyl carrier protein, indicating that FabI functions in the apicoplast. We further analyze the FAS-II pathway in Plasmodium falciparum by assessing the functional consequences of deleting fabI and fabB/F. Targeted deletion or disruption of these genes in P. falciparum did not affect asexual blood-stage replication or the generation of midgut oocysts; however, subsequent sporozoite development was abolished. We conclude that the P. falciparum FAS-II pathway is essential for sporozoite development within the midgut oocyst. These findings reveal an important distinction from the rodent Plasmodium parasites P. berghei and P. yoelii, where the FAS-II pathway is known to be required for normal parasite progression through the liver stage but is not required for oocyst development in the Anopheles mosquito midgut.

  12. Cloning, expression and functional characterization of heme detoxification protein (HDP) from the rodent malaria parasite Plasmodium vinckei.

    Science.gov (United States)

    Soni, Awakash; Goyal, Manish; Prakash, Kirtika; Bhardwaj, Jyoti; Siddiqui, Arif Jamal; Puri, Sunil K

    2015-07-15

    Malaria parasite resides within the host red blood cells, where it degrades vast amount of haemoglobin. During haemoglobin degradation, toxic free heme is liberated which subsequently gets converted into hemozoin. This process is facilitated by action of various proteins viz. heme detoxification protein (HDP), and histidine rich proteins II and III (HRP II & III). Out of these, HDP is the most potent in hemozoin formation and plays indispensible role for parasite survival. Despite this, the detailed study of HDP from rodent and simian parasite has not been performed till date. Here, we have cloned and sequenced hdp gene from different malaria parasites Plasmodium vinckei, Plasmodium yoelii, Plasmodium knowlesi, and Plasmodium cynomolgi. Furthermore, HDP from P. vinckei (PvHDP) was over-expressed and purified for detailed characterization. The PvHDP is cytosolic, expressed throughout the intra erythrocytic stages and its expression is higher in late trophozoite and schizont stages of parasite. The PvHDP interacts with free heme (KD=89 nM) and efficiently converts heme into hemozoin in a time and concentration dependent manner. Moreover, PvHDP showed activity in acidic pH and over a broad range of temperature. Histidine modification of PvHDP using DEPC showed reduction in heme binding and hemozoin formation, thus emphasizing the importance of histidine residues in heme binding and subsequent hemozoin production. Furthermore, applicability of PvHDP to screen anti-plasmodial agents (targeting heme to hemozoin conversion) was also determined using chloroquine, and mefloquine as reference antimalarials. Results showed that these drugs inhibit heme polymerization effectively in a concentration dependent manner. In conclusion, our study identified and biochemically characterized HDP from rodent malaria parasite P. vinckei and this will help to develop a high throughput assay to evaluate new antimalarials targeting hemozoin pathway. Copyright © 2015 Elsevier B.V. All

  13. Specification of Concurrent Objects

    DEFF Research Database (Denmark)

    Sørensen, Morten U.

    relation over two objects and an event. In the model, objects can be composed by parallel composition, encapsulation, and hiding of operations. Refinement between objects is defined as fair trace inclusion.A specification language is presented where objects can be specified operationally by abstract......Concurrent objects are named concurrent processes that interact by invoking each other's operations. We describe how such concurrent objects can be specified, how objects can be composed, and how it can be shown that one object refines another.First a model is defined, based on a transition...

  14. Plasmodium chabaudi chabaudi malaria parasites can develop stable resistance to atovaquone with a mutation in the cytochrome b gene

    Directory of Open Access Journals (Sweden)

    Alves Ana C

    2010-05-01

    Full Text Available Abstract Background Plasmodium falciparum, has developed resistance to many of the drugs in use. The recommended treatment policy is now to use drug combinations. The atovaquone-proguanil (AP drug combination, is one of the treatment and prophylaxis options. Atovaquone (ATQ exerts its action by inhibiting plasmodial mitochondria electron transport at the level of the cytochrome bc1 complex. Plasmodium falciparum in vitro resistance to ATQ has been associated with specific point mutations in the region spanning codons 271-284 of the cytochrome b gene. ATQ -resistant Plasmodium yoelii and Plasmodium berghei lines have been obtained and resistant lines have amino acid mutations in their CYT b protein sequences. Plasmodium chabaudi model for studying drug-responses and drug-resistance selection is a very useful rodent malaria model but no ATQ resistant parasites have been reported so far. The aim of this study was to determine the ATQ sensitivity of the P. chabaudi clones, to select a resistant parasite line and to perform genotypic characterization of the cytb gene of these clones. Methods To select for ATQ resistance, Plasmodium. chabaudi chabaudi clones were exposed to gradually increasing concentrations of ATQ during several consecutive passages in mice. Plasmodium chabaudi cytb gene was amplified and sequenced. Results ATQ resistance was selected from the clone AS-3CQ. In order to confirm whether an heritable genetic mutation underlies the response of AS-ATQ to ATQ, the stability of the drug resistance phenotype in this clone was evaluated by measuring drug responses after (i multiple blood passages in the absence of the drug, (ii freeze/thawing of parasites in liquid nitrogen and (iii transmission through a mosquito host, Anopheles stephensi. ATQ resistance phenotype of the drug-selected parasite clone kept unaltered. Therefore, ATQ resistance in clone AS-ATQ is genetically encoded. The Minimum Curative Dose of AS-ATQ showed a six

  15. NCBI nr-aa BLAST: CBRC-DRER-11-0077 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DRER-11-0077 ref|XP_728219.1| isoleucyl-tRNA syntehtase [Plasmodium yoelii yoe...lii str. 17XNL] gb|EAA19784.1| isoleucyl-tRNA syntehtase-related [Plasmodium yoelii yoelii] XP_728219.1 7e-11 51% ...

  16. NCBI nr-aa BLAST: CBRC-PHAM-01-1809 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-PHAM-01-1809 ref|XP_728219.1| isoleucyl-tRNA syntehtase [Plasmodium yoelii yoe...lii str. 17XNL] gb|EAA19784.1| isoleucyl-tRNA syntehtase-related [Plasmodium yoelii yoelii] XP_728219.1 7e-05 37% ...

  17. NCBI nr-aa BLAST: CBRC-GACU-23-0103 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-GACU-23-0103 ref|XP_728219.1| isoleucyl-tRNA syntehtase [Plasmodium yoelii yoe...lii str. 17XNL] gb|EAA19784.1| isoleucyl-tRNA syntehtase-related [Plasmodium yoelii yoelii] XP_728219.1 9e-15 29% ...

  18. NCBI nr-aa BLAST: CBRC-MMUS-12-0034 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-MMUS-12-0034 ref|XP_728219.1| isoleucyl-tRNA syntehtase [Plasmodium yoelii yoe...lii str. 17XNL] gb|EAA19784.1| isoleucyl-tRNA syntehtase-related [Plasmodium yoelii yoelii] XP_728219.1 8e-18 29% ...

  19. NCBI nr-aa BLAST: CBRC-ETEL-01-1307 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-ETEL-01-1307 ref|XP_728219.1| isoleucyl-tRNA syntehtase [Plasmodium yoelii yoe...lii str. 17XNL] gb|EAA19784.1| isoleucyl-tRNA syntehtase-related [Plasmodium yoelii yoelii] XP_728219.1 8e-13 42% ...

  20. NCBI nr-aa BLAST: CBRC-DRER-26-0267 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DRER-26-0267 ref|XP_728219.1| isoleucyl-tRNA syntehtase [Plasmodium yoelii yoe...lii str. 17XNL] gb|EAA19784.1| isoleucyl-tRNA syntehtase-related [Plasmodium yoelii yoelii] XP_728219.1 2e-07 36% ...

  1. NCBI nr-aa BLAST: CBRC-DRER-16-0008 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-DRER-16-0008 ref|XP_728219.1| isoleucyl-tRNA syntehtase [Plasmodium yoelii yoe...lii str. 17XNL] gb|EAA19784.1| isoleucyl-tRNA syntehtase-related [Plasmodium yoelii yoelii] XP_728219.1 8e-11 35% ...

  2. NCBI nr-aa BLAST: CBRC-RNOR-16-0095 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-RNOR-16-0095 ref|XP_728219.1| isoleucyl-tRNA syntehtase [Plasmodium yoelii yoe...lii str. 17XNL] gb|EAA19784.1| isoleucyl-tRNA syntehtase-related [Plasmodium yoelii yoelii] XP_728219.1 3e-17 53% ...

  3. Vaccine efficacy against malaria by the combination of porcine parvovirus-like particles and vaccinia virus vectors expressing CS of Plasmodium.

    Directory of Open Access Journals (Sweden)

    Dolores Rodríguez

    Full Text Available With the aim to develop an efficient and cost-effective approach to control malaria, we have generated porcine parvovirus-like particles (PPV-VLPs carrying the CD8(+ T cell epitope (SYVPSAEQI of the circumsporozoite (CS protein from Plasmodium yoelii fused to the PPV VP2 capsid protein (PPV-PYCS, and tested in prime/boost protocols with poxvirus vectors for efficacy in a rodent malaria model. As a proof-of concept, we have characterized the anti-CS CD8(+ T cell response elicited by these hybrid PPV-VLPs in BALB/c mice after immunizations with the protein PPV-PYCS administered alone or in combination with recombinant vaccinia virus (VACV vectors from the Western Reserve (WR and modified virus Ankara (MVA strains expressing the entire P. yoelii CS protein. The results of different immunization protocols showed that the combination of PPV-PYCS prime/poxvirus boost was highly immunogenic, inducing specific CD8+ T cell responses to CS resulting in 95% reduction in liver stage parasites two days following sporozoite challenge. In contrast, neither the administration of PPV-PYCS alone nor the immunization with the vectors given in the order poxvirus/VLPs was as effective. The immune profile induced by VLPs/MVA boost was associated with polyfunctional and effector memory CD8+ T cell responses. These findings highlight the use of recombinant parvovirus PPV-PYCS particles as priming agents and poxvirus vectors, like MVA, as booster to enhance specific CD8+ T cell responses to Plasmodium antigens and to control infection. These observations are relevant in the design of T cell-inducing vaccines against malaria.

  4. Building Safe Concurrency Abstractions

    DEFF Research Database (Denmark)

    Madsen, Ole Lehrmann

    2014-01-01

    Concurrent object-oriented programming in Beta is based on semaphores and coroutines and the ability to define high-level concurrency abstractions like monitors, and rendezvous-based communication, and their associated schedulers. The coroutine mechanism of SIMULA has been generalized...... into the notions of concurrent and alternating objects. Alternating objects may be used to start a cooperative thread for each possible blocking communication and is thus an alternative to asynchronous messages and guarded commands. Beta like SIMULA, the first OO language, was designed as a language for modeling...... as well as programming, and we describe how this has had an impact on the design of the language. Although Beta supports the definition of high-level concurrency abstractions, the use of these rely on the discipline of the programmer as is the case for Java and other mainstream OO languages. We introduce...

  5. Concurrent bisimulation algorithm

    OpenAIRE

    Kułakowski, Konrad

    2013-01-01

    The coarsest bisimulation-finding problem plays an important role in the formal analysis of concurrent systems. For example, solving this problem allows the behavior of different processes to be compared or specifications to be verified. Hence, in this paper an efficient concurrent bisimulation algorithm is presented. It is based on the sequential Paige and Tarjan algorithm and the concept of the state signatures. The original solution follows Hopcroft's principle "process the smaller half". ...

  6. Two Plasmodium 6-Cys family-related proteins have distinct and critical roles in liver-stage development.

    Science.gov (United States)

    Annoura, Takeshi; van Schaijk, Ben C L; Ploemen, Ivo H J; Sajid, Mohammed; Lin, Jing-wen; Vos, Martijn W; Dinmohamed, Avinash G; Inaoka, Daniel K; Rijpma, Sanna R; van Gemert, Geert-Jan; Chevalley-Maurel, Severine; Kiełbasa, Szymon M; Scheltinga, Fay; Franke-Fayard, Blandine; Klop, Onny; Hermsen, Cornelus C; Kita, Kiyoshi; Gego, Audrey; Franetich, Jean-Francois; Mazier, Dominique; Hoffman, Stephen L; Janse, Chris J; Sauerwein, Robert W; Khan, Shahid M

    2014-05-01

    The 10 Plasmodium 6-Cys proteins have critical roles throughout parasite development and are targets for antimalaria vaccination strategies. We analyzed the conserved 6-cysteine domain of this family and show that only the last 4 positionally conserved cysteine residues are diagnostic for this domain and identified 4 additional "6-Cys family-related" proteins. Two of these, sequestrin and B9, are critical to Plasmodium liver-stage development. RT-PCR and immunofluorescence assays show that B9 is translationally repressed in sporozoites and is expressed after hepatocyte invasion where it localizes to the parasite plasma membrane. Mutants lacking B9 expression in the rodent malaria parasites P. berghei and P. yoelii and the human parasite P. falciparum developmentally arrest in hepatocytes. P. berghei mutants arrest in the livers of BALB/c (100%) and C57BL6 mice (>99.9%), and in cultures of Huh7 human-hepatoma cell line. Similarly, P. falciparum mutants while fully infectious to primary human hepatocytes abort development 3 d after infection. This growth arrest is associated with a compromised parasitophorous vacuole membrane a phenotype similar to, but distinct from, mutants lacking the 6-Cys sporozoite proteins P52 and P36. Our results show that 6-Cys proteins have critical but distinct roles in establishment and maintenance of a parasitophorous vacuole and subsequent liver-stage development.

  7. Concurrent dengue and malaria in an area in Kolkata

    Institute of Scientific and Technical Information of China (English)

    Amiya Kumar Hati; Indranil Bhattacharjee; Hiranmoy Mukherjee; Bhaswati Bandyopadhayay; Deban Bandyopadhyay; Rajyasree De; Goutam Chandra

    2012-01-01

    ABSTRACT Objective:To establish the nature and extent of dual dengue and malaria infections in an endemic area through a longitudinal study.Methods: A prospective study was conducted from August2005to December2010to document the nature and extent of concurrent dengue and malaria infections in an area in central Kolkata, endemic both for dengue and malaria.Results:Of2 971 suspected cases of dengue fever, in605 (20.36%)persons dengue infection was detected, of whom46 (7.60%, 46/605)patients (40 and6suffered from secondary and primary dengue fever respectively) were simultaneously suffering from malaria (28 and18 were infected with Plasmodium vivax (P.vivax) andPlasmodium falciparum (P. falciparum) respectively, such dual infections of dengue and malaria were detected in all the years of the study period, except 2007, indicating intense transmission of both dengue and malaria in the study area, and the phenomenon was not an isolated one, the rate of concomitant infections ranged from25% in2009 to4.9% in 2005. Out of total population surveyed,1.54% (46/2 971)had concurrent dengue and malaria infection.Conclusions: These findings added a new dimension in diagnosis, treatment, epidemiology and control of dengue and malaria. The possible risk of concurrent dengue and malaria infections should always be kept in mind in endemic areas for early diagnosis employing modern technology and prompt and effective treatment to avoid serious complications.

  8. Channel's Concurrence and Quantum Teleportation

    Institute of Scientific and Technical Information of China (English)

    LING Yin-Sheng

    2005-01-01

    Concurrence can measure the entanglement property of a system. If the channel is a pure state, positive concurrence state can afford the good performance in the teleportation process. If the channel ia a mixed state, positive concurrence state cannot assure the good performance in the teleportation. The conditions of the positive concurrence and the quantum teleportation in the Heisenberg spin ring is derived.

  9. Building Safe Concurrency Abstractions

    DEFF Research Database (Denmark)

    Madsen, Ole Lehrmann

    2014-01-01

    into the notions of concurrent and alternating objects. Alternating objects may be used to start a cooperative thread for each possible blocking communication and is thus an alternative to asynchronous messages and guarded commands. Beta like SIMULA, the first OO language, was designed as a language for modeling...... as well as programming, and we describe how this has had an impact on the design of the language. Although Beta supports the definition of high-level concurrency abstractions, the use of these rely on the discipline of the programmer as is the case for Java and other mainstream OO languages. We introduce...

  10. The utility of Plasmodium berghei as a rodent model for anti-merozoite malaria vaccine assessment.

    Science.gov (United States)

    Goodman, Anna L; Forbes, Emily K; Williams, Andrew R; Douglas, Alexander D; de Cassan, Simone C; Bauza, Karolis; Biswas, Sumi; Dicks, Matthew D J; Llewellyn, David; Moore, Anne C; Janse, Chris J; Franke-Fayard, Blandine M; Gilbert, Sarah C; Hill, Adrian V S; Pleass, Richard J; Draper, Simon J

    2013-01-01

    Rodent malaria species Plasmodium yoelii and P. chabaudi have been widely used to validate vaccine approaches targeting blood-stage merozoite antigens. However, increasing data suggest the P. berghei rodent malaria may be able to circumvent vaccine-induced anti-merozoite responses. Here we confirm a failure to protect against P. berghei, despite successful antibody induction against leading merozoite antigens using protein-in-adjuvant or viral vectored vaccine delivery. No subunit vaccine approach showed efficacy in mice following immunization and challenge with the wild-type P. berghei strains ANKA or NK65, or against a chimeric parasite line encoding a merozoite antigen from P. falciparum. Protection was not improved in knockout mice lacking the inhibitory Fc receptor CD32b, nor against a Δsmac P. berghei parasite line with a non-sequestering phenotype. An improved understanding of the mechanisms responsible for protection, or failure of protection, against P. berghei merozoites could guide the development of an efficacious vaccine against P. falciparum.

  11. Arrest of Nuclear Division in Plasmodium through Blockage of Erythrocyte Surface Exposed Ribosomal Protein P2

    Science.gov (United States)

    Das, Sudipta; Basu, Himanish; Korde, Reshma; Tewari, Rita; Sharma, Shobhona

    2012-01-01

    Malaria parasites reside inside erythrocytes and the disease manifestations are linked to the growth inside infected erythrocytes (IE). The growth of the parasite is mostly confined to the trophozoite stage during which nuclear division occurs followed by the formation of cell bodies (schizogony). The mechanism and regulation of schizogony are poorly understood. Here we show a novel role for a Plasmodium falciparum 60S stalk ribosomal acidic protein P2 (PfP2) (PFC0400w), which gets exported to the IE surface for 6–8 hrs during early schizogony, starting around 26–28 hrs post-merozoite invasion. The surface exposure is demonstrated using multiple PfP2-specific monoclonal antibodies, and is confirmed through transfection using PfP2-GFP. The IE surface-exposed PfP2-protein occurs mainly as SDS-resistant P2-homo-tetramers. Treatment with anti-PfP2 monoclonals causes arrest of IEs at the first nuclear division. Upon removal of the antibodies, about 80–85% of synchronized parasites can be released even after 24 hrs of antibody treatment. It has been reported that a tubovesicular network (TVN) is set up in early trophozoites which is used for nutrient import. Anti-P2 monoclonal antibodies cause a complete fragmentation of TVN by 36 hrs, and impairs lipid import in IEs. These may be downstream causes for the cell-cycle arrest. Upon antibody removal, the TVN is reconstituted, and the cell division progresses. Each of the above properties is observed in the rodent malaria parasite species P. yoelii and P. berghei. The translocation of the P2 protein to the IE surface is therefore likely to be of fundamental importance in Plasmodium cell division. PMID:22912579

  12. Coalgebra, concurrency and control

    NARCIS (Netherlands)

    J.J.M.M. Rutten (Jan)

    1999-01-01

    textabstractCoalgebra is used to generalize notions and techniques from concurrency theory, in order to apply them to problems concerning the supervisory control of discrete event systems. The main ingredients of this approach are the characterization of controllability in terms of (a variant of)

  13. Morse Theory and Concurrency

    DEFF Research Database (Denmark)

    Wisniewski, Rafal

    2003-01-01

    The work is intended to provide some insight about concurrency theory using ideas from geometry and algebraic topology. We define a topological space containing all traces of execution of the computer program and the information about how time flows. This is the main difference with standard...

  14. Composing Concurrent Objects

    NARCIS (Netherlands)

    Bergmans, Lodewijk

    1994-01-01

    Adopting the object-oriented paradigm for the development of large and complex software systems offers several advantages, of which increased extensibility and reusability are the most prominent ones. The object-oriented model is also quite suitable for modelling concurrent systems. However, it

  15. Innexin AGAP001476 is critical for mediating anti-Plasmodium responses in Anopheles mosquitoes.

    Science.gov (United States)

    Li, Michelle W M; Wang, Jiuling; Zhao, Yang O; Fikrig, Erol

    2014-09-05

    The Toll and IMD pathways are known to be induced upon Plasmodium berghei and Plasmodium falciparum infection, respectively. It is unclear how Plasmodium or other pathogens in the blood meal and their invasion of the midgut epithelium would trigger the innate immune responses in immune cells, in particular hemocytes. Gap junctions, which can mediate both cell-to-cell and cell-to-extracellular communication, may participate in this signal transduction. This study examined whether innexins, gap junction proteins in insects, are involved in anti-Plasmodium responses in Anopheles gambiae. Inhibitor studies using carbenoxolone indicated that blocking innexons resulted in an increase in Plasmodium oocyst number and infection prevalence. This was accompanied by a decline in TEP1 levels in carbenoxolone-treated mosquitoes. Innexin AGAP001476 mRNA levels in midguts were induced during Plasmodium infection and a knockdown of AGAP001476, but not AGAP006241, caused an induction in oocyst number. Silencing AGAP001476 caused a concurrent increase in vitellogenin levels, a TEP1 inhibitor, in addition to a reduced level of TEP1-LRIM1-APL1C complex in hemolymph. Both vitellogenin and TEP1 are regulated by Cactus under the Toll pathway. Simultaneous knockdown of cactus and AGAP001476 failed to reverse the near refractoriness induced by the knockdown of cactus, suggesting that the AGAP001476-mediated anti-Plasmodium response is Cactus-dependent. These data demonstrate a critical role for innexin AGAP001476 in mediating innate immune responses against Plasmodium through Toll pathway in mosquitoes. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. 长效和短效NO发生剂体内干预疟原虫红内期重要侵袭分子转录水平的观察%Transcription Levels of Important Invasive Molecules after Long-Acting and Short-Acting NO Donor to Interfere Plasmodium during Erythrocytic Stage in vivo

    Institute of Scientific and Technical Information of China (English)

    郑丽; 李银燕; 刘军; 潘艳艳; 李莹; 延娟; 曹雅明

    2011-01-01

    为探讨NO对疟原虫红内期侵袭相关分子MSP-1、AMA-1和RhopH complex转录水平的影响.通过雌性BALB/c小鼠腹腔感染1 ×106致死型约氏疟原虫P.yoelii 17XL,体内给予NO长效(NOC18)和短效( NOC5)发生剂进行干预后,纯化疟原虫成熟裂殖体,提取总RNA,通过Real-time PCR相对定量方法检测MSP-1、AMA-1和RhopH complex的转录水平.结果显示和正常感染组相比,NOC5处理后疟原虫侵入的关键分子MSP-1、AMA-1和RhopH complex的转录水平明显下降;而NOC18处理则未见这一现象.本研究结果提示NO抑制疟原虫侵袭关键分子的转录水平,进而可能下调疟原虫相应蛋白的表达,从而影响疟原虫的侵入过程.%The effects of NO on the transcription levels of correlated invasive molecules MSP-1, AMA-1, and RhopH complex during Plasmodium erythrocytic stage were investigated. Female BALB/c mice were infected with 1 x 106 lethal type Plasmodium yoelii 17XL in abdominal cavity, then the mice were treated with long-acting NO (NOC18) and short-acting NO ( N0C5 ) donors in vivo to cany out interference. Mature Plasmodium schizonts were purified and extracted their total RNA. The transcription levels of MSP-1, AMA-1, and RhopH complex were detected by real-time PCR relative quantitative determination. The results showed that the transcription levels of key molecules of MSP-1, AMA-1, and RhopH complex of Plasmodium invasion after treated with NOC5 decreased tangibly as compared with normal infected groups. However, the phenomenon was not seen in the groups treated with NOC18. These result indicated that NO inhibited the transcription levels of Plasmodium invasive key molecules, and proceeded to reduce the expression of Plasmodium corresponding protein, therefore, affected the Plasmodium invasive process.

  17. A Concurrent Logical Relation

    DEFF Research Database (Denmark)

    Birkedal, Lars; Sieczkowski, Filip; Thamsborg, Jacob Junker

    2012-01-01

    We present a logical relation for showing the correctness of program transformations based on a new type-and-effect system for a concurrent extension of an ML-like language with higher-order functions, higher-order store and dynamic memory allocation. We show how to use our model to verify a number...... of interesting program transformations that rely on effect annotations. In particular, we prove a Parallelization Theorem, which expresses when it is sound to run two expressions in parallel instead of sequentially. The conditions are expressed solely in terms of the types and effects of the expressions....... To the best of our knowledge, this is the first such result for a concurrent higher-order language with higher-order store and dynamic memory allocation....

  18. Algebraic topology and concurrency

    DEFF Research Database (Denmark)

    Fajstrup, Lisbeth; Raussen, Martin; Goubault, Eric

    2006-01-01

    We show in this article that some concepts from homotopy theory, in algebraic topology,are relevant for studying concurrent programs. We exhibit a natural semantics of semaphore programs, based on partially ordered topological spaces, which are studied up to “elastic deformation” or homotopy......, giving information about important properties of the program, such as deadlocks, unreachables, serializability, essential schedules, etc. In fact, it is not quite ordinary homotopy that has to be used, but rather a “directed homotopy” that does not reverse the flow of time. We show some of the essential...... differences between ordinary and directed homotopy through examples. We also relate the topological view to a combinatorial view of concurrent programs closer to transition systems, through the notion of a cubical set. Finally we apply some of these concepts to the proof of the safeness of a two...

  19. Morse Theory and Concurrency

    DEFF Research Database (Denmark)

    Wisniewski, Rafal

    2003-01-01

    The work is intended to provide some insight about concurrency theory using ideas from geometry and algebraic topology. We define a topological space containing all traces of execution of the computer program and the information about how time flows. This is the main difference with standard...... with piecewise-smooth boundary. Our aim is to identify the equivalence classes with the critical points of a certain Morse function....

  20. Morse Theory and Concurrency

    DEFF Research Database (Denmark)

    Wisniewski, Rafal

    2003-01-01

    The work is intended to provide some insight about concurrency theory using ideas from geometry and algebraic topology. We define a topological space containing all traces of execution of the computer program and the information about how time flows. This is the main difference with standard...... with piecewise-smooth boundary. Our aim is to identify the equivalence classes with the critical points of a certain Morse function....

  1. Feature conversion for concurrent engineering

    NARCIS (Netherlands)

    De Kraker, J.K.

    1998-01-01

    Feature conversion for concurrent engineering integrates two modern product development paradigms. Concurrent engineering is a product development paradigm in which multiple engineering disciplines participate. It optimizes a product with respect to available resources and product quality, for which

  2. High levels of immunoglobulin E autoantibody to 14-3-3 epsilon protein correlate with protection against severe Plasmodium falciparum malaria.

    Science.gov (United States)

    Duarte, Joana; Herbert, Fabien; Guiyedi, Vincent; Franetich, Jean-François; Roland, Jacques; Cazenave, Pierre-André; Mazier, Dominique; Kombila, Maryvonne; Fesel, Constantin; Pied, Sylviane

    2012-12-01

    Plasmodium falciparum infection generally induces elevated total plasma levels of immunoglobulins, some of which recognize self- or parasite-specific antigens. To our knowledge, we are the first to report high levels of functional immunoglobulin E (IgE) autoantibodies recognizing brain 14-3-3 protein ε in asymptomatic P. falciparum malaria. 14-3-3 ε protein belongs to a family of proteins that binds to CD81, a member of the tetraspanin superfamily elicited in hepatocyte invasion by sporozoites. Levels of expression of 14-3-3 ε protein were found to be increased in vivo and in vitro during Plasmodium yoelii and P. falciparum intrahepatic development. Collectively, these results indicate that self-reactive IgE is produced during malaria. In addition, the negative correlation between levels of self-reactive IgE to 14-3-3 ε protein and parasitemia in asymptomatic malaria due to P. falciparum supports a role for these IgE molecules in defense mechanisms, probably by interfering with development of liver-stage parasites through the CD81 pathway.

  3. Morse Theory and Concurrency

    DEFF Research Database (Denmark)

    Wisniewski, Rafal

    2003-01-01

    The work is intended to provide some insight about concurrency theory using ideas from geometry and algebraic topology. We define a topological space containing all traces of execution of the computer program and the information about how time flows. This is the main difference with standard...... topological reasoning in which there is no information about relation "in time" among points. The main task is to define equivalence of paths reflecting execution of a program. We use the notion of homotopy history equivalence relation. The model space considered in this work is a differentiable manifold...

  4. Mastering concurrency in Go

    CERN Document Server

    Kozyra, Nathan

    2014-01-01

    A practical approach covering everything you need to know to get up and running with Go, starting with the basics and imparting increasingly more detail as the examples and topics become more complicated. The book utilizes a casual, conversational style, rife with actual code and historical anecdotes for perspective, as well as usable and extensible example applications. This book is intended for systems developers and programmers with some experience in either Go and/or concurrent programming who wish to become fluent in building high-performance applications that scale by leveraging single-c

  5. A Plasmodium Promiscuous T Cell Epitope Delivered within the Ad5 Hexon Protein Enhances the Protective Efficacy of a Protein Based Malaria Vaccine.

    Directory of Open Access Journals (Sweden)

    Jairo Andres Fonseca

    Full Text Available A malaria vaccine is a public health priority. In order to produce an effective vaccine, a multistage approach targeting both the blood and the liver stage infection is desirable. The vaccine candidates also need to induce balanced immune responses including antibodies, CD4+ and CD8+ T cells. Protein-based subunit vaccines like RTS,S are able to induce strong antibody response but poor cellular reactivity. Adenoviral vectors have been effective inducing protective CD8+ T cell responses in several models including malaria; nonetheless this vaccine platform exhibits a limited induction of humoral immune responses. Two approaches have been used to improve the humoral immunogenicity of recombinant adenovirus vectors, the use of heterologous prime-boost regimens with recombinant proteins or the genetic modification of the hypervariable regions (HVR of the capsid protein hexon to express B cell epitopes of interest. In this study, we describe the development of capsid modified Ad5 vectors that express a promiscuous Plasmodium yoelii T helper epitope denominated PyT53 within the hexon HVR2 region. Several regimens were tested in mice to determine the relevance of the hexon modification in enhancing protective immune responses induced by the previously described protein-based multi-stage experimental vaccine PyCMP. A heterologous prime-boost immunization regime that combines a hexon modified vector with transgenic expression of PyCMP followed by protein immunizations resulted in the induction of robust antibody and cellular immune responses in comparison to a similar regimen that includes a vector with unmodified hexon. These differences in immunogenicity translated into a better protective efficacy against both the hepatic and red blood cell stages of P. yoelii. To our knowledge, this is the first time that a hexon modification is used to deliver a promiscuous T cell epitope. Our data support the use of such modification to enhance the immunogenicity

  6. Recursive Concurrent Stochastic Games

    CERN Document Server

    Etessami, Kousha

    2008-01-01

    We study Recursive Concurrent Stochastic Games (RCSGs), extending our recent analysis of recursive simple stochastic games [16,17] to a concurrent setting where the two players choose moves simultaneously and independently at each state. For multi-exit games, our earlier work already showed undecidability for basic questions like termination, thus we focus on the important case of single-exit RCSGs (1-RCSGs). We first characterize the value of a 1-RCSG termination game as the least fixed point solution of a system of nonlinear minimax functional equations, and use it to show PSPACE decidability for the quantitative termination problem. We then give a strategy improvement technique, which we use to show that player 1 (maximizer) has \\epsilon-optimal randomized Stackless & Memoryless (r-SM) strategies for all \\epsilon > 0, while player 2 (minimizer) has optimal r-SM strategies. Thus, such games are r-SM-determined. These results mirror and generalize in a strong sense the randomized memoryless determinacy r...

  7. 21 CFR 866.3402 - Plasmodium species antigen detection assays.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Plasmodium species antigen detection assays. 866... Plasmodium species antigen detection assays. (a) Identification. A Plasmodium species antigen detection assay... malaria caused by the four malaria species capable of infecting humans: Plasmodium falciparum, Plasmodium...

  8. Domain Theory for Concurrency

    DEFF Research Database (Denmark)

    Nygaard, Mikkel

    a process is capable. HOPLA can directly encode calculi like CCS, CCS with process passing, and mobile ambients with public names, and it can be given a straightforward operational semantics supporting a standard bisimulation congruence. The denotational and operational semantics are related with simple...... and associated comonads, it highlights the role of linearity in concurrent computation. Two choices of comonad yield two expressive metalanguages for higher-order processes, both arising from canonical constructions in the model. Their denotational semantics are fully abstract with respect to contextual...... input necessary for it. Such a semantics is provided, based on event structures; it agrees with the presheaf semantics at first order and exposes the tensor operation as a simple parallel composition of event structures. The categorical model obtained from presheaves is very rich in structure and points...

  9. Concurrent Quantum Computation

    CERN Document Server

    Yamaguchi, F; Yamamoto, Y

    2000-01-01

    A quantum computer is a multi-particle interferometer that comprises beam splitters at both ends and arms, where the n two-level particles undergo the interactions among them. The arms are designed so that relevant functions required to produce a computational result is stored in the phase shifts of the 2^n arms. They can be detected by interferometry that allows us to utilize quantum parallelism. Quantum algorithms are accountable for what interferometers to be constructed to compute particular problems. A standard formalism for constructing the arms has been developed by the extension of classical reversible gate arrays. By its nature of sequential applications of logic operations, the required number of gates increases exponentially as the problem size grows. This may cause a crucial obstacle to perform a quantum computation within a limited decoherence time. We propose a direct and concurrent construction of the interferometer arms by one-time evolution of a physical system with arbitrary multi-particle i...

  10. Concurrent engineering research center

    Science.gov (United States)

    Callahan, John R.

    1995-01-01

    The projects undertaken by The Concurrent Engineering Research Center (CERC) at West Virginia University are reported and summarized. CERC's participation in the Department of Defense's Defense Advanced Research Project relating to technology needed to improve the product development process is described, particularly in the area of advanced weapon systems. The efforts committed to improving collaboration among the diverse and distributed health care providers are reported, along with the research activities for NASA in Independent Software Verification and Validation. CERC also takes part in the electronic respirator certification initiated by The National Institute for Occupational Safety and Health, as well as in the efforts to find a solution to the problem of producing environment-friendly end-products for product developers worldwide. The 3M Fiber Metal Matrix Composite Model Factory Program is discussed. CERC technologies, facilities,and personnel-related issues are described, along with its library and technical services and recent publications.

  11. Modal abstractions of concurrent behavior

    DEFF Research Database (Denmark)

    Nielson, Flemming; Nanz, Sebastian; Nielson, Hanne Riis

    2011-01-01

    We present an effective algorithm for the automatic construction of finite modal transition systems as abstractions of potentially infinite concurrent processes. Modal transition systems are recognized as valuable abstractions for model checking because they allow for the validation as well...... as refutation of safety and liveness properties. However, the algorithmic construction of finite abstractions from potentially infinite concurrent processes is a missing link that prevents their more widespread usage for model checking of concurrent systems. Our algorithm is a worklist algorithm using concepts...

  12. Plasmodium vivax: who cares?

    Directory of Open Access Journals (Sweden)

    Barnwell John W

    2008-12-01

    Full Text Available Abstract More attention is being focused on malaria today than any time since the world's last efforts to achieve eradication over 40 years ago. The global community is now discussing strategies aimed at dramatically reducing malarial disease burden and the eventual eradication of all types of malaria, everywhere. As a consequence, Plasmodium vivax, which has long been neglected and mistakenly considered inconsequential, is now entering into the strategic debates taking place on malaria epidemiology and control, drug resistance, pathogenesis and vaccines. Thus, contrary to the past, the malaria research community is becoming more aware and concerned about the widespread spectrum of illness and death caused by up to a couple of hundred million cases of vivax malaria each year. This review brings these issues to light and provides an overview of P. vivax vaccine development, then and now. Progress had been slow, given inherent research challenges and minimal support in the past, but prospects are looking better for making headway in the next few years. P. vivax, known to invade the youngest red blood cells, the reticulocytes, presents a strong challenge towards developing a reliable long-term culture system to facilitate needed research. The P. vivax genome was published recently, and vivax researchers now need to coordinate efforts to discover new vaccine candidates, establish new vaccine approaches, capitalize on non-human primate models for testing, and investigate the unique biological features of P. vivax, including the elusive P. vivax hypnozoites. Comparative studies on both P. falciparum and P. vivax in many areas of research will be essential to eradicate malaria. And to this end, the education and training of future generations of dedicated "malariologists" to advance our knowledge, understanding and the development of new interventions against each of the malaria species infecting humans also will be essential.

  13. Involvement of β-defensin 130 (DEFB130) in the macrophage microbicidal mechanisms for killing Plasmodium falciparum

    Science.gov (United States)

    Terkawi, Mohamad Alaa; Takano, Ryo; Furukawa, Atsushi; Murakoshi, Fumi; Kato, Kentaro

    2017-01-01

    Understanding the molecular defense mechanism of macrophages and identifying their effector molecules against malarial parasites may provide important clues for the discovery of new therapies. To analyze the immunological responses of malarial parasite-induced macrophages, we used DNA microarray technology to examine the gene profile of differentiated macrophages phagocytizing Plasmodium falciparum-parasitized erythrocytes (iRBC). The transcriptional gene profile of macrophages in response to iRBCs represented 168 down-regulated genes, which were mainly involved in the cellular immune response, and 216 upregulated genes, which were involved in cellular proteolysis, growth, and adhesion. Importantly, the specific upregulation of β-defensin 130 (DEFB130) in these macrophages suggested a possible role for DEFB130 in malarial parasite elimination. Differentiated macrophages phagocytizing iRBCs exhibited an increase in intracellular DEFB130 levels and DEFB130 appeared to accumulate at the site of iRBC engulfment. Transfection of esiRNA-mediated knockdown of DEFB130 into macrophages resulted in a remarkable reduction in their antiplasmodial activity in vitro. Furthermore, DEFB130 synthetic peptide exhibited a modest toxic effect on P. falciparum in vitro and P. yoelii in vivo, unlike scrambled DEFB130 peptide, which showed no antiplasmodial activity. Together, these results suggest that DEFB130 might be one of the macrophage effector molecules for eliminating malarial parasites. Our data broaden our knowledge of the immunological response of macrophages to iRBCs and shed light on a new target for therapeutic intervention. PMID:28181499

  14. Economic explanations for concurrent sourcing

    DEFF Research Database (Denmark)

    Mols, Niels Peter

    2010-01-01

    Concurrent sourcing is a phenomenon where firms simultaneously make and buy the same good, i.e. they simultaneously use the governance modes of market and hierarchy. Though concurrent sourcing seems to be widespread, few studies of sourcing have focused on this phenomenon. This paper reviews diff...... different economic explanations for why firms use concurrent sourcing. The distinctive features of the explanations are compared, and it is discussed how they may serve as a springboard for research on concurrent sourcing. Managerial implications are also offered....

  15. IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection

    Science.gov (United States)

    Sebina, Ismail; James, Kylie R.; Soon, Megan S. F.; Best, Shannon E.; Montes de Oca, Marcela; Amante, Fiona H.; Thomas, Bryce S.; Beattie, Lynette; Souza-Fonseca-Guimaraes, Fernando; Smyth, Mark J.; Hertzog, Paul J.; Hill, Geoffrey R.; Engwerda, Christian R.

    2016-01-01

    Parasite-specific antibodies protect against blood-stage Plasmodium infection. However, in malaria-endemic regions, it takes many months for naturally-exposed individuals to develop robust humoral immunity. Explanations for this have focused on antigenic variation by Plasmodium, but have considered less whether host production of parasite-specific antibody is sub-optimal. In particular, it is unclear whether host immune factors might limit antibody responses. Here, we explored the effect of Type I Interferon signalling via IFNAR1 on CD4+ T-cell and B-cell responses in two non-lethal murine models of malaria, P. chabaudi chabaudi AS (PcAS) and P. yoelii 17XNL (Py17XNL) infection. Firstly, we demonstrated that CD4+ T-cells and ICOS-signalling were crucial for generating germinal centre (GC) B-cells, plasmablasts and parasite-specific antibodies, and likewise that T follicular helper (Tfh) cell responses relied on B cells. Next, we found that IFNAR1-signalling impeded the resolution of non-lethal blood-stage infection, which was associated with impaired production of parasite-specific IgM and several IgG sub-classes. Consistent with this, GC B-cell formation, Ig-class switching, plasmablast and Tfh differentiation were all impaired by IFNAR1-signalling. IFNAR1-signalling proceeded via conventional dendritic cells, and acted early by limiting activation, proliferation and ICOS expression by CD4+ T-cells, by restricting the localization of activated CD4+ T-cells adjacent to and within B-cell areas of the spleen, and by simultaneously suppressing Th1 and Tfh responses. Finally, IFNAR1-deficiency accelerated humoral immune responses and parasite control by boosting ICOS-signalling. Thus, we provide evidence of a host innate cytokine response that impedes the onset of humoral immunity during experimental malaria. PMID:27812214

  16. A new Apicomplexa-specific protein kinase family : multiple members in Plasmodium falciparum, all with an export signature

    Directory of Open Access Journals (Sweden)

    Mercereau-Puijalon Odile

    2005-03-01

    Full Text Available Abstract Background Malaria caused by protozoan parasites of the genus Plasmodium spp. is a major health burden in tropical countries. The development of new control tools, including vaccines and drugs, is urgently needed. The availability of genome sequences from several malaria parasite species provides a basis on which to identify new potential intervention targets. Database mining for orthologs to the Plasmodium falciparum trophozoite protein R45, a vaccine candidate, led us identify a new gene family. Results Orthologs to the P. falciparum trophozoite protein R45 were detected exclusively in protozoan parasites of the phylum Apicomplexa, including several Plasmodium spp., Toxoplasma gondii and Cryptosporidium parvum. All family members are hybrid genes with a conserved C-terminal protein kinase domain of a novel type, recently called FIKK kinase, associated with a non conserved N-terminal region without any known functional signature. While a single copy gene was detected in most species, considerable gene expansion was observed in P. falciparum and its closest phylogenic relative P. reichenowi, with 20 and six copies, respectively, each with a distinct N-terminal domain. Based on full length protein sequence, pairs of orthologs were observed in closely related species, such as P. berghei and P.y. yoelii, P. vivax and P. knowlesi, or P. reichenowi and P. falciparum. All 20 P. falciparum paralogs possess a canonical Plasmodium export element downstream of a signal / anchor sequence required for exportation outside the parasitophorous vacuole. This is consistent with the reported association of the trophozoite protein R45, the only paralog characterised to date, with the infected red blood cell membrane. Interestingly, most genes are located in the subtelomeric region of chromosomes, in association with other multigene families contributing to the remodelling of the infected red blood cell membrane, in particular the ring erythrocyte surface

  17. Antibodies and Plasmodium falciparum merozoites

    NARCIS (Netherlands)

    Ramasamy, R; Ramasamy, M; Yasawardena, S

    There is considerable interest in using merozoite proteins in a vaccine against falciparum malaria. Observations that antibodies to merozoite surface proteins block invasion are a basis for optimism. This article draws attention to important and varied aspects of how antibodies to Plasmodium

  18. CRDTs: Consistency without concurrency control

    CERN Document Server

    Letia, Mihai; Shapiro, Marc

    2009-01-01

    A CRDT is a data type whose operations commute when they are concurrent. Replicas of a CRDT eventually converge without any complex concurrency control. As an existence proof, we exhibit a non-trivial CRDT: a shared edit buffer called Treedoc. We outline the design, implementation and performance of Treedoc. We discuss how the CRDT concept can be generalised, and its limitations.

  19. A Lower Bound on Concurrence

    Institute of Scientific and Technical Information of China (English)

    LIU Li-Guo; TIAN Cheng-Lin; CHEN Ping-Xing; YUAN Nai-Chang

    2009-01-01

    We derive an analytical lower bound on the concurrence for bipartite quantum systems with an improved computable cross norm or realignment criterion and an improved positive partial transpose criterion respectively.Furthermore we demonstrate that our bound is better than that obtained from the local uncertainty relations criterion with optimal local orthogonal observables which is known as one of the best estimations of concurrence.

  20. Concurrent Validity and Holland's Theory

    Science.gov (United States)

    Gaffey, Robert L.; Walsh, W. Bruce

    1974-01-01

    This study was designed to explore two areas: (1) the concurrent validity of Holland's theory for employed men using four different operational definitions of vocational orientation, and (2) the relationships among all possible combinations of same named scales across the four inventories. Findings tend to support the concurrent validity of…

  1. Concurrent Validity and Holland's Theory

    Science.gov (United States)

    Gaffey, Robert L.; Walsh, W. Bruce

    1974-01-01

    This study was designed to explore two areas: (1) the concurrent validity of Holland's theory for employed men using four different operational definitions of vocational orientation, and (2) the relationships among all possible combinations of same named scales across the four inventories. Findings tend to support the concurrent validity of…

  2. Partnership concurrency and coital frequency.

    Science.gov (United States)

    Gaydosh, Lauren; Reniers, Georges; Helleringer, Stéphane

    2013-09-01

    National HIV prevalence estimates across sub-Saharan Africa range from less than 1 percent to over 25 percent. Recent research proposes several explanations for the observed variation, including prevalence of male circumcision, levels of condom use, presence of other sexually transmitted infections, and practice of multiple concurrent partnerships. However, the importance of partnership concurrency for HIV transmission may depend on how it affects coital frequency with each partner. The coital dilution hypothesis suggests that coital frequency within a partnership declines with the addition of concurrent partners. Using sexual behavior data from rural Malawi and urban Kenya, we investigate the relationship between partnership concurrency and coital frequency, and find partial support for the coital dilution hypothesis. We conclude the paper with a discussion of our findings in light of the current literature on concurrency.

  3. Food vacuole associated enolase in plasmodium undergoes multiple post-translational modifications: evidence for atypical ubiquitination.

    Directory of Open Access Journals (Sweden)

    Saudamini Shevade

    Full Text Available Plasmodium enolase localizes to several sub-cellular compartments viz. cytosol, nucleus, cell membrane, food vacuole (FV and cytoskeleton, without having any organelle targeting signal sequences. This enzyme has been shown to undergo multiple post-translational modifications (PTMs giving rise to several variants that show organelle specific localization. It is likely that these PTMs may be responsible for its diverse distribution and moonlighting functions. While most variants have a MW of ~50 kDa and are likely to arise due to changes in pI, food vacuole (FV associated enolase showed three forms with MW~50, 65 and 75 kDa. Evidence from immuno-precipitation and western analysis indicates that the 65 and 75 kDa forms of FV associated enolase are ubiquitinated. Using mass spectrometry (MS, definitive evidence is obtained for the nature of PTMs in FV associated variants of enolase. Results showed several modifications, viz. ubiquitination at K147, phosphorylation at Y148 and acetylation at K142 and K384. MS data also revealed the conjugation of three ubiquitin (Ub molecules to enolase through K147. Trimeric ubiquitin has a linear peptide linkage between the NH2-terminal methionine of the first ubiquitin (Ub1 and the C-terminal G76 of the second (Ub2. Ub2 and third ubiquitin (Ub3 were linked through an atypical isopeptide linkage between K6 of Ub2 and G76 of Ub3, respectively. Further, the tri-ubiquitinated form was found to be largely associated with hemozoin while the 50 and 65 kDa forms were present in the NP-40 soluble fraction of FV. Mass spectrometry results also showed phosphorylation of S42 in the cytosolic enolase from P. falciparum and T337 in the cytoskeleton associated enolase from P. yoelii. The composition of food vacuolar proteome and likely interactors of enolase are also being reported.

  4. Genetic diversity of Plasmodium vivax and Plasmodium falciparum in Honduras

    Directory of Open Access Journals (Sweden)

    Lopez Ana

    2012-11-01

    Full Text Available Abstract Background Understanding the population structure of Plasmodium species through genetic diversity studies can assist in the design of more effective malaria control strategies, particularly in vaccine development. Central America is an area where malaria is a public health problem, but little is known about the genetic diversity of the parasite’s circulating species. This study aimed to investigate the allelic frequency and molecular diversity of five surface antigens in field isolates from Honduras. Methods Five molecular markers were analysed to determine the genotypes of Plasmodium vivax and Plasmodium falciparum from endemic areas in Honduras. Genetic diversity of ama-1, msp-1 and csp was investigated for P. vivax, and msp-1 and msp-2 for P. falciparum. Allelic frequencies were calculated and sequence analysis performed. Results and conclusion A high genetic diversity was observed within Plasmodium isolates from Honduras. A different number of genotypes were elucidated: 41 (n = 77 for pvama-1; 23 (n = 84 for pvcsp; and 23 (n = 35 for pfmsp-1. Pvcsp sequences showed VK210 as the only subtype present in Honduran isolates. Pvmsp-1 (F2 was the most polymorphic marker for P. vivax isolates while pvama-1 was least variable. All three allelic families described for pfmsp-1 (n = 30 block 2 (K1, MAD20, and RO33, and both allelic families described for the central domain of pfmsp-2 (n = 11 (3D7 and FC27 were detected. However, K1 and 3D7 allelic families were predominant. All markers were randomly distributed across the country and no geographic correlation was found. To date, this is the most complete report on molecular characterization of P. vivax and P. falciparum field isolates in Honduras with regards to genetic diversity. These results indicate that P. vivax and P. falciparum parasite populations are highly diverse in Honduras despite the low level of transmission.

  5. Multiplicity of Infection and Disease Severity in Plasmodium vivax.

    Directory of Open Access Journals (Sweden)

    M Andreína Pacheco

    2016-01-01

    Full Text Available Multiplicity of infection (MOI refers to the average number of distinct parasite genotypes concurrently infecting a patient. Although several studies have reported on MOI and the frequency of multiclonal infections in Plasmodium falciparum, there is limited data on Plasmodium vivax. Here, MOI and the frequency of multiclonal infections were studied in areas from South America where P. vivax and P. falciparum can be compared.As part of a passive surveillance study, 1,328 positive malaria patients were recruited between 2011 and 2013 in low transmission areas from Colombia. Of those, there were only 38 P. vivax and 24 P. falciparum clinically complicated cases scattered throughout the time of the study. Samples from uncomplicated cases were matched in time and location with the complicated cases in order to compare the circulating genotypes for these two categories. A total of 92 P. vivax and 57 P. falciparum uncomplicated cases were randomly subsampled. All samples were genotyped by using neutral microsatellites. Plasmodium vivax showed more multiclonal infections (47.7% than P. falciparum (14.8%. Population genetics and haplotype network analyses did not detect differences in the circulating genotypes between complicated and uncomplicated cases in each parasite. However, a Fisher exact test yielded a significant association between having multiclonal P. vivax infections and complicated malaria. No association was found for P. falciparum infections.The association between multiclonal infections and disease severity in P. vivax is consistent with previous observations made in rodent malaria. The contrasting pattern between P. vivax and P. falciparum could be explained, at least in part, by the fact that P. vivax infections have lineages that were more distantly related among them than in the case of the P. falciparum multiclonal infections. Future research should address the possible role that acquired immunity and exposure may have on multiclonal

  6. Distinct temporal recruitment of Plasmodium alveolins to the subpellicular network.

    Science.gov (United States)

    Tremp, Annie Z; Al-Khattaf, Fatimah S; Dessens, Johannes T

    2014-11-01

    The zoite stages of malaria parasites (merozoite, ookinete and sporozoite) possess a distinctive cortical structure termed the pellicle, which is defined by a double membrane layer named the inner membrane complex (IMC). The IMC is supported by a cytoskeleton of intermediate filaments, termed the subpellicular network (SPN). Plasmodium IMC1 proteins, or alveolins, make up a conserved family of structurally related proteins that comprise building blocks of the SPN. Here, using green fluorescent protein (GFP) tagging in P. berghei, we show that the alveolins PbIMC1c and PbIMC1e are expressed in all three zoite stages. Our data reveal that PbIMC1e is assembled into the SPN concurrent with pellicle development, while PbIMC1c is assembled after pellicle formation. In the sexual stages, these processes are accompanied by different gene expressions from maternal and paternal alleles: PbIMC1e is expressed uniquely from the maternal allele, while PbIMC1c is expressed from the maternal allele in gametocytes, but from both parental alleles during ookinete development. These findings establish biogenesis of the cortical cytoskeleton in Plasmodium to be a complex and dynamic process, involving distinct parental gene expression and chronological recruitment of its protein constituents. While allelic replacement of the pbimc1c and pbimc1e genes with GFP-tagged versions was readily achieved using double crossover homologous recombination, attempts to disrupt these genes by this strategy only resulted in the integration of the selectable marker and GFP reporter into non-specific genomic locations. The recurrent inability to disrupt these genes provides the first genetic evidence that alveolins are necessary for asexual blood-stage parasite development in Plasmodium.

  7. New methods of concurrent checking

    CERN Document Server

    Goessel, Michael; Sogomonyan, Egor; Marienfeld, Daniel

    2008-01-01

    Written by a team of two leading experts and two very successful young former PhD students, New Methods of Concurrent Checking describes new methods of concurrent checking, such as partial duplication, use of output dependencies, complementary circuits, self-dual parity, self-dual duplication and others. A special chapter demonstrates how the new general methods of concurrent checking can be more specifically applied to regular structures to obtain optimum results. This is exemplified for all types of adders up to 64 bits with a level of detail never before presented in the literature. The cle

  8. Complement evasion by Plasmodium falciparum

    OpenAIRE

    Holopainen, Saila

    2008-01-01

    Patologian oppiaine Malaria remains one of the major health problems in many tropical countries, especially in sub-Saharan Africa. Among the most characteristic features of the malaria pathogens, protozoan parasites of the genus Plasmodium, is their ability to evade the immune defences of the host for extended periods of time. The complement system (C) is an essential part of the innate system in the first line of defense. It consists of over 30 soluble or membrane-bound components. C...

  9. Tetany with Plasmodium falciparum infection.

    Science.gov (United States)

    Singh, P S; Singh, Neha

    2012-07-01

    Plasmodium falciparum is a malarial infection with high morbidity and wide spectrum of atypical presentation. Here we report an unusual presentation of malaria as tetany with alteration in calcium,phosphate and magnesium metabolism Hypocalcaemia in malaria can cause prolonged Q-Tc interval which could be arisk factor for quinine cardiotoxicity and sudden death Hence monitoring of serum calcium in severe malarial infection and cautious use of quinine in such patients is very important in management

  10. A CAD MODEL FOR FUZZY CONCURRENT TOLERANCE

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Research situation of concurrent tolerance design has been analyzed. As fuzzy factors are objective and unavoidable in concurrent tolerance design, fuzzy optimization theory is applied in the design. A new mathematical model of concurrent tolerance design is constructed.

  11. Reference Capabilities for Concurrency Control

    OpenAIRE

    Castegren, Elias; Wrigstad, Tobias

    2016-01-01

    The proliferation of shared mutable state in object-oriented programming complicates software development as two seemingly unrelated operations may interact via an alias and produce unexpected results. In concurrent programming this manifests itself as data-races. Concurrent object-oriented programming further suffers from the fact that code that warrants synchronisation cannot easily be distinguished from code that does not. The burden is placed solely on the programmer to reason ab...

  12. Concurrent engineering: effective deployment strategies

    Directory of Open Access Journals (Sweden)

    Unny Menon

    1996-12-01

    Full Text Available This paper provides a comprehensive insight into current trends and developments in Concurrent Engineering for integrated development of products and processes with the goal of completing the entire cycle in a shorter time, at lower overall cost and with fewer engineering design changes after product release. The evolution and definition of Concurrent Engineering are addressed first, followed by a concise review of the following elements of the concurrent engineering approach to product development: Concept Development: The Front-End Process, identifying Customer Needs and Quality Function Deployment, Establishing Product Specifications, Concept Selection, Product Architecture, Design for Manufacturing, Effective Rapid Prototyping, and The Economics of Product Development. An outline of a computer-based tutorial developed by the authors and other graduate students funded by NASA ( accessible via the world-wide-web . is provided in this paper. A brief discussion of teamwork for successful concurrent engineering is included, t'ase histories of concurrent engineering implementation at North American and European companies are outlined with references to textbooks authored by Professor Menon and other writers. A comprehensive bibliography on concurrent engineering is included in the paper.

  13. Detection of Plasmodium sp. in capybara.

    Science.gov (United States)

    dos Santos, Leonilda Correia; Curotto, Sandra Mara Rotter; de Moraes, Wanderlei; Cubas, Zalmir Silvino; Costa-Nascimento, Maria de Jesus; de Barros Filho, Ivan Roque; Biondo, Alexander Welker; Kirchgatter, Karin

    2009-07-07

    In the present study, we have microscopically and molecularly surveyed blood samples from 11 captive capybaras (Hydrochaeris hydrochaeris) from the Sanctuary Zoo for Plasmodium sp. infection. One animal presented positive on blood smear by light microscopy. Polymerase chain reaction was carried out accordingly using a nested genus-specific protocol, which uses oligonucleotides from conserved sequences flanking a variable sequence region in the small subunit ribosomal RNA (ssrRNA) of all Plasmodium organisms. This revealed three positive animals. Products from two samples were purified and sequenced. The results showed less than 1% divergence between the two capybara sequences. When compared with GenBank sequences, a 55% similarity was obtained to Toxoplasma gondii and a higher similarity (73-77.2%) was found to ssrRNAs from Plasmodium species that infect reptile, avian, rodents, and human beings. The most similar Plasmodium sequence was from Plasmodium mexicanum that infects lizards of North America, where around 78% identity was found. This work is the first report of Plasmodium in capybaras, and due to the low similarity with other Plasmodium species, we suggest it is a new species, which, in the future could be denominated "Plasmodium hydrochaeri".

  14. Plasmodium vivax malaria: An unusual presentation

    Directory of Open Access Journals (Sweden)

    Kasliwal Prasad

    2009-01-01

    Full Text Available Acute renal failure, disseminated intravascular coagulation (DIC, acute respiratory distress syndrome (ARDS, hypoglycemia, coma, or epileptic seizures are manifestations of severe Plasmodium falciparum malaria. On the other hand, Plasmodium vivax malaria seldom results in pulmonary damage, and pulmonary complications are exceedingly rare. We report the case of a 42-year-old male living in a malaria-endemic area who presented with ARDS and was diagnosed as having Plasmodium vivax malaria. A diagnosis of Plasmodium vivax malaria was established by a positive Plasmodium LDH immunochromatographic assay while a negative PfHRP2 based assay ruled out P. falciparum malaria. After specific anti-plasmodial therapy and intensive supportive care, the patient recovered and was discharged from hospital. The use of NIPPV in vivax-malaria related ARDS was associated with a good outcome.

  15. Managing Complexity of Control Software through Concurrency

    NARCIS (Netherlands)

    Hilderink, G.H.

    2005-01-01

    In this thesis, we are concerned with the development of concurrent software for embedded systems. The emphasis is on the development of control software. Embedded systems are concurrent systems whereby hardware and software communicate with the concurrent world. Concurrency is essential, which

  16. Control of Plasmodium knowlesi malaria

    Science.gov (United States)

    Abdullahi, Mohammed Baba; Hasan, Yahya Abu; Abdullah, Farah Aini

    2015-10-01

    The most significant and efficient measures against Plasmodium knowlesi outbreaks are efficient anti malaria drug, biological control in form of predatory mosquitoes and culling control strategies. In this paper optimal control theory is applied to a system of ordinary differential equation. It describes the disease transmission and Pontryagin's Maximum Principle is applied for analysis of the control. To this end, three control strategies representing biological control, culling and treatment were incorporated into the disease transmission model. The simulation results show that the implementation of the combination strategy during the epidemic is the most cost-effective strategy for disease transmission.

  17. The periodicity of Plasmodium vivax and Plasmodium falciparum in Venezuela.

    Science.gov (United States)

    Grillet, María-Eugenia; El Souki, Mayida; Laguna, Francisco; León, José Rafael

    2014-01-01

    We investigated the periodicity of Plasmodium vivax and P. falciparum incidence in time-series of malaria data (1990-2010) from three endemic regions in Venezuela. In particular, we determined whether disease epidemics were related to local climate variability and regional climate anomalies such as the El Niño Southern Oscillation (ENSO). Malaria periodicity was found to exhibit unique features in each studied region. Significant multi-annual cycles of 2- to about 6-year periods were identified. The inter-annual variability of malaria cases was coherent with that of SSTs (ENSO), mainly at temporal scales within the 3-6 year periods. Additionally, malaria cases were intensified approximately 1 year after an El Niño event, a pattern that highlights the role of climate inter-annual variability in the epidemic patterns. Rainfall mediated the effect of ENSO on malaria locally. Particularly, rains from the last phase of the season had a critical role in the temporal dynamics of Plasmodium. The malaria-climate relationship was complex and transient, varying in strength with the region and species. By identifying temporal cycles of malaria we have made a first step in predicting high-risk years in Venezuela. Our findings emphasize the importance of analyzing high-resolution spatial-temporal data to better understand malaria transmission dynamics. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Concurrent Engineering Research and Application

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Research and application of Concurrent Engineering have produced good results. A Chinese style concurrent engineering architecture and reference mode has been produced. A series of break thoughts in BPR (Business Process Reengineering) have been made with organization of the IPT (Integrated Product Development Team) and engineering support technologies. Several prototype tools were developed, including product development process modeling and management, QFD-based schema design and decision making, PDM-based concurrent design, STEP-based CAD/CAPP/CAM integration, design for assembly, design for manufacturing, computer aided fixture design, and machining process simulation. Finally, the research results were used in the development of two complex components in an aerospace application, and satisfactory results were obtained.

  19. STU attractors from vanishing concurrence

    CERN Document Server

    Lévay, Péter

    2010-01-01

    Concurrence is an entanglement measure characterizing the {\\it mixed} state bipartite correlations inside of a pure state of an $n$-qubit system. We show that after organizing the charges and the moduli in the STU model of $N=2$, $d=4$ supergravity to a three-qubit state, for static extremal spherically symmetric BPS black hole solutions the vanishing condition for all of the bipartite concurrences on the horizon is equivalent to the attractor equations. As a result of this the macroscopic black hole entropy given by the three-tangle can be reinterpreted as a linear entropy characterizing the {\\it pure} state entanglement for an arbitrary bipartite split. Both for the BPS and non-BPS cases explicit expressions for the concurrences are obtained, with their vanishing on the horizon is demonstrated.

  20. Fuzzy simulation in concurrent engineering

    Science.gov (United States)

    Kraslawski, A.; Nystrom, L.

    1992-01-01

    Concurrent engineering is becoming a very important practice in manufacturing. A problem in concurrent engineering is the uncertainty associated with the values of the input variables and operating conditions. The problem discussed in this paper concerns the simulation of processes where the raw materials and the operational parameters possess fuzzy characteristics. The processing of fuzzy input information is performed by the vertex method and the commercial simulation packages POLYMATH and GEMS. The examples are presented to illustrate the usefulness of the method in the simulation of chemical engineering processes.

  1. Concurrency & Asynchrony in Declarative Workflows

    DEFF Research Database (Denmark)

    Debois, Søren; Hildebrandt, Thomas; Slaats, Tijs

    2015-01-01

    Declarative or constraint-based business process and workflow notations have received increasing interest in the last decade as possible means of addressing the challenge of supporting at the same time flexibility in execution, adaptability and compliance. However, the definition of concurrent...... of concurrency in DCR Graphs admits asynchronous execution of declarative workflows both conceptually and by reporting on a prototype implementation of a distributed declarative workflow engine. Both the theoretical development and the implementation is supported by an extended example; moreover, the theoretical...

  2. Fuzzy simulation in concurrent engineering

    Science.gov (United States)

    Kraslawski, A.; Nystrom, L.

    1992-01-01

    Concurrent engineering is becoming a very important practice in manufacturing. A problem in concurrent engineering is the uncertainty associated with the values of the input variables and operating conditions. The problem discussed in this paper concerns the simulation of processes where the raw materials and the operational parameters possess fuzzy characteristics. The processing of fuzzy input information is performed by the vertex method and the commercial simulation packages POLYMATH and GEMS. The examples are presented to illustrate the usefulness of the method in the simulation of chemical engineering processes.

  3. Session-based concurrency, reactively

    NARCIS (Netherlands)

    M. Cano (Mauricio); J. Arias (Jaime); J.A. Pérez Parra (Jorge)

    2017-01-01

    textabstractThis paper concerns formal models for the analysis of communication-centric software systems that feature declarative and reactive behaviors. We focus on session-based concurrency, the interaction model induced by session types, which uses (variants of) the Π-calculus as specification

  4. Teaching Concurrency: Theory in Practice

    DEFF Research Database (Denmark)

    Aceto, Luca; Ingolfsdottir, Anna; Larsen, Kim Guldstrand

    2009-01-01

    in mathematics. We report here on our experiences in teaching concurrency theory over the last twenty years or so to students ranging from mathsphobic bachelor students to sophisticated doctoral students. The contents of the courses, the material on which they are based and the pedagogical philosophy underlying...

  5. Concurrency & Asynchrony in Declarative Workflows

    DEFF Research Database (Denmark)

    Debois, Søren; Hildebrandt, Thomas; Slaats, Tijs

    2015-01-01

    Declarative or constraint-based business process and workflow notations have received increasing interest in the last decade as possible means of addressing the challenge of supporting at the same time flexibility in execution, adaptability and compliance. However, the definition of concurrent se...... development has been verified correct in the Isabelle-HOL interactive theorem prover....

  6. Relationships between models of concurrency

    DEFF Research Database (Denmark)

    Nielsen, Mogens; Sassone, Vladimiro; Winskel, Glynn

    1994-01-01

    Models for concurrency can be classified with respect to the three relevant parameters: behaviour/system, interleaving/noninterleaving, linear/branching time. When modelling a process, a choice concerning such parameters corresponds to choosing the level of abstraction of the resulting semantics....... The classifications are formalized through the medium of category theory....

  7. Bisimulation for models in concurrency

    DEFF Research Database (Denmark)

    Nielsen, Mogens; Clausen, Christian

    1994-01-01

    Recently, Joyal, Nielsen and Winskel suggested a categorical definition of bisimulation, applicable to a wide range of models in concurrency with an accompanying notion af observations. The definition is in terms of span of open maps, and it coincides with Park and Milner's strong bisimulation...

  8. The system of concurrent engineering

    NARCIS (Netherlands)

    Wognum, Nel; Trienekens, Jacques

    2015-01-01

    Concurrent engineering (CE) has been a major theme in the 80s and 90s of the previous century in research and practice. Its main aim is to reduce time-tomarket, improve quality and reduce costs by taking into account downstream requirements and constraints already in the design phase. While start

  9. Visualization of Concurrent Program Executions

    Science.gov (United States)

    Artho, Cyrille; Havelund, Klaus; Honiden, Shinichi

    2007-01-01

    Various program analysis techniques are efficient at discovering failures and properties. However, it is often difficult to evaluate results, such as program traces. This calls for abstraction and visualization tools. We propose an approach based on UML sequence diagrams, addressing shortcomings of such diagrams for concurrency. The resulting visualization is expressive and provides all the necessary information at a glance.

  10. Concurrency & Asynchrony in Declarative Workflows

    DEFF Research Database (Denmark)

    Debois, Søren; Hildebrandt, Thomas; Slaats, Tijs

    2015-01-01

    Declarative or constraint-based business process and workflow notations have received increasing interest in the last decade as possible means of addressing the challenge of supporting at the same time flexibility in execution, adaptability and compliance. However, the definition of concurrent se...... development has been verified correct in the Isabelle-HOL interactive theorem prover....

  11. True Concurrency can be Traced

    DEFF Research Database (Denmark)

    Engberg, Uffe Henrik

    1990-01-01

    In this paper sets of labelled partial orders are employed as fundamental mathematical entities for modelling nondeterministic and concurrent processes thereby obtaining so-called noninterleaving semantics. Based on closures of sets of labelled partial orders, a simple algebraic language with ref...

  12. The composition of concurrent programs

    Science.gov (United States)

    Chandy, K. Mani; Taylor, Stephen

    1989-01-01

    A notation is presented for concurrent programs called program composition notation (PCN). The notation is being implemented at Caltech on multicomputers (a network of computers that communicate by sending and receiving messages). A fragment of this notation has been implemented on a data-parallel computer, the Connection Machine. The central ideas underlying PCN are discussed.

  13. Modal abstractions of concurrent behavior

    DEFF Research Database (Denmark)

    Nielson, Flemming; Nanz, Sebastian; Nielson, Hanne Riis

    2011-01-01

    We present an effective algorithm for the automatic construction of finite modal transition systems as abstractions of potentially infinite concurrent processes. Modal transition systems are recognized as valuable abstractions for model checking because they allow for the validation as well as re...

  14. A Model for Concurrent Objects

    DEFF Research Database (Denmark)

    Sørensen, Morten U.

    1996-01-01

    We present a model for concurrent objects where obejcts interact by taking part in common events that are closely matched to form call-response pairs, resulting in resulting in rendez-vous like communications. Objects are built from primitive objects by parallel composition, encapsulation and hid...

  15. True Concurrency can be Traced

    DEFF Research Database (Denmark)

    Engberg, Uffe Henrik

    1990-01-01

    In this paper sets of labelled partial orders are employed as fundamental mathematical entities for modelling nondeterministic and concurrent processes thereby obtaining so-called noninterleaving semantics. Based on closures of sets of labelled partial orders, a simple algebraic language with ref...

  16. Plasmodium falciparum malaria associated with ABO blood ...

    African Journals Online (AJOL)

    Plasmodium falciparum malaria associated with ABO blood phenotypes and ... out to investigate the relationship between blood group types and P. falciparum ... of long lasting treated (LLT) mosquito bed nets and the prevalence of infection.

  17. Limitations of microscopy to differentiate Plasmodium species in a region co-endemic for Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi

    OpenAIRE

    Barber Bridget E; William Timothy; Grigg Matthew J; Yeo Tsin W; Anstey Nicholas M

    2013-01-01

    Abstract Background In areas co-endemic for multiple Plasmodium species, correct diagnosis is crucial for appropriate treatment and surveillance. Species misidentification by microscopy has been reported in areas co-endemic for vivax and falciparum malaria, and may be more frequent in regions where Plasmodium knowlesi also commonly occurs. Methods This prospective study in Sabah, Malaysia, evaluated the accuracy of routine district and referral hospital-based microscopy, and microscopy perfor...

  18. Genome-scale comparison of expanded gene families in Plasmodium ovale wallikeri and Plasmodium ovale curtisi with Plasmodium malariae and with other Plasmodium species

    KAUST Repository

    Ansari, Hifzur Rahman

    2016-07-05

    Malaria in humans is caused by six species of Plasmodium parasites, of which the nuclear genome sequences for the two Plasmodium ovale spp., P. ovale curtisi and P. ovale wallikeri, and Plasmodium malariae have not yet been analyzed. Here we present an analysis of the nuclear genome sequences of these three parasites, and describe gene family expansions therein. Plasmodium ovale curtisi and P. ovale wallikeri are genetically distinct but morphologically indistinguishable and have sympatric ranges through the tropics of Africa, Asia and Oceania. Both P. ovale spp. show expansion of the surfin variant gene family, and an amplification of the Plasmodium interspersed repeat (pir) superfamily which results in an approximately 30% increase in genome size. For comparison, we have also analyzed the draft nuclear genome of P. malariae, a malaria parasite causing mild malaria symptoms with a quartan life cycle, long-term chronic infections, and wide geographic distribution. Plasmodium malariae shows only a moderate level of expansion of pir genes, and unique expansions of a highly diverged transmembrane protein family with over 550 members and the gamete P25/27 gene family. The observed diversity in the P. ovale wallikeri and P. ovale curtisi surface antigens, combined with their phylogenetic separation, supports consideration that the two parasites be given species status.

  19. Telomeric Heterochromatin in Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Rosaura Hernandez-Rivas

    2010-01-01

    Full Text Available Until very recently, little was known about the chromatin structure of the telomeres and subtelomeric regions in Plasmodium falciparum. In yeast and Drosophila melanogaster, chromatin structure has long been known to be an important aspect in the regulation and functioning of these regions. Telomeres and subtelomeric regions are enriched in epigenetic marks that are specific to heterochromatin, such as methylation of lysine 9 of histone H3 and lysine 20 of histone H4. In P. falciparum, histone modifications and the presence of both the heterochromatin “writing” (PfSir2, PKMT and “reading” (PfHP1 machinery at telomeric and subtelomeric regions indicate that these regions are likely to have heterochromatic structure that is epigenetically regulated. This structure may be important for telomere functions such as the silencing of the var gene family implicated in the cytoadherence and antigenic variation of these parasites.

  20. Plasmodium vivax Transmission in Africa.

    Directory of Open Access Journals (Sweden)

    Rosalind E Howes

    2015-11-01

    Full Text Available Malaria in sub-Saharan Africa has historically been almost exclusively attributed to Plasmodium falciparum (Pf. Current diagnostic and surveillance systems in much of sub-Saharan Africa are not designed to identify or report non-Pf human malaria infections accurately, resulting in a dearth of routine epidemiological data about their significance. The high prevalence of Duffy negativity provided a rationale for excluding the possibility of Plasmodium vivax (Pv transmission. However, review of varied evidence sources including traveller infections, community prevalence surveys, local clinical case reports, entomological and serological studies contradicts this viewpoint. Here, these data reports are weighted in a unified framework to reflect the strength of evidence of indigenous Pv transmission in terms of diagnostic specificity, size of individual reports and corroboration between evidence sources. Direct evidence was reported from 21 of the 47 malaria-endemic countries studied, while 42 countries were attributed with infections of visiting travellers. Overall, moderate to conclusive evidence of transmission was available from 18 countries, distributed across all parts of the continent. Approximately 86.6 million Duffy positive hosts were at risk of infection in Africa in 2015. Analysis of the mechanisms sustaining Pv transmission across this continent of low frequency of susceptible hosts found that reports of Pv prevalence were consistent with transmission being potentially limited to Duffy positive populations. Finally, reports of apparent Duffy-independent transmission are discussed. While Pv is evidently not a major malaria parasite across most of sub-Saharan Africa, the evidence presented here highlights its widespread low-level endemicity. An increased awareness of Pv as a potential malaria parasite, coupled with policy shifts towards species-specific diagnostics and reporting, will allow a robust assessment of the public health

  1. Data refinement for true concurrency

    Directory of Open Access Journals (Sweden)

    Brijesh Dongol

    2013-05-01

    Full Text Available The majority of modern systems exhibit sophisticated concurrent behaviour, where several system components modify and observe the system state with fine-grained atomicity. Many systems (e.g., multi-core processors, real-time controllers also exhibit truly concurrent behaviour, where multiple events can occur simultaneously. This paper presents data refinement defined in terms of an interval-based framework, which includes high-level operators that capture non-deterministic expression evaluation. By modifying the type of an interval, our theory may be specialised to cover data refinement of both discrete and continuous systems. We present an interval-based encoding of forward simulation, then prove that our forward simulation rule is sound with respect to our data refinement definition. A number of rules for decomposing forward simulation proofs over both sequential and parallel composition are developed.

  2. Antimalarial iron chelator, FBS0701, shows asexual and gametocyte Plasmodium falciparum activity and single oral dose cure in a murine malaria model.

    Directory of Open Access Journals (Sweden)

    Patricia Ferrer

    Full Text Available Iron chelators for the treatment of malaria have proven therapeutic activity in vitro and in vivo in both humans and mice, but their clinical use is limited by the unsuitable absorption and pharmacokinetic properties of the few available iron chelators. FBS0701, (S3"-(HO-desazadesferrithiocin-polyether [DADFT-PE], is an oral iron chelator currently in Phase 2 human studies for the treatment of transfusional iron overload. The drug has very favorable absorption and pharmacokinetic properties allowing for once-daily use to deplete circulating free iron with human plasma concentrations in the high µM range. Here we show that FBS0701 has inhibition concentration 50% (IC(50 of 6 µM for Plasmodium falciparum in contrast to the IC(50 for deferiprone and deferoxamine at 15 and 30 µM respectively. In combination, FBS0701 interfered with artemisinin parasite inhibition and was additive with chloroquine or quinine parasite inhibition. FBS0701 killed early stage P. falciparum gametocytes. In the P. berghei Thompson suppression test, a single dose of 100 mg/kg reduced day three parasitemia and prolonged survival, but did not cure mice. Treatment with a single oral dose of 100 mg/kg one day after infection with 10 million lethal P. yoelii 17XL cured all the mice. Pretreatment of mice with a single oral dose of FBS0701 seven days or one day before resulted in the cure of some mice. Plasma exposures and other pharmacokinetics parameters in mice of the 100 mg/kg dose are similar to a 3 mg/kg dose in humans. In conclusion, FBS0701 demonstrates a single oral dose cure of the lethal P. yoelii model. Significantly, this effect persists after the chelator has cleared from plasma. FBS0701 was demonstrated to remove labile iron from erythrocytes as well as enter erythrocytes to chelate iron. FBS0701 may find clinically utility as monotherapy, a malarial prophylactic or, more likely, in combination with other antimalarials.

  3. PyCSP - controlled concurrency

    DEFF Research Database (Denmark)

    Vinter, Brian; Friborg, Rune Møllegaard; Bjørndalen, John Markus

    2010-01-01

    Producing readable and correct programs while at the same time taking advantage of multi-core architectures is a challenge. PyCSP is an implementation of Communicating Sequential Processes algebra (CSP) for the Python programming language, that take advantage of CSP's formal and verifiable approach...... to controlling concurrency and the readability of Python source code. We describe PyCSP, demonstrate it through examples and demonstrate how PyCSP compares to Pthreads in a master-worker benchmark....

  4. PyCSP - controlled concurrency

    DEFF Research Database (Denmark)

    Friborg, Rune Møllegaard; Vinter, Brian; Bjørndalen, John Markus

    Producing readable and correct programs while at the same time taking advantage of multi-core architectures is a challenge. PyCSP is an implementation of Communicating Sequential Processes algebra (CSP) for the Python programming language, taking advantage of CSP’s formal and verifiable approach...... to controlling concurrency and the readability of Python source code. We describe PyCSP, demonstrate it through examples and demonstrate how PyCSP compares to Pthreads using a benchmark....

  5. Debugging Concurrent Software:Advances and Challenges

    Institute of Scientific and Technical Information of China (English)

    Jeff Huang; Charles Zhang

    2016-01-01

    Concurrency debugging is an extremely important yet challenging problem that has been hampering developer productivity and software reliability in the multicore era. We have worked on this problem in the past eight years and have developed several effective methods and automated tools for helping developers debugging shared memory concurrent programs. This article discusses challenges in concurrency debugging and summarizes our research contributions in four important directions: concurrency bug reproduction, detection, understanding, and fixing. It also discusses other recent advances in tackling these challenges.

  6. Concurrent chemoradiation for vaginal cancer.

    Directory of Open Access Journals (Sweden)

    David T Miyamoto

    Full Text Available BACKGROUND: It is not known whether the addition of chemotherapy to radiation therapy improves outcomes in primary vaginal cancer. Here, we review clinical outcomes in patients with primary vaginal cancer treated with radiation therapy (RT or concurrent chemoradiation therapy (CRT. METHODS: Seventy-one patients with primary vaginal cancer treated with definitive RT with or without concurrent chemotherapy at a single institution were identified and their records reviewed. A total of 51 patients were treated with RT alone; 20 patients were treated with CRT. Recurrences were analyzed. Overall survival (OS and disease-free survival (DFS rates were estimated using the Kaplan-Meier method. Cox regression analysis was performed. RESULTS: The median age at diagnosis was 61 years (range, 18-92 years and the median follow-up time among survivors was 3.0 years. Kaplan-Meier estimates for OS and DFS differed significantly between the RT and CRT groups (3-yr OS = 56% vs. 79%, log-rank p = 0.037; 3-yr DFS = 43% vs. 73%, log-rank p = 0.011. Twenty-three patients (45% in the RT group had a relapse at any site compared to 3 (15% in the CRT group (p = 0.027. With regard to the sites of first relapse, 10 patients (14% had local only, 4 (6% had local and regional, 9 (13% had regional only, 1 (1% had regional and distant, and 2 (3% had distant only relapse. On univariate analysis, the use of concurrent chemotherapy, FIGO stage, tumor size, and date of diagnosis were significant predictors of DFS. On multivariate analysis, the use of concurrent chemotherapy remained a significant predictor of DFS (hazard ratio 0.31 (95% CI, 0.10-0.97; p = 0.04. CONCLUSIONS: Vaginal cancer results in poor outcomes. Adequate radiation dose is essential to ensure curative management. Concurrent chemotherapy should be considered for vaginal cancer patients.

  7. Simple concurrent garbage collection almost without synchronization

    NARCIS (Netherlands)

    Hesselink, Wim H.; Lali, M.I.

    2010-01-01

    We present two simple mark and sweep algorithms, A and B, for concurrent garbage collection by a single collector running concurrently with a number of mutators that concurrently modify shared data. Both algorithms are based on the ideas of Ben-Ari's classical algorithm for on-the-fly garbage collec

  8. Simple concurrent garbage collection almost without synchronization

    NARCIS (Netherlands)

    Hesselink, Wim H.; Lali, M.I.

    We present two simple mark and sweep algorithms, A and B, for concurrent garbage collection by a single collector running concurrently with a number of mutators that concurrently modify shared data. Both algorithms are based on the ideas of Ben-Ari's classical algorithm for on-the-fly garbage

  9. Immunologic effects of mononuclear-macrophages on parasites during the infection of Plasmodium yoelii%抗约氏疟原虫感染过程中单核-巨噬细胞免疫效应的研究

    Institute of Scientific and Technical Information of China (English)

    刘英杰; 曹雅明; 阎建忠

    2002-01-01

    目的探讨单核-巨噬细胞及其分泌的NO在抗疟原虫感染过程中的作用.方法应用吉姆萨薄血膜染色法和腹腔注射鸡红细胞法分别检测红细胞感染率及单核细胞和腹腔MΦ的吞噬能力;通过Griess反应检测小鼠腹腔MΦ合成NO水平.结果腹腔MΦ在感染后6d吞噬率即达到高峰,单核细胞的数目和吞噬能力在感染6d后开始增加,同时,虫体血症水平升高的趋势受到遏制;感染早期MΦ合成NO水平逐渐升高,但对虫体血症没有影响.结论单核-巨噬细胞数量的增加和巨大吞噬杀伤作用的发挥可削减并最终清除虫体血症;但感染早期MΦ合成NO水平逐渐升高的意义尚需进一步研究.

  10. In vitro Observation on Effect of Nitric Oxide on Exflagellation of Plasmodium yoelii%体外观察一氧化氮对约氏疟原虫雄配子形成的影响

    Institute of Scientific and Technical Information of China (English)

    刘英杰; 王继春; 冯辉; 朱晓彤; 安春丽; 曹雅明

    2007-01-01

    目的 体外观察一氧化氮(NO)对疟原虫雄配子形成的影响.方法 约氏疟原虫感染DBA/2小鼠,制备薄血膜吉氏(Giemsa)染色观察小鼠原虫血症和配子体血症水平.并通过Griess反应检测脾细胞产生的NO水平.感染第4天,实验组小鼠注射不同剂量的一氧化氮发生剂(NOC5),对照组小鼠注射NOG5前体物质,分别采集其注射前、注射后30 min和60 min的尾静脉血;感染第6天,实验组小鼠注射一氧化氮合酶抑制剂(L-NMMA),对照组小鼠分别注射D-NMMA和PBS,分别采集其注射前、注射后4 h和8 h的尾静脉血.体外培养采集的血液,观察雄配子形成.结果 感染后第4天和第6天,小鼠脾细胞合成NO水平分别为16.5 mmol/L和30.4 mmol/L,而雄配子形成数分别为11.33和0.66;感染第4天小鼠注射1 mg NOC5后30 min和60 min的雄配子形成数分别为5.33和2.66,显著低于其对照组(P<0.01);感染第6天小鼠注射L-NMMA后8 h的雄配子形成数为1.83,显著高于其对照组(P<0.01).结论 NO可直接抑制疟原虫雄配子形成,是导致疟疾自然传播阻断现象发生的主要效应分子.

  11. Survival strategies of the malarial parasite Plasmodium falciparum

    OpenAIRE

    Ramya, TNC; Surolia, Namita; Surolia, Avadhesha

    2002-01-01

    Plasmodium falciparum, the protozoan parasite causing falciparum malaria, is undoubtedly highly versatile when it comes to survival and defence strategies. Strategies adopted by the asexual blood stages of Plasmodium range from unique pathways of nutrient uptake to immune evasion strategies and multiple drug resistance. Studying the survival strategies of Plasmodium could help us envisage strategies of tackling one of the worst scourges of mankind.

  12. Concurrent fractional and equilibrium crystallisation

    Science.gov (United States)

    Sha, Lian-Kun

    2012-06-01

    This paper proposes the concept of concurrent fractional and equilibrium crystallisation (CFEC) in a multi-phase magmatic system in light of experimental results on diffusivities of elements and other species in minerals and melts. A group of equations are presented to describe how the concentrations of an element or isotope change in fractionated solid, equilibrated solid, melt, liquid, and gas phases, as well as in magma, as a function of distribution coefficients and mass fractions during the CFEC process. CFEC model is a generalised and unified formulation that is valid, not only for pure fractional crystallisation (FC) and perfect equilibrium crystallisation (EC) singly, as two of its limiting end-member cases, but also for the geologically more important process of concurrent fractional and equilibrium crystallisation. The concept that both fractional and equilibrium crystallisation can operate concurrently in a magmatic system, for a given element, among different minerals, and even within different-sized crystal grains of the very same mineral phase, is of fundamental importance in deepening our current understanding of magmatic differentiation processes. CFEC probably occurs more frequently in the natural world than either pure fractional or perfect equilibrium crystallisation alone, as a result of the interplay of varying diffusivities of elements under diverse physicochemical conditions, different residence time and growth rates of mineral phases in magmas, and varying grain sizes within each phase and among different phases. The marked systematic variations in trace element concentrations in the melts of the Bishop Tuff have long been perplexing and difficult to reconcile with existing models of differentiation. CFEC, which is able to better explain the scatter trends in a systematic way than fractional crystallisation, is considered to be the cause.

  13. Concurrent engineering teams. Volume 2: Annotated bibliography

    Science.gov (United States)

    Richter, Karen J.; Dierolf, David A.

    1990-11-01

    Specific concurrent engineering practices vary among organizations. There are, however, various management practices that appear to work well for most organizations. This paper presents the reader with specific, useful examples from several defense contractors illustrating how multifunctional concurrent engineering teams are being organized and managed and how concurrent engineering team meetings are conducted and supported. The types of computer support that could be used to enhance the efficiency and effectiveness of concurrent engineering team meetings are identified. The general findings are that there exists a direct relationship between total quality management (TQM) and concurrent engineering, and that many applications of computer-aided group problem solving are possible and practical today for the concurrent engineering team meetings. Areas identified for additional research are the documentation of the decision process and rationale during the product and process definition, the capturing of lessons learned during the implementation of concurrent engineering, and the performance evaluation and training of team members.

  14. Helminth Parasites Alter Protection against Plasmodium Infection

    Directory of Open Access Journals (Sweden)

    Víctor H. Salazar-Castañon

    2014-01-01

    Full Text Available More than one-third of the world’s population is infected with one or more helminthic parasites. Helminth infections are prevalent throughout tropical and subtropical regions where malaria pathogens are transmitted. Malaria is the most widespread and deadliest parasitic disease. The severity of the disease is strongly related to parasite density and the host’s immune responses. Furthermore, coinfections between both parasites occur frequently. However, little is known regarding how concomitant infection with helminths and Plasmodium affects the host’s immune response. Helminthic infections are frequently massive, chronic, and strong inductors of a Th2-type response. This implies that infection by such parasites could alter the host’s susceptibility to subsequent infections by Plasmodium. There are a number of reports on the interactions between helminths and Plasmodium; in some, the burden of Plasmodium parasites increased, but others reported a reduction in the parasite. This review focuses on explaining many of these discrepancies regarding helminth-Plasmodium coinfections in terms of the effects that helminths have on the immune system. In particular, it focuses on helminth-induced immunosuppression and the effects of cytokines controlling polarization toward the Th1 or Th2 arms of the immune response.

  15. Helminth Parasites Alter Protection against Plasmodium Infection

    Science.gov (United States)

    Salazar-Castañon, Víctor H.; Legorreta-Herrera, Martha

    2014-01-01

    More than one-third of the world's population is infected with one or more helminthic parasites. Helminth infections are prevalent throughout tropical and subtropical regions where malaria pathogens are transmitted. Malaria is the most widespread and deadliest parasitic disease. The severity of the disease is strongly related to parasite density and the host's immune responses. Furthermore, coinfections between both parasites occur frequently. However, little is known regarding how concomitant infection with helminths and Plasmodium affects the host's immune response. Helminthic infections are frequently massive, chronic, and strong inductors of a Th2-type response. This implies that infection by such parasites could alter the host's susceptibility to subsequent infections by Plasmodium. There are a number of reports on the interactions between helminths and Plasmodium; in some, the burden of Plasmodium parasites increased, but others reported a reduction in the parasite. This review focuses on explaining many of these discrepancies regarding helminth-Plasmodium coinfections in terms of the effects that helminths have on the immune system. In particular, it focuses on helminth-induced immunosuppression and the effects of cytokines controlling polarization toward the Th1 or Th2 arms of the immune response. PMID:25276830

  16. Concurrent Delay in Construction Disputes

    DEFF Research Database (Denmark)

    Cavaleri, Sylvie Cécile

    period of delay can potentially be attributed to several events falling within both parties' spheres of responsibility, commonly termed concurrent delay, is rarely regulated in construction contracts in spite of its common occurrence. This book analyses both the theoretical foundations and the practical......Delay is one of the issues most frequently encountered in today’s construction industry; it causes significant economic damage to all parties involved. Construction contracts, standard and bespoke, almost invariably consider delay from a perspective of single liability. If the event causing...

  17. Concurrent Delay in Construction Disputes

    DEFF Research Database (Denmark)

    Cavaleri, Sylvie Cécile

    Delay is one of the issues most frequently encountered in today’s construction industry; it causes significant economic damage to all parties involved. Construction contracts, standard and bespoke, almost invariably consider delay from a perspective of single liability. If the event causing...... period of delay can potentially be attributed to several events falling within both parties' spheres of responsibility, commonly termed concurrent delay, is rarely regulated in construction contracts in spite of its common occurrence. This book analyses both the theoretical foundations and the practical...

  18. Barriers in Concurrent Separation Logic

    Science.gov (United States)

    Hobor, Aquinas; Gherghina, Cristian

    We develop and prove sound a concurrent separation logic for Pthreads-style barriers. Although Pthreads barriers are widely used in systems, and separation logic is widely used for verification, there has not been any effort to combine the two. Unlike locks and critical sections, Pthreads barriers enable simultaneous resource redistribution between multiple threads and are inherently stateful, leading to significant complications in the design of the logic and its soundness proof. We show how our logic can be applied to a specific example program in a modular way. Our proofs are machine-checked in Coq.

  19. Accurate identification of the six human Plasmodium spp. causing imported malaria, including Plasmodium ovale wallikeri and Plasmodium knowlesi.

    Science.gov (United States)

    Calderaro, Adriana; Piccolo, Giovanna; Gorrini, Chiara; Rossi, Sabina; Montecchini, Sara; Dell'Anna, Maria Loretana; De Conto, Flora; Medici, Maria Cristina; Chezzi, Carlo; Arcangeletti, Maria Cristina

    2013-09-13

    Accurate identification of Plasmodium infections in non-endemic countries is of critical importance with regard to the administration of a targeted therapy having a positive impact on patient health and management and allowing the prevention of the risk of re-introduction of endemic malaria in such countries. Malaria is no longer endemic in Italy where it is the most commonly imported disease, with one of the highest rates of imported malaria among European non-endemic countries including France, the UK and Germany, and with a prevalence of 24.3% at the University Hospital of Parma. Molecular methods showed high sensitivity and specificity and changed the epidemiology of imported malaria in several non-endemic countries, highlighted a higher prevalence of Plasmodium ovale, Plasmodium vivax and Plasmodium malariae underestimated by microscopy and, not least, brought to light both the existence of two species of P. ovale (Plasmodium ovale curtisi and Plasmodium ovale wallikeri) and the infection in humans by Plasmodium knowlesi, otherwise not detectable by microscopy. In this retrospective study an evaluation of two real-time PCR assays able to identify P. ovale wallikeri, distinguishing it from P. ovale curtisi, and to detect P. knowlesi, respectively, was performed applying them on a subset of 398 blood samples belonging to patients with the clinical suspicion of malaria. These assays revealed an excellent analytical sensitivity and no cross-reactivity versus other Plasmodium spp. infecting humans, suggesting their usefulness for an accurate and complete diagnosis of imported malaria. Among the 128 patients with malaria, eight P. ovale curtisi and four P. ovale wallikeri infections were detected, while no cases of P. knowlesi infection were observed. Real-time PCR assays specific for P. ovale wallikeri and P. knowlesi were included in the panel currently used in the University Hospital of Parma for the diagnosis of imported malaria, accomplishing the goal of

  20. Occurrence of Plasmodium in Anatidae

    Science.gov (United States)

    Herman, C.M.; Kocan, R.M.

    1970-01-01

    Until a little over a decade ago reports of Plasrnodium in geese, ducks, and swans were the result of examination of single blood smears from wild birds. One would gather from the earlier studies that Anatidae are infrequently infected. During the past decade we have conducted studies on prevalence of Plasmodium by an isodiagnosis technique, inoculating blood from wild birds into captive young geese, ducks, and other species of birds and determining the status of infection in the donors by examination of repetitive blood smears from the recipients. Examination by this technique of a series of adult Canada geese from the Seney National Wildlife Refuge in northern Michigan uncovered a prevalence of 60% during five successive years. Domestic geese were the primary recipients but we found that several other species of geese, ducks, and gulls were also susceptible. Similar studies on Canada geese from other areas (Maryland, New Jersey, New York, and southern Michigan) uncovered infection rates from zero to 27%. Following isolation of Plasmodlum in a single canvasback duck (Aythya valisineria) in southern Michigan by inoculation into a domestic duck, a series of 88 canvasbacks from Chesapeake Bay in Maryland this winter uncovered an infection rate of 27%. The most common parasite observed in both the geese and was as P. circumflexum.

  1. Preparing HEP software for concurrency

    Science.gov (United States)

    Clemencic, M.; Hegner, B.; Mato, P.; Piparo, D.

    2014-06-01

    The necessity for thread-safe experiment software has recently become very evident, largely driven by the evolution of CPU architectures towards exploiting increasing levels of parallelism. For high-energy physics this represents a real paradigm shift, as concurrent programming was previously only limited to special, well-defined domains like control software or software framework internals. This paradigm shift, however, falls into the middle of the successful LHC programme and many million lines of code have already been written without the need for parallel execution in mind. In this paper we have a closer look at the offline processing applications of the LHC experiments and their readiness for the many-core era. We review how previous design choices impact the move to concurrent programming. We present our findings on transforming parts of the LHC experiment reconstruction software to thread-safe code, and the main design patterns that have emerged during the process. A plethora of parallel-programming patterns are well known outside the HEP community, but only a few have turned out to be straightforward enough to be suited for non-expert physics programmers. Finally, we propose a potential strategy for the migration of existing HEP experiment software to the many-core era.

  2. Analysis of Breath Specimens for Biomarkers of Plasmodium falciparum Infection.

    Science.gov (United States)

    Berna, Amalia Z; McCarthy, James S; Wang, Rosalind X; Saliba, Kevin J; Bravo, Florence G; Cassells, Julie; Padovan, Benjamin; Trowell, Stephen C

    2015-10-01

    Currently, the majority of diagnoses of malaria rely on a combination of the patient's clinical presentation and the visualization of parasites on a stained blood film. Breath offers an attractive alternative to blood as the basis for simple, noninvasive diagnosis of infectious diseases. In this study, breath samples were collected from individuals during controlled malaria to determine whether specific malaria-associated volatiles could be detected in breath. We identified 9 compounds whose concentrations varied significantly over the course of malaria: carbon dioxide, isoprene, acetone, benzene, cyclohexanone, and 4 thioethers. The latter group, consisting of allyl methyl sulfide, 1-methylthio-propane, (Z)-1-methylthio-1-propene, and (E)-1-methylthio-1-propene, had not previously been associated with any disease or condition. Before the availability of antimalarial drug treatment, there was evidence of concurrent 48-hour cyclical changes in the levels of both thioethers and parasitemia. When thioether concentrations were subjected to a phase shift of 24 hours, a direct correlation between the parasitemia and volatile levels was revealed. Volatile levels declined monotonically approximately 6.5 hours after initial drug treatment, correlating with clearance of parasitemia. No thioethers were detected in in vitro cultures of Plasmodium falciparum. The metabolic origin of the thioethers is not known, but results suggest that interplay between host and parasite metabolic pathways is involved in the production of these thioethers.

  3. Epidemiology of Plasmodium vivax Malaria in India

    OpenAIRE

    Anvikar, Anupkumar R; Shah, Naman; Dhariwal, Akshay C.; Sonal, Gagan Singh; Pradhan, Madan Mohan; Ghosh, Susanta K; Valecha, Neena

    2016-01-01

    Historically, malaria in India was predominantly caused by Plasmodium vivax, accounting for 53% of the estimated cases. After the spread of drug-resistant Plasmodium falciparum in the 1990s, the prevalence of the two species remained equivalent at the national level for a decade. By 2014, the proportion of P. vivax has decreased to 34% nationally, but with high regional variation. In 2014, P. vivax accounted for around 380,000 malaria cases in India; almost a sixth of all P. vivax cases repor...

  4. 47 CFR 61.136 - Revocation of concurrences.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Revocation of concurrences. 61.136 Section 61...) TARIFFS Concurrences § 61.136 Revocation of concurrences. A concurrence may be revoked by a revocation notice or cancelled by a new concurrence. A revocation notice or a new concurrence, if less broad...

  5. High prevalence of drug-resistance mutations in Plasmodium falciparum and Plasmodium vivax in southern Ethiopia

    OpenAIRE

    Schunk, Mirjam; Kumma, Wondimagegn P.; Barreto Miranda, Isabel; Maha E. Osman; Roewer, Susanne; Alano, Abraham; Loescher, Thomas; Bienzle, Ulrich; Mockenhaupt, Frank P

    2006-01-01

    Background: In Ethiopia, malaria is caused by both Plasmodium falciparum and Plasmodium vivax. Drug resistance of P. falciparum to sulfadoxine-pyrimethamine (SP) and chloroquine (CQ) is frequent and intense in some areas. Methods: In 100 patients with uncomplicated malaria from Dilla, southern Ethiopia, P. falciparum dhfr and dhps mutations as well as P. vivax dhfr polymorphisms associated with resistance to SP and P. falciparum pfcrt and pfmdr1 mutations conferring CQ resistance were assesse...

  6. Promoter regions of Plasmodium vivax are poorly or not recognized by Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    del Portillo Hernando A

    2007-02-01

    Full Text Available Abstract Background Heterologous promoter analysis in Plasmodium has revealed the existence of conserved cis regulatory elements as promoters from different species can drive expression of reporter genes in heterologous transfection assays. Here, the functional characterization of different Plasmodium vivax promoters in Plasmodium falciparum using luciferase as the reporter gene is presented. Methods Luciferase reporter plasmids harboring the upstream regions of the msp1, dhfr, and vir3 genes as well as the full-length intergenic regions of the vir23/24 and ef-1α genes of P. vivax were constructed and transiently transfected in P. falciparum. Results Only the constructs with the full-length intergenic regions of the vir23/24 and ef-1α genes were recognized by the P. falciparum transcription machinery albeit to values approximately two orders of magnitude lower than those reported by luc plasmids harbouring promoter regions from P. falciparum and Plasmodium berghei. A bioinformatics approach allowed the identification of a motif (GCATAT in the ef-1α intergenic region that is conserved in five Plasmodium species but is degenerate (GCANAN in P. vivax. Mutations of this motif in the P. berghei ef-1α promoter region decreased reporter expression indicating it is active in gene expression in Plasmodium. Conclusion Together, this data indicates that promoter regions of P. vivax are poorly or not recognized by the P. falciparum transcription machinery suggesting the existence of P. vivax-specific transcription regulatory elements.

  7. Concurrent Process Planning for Machined Parts

    Institute of Scientific and Technical Information of China (English)

    吴丹; 王先逵; 李志忠

    2002-01-01

    Detailed manufacturing information about the parts can help designers produce better designs. Detailed manufacturing information is conveyed to the designer through micro-circles within the concurrent design process for machined parts, focusing on instantaneous product design and process planning. The process has three key elements: a hierarchical architecture design of the concurrent process planning system, modeling and reengineering of the concurrent process planning, and modeling of information. The approach is successfully implemented and applied for concurrent design and process planning of some complicated parts.

  8. Automated Concurrent Blackboard System Generation in C++

    Science.gov (United States)

    Kaplan, J. A.; McManus, J. W.; Bynum, W. L.

    1999-01-01

    In his 1992 Ph.D. thesis, "Design and Analysis Techniques for Concurrent Blackboard Systems", John McManus defined several performance metrics for concurrent blackboard systems and developed a suite of tools for creating and analyzing such systems. These tools allow a user to analyze a concurrent blackboard system design and predict the performance of the system before any code is written. The design can be modified until simulated performance is satisfactory. Then, the code generator can be invoked to generate automatically all of the code required for the concurrent blackboard system except for the code implementing the functionality of each knowledge source. We have completed the port of the source code generator and a simulator for a concurrent blackboard system. The source code generator generates the necessary C++ source code to implement the concurrent blackboard system using Parallel Virtual Machine (PVM) running on a heterogeneous network of UNIX(trademark) workstations. The concurrent blackboard simulator uses the blackboard specification file to predict the performance of the concurrent blackboard design. The only part of the source code for the concurrent blackboard system that the user must supply is the code implementing the functionality of the knowledge sources.

  9. A Reference Framework for Concurrent Engineering

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Considering the diversity of methods and tools offered to concurrent engineering, the aspects playing important roles in the concurrent engineering c ontext have been pinpointed as being four core elements which are Activity, Meth od, Object and Information. Based on these four elements, a reference framework called AMOI is proposed to be the guideline for the systematic concurrent produc t design. Using the AMOI reference framework, concurrent product development sys tem can be structured into four function models (including the activity model, m ethod model, object model and information model) which are interconnected with e ach other.

  10. Epidemiology of Plasmodium vivax Malaria in India.

    Science.gov (United States)

    Anvikar, Anupkumar R; Shah, Naman; Dhariwal, Akshay C; Sonal, Gagan Singh; Pradhan, Madan Mohan; Ghosh, Susanta K; Valecha, Neena

    2016-12-28

    Historically, malaria in India was predominantly caused by Plasmodium vivax, accounting for 53% of the estimated cases. After the spread of drug-resistant Plasmodium falciparum in the 1990s, the prevalence of the two species remained equivalent at the national level for a decade. By 2014, the proportion of P. vivax has decreased to 34% nationally, but with high regional variation. In 2014, P. vivax accounted for around 380,000 malaria cases in India; almost a sixth of all P. vivax cases reported globally. Plasmodium vivax has remained resistant to control measures, particularly in urban areas. Urban malaria is predominantly caused by P. vivax and is subject to outbreaks, often associated with increased mortality, and triggered by bursts of migration and construction. The epidemiology of P. vivax varies substantially within India, including multiple relapse phenotypes with varying latencies between primary infection and relapse. Moreover, the hypnozoite reservoir maintains transmission potential and enables reestablishment of the parasite in areas in which it was thought eradicated. The burden of malaria in India is complex because of the highly variable malaria eco-epidemiological profiles, transmission factors, and the presence of multiple Plasmodium species and Anopheles vectors. This review of P. vivax malaria in India describes epidemiological trends with particular attention to four states: Gujarat, Karnataka, Haryana, and Odisha.

  11. Plasmodium falciparum Malaria, Southern Algeria, 2007

    OpenAIRE

    Boubidi, Saïd C; Gassen, Ibrahim; Khechache, Yacine; Lamali, Karima; Tchicha, Boualem; Brengues, Cécile; Menegon, Michela; Severini, Carlo; Fontenille, Didier; Harrat, Zoubir

    2010-01-01

    An outbreak of Plasmodium falciparum malaria occurred in Tinzaouatine in southern Algeria in 2007. The likely vector, Anopheles gambiae mosquitoes, had not been detected in Algeria. Genes for resistance to chloroquine were detected in the parasite. The outbreak shows the potential for an increase in malaria vectors in Algeria.

  12. Congenital Plasmodium falciparum Malaria in Washington, DC.

    Science.gov (United States)

    Del Castillo, Melissa; Szymanski, Ann Marie; Slovin, Ariella; Wong, Edward C C; DeBiasi, Roberta L

    2017-01-11

    Congenital malaria is rare in the United States, but is an important diagnosis to consider when evaluating febrile infants. Herein, we describe a case of congenital Plasmodium falciparum malaria in a 2-week-old infant born in the United States to a mother who had emigrated from Nigeria 3 months before delivery. © The American Society of Tropical Medicine and Hygiene.

  13. Plasmodium falciparum Malaria, Southern Algeria, 2007

    Science.gov (United States)

    Gassen, Ibrahim; Khechache, Yacine; Lamali, Karima; Tchicha, Boualem; Brengues, Cécile; Menegon, Michela; Severini, Carlo; Fontenille, Didier; Harrat, Zoubir

    2010-01-01

    An outbreak of Plasmodium falciparum malaria occurred in Tinzaouatine in southern Algeria in 2007. The likely vector, Anopheles gambiae mosquitoes, had not been detected in Algeria. Genes for resistance to chloroquine were detected in the parasite. The outbreak shows the potential for an increase in malaria vectors in Algeria. PMID:20113565

  14. Plasmodium falciparum Malaria, Southern Algeria, 2007

    OpenAIRE

    Boubidi, Saïd C; Gassen, Ibrahim; Khechache, Yacine; Lamali, Karima; Tchicha, Boualem; Brengues, Cécile; Menegon, Michela; Severini, Carlo; Fontenille, Didier; Harrat, Zoubir

    2010-01-01

    An outbreak of Plasmodium falciparum malaria occurred in Tinzaouatine in southern Algeria in 2007. The likely vector, Anopheles gambiae mosquitoes, had not been detected in Algeria. Genes for resistance to chloroquine were detected in the parasite. The outbreak shows the potential for an increase in malaria vectors in Algeria.

  15. Plasmodium knowlesi in travellers, update 2014.

    Science.gov (United States)

    Müller, Mattia; Schlagenhauf, Patricia

    2014-05-01

    Since the initial discovery of Plasmodium knowlesi in Malaysia, cases have been reported from several neighbouring countries. Tourism has also resulted in an increasing number of cases diagnosed in Europe, America, and Oceania. In this review we focus on the risk of the travel-associated acquisition of P. knowlesi malaria. A search of the literature in PubMed was carried out to identify articles and literature on the distribution of P. knowlesi infections in Southeast Asia and details of its acquisition and importation by travellers to other continents. The cut-off date for the search was December 1, 2013. Search words used were: "Plasmodium knowlesi", "Plasmodium knowlesi infections", "Plasmodium knowlesi travellers", "Plasmodium knowlesi prevalence", "Plasmodium knowlesi host", "Plasmodium knowlesi vector" "Plasmodium knowlesi RDT", and "Plasmodium knowlesi Malaysia". Traveller numbers to Malaysia were obtained from the Tourism Malaysia website. A total of 103 articles were found. Using a selection of these and others identified from the reference lists of the papers, we based our review on a total of 66 articles. P. knowlesi malaria appears to be the most common malaria species in Malaysian Borneo and is also widely distributed on the Malaysian mainland. Furthermore, locally transmitted cases of P. knowlesi malaria have been reported in Thailand, the Philippines, Vietnam, Singapore, Myanmar, Indonesian Borneo, and Cambodia. Two cases have been reported from non-endemic countries in Asia (Japan and Taiwan) in people with a history of travel to Malaysia and the Philippines. Twelve cases were imported to their home countries by travellers from other continents: two from the USA, two from the Netherlands, two from Germany, and one each from Spain, France, Sweden, Finland, Australia, and New Zealand. In most cases, the infection was associated with a trip to or near forested areas. The symptoms were fever (n=12), headache (n=6), chills (n=6), nausea (n=4), myalgia (n

  16. Concurrent partnerships and HIV: an inconvenient truth

    Directory of Open Access Journals (Sweden)

    Epstein Helen

    2011-03-01

    Full Text Available Abstract The strength of the evidence linking concurrency to HIV epidemic severity in southern and eastern Africa led the Joint United Nations Programme on HIV/AIDS and the Southern African Development Community in 2006 to conclude that high rates of concurrent sexual partnerships, combined with low rates of male circumcision and infrequent condom use, are major drivers of the AIDS epidemic in southern Africa. In a recent article in the Journal of the International AIDS Society, Larry Sawers and Eileen Stillwaggon attempt to challenge the evidence for the importance of concurrency and call for an end to research on the topic. However, their "systematic review of the evidence" is not an accurate summary of the research on concurrent partnerships and HIV, and it contains factual errors concerning the measurement and mathematical modelling of concurrency. Practical prevention-oriented research on concurrency is only just beginning. Most interventions to raise awareness about the risks of concurrency are less than two years old; few evaluations and no randomized-controlled trials of these programmes have been conducted. Determining whether these interventions can help people better assess their own risks and take steps to reduce them remains an important task for research. This kind of research is indeed the only way to obtain conclusive evidence on the role of concurrency, the programmes needed for effective prevention, the willingness of people to change behaviour, and the obstacles to change.

  17. Petri nets and other models of concurrency

    DEFF Research Database (Denmark)

    Nielsen, Mogens; Sassone, Vladimiro

    1998-01-01

    This paper retraces, collects, and summarises contributions of the authors - in collaboration with others - on the theme of Petri nets and their categorical relationships to other models of concurrency.......This paper retraces, collects, and summarises contributions of the authors - in collaboration with others - on the theme of Petri nets and their categorical relationships to other models of concurrency....

  18. Safety and Liveness in Concurrent Pointer Programs

    NARCIS (Netherlands)

    Distefano, Dino; Katoen, Joost-Pieter; Rensink, Arend; Boer, de Frank S.; Bonsangue, Marcello M.; Graf, Susanne; Roever, de Willem-Paul

    2006-01-01

    The incorrect use of pointers is one of the most common source of software errors. Concurrency has a similar characteristic. Proving the correctness of concurrent pointer manipulating programs, let alone algorithmically, is a highly non-trivial task. This paper proposes an automated verification tec

  19. Steps in Modular Specifications for Concurrent Modules

    DEFF Research Database (Denmark)

    Da Rocha Pinto, Pedro; Dinsdale-Young, Thomas; Gardner, Philippa

    2015-01-01

    The specification of a concurrent program module is a difficult problem. The specifications must be strong enough to enable reasoning about the intended clients without reference to the underlying module implementation. We survey a range of verification techniques for specifying concurrent module...

  20. Concurrent sourcing and external supplier opportunism

    DEFF Research Database (Denmark)

    Mols, Niels Peter

    When a firm simultaneously makes and buys the same components then the firm uses concurrent sourcing. This paper presents an agency model for explaining how and when concurrent sourcing reduces the likelihood of external supplier opportunism. In the proposed model, the external supplier’s expected...

  1. Interval-based Specification of Concurrent Objects

    DEFF Research Database (Denmark)

    Løvengreen, Hans Henrik; Sørensen, Morten U.

    1998-01-01

    We propose a logic for specifying the behaviour of concurrent objects, ie. concurrent entities that invoke operation of each other. The logic is an interval logic whith operation invocatins as primitive formulas. The strengths and deficiencies of the logic are illustrated by specifying a variety...

  2. A Temporal Concurrent Constraint Programming Calculus

    DEFF Research Database (Denmark)

    Palamidessi, Catuscia; Valencia Posso, Frank Darwin

    2001-01-01

    The tcc model is a formalism for reactive concurrent constraint programming. In this paper we propose a model of temporal concurrent constraint programming which adds to tcc the capability of modeling asynchronous and non-deterministic timed behavior. We call this tcc extension the ntcc calculus...

  3. Lower Bounds of Concurrence for Multipartite States

    CERN Document Server

    Zhu, Xue-Na; Fei, Shao-Ming

    2012-01-01

    We study the entanglement of multipartite quantum states. Some lower bounds of the multipartite concurrence are reviewed. We further present more effective lower bounds for detecting and qualifying entanglement, by establishing functional relations between the concurrence and the generalized partial transpositions of the multipartite systems.

  4. New concurrent iterative methods with monotonic convergence

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Qingchuan [Michigan State Univ., East Lansing, MI (United States)

    1996-12-31

    This paper proposes the new concurrent iterative methods without using any derivatives for finding all zeros of polynomials simultaneously. The new methods are of monotonic convergence for both simple and multiple real-zeros of polynomials and are quadratically convergent. The corresponding accelerated concurrent iterative methods are obtained too. The new methods are good candidates for the application in solving symmetric eigenproblems.

  5. A Temporal Concurrent Constraint Programming Calculus

    DEFF Research Database (Denmark)

    Palamidessi, Catuscia; Valencia Posso, Frank Darwin

    2001-01-01

    The tcc model is a formalism for reactive concurrent constraint programming. In this paper we propose a model of temporal concurrent constraint programming which adds to tcc the capability of modeling asynchronous and non-deterministic timed behavior. We call this tcc extension the ntcc calculus...

  6. Gaudi components for concurrency: Concurrency for existing and future experiments

    Science.gov (United States)

    Clemencic, M.; Funke, D.; Hegner, B.; Mato, P.; Piparo, D.; Shapoval, I.

    2015-05-01

    HEP experiments produce enormous data sets at an ever-growing rate. To cope with the challenge posed by these data sets, experiments’ software needs to embrace all capabilities modern CPUs offer. With decreasing memory/core ratio, the one-process-per-core approach of recent years becomes less feasible. Instead, multi-threading with fine-grained parallelism needs to be exploited to benefit from memory sharing among threads. Gaudi is an experiment-independent data processing framework, used for instance by the ATLAS and LHCbexperiments at CERN's Large Hadron Collider. It has originally been designed with only sequential processing in mind. In a recent effort, the frame work has been extended to allow for multi-threaded processing. This includes components for concurrent scheduling of several algorithms - either processingthe same or multiple events, thread-safe data store access and resource management. In the sequential case, the relationships between algorithms are encoded implicitly in their pre-determined execution order. For parallel processing, these relationships need to be expressed explicitly, in order for the scheduler to be able to exploit maximum parallelism while respecting dependencies between algorithms. Therefore, means to express and automatically track these dependencies need to be provided by the framework. In this paper, we present components introduced to express and track dependencies of algorithms to deduce a precedence-constrained directed acyclic graph, which serves as basis for our algorithmically sophisticated scheduling approach for tasks with dynamic priorities. We introduce an incremental migration path for existing experiments towards parallel processing and highlight the benefits of explicit dependencies even in the sequential case, such as sanity checks and sequence optimization by graph analysis.

  7. How does concurrent sourcing affect performance?

    DEFF Research Database (Denmark)

    Mols, Niels Peter

    2010-01-01

    Abstract Purpose – “Concurrent sourcing” is a term used by Parmigiani to describe the phenomenon where a firm simultaneously buys and makes the same good or service. The purpose of this paper is to develop propositions that suggest how concurrent sourcing affects performance. Design....../methodology/approach – Based on transaction cost, agency, neoclassical economic, knowledge-based, and resource-based theory, it is proposed to show how concurrent sourcing affects performance. Findings – The paper argues that concurrent sourcing improves performance when firms face a combination of volume uncertainty......, technological uncertainty, performance uncertainty, non-decomposability, transaction-specific investments, and strong internal and external capabilities. Research limitations/implications – The paper maps the relationships between concurrent sourcing and performance and discusses how these relationships can...

  8. Multiparty Compatibility for Concurrent Objects

    Directory of Open Access Journals (Sweden)

    Roly Perera

    2016-06-01

    Full Text Available Objects and actors are communicating state machines, offering and consuming different services at different points in their lifecycle. Two complementary challenges arise when programming such systems. When objects interact, their state machines must be "compatible", so that services are requested only when they are available. Dually, when objects refine other objects, their state machines must be "compliant", so that services are honoured whenever they are promised. In this paper we show how the idea of multiparty compatibility from the session types literature can be applied to both of these problems. We present an untyped language in which concurrent objects are checked automatically for compatibility and compliance. For simple objects, checking can be exhaustive and has the feel of a type system. More complex objects can be partially validated via test cases, leading to a methodology closer to continuous testing. Our proof-of-concept implementation is limited in some important respects, but demonstrates the potential value of the approach and the relationship to existing software development practices.

  9. Both mosquito-derived xanthurenic acid and a host blood-derived factor regulate gametogenesis of Plasmodium in the midgut of the mosquito.

    Science.gov (United States)

    Arai, M; Billker, O; Morris, H R; Panico, M; Delcroix, M; Dixon, D; Ley, S V; Sinden, R E

    2001-08-01

    Gametogenesis of Plasmodium in vitro can be induced by the combined stimulus of a 5 degrees C fall in temperature and the presence of xanthurenic acid (XA). In-vitro experiments showed that P. gallinaceum (EC(50)=80 nM) is much more sensitive to XA than P. berghei (9 microM), P. yoelii (8 microM), and P. falciparum (2 microM). However, in the mosquito vector, we do not know whether the temperature shift and XA are the only gametocyte-activating factors (GAF), nor do we know with certainty the true source(s) of XA in the mosquito blood meal. Previous studies indicate that XA is the only source of GAF in the mosquito. By defining, and then contrasting, the ability of an XA-deficient mutant of Aedes aegypti, with the wild-type mosquito to support exflagellation and ookinete formation in vivo, we determined the roles of parasite-, mosquito- and host blood-derived GAF in the regulation of gametogenesis of P. gallinaceum. Removal of both host and vector sources of GAF totally inhibited both exflagellation and ookinete production, whilst the lack of either single source resulted in only a partial reduction of exflagellation and ookinete formation in the mosquito gut. Both sources can be effectively replaced/substituted by synthetic XA. This suggests (1) both mosquito- and vertebrate-derived factors act as GAF in the mosquito gut in vivo; (2) the parasite itself is unable to produce any significant GAF activity. Studies are underway to determine whether vertebrate-derived GAF is XA. These data may form the basis of further studies of the development of new methods of interrupting malarial transmission.

  10. The Activities of Current Antimalarial Drugs on the Life Cycle Stages of Plasmodium: A Comparative Study with Human and Rodent Parasites

    Science.gov (United States)

    Delves, Michael; Plouffe, David; Scheurer, Christian; Meister, Stephan; Wittlin, Sergio; Winzeler, Elizabeth A.; Sinden, Robert E.; Leroy, Didier

    2012-01-01

    Background Malaria remains a disease of devastating global impact, killing more than 800,000 people every year—the vast majority being children under the age of 5. While effective therapies are available, if malaria is to be eradicated a broader range of small molecule therapeutics that are able to target the liver and the transmissible sexual stages are required. These new medicines are needed both to meet the challenge of malaria eradication and to circumvent resistance. Methods and Findings Little is known about the wider stage-specific activities of current antimalarials that were primarily designed to alleviate symptoms of malaria in the blood stage. To overcome this critical gap, we developed assays to measure activity of antimalarials against all life stages of malaria parasites, using a diverse set of human and nonhuman parasite species, including male gamete production (exflagellation) in Plasmodium falciparum, ookinete development in P. berghei, oocyst development in P. berghei and P. falciparum, and the liver stage of P. yoelii. We then compared 50 current and experimental antimalarials in these assays. We show that endoperoxides such as OZ439, a stable synthetic molecule currently in clinical phase IIa trials, are strong inhibitors of gametocyte maturation/gamete formation and impact sporogony; lumefantrine impairs development in the vector; and NPC-1161B, a new 8-aminoquinoline, inhibits sporogony. Conclusions These data enable objective comparisons of the strengths and weaknesses of each chemical class at targeting each stage of the lifecycle. Noting that the activities of many compounds lie within achievable blood concentrations, these results offer an invaluable guide to decisions regarding which drugs to combine in the next-generation of antimalarial drugs. This study might reveal the potential of life-cycle–wide analyses of drugs for other pathogens with complex life cycles. Please see later in the article for the Editors' Summary PMID

  11. Using Click Chemistry to Identify Potential Drug Targets in Plasmodium

    Science.gov (United States)

    2015-04-01

    AWARD NUMBER: W81XWH-13-1-0429 TITLE: Using "Click Chemistry" to Identify Potential Drug Targets in Plasmodium PRINCIPAL INVESTIGATOR: Dr. Purnima...SUBTITLE Sa. CONTRACT NUMBER W81XWH-1 3-1-0429 Using "Click Chemistry" to Identify Potential Drug Targets in Plasmodium 5b. GRANT NUMBER 5c. PROGRAM...Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Sporozo ite infection of the liver is the first obl igate step of the Plasmodium

  12. Filarial worms reduce Plasmodium infectivity in mosquitoes.

    Directory of Open Access Journals (Sweden)

    Matthew T Aliota

    Full Text Available BACKGROUND: Co-occurrence of malaria and filarial worm parasites has been reported, but little is known about the interaction between filarial worm and malaria parasites with the same Anopheles vector. Herein, we present data evaluating the interaction between Wuchereria bancrofti and Anopheles punctulatus in Papua New Guinea (PNG. Our field studies in PNG demonstrated that An. punctulatus utilizes the melanization immune response as a natural mechanism of filarial worm resistance against invading W. bancrofti microfilariae. We then conducted laboratory studies utilizing the mosquitoes Armigeres subalbatus and Aedes aegypti and the parasites Brugia malayi, Brugia pahangi, Dirofilaria immitis, and Plasmodium gallinaceum to evaluate the hypothesis that immune activation and/or development by filarial worms negatively impact Plasmodium development in co-infected mosquitoes. Ar. subalbatus used in this study are natural vectors of P. gallinaceum and B. pahangi and they are naturally refractory to B. malayi (melanization-based refractoriness. METHODOLOGY/PRINCIPAL FINDINGS: Mosquitoes were dissected and Plasmodium development was analyzed six days after blood feeding on either P. gallinaceum alone or after taking a bloodmeal containing both P. gallinaceum and B. malayi or a bloodmeal containing both P. gallinaceum and B. pahangi. There was a significant reduction in the prevalence and mean intensity of Plasmodium infections in two species of mosquito that had dual infections as compared to those mosquitoes that were infected with Plasmodium alone, and was independent of whether the mosquito had a melanization immune response to the filarial worm or not. However, there was no reduction in Plasmodium development when filarial worms were present in the bloodmeal (D. immitis but midgut penetration was absent, suggesting that factors associated with penetration of the midgut by filarial worms likely are responsible for the observed reduction in malaria

  13. Bifurcation in the chemotactic behavior of Physarum plasmodium

    Science.gov (United States)

    Shirakawa, Tomohiro; Gunji, Yukio-Pegio; Sato, Hiroshi; Tsubakino, Hiroto

    2017-07-01

    The plasmodium of true slime mold Physarum polycephalum is a unicellular and multinuclear giant amoeba. Since the cellular organism has some computational abilities, it is attracting much attention in the field of information science. However, previous studies have mainly focused on the optimization behavior of the plasmodium for a single-modality stimulus, and there are few studies on how the organism adapts to multi-modal stimuli. We stimulated the plasmodium with mixture of attractant and repellent stimuli, and we observed bifurcation in the chemotactic behavior of the plasmodium.

  14. Partnering parasites: evidence of synergism between heavy Schistosoma haematobium and Plasmodium species infections in Kenyan children.

    Directory of Open Access Journals (Sweden)

    Lia S Florey

    Full Text Available BACKGROUND: Residents of resource-poor tropical countries carry heavy burdens of concurrent parasitic infections, leading to high rates of morbidity and mortality. This study was undertaken to help identify the social and environmental determinants of multiple parasite infection in one such community. METHODOLOGY/PRINCIPAL FINDINGS: Residents of Kingwede, Kenya aged 8 years and older were tested for presence and intensity of S. haematobium and Plasmodium spp. infections in a cross-sectional, household-based, community survey. Using General Estimating Equation (GEE models, social and environmental determinants associated with patterns of co-infection were identified, with age being one of the most important factors. Children had 9.3 times the odds of co-infection compared to adults (95%CI=5.3-16.3. Even after controlling for age, socio-economic position, and other correlates of co-infection, intense concomitant infections with the two parasites were found to cluster in a subset of individuals: the odds of heavy vs. light S. haematobium infection increased with increasing Plasmodium infection intensity suggesting the importance of unmeasured biological factors in determining intensity of co-infection. CONCLUSIONS/SIGNIFICANCE: Children in this community are more likely to be infected with multiple parasites than are adults and should therefore be targeted for prevention and control interventions. More importantly, heavy infections with multiple parasite species appear to cluster within a subset of individuals. Further studies focusing on these most vulnerable people are warranted.

  15. Automatic and Hierarchical Verification for Concurrent Systems

    Institute of Scientific and Technical Information of China (English)

    赵旭东; 冯玉琳

    1990-01-01

    Proving correctness of concurrent systems is quite difficult because of the high level of nondeterminism,especially in large and complex ones.AMC is a model checking system for verifying asynchronous concurrent systems by using branching time temporal logic.This paper introduces the techniques of the modelling approach,especially how to construct models for large concurrent systems with the concept of hierarchy,which has been proved to be effective and practical in verifying large systems without a large growth of cost.

  16. Concurrent Manipulation of Expanded AVL Trees

    Institute of Scientific and Technical Information of China (English)

    章寅; 许卓群

    1998-01-01

    The concurrent manipulation of an expanded AVL tree(EAVL tree)s considered in this paper.The presented system can support any number of concurrent processes which perform searching,insertion and deletion on the tree.Simulation results indicate the high performance of the system.Elaborate techniques are used to achieve such a system unavailable based on any known algorithms.Methods developed in this paper may provide new insights into other problems in the area of concurrent search structure manipulation.

  17. Plasmodium Oocysts: Overlooked Targets of Mosquito Immunity.

    Science.gov (United States)

    Smith, Ryan C; Barillas-Mury, Carolina

    2016-12-01

    Although the ability of mosquitoes to limit Plasmodium infection is well documented, many questions remain as to how malaria parasites are recognized and killed by the mosquito host. Recent evidence suggests that anti-Plasmodium immunity is multimodal, with different immune mechanisms regulating ookinete and oocyst survival. However, most experiments determine the number of mature oocysts, without considering that different immune mechanisms may target different developmental stages of the parasite. Complement-like proteins have emerged as important determinants of early immunity targeting the ookinete stage, yet the mechanisms by which the mosquito late-phase immune response limits oocyst survival are less understood. Here, we describe the known components of the mosquito immune system that limit oocyst development, and provide insight into their possible mechanisms of action. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Plasmodium knowlesi malaria in Vietnam: some clarifications

    Directory of Open Access Journals (Sweden)

    Hung Le

    2010-01-01

    Full Text Available Abstract A recently published comment on a report of Plasmodium knowlesi infections in Vietnam states that this may not accurately represent the situation in the study area because the PCR primers used may cross-hybridize with Plasmodium vivax. Nevertheless, P. knowlesi infections have been confirmed by sequencing. In addition, a neighbour-joining tree based on the 18S S-Type SSUrRNA gene shows that the Vietnamese samples clearly cluster with the P. knowlesi isolates identified in Malaysia and are distinct from the corresponding P. vivax sequences. All samples came from asymptomatic individuals who did not consult for fever during the months preceding or following the survey, indicating that asymptomatic P. knowlesi infections occur in this population, although this does not exclude the occurrence of symptomatic cases. Large-scale studies to determine the extent and the epidemiology of P. knowlesi malaria in Vietnam are further needed.

  19. Engineered anopheles immunity to Plasmodium infection.

    Directory of Open Access Journals (Sweden)

    Yuemei Dong

    2011-12-01

    Full Text Available A causative agent of human malaria, Plasmodium falciparum, is transmitted by Anopheles mosquitoes. The malaria parasite is under intensive attack from the mosquito's innate immune system during its sporogonic development. We have used genetic engineering to create immune-enhanced Anopheles stephensi mosquitoes through blood meal-inducible expression of a transgene encoding the IMD pathway-controlled NF-kB Rel2 transcription factor in the midgut and fat-body tissue. Transgenic mosquitoes showed greater resistance to Plasmodium and microbial infection as a result of timely concerted tissue-specific immune attacks involving multiple effectors. The relatively weak impact of this genetic modification on mosquito fitness under laboratory conditions encourages further investigation of this approach for malaria control.

  20. Exploring the folate pathway in Plasmodium falciparum

    OpenAIRE

    Hyde, John E.

    2005-01-01

    As in centuries past, the main weapon against human malaria infections continues to be intervention with drugs, despite the widespread and increasing frequency of parasite populations that are resistant to one or more of the available compounds. This is a particular problem with the lethal species of parasite, Plasmodium falciparum, which claims some two million lives per year as well as causing enormous social and economic problems. Amongst the antimalarial drugs currently in clinical use, t...

  1. Plasmodium falciparum drug resistance in Angola

    OpenAIRE

    Fançony, Cláudia; Brito, Miguel; Gil, Jose Pedro

    2016-01-01

    Facing chloroquine drug resistance, Angola promptly adopted artemisinin-based combination therapy as the first-line to treat malaria. Currently, the country aims to consolidate malaria control, while preparing for the elimination of the disease, along with others African countries in the region. However, the remarkable capacity of Plasmodium to develop drug resistance represents an alarming threat for those achievements. Herein, the available, but relatively scarce and dispersed, information ...

  2. Epidemiology of Plasmodium vivax in Indonesia.

    Science.gov (United States)

    Surjadjaja, Claudia; Surya, Asik; Baird, J Kevin

    2016-12-28

    Endemic malaria occurs across much of the vast Indonesian archipelago. All five species of Plasmodium known to naturally infect humans occur here, along with 20 species of Anopheles mosquitoes confirmed as carriers of malaria. Two species of plasmodia cause the overwhelming majority and virtually equal shares of malaria infections in Indonesia: Plasmodium falciparum and Plasmodium vivax The challenge posed by P. vivax is especially steep in Indonesia because chloroquine-resistant strains predominate, along with Chesson-like strains that relapse quickly and multiple times at short intervals in almost all patients. Indonesia's hugely diverse human population carries many variants of glucose-6-phosphate dehydrogenase (G6PD) deficiency, most of them exhibiting severely impaired enzyme activity. Therefore, the patients most likely to benefit from primaquine therapy by preventing aggressive relapse, may also be most likely to suffer harm without G6PD deficiency screening. Indonesia faces the challenge of controlling and eventually eliminating malaria across > 13,500 islands stretching > 5,000 km and an enormous diversity of ecological, ethnographic, and socioeconomic settings, and extensive human migrations. This article describes the occurrence of P. vivax in Indonesia and the obstacles faced in eliminating its transmission. © The American Society of Tropical Medicine and Hygiene.

  3. Plasmodium simium/Plasmodium vivax infections in southern brown howler monkeys from the Atlantic Forest

    Directory of Open Access Journals (Sweden)

    Daniela Camargos Costa

    2014-08-01

    Full Text Available Blood infection by the simian parasite, Plasmodium simium, was identified in captive (n = 45, 4.4% and in wild Alouatta clamitans monkeys (n = 20, 35% from the Atlantic Forest of southern Brazil. A single malaria infection was symptomatic and the monkey presented clinical and haematological alterations. A high frequency of Plasmodium vivax-specific antibodies was detected among these monkeys, with 87% of the monkeys testing positive against P. vivax antigens. These findings highlight the possibility of malaria as a zoonosis in the remaining Atlantic Forest and its impact on the epidemiology of the disease.

  4. Similarity based mixed transaction concurrency control protocol

    Institute of Scientific and Technical Information of China (English)

    PAN Yi; LU Yan-sheng

    2005-01-01

    Due to the various performance requirements and data access restrictions of different types of real-time transactions, concurrency control protocols which had been designed for the systems with single type of transactions are not sufficient for mixed real-time database systems (MRTDBS), where different types of real-time transactions coexist in the systems concurrently. In this paper, a new concurrency control protocol MRTT_CC for mixed real-time transactions is proposed. The new strategy integrates with different concurrency control protocols to meet the deadline requirements of different types of real-time transactions. The data similarity concept is also explored in the new protocol to reduce the blocking time of soft real-time transactions, which increases their chances to meet the deadlines. Simulation experiments show that the new protocol has gained good performance.

  5. 33 CFR 385.7 - Concurrency statements.

    Science.gov (United States)

    2010-07-01

    ... DEFENSE PROGRAMMATIC REGULATIONS FOR THE COMPREHENSIVE EVERGLADES RESTORATION PLAN General Provisions § 385.7 Concurrency statements. The administrative record of the programmatic regulations in this part..., Jacksonville District, 701 San Marco Blvd., Jacksonville, Florida 32207, or by accessing the...

  6. Strategy Improvement for Concurrent Safety Games

    CERN Document Server

    Chatterjee, Krishnendu; Henzinger, Thomas A

    2008-01-01

    We consider concurrent games played on graphs. At every round of the game, each player simultaneously and independently selects a move; the moves jointly determine the transition to a successor state. Two basic objectives are the safety objective: ``stay forever in a set F of states'', and its dual, the reachability objective, ``reach a set R of states''. We present in this paper a strategy improvement algorithm for computing the value of a concurrent safety game, that is, the maximal probability with which player 1 can enforce the safety objective. The algorithm yields a sequence of player-1 strategies which ensure probabilities of winning that converge monotonically to the value of the safety game. The significance of the result is twofold. First, while strategy improvement algorithms were known for Markov decision processes and turn-based games, as well as for concurrent reachability games, this is the first strategy improvement algorithm for concurrent safety games. Second, and most importantly, the impro...

  7. Tools and Patterns for Dependable Concurrent Software

    NARCIS (Netherlands)

    Jovanovic, D.S.; Broenink, Johannes F.

    2005-01-01

    First, we give reasons for choosing a process-oriented approach for building complex concurrent systems. Upon a brief review of dependability attributes of software-supported systems, means for increasing dependability in process-oriented architectures are illustrated

  8. CilkSpec: Optimistic Concurrency for Cilk

    Energy Technology Data Exchange (ETDEWEB)

    Aga, Shaizeen D.; Krishnamoorthy, Sriram; Narayanasamy, Satish

    2015-11-15

    Recursive parallel programming models such as Cilk strive to simplify the task of parallel programming by enabling a simple divide-and-conquer model of programming. This model is effective in re- cursively partitioning work into smaller parts and combining their results. However, recursive work partitioning can impose additional constraints on concurrency than is implied by the true dependences in a program. In this paper, we present a speculation-based approach to alleviate the concurrency constraints imposed by such recursive parallel programs. We design a runtime infrastructure that supports speculative execution and a predictor to accurately learn and identify opportunities to relax extraneous concurrency constraints. Experimental evaluation demonstrates that speculative relaxation of concurrency constraints can deliver gains of up to 1.6× on 30 cores over baseline Cilk.

  9. Heterogeneous concurrent computing with exportable services

    Science.gov (United States)

    Sunderam, Vaidy

    1995-01-01

    Heterogeneous concurrent computing, based on the traditional process-oriented model, is approaching its functionality and performance limits. An alternative paradigm, based on the concept of services, supporting data driven computation, and built on a lightweight process infrastructure, is proposed to enhance the functional capabilities and the operational efficiency of heterogeneous network-based concurrent computing. TPVM is an experimental prototype system supporting exportable services, thread-based computation, and remote memory operations that is built as an extension of and an enhancement to the PVM concurrent computing system. TPVM offers a significantly different computing paradigm for network-based computing, while maintaining a close resemblance to the conventional PVM model in the interest of compatibility and ease of transition Preliminary experiences have demonstrated that the TPVM framework presents a natural yet powerful concurrent programming interface, while being capable of delivering performance improvements of upto thirty percent.

  10. Abstract Diagnosis for Timed Concurrent Constraint programs

    CERN Document Server

    Comini, Marco; Villanueva, Alicia

    2011-01-01

    The Timed Concurrent Constraint Language (tccp in short) is a concurrent logic language based on the simple but powerful concurrent constraint paradigm of Saraswat. In this paradigm, the notion of store-as-value is replaced by the notion of store-as-constraint, which introduces some differences w.r.t. other approaches to concurrency. In this paper, we provide a general framework for the debugging of tccp programs. To this end, we first present a new compact, bottom-up semantics for the language that is well suited for debugging and verification purposes in the context of reactive systems. We also provide an abstract semantics that allows us to effectively implement debugging algorithms based on abstract interpretation. Given a tccp program and a behavior specification, our debugging approach automatically detects whether the program satisfies the specification. This differs from other semiautomatic approaches to debugging and avoids the need to provide symptoms in advance. We show the efficacy of our approach...

  11. Inheritance and Synchronization in Concurrent OOP

    Science.gov (United States)

    Briot, Jean-Pierre; Yonezawa, Akinori

    This paper discusses knowledge sharing (inheritance) mechanisms for Object-Oriented Programming (OOP) in the context of concurrent (distributed) languages. We review three different schemes: inheritance, delegation and copy. A fourth model, called recipe-query, is presented and all are compared and criticized. Techniques relying on the shared memory assumption are rejected. We point out the conflict between distributing knowledge among objects and the synchronization of concurrent objects.

  12. A Concurrent Object-Oriented Language Ondine

    OpenAIRE

    Arisawa, Makoto; Ogihara, Takeshi; Kajihara, Yoichi

    1988-01-01

    A new concurrent object-oriented language Ondine is described. The Ondine design goals are strong information hiding within objects, concurrent programming, and pointerless programming. Ondine has ordinary control statements and types so that Ada or C programmers can easily handle it. By introducing by copy and by object assignment/argument passing, an Ondine object can be accessed from only one other object thus accomplishing pointerless structure. Ondine channels are used for constructing o...

  13. Noninterference for Concurrent Programs and Thread Systems

    OpenAIRE

    Boudol, Gérard; Castellani, Ilaria

    2001-01-01

    We propose a type system to ensure the property of noninterference in a system of concurrent programs, described in a standard imperative language enriched with parallelism. Our proposal is in the line of some recent work by Irvine, Volpano and Smith. Our type system seems more natural and less restrictive than that originally presented by these authors for the concurrent case. Moreover, we show how to extend the language in order to formalise scheduling policies for systems of sequential thr...

  14. Mosquito transmission of wild turkey malaria, Plasmodium hermani.

    Science.gov (United States)

    Young, M D; Nayar, J K; Forrester, D J

    1977-04-01

    Culex nigripalpus experimentally transmitted Plasmodium hermani, a plasmodium of wild turkeys (Meleagris gallopavo) in Florida. The mosquitoes were infected by feeding upon blood induced parasitemias in domestic turkey poults. The resulting sporozoites, transmitted by either mosquito bites or injection, produced malaria infections in domestic poults.

  15. Plasmodium vivax induced myocarditis: A rare case report

    Directory of Open Access Journals (Sweden)

    N Gupta

    2013-01-01

    Full Text Available Malaria is one of the commonest parasitic disease in the tropics since ages. However the plasmodium still continues to give surprises to all of us. In the similar context we report a case of Plasmodium vivax induced myocarditis in a 20 year old male and review the literature related to this rare entitiy.

  16. Severe sepsis and septic shock due to Plasmodium vivax infection.

    Science.gov (United States)

    Chalkias, Athanasios; Aridas, Sotirios; Karageorgopoulos, Drosos E; Stratiotis, Georgios; Mystrioti, Dimitra; Mallios, Athanasios; Nakos, Ioannis; Mpellos, Nikolaos; Ganotopoulou, Asimina; Xanthos, Theodoros

    2013-04-01

    Plasmodium vivax malaria is typically characterized by a mild and benign clinical course. Organ dysfunction is rarely seen, whereas acute lung injury has been found to occur after starting antimalarial treatment. We present an unusual case of severe sepsis and septic shock due to Plasmodium vivax monoinfection.

  17. Characterizing Distributed Concurrent Engineering Teams: A Descriptive Framework for Aerospace Concurrent Engineering Design Teams

    Science.gov (United States)

    Chattopadhyay, Debarati; Hihn, Jairus; Warfield, Keith

    2011-01-01

    As aerospace missions grow larger and more technically complex in the face of ever tighter budgets, it will become increasingly important to use concurrent engineering methods in the development of early conceptual designs because of their ability to facilitate rapid assessments and trades in a cost-efficient manner. To successfully accomplish these complex missions with limited funding, it is also essential to effectively leverage the strengths of individuals and teams across government, industry, academia, and international agencies by increased cooperation between organizations. As a result, the existing concurrent engineering teams will need to increasingly engage in distributed collaborative concurrent design. This paper is an extension of a recent white paper written by the Concurrent Engineering Working Group, which details the unique challenges of distributed collaborative concurrent engineering. This paper includes a short history of aerospace concurrent engineering, and defines the terms 'concurrent', 'collaborative' and 'distributed' in the context of aerospace concurrent engineering. In addition, a model for the levels of complexity of concurrent engineering teams is presented to provide a way to conceptualize information and data flow within these types of teams.

  18. Plasmodium vivax cerebral malaria complicated with venous sinus thrombosis in Colombia

    Institute of Scientific and Technical Information of China (English)

    Miguel A Pinzn; Juan C Pineda; Fernando Rosso; Masaru Shinchi; Fabio Bonilla-Abada

    2013-01-01

    Complicated malaria is usually due to Plasmodium falciparum. Nevertheless, Plasmodium vivax is infrequently related with life-threatening complications. Few cases have been reported of severe Plasmodium vivax infection, and most of them from Southeast Asia and India. We report the first case of cerebral malaria due to Plasmodium vivax in Latin America, complicated with sagittal sinus thrombosis and confirmed by a molecular method.

  19. Construction of living cellular automata using the Physarum plasmodium

    Science.gov (United States)

    Shirakawa, Tomohiro; Sato, Hiroshi; Ishiguro, Shinji

    2015-04-01

    The plasmodium of Physarum polycephalum is a unicellular and multinuclear giant amoeba that has an amorphous cell body. To clearly observe how the plasmodium makes decisions in its motile and exploratory behaviours, we developed a new experimental system to pseudo-discretize the motility of the organism. In our experimental space that has agar surfaces arranged in a two-dimensional lattice, the continuous and omnidirectional movement of the plasmodium was limited to the stepwise one, and the direction of the locomotion was also limited to four neighbours. In such an experimental system, a cellular automata-like system was constructed using the living cell. We further analysed the exploratory behaviours of the plasmodium by duplicating the experimental results in the simulation models of cellular automata. As a result, it was revealed that the behaviours of the plasmodium are not reproduced by only local state transition rules; and for the reproduction, a kind of historical rule setting is needed.

  20. Response to various periods of mechanical stimuli in Physarum plasmodium

    Science.gov (United States)

    Umedachi, Takuya; Ito, Kentaro; Kobayashi, Ryo; Ishiguro, Akio; Nakagaki, Toshiyuki

    2017-06-01

    Response to mechanical stimuli is a fundamental and critical ability for living cells to survive in hazardous conditions or to form adaptive and functional structures against force(s) from the environment. Although this ability has been extensively studied by molecular biology strategies, it is also important to investigate the ability from the viewpoint of biological rhythm phenomena so as to reveal the mechanisms that underlie these phenomena. Here, we use the plasmodium of the true slime mold Physarum polycephalum as the experimental system for investigating this ability. The plasmodium was repetitively stretched for various periods during which its locomotion speed was observed. Since the plasmodium has inherent oscillation cycles of protoplasmic streaming and thickness variation, how the plasmodium responds to various periods of external stretching stimuli can shed light on the other biological rhythm phenomena. The experimental results show that the plasmodium exhibits response to periodic mechanical stimulation and changes its locomotion speed depending on the period of the stretching stimuli.

  1. Mitosis in the Human Malaria Parasite Plasmodium falciparum ▿

    Science.gov (United States)

    Gerald, Noel; Mahajan, Babita; Kumar, Sanjai

    2011-01-01

    Malaria is caused by intraerythrocytic protozoan parasites belonging to Plasmodium spp. (phylum Apicomplexa) that produce significant morbidity and mortality, mostly in developing countries. Plasmodium parasites have a complex life cycle that includes multiple stages in anopheline mosquito vectors and vertebrate hosts. During the life cycle, the parasites undergo several cycles of extreme population growth within a brief span, and this is critical for their continued transmission and a contributing factor for their pathogenesis in the host. As with other eukaryotes, successful mitosis is an essential requirement for Plasmodium reproduction; however, some aspects of Plasmodium mitosis are quite distinct and not fully understood. In this review, we will discuss the current understanding of the architecture and key events of mitosis in Plasmodium falciparum and related parasites and compare them with the traditional mitotic events described for other eukaryotes. PMID:21317311

  2. Theta oscillations accompanying concurrent auditory stream segregation.

    Science.gov (United States)

    Tóth, Brigitta; Kocsis, Zsuzsanna; Urbán, Gábor; Winkler, István

    2016-08-01

    The ability to isolate a single sound source among concurrent sources is crucial for veridical auditory perception. The present study investigated the event-related oscillations evoked by complex tones, which could be perceived as a single sound and tonal complexes with cues promoting the perception of two concurrent sounds by inharmonicity, onset asynchrony, and/or perceived source location difference of the components tones. In separate task conditions, participants performed a visual change detection task (visual control), watched a silent movie (passive listening) or reported for each tone whether they perceived one or two concurrent sounds (active listening). In two time windows, the amplitude of theta oscillation was modulated by the presence vs. absence of the cues: 60-350ms/6-8Hz (early) and 350-450ms/4-8Hz (late). The early response appeared both in the passive and the active listening conditions; it did not closely match the task performance; and it had a fronto-central scalp distribution. The late response was only elicited in the active listening condition; it closely matched the task performance; and it had a centro-parietal scalp distribution. The neural processes reflected by these responses are probably involved in the processing of concurrent sound segregation cues, in sound categorization, and response preparation and monitoring. The current results are compatible with the notion that theta oscillations mediate some of the processes involved in concurrent sound segregation.

  3. Completing the hypusine pathway in Plasmodium.

    Science.gov (United States)

    Frommholz, David; Kusch, Peter; Blavid, Robert; Scheer, Hugo; Tu, Jun-Ming; Marcus, Katrin; Zhao, Kai-Hong; Atemnkeng, Veronica; Marciniak, Jana; Kaiser, Annette E

    2009-10-01

    In searching for new targets for antimalarials we investigated the biosynthesis of hypusine present in eukaryotic initiation factor-5A (eIF-5A) in Plasmodium. Here, we describe the cloning and expression of deoxyhypusine hydroxylase (DOHH), which completes the modification of eIF-5A through hydroxylation of deoxyhypusine. The dohh cDNA sequence revealed an ORF of 1236 bp encoding a protein of 412 amino acids with a calculated molecular mass of 46.45 kDa and an isoelectric point of 4.96. Interestingly, DOHH from Plasmodium has a FASTA SCORE of only 27 compared with its human ortholog and contains several matches similar to E-Z-type HEAT-like repeat proteins (IPR004155 (InterPro), PF03130 (Pfam), SM00567 (SMART) present in the phycocyanin lyase subunits of cyanobacteria. Purified DOHH protein displayed hydroxylase activity in a novel in vitro DOHH assay, but phycocyanin lyase activity was absent. dohh is present as a single-copy gene and is transcribed in the asexual blood stages of the parasite. A signal peptide at the N-terminus might direct the protein to a different cellular compartment. During evolution, Plasmodium falciparum acquired an apicoplast that lost its photosynthetic function. It is possible that plasmodial DOHH arose from an E/F-type phycobilin lyase that gained a new role in hydroxylation. Structured digital abstract: * MINT-7255047: DHS (uniprotkb:P49366) enzymaticly reacts (MI:0414) with eIF-5A (uniprotkb:Q710D1) by enzymatic studies (MI:0415) * MINT-7255326: DOHH (uniprotkb:Q8I701) enzymaticly reacts (MI:0414) with eIF-5A (uniprotkb:Q710D1) by enzymatic studies (MI:0415).

  4. Prevalence of Malaria Plasmodium in Abeokuta, Nigeria

    Directory of Open Access Journals (Sweden)

    Okonko, I. O.

    2009-01-01

    Full Text Available This study reports the prevalence of malaria caused by plasmodium between genders in Abeokuta, the capital city of Ogun State located in the forest zone of southwestern Nigeria between January 2002 and December 2004. Blood film examination for malaria parasites in 708 patients; 366 males and 342 females. Microscopic examination of thick films techniques was employed for this study. Of the 708 (100% patients examined, 577 (81.5% were Plasmodium-positive. A high malaria parasite prevalence rate of 81.5% was noted in this study. Female subjects were more infected (42.4% than males (41.9% however, there was no significant difference in the sex of the subjects studied (p=0.05. A high malaria parasite prevalence rate of 86.9% was noted in samples collected in year 2003 than in other years studied. There was significant difference in the years under study (p=0.05. This study shows that a good percentage of people were infested by malaria Plasmodium. This could be attributed to lack of adequate accommodation and poor sanitary conditions in the area under study. Although several efforts have been made to effectively control the high incidence of malaria in Nigeria, these have been largely unsuccessful due to a number of reasons such as irrigated urban agriculture which can be the malaria vector’s breeding ground in the city, stagnant gutters and swamps in our environment where mosquitoes breed in millions, and lack of political will and commitment of the government in its disease management program, low awareness of the magnitude of malaria problem, poor health practices by individuals and communities and resistance to drugs. Therefore, future interventions in Nigeria should be directed toward controlling malaria in the context of a moderate transmission setting; thus, large-scale distribution of insecticide-treated nets or widespread use of indoor residual spraying may be less cost-effective than enhanced surveillance with effective case management or

  5. High Rates of Asymptomatic, Sub-microscopic Plasmodium vivax Infection and Disappearing Plasmodium falciparum Malaria in an Area of Low Transmission in Solomon Islands.

    Science.gov (United States)

    Waltmann, Andreea; Darcy, Andrew W; Harris, Ivor; Koepfli, Cristian; Lodo, John; Vahi, Ventis; Piziki, David; Shanks, G Dennis; Barry, Alyssa E; Whittaker, Maxine; Kazura, James W; Mueller, Ivo

    2015-05-01

    Solomon Islands is intensifying national efforts to achieve malaria elimination. A long history of indoor spraying with residual insecticides, combined recently with distribution of long lasting insecticidal nets and artemether-lumefantrine therapy, has been implemented in Solomon Islands. The impact of these interventions on local endemicity of Plasmodium spp. is unknown. In 2012, a cross-sectional survey of 3501 residents of all ages was conducted in Ngella, Central Islands Province, Solomon Islands. Prevalence of Plasmodium falciparum, P. vivax, P. ovale and P. malariae was assessed by quantitative PCR (qPCR) and light microscopy (LM). Presence of gametocytes was determined by reverse transcription quantitative PCR (RT-qPCR). By qPCR, 468 Plasmodium spp. infections were detected (prevalence = 13.4%; 463 P. vivax, five mixed P. falciparum/P. vivax, no P. ovale or P. malariae) versus 130 by LM (prevalence = 3.7%; 126 P. vivax, three P. falciparum and one P. falciparum/P. vivax). The prevalence of P. vivax infection varied significantly among villages (range 3.0-38.5%, p<0.001) and across age groups (5.3-25.9%, p<0.001). Of 468 P. vivax infections, 72.9% were sub-microscopic, 84.5% afebrile and 60.0% were both sub-microscopic and afebrile. Local residency, low education level of the household head and living in a household with at least one other P. vivax infected individual increased the risk of P. vivax infection. Overall, 23.5% of P. vivax infections had concurrent gametocytaemia. Of all P. vivax positive samples, 29.2% were polyclonal by MS16 and msp1F3 genotyping. All five P. falciparum infections were detected in residents of the same village, carried the same msp2 allele and four were positive for P. falciparum gametocytes. P. vivax infection remains endemic in Ngella, with the majority of cases afebrile and below the detection limit of LM. P. falciparum has nearly disappeared, but the risk of re-introductions and outbreaks due to travel to nearby islands

  6. Gametocitos de Plasmodium vivax y Plasmodium falciparum: etapas relegadas en el desarrollo de vacunas Plasmodium vivax and Plasmodium falciparum gametocyte stages are neglected in vaccine development

    Directory of Open Access Journals (Sweden)

    Carla Contreras-Ochoa

    2004-02-01

    Full Text Available Los gametocitos de Plasmodium son los responsables de la transmisión del huésped vertebrado al mosquito vector. Sufren un proceso de desarrollo complejo a partir de parásitos asexuales, que no está completamente entendido, expresando proteínas y moléculas de adhesión específicas. Son capaces de inducir una respuesta inmune humoral específica con anticuerpos IgG, y celular específica, con producción de TNFa, IFNg y proliferación de linfocitos gd+, aun cuando existen respuestas inducidas en contra de las etapas previas del parásito (esporozoito, exo-eritrocítica y eritrocítica. Las vacunas destinadas a bloquear la transmisión del parásito no contemplan a los gametocitos circulantes en el huésped como blancos de acción, sino que van enfocadas contra antígenos expresados en los gametos y en las etapas posfertilización. El estudio de los mecanismos que regulan la producción de gametocitos y de la respuesta inmune contra éstos, ofrece una oportunidad para el desarrollo de estrategias adicionales para el control de la transmisión.Plasmodium gametocytes are responsible for transmission from the vertebrate host to the mosquito. Plasmodium gametocytes undergo a complex cycle from asexual stages, through a poorly understood process characterized by expression of stage-specific proteins and adhesion molecules. Gametocytes are capable of inducing specific humoral IgG, and cellular responses, which include induction of TNFa, IFNg and gd+ lymphocyte proliferation, in addition to immune responses to other stages of the parasite (sporozoite, exo-erythrocytic stages, erythrocytic stages. Although transmission-blocking vaccines against Plasmodium do not currently include components against the gametocytes (rather they focus on gametes, zygotes or ookinetes, stages which occur in the mosquito, further understanding of the mechanisms underlying gametocytogenesis and immune responses against these stages may provide additional strategies for

  7. Gametocitos de Plasmodium vivax y Plasmodium falciparum: etapas relegadas en el desarrollo de vacunas Plasmodium vivax and Plasmodium falciparum gametocyte stages are neglected in vaccine development

    OpenAIRE

    Carla Contreras-Ochoa; Ramsey, Janine M.

    2004-01-01

    Los gametocitos de Plasmodium son los responsables de la transmisión del huésped vertebrado al mosquito vector. Sufren un proceso de desarrollo complejo a partir de parásitos asexuales, que no está completamente entendido, expresando proteínas y moléculas de adhesión específicas. Son capaces de inducir una respuesta inmune humoral específica con anticuerpos IgG, y celular específica, con producción de TNFa, IFNg y proliferación de linfocitos gd+, aun cuando existen respuestas inducidas en con...

  8. Mosquito transgenic technologies to reduce Plasmodium transmission.

    Science.gov (United States)

    Fuchs, Silke; Nolan, Tony; Crisanti, Andrea

    2013-01-01

    The ability to introduce genetic constructs of choice into the genome of Anopheles mosquitoes provides a valuable tool to study the molecular interactions between the Plasmodium parasite and its insect host. In the long term, this technology could potentially offer new ways to control vector-borne diseases through the suppression of target mosquito populations or through the introgression of traits that preclude pathogen transmission. Here, we describe in detail protocols for the generation of transgenic Anopheles gambiae mosquitoes based on germ-line transformation using either modified transposable elements or the site-specific PhiC31 recombinase.

  9. An Algorithm to Construct Concurrent Reachability Graph of Petri Nets

    Institute of Scientific and Technical Information of China (English)

    张金泉; 倪丽娜; 蒋昌俊

    2004-01-01

    Reachability graph is a very important tool to analyze the dynamic properties of Petri nets, but the concurrent relation of transitions in Petri nets cannot be represented by reachability graph. Petri net is a concurrent system, while reachability graph is a serial one. However, concurrency is a kind of property which is not only very significant but also difficult to be analyzed and controlled. This paper presents the concepts of concurrent reachable marking and concurrent reachable graph in order to represent and analyze the concurrent system. The algorithm constructing concurrent reachable marking set and concurrent reachability graph is also shown so that we can study the response problems among services in a network computing environment and analyze the throughput of the system. The Dining Philosophers Problem, which is a classic problem of describing the management of concurrent resources, is given as an example to illustrate the significance of concurrent reachability graph.

  10. No evidence for ape Plasmodium infections in humans in Gabon.

    Science.gov (United States)

    Délicat-Loembet, Lucresse; Rougeron, Virginie; Ollomo, Benjamin; Arnathau, Céline; Roche, Benjamin; Elguero, Eric; Moukodoum, Nancy Diamella; Okougha, Alain-Prince; Mve Ondo, Bertrand; Boundenga, Larson; Houzé, Sandrine; Galan, Maxime; Nkoghé, Dieudonné; Leroy, Eric M; Durand, Patrick; Paupy, Christophe; Renaud, François; Prugnolle, Franck

    2015-01-01

    African great apes are naturally infected by a multitude of Plasmodium species most of them recently discovered, among which several are closely related to human malaria agents. However, it is still unknown whether these animals can serve as source of infections for humans living in their vicinity. To evaluate this possibility, we analysed the nature of Plasmodium infections from a bank of 4281 human blood samples collected in 210 villages of Gabon, Central Africa. Among them, 2255 were detected positive to Plasmodium using molecular methods (Plasmodium Cytochrome b amplification). A high throughput sequencing technology (454 GS-FLX Titanium technology, Roche) was then used to identify the Plasmodium species present within each positive sample. Overall, we identified with confidence only three species infecting humans in Gabon: P. falciparum, P. malariae and P. ovale. None of the species known to infect non-human primates in Central Africa was found. Our study shows that ape Plasmodium parasites of the subgenus Laverania do not constitute a frequent source of infection for humans. It also suggests that some strong host genetic barriers must exist to prevent the cross species transmission of ape Plasmodium in a context of ever increasing contacts between humans and wildlife.

  11. Prevalence and distribution of human Plasmodium infection in Pakistan.

    Science.gov (United States)

    Khattak, Aamer A; Venkatesan, Meera; Nadeem, Muhammad F; Satti, Humayoon S; Yaqoob, Adnan; Strauss, Kathy; Khatoon, Lubna; Malik, Salman A; Plowe, Christopher V

    2013-08-28

    Both Plasmodium vivax and Plasmodium falciparum are prevalent in Pakistan, yet up-to-date data on the epidemiology of malaria in Pakistan are not available. This study was undertaken to determine the current prevalence and distribution of Plasmodium species across the country. A malariometric population survey was conducted in 2011 using blood samples collected from 801 febrile patients of all ages in four provinces and the capital city of Islamabad. Microscopically confirmed Plasmodium-positive blood samples were reconfirmed by polymerase chain reaction (PCR). Confirmed parasite-positive samples were subjected to species-specific PCR capable of detecting four species of human malaria. Of the 707 PCR-positive samples, 128 (18%) were P. falciparum, 536 (76%) were P. vivax, and 43 (6%) were mixed P. falciparum and P. vivax. Ninety-four microscopy-positive samples were PCR-negative, and Plasmodium malariae and Plasmodium ovale were not detected. Prevalence of P. vivax ranged from 2.4% in Punjab Province to 10.8% in Sindh Province and prevalence of P. falciparum ranged from 0.1% in Islamabad to 3.8% in Balochistan. Plasmodium infections in Pakistan are largely attributed to P. vivax but P. falciparum and mixed species infections are also prevalent. In addition, regional variation in the prevalence and species composition of malaria is high.

  12. Plasmodium infection decreases fecundity and increases survival of mosquitoes.

    Science.gov (United States)

    Vézilier, J; Nicot, A; Gandon, S; Rivero, A

    2012-10-07

    Long-lived mosquitoes maximize the chances of Plasmodium transmission. Yet, in spite of decades of research, the effect of Plasmodium parasites on mosquito longevity remains highly controversial. On the one hand, many studies report shorter lifespans in infected mosquitoes. On the other hand, parallel (but separate) studies show that Plasmodium reduces fecundity and imply that this is an adaptive strategy of the parasite aimed at redirecting resources towards longevity. No study till date has, however, investigated fecundity and longevity in the same individuals to see whether this prediction holds. In this study, we follow for both fecundity and longevity in Plasmodium-infected and uninfected mosquitoes using a novel, albeit natural, experimental system. We also explore whether the genetic variations that arise through the evolution of insecticide resistance modulate the effect of Plasmodium on these two life-history traits. We show that (i) a reduction in fecundity in Plasmodium-infected mosquitoes is accompanied by an increase in longevity; (ii) this increase in longevity arises through a trade-off between reproduction and survival; and (iii) in insecticide-resistant mosquitoes, the slope of this trade-off is steeper when the mosquito is infected by Plasmodium (cost of insecticide resistance).

  13. Concurrent Scheduling of Event-B Models

    CERN Document Server

    Boström, Pontus; Sere, Kaisa; Waldén, Marina; 10.4204/EPTCS.55.11

    2011-01-01

    Event-B is a refinement-based formal method that has been shown to be useful in developing concurrent and distributed programs. Large models can be decomposed into sub-models that can be refined semi-independently and executed in parallel. In this paper, we show how to introduce explicit control flow for the concurrent sub-models in the form of event schedules. We explore how schedules can be designed so that their application results in a correctness-preserving refinement step. For practical application, two patterns for schedule introduction are provided, together with their associated proof obligations. We demonstrate our method by applying it on the dining philosophers problem.

  14. Models for concurrency: towards a classification

    DEFF Research Database (Denmark)

    Sassone, Vladimiro; Nielsen, Mogens; Winskel, Glynn

    1996-01-01

    Models for concurrency can be classified with respect to three relevant parameters: behaviour/ system, interleaving/noninterleaving, linear/branching time. When modelling a process, a choice concerning such parameters corresponds to choosing the level of abstraction of the resulting semantics....... In this paper, we move a step towards a classification of models for concurrency based on the parameters above. Formally, we choose a representative of any of the eight classes of models obtained by varying the three parameters, and we study the formal relationships between them using the language of category...

  15. Towards Interaction Reliability in Concurrent Applications

    Directory of Open Access Journals (Sweden)

    A. Silva

    2012-01-01

    Full Text Available Developing trustworthy concurrent applications is a seemingly never ending quest, which is necessary but difficult. It is necessary because mainstream systems and applications are inherently concurrent and they are pervasive to our daily life activities. It is difficult because such systems are inherently interactive and heterogeneous, so that boundaries can hardly be established for studying subsystems in isolation. Formal methods are a key instrument in resolving ambiguities and design reliable applications in a rigorous way. The authors overview major problems in the application of formal methods and outline how they are tackled by the papers collected in this volume.

  16. Concurrent sourcing and external supplier opportunism

    DEFF Research Database (Denmark)

    Mols, Niels Peter

    When a firm simultaneously makes and buys the same components then the firm uses concurrent sourcing. This paper presents an agency model for explaining how and when concurrent sourcing reduces the likelihood of external supplier opportunism. In the proposed model, the external supplier’s expected...... costs of opportunism are determined as a product of four factors. The four factors are: likelihood of discovering supplier opportunism, buyer’s internalized quantity as reaction to supplier opportunism, asset specificity of external supplier’s investments, and multiplicator effects. Each...

  17. Notes on Timed Concurrent Constraint Programming

    DEFF Research Database (Denmark)

    Nielsen, Mogens; Valencia, Frank D.

    2004-01-01

    and program reactive systems. This note provides a comprehensive introduction to the background for and central notions from the theory of tccp. Furthermore, it surveys recent results on a particular tccp calculus, ntcc, and it provides a classification of the expressive power of various tccp languages.......A constraint is a piece of (partial) information on the values of the variables of a system. Concurrent constraint programming (ccp) is a model of concurrency in which agents (also called processes) interact by telling and asking information (constraints) to and from a shared store (a constraint...

  18. Authentic And Concurrent Evaluation-refining

    DEFF Research Database (Denmark)

    Eriksson, Carina Ihlström; Åkesson, Maria; Kautz, Karlheinz

    2011-01-01

    This paper addresses the need for more detailed accounts for evaluation in design science research literature. By revisiting a design project regarding the future e-newspaper we give detailed descriptions of its authentic and concurrent evaluation approach by illustrating the what, why and how...... as well as decisions on strategic levels. We emphasize a holistic and concurrent approach to evaluation compared to the general design science research thinking and argue that reflecting on how to seek authenticity is important. By authenticity we refer to the notion of how closely an evaluation captures...

  19. Micro-transactions for concurrent data structures

    DEFF Research Database (Denmark)

    Meawad, Fadi; Iyer, Karthik; Schoeberl, Martin;

    2013-01-01

    Transactional memory is a promising technique for enforcing disciplined access to shared data in a multiprocessor system. Transactional memory simplifies the implementation of a variety of concurrent data structures. In this paper, we study the benefits of a modest, real-time aware, hardware...... implementation of transactional memory that we call micro-transactions. In particular, we argue that hardware support for micro-transactions allows us to efficiently implement certain data structures. Those data structures are difficult to realize with the atomic operations provided by stock hardware and provide......, atomic instructions, and micro-transactions. Our results suggest that transactional memory is an interesting alternative to traditional concurrency control mechanisms....

  20. Concurrent Engineering in seafood product development

    DEFF Research Database (Denmark)

    Jonsdottir, Stella; Vesterager, Johan; Børresen, Torger

    1998-01-01

    Concurrent Engineering (CE) can provide an improved approach to product development for extending the lines of seafood products. Information technology support tools based on product models can provide an integrated and simultaneous approach for specifying new recipes. The seafood industry can...... benefit from the CE approach which can support product developers to provide concurrent specifications for raw materials, ingredients, packaging, and production methods. The approach involves the use of product models from which line extensions are more easily generated than by use of customary stepwise...

  1. The concurrent common Lisp development environment

    Science.gov (United States)

    1988-01-01

    A discussion of the Concurrent Common Lisp Development Environment on the iNTEL Personal Super Computer (iPSC) is presented. The advent of AI based engineering design tools has lead to a need for increased performance of computational facilities which support those tools. Gold Hill has approached this problem by directing its efforts to the creation of a concurrent, distributed AI development environment. This discussion focuses on the development tools aspect of the CCLISP environment. The future direction of Gold Hill in the area of distributed AI support environments is also presented.

  2. Compositional Formal Analysis for Concurrent Object-Oriented Languages

    OpenAIRE

    Tran, Thi Mai Thuong

    2013-01-01

    Concurrency is a ubiquitous phenomenon in modern software ranging from distributed systems communicating over the Internet to communicating processes running on multi-core processors and multi-processors. Therefore modern programming languages offer ways to program concurrency effectively. Still, writing correct concurrent programs is notoriously difficult because of the complexity of possible interactions between concurrent processes and because concurrency-related errors are often subtle an...

  3. Human infections and detection of Plasmodium knowlesi.

    Science.gov (United States)

    Singh, Balbir; Daneshvar, Cyrus

    2013-04-01

    Plasmodium knowlesi is a malaria parasite that is found in nature in long-tailed and pig-tailed macaques. Naturally acquired human infections were thought to be extremely rare until a large focus of human infections was reported in 2004 in Sarawak, Malaysian Borneo. Human infections have since been described throughout Southeast Asia, and P. knowlesi is now recognized as the fifth species of Plasmodium causing malaria in humans. The molecular, entomological, and epidemiological data indicate that human infections with P. knowlesi are not newly emergent and that knowlesi malaria is primarily a zoonosis. Human infections were undiagnosed until molecular detection methods that could distinguish P. knowlesi from the morphologically similar human malaria parasite P. malariae became available. P. knowlesi infections cause a spectrum of disease and are potentially fatal, but if detected early enough, infections in humans are readily treatable. In this review on knowlesi malaria, we describe the early studies on P. knowlesi and focus on the epidemiology, diagnosis, clinical aspects, and treatment of knowlesi malaria. We also discuss the gaps in our knowledge and the challenges that lie ahead in studying the epidemiology and pathogenesis of knowlesi malaria and in the prevention and control of this zoonotic infection.

  4. Plasmodium vivax malaria during pregnancy, Bolivia.

    Science.gov (United States)

    Brutus, Laurent; Santalla, José; Schneider, Dominique; Avila, Juan Carlos; Deloron, Philippe

    2013-10-01

    Plasmodium vivax is a major cause of illness in areas with low transmission of malaria in Latin America, Asia, and the Horn of Africa. However, pregnancy-associated malaria remains poorly characterized in such areas. Using a hospital-based survey of women giving birth and an antenatal survey, we assessed the prevalence rates of Plasmodium spp. infections in pregnant women in Bolivia, and evaluated the consequences of malaria during pregnancy on the health of mothers and newborns. P. vivax infection was detected in 7.9% of pregnant women attending antenatal visits, and placental infection occurred in 2.8% of deliveries; these rates did not vary with parity. Forty-two percent of all P. vivax malaria episodes were symptomatic. P. vivax-infected pregnant women were frequently anemic (6.5%) and delivered babies of reduced birthweight. P. vivax infections during pregnancy are clearly associated with serious adverse outcomes and should be considered in prevention strategies of pregnancy-associated malaria.

  5. Severe Plasmodium knowlesi with dengue coinfection.

    Science.gov (United States)

    Che Rahim, Mohd Jazman; Mohammad, Nurashikin; Besari, Alwi Muhd; Wan Ghazali, Wan Syamimee

    2017-02-20

    We report a case of severe Plasmodium knowlesi and dengue coinfection in a previously healthy 59-year-old Malay man who presented with worsening shortness of breath, high-grade fever with chills and rigors, dry cough, myalgia, arthralgia, chest discomfort and poor appetite of 1 week duration. There was a history mosquito fogging around his neighbourhood in his hometown. Further history revealed that he went to a forest in Jeli (northern part of Kelantan) 3 weeks prior to the event. Initially he was treated as severe dengue with plasma leakage complicated with type 1 respiratory failure as evidenced by positive serum NS1-antigen and thrombocytopenia. Blood for malarial parasite (BFMP) was sent for test as there was suspicion of malaria due to persistent thrombocytopenia despite recovering from dengue infection and the presence of a risk factor. The test revealed high count of malaria parasite. Confirmatory PCR identified the parasite to be Plasmodium knowlesi Intravenous artesunate was administered to the patient immediately after acquiring the BFMP result. Severe malaria was complicated with acute kidney injury and septicaemic shock. Fortunately the patient made full recovery and was discharged from the ward after 2 weeks of hospitalisation. 2017 BMJ Publishing Group Ltd.

  6. RETINAL HAEMORRHAGE IN PLASMODIUM VIVAX PATIENTS- 2 RARE CASE REPORTS

    Directory of Open Access Journals (Sweden)

    Sangeeta

    2012-12-01

    Full Text Available ABSTRACT: Retinal haemorrhage is commonly detected during opht halmoscopic examination of patients with Plasmodium falciparum infections. Ho wever, it is observed very rarely in Plasmodium vivax infections. Only six cases of reti nal haemorrhage have been reported so far in Plasmodium vivax infections. We review the literatu re and discuss two such cases of retinal haemorrhage that presented at our hospital. It is sug gested that retinal haemorrhage be routinely ruled out in all malaria patients, and Pla smodium vivax infection be considered in patients with unexplained retinal haemorrhage and fev er.

  7. Concurrent Meta-Evaluation: A Critique

    Science.gov (United States)

    Hanssen, Carl E.; Lawrenz, Frances; Dunet, Diane O.

    2008-01-01

    Meta-evaluations reported in the literature, although rare, often have focused on retrospective assessment of completed evaluations. Conducting a meta-evaluation concurrently with the evaluation modifies this approach. This method provides the opportunity for the meta-evaluators to advise the evaluators and provides the basis for a summative…

  8. CAPP Framework System for Concurrent Engineering

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Difficulty in generalizing and lack of adaptability are important factors that hamper a computer aided process planning (CAPP) system from being popular and practical. New manufacturing philosophies such as Concurrent Engineering require special characteristic of a CAPP system. Proposed in this paper is a CAPP framework system for Concurrent Engineering (CAPPFS-CE) which can meet the requirements of Concurrent Engineering and whose information models, function models and decision logic can be customized by users to form various CAPP application systems. Its function requirements are discussed broadly. An architecture for CAPPFS-CE is presented. It is based on abstract information models (AIMs) and abstract function models (AFMs). The kernel is formed by customization interpretation, internal process control and decision engine. A new information modeling and system development method, information element method (IEM), is introduced to build up AIMs, decision engine, and AFMs and then realize a CAPPFS-CE. THCAPP-SHELL, a CAPPFS-CE developed by IEM, is demonstrated. A CAPP system produced by customizing THCAPP-SHELL for complex structural parts in a concurrent engineering environment is shown.

  9. Logics and Games for True Concurrency

    CERN Document Server

    Gutierrez, Julian

    2010-01-01

    We study the underlying mathematical properties of various partial order models of concurrency based on transition systems, Petri nets, and event structures, and show that the concurrent behaviour of these systems can be captured in a uniform way by two simple and general dualities of local behaviour. Such dualities are used to define new mu-calculi and logic games for the analysis of concurrent systems with partial order semantics. Some results of this work are: the definition of a number of mu-calculi which, in some classes of systems, induce the same identifications as some of the best known bisimulation equivalences for concurrency; and the definition of (infinite) higher-order logic games for bisimulation and model-checking, where the players of the games are given (local) monadic second-order power on the sets of elements they are allowed to play. More specifically, we show that our games are sound and complete, and therefore, determined; moreover, they are decidable in the finite case and underpin nove...

  10. Declarative interpretations of session-based concurrency

    DEFF Research Database (Denmark)

    Cano, Mauricio; Rueda, Camilo; López-Acosta, Hugo-Andrés;

    2015-01-01

    Session-based concurrency is a type-based approach to the analysis of communication-intensive systems. Correct behavior in these systems may be specified in an operational or declarative style: the former defines how interactions are structured; the latter defines governing conditions. In this pa...

  11. Concurrent Engineering Design Using Intelligent Agents.

    Science.gov (United States)

    Parkinson, Brian

    1998-01-01

    Describes Design Builder, interactive multimedia software that was developed to enable undergraduate engineers to experience working in a concurrent environment without direct and specialized teaching-staff support, and to provide an interactive and intelligent simulation environment from which users may develop a culture that introduces…

  12. Concurrent Engineering in the 21st Century

    NARCIS (Netherlands)

    Stjepandic, Josip; Wognum, P.M.; Verhagen, Wim

    2015-01-01

    Presenting the gradual evolution of the concept of Concurrent Engineering (CE), and the technical, social methods and tools that have been developed, including the many theoretical and practical challenges that still exist, this book serves to summarize the achievements and current challenges of CE

  13. Concurrent Engineering Teams. Volume 2: Annotated Bibliography

    Science.gov (United States)

    1990-11-01

    Feigenbaum. A.V., Total Quality Control, McGraw-Hill Book Company, NY, 1983. Goldratt , Eliyahu and Jeff Cox, The Goal, A Process of Ongoing Improvement...design, namely concurrent engineering design for the life cycle. We introduce the emergent notion of Meta -Design, which we believe can be understood

  14. Formal Derivation of Concurrent Garbage Collectors

    NARCIS (Netherlands)

    Pavlovic, Dusko; Pepper, Peter; Smith, Douglas R.

    Concurrent garbage collectors are notoriously difficult to implement correctly. Previous approaches to the issue of producing correct collectors have mainly been based on posit-and-prove verification or on the application of domain-specific templates and transformations. We show how to derive the

  15. Concurrent Validity of a Pragmatic Protocol.

    Science.gov (United States)

    Duncan, Julie Condon; Perozzi, Joseph A.

    1987-01-01

    The scores of 11 non-handicapped kindergarten children on the Pragmatic Protocol (used in assessing language-handicapped children) were correlated with their ratings by five experienced judges on a 7-point equal-appearing interval scale of communicative competence. The concurrent validity of the Protocol and interobserver reliability were…

  16. On run-time exploitation of concurrency

    NARCIS (Netherlands)

    Hölzenspies, Philip Kaj Ferdinand

    2010-01-01

    The `free' speed-up stemming from ever increasing processor speed is over. Performance increase in computer systems can now only be achieved through parallelism. One of the biggest challenges in computer science is how to map applications onto parallel computers. Concurrency, seen as the set of v

  17. Concurrent Engineering Teams. Volume 1: Main Text

    Science.gov (United States)

    1990-11-01

    Delphi Processes. Scott, Foresman, and Co. Glenview, IL. Dertouzos, Michael L.; Lester, Rizhard K.; and Solow , Robert M. 1989. Made in America. Regaining...Nc:%* York. Nevins, James L. and Whitney, Daniel E. 1989. Concurrent Design of F-,oducts and Processes: a Strategy for the Next Generation in

  18. Nonlinear Inequalities and Entropy-Concurrence Plane

    CERN Document Server

    Bovino, F A

    2006-01-01

    Nonlinear inequalities based on the quadratic Renyi entropy for mixed two-qubit states are characterized on the Entropy-Concurrence plane. This class of inequalities is stronger than Clauser-Horne-Shimony-Holt (CHSH) inequalities and, in particular, are violated "in toto" by the set of Type I Maximally-Entangled-Mixture States (MEMS I).

  19. On run-time exploitation of concurrency

    NARCIS (Netherlands)

    Holzenspies, P.K.F.

    2010-01-01

    The `free' speed-up stemming from ever increasing processor speed is over. Performance increase in computer systems can now only be achieved through parallelism. One of the biggest challenges in computer science is how to map applications onto parallel computers. Concurrency, seen as the set of vali

  20. SCOOP Structured Concurrent Object Oriented Prolog

    Science.gov (United States)

    Vaucher, Jean; Lapalme, Guy; Malenfant, Jacques

    SCOOP is an experimental language implemented in Prolog that tries to combine the best of logic, object-oriented and concurrent programming in a structured, natural and efficient manner. SCOOP provides hierarchies of object classes. These objects behave as independent Prolog programs with private databases which can execute goals within other objects.

  1. Verifying Functional Behaviour of Concurrent Programs

    NARCIS (Netherlands)

    Zaharieva, M.; Huisman, Marieke; Blom, Stefan; Pearce, D.

    Specifying the functional behaviour of a concurrent program can often be quite troublesome: it is hard to provide a stable method contract that can not be invalidated by other threads. In this paper we propose a novel modular technique for specifying and verifying behavioural properties in

  2. Integrated concurrent utilization quality review, Part one.

    Science.gov (United States)

    Caterinicchio, R P

    1987-01-01

    This article is the first of a two-part series which argues for the concurrent management of the appropriateness, necessity, and quality of patient care. Intensifying scrutiny by the credentialing groups, the PROs and all third-party payors underscores the vital need to implement cost-effective information systems which integrate the departmentalized functions of patient-physician profiling, DRG case-mix analyses, length of stay monitoring, pre-admission/admission and continued stay review, discharge planning, risk management, incident reporting and quality review. In the domain of physician performance regarding admitting and practice patterns, the ability to exercise concurrent utilization-quality review means early detection and prevention of events which would otherwise result in denials of payment and/or compromised patient care. Concurrent utilization-quality review must, by definition, be managerially invasive and focused; hence, it is integral to maintaining the integrity of the services and product lines offered by the provider. In fact, if PPO status is a marketing agenda, then the institutional objectives of cost-effectiveness, productivity, value, and competitiveness can only be achieved through concurrent utilization-quality review.

  3. Plasmodium falciparum full life cycle and Plasmodium ovale liver stages in humanized mice

    Science.gov (United States)

    Soulard, Valérie; Bosson-Vanga, Henriette; Lorthiois, Audrey; Roucher, Clémentine; Franetich, Jean- François; Zanghi, Gigliola; Bordessoulles, Mallaury; Tefit, Maurel; Thellier, Marc; Morosan, Serban; Le Naour, Gilles; Capron, Frédérique; Suemizu, Hiroshi; Snounou, Georges; Moreno-Sabater, Alicia; Mazier, Dominique

    2015-01-01

    Experimental studies of Plasmodium parasites that infect humans are restricted by their host specificity. Humanized mice offer a means to overcome this and further provide the opportunity to observe the parasites in vivo. Here we improve on previous protocols to achieve efficient double engraftment of TK-NOG mice by human primary hepatocytes and red blood cells. Thus, we obtain the complete hepatic development of P. falciparum, the transition to the erythrocytic stages, their subsequent multiplication, and the appearance of mature gametocytes over an extended period of observation. Furthermore, using sporozoites derived from two P. ovale-infected patients, we show that human hepatocytes engrafted in TK-NOG mice sustain maturation of the liver stages, and the presence of late-developing schizonts indicate the eventual activation of quiescent parasites. Thus, TK-NOG mice are highly suited for in vivo observations on the Plasmodium species of humans. PMID:26205537

  4. Plasmodium vivax and Plasmodium falciparum are Common Malaria Species in Pakistan

    Directory of Open Access Journals (Sweden)

    Tauseef Ahmad

    2016-06-01

    Full Text Available The microbes have a diverse nature, it makes human laugh and cry. Some microbes are fruitful for humans while others are harmful. Infectious diseases are a key problem in the modern world. In the last few decades, million of peoples have died from different diseases, including bacterial, viral, fungal, parasitic, etc. Among these diseases, malaria is one of the major health problems for developing countries including Pakistan. This study was undertaken to provide baseline information about the prevalence of malaria, species distribution and to contribute to the data regarding epidemiology in Pakistan. For a collection of literature, the electronic search engine was used, using different key words i.e. prevalence, species distribution, epidemiology of malaria in Pakistan, etc. The time frame of the obtained articles was from 2000 to 2014. The two species of malaria Plasmodium vivax and Plasmodium falciparum are common in Pakistan. [Biomed Res Ther 2016; 3(6.000: 666-672

  5. Plasmodium species: master renovators of their host cells.

    Science.gov (United States)

    de Koning-Ward, Tania F; Dixon, Matthew W A; Tilley, Leann; Gilson, Paul R

    2016-08-01

    Plasmodium parasites, the causative agents of malaria, have developed elaborate strategies that they use to survive and thrive within different intracellular environments. During the blood stage of infection, the parasite is a master renovator of its erythrocyte host cell, and the changes in cell morphology and function that are induced by the parasite promote survival and contribute to the pathogenesis of severe malaria. In this Review, we discuss how Plasmodium parasites use the protein trafficking motif Plasmodium export element (PEXEL), protease-mediated polypeptide processing, a novel translocon termed the Plasmodium translocon of exported proteins (PTEX) and exomembranous structures to export hundreds of proteins to discrete subcellular locations in the host erythrocytes, which enables the parasite to gain access to vital nutrients and to evade the immune defence mechanisms of the host.

  6. STUDY ON RELATIVE ABUNDANCE OF Plasmodium SPECIES: A ...

    African Journals Online (AJOL)

    DR. AMINU

    2013-06-01

    Jun 1, 2013 ... Keywords: abundance, plasmodium, relative, thin blood film, malaria control programmes. INTRODUCTION ... When an infected female Anopheles mosquito bites a ... the understanding of the type of infection as well as.

  7. Plasmodium infection in a Leadbeater's possum (Gymnobelideus leadbeateri).

    Science.gov (United States)

    Scheelings, T F; McLaren, P J; Tatarczuch, L; Slocombe, R F

    2016-08-01

    A wild-caught, adult female Leadbeater's possum (Gymnobelideus leadbeateri) died while in captivity after suffering from chronic ill-thrift that progressed to acute respiratory distress. On histopathological examination of tissues, the cause of death was determined to be severe acute pneumonia with pulmonary oedema associated with an intracellular protozoan parasite present within erythrocytes. Transmission electron microscopy was performed on lung tissues and organisms consistent for Plasmodium sp. were identified within numerous erythrocytes. Molecular characterisation of the parasite from DNA extracted from tissue blocks of fixed lung determined the organism to belong to the genus Plasmodium (100% similarity to Plasmodium species when a BLAST analysis was performed); however, speciation of the organism was not possible. This is the first report of Plasmodium sp. infection and subsequent disease in a native Australian mammal. The lifecycle of this parasite remains unknown. It is also unknown what effects haemoparasitism may have on the population dynamics of this endangered possum species. © 2016 Australian Veterinary Association.

  8. International population movements and regional Plasmodium falciparum malaria elimination strategies

    National Research Council Canada - National Science Library

    Andrew J. Tatem; David L. Smith; Susan Hanson

    2010-01-01

    ... to areas targeted for elimination. Here, census-based migration data were analyzed with network analysis tools, Plasmodium falciparum malaria transmission maps, and global population databases to map globally communities of countries...

  9. Peripheral blood cell signatures of Plasmodium falciparum infection during pregnancy

    DEFF Research Database (Denmark)

    Ibitokou, Samad; Oesterholt, Mayke; Brutus, Laurent;

    2012-01-01

    Sequestration of Plasmodium falciparum-infected erythrocytes in placental intervillous spaces causes inflammation and pathology. Knowledge of the profiles of immune cells associated with the physiopathology of pregnancy-associated malaria (PAM) is scarce. We conducted a longitudinal, prospective...

  10. Heterologous Protection against Malaria after Immunization with Plasmodium falciparum Sporozoites

    NARCIS (Netherlands)

    Schats, R.; Bijker, E.M.; Gemert, G.J.A. van; Graumans, W.; Vegte-Bolmer, M. van de; Lieshout, L. van; Haks, M.C.; Hermsen, C.C.; Scholzen, A.; Visser, L.G.; Sauerwein, R.W.

    2015-01-01

    BACKGROUND: Sterile protection in >90% of volunteers against homologous Plasmodium falciparum infection has been achieved only using the controlled human malaria infection (CHMI) model. This efficient model involves whole parasite immunizations under chloroquine prophylaxis (CPS-immunization),

  11. Guillain-Barré syndrome in Plasmodium falciparum malaria.

    OpenAIRE

    Wijesundere, A.

    1992-01-01

    A patient with Plasmodium falciparum malaria developed peripheral neuropathy. Clinical, cerebro-spinal fluid examination and nerve conduction studies confirmed Guillain-Barré syndrome, not previously reported in P. falciparum malaria.

  12. Anti-Plasmodium activity of ceramide analogs

    Directory of Open Access Journals (Sweden)

    Gatt Shimon

    2004-12-01

    Full Text Available Abstract Background Sphingolipids are key molecules regulating many essential functions in eukaryotic cells and ceramide plays a central role in sphingolipid metabolism. A sphingolipid metabolism occurs in the intraerythrocytic stages of Plasmodium falciparum and is associated with essential biological processes. It constitutes an attractive and potential target for the development of new antimalarial drugs. Methods The anti-Plasmodium activity of a series of ceramide analogs containing different linkages (amide, methylene or thiourea linkages between the fatty acid part of ceramide and the sphingoid core was investigated in culture and compared to the sphingolipid analog PPMP (d,1-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol. This analog is known to inhibit the parasite sphingomyelin synthase activity and block parasite development by preventing the formation of the tubovesicular network that extends from the parasitophorous vacuole to the red cell membrane and delivers essential extracellular nutrients to the parasite. Results Analogs containing methylene linkage showed a considerably higher anti-Plasmodium activity (IC50 in the low nanomolar range than PPMP and their counterparts with a natural amide linkage (IC50 in the micromolar range. The methylene analogs blocked irreversibly P. falciparum development leading to parasite eradication in contrast to PPMP whose effect is cytostatic. A high sensitivity of action towards the parasite was observed when compared to their effect on the human MRC-5 cell growth. The toxicity towards parasites did not correlate with the inhibition by methylene analogs of the parasite sphingomyelin synthase activity and the tubovesicular network formation, indicating that this enzyme is not their primary target. Conclusions It has been shown that ceramide analogs were potent inhibitors of P. falciparum growth in culture. Interestingly, the nature of the linkage between the fatty acid part and the

  13. Placental histopathological changes associated with Plasmodium vivax infection during pregnancy.

    Directory of Open Access Journals (Sweden)

    Rodrigo M Souza

    Full Text Available Histological evidence of Plasmodium in the placenta is indicative of placental malaria, a condition associated with severe outcomes for mother and child. Histological lesions found in placentas from Plasmodium-exposed women include syncytial knotting, syncytial rupture, thickening of the placental barrier, necrosis of villous tissue and intervillositis. These histological changes have been associated with P. falciparum infections, but little is known about the contribution of P. vivax to such changes. We conducted a cross-sectional study with pregnant women at delivery and assigned them to three groups according to their Plasmodium exposure during pregnancy: no Plasmodium exposure (n = 41, P. vivax exposure (n = 59 or P. falciparum exposure (n = 19. We evaluated their placentas for signs of Plasmodium and placental lesions using ten histological parameters: syncytial knotting, syncytial rupture, placental barrier thickness, villi necrosis, intervillous space area, intervillous leucocytes, intervillous mononucleates, intervillous polymorphonucleates, parasitized erythrocytes and hemozoin. Placentas from P. vivax-exposed women showed little evidence of Plasmodium or hemozoin but still exhibited more lesions than placentas from women not exposed to Plasmodium, especially when infections occurred twice or more during pregnancy. In the Brazilian state of Acre, where diagnosis and primary treatment are readily available and placental lesions occur in the absence of detected placental parasites, relying on the presence of Plasmodium in the placenta to evaluate Plasmodium-induced placental pathology is not feasible. Multivariate logistic analysis revealed that syncytial knotting (odds ratio [OR], 4.21, P = 0.045, placental barrier thickness (OR, 25.59, P = 0.021 and mononuclear cells (OR, 4.02, P = 0.046 were increased in placentas from P. vivax-exposed women when compared to women not exposed to Plasmodium during pregnancy. A

  14. Limitations of microscopy to differentiate Plasmodium species in a region co-endemic for Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi

    OpenAIRE

    Barber Bridget E; William Timothy; Grigg Matthew J; Yeo Tsin W; Anstey Nicholas M

    2013-01-01

    Abstract Background In areas co-endemic for multiple Plasmodium species, correct diagnosis is crucial for appropriate treatment and surveillance. Species misidentification by microscopy has been reported in areas co-endemic for vivax and falciparum malaria, and may be more frequent in regions where Plasmodium knowlesi also commonly occurs. Methods This prospective study in Sabah, Malaysia, evaluated the accuracy of routine district and referral hospital-based microscopy, and microscopy perfor...

  15. Desferrioxamine suppresses Plasmodium falciparum in Aotus monkeys.

    Science.gov (United States)

    Pollack, S; Rossan, R N; Davidson, D E; Escajadillo, A

    1987-02-01

    Clinical observation has suggested that iron deficiency may be protective in malaria, and we have found that desferrioxamine (DF), an iron-specific chelating agent, inhibited Plasmodium falciparum growth in vitro. It was difficult to be confident that DF would be effective in an intact animal, however, because continuous exposure to DF was required in vitro and, in vivo, DF is rapidly excreted. Also, the in vitro effect of DF was overcome by addition of iron to the culture and in vivo there are potentially high local iron concentrations when iron is absorbed from the diet or released from reticuloendothelial cells. We now show that DF given by constant subcutaneous infusion does suppress parasitemia in P. falciparum-infected Aotus monkeys.

  16. Development of vaccines for Plasmodium vivax malaria.

    Science.gov (United States)

    Mueller, Ivo; Shakri, Ahmad Rushdi; Chitnis, Chetan E

    2015-12-22

    Plasmodium vivax continues to cause significant morbidity outside Africa with more than 50% of malaria cases in many parts of South and South-east Asia, Pacific islands, Central and South America being attributed to P. vivax infections. The unique biology of P. vivax, including its ability to form latent hypnozoites that emerge months to years later to cause blood stage infections, early appearance of gametocytes before clinical symptoms are apparent and a shorter development cycle in the vector makes elimination of P. vivax using standard control tools difficult. The availability of an effective vaccine that provides protection and prevents transmission would be a valuable tool in efforts to eliminate P. vivax. Here, we review the latest developments related to P. vivax malaria vaccines and discuss the challenges as well as directions toward the goal of developing highly efficacious vaccines against P. vivax malaria.

  17. Wanted Plasmodium falciparum, dead or alive

    Directory of Open Access Journals (Sweden)

    Fatimata Sow

    2015-07-01

    Full Text Available Mechanisms of cell death in unicellular parasites have been subjects of debate for the last decade, with studies demonstrating evidence of apoptosis or non-apoptosis like mechanisms, including necrosis, and autophagy. Recent clarifications on the definition of regulated or accidental cell death by The Nomenclature Committee on Cell Death provides an opportunity to reanalyze some data, re-evaluate conclusions in the light of parasite diversity, and to propose alternative arguments in the context of malaria drug resistance, considering lack of really new drugs in the pipeline. Deciphering the mechanisms of death may help in detection of new drug targets and the design of innovative drugs. However, classifications have been evolving rapidly since initial description of “programmed cell death”, leading to some uncertainty as to whether Plasmodium cell death is accidental or regulated.

  18. Plasmodium falciparum drug resistance in Angola.

    Science.gov (United States)

    Fançony, Cláudia; Brito, Miguel; Gil, Jose Pedro

    2016-02-09

    Facing chloroquine drug resistance, Angola promptly adopted artemisinin-based combination therapy as the first-line to treat malaria. Currently, the country aims to consolidate malaria control, while preparing for the elimination of the disease, along with others African countries in the region. However, the remarkable capacity of Plasmodium to develop drug resistance represents an alarming threat for those achievements. Herein, the available, but relatively scarce and dispersed, information on malaria drug resistance in Angola, is reviewed and discussed. The review aims to inform but also to encourage future research studies that monitor and update the information on anti-malarial drug efficacy and prevalence of molecular markers of drug resistance, key fields in the context and objectives of elimination.

  19. Gametocytogenesis : the puberty of Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Ariey Frédéric

    2004-07-01

    Full Text Available Abstract The protozoan Plasmodium falciparum has a complex life cycle in which asexual multiplication in the vertebrate host alternates with an obligate sexual reproduction in the anopheline mosquito. Apart from the apparent recombination advantages conferred by sex, P. falciparum has evolved a remarkable biology and adaptive phenotypes to insure its transmission despite the dangers of sex. This review mainly focuses on the current knowledge on commitment to sexual development, gametocytogenesis and the evolutionary significance of various aspects of gametocyte biology. It goes further than pure biology to look at the strategies used to improve successful transmission. Although gametocytes are inevitable stages for transmission and provide a potential target to fight malaria, they have received less attention than the pathogenic asexual stages. There is a need for research on gametocytes, which are a fascinating stage, responsible to a large extent for the success of P. falciparum.

  20. Epidemiology of Plasmodium vivax Malaria in Peru.

    Science.gov (United States)

    Rosas-Aguirre, Angel; Gamboa, Dionicia; Manrique, Paulo; Conn, Jan E; Moreno, Marta; Lescano, Andres G; Sanchez, Juan F; Rodriguez, Hugo; Silva, Hermann; Llanos-Cuentas, Alejandro; Vinetz, Joseph M

    2016-12-28

    Malaria in Peru, dominated by Plasmodium vivax, remains a public health problem. The 1990s saw newly epidemic malaria emerge, primarily in the Loreto Department in the Amazon region, including areas near to Iquitos, the capital city, but sporadic malaria transmission also occurred in the 1990s-2000s in both north-coastal Peru and the gold mining regions of southeastern Peru. Although a Global Fund-supported intervention (PAMAFRO, 2005-2010) was temporally associated with a decrease of malaria transmission, from 2012 to the present, both P. vivax and Plasmodium falciparum malaria cases have rapidly increased. The Peruvian Ministry of Health continues to provide artemesinin-based combination therapy for microscopy-confirmed cases of P. falciparum and chloroquine-primaquine for P. vivax Malaria transmission continues in remote areas nonetheless, where the mobility of humans and parasites facilitates continued reintroduction outside of ongoing surveillance activities, which is critical to address for future malaria control and elimination efforts. Ongoing P. vivax research gaps in Peru include the following: identification of asymptomatic parasitemics, quantification of the contribution of patent and subpatent parasitemics to mosquito transmission, diagnosis of nonparasitemic hypnozoite carriers, and implementation of surveillance for potential emergence of chloroquine- and 8-aminoquinoline-resistant P. vivax Clinical trials of tafenoquine in Peru have been promising, and glucose-6-phosphate dehydrogenase deficiency in the region has not been observed to be a limitation to its use. Larger-scale challenges for P. vivax (and malaria in general) in Peru include logistical difficulties in accessing remote riverine populations, consequences of government policy and poverty trends, and obtaining international funding for malaria control and elimination.

  1. Plasmodium vivax adherence to placental glycosaminoglycans.

    Directory of Open Access Journals (Sweden)

    Kesinee Chotivanich

    Full Text Available BACKGROUND: Plasmodium vivax infections seldom kill directly but do cause indirect mortality by reducing birth weight and causing abortion. Cytoadherence and sequestration in the microvasculature are central to the pathogenesis of severe Plasmodium falciparum malaria, but the contribution of cytoadherence to pathology in other human malarias is less clear. METHODOLOGY: The adherence properties of P. vivax infected red blood cells (PvIRBC were evaluated under static and flow conditions. PRINCIPAL FINDINGS: P. vivax isolates from 33 patients were studied. None adhered to immobilized CD36, ICAM-1, or thrombospondin, putative ligands for P. falciparum vascular cytoadherence, or umbilical vein endothelial cells, but all adhered to immobilized chondroitin sulphate A (CSA and hyaluronic acid (HA, the receptors for adhesion of P. falciparum in the placenta. PvIRBC also adhered to fresh placental cells (N = 5. Pre-incubation with chondroitinase prevented PvIRBC adherence to CSA, and reduced binding to HA, whereas preincubation with hyaluronidase prevented adherence to HA, but did not reduce binding to CSA significantly. Pre-incubation of PvIRBC with soluble CSA and HA reduced binding to the immobilized receptors and prevented placental binding. PvIRBC adhesion was prevented by pre-incubation with trypsin, inhibited by heparin, and reduced by EGTA. Under laminar flow conditions the mean (SD shear stress reducing maximum attachment by 50% was 0.06 (0.02 Pa but, having adhered, the PvIRBC could then resist detachment by stresses up to 5 Pa. At 37 °C adherence began approximately 16 hours after red cell invasion with maximal adherence at 30 hours. At 39 °C adherence began earlier and peaked at 24 hours. SIGNIFICANCE: Adherence of P. vivax-infected erythrocytes to glycosaminoglycans may contribute to the pathogenesis of vivax malaria and lead to intrauterine growth retardation.

  2. Epidemiology of Plasmodium vivax Malaria in Peru

    Science.gov (United States)

    Rosas-Aguirre, Angel; Gamboa, Dionicia; Manrique, Paulo; Conn, Jan E.; Moreno, Marta; Lescano, Andres G.; Sanchez, Juan F.; Rodriguez, Hugo; Silva, Hermann; Llanos-Cuentas, Alejandro; Vinetz, Joseph M.

    2016-01-01

    Malaria in Peru, dominated by Plasmodium vivax, remains a public health problem. The 1990s saw newly epidemic malaria emerge, primarily in the Loreto Department in the Amazon region, including areas near to Iquitos, the capital city, but sporadic malaria transmission also occurred in the 1990s–2000s in both north-coastal Peru and the gold mining regions of southeastern Peru. Although a Global Fund-supported intervention (PAMAFRO, 2005–2010) was temporally associated with a decrease of malaria transmission, from 2012 to the present, both P. vivax and Plasmodium falciparum malaria cases have rapidly increased. The Peruvian Ministry of Health continues to provide artemesinin-based combination therapy for microscopy-confirmed cases of P. falciparum and chloroquine–primaquine for P. vivax. Malaria transmission continues in remote areas nonetheless, where the mobility of humans and parasites facilitates continued reintroduction outside of ongoing surveillance activities, which is critical to address for future malaria control and elimination efforts. Ongoing P. vivax research gaps in Peru include the following: identification of asymptomatic parasitemics, quantification of the contribution of patent and subpatent parasitemics to mosquito transmission, diagnosis of nonparasitemic hypnozoite carriers, and implementation of surveillance for potential emergence of chloroquine- and 8-aminoquinoline-resistant P. vivax. Clinical trials of tafenoquine in Peru have been promising, and glucose-6-phosphate dehydrogenase deficiency in the region has not been observed to be a limitation to its use. Larger-scale challenges for P. vivax (and malaria in general) in Peru include logistical difficulties in accessing remote riverine populations, consequences of government policy and poverty trends, and obtaining international funding for malaria control and elimination. PMID:27799639

  3. Discordance in drug resistance-associated mutation patterns in marker genes of Plasmodium falciparum and Plasmodium knowlesi during coinfections.

    Science.gov (United States)

    Tyagi, Rupesh K; Das, Manoj K; Singh, Shiv S; Sharma, Yagya D

    2013-05-01

    Human Plasmodium knowlesi infections have been reported from several South-East Asian countries, excluding India, but its drug susceptibility profile in mixed-infection cases remains unknown. The chloroquine resistance transporter (CRT) and dihydrofolate reductase (DHFR) genes of P. knowlesi and other Plasmodium species were sequenced from clinical isolates obtained from malaria patients living in the Andaman and Nicobar Islands, India. The merozoite surface protein-1 and 18S rRNA genes of P. knowlesi were also sequenced from these isolates. Among 445 samples analysed, only 53 of them had P. knowlesi-specific gene sequences. While 3 of the 53 cases (5.66%) had P. knowlesi monoinfection, the rest were coinfected with Plasmodium falciparum (86.79%, n = 46) or Plasmodium vivax (7.55%, n = 4), but none with Plasmodium malariae or Plasmodium ovale. There was discordance in the drug resistance-associated mutations among the coinfecting Plasmodium species. This is because the P. knowlesi isolates contained wild-type sequences, while P. falciparum isolates had mutations in the CRT and DHFR marker genes associated with a higher level of chloroquine and antifolate drug resistance, respectively. The mutation pattern indicates that the same patient, having a mixed infection, may be harbouring the drug-susceptible P. knowlesi parasite and a highly drug-resistant P. falciparum parasite. A larger human population in South-East Asia may be at risk of P. knowlesi infection than reported so far. The different drug susceptibility genotypes of P. knowlesi from its coinfecting Plasmodium species in mixed infections adds a new dimension to the malaria control programme, requiring formulation of an appropriate drug policy.

  4. Aerospace concurrent engineering: a modern global approach

    Science.gov (United States)

    Imbert, Mariano; Li, Xiaoxing

    2009-12-01

    System engineering aspects, like concurrent engineering (CE) in the aerospace sector, has been studied by many authors. The change and evolution in this regard is continually influenced by the information technology advances. But global cooperation is only discussed by developed countries and high technology corporations. A review of CE and its ramifications in the aerospace industry is presented. Based on the current literature, the general lifecycle of a spacecraft and its phases are explained as well as the tools that are implemented in today's industry. In this paper we propose a new approach for the product development process in the spacecraft production industry the Aerospace Concurrent Engineering (ACE), which is mainly focused in the technology itself, its optimal design and environment impact rather than costs and marketing impact. And the potential of globally oriented research and implementation of space programs is discussed for its consideration.

  5. Transactions Concurrency Control in Web Service Environment

    DEFF Research Database (Denmark)

    Alrifai, Mohammad; Dolog, Peter; Nejdl, Wolfgang

    2006-01-01

    an engineering point of view as it does not change the way consumers or clients of web services have to be programmed. Furthermore, it avoids direct communication between transaction coordinators which preserves security by keeping the information about business transactions restricted to the coordinators which......Business transactions in web service environments run with relaxed isolation and atomicity property. In such environments, transactions can commit and roll back independently on each other. Transaction management has to reflect this issue and address the problems which result for example from...... concurrent access to web service resources and data. In this paper we propose an extension to the WS-Transaction Protocol which ensures the consistency of the data when independent business transactions access the data concurrently under the relaxed transaction properties. Our extension is based...

  6. Nautilus: A Concurrent Anticipatory Programming Language

    Science.gov (United States)

    Menezes, P. Blauth; Costa, Simone A.; Machado, Júlio P.; Ramos, Jaime

    2002-09-01

    Nautilus is a concurrent anticipatory programming language based on the object-oriented language GNOME which is a simplified and revised version of OBLOG. A semantics for Nautilus is given by Nonsequencial Automata, that is a categorial semantic domain based on labeled transition system with full concurrency, where a class of morphisms stands for anticipation. The semantics of an object in Nautilus is given by an anticipation morphism, which is viewed as a special automaton morphism where target automata, called base, is determined by the computations of a freely generated automata able to simulate any object specified over the involved attributes, and the source automata is a relabelled restriction of the base. In order to introduce the anticipation of Nautilus, some examples are presented depicting the features of the language.

  7. Transparent concurrent execution of mutually exclusive alternatives

    OpenAIRE

    Smith, Jonathan M.; Gerald Q. Maguire Jr.

    1988-01-01

    We examine the task of concurrently computing alternative solutions to a problem. We restrict our interest to the case where only one of the solutions is needed; in this case we need some rule for selecting between the solutions. We use "fastest first," where the first successful alternative is selected. For problems where the required execution time is unpredictable, such as database queries. this method can show substantial execution time performance increases. These increases are dependent...

  8. Concurrency Control Mechanism of Complex Objects

    Institute of Scientific and Technical Information of China (English)

    徐庆云; 王能斌

    1992-01-01

    A complex object is an abstraction and description of a complex entity of the real world.Many applications in such domains as CIMS,CAD and OA define and manipulate a complex object as a single unit.In this paper,a definition of the model of complex objects is given,and the concurrency control mechanism of complex objects in WHYMX object-oriented database system is described.

  9. Verification of concurrent programs with Chalice

    OpenAIRE

    K. Rustan M. Leino; Müller, Peter; Smans, Jan

    2009-01-01

    A program verifier is a tool that allows developers to prove that their code satisfies its specification for every possible input and every thread schedule. These lecture notes describe a verifier for concurrent programs called Chalice. Chalice's verification methodology centers around permissions and permission transfer. In particular, a memory location may be accessed by a thread only if that thread has permission to do so. Proper use of permissions allows Chalice to deduce upper bound...

  10. Preliminary Proceedings 15th International Workshop on Expressiveness in Concurrency

    DEFF Research Database (Denmark)

    The EXPRESS workshops aim at bringing together researchers interested in the relations between various formal systems, particularly in the field of Concurrency. More specifically, they focus on the comparison between programming concepts (such as concurrent, functional, imperative, logic and object...

  11. Construction disputes in Denmark: the case of concurrent delay

    DEFF Research Database (Denmark)

    Cavaleri, Sylvie Cécile

    2015-01-01

    Through a case study of decisions on concurrent delay, the article discusses the defining features of Danish construction arbitration.......Through a case study of decisions on concurrent delay, the article discusses the defining features of Danish construction arbitration....

  12. A Framework of Concurrent Mechanism Based on Java Multithread

    Directory of Open Access Journals (Sweden)

    Wuxue Jiang

    2013-09-01

    Full Text Available The continuously increased demand for paralleling multitask in domains such as grid computing and cloud computing has significantly promoted research on concurrent mechanism and concurrent programming. The Java programming language supports multithread mechanism for developing paralleling programs, however, it is difficult to apply Java concurrent primitives to specific problems. Thus, for the development of high reliable and qualitative Java concurrent programs, this paper analyses Java multithread mechanism and it’s realization, studies the concurrent mechanism based on Java synchronization and interactive communication mechanism , compares the concurrent structure based on operating system and based on Java multithread, sums up some concurrent programming rules and strategies to prevent deadlock. A frame instance based on entire synchronization is presented, which can help to develop concurrent programs quickly.  

  13. Managing Asynchronous Data in ATLAS's Concurrent Framework

    CERN Document Server

    Leggett, Charles; The ATLAS collaboration

    2016-01-01

    In order to be able to make effective use of emerging hardware, where the amount of memory available to any CPU is rapidly decreasing as the core count continues to rise, ATLAS has begun a migration to a concurrent, multi-threaded software framework, known as AthenaMT. Significant progress has been made in implementing AthenaMT - we can currently run realistic Geant4 simulations on massively concurrent machines. the migration of realistic prototypes of reconstruction workflows is more difficult, given the large amounts of legacy code and the complexity and challenges of reconstruction software. These types of workflows, however, are the types that will most benefit from the memory reduction features of a multi-threaded framework. One of the challenges that we will report on in this paper is the re-design and implementation of several key asynchronous technologies whose behaviour is radically different in a concurrent environment than in a serial one, namely the management of Conditions data and the Detector D...

  14. Symbolic Analysis of Concurrent Programs with Polymorphism

    Science.gov (United States)

    Rungta, Neha Shyam

    2010-01-01

    The current trend of multi-core and multi-processor computing is causing a paradigm shift from inherently sequential to highly concurrent and parallel applications. Certain thread interleavings, data input values, or combinations of both often cause errors in the system. Systematic verification techniques such as explicit state model checking and symbolic execution are extensively used to detect errors in such systems [7, 9]. Explicit state model checking enumerates possible thread schedules and input data values of a program in order to check for errors [3, 9]. To partially mitigate the state space explosion from data input values, symbolic execution techniques substitute data input values with symbolic values [5, 7, 6]. Explicit state model checking and symbolic execution techniques used in conjunction with exhaustive search techniques such as depth-first search are unable to detect errors in medium to large-sized concurrent programs because the number of behaviors caused by data and thread non-determinism is extremely large. We present an overview of abstraction-guided symbolic execution for concurrent programs that detects errors manifested by a combination of thread schedules and data values [8]. The technique generates a set of key program locations relevant in testing the reachability of the target locations. The symbolic execution is then guided along these locations in an attempt to generate a feasible execution path to the error state. This allows the execution to focus in parts of the behavior space more likely to contain an error.

  15. Managing Asynchronous Data in ATLAS's Concurrent Framework

    CERN Document Server

    Baines, John; The ATLAS collaboration

    2016-01-01

    In order to be able to make effective use of emerging hardware, where the amount of memory available to any CPU is rapidly decreasing as the core count continues to rise, ATLAS has begun a migration to a concurrent, multi-threaded software framework, known as AthenaMT. Significant progress has been made in implementing AthenaMT - we can currently run realistic Geant4 simulations on massively concurrent machines. the migration of realistic prototypes of reconstruction workflows is more difficult, given the large amounts of legacy code and the complexity and challenges of reconstruction software. These types of workflows, however, are the types that will most benefit from the memory reduction features of a multi-threaded framework. One of the challenges that we will report on in this paper is the re-design and implementation of several key asynchronous technologies whose behaviour is radically different in a concurrent environment than in a serial one, namely the management of Conditions data and the Detector D...

  16. Primate malarias: Diversity, distribution and insights for zoonotic Plasmodium

    Directory of Open Access Journals (Sweden)

    Christina Faust

    2015-12-01

    Full Text Available Protozoans within the genus Plasmodium are well-known as the causative agents of malaria in humans. Numerous Plasmodium species parasites also infect a wide range of non-human primate hosts in tropical and sub-tropical regions worldwide. Studying this diversity can provide critical insight into our understanding of human malarias, as several human malaria species are a result of host switches from non-human primates. Current spillover of a monkey malaria, Plasmodium knowlesi, in Southeast Asia highlights the permeability of species barriers in Plasmodium. Also recently, surveys of apes in Africa uncovered a previously undescribed diversity of Plasmodium in chimpanzees and gorillas. Therefore, we carried out a meta-analysis to quantify the global distribution, host range, and diversity of known non-human primate malaria species. We used published records of Plasmodium parasites found in non-human primates to estimate the total diversity of non-human primate malarias globally. We estimate that at least three undescribed primate malaria species exist in sampled primates, and many more likely exist in unstudied species. The diversity of malaria parasites is especially uncertain in regions of low sampling such as Madagascar, and taxonomic groups such as African Old World Monkeys and gibbons. Presence–absence data of malaria across primates enables us to highlight the close association of forested regions and non-human primate malarias. This distribution potentially reflects a long coevolution of primates, forest-adapted mosquitoes, and malaria parasites. The diversity and distribution of primate malaria are an essential prerequisite to understanding the mechanisms and circumstances that allow Plasmodium to jump species barriers, both in the evolution of malaria parasites and current cases of spillover into humans.

  17. Plasmodium malariae and Plasmodium ovale infections in the China-Myanmar border area.

    Science.gov (United States)

    Li, Peipei; Zhao, Zhenjun; Xing, Hua; Li, Wenli; Zhu, Xiaotong; Cao, Yaming; Yang, Zhaoqing; Sattabongkot, Jetsumon; Yan, Guiyun; Fan, Qi; Cui, Liwang

    2016-11-15

    The Greater Mekong Subregion is aiming to achieve regional malaria elimination by 2030. Though a shift in malaria parasite species predominance by Plasmodium vivax has been recently documented, the transmission of the two minor Plasmodium species, Plasmodium malariae and Plasmodium ovale spp., is poorly characterized in the region. This study aims to determine the prevalence of these minor species in the China-Myanmar border area and their genetic diversity. Epidemiology study was conducted during passive case detection in hospitals and clinics in Myanmar and four counties in China along the China-Myanmar border. Cross-sectional surveys were conducted in villages and camps for internally displaced persons to determine the prevalence of malaria infections. Malaria infections were diagnosed initially by microscopy and later in the laboratory using nested PCR for the SSU rRNA genes. Plasmodium malariae and P. ovale infections were confirmed by sequencing the PCR products. The P. ovale subtypes were determined by sequencing the Pocytb, Pocox1 and Pog3p genes. Parasite populations were evaluated by PCR amplification and sequencing of the MSP-1 genes. Antifolate sensitivity was assessed by sequencing the dhfr-ts and dhps genes from the P. malariae and P. ovale isolates. Analysis of 2701 blood samples collected from the China-Myanmar border by nested PCR targeting the parasite SSU rRNA genes identified 561 malaria cases, including 161 Plasmodium falciparum, 327 P. vivax, 66 P. falciparum/P. vivax mixed infections, 4 P. malariae and 3 P. ovale spp. P. vivax and P. falciparum accounted for >60 and ~30% of all malaria cases, respectively. In comparison, the prevalence of P. malariae and P. ovale spp. was very low and only made up ~1% of all PCR-positive cases. Nevertheless, these two species were often misidentified as P. vivax infections or completely missed by microscopy even among symptomatic patients. Phylogenetic analysis of the SSU rRNA, Pocytb, Pocox1 and Pog3p genes

  18. Anti-relapse activity of mirincamycin in the Plasmodium cynomolgi sporozoite-infected Rhesus monkey model

    OpenAIRE

    Fracisco, Susan; Teja-Isavadharm, Paktiya; Gettayacamin, Montip; Berman, Jonathan; Li, Qigui; Melendez, Victor; Saunders, David; Xie, Lisa; Ohrt, Colin

    2014-01-01

    Background Mirincamycin is a close analog of the drug clindamycin used to treat Plasmodium falciparum blood stages. The clinical need to treat Plasmodium vivax dormant liver stages and prevent relapse with a drug other than primaquine led to the evaluation of mirinicamycin against liver stages in animals. Methods cis-mirinicamycin and trans-mirinicamycin were evaluated as prophylaxis against early liver stages of Plasmodium berghei in mice and as antirelapse hypnozoiticides against Plasmodium...

  19. Rediscovery and redescription of Plasmodium pifanoi and description of two additional Plasmodium parasites of Venezuelan lizards.

    Science.gov (United States)

    Telford, Sam R; Telford, Sam R

    2003-04-01

    Plasmodium pifanoi Scorza and Dagert B., known only from the type host, Ameiva ameiva, is redescribed from Kentropyx calcarata collected in Territorio Amazonas, Venezuela. Schizonts, 6.2 x 4.5 (4-8 x 3-6), produce on average 11.9 (7-16) merozoites. Gametocytes average 12.4 x 6.0 (8-16 x 4-10), with length x width (LW) 72.9 (52-112) and L/W 2.18 (1.1-3.3), and always contain 1-5 prominent vacuoles. Macrogametocytes in active infection are longer than microgametocytes, with greater LW, but gametocytes in chronic infection are not sexually dimorphic in dimension and are slightly smaller. Two additional malarial parasites are described from K. calcarata. Plasmodium lepidoptiformis has small schizonts, 4.6 x 3.2 (3-6 x 2.5-3), that produce 5.1 (4-8) merozoites and commonly resemble a butterfly in appearance. Gametocytes are elongate, 9.0 x 4.3 (7-10 x 3-6), with LW 38.3 (24-51) and L/W 2.2 (1.3-3.3), and sexually dimorphic, with macrogametocytes longer than microgametocytes, with greater LW. Plasmodium minasense calcaratae is characterized by very small, usually fan-shaped, schizonts. 3.4 x 2.6 (2.5-4.5 x 2.0-3.0), that produce 3.9 (3-4) merozoites. Gametocytes are spherical or ovoid, 6.7 x 5.0 (4.5-9.0 x 3.0-7.0), with LW 33.7 (15-54) and L/W 1.4 (1.0-2.3), with no sexual dimorphism in dimensions.

  20. Maternal-foetal transfer of Plasmodium falciparum and Plasmodium vivax antibodies in a low transmission setting

    Science.gov (United States)

    Charnaud, Sarah C.; McGready, Rose; Herten-Crabb, Asha; Powell, Rosanna; Guy, Andrew; Langer, Christine; Richards, Jack S.; Gilson, Paul R.; Chotivanich, Kesinee; Tsuboi, Takafumi; Narum, David L.; Pimanpanarak, Mupawjay; Simpson, Julie A.; Beeson, James G.; Nosten, François; Fowkes, Freya J. I.

    2016-01-01

    During pregnancy immunolglobulin G (IgG) antibodies are transferred from mother to neonate across the placenta. Studies in high transmission areas have shown transfer of P. falciparum-specific IgG, but the extent and factors influencing maternal-foetal transfer in low transmission areas co-endemic for both P. falciparum and P. vivax are unknown. Pregnant women were screened weekly for Plasmodium infection. Mother-neonate paired serum samples at delivery were tested for IgG to antigens from P. falciparum, P. vivax and other infectious diseases. Antibodies to malarial and non-malarial antigens were highly correlated between maternal and neonatal samples (median [range] spearman ρ = 0.78 [0.57–0.93]), although Plasmodium spp. antibodies tended to be lower in neonates than mothers. Estimated gestational age at last P. falciparum infection, but not P. vivax infection, was positively associated with antibody levels in the neonate (P. falciparum merozoite, spearman ρ median [range] 0.42 [0.33–0.66], PfVAR2CSA 0.69; P. vivax ρ = 0.19 [0.09–0.3]). Maternal-foetal transfer of anti-malarial IgG to Plasmodium spp. antigens occurs in low transmission settings. P. vivax IgG acquisition is not associated with recent exposure unlike P. falciparum IgG, suggesting a difference in acquisition of antibodies. IgG transfer is greatest in the final weeks of pregnancy which has implications for the timing of future malaria vaccination strategies in pregnant women. PMID:26861682

  1. Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia

    Science.gov (United States)

    2013-01-02

    Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia Shannon Takala-Harrisona...resistant Plasmodium falcipa- rum malaria in western Cambodia could threaten prospects for malaria elimination. Identification of the genetic basis of...molecular markers Artemisinin-based combination therapies (ACTs) are the lead-ing treatment for Plasmodium falciparum malaria (1), and their use with

  2. Analyzing Plasmodium falciparum erythrocyte membrane protein 1 gene expression by a next generation sequencing based method

    DEFF Research Database (Denmark)

    Jespersen, Jakob S.; Petersen, Bent; Seguin-Orlando, Andaine;

    2013-01-01

    Plasmodium falciparum is responsible for most cases of severe malaria and causes >1 million deaths every year. The particular virulence of this Plasmodium species is highly associated with the expression of certain members of the Plasmodium falciparum erythrocyte membrane protein 1(PfEMP1) family...

  3. Creating components object oriented, concurrent, and distributed computing in Java

    CERN Document Server

    Kann, Charles W

    2003-01-01

    INTRODUCTION TO CONCURRENT PROGRAMMING AND COMPONENTSChapter GoalsWhat is Concurrent Programming?ComponentsTypes of Concurrent ProgrammingTHREADS AND PROGRAM CONTEXTSWriting threads in JavaA Simple Execution ModelProgram SafetyDeadlockDESIGNING AND IMPLEMENTING CONCURRENT PROGRAMS WITH STATE DIAGRAMSBackgroundSteps to Create a Concurrent ProgramThe Producer/Consumer ProblemWhy Passive Objects are ComponentsGas Station Simulation ProblemIdentifiers, Variables, Objects, and Collection ClassesIdentifiers and VariablesJava Identifiers and VariablesPrimitivesObjectsCollection Classes in JavaPROGRAM

  4. Concurrent conditional clustering of multiple networks: COCONETS.

    Directory of Open Access Journals (Sweden)

    Sabrina Kleessen

    Full Text Available The accumulation of high-throughput data from different experiments has facilitated the extraction of condition-specific networks over the same set of biological entities. Comparing and contrasting of such multiple biological networks is in the center of differential network biology, aiming at determining general and condition-specific responses captured in the network structure (i.e., included associations between the network components. We provide a novel way for comparison of multiple networks based on determining network clustering (i.e., partition into communities which is optimal across the set of networks with respect to a given cluster quality measure. To this end, we formulate the optimization-based problem of concurrent conditional clustering of multiple networks, termed COCONETS, based on the modularity. The solution to this problem is a clustering which depends on all considered networks and pinpoints their preserved substructures. We present theoretical results for special classes of networks to demonstrate the implications of conditionality captured by the COCONETS formulation. As the problem can be shown to be intractable, we extend an existing efficient greedy heuristic and applied it to determine concurrent conditional clusters on coexpression networks extracted from publically available time-resolved transcriptomics data of Escherichia coli under five stresses as well as on metabolite correlation networks from metabolomics data set from Arabidopsis thaliana exposed to eight environmental conditions. We demonstrate that the investigation of the differences between the clustering based on all networks with that obtained from a subset of networks can be used to quantify the specificity of biological responses. While a comparison of the Escherichia coli coexpression networks based on seminal properties does not pinpoint biologically relevant differences, the common network substructures extracted by COCONETS are supported by

  5. Wolbachia increases susceptibility to Plasmodium infection in a natural system.

    Science.gov (United States)

    Zélé, F; Nicot, A; Berthomieu, A; Weill, M; Duron, O; Rivero, A

    2014-03-22

    Current views about the impact of Wolbachia on Plasmodium infections are almost entirely based on data regarding artificially transfected mosquitoes. This work has shown that Wolbachia reduces the intensity of Plasmodium infections in mosquitoes, raising the exciting possibility of using Wolbachia to control or limit the spread of malaria. Whether natural Wolbachia infections have the same parasite-inhibiting properties is not yet clear. Wolbachia-mosquito combinations with a long evolutionary history are, however, key for understanding what may happen with Wolbachia-transfected mosquitoes after several generations of coevolution. We investigate this issue using an entirely natural mosquito-Wolbachia-Plasmodium combination. In contrast to most previous studies, which have been centred on the quantification of the midgut stages of Plasmodium, we obtain a measurement of parasitaemia that relates directly to transmission by following infections to the salivary gland stages. We show that Wolbachia increases the susceptibility of Culex pipiens mosquitoes to Plasmodium relictum, significantly increasing the prevalence of salivary gland stage infections. This effect is independent of the density of Wolbachia in the mosquito. These results suggest that naturally Wolbachia-infected mosquitoes may, in fact, be better vectors of malaria than Wolbachia-free ones.

  6. Chimpanzee malaria parasites related to Plasmodium ovale in Africa.

    Directory of Open Access Journals (Sweden)

    Linda Duval

    Full Text Available Since the 1970's, the diversity of Plasmodium parasites in African great apes has been neglected. Surprisingly, P. reichenowi, a chimpanzee parasite, is the only such parasite to have been molecularly characterized. This parasite is closely phylogenetically related to P. falciparum, the principal cause of the greatest malaria burden in humans. Studies of malaria parasites from anthropoid primates may provide relevant phylogenetic information, improving our understanding of the origin and evolutionary history of human malaria species. In this study, we screened 130 DNA samples from chimpanzees (Pan troglodytes and gorillas (Gorilla gorilla from Cameroon for Plasmodium infection, using cytochrome b molecular tools. Two chimpanzees from the subspecies Pan t. troglodytes presented single infections with Plasmodium strains molecularly related to the human malaria parasite P. ovale. These chimpanzee parasites and 13 human strains of P. ovale originated from a various sites in Africa and Asia were characterized using cytochrome b and cytochrome c oxidase 1 mitochondrial partial genes and nuclear ldh partial gene. Consistent with previous findings, two genetically distinct types of P. ovale, classical and variant, were observed in the human population from a variety of geographical locations. One chimpanzee Plasmodium strain was genetically identical, on all three markers tested, to variant P. ovale type. The other chimpanzee Plasmodium strain was different from P. ovale strains isolated from humans. This study provides the first evidence of possibility of natural cross-species exchange of P. ovale between humans and chimpanzees of the subspecies Pan t. troglodytes.

  7. Aortopulmonary ectopic parathyroid gland and concurrent thymolipoma.

    Science.gov (United States)

    Abu Abeeleh, Mahmoud; Bani Hani, Amjad; Ghaith, Ata; Alodwan, Tareq; Bani Ismail, Zuhair; Alshehabat, Musa

    2016-10-01

    Ectopic parathyroid adenomas are considered the main cause of primary hyperparathyroidism. However, concurrent parathyroid and thymic pathologies are rarely diagnosed in the same patient. A 47-year-old man with history of diabetes mellitus, hypertension, and myasthenia gravis presented with persistent hypercalcemia. Laboratory investigations, computed tomography, and technetium-99 m sestamibi scintigraphy revealed ectopic parathyroid glands, a mediastinal mass, and an enlarged thymus. The patient underwent thymectomy and mass excision via a median sternotomy. Histopathology was consistent with ectopic parathyroid adenoma and thymolipoma. The serum calcium and parathormone concentrations normalized within 48 hours after surgery. © The Author(s) 2016.

  8. Concurrent Kimura disease and lupus nephritis

    Science.gov (United States)

    Wang, Haitao; Fang, Fang; Sun, Ying; Wang, Songlan; Mao, Yonghui

    2016-01-01

    Abstract Background: Kimura disease is a rare chronic inflammatory disorder with peripheral eosinophilia and elevated serum IgE and is also frequently complicated by nephropathy. Methods: We report a rare case of Kimura disease concomitant with lupus nephritis in a 72-year old male patient with recurrent unexplained lymphadenopathy, renal lesions, and immunologic abnormalities. Results: The patient was successfully managed with gamma immunoglobulin, intravenous pulse methylprednisolone therapy, hydroxychloroquine, and prednisone. Conclusion: This is the first report of a case of Kimura disease concomitant with lupus nephritis and highlights the importance of considering lupus nephritis as a possible concurrent disease in patients with Kimura disease that have immunologic abnormalities. PMID:27741124

  9. Concurrency control in distributed database systems

    CERN Document Server

    Cellary, W; Gelenbe, E

    1989-01-01

    Distributed Database Systems (DDBS) may be defined as integrated database systems composed of autonomous local databases, geographically distributed and interconnected by a computer network.The purpose of this monograph is to present DDBS concurrency control algorithms and their related performance issues. The most recent results have been taken into consideration. A detailed analysis and selection of these results has been made so as to include those which will promote applications and progress in the field. The application of the methods and algorithms presented is not limited to DDBSs but a

  10. Proceedings 8th Interaction and Concurrency Experience

    DEFF Research Database (Denmark)

    2015-01-01

    This volume contains the proceedings of ICE 2015, the 8th Interaction and Concurrency Experience, which was held in Grenoble, France on the 4th and 5th of June 2015 as a satellite event of DisCoTec 2015. The ICE procedure for paper selection allows PC members to interact, anonymously, with authors......, and altogether 9 papers, including 1 short paper, were accepted for publication (the workshop also featured 4 brief announcements which are not part of this volume). We were proud to host three invited talks, by Leslie Lamport (shared with the FRIDA workshop), Joseph Sifakis and Steve Ross-Talbot. The abstracts...

  11. Reliability-based concurrent subspace optimization method

    Institute of Scientific and Technical Information of China (English)

    FAN Hui; LI Wei-ji

    2008-01-01

    To avoid the high computational cost and much modification in the process of applying traditional re-liability-based design optimization method, a new reliability-based concurrent subspace optimization approach is proposed based on the comparison and analysis of the existing muhidisciplinary optimization techniques and reli-ability assessment methods. It is shown through a canard configuration optimization for a three-surface transport that the proposed method is computationally efficient and practical with the least modification to the current de-terministic optimization process.

  12. Concurrency-based approaches to parallel programming

    Science.gov (United States)

    Kale, L.V.; Chrisochoides, N.; Kohl, J.; Yelick, K.

    1995-01-01

    The inevitable transition to parallel programming can be facilitated by appropriate tools, including languages and libraries. After describing the needs of applications developers, this paper presents three specific approaches aimed at development of efficient and reusable parallel software for irregular and dynamic-structured problems. A salient feature of all three approaches in their exploitation of concurrency within a processor. Benefits of individual approaches such as these can be leveraged by an interoperability environment which permits modules written using different approaches to co-exist in single applications.

  13. Relaxed Operational Semantics of Concurrent Programming Languages

    Directory of Open Access Journals (Sweden)

    Gustavo Petri

    2012-08-01

    Full Text Available We propose a novel, operational framework to formally describe the semantics of concurrent programs running within the context of a relaxed memory model. Our framework features a "temporary store" where the memory operations issued by the threads are recorded, in program order. A memory model then specifies the conditions under which a pending operation from this sequence is allowed to be globally performed, possibly out of order. The memory model also involves a "write grain," accounting for architectures where a thread may read a write that is not yet globally visible. Our formal model is supported by a software simulator, allowing us to run litmus tests in our semantics.

  14. The Family of Concurrent Logic Programming Languages

    Science.gov (United States)

    1989-05-01

    193]. - 85 - 19.3 Proces to proceso mapping The question of how to map processes to processors is not unique to concurrent logic programming, and any...procinors(N,ToQ) queue(ToQ), -8 7 - procemorie(N,ToQ)Qnext. processors’(0,_). procesos (N,ToQ) - N>O I N’:=N-1, procesior(ToQ), processor’(N’ ,ToQ)Onext...of Computing, Imperial College, London, 1988. [35] Davison, A., POOL: A PARLOG object oriented language, Department of Computing, Im- penal College

  15. Cellular effector mechanisms against Plasmodium liver stages.

    Science.gov (United States)

    Frevert, Ute; Nardin, Elizabeth

    2008-10-01

    Advances in our understanding of the molecular and cell biology of the malaria parasite have led to new vaccine development efforts resulting in a pipeline of over 40 candidates undergoing clinical phase I-III trials. Vaccine-induced CD4+ and CD8+ T cells specific for pre-erythrocytic stage antigens have been found to express cytolytic and multi-cytokine effector functions that support a key role for these T cells within the hepatic environment. However, little is known of the cellular interactions that occur during the effector phase in which the intracellular hepatic stage of the parasite is targeted and destroyed. This review focuses on cell biological aspects of the interaction between malaria-specific effector cells and the various antigen-presenting cells that are known to exist within the liver, including hepatocytes, dendritic cells, Kupffer cells, stellate cells and sinusoidal endothelia. Considering the unique immune properties of the liver, it is conceivable that these different hepatic antigen-presenting cells fulfil distinct but complementary roles during the effector phase against Plasmodium liver stages.

  16. Exploring the folate pathway in Plasmodium falciparum.

    Science.gov (United States)

    Hyde, John E

    2005-06-01

    As in centuries past, the main weapon against human malaria infections continues to be intervention with drugs, despite the widespread and increasing frequency of parasite populations that are resistant to one or more of the available compounds. This is a particular problem with the lethal species of parasite, Plasmodium falciparum, which claims some two million lives per year as well as causing enormous social and economic problems. Amongst the antimalarial drugs currently in clinical use, the antifolates have the best defined molecular targets, namely the enzymes dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS), which function in the folate metabolic pathway. The products of this pathway, reduced folate cofactors, are essential for DNA synthesis and the metabolism of certain amino acids. Moreover, their formation and interconversions involve a number of other enzymes that have not as yet been exploited as drug targets. Antifolates are of major importance as they currently represent the only inexpensive regime for combating chloroquine-resistant malaria, and are now first-line drugs in a number of African countries. Aspects of our understanding of this pathway and antifolate drug resistance are reviewed here, with a particular emphasis on approaches to analysing the details of, and balance between, folate biosynthesis by the parasite and salvage of pre-formed folate from exogenous sources.

  17. New synchronization method for Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Mwangi Jonathan M

    2010-06-01

    Full Text Available Abstract Background Plasmodium falciparum is usually asynchronous during in vitro culture. Although various synchronization methods are available, they are not able to narrow the range of ages of parasites. A newly developed method is described that allows synchronization of parasites to produce cultures with an age range as low as 30 minutes. Methods Trophozoites and schizonts are enriched using Plasmion. The enriched late stage parasites are immobilized as a monolayer onto plastic Petri dishes using concanavalin A. Uninfected erythrocytes are placed onto the monolayer for a limited time period, during which time schizonts on the monolayer rupture and the released merozoites invade the fresh erythrocytes. The overlay is then taken off into a culture flask, resulting in a highly synchronized population of parasites. Results Plasmion treatment results in a 10- to 13-fold enrichment of late stage parasites. The monolayer method results in highly synchronized cultures of parasites where invasion has occurred within a very limited time window, which can be as low as 30 minutes. The method is simple, requiring no specialized equipment and relatively cheap reagents. Conclusions The new method for parasite synchronization results in highly synchronized populations of parasites, which will be useful for studies of the parasite asexual cell cycle.

  18. Latent Infections with Plasmodium ovale Malaria

    Science.gov (United States)

    Miller, Max J.; Marcus, David M.; Cameron, Douglas G.

    1965-01-01

    Two cases of Plasmodium ovale malaria acquired in West Africa appeared as primary delayed attacks after one year's continuous residence in Canada. Both patients took full prophylactic doses of chloroquine before, during, and for several weeks after exposure. The inadequacy of the 4-aminoquinolines for protection against latent benign tertian malaria is noted, and the use of primaquine is recommended. Paroxysms occurred in the evening and were accompanied by severe muscle pain, features considered typical of ovale malaria. One patient showed electrocardiographic changes and clinical signs of cardiac malfunction; these disappeared following specific treatment for malaria. In this age of accelerated travel and international movements of people it is important that physicians in temperate regions be aware of the exotic infections of the tropics, as well as of the need for protective measures for travellers to areas where these diseases are endemic. ImagesFig. 1aFig. 1b,1cFig. 3 a-dFig. 3 e-h PMID:14296004

  19. Plasmodium falciparum secretome in erythrocyte and beyond

    Directory of Open Access Journals (Sweden)

    Rani eSoni

    2016-02-01

    Full Text Available Plasmodium falciparum is the causative agent of deadly malaria disease. It is an intracellular eukaryote and completes its multi-stage life cycle spanning the two hosts viz, mosquito and human. In order to habituate within host environment, parasite conform several strategies to evade host immune responses such as surface antigen polymorphism or modulation of host immune system and it is mediated by secretion of proteins from parasite to the host erythrocyte and beyond, collectively known as, malaria secretome. In this review, we will discuss about the deployment of parasitic secretory protein in mechanism implicated for immune evasion, protein trafficking, providing virulence, changing permeability and cyto-adherence of infected erythrocyte. We will be covering the possibilities of developing malaria secretome as a drug/vaccine target. This gathered information will be worthwhile in depicting a well-organized picture for host-pathogen interplay during the malaria infection and may also provide some clues for development of novel anti-malarial therapies.

  20. Artificial concurrent catalytic processes involving enzymes.

    Science.gov (United States)

    Köhler, Valentin; Turner, Nicholas J

    2015-01-11

    The concurrent operation of multiple catalysts can lead to enhanced reaction features including (i) simultaneous linear multi-step transformations in a single reaction flask (ii) the control of intermediate equilibria (iii) stereoconvergent transformations (iv) rapid processing of labile reaction products. Enzymes occupy a prominent position for the development of such processes, due to their high potential compatibility with other biocatalysts. Genes for different enzymes can be co-expressed to reconstruct natural or construct artificial pathways and applied in the form of engineered whole cell biocatalysts to carry out complex transformations or, alternatively, the enzymes can be combined in vitro after isolation. Moreover, enzyme variants provide a wider substrate scope for a given reaction and often display altered selectivities and specificities. Man-made transition metal catalysts and engineered or artificial metalloenzymes also widen the range of reactivities and catalysed reactions that are potentially employable. Cascades for simultaneous cofactor or co-substrate regeneration or co-product removal are now firmly established. Many applications of more ambitious concurrent cascade catalysis are only just beginning to appear in the literature. The current review presents some of the most recent examples, with an emphasis on the combination of transition metal with enzymatic catalysis and aims to encourage researchers to contribute to this emerging field.

  1. Concurrent Initialization for Bearing-Only SLAM

    Directory of Open Access Journals (Sweden)

    Antoni Grau

    2010-03-01

    Full Text Available Simultaneous Localization and Mapping (SLAM is perhaps the most fundamental problem to solve in robotics in order to build truly autonomous mobile robots. The sensors have a large impact on the algorithm used for SLAM. Early SLAM approaches focused on the use of range sensors as sonar rings or lasers. However, cameras have become more and more used, because they yield a lot of information and are well adapted for embedded systems: they are light, cheap and power saving. Unlike range sensors which provide range and angular information, a camera is a projective sensor which measures the bearing of images features. Therefore depth information (range cannot be obtained in a single step. This fact has propitiated the emergence of a new family of SLAM algorithms: the Bearing-Only SLAM methods, which mainly rely in especial techniques for features system-initialization in order to enable the use of bearing sensors (as cameras in SLAM systems. In this work a novel and robust method, called Concurrent Initialization, is presented which is inspired by having the complementary advantages of the Undelayed and Delayed methods that represent the most common approaches for addressing the problem. The key is to use concurrently two kinds of feature representations for both undelayed and delayed stages of the estimation. The simulations results show that the proposed method surpasses the performance of previous schemes.

  2. Concurrent initialization for Bearing-Only SLAM.

    Science.gov (United States)

    Munguía, Rodrigo; Grau, Antoni

    2010-01-01

    Simultaneous Localization and Mapping (SLAM) is perhaps the most fundamental problem to solve in robotics in order to build truly autonomous mobile robots. The sensors have a large impact on the algorithm used for SLAM. Early SLAM approaches focused on the use of range sensors as sonar rings or lasers. However, cameras have become more and more used, because they yield a lot of information and are well adapted for embedded systems: they are light, cheap and power saving. Unlike range sensors which provide range and angular information, a camera is a projective sensor which measures the bearing of images features. Therefore depth information (range) cannot be obtained in a single step. This fact has propitiated the emergence of a new family of SLAM algorithms: the Bearing-Only SLAM methods, which mainly rely in especial techniques for features system-initialization in order to enable the use of bearing sensors (as cameras) in SLAM systems. In this work a novel and robust method, called Concurrent Initialization, is presented which is inspired by having the complementary advantages of the Undelayed and Delayed methods that represent the most common approaches for addressing the problem. The key is to use concurrently two kinds of feature representations for both undelayed and delayed stages of the estimation. The simulations results show that the proposed method surpasses the performance of previous schemes.

  3. Concurrent work with parents of adolescent patients.

    Science.gov (United States)

    Novick, Kerry Kelly; Novick, Jack

    2013-01-01

    Over the last ten years we have seen an increasing acceptance of the general idea of working with parents of child patients. What remains, however, as an area of controversy, conflict, and resistance, is the question of whether and how much therapists should or can work with the parents of adolescent patients. Questions cluster around how to maintain confidentiality and lead to the even larger issue of conceptualizing the developmental goals of the phase of adolescence. We see the major developmental tasks for both parents and adolescents as involving transformation of the self and the relationship, in the context of separateness rather than separation. If adolescent therapists work from the assumption that the goal of adolescence is transformation, concurrent work with parents and adolescents will move them all into a new level of relationship. Without concomitant change in parents, it is doubly hard for adolescents to progress into adulthood. In this paper we offer clinical material from five older adolescents and their parents to illustrate the techniques that follow from our model of dynamic concurrent parent work throughout the phases of treatment. Using the tasks of the therapeutic alliance as a conceptual framework, we describe working toward the dual goals of restoration to the path of progressive development and restoration of the parent-child relationship. We pay particular attention to the unfolding of conflicts between closed-system omnipotent functioning and open-system reality mastery, and the role offathers in late-adolescent development.

  4. Concurrent bilateral ectopic pregnancy: a rarity

    Directory of Open Access Journals (Sweden)

    Prabhleen Kaur

    2015-08-01

    Full Text Available Bilateral ectopic pregnancy is a rare twin gestation with only a few cases reported in the literature. We report a 30 year old woman without any high risk factor for ectopic pregnancy, who had concurrent bilateral ectopic pregnancy. A 30 year old female presented to the Gynecology emergency department complaining of vaginal bleeding and abdominal pain. The presumptive diagnosis of ruptured left sided ectopic pregnancy was made on basis of clinical findings and ultrasound finings. An emergency laparotomy was done revealed a hemoperitoneum of 1.5 liters, a ruptured left tubal pregnancy with active bleeding and right tubal un-ruptured ectopic was found. A bilateral salpingectomy was performed. Histopathology confirmed presence of chorionic villi in both tubes. In theory, laparoscopic salpingostomy is the best surgical approach in bilateral tubal pregnancy. However, bilateral salpingectomy may be necessary when both tubes are extensively damaged or are actively bleeding. Successful pregnancies have been reported after conservative surgical treatment of bilateral ectopic, but the risk of recurrence is high. Our decision for an emergency laparotomy followed by bilateral salpingectomy was based on the fact that the patient presented with acute abdomen and was haemodynamically unstable and there was extensive bilateral tubal damage. As the incidence of ectopic pregnancies is increasing concurrently with the incidences of pelvic inflammatory disease and use of assisted fertility techniques; it may be that these and ldquo;rare ectopics and rdquo; will become less uncommon. [Int J Reprod Contracept Obstet Gynecol 2015; 4(4.000: 1197-1199

  5. Malaria-like symptoms associated with a natural Plasmodium reichenowi infection in a chimpanzee.

    Science.gov (United States)

    Herbert, Anaïs; Boundenga, Larson; Meyer, Anne; Moukodoum, Diamella Nancy; Okouga, Alain Prince; Arnathau, Céline; Durand, Patrick; Magnus, Julie; Ngoubangoye, Barthélémy; Willaume, Eric; Ba, Cheikh Tidiane; Rougeron, Virginie; Renaud, François; Ollomo, Benjamin; Prugnolle, Franck

    2015-05-28

    Although Plasmodium infections have never been clearly associated with symptoms in non-human primates, the question of the pathogenicity of Plasmodium parasites in non-human primates still remains unanswered. A young chimpanzee, followed before and after release to a sanctuary, in a semi-free ranging enclosure located in an equatorial forest, showed fever and strong anaemia associated with a high Plasmodium reichenowi infection, shortly after release. The animal recovered from anaemia after several months despite recurrent infection with other Plasmodium species. This may be the first description of malaria-like symptoms in a chimpanzee infected with Plasmodium.

  6. Optimal strategy for controlling the spread of Plasmodium Knowlesi malaria: Treatment and culling

    Science.gov (United States)

    Abdullahi, Mohammed Baba; Hasan, Yahya Abu; Abdullah, Farah Aini

    2015-05-01

    Plasmodium Knowlesi malaria is a parasitic mosquito-borne disease caused by a eukaryotic protist of genus Plasmodium Knowlesi transmitted by mosquito, Anopheles leucosphyrus to human and macaques. We developed and analyzed a deterministic Mathematical model for the transmission of Plasmodium Knowlesi malaria in human and macaques. The optimal control theory is applied to investigate optimal strategies for controlling the spread of Plasmodium Knowlesi malaria using treatment and culling as control strategies. The conditions for optimal control of the Plasmodium Knowlesi malaria are derived using Pontryagin's Maximum Principle. Finally, numerical simulations suggested that the combination of the control strategies is the best way to control the disease in any community.

  7. Diagnosis of an imported Plasmodium ovale wallikeri infection in Malaysia.

    Science.gov (United States)

    Liew, Jonathan Wee Kent; Mahmud, Rohela; Tan, Lian Huat; Lau, Yee Ling

    2016-01-06

    Plasmodium ovale is rare and not exactly known to be autochthonous in Malaysia. There are two distinct forms of the parasite, namely P. ovale curtisi (classic form) and P. ovale wallikeri (variant form). Here, the first sequence confirmed case of an imported P. ovale wallikeri infection in Malaysia is presented. Microscopy found Plasmodium parasites with morphology similar to P. ovale or Plasmodium vivax in the blood films. Further confirmation using polymerase chain reaction (PCR) targeting the small-subunit rRNA gene of the parasite was unsuccessful. Genus-specific PCR was then performed and the product was sequenced and analysed. Sequence analyses confirmed the aetiological agent as P. ovale wallikeri. New species-specific primers (rOVA1v and rOVA2v) were employed and P. ovale wallikeri was finally confirmed. The findings highlight the need to look out for imported malaria infections in Malaysia and the importance of a constantly updated and validated diagnostic technique.

  8. Plasmodium knowlesi: from severe zoonosis to animal model.

    Science.gov (United States)

    Cox-Singh, Janet; Culleton, Richard

    2015-06-01

    Plasmodium knowlesi malaria is a newly described zoonosis in Southeast Asia. Similarly to Plasmodium falciparum, P. knowlesi can reach high parasitaemia in the human host and both species cause severe and fatal illness. Interpretation of host-parasite interactions in studies of P. knowlesi malaria adds a counterpoint to studies on P. falciparum. However, there is no model system for testing the resulting hypotheses on malaria pathophysiology or for developing new interventions. Plasmodium knowlesi is amenable to genetic manipulation in vitro and several nonhuman primate species are susceptible to experimental infection. Here, we make a case for drawing on P. knowlesi as both a human pathogen and an experimental model to lift the roadblock between malaria research and its translation into human health benefits.

  9. Concurrent Engineering Working Group White Paper Distributed Collaborative Design: The Next Step in Aerospace Concurrent Engineering

    Science.gov (United States)

    Hihn, Jairus; Chattopadhyay, Debarati; Karpati, Gabriel; McGuire, Melissa; Panek, John; Warfield, Keith; Borden, Chester

    2011-01-01

    As aerospace missions grow larger and more technically complex in the face of ever tighter budgets, it will become increasingly important to use concurrent engineering methods in the development of early conceptual designs because of their ability to facilitate rapid assessments and trades of performance, cost and schedule. To successfully accomplish these complex missions with limited funding, it is essential to effectively leverage the strengths of individuals and teams across government, industry, academia, and international agencies by increased cooperation between organizations. As a result, the existing concurrent engineering teams will need to increasingly engage in distributed collaborative concurrent design. The purpose of this white paper is to identify a near-term vision for the future of distributed collaborative concurrent engineering design for aerospace missions as well as discuss the challenges to achieving that vision. The white paper also documents the advantages of creating a working group to investigate how to engage the expertise of different teams in joint design sessions while enabling organizations to maintain their organizations competitive advantage.

  10. Molecular identification of the chitinase genes in Plasmodium relictum.

    Science.gov (United States)

    Garcia-Longoria, Luz; Hellgren, Olof; Bensch, Staffan

    2014-06-18

    Malaria parasites need to synthesize chitinase in order to go through the peritrophic membrane, which is created around the mosquito midgut, to complete its life cycle. In mammalian malaria species, the chitinase gene comprises either a large or a short copy. In the avian malaria parasites Plasmodium gallinaceum both copies are present, suggesting that a gene duplication in the ancestor to these extant species preceded the loss of either the long or the short copy in Plasmodium parasites of mammals. Plasmodium gallinaceum is not the most widespread and harmful parasite of birds. This study is the first to search for and identify the chitinase gene in one of the most prevalent avian malaria parasites, Plasmodium relictum. Both copies of P. gallinaceum chitinase were used as reference sequences for primer design. Different sequences of Plasmodium spp. were used to build the phylogenetic tree of chitinase gene. The gene encoding for chitinase was identified in isolates of two mitochondrial lineages of P. relictum (SGS1 and GRW4). The chitinase found in these two lineages consists both of the long (PrCHT1) and the short (PrCHT2) copy. The genetic differences found in the long copy of the chitinase gene between SGS1 and GRW4 were higher than the difference observed for the cytochrome b gene. The identification of both copies in P. relictum sheds light on the phylogenetic relationship of the chitinase gene in the genus Plasmodium. Due to its high variability, the chitinase gene could be used to study the genetic population structure in isolates from different host species and geographic regions.

  11. [From malaria parasite point of view--Plasmodium falciparum evolution].

    Science.gov (United States)

    Zerka, Agata; Kaczmarek, Radosław; Jaśkiewicz, Ewa

    2015-12-31

    Malaria is caused by infection with protozoan parasites belonging to the genus Plasmodium, which have arguably exerted the greatest selection pressure on humans in the history of our species. Besides humans, different Plasmodium parasites infect a wide range of animal hosts, from marine invertebrates to primates. On the other hand, individual Plasmodium species show high host specificity. The extraordinary evolution of Plasmodium probably began when a free-living red algae turned parasitic, and culminated with its ability to thrive inside a human red blood cell. Studies on the African apes generated new data on the evolution of malaria parasites in general and the deadliest human-specific species, Plasmodium falciparum, in particular. Initially, it was hypothesized that P. falciparum descended from the chimpanzee malaria parasite P. reichenowi, after the human and the chimp lineage diverged about 6 million years ago. However, a recently identified new species infecting gorillas, unexpectedly showed similarity to P. falciparum and was therefore named P. praefalciparum. That finding spurred an alternative hypothesis, which proposes that P. falciparum descended from its gorilla rather than chimp counterpart. In addition, the gorilla-to-human host shift may have occurred more recently (about 10 thousand years ago) than the theoretical P. falciparum-P. reichenowi split. One of the key aims of the studies on Plasmodium evolution is to elucidate the mechanisms that allow the incessant host shifting and retaining the host specificity, especially in the case of human-specific species. Thorough understanding of these phenomena will be necessary to design effective malaria treatment and prevention strategies.

  12. The SLC4A1 gene is under differential selective pressure in primates infected by Plasmodium falciparum and related parasites

    OpenAIRE

    Steiper, Michael E.; Walsh, Fiona; Zichello, Julia M.

    2012-01-01

    Malaria is a disease caused by Plasmodium parasites and is responsible for high mortality in humans. This disease is caused by four different species of Plasmodium though the main source of mortality is Plasmodium falciparum. Humans have a number of genetic adaptations that act to combat Plasmodium. One adaptation is a deletion in the SLC4A1 gene that leads to Southeast Asian ovalocytosis (SAO). There is evidence that SAO erythrocytes are resistant to multiple Plasmodium species. Here we anal...

  13. [Erythrocytes infected by Plasmodium falciparum activate human platelets].

    Science.gov (United States)

    Polack, B; Peyron, F; Sheick Zadiuddin, I; Kolodié, L; Ambroise-Thomas, P

    1990-01-01

    Blood platelets are involved in Plasmodium falciparum malaria pathology as shown by thrombocytopenia and increased plasma level of two alpha granule proteins: beta thromboglobulin (beta TG) and platelet factor 4 (PF4). In this study we demonstrate that Plasmodium falciparum parasitized erythrocytes activate directly the secretion of beta TG and PF4 by human platelets. This secretion is related to parasitemia and occurs immediately after contact. Treatment of parasited erythrocytes by trypsin and diffusion chamber experiments suggest that platelet activation is triggered by parasitic substances shed on erythrocyte membrane and released in the culture medium.

  14. Analysis of expressed sequence tags from Plasmodium falciparum.

    Science.gov (United States)

    Chakrabarti, D; Reddy, G R; Dame, J B; Almira, E C; Laipis, P J; Ferl, R J; Yang, T P; Rowe, T C; Schuster, S M

    1994-07-01

    An initiative was undertaken to sequence all genes of the human malaria parasite Plasmodium falciparum in an effort to gain a better understanding at the molecular level of the parasite that inflicts much suffering in the developing world. 550 random complimentary DNA clones were partially sequenced from the intraerythrocytic form of the parasite as one of the approaches to analyze the transcribed sequences of its genome. The sequences, after editing, generated 389 expressed sequence tag sites and over 105 kb of DNA sequences. About 32% of these clones showed significant homology with other genes in the database. These clones represent 340 new Plasmodium falciparum expressed sequence tags.

  15. Backward bifurcation and optimal control of Plasmodium Knowlesi malaria

    Science.gov (United States)

    Abdullahi, Mohammed Baba; Hasan, Yahya Abu; Abdullah, Farah Aini

    2014-07-01

    A deterministic model for the transmission dynamics of Plasmodium Knowlesi malaria with direct transmission is developed. The model is analyzed using dynamical system techniques and it shows that the backward bifurcation occurs for some range of parameters. The model is extended to assess the impact of time dependent preventive (biological and chemical control) against the mosquitoes and vaccination for susceptible humans, while treatment for infected humans. The existence of optimal control is established analytically by the use of optimal control theory. Numerical simulations of the problem, suggest that applying the four control measure can effectively reduce if not eliminate the spread of Plasmodium Knowlesi in a community.

  16. Concurrent radiochemotherapy in advanced hypopharyngeal cancer

    Directory of Open Access Journals (Sweden)

    Lukarski Dusko

    2010-05-01

    Full Text Available Abstract Background Concurrent platinum-based radiochemotherapy has been recommended as a standard of care in patients with locally advanced squamous cell head and neck carcinomas. Unfortunately, there is a lack of level one evidence on best treatment approach for advanced hypopharyngeal cancer. This report aims to summarize the results of our study on concurrent radiochemotherapy in patients with advanced hypopharyngeal cancer. Methods A retrospective analysis of 41 patients with stage III-IV hypopharyngeal cancer was performed. All patients were treated with three dimensional conformal radiotherapy and received 70 Gy in 35 fractions (2 Gy per fraction, 5 fractions per week. In dependence of the period when radiotherapy was realized, two different treatment techniques were used. Concurrent chemotherapy consisted of cisplatin 30 mg/m2 given on a weekly basis. Results The median age was 52 years (range 29-70. Stage IV disease was recognized in 73.2% of the patients. Complete response rates at the primary site and at the metastatic neck lymph nodes were 68.3% and 36.6%, respectively. A complete composite response was present in 27 patients (65.9%. Median follow-up was 13 months (range 7-36. Distant metastases as initial failure occurred in 7 patients (46.7%. The 2-year local relapse-free survival and regional relapse-free survival rates were 55.2% and 75.8%, respectively. The 2-year locoregional relapse-free survival rate was 51.3%. The 2-year disease-free survival and overall survival rates were 29.3% and 32.8%, respectively. Confluent mucositis was developed in 46.3% of patients. Leucopenia grade 1 was the most frequent hematological toxicity. The median weight loss at the end of treatment was 12% (range 5-21. The worst grade of late toxicity was most commonly pronounced in the skin and in the subcutaneous tissue. Conclusions Based on unsatisfactory results in our study we suggest that the use of sequential radiochemotherapy or chemotherapy

  17. Modeling disease spread in populations with birth, death, and concurrency

    CERN Document Server

    Millera, Joel C

    2016-01-01

    The existence of sexual partnerships that overlap in time (concurrent relationships) is believed by some to be a significant contributing factor to the spread of HIV, although this is controversial. We derive an analytic model which allows us to investigate and compare disease spread in populations with and without concurrency. We can identify regions of parameter space in which its impact is negligible, and other regions in which it plays a major role. We also see that the impact of concurrency on the initial growth phase can be much larger than its impact on the equilibrium size. We see that the effect of concurrency saturates, which leads to the perhaps surprising conclusion that interventions targeting concurrency may be most effective in populations with low to moderate levels of concurrency.

  18. Correlation between Trichomonas vaginalis and Concurrency: An Ecological Study.

    Science.gov (United States)

    Kenyon, Chris R; Hamilton, Deven T

    2016-01-01

    Objective. There is a large variation in the prevalence of Trichomonas vaginalis (TV) between different countries and between racial groups within countries. Sexual partner concurrency may play a role. We investigate the correlation between the prevalence of sexual partner concurrency and TV prevalence. Methods. Spearman's correlation to assess relationship between TV prevalence in women and point prevalence of concurrency in men in (1) 11 countries with comparable data (concurrency data from WHO Survey and TV prevalence data from Global Burden of Disease estimates) and (2) three racial groups in the United States (Add Health Study). Results. The prevalence of TV and concurrency was positively correlated in the international (rho = 0.84, P = 0.001) and USA study (rho = 1.0, P < 0.001). Conclusion. Prospective longitudinal studies that include measures of partner behavior are required to definitively establish the role of concurrency in the spread of TV.

  19. Artemisinin-Resistant Plasmodium falciparum Malaria.

    Science.gov (United States)

    Fairhurst, Rick M; Dondorp, Arjen M

    2016-06-01

    For more than five decades, Southeast Asia (SEA) has been fertile ground for the emergence of drug-resistant Plasmodium falciparum malaria. After generating parasites resistant to chloroquine, sulfadoxine, pyrimethamine, quinine, and mefloquine, this region has now spawned parasites resistant to artemisinins, the world's most potent antimalarial drugs. In areas where artemisinin resistance is prevalent, artemisinin combination therapies (ACTs)-the first-line treatments for malaria-are failing fast. This worrisome development threatens to make malaria practically untreatable in SEA, and threatens to compromise global endeavors to eliminate this disease. A recent series of clinical, in vitro, genomics, and transcriptomics studies in SEA have defined in vivo and in vitro phenotypes of artemisinin resistance, identified its causal genetic determinant, explored its molecular mechanism, and assessed its clinical impact. Specifically, these studies have established that artemisinin resistance manifests as slow parasite clearance in patients and increased survival of early-ring-stage parasites in vitro; is caused by single nucleotide polymorphisms in the parasite's K13 gene, is associated with an upregulated "unfolded protein response" pathway that may antagonize the pro-oxidant activity of artemisinins, and selects for partner drug resistance that rapidly leads to ACT failures. In SEA, clinical studies are urgently needed to monitor ACT efficacy where K13 mutations are prevalent, test whether new combinations of currently available drugs cure ACT failures, and advance new antimalarial compounds through preclinical pipelines and into clinical trials. Intensifying these efforts should help to forestall the spread of artemisinin and partner drug resistance from SEA to sub-Saharan Africa, where the world's malaria transmission, morbidity, and mortality rates are highest.

  20. Combating multidrug-resistant Plasmodium falciparum malaria.

    Science.gov (United States)

    Thu, Aung Myint; Phyo, Aung Pyae; Landier, Jordi; Parker, Daniel M; Nosten, François H

    2017-08-01

    Over the past 50 years, Plasmodium falciparum has developed resistance against all antimalarial drugs used against it: chloroquine, sulphadoxine-pyrimethamine, quinine, piperaquine and mefloquine. More recently, resistance to the artemisinin derivatives and the resulting failure of artemisinin-based combination therapy (ACT) are threatening all major gains made in malaria control. Each time resistance has developed progressively, with delayed clearance of parasites first emerging only in a few regions, increasing in prevalence and geographic range, and then ultimately resulting in the complete failure of that antimalarial. Drawing from this repeated historical chain of events, this article presents context-specific approaches for combating drug-resistant P. falciparum malaria. The approaches begin with a context of drug-sensitive parasites and focus on the prevention of the emergence of drug resistance. Next, the approaches address a scenario in which resistance has emerged and is increasing in prevalence and geographic extent, with interventions focused on disrupting transmission through vector control, early diagnosis and treatment, and the use of new combination therapies. Elimination is also presented as an approach for addressing the imminent failure of all available antimalarials. The final drug resistance context presented is one in which all available antimalarials have failed; leaving only personal protection and the use of new antimalarials (or new combinations of antimalarials) as a viable strategy for dealing with complete resistance. All effective strategies and contexts require a multipronged, holistic approach. © 2017 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  1. The dynamics of natural Plasmodium falciparum infections.

    Directory of Open Access Journals (Sweden)

    Ingrid Felger

    Full Text Available BACKGROUND: Natural immunity to Plasmodium falciparum has been widely studied, but its effects on parasite dynamics are poorly understood. Acquisition and clearance rates of untreated infections are key elements of the dynamics of malaria, but estimating these parameters is challenging because of frequent super-infection and imperfect detectability of parasites. Consequently, information on effects of host immune status or age on infection dynamics is fragmentary. METHODS: An age-stratified cohort of 347 individuals from Northern Ghana was sampled six times at 2 month intervals. High-throughput capillary electrophoresis was used to genotype the msp-2 locus of all P. falciparum infections detected by PCR. Force of infection (FOI and duration were estimated for each age group using an immigration-death model that allows for imperfect detection of circulating parasites. RESULTS: Allowing for imperfect detection substantially increased estimates of FOI and duration. Effects of naturally acquired immunity on the FOI and duration would be reflected in age dependence in these indices, but in our cohort data FOI tended to increase with age in children. Persistence of individual parasite clones was characteristic of all age-groups. Duration peaked in 5-9 year old children (average duration 319 days, 95% confidence interval 318;320. CONCLUSIONS: The main age-dependence is on parasite densities, with only small age-variations in the FOI and persistence of infections. This supports the hypothesis that acquired immunity controls transmission mainly by limiting blood-stage parasite densities rather than changing rates of acquisition or clearance of infections.

  2. Unique properties of Plasmodium falciparum porphobilinogen deaminase.

    Science.gov (United States)

    Nagaraj, Viswanathan Arun; Arumugam, Rajavel; Gopalakrishnan, Bulusu; Jyothsna, Yeleswarapu Sri; Rangarajan, Pundi N; Padmanaban, Govindarajan

    2008-01-04

    The hybrid pathway for heme biosynthesis in the malarial parasite proposes the involvement of parasite genome-coded enzymes of the pathway localized in different compartments such as apicoplast, mitochondria, and cytosol. However, knowledge on the functionality and localization of many of these enzymes is not available. In this study, we demonstrate that porphobilinogen deaminase encoded by the Plasmodium falciparum genome (PfPBGD) has several unique biochemical properties. Studies carried out with PfPBGD partially purified from parasite membrane fraction, as well as recombinant PfPBGD lacking N-terminal 64 amino acids expressed and purified from Escherichia coli cells (DeltaPfPBGD), indicate that both the proteins are catalytically active. Surprisingly, PfPBGD catalyzes the conversion of porphobilinogen to uroporphyrinogen III (UROGEN III), indicating that it also possesses uroporphyrinogen III synthase (UROS) activity, catalyzing the next step. This obviates the necessity to have a separate gene for UROS that has not been so far annotated in the parasite genome. Interestingly, DeltaPfP-BGD gives rise to UROGEN III even after heat treatment, although UROS from other sources is known to be heat-sensitive. Based on the analysis of active site residues, a DeltaPfPBGDL116K mutant enzyme was created and the specific activity of this recombinant mutant enzyme is 5-fold higher than DeltaPfPBGD. More interestingly, DeltaPfPBGDL116K catalyzes the formation of uroporphyrinogen I (UROGEN I) in addition to UROGEN III, indicating that with increased PBGD activity the UROS activity of PBGD may perhaps become rate-limiting, thus leading to non-enzymatic cyclization of preuroporphyrinogen to UROGEN I. PfPBGD is localized to the apicoplast and is catalytically very inefficient compared with the host red cell enzyme.

  3. A nuclear targeting system in Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Kochakarn Theerarat

    2010-05-01

    Full Text Available Abstract Background The distinct differences in gene control mechanisms acting in the nucleus between Plasmodium falciparum and the human host could lead to new potential drug targets for anti-malarial development. New molecular toolkits are required for dissecting molecular machineries in the P. falciparum nucleus. One valuable tool commonly used in model organisms is protein targeting to specific sub-cellular locations. Targeting proteins to specified locations allows labeling of organelles for microscopy, or testing of how the protein of interest modulates organelle function. In recent years, this approach has been developed for various malaria organelles, such as the mitochondrion and the apicoplast. A tool for targeting a protein of choice to the P. falciparum nucleus using an exogenous nuclear localization sequence is reported here. Methods To develop a nuclear targeting system, a putative nuclear localization sequence was fused with green fluorescent protein (GFP. The nuclear localization sequence from the yeast transcription factor Gal4 was chosen because of its well-defined nuclear localization signal. A series of truncated Gal4 constructs was also created to narrow down the nuclear localization sequence necessary for P. falciparum nuclear import. Transfected parasites were analysed by fluorescent and laser-scanning confocal microscopy. Results The nuclear localization sequence of Gal4 is functional in P. falciparum. It effectively transported GFP into the nucleus, and the first 74 amino acid residues were sufficient for nuclear localization. Conclusions The Gal4 fusion technique enables specific transport of a protein of choice into the P. falciparum nucleus, and thus provides a tool for labeling nuclei without using DNA-staining dyes. The finding also indicates similarities between the nuclear transport mechanisms of yeast and P. falciparum. Since the nuclear transport system has been thoroughly studied in yeast, this could give clues

  4. Concurrent Imitation Dynamics in Congestion Games

    CERN Document Server

    Ackermann, Heiner; Fischer, Simon; Hoefer, Martin

    2008-01-01

    Imitating successful behavior is a natural and frequently applied approach to trust in when facing scenarios for which we have little or no experience upon which we can base our decision. In this paper, we consider such behavior in atomic congestion games. We propose to study concurrent imitation dynamics that emerge when each player samples another player and possibly imitates this agents' strategy if the anticipated latency gain is sufficiently large. Our main focus is on convergence properties. Using a potential function argument, we how that our dynamics converge in a monotonic fashion to stable states. In such a state none of the players can improve its latency by imitating somebody else. As our main result, we show rapid convergence to approximate equilibria. At an approximate equilibrium only a small fraction of agents sustains a latency significantly above or below average. In particular, imitation dynamics behave like fully polynomial time approximation schemes (FPTAS). Fixing all other parameters, t...

  5. The fallacies of concurrent climate policy efforts.

    Science.gov (United States)

    Radetzki, Marian

    2010-05-01

    Climate policy has assumed an extreme degree of urgency in the international debate in recent years. This article begins by taking a critical look at the scientific underpinnings of the efforts to stabilize the climate. It points to several serious question marks on the purported relationship between greenhouse gas emissions and global warming, and expresses distrust about claims of impending catastrophes related to rising sea levels, hurricanes, and spread of infectious disease. It then reviews the concurrent climate policy efforts and concludes that they are incoherent, misguided and unduly costly, and that they have so far had no perceptible impact on anthropogenic greenhouse gas emissions. The exceedingly ambitious policy plans currently under preparation suffer from similar fallacies. For these reasons, but also because of the remaining scientific doubts and the exorbitant costs that have to be incurred, skepticism is expressed about the preparedness to implement the climate policy plans currently on the table.

  6. Distributed Management of Concurrent Web Service Transactions

    DEFF Research Database (Denmark)

    Alrifai, Mohammad; Dolog, Peter; Balke, Wolf-Tilo

    2009-01-01

    Business processes involve dynamic compositions of interleaved tasks. Therefore, ensuring reliable transactional processing of Web services is crucial for the success of Web service-based B2B and B2C applications. But the inherent autonomy and heterogeneity of Web services render the applicability...... of conventional ACID transaction models for Web services far from being straightforward. Current Web service transaction models relax the isolation property and rely on compensation mechanisms to ensure atomicity of business transactions in the presence of service failures. However, ensuring consistency...... in the open and dynamic environment of Web services, where interleaving business transactions enter and exit the system independently, remains an open issue. In this paper, we address this problem and propose an architecture that supports concurrency control on the Web services level. An extension...

  7. Certifying Concurrent Programs Using Transactional Memory

    Institute of Scientific and Technical Information of China (English)

    Long Li; Yu Zhang; Yi-Yun Chen; Yong Li

    2009-01-01

    Transactional memory (TM) is a new promising concurrency-control mechanism that can avoid many of the pitfalls of the traditional lock-based techniques. TM systems handle data races between threads automatically so that programmers do not have to reason about the interaction of threads manually. TM provides a programming model that may make the development of multi-threaded programs easier. Much work has been done to explore the various implementation strategies of TM systems and to achieve better performance, but little has been done on how to formally reason about programs using TM and how to make sure that such reasoning is sound. In this paper, we focus on the semantics of transactional memory and present a proof-carrying code (PCC) system for reasoning about programs using TM . We formalize our reasoning with respect to the TM semantics, prove its soundness, and use examples to demonstrate its effectiveness.

  8. Concurrent remote entanglement with continuous variables

    Science.gov (United States)

    Zalys-Geller, E.; Narla, A.; Shankar, S.; Hatridge, M.; Silveri, M.; Sliwa, K. M.; Mundhada, S. O.; Girvin, S. M.; Devoret, M. H.

    A necessary ingredient for large scale quantum information processing is the ability to entangle distant qubits on demand. In the field of superconducting quantum information, this process can be achieved by entangling stationary superconducting qubits with flying coherent states of microwave light, which are then co-amplified by a Josephson Parametric Converter (JPC). The JPC also serves as a which-path information eraser, causing the probabilistic continuous measurement process to concurrently entangle the qubits. We discuss the sensitivity of the experiment to the loss of quantum information during the flight of the coherent states, as well as strategies to improve which-path information erasure and reduce information loss to the degree required for entanglement generation. Work supported by ARO, AFOSR, NSF, and YINQE.

  9. Concurrent hypokalemic periodic paralysis and bipolar disorder

    Directory of Open Access Journals (Sweden)

    Chia-Lin Lin

    2015-01-01

    Full Text Available Primary periodic paralysis is a rare autosomal dominant disorder of ion-channel dysfunction, manifested by episodic flaccid paresis secondary to abnormal sarcolemma excitability. Membrane destabilization involving Na, K-ATPase has been hypothesized to be a biological etiology of the bipolar disorder (BD and the mechanisms underlying lithium therapy have been linked to it. To date, there has been only one reported case of BD comorbid with periodic paralysis. Herein, we reported another case of concurrent bipolar mania and hypokalemic periodic paralysis (HPP, one special form of periodic paralysis. Consistent with the previous case, our patient responded well to lithium treatment for both bipolar mania and HPP. This might provide some support to the hypothesis that the therapeutic effects of lithium in both BD and HPP could be due to the correction of the underlying common pathophysiology.

  10. Mining Concurrent Topical Activity in Microblog Streams

    CERN Document Server

    Panisson, A; Quaggiotto, M; Cattuto, C

    2014-01-01

    Streams of user-generated content in social media exhibit patterns of collective attention across diverse topics, with temporal structures determined both by exogenous factors and endogenous factors. Teasing apart different topics and resolving their individual, concurrent, activity timelines is a key challenge in extracting knowledge from microblog streams. Facing this challenge requires the use of methods that expose latent signals by using term correlations across posts and over time. Here we focus on content posted to Twitter during the London 2012 Olympics, for which a detailed schedule of events is independently available and can be used for reference. We mine the temporal structure of topical activity by using two methods based on non-negative matrix factorization. We show that for events in the Olympics schedule that can be semantically matched to Twitter topics, the extracted Twitter activity timeline closely matches the known timeline from the schedule. Our results show that, given appropriate techn...

  11. Concurrent programming notations in the object-oriented language Arche

    OpenAIRE

    Benveniste, Marc; Issarny, Valérie

    1992-01-01

    Paradigms of object-oriented programming are attractive for the design of large distributed software. They notably provide a sound basis to develop applications that are easy to maintain and reuse. However, expressing concurrency in object-oriented languages raises some difficulties. For instance, integrating concurrency together with inheritance may lead to violate the encapsulation property of object-oriented programming. In this paper we present a new strongly-typed, concurrent object-orie...

  12. An Efficient Secure Real-Time Concurrency Control Protocol

    Institute of Scientific and Technical Information of China (English)

    XIAO Yingyuan; LIU Yunsheng; CHEN Xiangyang

    2006-01-01

    Secure real-time databases must simultaneously satisfy two requirements in guaranteeing data security and minimizing the missing deadlines ratio of transactions. However, these two requirements can conflict with each other and achieve one requirement is to sacrifice the other. This paper presents a secure real-time concurrency control protocol based on optimistic method. The concurrency control protocol incorporates security constraints in a real-time optimistic concurrency control protocol and makes a suitable tradeoff between security and real-time requirements by introducing secure influence factor and real-time influence factor. The experimental results show the concurrency control protocol achieves data security without degrading real-time performance significantly.

  13. Concurrence vectors for entanglement of high dimensional systems

    Institute of Scientific and Technical Information of China (English)

    You-quan LI; Guo-qiang ZHU

    2008-01-01

    The concurrence vectors are proposed by employing the fundamental representation of An Lie algebra,which provides a clear criterion to evaluate the entanglement of bipartite systems of arbitrary dimension.Accordingly,a state is separable if the norm of its concurrence vector vanishes.The state vectors related to SU(3)states and SO(3) states are discussed in detail.The sign situation of nonzero components of concurrence vectors of entangled bases presents a simple criterion to judge whether the whole Hilbert subspace spanned by those bases is entangled,or there exists an entanglement edge.This is illustrated in terms of the concurrence surfaces of several concrete examples.

  14. Distribution of two species of malaria, Plasmodium falciparum and Plasmodium vivax, on Lombok Island, Indonesia.

    Science.gov (United States)

    Nagao, Yoshiro; Dachlan, Yoes Prijatna; Soedarto; Hidajati, Sri; Yotopranoto, Subagyo; Kusmartisnawati; Subekti, Sri; Ideham, Bariah; Tsuda, Yoshio; Kawabata, Masato; Takagi, Masahiro; Looareesuwan, Somchai

    2003-09-01

    Medical and entomological surveys were conducted to determine the risk factors of Plasmodium falciparum and P. vivax infections on Lombok Island, Indonesia, to find the risk factors and the main mosquito vectors for each malaria. Multivariate longitudinal analysis demonstrated two significant risk factors for infection with P. falciparum: disappearance of P. vivax parasitemia (p<0.001) and a specific study site (p<0.001). In contrast, younger age (p=0.024) and the interpolated virtual density of An. subpictus (p=0.041) were significantly associated with increased risk of infection with P. vivax. Thus, it seems that the distribution of P. vivax was determined largely by the presence of An. subpictus, whilst that of P. falciparum was influenced by antagonism with P. vivax. This result shows the importance of following-up treated P. vivax patients to identify recrudescence of P. falciparum in this area.

  15. Dicty_cDB: SFJ805 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available cDNA #17, Tommaso Pace, Marta Ponzi, and Clara Frontali Plasmodium berghei cDNA 5...asmodium yoelii yoelii cDNA clone PYCNC01 5' end, mRNA sequence. 48 0.19 1 BF296929 |BF296929.1 044PbF11 Pb

  16. Modelling the incidence of Plasmodium vivax and Plasmodium falciparum malaria in Afghanistan 2006-2009.

    Science.gov (United States)

    Alegana, Victor A; Wright, Jim A; Nahzat, Sami M; Butt, Waqar; Sediqi, Amad W; Habib, Naeem; Snow, Robert W; Atkinson, Peter M; Noor, Abdisalan M

    2014-01-01

    Identifying areas that support high malaria risks and where populations lack access to health care is central to reducing the burden in Afghanistan. This study investigated the incidence of Plasmodium vivax and Plasmodium falciparum using routine data to help focus malaria interventions. To estimate incidence, the study modelled utilisation of the public health sector using fever treatment data from the 2012 national Malaria Indicator Survey. A probabilistic measure of attendance was applied to population density metrics to define the proportion of the population within catchment of a public health facility. Malaria data were used in a Bayesian spatio-temporal conditional-autoregressive model with ecological or environmental covariates, to examine the spatial and temporal variation of incidence. From the analysis of healthcare utilisation, over 80% of the population was within 2 hours' travel of the nearest public health facility, while 64.4% were within 30 minutes' travel. The mean incidence of P. vivax in 2009 was 5.4 (95% Crl 3.2-9.2) cases per 1000 population compared to 1.2 (95% Crl 0.4-2.9) cases per 1000 population for P. falciparum. P. vivax peaked in August while P. falciparum peaked in November. 32% of the estimated 30.5 million people lived in regions where annual incidence was at least 1 case per 1,000 population of P. vivax; 23.7% of the population lived in areas where annual P. falciparum case incidence was at least 1 per 1000. This study showed how routine data can be combined with household survey data to model malaria incidence. The incidence of both P. vivax and P. falciparum in Afghanistan remain low but the co-distribution of both parasites and the lag in their peak season provides challenges to malaria control in Afghanistan. Future improved case definition to determine levels of imported risks may be useful for the elimination ambitions in Afghanistan.

  17. Plasmodium falciparum and Plasmodium vivax specific lactate dehydrogenase: genetic polymorphism study from Indian isolates.

    Science.gov (United States)

    Keluskar, Priyadarshan; Singh, Vineeta; Gupta, Purva; Ingle, Sanjay

    2014-08-01

    Control and eradication of malaria is hindered by the acquisition of drug resistance by Plasmodium species. This has necessitated a persistent search for novel drugs and more efficient targets. Plasmodium species specific lactate dehydrogenase is one of the potential therapeutic and diagnostic targets, because of its indispensable role in endoerythrocytic stage of the parasite. A target molecule that is highly conserved in the parasite population can be more effectively used in diagnostics and therapeutics, hence, in the present study polymorphism in PfLDH (Plasmodiumfalciparum specific LDH) and PvLDH (Plasmodiumvivax specific LDH) genes was analyzed using PCR-single strand confirmation polymorphism (PCR-SSCP) and sequencing. Forty-six P. falciparum and thirty-five P. vivax samples were screened from different states of India. Our findings have revealed presence of a single PfLDH genotype and six PvLDH genotypes among the studied samples. Interestingly, along with synonymous substitutions, nonsynonymous substitutions were reported to be present for the first time in the PvLDH genotypes. Further, through amino acid sequence alignment and homology modeling studies we observed that the catalytic residues were conserved in all PvLDH genotypes and the nonsynonymous substitutions have not altered the enzyme structure significantly. Evolutionary genetics studies have confirmed that PfLDH and PvLDH loci are under strong purifying selection. Phylogenetic analysis of the pLDH gene sequences revealed that P. falciparum compared to P. vivax, has recent origin. The study therefore supports PfLDH and PvLDH as suitable therapeutic and diagnostic targets as well as phylogenetic markers to understand the genealogy of malaria species.

  18. Biguanide-Atovaquone Synergy against Plasmodium falciparum In Vitro

    OpenAIRE

    2002-01-01

    The synergistic potential of a range of biguanides, their triazine metabolites, tetracyclines, and pyrimethamine in combination with atovaquone has been assessed. All five biguanides tested interacted synergistically with atovaquone against Plasmodium falciparum in vitro. All of the other compounds tested were either additive or antagonistic.

  19. Antibodies to a recombinant glutamate-rich Plasmodium falciparum protein

    DEFF Research Database (Denmark)

    Hogh, B; Petersen, E; Dziegiel, Morten Hanefeld

    1992-01-01

    A Plasmodium falciparum antigen gene coding for a 220-kD glutamate-rich protein (GLURP) has been cloned, and the 783 C-terminal amino acids of this protein (GLURP489-1271) have been expressed as a beta-galactosidase fusion protein in Escherichia coli. The encoded 783 amino acid residues contain two...

  20. Positive blood culture with Plasmodium falciparum : Case report

    NARCIS (Netherlands)

    De Vries, Jutte J. C.; Van Assen, Sander; Mulder, André B.; Kampinga, Greetje A.

    2007-01-01

    An adult traveler presented with fever and malaise after returning from Sierra Leone. Young trophozoites of Plasmodium falciparum were seen in a blood smear, with parasitemia being 10%. Moreover, blood cultures drawn on admission signaled as "positive" after 1 day of incubation, but no bacteria were

  1. Genotyping Plasmodium vivax isolates from the 2011 outbreak in Greece

    DEFF Research Database (Denmark)

    Spanakos, Gregory; Alifrangis, Michael; Schousboe, Mette L

    2013-01-01

    Plasmodium vivax malaria was common in Greece until the 1950s with epidemics involving thousands of cases every year. Greece was declared free of malaria by the World Health Organization in 1974. From 1974 to 2010, an average of 39 cases per year were reported, which were mainly imported. However...

  2. The isoprenoid-precursor dependence of Plasmodium spp

    NARCIS (Netherlands)

    van der Meer, Jan-Ytzen; Hirsch, Anna K. H.

    2012-01-01

    Due to the increase in resistance of Plasmodium spp. against available antimalarials, there is a need for new, effective and innovative drugs. The non-mevalonate pathway for the biosynthesis of the universal isoprenoid precursors, which is absent in humans, is suggested as an attractive source of

  3. Structural Differences Explain Diverse Functions of Plasmodium Actins

    Science.gov (United States)

    Vahokoski, Juha; Martinez, Silvia Muñico; Ignatev, Alexander; Lepper, Simone; Frischknecht, Friedrich; Sidén-Kiamos, Inga; Sachse, Carsten; Kursula, Inari

    2014-01-01

    Actins are highly conserved proteins and key players in central processes in all eukaryotic cells. The two actins of the malaria parasite are among the most divergent eukaryotic actins and also differ from each other more than isoforms in any other species. Microfilaments have not been directly observed in Plasmodium and are presumed to be short and highly dynamic. We show that actin I cannot complement actin II in male gametogenesis, suggesting critical structural differences. Cryo-EM reveals that Plasmodium actin I has a unique filament structure, whereas actin II filaments resemble canonical F-actin. Both Plasmodium actins hydrolyze ATP more efficiently than α-actin, and unlike any other actin, both parasite actins rapidly form short oligomers induced by ADP. Crystal structures of both isoforms pinpoint several structural changes in the monomers causing the unique polymerization properties. Inserting the canonical D-loop to Plasmodium actin I leads to the formation of long filaments in vitro. In vivo, this chimera restores gametogenesis in parasites lacking actin II, suggesting that stable filaments are required for exflagellation. Together, these data underline the divergence of eukaryotic actins and demonstrate how structural differences in the monomers translate into filaments with different properties, implying that even eukaryotic actins have faced different evolutionary pressures and followed different paths for developing their polymerization properties. PMID:24743229

  4. Plasmodium cellular effector mechanisms and the hepatic microenvironment

    Science.gov (United States)

    Frevert, Ute; Krzych, Urszula

    2015-01-01

    Plasmodium falciparum malaria remains one of the most serious health problems globally. Immunization with attenuated parasites elicits multiple cellular effector mechanisms capable of eliminating Plasmodium liver stages. However, malaria liver stage (LS) immunity is complex and the mechanisms effector T cells use to locate the few infected hepatocytes in the large liver in order to kill the intracellular LS parasites remain a mystery to date. Here, we review our current knowledge on the behavior of CD8 effector T cells in the hepatic microvasculature, in malaria and other hepatic infections. Taking into account the unique immunological and lymphogenic properties of the liver, we discuss whether classical granule-mediated cytotoxicity might eliminate infected hepatocytes via direct cell contact or whether cytokines might operate without cell–cell contact and kill Plasmodium LSs at a distance. A thorough understanding of the cellular effector mechanisms that lead to parasite death hence sterile protection is a prerequisite for the development of a successful malaria vaccine to protect the 40% of the world’s population currently at risk of Plasmodium infection. PMID:26074888

  5. Phospholipid organization in monkey erythrocytes upon Plasmodium knowlesi infection

    NARCIS (Netherlands)

    Schaft, P.H. van der; Beaumelle, B.; Vial, H.; Roelofsen, B.; Kamp, J.A.F. op den; Deenen, L.L.M. van

    1987-01-01

    The phospholipid organization in monkey erythrocytes upon Plasmodium knowlesi infection has been studied. Parasitized and nonparasitized erythrocytes from malaria-infected blood were separated and pure erythrocyte membranes from parasitized cells were isolated using Affi-Gel beads. In this way, the

  6. Plasmodium falciparum transcriptome analysis reveals pregnancy malaria associated gene expression

    DEFF Research Database (Denmark)

    Tuikue Ndam, Nicaise; Bischoff, Emmanuel; Proux, Caroline

    2008-01-01

    BACKGROUND: Pregnancy-associated malaria (PAM) causing maternal anemia and low birth weight is among the multiple manifestations of Plasmodium falciparum malaria. Infected erythrocytes (iEs) can acquire various adhesive properties that mediate the clinical severity of malaria. Recent advances...

  7. Artemether-lumefantrine treatment of uncomplicated Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Kofoed, Poul-Erik

    2015-01-01

    -lumefantrine for uncomplicated Plasmodium falciparum malaria, to define therapeutic day 7 lumefantrine concentrations and identify patient factors that substantially alter these concentrations. A systematic review of PubMed, Embase, Google Scholar, ClinicalTrials.gov and conference proceedings identified all relevant studies...

  8. Acute kidney injury in imported Plasmodium falciparum malaria

    NARCIS (Netherlands)

    L.C. Koopmans (Liese); M.E. van Wolfswinkel (Marlies); D.A. Hesselink (Dennis); E.J. Hoorn (Ewout); R. Koelewijn (Rob); J.J. van Hellemond (Jaap); P.J.J. van Genderen (Perry)

    2015-01-01

    textabstractBackground: Acute kidney injury (AKI) is a known complication of malaria, and is reported to occur in up to 40 % of adult patients with a severe Plasmodium falciparum infection in endemic regions. To gain insight in the incidence and risk factors of AKI in imported P. falciparum malaria,

  9. Exploring Anopheles gut bacteria for Plasmodium blocking activity

    Science.gov (United States)

    Bahia, Ana C; Dong, Yuemei; Blumberg, Benjamin J; Mlambo, Godfree; Tripathi, Abhai; BenMarzouk-Hidalgo, Omar J; Chandra, Ramesh; Dimopoulos, George

    2014-01-01

    SUMMARY Malaria parasite transmission requires the successful development of Plasmodium gametocytes into flagellated microgametes upon mosquito blood ingestion, and the subsequent fertilization of microgametes and macrogametes for the development of motile zygotes, called ookinetes, which invade and transverse the Anopheles vector mosquito midgut at around 18-36 h after blood ingestion. Within the mosquito midgut, the malaria parasite has to withstand the mosquito's innate immune response and the detrimental effect of its commensal bacterial flora. We have assessed the midgut colonization capacity of 5 gut bacterial isolates from field-derived, and 2 from laboratory colony, mosquitoes and their effect on Plasmodium development in vivo and in vitro, along with their impact on mosquito survival. Some bacterial isolates activated the mosquito's immune system, affected the mosquito's life span, and were capable of blocking Plasmodium development. We have also shown that the ability of these bacteria to inhibit the parasites is likely to involve different mechanisms and factors. A Serratia marcescens isolate was particularly efficient in colonizing the mosquitoes’ gut, compromising mosquito survival, and inhibiting both sexual- and asexual-stage Plasmodium through secreted factors, thereby rendering it a potential candidate for the development of a malaria transmission intervention strategy. PMID:24428613

  10. Molecular make-up of the Plasmodium parasitophorous vacuolar membrane.

    Science.gov (United States)

    Spielmann, Tobias; Montagna, Georgina N; Hecht, Leonie; Matuschewski, Kai

    2012-10-01

    Plasmodium, the causative agent of malaria, is an obligate, intracellular, eukaryotic cell that invades, replicates, and differentiates within hepatocytes and erythrocytes. Inside a host cell, a second membrane delineates the developing pathogen in addition to the parasite plasma membrane, resulting in a distinct cellular compartment, termed parasitophorous vacuole (PV). The PV membrane (PVM) constitutes the parasite-host cell interface and is likely central to nutrient acquisition, host cell remodeling, waste disposal, environmental sensing, and protection from innate defense. Over the past two decades, a number of parasite-encoded PVM proteins have been identified. They include multigene families and protein complexes, such as early-transcribed membrane proteins (ETRAMPs) and the Plasmodium translocon for exported proteins (PTEX). Nearly all Plasmodium PVM proteins are restricted to this genus and display transient and stage-specific expression. Here, we provide an overview of the PVM proteins of Plasmodium blood and liver stages. Biochemical and experimental genetics data suggest that some PVM proteins are ideal targets for novel anti-malarial intervention strategies.

  11. Plasmodium falciparum infection causes proinflammatory priming of human TLR responses.

    NARCIS (Netherlands)

    McCall, M.B.B.; Netea, M.G.; Hermsen, C.C.; Jansen, T.; Jacobs, L.; Golenbock, D.; Ven, A.J.A.M. van der; Sauerwein, R.W.

    2007-01-01

    TLRs are a major group of pattern recognition receptors that are crucial in initiating innate immune responses and are capable of recognizing Plasmodium ligands. We have investigated TLR responses during acute experimental P. falciparum (P.f.) infection in 15 malaria-naive volunteers. TLR-4 response

  12. Scavenger receptor BI boosts hepatocyte permissiveness to Plasmodium infection.

    NARCIS (Netherlands)

    Yalaoui, S.; Huby, T.; Franetich, J.F.; Gego, A.; Rametti, A.; Moreau, M.; Collet, X.; Siau, A.; Gemert, G.J.A. van; Sauerwein, R.W.; Luty, A.J.F.; Vaillant, J.C.; Hannoun, L.; Chapman, J.; Mazier, D.; Froissard, P.

    2008-01-01

    Infection of hepatocytes by Plasmodium falciparum sporozoites requires the host tetraspanin CD81. CD81 is also predicted to be a coreceptor, along with scavenger receptor BI (SR-BI), for hepatitis C virus. Using SR-BI-knockout, SR-BI-hypomorphic and SR-BI-transgenic primary hepatocytes, as well as s

  13. Positive blood culture with Plasmodium falciparum: Case report

    NARCIS (Netherlands)

    De Vries, Jutte J. C.; Van Assen, Sander; Mulder, André B.; Kampinga, Greetje A.

    2007-01-01

    An adult traveler presented with fever and malaise after returning from Sierra Leone. Young trophozoites of Plasmodium falciparum were seen in a blood smear, with parasitemia being 10%. Moreover, blood cultures drawn on admission signaled as "positive" after 1 day of incubation, but no bacteria were

  14. Positive blood culture with Plasmodium falciparum : Case report

    NARCIS (Netherlands)

    De Vries, Jutte J. C.; Van Assen, Sander; Mulder, André B.; Kampinga, Greetje A.

    2007-01-01

    An adult traveler presented with fever and malaise after returning from Sierra Leone. Young trophozoites of Plasmodium falciparum were seen in a blood smear, with parasitemia being 10%. Moreover, blood cultures drawn on admission signaled as "positive" after 1 day of incubation, but no bacteria were

  15. The prognostic value of schizontaemia in imported Plasmodium falciparum malaria

    NARCIS (Netherlands)

    M.E. van Wolfswinkel (Marlies); M. De Mendonça Melo (Mariana); K. Vliegenthart-Jongbloed (Klaske); R. Koelewijn (Rob); J.J. van Hellemond (Jaap); P.J.J. van Genderen (Perry)

    2012-01-01

    textabstractBackground: In Plasmodium falciparum infection, peripheral parasite counts do not always correlate well with the sequestered parasite burden. As erythrocytes parasitized with mature trophozoites and schizonts have a high tendency to adhere to the microvascular endothelium, they are often

  16. The prognostic value of schizontaemia in imported Plasmodium falciparum malaria

    NARCIS (Netherlands)

    M.E. van Wolfswinkel (Marlies); M. De Mendonça Melo (Mariana); K. Vliegenthart-Jongbloed (Klaske); R. Koelewijn (Rob); J.J. van Hellemond (Jaap); P.J.J. van Genderen (Perry)

    2012-01-01

    textabstractBackground: In Plasmodium falciparum infection, peripheral parasite counts do not always correlate well with the sequestered parasite burden. As erythrocytes parasitized with mature trophozoites and schizonts have a high tendency to adhere to the microvascular endothelium, they are often

  17. Acute kidney injury in imported Plasmodium falciparum malaria

    NARCIS (Netherlands)

    L.C. Koopmans, L.C. (Liese); M.E. van Wolfswinkel (Marlies); D.A. Hesselink (Dennis); E.J. Hoorn (Ewout); R. Koelewijn (Rob); J.J. van Hellemond (Jaap); P.J. van Genderen (P.)

    2015-01-01

    textabstractBackground: Acute kidney injury (AKI) is a known complication of malaria, and is reported to occur in up to 40 % of adult patients with a severe Plasmodium falciparum infection in endemic regions. To gain insight in the incidence and risk factors of AKI in imported P. falciparum malaria,

  18. The epidemiology of Plasmodium falciparum gametocytes: weapons of mass dispersion.

    NARCIS (Netherlands)

    Drakeley, C.; Sutherland, C.; Bousema, J.T.; Sauerwein, R.W.; Targett, G.A.T.

    2006-01-01

    Much of the epidemiology of Plasmodium falciparum in Sub-Saharan Africa focuses on the prevalence patterns of asexual parasites in people of different ages, whereas the gametocytes that propagate the disease are often neglected. One expected benefit of the widespread introduction of artemisinin-base

  19. Genomics and epigenetics of sexual commitment in Plasmodium.

    Science.gov (United States)

    Bechtsi, D P; Waters, A P

    2017-06-01

    Malaria is the disease caused by the apicomplexan parasites belonging to the genus Plasmodium. Expanding our arsenal to include transmission-blocking agents in our fight against malaria is becoming increasingly important. Such an implementation requires detailed understanding of the biology of the Plasmodium life cycle stages that are transmissible. Plasmodium gametocytes are the only parasite stage that can be transmitted to the mosquito vector and are the product of sexual development in a small percentage of parasites that continually proliferate in host blood. The critical decision made by asexual erythrocytic stages to cease further proliferation and differentiate into gametocytes, as well as the first steps they take into maturity, have long remained unknown. Recent studies have contributed to a breakthrough in our understanding of this branch point in development. In this review, we will discuss the findings that have allowed us to make this major leap forward in our knowledge of sexual commitment in Plasmodium. We will further propose a model for the mechanism triggering the switch to sexual development, constructed around the proteins currently known to regulate this process. Further insight into sexual commitment and gametocyte development will help identify targets for the development of transmission-blocking malaria therapies. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  20. The isoprenoid-precursor dependence of Plasmodium spp

    NARCIS (Netherlands)

    van der Meer, Jan-Ytzen; Hirsch, Anna K. H.

    2012-01-01

    Due to the increase in resistance of Plasmodium spp. against available antimalarials, there is a need for new, effective and innovative drugs. The non-mevalonate pathway for the biosynthesis of the universal isoprenoid precursors, which is absent in humans, is suggested as an attractive source of ta

  1. Plasmodium knowlesi in humans, macaques and mosquitoes in peninsular Malaysia

    Directory of Open Access Journals (Sweden)

    NorParina Ismail

    2008-08-01

    Full Text Available Abstract Background Since a large focus of human infection with Plasmodium knowlesi, a simian malaria parasite naturally found in long-tailed and pig tailed macaques, was reported in Sarawak, Malaysian Borneo, it was pertinent to study the situation in peninsular Malaysia. A study was thus initiated to screen human cases of Plasmodium malariae using molecular techniques, to determine the presence of P. knowlesi in non- human primates and to elucidate its vectors. Methods Nested polymerase chain reaction (PCR was used to identify all Plasmodium species present in the human blood samples sent to the Parasitology laboratory of Institute for Medical Research. At the same time, non-human primates were also screened for malaria parasites and nested PCR was carried out to determine the presence of P. knowlesi. Mosquitoes were collected from Pahang by human landing collection and monkey-baited-traps situated on three different levels. All mosquitoes were identified and salivary glands and midguts of anopheline mosquitoes were dissected to determine the presence of malaria parasites and nested PCR was carried out on positive glands. Sequencing of the csp genes were carried on P. knowlesi samples from humans, monkeys and mosquitoes, positive by PCR. Results and Discussion Plasmodium knowlesi was detected in 77 (69.37% of the 111 human samples, 10 (6.90% of the 145 monkey blood and in 2 (1.7% Anopheles cracens. Sequence of the csp gene clustered with other P. knowlesi isolates. Conclusion Human infection with Plasmodium knowlesi is occurring in most states of peninsular Malaysia. An. cracens is the main vector. Economic exploitation of the forest is perhaps bringing monkeys, mosquitoes and humans into increased contact. A single bite from a mosquito infected with P. knowlesi is sufficient to introduce the parasite to humans. Thus, this zoonotic transmission has to be considered in the future planning of malaria control.

  2. Small molecule screen for candidate antimalarials targeting Plasmodium Kinesin-5.

    Science.gov (United States)

    Liu, Liqiong; Richard, Jessica; Kim, Sunyoung; Wojcik, Edward J

    2014-06-06

    Plasmodium falciparum and vivax are responsible for the majority of malaria infections worldwide, resulting in over a million deaths annually. Malaria parasites now show measured resistance to all currently utilized drugs. Novel antimalarial drugs are urgently needed. The Plasmodium Kinesin-5 mechanoenzyme is a suitable "next generation" target. Discovered via small molecule screen experiments, the human Kinesin-5 has multiple allosteric sites that are "druggable." One site in particular, unique in its sequence divergence across all homologs in the superfamily and even within the same family, exhibits exquisite drug specificity. We propose that Plasmodium Kinesin-5 shares this allosteric site and likewise can be targeted to uncover inhibitors with high specificity. To test this idea, we performed a screen for inhibitors selective for Plasmodium Kinesin-5 ATPase activity in parallel with human Kinesin-5. Our screen of nearly 2000 compounds successfully identified compounds that selectively inhibit both P. vivax and falciparum Kinesin-5 motor domains but, as anticipated, do not impact human Kinesin-5 activity. Of note is a candidate drug that did not biochemically compete with the ATP substrate for the conserved active site or disrupt the microtubule-binding site. Together, our experiments identified MMV666693 as a selective allosteric inhibitor of Plasmodium Kinesin-5; this is the first identified protein target for the Medicines of Malaria Venture validated collection of parasite proliferation inhibitors. This work demonstrates that chemical screens against human kinesins are adaptable to homologs in disease organisms and, as such, extendable to strategies to combat infectious disease. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Small Molecule Screen for Candidate Antimalarials Targeting Plasmodium Kinesin-5*

    Science.gov (United States)

    Liu, Liqiong; Richard, Jessica; Kim, Sunyoung; Wojcik, Edward J.

    2014-01-01

    Plasmodium falciparum and vivax are responsible for the majority of malaria infections worldwide, resulting in over a million deaths annually. Malaria parasites now show measured resistance to all currently utilized drugs. Novel antimalarial drugs are urgently needed. The Plasmodium Kinesin-5 mechanoenzyme is a suitable “next generation” target. Discovered via small molecule screen experiments, the human Kinesin-5 has multiple allosteric sites that are “druggable.” One site in particular, unique in its sequence divergence across all homologs in the superfamily and even within the same family, exhibits exquisite drug specificity. We propose that Plasmodium Kinesin-5 shares this allosteric site and likewise can be targeted to uncover inhibitors with high specificity. To test this idea, we performed a screen for inhibitors selective for Plasmodium Kinesin-5 ATPase activity in parallel with human Kinesin-5. Our screen of nearly 2000 compounds successfully identified compounds that selectively inhibit both P. vivax and falciparum Kinesin-5 motor domains but, as anticipated, do not impact human Kinesin-5 activity. Of note is a candidate drug that did not biochemically compete with the ATP substrate for the conserved active site or disrupt the microtubule-binding site. Together, our experiments identified MMV666693 as a selective allosteric inhibitor of Plasmodium Kinesin-5; this is the first identified protein target for the Medicines of Malaria Venture validated collection of parasite proliferation inhibitors. This work demonstrates that chemical screens against human kinesins are adaptable to homologs in disease organisms and, as such, extendable to strategies to combat infectious disease. PMID:24737313

  4. Changing trends in prevalence of different Plasmodium species with dominance of Plasmodium falciparum malaria infection in Aligarh (India).

    Science.gov (United States)

    Khan, Haris M; Shujatullah, Fatima; Ashfaq, Mohammad; Raza, Adil

    2011-01-01

    To determine the prevalence of malaria in Aligarh and analyze species dominance in different years over a decade. Diagnosis of malaria was done using microscopy as gold standard, rapid antigen detection assays and quantitative buffy coat (QBC) assays. Giemsa stained blood smear examination was done, thick and thin films were examined for presence of different Plasmodium spp. Rapid antigen detection assays employing detection of HRP-2 and parasite lactate dehydrogenase antigen (pLDH) by immunochromatography was done in patients whose blood smear found to be negative by conventional Giemsa slide examination. QBC was done in cases where there is strong clinical suspicion of malaria with blood smear negative, in patients with chronic malaria, splenomegaly, or in those patients who had inadequate treatment and for post-treatment follow up. Plasmodium vivax and Plasmodium falciparum were only species detected in our hospital. Overall prevalence of malaria in Aligarh was found to be 8.8%. The maximum prevalence of 20.1% was observed in year 2008 and lowest 2.3% in 2002. High prevalence of malaria is observed in this part of country with dominance of both species particularly Plasmodium falciparum should be monitored and factors accounting for occurrence should be studied to employ effective control measures. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  5. Anopheles moucheti and Anopheles vinckei are candidate vectors of ape Plasmodium parasites, including Plasmodium praefalciparum in Gabon.

    Science.gov (United States)

    Paupy, Christophe; Makanga, Boris; Ollomo, Benjamin; Rahola, Nil; Durand, Patrick; Magnus, Julie; Willaume, Eric; Renaud, François; Fontenille, Didier; Prugnolle, Franck

    2013-01-01

    During the last four years, knowledge about the diversity of Plasmodium species in African great apes has considerably increased. Several new species were described in chimpanzees and gorillas, and some species that were previously considered as strictly of human interest were found to be infecting African apes. The description in gorillas of P. praefalciparum, the closest relative of P. falciparum which is the main malignant agent of human malaria, definitively changed the way we understand the evolution and origin of P. falciparum. This parasite is now considered to have appeared recently, following a cross-species transfer from gorillas to humans. However, the Plasmodium vector mosquito species that have served as bridge between these two host species remain unknown. In order to identify the vectors that ensure ape Plasmodium transmission and evaluate the risk of transfer of these parasites to humans, we carried out a field study in Gabon to capture Anopheles in areas where wild and semi-wild ape populations live. We collected 1070 Anopheles females belonging to 15 species, among which An. carnevalei, An. moucheti and An. marshallii were the most common species. Using mtDNA-based PCR tools, we discovered that An. moucheti, a major human malaria vector in Central Africa, could also ensure the natural transmission of P. praefalciparum among great apes. We also showed that, together with An. vinckei, An. moucheti was infected with P. vivax-like parasites. An. moucheti constitutes, therefore, a major candidate for the transfer of Plasmodium parasites from apes to humans.

  6. Plasmodium-specific molecular assays produce uninterpretable results and non-Plasmodium spp. sequences in field-collected Anopheles vectors.

    Science.gov (United States)

    Harrison, Genelle F; Foley, Desmond H; Rueda, Leopoldo M; Melanson, Vanessa R; Wilkerson, Richard C; Long, Lewis S; Richardson, Jason H; Klein, Terry A; Kim, Heung-Chul; Lee, Won-Ja

    2013-12-01

    The Malaria Research and Reference Reagent Resource-recommended PLF/UNR/VIR polymerase chain reaction (PCR) was used to detect Plasmodium vivax in Anopheles spp. mosquitoes collected in South Korea. Samples that were amplified were sequenced and compared with known Plasmodium spp. by using the PlasmoDB.org Basic Local Alignment Search Tool/n and the National Center for Biotechnology Information Basic Local Alignment Search Tool/n tools. Results show that the primers PLF/UNR/VIR used in this PCR can produce uninterpretable results and non-specific sequences in field-collected mosquitoes. Three additional PCRs (PLU/VIV, specific for 18S small subunit ribosomal DNA; Pvr47, specific for a nuclear repeat; and GDCW/PLAS, specific for the mitochondrial marker, cytB) were then used to find a more accurate and interpretable assay. Samples that were amplified were again sequenced. The PLU/VIV and Pvr47 assays showed cross-reactivity with non-Plasmodium spp. and an arthropod fungus (Zoophthora lanceolata). The GDCW/PLAS assay amplified only Plasmodium spp. but also amplified the non-human specific parasite P. berghei from an Anopheles belenrae mosquito. Detection of P. berghei in South Korea is a new finding.

  7. Changing trends in prevalence of different Plasmodium species with dominance of Plasmodium falciparum malaria infection in Aligarh (India)

    Institute of Scientific and Technical Information of China (English)

    Haris M Khan; Fatima Shujatullah; Mohammad Ashfaq; Adil Raza

    2011-01-01

    Objective: To determine the prevalence of malaria in Aligarh and analyze species dominance in different years over a decade. Methods: Diagnosis of malaria was done using microscopy as gold standard, rapid antigen detection assays and quantitative buffy coat (QBC) assays. Giemsa stained blood smear examination was done, thick and thin films were examined for presence of different Plasmodium spp. Rapid antigen detection assays employing detection of HRP-2 and parasite lactate dehydrogenase antigen (pLDH) by immunochromatography was done in patients whose blood smear found to be negative by conventional Giemsa slide examination. QBC was done in cases where there is strong clinical suspicion of malaria with blood smear negative, in patients with chronic malaria, splenomegaly, or in those patients who had inadequate treatment and for post-treatment follow up. Results: Plasmodium vivax and Plasmodium falciparum were only species detected in our hospital. Overall prevalence of malaria in Aligarh was found to be 8.8%. The maximum prevalence of 20.1% was observed in year 2008 and lowest 2.3% in 2002.Conclusions:High prevalence of malaria is observed in this part of country with dominance of both species particularly Plasmodium falciparum should be monitored and factors accounting for occurrence should be studied to employ effective control measures.

  8. Verification of concurrent systems with VerCors

    NARCIS (Netherlands)

    Amighi, A.; Blom, Stefan; Darabi, Saeed; Huisman, Marieke; Mostowski, Wojciech; Zaharieva, M.; Bernardo, Marco; Damiani, Ferruccio; Hahnle, Reiner; Johnsen, Einar; Schaefer, Ina

    This paper presents the VerCors approach to verification of concurrent software. It first discusses why verification of concurrent software is important, but also challenging. Then it shows how within the VerCors project we use permission-based separation logic to reason about multithreaded Java

  9. 28 CFR 0.56 - Exclusive or concurrent jurisdiction.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Exclusive or concurrent jurisdiction. 0.56 Section 0.56 Judicial Administration DEPARTMENT OF JUSTICE ORGANIZATION OF THE DEPARTMENT OF JUSTICE Criminal Division § 0.56 Exclusive or concurrent jurisdiction. The Assistant Attorney General...

  10. Graphical modelling language for spycifying concurrency based on CSP

    NARCIS (Netherlands)

    Hilderink, G.H.

    2003-01-01

    Introduced in this (shortened) paper is a graphical modelling language for specifying concurrency in software designs. The language notations are derived from CSP and the resulting designs form CSP diagrams. The notations reflect both data-flow and control-flow aspects of concurrent software

  11. Reasoning about Concurrent Actionsin Multi-Agent Systems

    Institute of Scientific and Technical Information of China (English)

    FAN Xiaocong; XU Dianxiang; HOU Jianmin; ZHENG Guoliang

    1999-01-01

    Concurrence is an important researcharea in collaborative problem solving.This paper offers a formaldefinition for cooperative sequences in multi-agentsystems, discussesthe different categories of concurrent actions, and proposes somerules forsituation revision and an algorithm used to generate resultingsituations.An example is also given to show how to solve concurrentproblems occurring inmulti-agent systems.

  12. Concurrent Lexicalized Dependency Parsing The ParseTalk Model

    CERN Document Server

    Broeker, N; Schacht, S; Broeker, Norbert; Hahn, Udo; Schacht, Susanne

    1994-01-01

    A grammar model for concurrent, object-oriented natural language parsing is introduced. Complete lexical distribution of grammatical knowledge is achieved building upon the head-oriented notions of valency and dependency, while inheritance mechanisms are used to capture lexical generalizations. The underlying concurrent computation model relies upon the actor paradigm. We consider message passing protocols for establishing dependency relations and ambiguity handling.

  13. Separate versus Concurrent Calibration Methods in Vertical Scaling.

    Science.gov (United States)

    Karkee, Thakur; Lewis, Daniel M.; Hoskens, Machteld; Yao, Lihua; Haug, Carolyn

    Two methods to establish a common scale across grades within a content area using a common item design (separate and concurrent) have previously been studied under simulated conditions. Separate estimation is accomplished through separate calibration and grade-by-grade chained linking. Concurrent calibration established the vertical scale in a…

  14. Dynamic Frames Based Verification Method for Concurrent Java Programs

    NARCIS (Netherlands)

    Mostowski, Wojciech

    2016-01-01

    In this paper we discuss a verification method for concurrent Java programs based on the concept of dynamic frames. We build on our earlier work that proposes a new, symbolic permission system for concurrent reasoning and we provide the following new contributions. First, we describe our approach

  15. Concurrent Object-Oriented Programming Based on MPI

    Institute of Scientific and Technical Information of China (English)

    鲁宏伟; 汪厚祥; 裴晓黎; 肖永玲

    2004-01-01

    Object-oriented model possesses inherent concurrency. Integration of concurrency and object-orientation is a promising new field. MPI is a message-passing standard and has been adopted by more and more systems. This paper proposes a novel approach to realize concurrent object-oriented programming based on Message-passing interface(MPI) in which future method communication is adopted between concurrent objects. A state behavior set is proposed to solve inheritance anomaly, and a bounded buffer is taken as an example to illustrate this proposal. The definition of ParaMPI class, which is the most important class in the concurrent class library,and implementation issues are briefly described.

  16. Proceedings Fourth Interaction and Concurrency Experience

    CERN Document Server

    Silva, Alexandra; Bruni, Roberto; Carbone, Marco; 10.4204/EPTCS.59

    2011-01-01

    This volume contains the pre-proceedings of ICE'11, the 4th Interaction and Concurrency Experience workshop, which was held in Reykjavik, Iceland on the 9th of June 2011 as a satellite event of DisCoTec'11. The topic of ICE'11 was Reliable and Contract-based Interaction. Reliable interactions are, e.g., those enjoying suitable logical, behavioural, or security properties, or adhering to certain QoS standards. Contract-based interactions are, e.g., those where the interacting entities are committed to give certain guarantees whenever certain assumptions are met by their operating environment. The ICE procedure for paper selection allows for PC members to interact, anonymously, with authors. During the review phase, each submitted paper is published on a Wiki and associated with a discussion forum whose access is restricted to the authors and to all the PC members not declaring a conflict of interests. The PC members post comments and questions that the authors reply to. Each paper was reviewed by four PC membe...

  17. Creatine and Caffeine: Considerations for Concurrent Supplementation.

    Science.gov (United States)

    Trexler, Eric T; Smith-Ryan, Abbie E

    2015-12-01

    Nutritional supplementation is a common practice among athletes, with creatine and caffeine among the most commonly used ergogenic aids. Hundreds of studies have investigated the ergogenic potential of creatine supplementation, with consistent improvements in strength and power reported for exercise bouts of short duration (≤ 30 s) and high intensity. Caffeine has been shown to improve endurance exercise performance, but results are mixed in the context of strength and sprint performance. Further, there is conflicting evidence from studies comparing the ergogenic effects of coffee and caffeine anhydrous supplementation. Previous research has identified independent mechanisms by which creatine and caffeine may improve strength and sprint performance, leading to the formulation of multi-ingredient supplements containing both ingredients. Although scarce, research has suggested that caffeine ingestion may blunt the ergogenic effect of creatine. While a pharmacokinetic interaction is unlikely, authors have suggested that this effect may be explained by opposing effects on muscle relaxation time or gastrointestinal side effects from simultaneous consumption. The current review aims to evaluate the ergogenic potential of creatine and caffeine in the context of high-intensity exercise. Research directly comparing coffee and caffeine anhydrous is discussed, along with previous studies evaluating the concurrent supplementation of creatine and caffeine.

  18. Physarum boats: If plasmodium sailed it would never leave a port

    CERN Document Server

    Adamatzky, Andrew

    2009-01-01

    Plasmodium of \\emph{Physarum polycephalum} is a single huge (visible by naked eye) cell with myriad of nuclei. The plasmodium is a promising substrate for non-classical, nature-inspired, computing devices. It is capable for approximation of shortest path, computation of planar proximity graphs and plane tessellations, primitive memory and decision-making. The unique properties of the plasmodium make it an ideal candidate for a role of amorphous biological robots with massive parallel information processing and distributed inputs and outputs. We show that when adhered to light-weight object resting on a water surface the plasmodium can propel the object by oscillating its protoplasmic pseudopodia. In experimental laboratory conditions and computational experiments we study phenomenology of the plasmodium-floater system, and possible mechanisms of controlling motion of objects propelled by on board plasmodium.

  19. Physarum Boats: If Plasmodium Sailed It Would Never Leave a Port

    Directory of Open Access Journals (Sweden)

    Andrew Adamatzky

    2010-01-01

    Full Text Available Plasmodium of Physarum polycephalum is a single huge (visible by naked eye cell with a myriad of nuclei. The plasmodium is a promising substrate for non-classical, nature-inspired computing devices. It is capable of approximation of the shortest path in a maze, computation of planar proximity graphs and plane tessellations, primitive memory and decision making. The unique properties of the plasmodium make it an ideal candidate for a role of amorphous biological robots with massive parallel information processing and distributed inputs and outputs. We show that when adhered to a lightweight object resting on a water surface the plasmodium can propel the object by oscillating its protoplasmic pseudopodia. In experimental laboratory conditions and computational experiments we study phenomenology of the plasmodium-floater system, and possible mechanisms of controlling motion of objects propelled by on-board plasmodium.

  20. Plasmodium Genus Assay Transition to the Joint Biological Agent Identification and Diagnostic System (JBAIDS)

    Science.gov (United States)

    2012-07-12

    AFRIMS), Bangkok, Thailand Final Report AFMSA O&M FY09 Project (FWH20090036H): Plasmodium Genus Assay Transition to the Joint Biological Agent...evaluation data to support AFPMB approval of the RAPID- based Plasmodium genus assay for use in vector/vector-borne disease surveillance on the RAPID...Objective 1 Results: Plasmodium genus RAPID/JBAIDS assay development activities conducted during the FY09 study did not resolve cross-reactivity

  1. Hemozoin activates the innate immune system and reduces Plasmodium berghei infection in Anopheles gambiae

    OpenAIRE

    Simões, Maria L; Gonçalves, Luzia; Silveira, Henrique

    2015-01-01

    Background Malaria is a worldwide infectious disease caused by Plasmodium parasites and transmitted by female Anopheles mosquitoes. The malaria vector mosquito Anopheles can trigger effective mechanisms to control completion of the Plasmodium lifecycle; the mosquito immune response to the parasite involves several pathways which are not yet well characterized. Plasmodium metabolite hemozoin has emerged as a potent immunostimulator of mammalian tissues. In this study, we aim to investigate the...

  2. Comparative population structure of Plasmodium malariae and Plasmodium falciparum under different transmission settings in Malawi

    Directory of Open Access Journals (Sweden)

    Molyneux Malcolm E

    2011-02-01

    Full Text Available Abstract Background Described here is the first population genetic study of Plasmodium malariae, the causative agent of quartan malaria. Although not as deadly as Plasmodium falciparum, P. malariae is more common than previously thought, and is frequently in sympatry and co-infection with P. falciparum, making its study increasingly important. This study compares the population parameters of the two species in two districts of Malawi with different malaria transmission patterns - one seasonal, one perennial - to explore the effects of transmission on population structures. Methods Six species-specific microsatellite markers were used to analyse 257 P. malariae samples and 257 P. falciparum samples matched for age, gender and village of residence. Allele sizes were scored to within 2 bp for each locus and haplotypes were constructed from dominant alleles in multiple infections. Analysis of multiplicity of infection (MOI, population differentiation, clustering of haplotypes and linkage disequilibrium was performed for both species. Regression analyses were used to determine association of MOI measurements with clinical malaria parameters. Results Multiple-genotype infections within each species were common in both districts, accounting for 86.0% of P. falciparum and 73.2% of P. malariae infections and did not differ significantly with transmission setting. Mean MOI of P. falciparum was increased under perennial transmission compared with seasonal (3.14 vs 2.59, p = 0.008 and was greater in children compared with adults. In contrast, P. malariae mean MOI was similar between transmission settings (2.12 vs 2.11 and there was no difference between children and adults. Population differentiation showed no significant differences between villages or districts for either species. There was no evidence of geographical clustering of haplotypes. Linkage disequilibrium amongst loci was found only for P. falciparum samples from the seasonal transmission

  3. Plasmodium knowlesi: from Malaysia, a novel health care threat.

    Science.gov (United States)

    Sabbatani, Sergio; Fiorino, Sirio; Manfredi, Roberto

    2012-03-01

    Epidemic foci of Plasmodium knowlesi malaria have been identified during the past ten years in Malaysia, in particular in the States of Sarawak and Sabah (Malaysia Borneo), and in the Pahang region (peninsular Malaysia). Based on a review of the available recent international literature, the authors underline the importance of molecular biology examinations, polymerase chain reactions (PCR), performed with primers specific for P. knowlesi, since the current microscopic examination (haemoscope) may fail to distinguish P. knowlesi from Plasmodium malariae, due to the very similar appearance of the two parasites. P. knowlesi has been described as the causal agent of life-threatening and lethal forms of malaria: its clinical picture is more severe when compared with that of P. malariae, since the disease is characterized by greater parasitaemia, as opposed to that documented in the course of P. malariae disease. The most effective carrier is Anopheles leucosphyrus: this mosquito is attracted by both humans and monkeys. Among primates, the natural hosts of P. knowlesi are Macaca fascicularis and Macaca nemestina, while Saimiri scirea and Macaca mulatta, which cannot become infected in nature, may be useful in experimental models. When underlining the potentially severe evolution, we note the key role played by prompt disease recognition, which is expected to be more straightforward in patients monitored in endemic countries at high risk, but should be carefully implemented for subjects being admitted to hospital in Western countries suffering from the typical signs and symptoms of malaria, after travelling in South-East Asia where they were engaged in excursions in the tropical forest (trekking, and similar outdoor activities). In these cases, the diagnosis should be prompt, and suitable treatment should follow. According to data in the literature, in non-severe cases chloroquine proves very effective against P. knowlesi, achieving the disappearance of signs and

  4. Trafficking of STEVOR to the Maurer's clefts in Plasmodium falciparum -infected erythrocytes

    National Research Council Canada - National Science Library

    Przyborski, Jude M; Miller, Susanne K; Rohrbach, Petra; Pfahler, Judith M; Crabb, Brendan S; Henrich, Philipp P; Lanzer, Michael

    2005-01-01

    The human malarial parasite Plasmodium falciparum exports proteins to destinations within its host erythrocyte, including cytosol, surface and membranous profiles of parasite origin termed Maurer's clefts...

  5. Plasmodium cynomolgi genome sequences provide insight into Plasmodium vivax and the monkey malaria clade.

    Science.gov (United States)

    Tachibana, Shin-Ichiro; Sullivan, Steven A; Kawai, Satoru; Nakamura, Shota; Kim, Hyunjae R; Goto, Naohisa; Arisue, Nobuko; Palacpac, Nirianne M Q; Honma, Hajime; Yagi, Masanori; Tougan, Takahiro; Katakai, Yuko; Kaneko, Osamu; Mita, Toshihiro; Kita, Kiyoshi; Yasutomi, Yasuhiro; Sutton, Patrick L; Shakhbatyan, Rimma; Horii, Toshihiro; Yasunaga, Teruo; Barnwell, John W; Escalante, Ananias A; Carlton, Jane M; Tanabe, Kazuyuki

    2012-09-01

    P. cynomolgi, a malaria-causing parasite of Asian Old World monkeys, is the sister taxon of P. vivax, the most prevalent malaria-causing species in humans outside of Africa. Because P. cynomolgi shares many phenotypic, biological and genetic characteristics with P. vivax, we generated draft genome sequences for three P. cynomolgi strains and performed genomic analysis comparing them with the P. vivax genome, as well as with the genome of a third previously sequenced simian parasite, Plasmodium knowlesi. Here, we show that genomes of the monkey malaria clade can be characterized by copy-number variants (CNVs) in multigene families involved in evasion of the human immune system and invasion of host erythrocytes. We identify genome-wide SNPs, microsatellites and CNVs in the P. cynomolgi genome, providing a map of genetic variation that can be used to map parasite traits and study parasite populations. The sequencing of the P. cynomolgi genome is a critical step in developing a model system for P. vivax research and in counteracting the neglect of P. vivax.

  6. In vivo resistance to chloroquine by Plasmodium vivax and Plasmodium falciparum at Nabire, Irian Jaya, Indonesia.

    Science.gov (United States)

    Baird, J K; Wiady, I; Fryauff, D J; Sutanihardja, M A; Leksana, B; Widjaya, H; Kysdarmanto; Subianto, B

    1997-06-01

    A survey of resistance to chloroquine by Plasmodium vivax and P. falciparum was conducted during May 1995 at three mesoendemic villages 30 km southeast of Nabire, near the central northern coast of Irian Jaya, Indonesia. The prevalence of malaria at Urusumu (n = 157), Margajaya (n = 573), and Topo (n = 199) was 18%. 9%, and 9%, respectively, with spleen rates among children of 79%, 10%, and 27%. Infected patients among those screened formed a study population of 64 subjects eligible for a 28-day in vivo test of resistance to chloroquine. Sixty-three patients successfully completed the test; 45 males and 18 females 1-60 years of age, of whom 29 were Javanese transmigrants of five years residence in Irian Jaya and 34 were native to Irian Jaya. The seven-day day cumulative incidence of therapeutic failure for P. vivax and P. falciparum was 15% (n = 34) and 30% (n = 37). The 14- and 28-day estimates of cumulative incidence were 45% and 64% for P. vivax and 58% and 89% for P. falciparum. Almost all recurrences appeared in the face of ordinarily effective levels of chloroquine and its major metabolite, desethylchloroquine, in whole blood (> or = 100 ng/ml). Four infections by P. malariae in subjects enrolled in this study cleared by day 2 and none reappeared within 28 days. Chloroquine no longer provides effective therapy for falciparum or vivax malaria along the northern coast of Irian Jaya, Indonesia.

  7. MOLECULAR SURVEILLANCE OF Plasmodium vivax AND Plasmodium falciparum DHFR MUTATIONS IN ISOLATES FROM SOUTHERN IRAN.

    Science.gov (United States)

    Sharifi-Sarasiabi, Khojasteh; Haghighi, Ali; Kazemi, Bahram; Taghipour, Niloofar; Mojarad, Ehsan Nazemalhosseini; Gachkar, Latif

    2016-01-01

    In Iran, both Plasmodium vivax and P. falciparum malaria have been detected, but P. vivax is the predominant species. Point mutations in dihydrofolate reductase (dhfr) gene in both Plasmodia are the major mechanisms of pyrimethamine resistance. From April 2007 to June 2009, a total of 134 blood samples in two endemic areas of southern Iran were collected from patients infected with P. vivax and P. falciparum. The isolates were analyzed for P. vivax dihydrofolate reductase (pvdhfr) and P. falciparum dihydrofolate reductase (pfdhfr) point mutations using various PCR-based methods. The majority of the isolates (72.9%) had wild type amino acids at five codons of pvdhfr. Amongst mutant isolates, the most common pvdhfr alleles were double mutant in 58 and 117 amino acids (58R-117N). Triple mutation in 57, 58, and 117 amino acids (57L/58R/117N) was identified for the first time in the pvdhfr gene of Iranian P. vivax isolates. All the P. falciparumsamples analyzed (n = 16) possessed a double mutant pfdhfrallele (59R/108N) and retained a wild-type mutation at position 51. This may be attributed to the fact that the falciparum malaria patients were treated using sulfadoxine-pyrimethamine (SP) in Iran. The presence of mutant haplotypes in P. vivax is worrying, but has not yet reached an alarming threshold regarding drugs such as SP. The results of this study reinforce the importance of performing a molecular surveillance by means of a continuous chemoresistance assessment.

  8. Deaths due to Plasmodium knowlesi malaria in Sabah, Malaysia: association with reporting as Plasmodium malariae and delayed parenteral artesunate

    Directory of Open Access Journals (Sweden)

    Rajahram Giri S

    2012-08-01

    Full Text Available Abstract Background The simian parasite Plasmodium knowlesi is recognized as a common cause of severe and fatal human malaria in Sabah, Malaysia, but is morphologically indistinguishable from and still commonly reported as Plasmodium malariae, despite the paucity of this species in Sabah. Since December 2008 Sabah Department of Health has recommended intravenous artesunate and referral to a general hospital for all severe malaria cases of any species. This paper reviews all malaria deaths in Sabah subsequent to the introduction of these measures. Reporting of malaria deaths in Malaysia is mandatory. Methods Details of reported malaria deaths during 2010-2011 were reviewed to determine the proportion of each Plasmodium species. Demographics, clinical presentations and management of severe malaria caused by each species were compared. Results Fourteen malaria deaths were reported, comprising seven Plasmodium falciparum, six P. knowlesi and one Plasmodium vivax (all PCR-confirmed. Of the six P. knowlesi deaths, five were attributable to knowlesi malaria and one was attributable to P. knowlesi-associated enterobacter sepsis. Patients with directly attributable P. knowlesi deaths (N = 5 were older than those with P. falciparum (median age 51 [IQR 50-65] vs 22 [IQR 9-55] years, p = 0.06. Complications in fatal P. knowlesi included respiratory distress (N = 5, 100%, hypotension (N = 4, 80%, and renal failure (N = 4, 80%. All patients with P. knowlesi were reported as P. malariae by microscopy. Only two of five patients with severe knowlesi malaria on presentation received immediate parenteral anti-malarial treatment. The patient with P. vivax-associated severe illness did not receive parenteral treatment. In contrast six of seven patients with severe falciparum malaria received immediate parenteral treatment. Conclusion Plasmodium knowlesi was responsible, either directly or through gram-negative bacteraemia, for almost half of

  9. Predictions of avian Plasmodium expansion under climate change

    Science.gov (United States)

    Loiseau, Claire; Harrigan, Ryan J.; Bichet, Coraline; Julliard, Romain; Garnier, Stéphane; Lendvai, Ádám Z.; Chastel, Olivier; Sorci, Gabriele

    2013-01-01

    Vector-borne diseases are particularly responsive to changing environmental conditions. Diurnal temperature variation has been identified as a particularly important factor for the development of malaria parasites within vectors. Here, we conducted a survey across France, screening populations of the house sparrow (Passer domesticus) for malaria (Plasmodium relictum). We investigated whether variation in remotely-sensed environmental variables accounted for the spatial variation observed in prevalence and parasitemia. While prevalence was highly correlated to diurnal temperature range and other measures of temperature variation, environmental conditions could not predict spatial variation in parasitemia. Based on our empirical data, we mapped malaria distribution under climate change scenarios and predicted that Plasmodium occurrence will spread to regions in northern France, and that prevalence levels are likely to increase in locations where transmission already occurs. Our findings, based on remote sensing tools coupled with empirical data suggest that climatic change will significantly alter transmission of malaria parasites. PMID:23350033

  10. Plasmodium vivax vaccine research - we've only just begun.

    Science.gov (United States)

    Tham, Wai-Hong; Beeson, James G; Rayner, Julian C

    2017-02-01

    Plasmodium vivax parasites cause the majority of malaria cases outside Africa, and are increasingly being acknowledged as a cause of severe disease. The unique attributes of P. vivax biology, particularly the capacity of the dormant liver stage, the hypnozoite, to maintain blood-stage infections even in the absence of active transmission, make blood-stage vaccines particularly attractive for this species. However, P. vivax vaccine development remains resolutely in first gear, with only a single blood-stage candidate having been evaluated in any depth. Experience with Plasmodium falciparum suggests that a much broader search for new candidates and a deeper understanding of high priority targets will be required to make significant advances. This review discusses some of the particular challenges of P. vivax blood-stage vaccine development, highlighting both recent advances and key remaining barriers to overcome in order to move development forward.

  11. Plasmodium vivax Landscape in Brazil: Scenario and Challenges.

    Science.gov (United States)

    Siqueira, Andre M; Mesones-Lapouble, Oscar; Marchesini, Paola; Sampaio, Vanderson de Souza; Brasil, Patricia; Tauil, Pedro L; Fontes, Cor Jesus; Costa, Fabio T M; Daniel-Ribeiro, Cláudio Tadeu; Lacerda, Marcus V G; Damasceno, Camila P; Santelli, Ana Carolina S

    2016-12-28

    Brazil is the largest country of Latin America, with a considerable portion of its territoritory within the malaria-endemic Amazon region in the North. Furthermore, a considerable portion of its territory is located within the Amazon region in the north. As a result, Brazil has reported half of the total malaria cases in the Americas in the last four decades. Recent progress in malaria control has been accompanied by an increasing proportion of Plasmodium vivax, underscoring a need for a better understanding of management and control of this species and associated challenges. Among these challenges, the contribution of vivax malaria relapses, earlier production of gametocytes (compared with Plasmodium falciparum), inexistent methods to diagnose hypnozoite carriers, and decreasing efficacy of available antimalarials need to be addressed. Innovative tools, strategies, and technologies are needed to achieve further progress toward sustainable malaria elimination. Further difficulties also arise from dealing with the inherent socioeconomic and environmental particularities of the Amazon region and its dynamic changes.

  12. Imaging Plasmodium immunobiology in the liver, brain, and lung.

    Science.gov (United States)

    Frevert, Ute; Nacer, Adéla; Cabrera, Mynthia; Movila, Alexandru; Leberl, Maike

    2014-02-01

    Plasmodium falciparum malaria is responsible for the deaths of over half a million African children annually. Until a decade ago, dynamic analysis of the malaria parasite was limited to in vitro systems with the typical limitations associated with 2D monocultures or entirely artificial surfaces. Due to extremely low parasite densities, the liver was considered a black box in terms of Plasmodium sporozoite invasion, liver stage development, and merozoite release into the blood. Further, nothing was known about the behavior of blood stage parasites in organs such as the brain where clinical signs manifest and the ensuing immune response of the host that may ultimately result in a fatal outcome. The advent of fluorescent parasites, advances in imaging technology, and availability of an ever-increasing number of cellular and molecular probes have helped illuminate many steps along the pathogenetic cascade of this deadly tropical parasite. © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. Imaging Plasmodium Immunobiology in Liver, Brain, and Lung

    Science.gov (United States)

    Frevert, Ute; Nacer, Adéla; Cabrera, Mynthia; Movila, Alexandru; Leberl, Maike

    2013-01-01

    Plasmodium falciparum malaria is responsible for the deaths of over half a million African children annually. Until a decade ago, dynamic analysis of the malaria parasite was limited to in vitro systems with the typical limitations associated with 2D monocultures or entirely artificial surfaces. Due to extremely low parasite densities, the liver was considered a black box in terms of Plasmodium sporozoite invasion, liver stage development, and merozoite release into the blood. Further, nothing was known about the behavior of blood stage parasites in organs such as brain where clinical signs manifest and the ensuing immune response of the host that may ultimately result in a fatal outcome. The advent of fluorescent parasites, advances in imaging technology, and availability of an ever-increasing number of cellular and molecular probes have helped illuminate many steps along the pathogenetic cascade of this deadly tropical parasite. PMID:24076429

  14. [Plasmodium falciparum malaria: epidemiology and clinical features at Tarapoto Hospital].

    Science.gov (United States)

    Calderon, J; Rodriguez, J; Romero, D

    1997-01-01

    A retrospective study was conducted of the clinical records of 41 patients discharged from a hospital in Tarapoto, Peru, between August 1992 and June 1996 following treatment for Plasmodium falciparum malaria. Patients ranged in age from 18 to 65 years; 25 were male. The cases were uniformly distributed throughout the year. The duration of illness averaged 11 days. At admission, 40 patients had fever, 36 had shaking chills, 29 had headache, 21 had nausea and vomiting, 21 had hyporexia, 15 had pallor, and 13 had splenomegaly. 3 of the 16 women were pregnant. 7 patients reported a history of malaria. The admission diagnosis was malaria in 33 cases. 31 patients were treated with chloroquine; 18 were subsequently treated with pyrimethamine-sulfadoxin and 1 received doxycycline. No cases of grave illness or death occurred. The increasing presence of Plasmodium falciparum malaria in the Peruvian lowlands should promote review of the adequacy of control programs.

  15. Driving mosquito refractoriness to Plasmodium falciparum with engineered symbiotic bacteria.

    Science.gov (United States)

    Wang, Sibao; Dos-Santos, André L A; Huang, Wei; Liu, Kun Connie; Oshaghi, Mohammad Ali; Wei, Ge; Agre, Peter; Jacobs-Lorena, Marcelo

    2017-09-29

    The huge burden of malaria in developing countries urgently demands the development of novel approaches to fight this deadly disease. Although engineered symbiotic bacteria have been shown to render mosquitoes resistant to the parasite, the challenge remains to effectively introduce such bacteria into mosquito populations. We describe a Serratia bacterium strain (AS1) isolated from Anopheles ovaries that stably colonizes the mosquito midgut, female ovaries, and male accessory glands and spreads rapidly throughout mosquito populations. Serratia AS1 was genetically engineered for secretion of anti-Plasmodium effector proteins, and the recombinant strains inhibit development of Plasmodium falciparum in mosquitoes. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  16. Mosquito Vectors and the Globalization of Plasmodium falciparum Malaria.

    Science.gov (United States)

    Molina-Cruz, Alvaro; Zilversmit, Martine M; Neafsey, Daniel E; Hartl, Daniel L; Barillas-Mury, Carolina

    2016-11-23

    Plasmodium falciparum malaria remains a devastating public health problem. Recent discoveries have shed light on the origin and evolution of Plasmodium parasites and their interactions with their vertebrate and mosquito hosts. P. falciparum malaria originated in Africa from a single horizontal transfer between an infected gorilla and a human, and became global as the result of human migration. Today, P. falciparum malaria is transmitted worldwide by more than 70 different anopheline mosquito species. Recent studies indicate that the mosquito immune system can be a barrier to malaria transmission and that the P. falciparum Pfs47 gene allows the parasite to evade mosquito immune detection. Here, we review the origin and globalization of P. falciparum and integrate this history with analysis of the biology, evolution, and dispersal of the main mosquito vectors. This new perspective broadens our understanding of P. falciparum population structure and the dispersal of important parasite genetic traits.

  17. RIFINs are adhesins implicated in severe Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Goel, Suchi; Palmkvist, Mia; Moll, Kirsten

    2015-01-01

    Rosetting is a virulent Plasmodium falciparum phenomenon associated with severe malaria. Here we demonstrate that P. falciparum–encoded repetitive interspersed families of polypeptides (RIFINs) are expressed on the surface of infected red blood cells (iRBCs), where they bind to RBCs—preferentiall......Rosetting is a virulent Plasmodium falciparum phenomenon associated with severe malaria. Here we demonstrate that P. falciparum–encoded repetitive interspersed families of polypeptides (RIFINs) are expressed on the surface of infected red blood cells (iRBCs), where they bind to RBCs......—preferentially of blood group A—to form large rosettes and mediate microvascular binding of iRBCs. We suggest that RIFINs have a fundamental role in the development of severe malaria and thereby contribute to the varying global distribution of ABO blood groups in the human population....

  18. Peptide Inhibition of Topoisomerase IB from Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Amit Roy

    2011-01-01

    Full Text Available Control of diseases inflicted by protozoan parasites such as Leishmania, Trypanosoma, and Plasmodium, which pose a serious threat to human health worldwide, depends on a rather small number of antiparasite drugs, of which many are toxic and/or inefficient. Moreover, the increasing occurrence of drug-resistant parasites emphasizes the need for new and effective antiprotozoan drugs. In the current study, we describe a synthetic peptide, WRWYCRCK, with inhibitory effect on the essential enzyme topoisomerase I from the malaria-causing parasite Plasmodium falciparum. The peptide inhibits specifically the transition from noncovalent to covalent DNA binding of P. falciparum topoisomerase I, while it does not affect the ligation step of catalysis. A mechanistic explanation for this inhibition is provided by molecular docking analyses. Taken together the presented results suggest that synthetic peptides may represent a new class of potential antiprotozoan drugs.

  19. Transactions on Petri Nets and Other Models of Concurrency VI

    DEFF Research Database (Denmark)

    The sixth volume of ToPNoC includes revised versions of selected papers from workshops and tutorials held at the 32nd International Conference on Application and Theory of Petri Nets and Concurrency. It also contains a special section on Networks, Protocols, and Services, as well as a contributed...... paper submitted through the regular submission track of ToPNoC. The 14 papers cover a diverse range of topics including model checking and system verification, synthesis, foundational work on specific classes of Petri nets, and innovative applications of Petri nets and other models of concurrency. Thus...... this volume gives a good view of ongoing concurrent systems and Petri nets research....

  20. Computational simulation of concurrent engineering for aerospace propulsion systems

    Science.gov (United States)

    Chamis, C. C.; Singhal, S. N.

    1992-01-01

    Results are summarized of an investigation to assess the infrastructure available and the technology readiness in order to develop computational simulation methods/software for concurrent engineering. These results demonstrate that development of computational simulations methods for concurrent engineering is timely. Extensive infrastructure, in terms of multi-discipline simulation, component-specific simulation, system simulators, fabrication process simulation, and simulation of uncertainties - fundamental in developing such methods, is available. An approach is recommended which can be used to develop computational simulation methods for concurrent engineering for propulsion systems and systems in general. Benefits and facets needing early attention in the development are outlined.

  1. Computational simulation for concurrent engineering of aerospace propulsion systems

    Science.gov (United States)

    Chamis, C. C.; Singhal, S. N.

    1993-01-01

    Results are summarized for an investigation to assess the infrastructure available and the technology readiness in order to develop computational simulation methods/software for concurrent engineering. These results demonstrate that development of computational simulation methods for concurrent engineering is timely. Extensive infrastructure, in terms of multi-discipline simulation, component-specific simulation, system simulators, fabrication process simulation, and simulation of uncertainties--fundamental to develop such methods, is available. An approach is recommended which can be used to develop computational simulation methods for concurrent engineering of propulsion systems and systems in general. Benefits and issues needing early attention in the development are outlined.

  2. Parasite virulence and disease severity in Plasmodium falciparum malaria.

    OpenAIRE

    Ribacke, Ulf

    2009-01-01

    Malaria stands out as one of the most important infectious diseases and one of the world s leading causes of death. Plasmodium falciparum is the parasite responsible for the great majority of severe disease syndromes and mortality, and affects mainly children and pregnant women. Despite intensive research efforts, the understanding of P. falciparum virulence is limited. Infections with the parasite cause everything from asymptomatic parasitemia to severe disease and death, a...

  3. Surface antigens and virulence in Plasmodium falciparum malaria

    OpenAIRE

    Normark, Johan

    2008-01-01

    Plasmodium falciparum is an intracellular protozoan that may cause severe forms of malaria. It is a major world health hazard and reaps the highest toll among the children and pregnant mothers of the developing world. An Anopheles mosquito vector injects the pathogen when taking a blood meal. After multiplication in cells of the liver, the parasite escapes and infects red blood cells in a cyclic manner and this is when the clinical manifestations of malaria as a disease beco...

  4. Cryo scanning electron microscopy of Plasmodium falciparum-infected erythrocytes

    DEFF Research Database (Denmark)

    Hempel, Casper

    2017-01-01

    Plasmodium falciparum invades erythrocytes as an essential part of their life cycle. While living inside erythrocytes, the parasite remodels the cell's intracellular organization as well as its outer surface. Late trophozoite-stage parasites and schizonts introduce numerous small protrusions on t...... microscopy under cryogenic conditions allowing for high resolution and magnification of erythrocytes. This novel technique can be used for precise estimates of knob density and for studies on cytoadhesion....

  5. Plasmodium vivax Landscape in Brazil: Scenario and Challenges

    OpenAIRE

    Siqueira, Andre M.; Mesones-Lapouble, Oscar; Marchesini, Paola; Sampaio, Vanderson Souza; Brasil, Patricia; Tauil, Pedro L; Fontes, Cor Jesus; COSTA, Fabio T. M.; Daniel-Ribeiro, Cláudio Tadeu; Lacerda, Marcus V. G.; Damasceno, Camila P.; Santelli, Ana Carolina S.

    2016-01-01

    Brazil is the largest country of Latin America, with a considerable portion of its territoritory within the malaria-endemic Amazon region in the North. Furthermore, a considerable portion of its territory is located within the Amazon region in the north. As a result, Brazil has reported half of the total malaria cases in the Americas in the last four decades. Recent progress in malaria control has been accompanied by an increasing proportion of Plasmodium vivax, underscoring a need for a bett...

  6. Genes for Glycosylphosphatidylinositol Toxin Biosynthesis in Plasmodium falciparum

    OpenAIRE

    Delorenzi, Mauro; Sexton, Adrienne; Shams-Eldin, Hosam; Schwarz, Ralph T.; Speed, Terry; Schofield, Louis

    2002-01-01

    About 2.5 million people die of Plasmodium falciparum malaria every year. Fatalities are associated with systemic and organ-specific inflammation initiated by a parasite toxin. Recent studies show that glycosylphosphatidylinositol (GPI) functions as the dominant parasite toxin in the context of infection. GPIs also serve as membrane anchors for several of the most important surface antigens of parasite invasive stages. GPI anchoring is a complex posttranslational modification produced through...

  7. Structure of Plasmodium falciparum ADP-ribosylation factor 1

    Energy Technology Data Exchange (ETDEWEB)

    Cook, William J.; Smith, Craig D.; Senkovich, Olga; Holder, Anthony A.; Chattopadhyay, Debasish (UAB); (NIMR)

    2011-09-26

    Vesicular trafficking may play a crucial role in the pathogenesis and survival of the malaria parasite. ADP-ribosylation factors (ARFs) are among the major components of vesicular trafficking pathways in eukaryotes. The crystal structure of ARF1 GTPase from Plasmodium falciparum has been determined in the GDP-bound conformation at 2.5 {angstrom} resolution and is compared with the structures of mammalian ARF1s.

  8. Using Click Chemistry to Identify Potential Drug Targets in Plasmodium

    Science.gov (United States)

    2016-06-01

    both enzymes are expressed cytoplasmically in sporozoites and liver stages. Using a specific and potent inhibitor of Plasmodium PKG and inhibitor... originally planned. Therefore, we modified our approach so that we could still fulfill the objective of identifying Tsp’s target in sporozoites. To fulfill...essential Ca(2)(+) signals at key decision points in the life cycle of malaria parasites. PLoS Biol 12: e1001806. 2. Falae A, Combe A, Amaladoss A

  9. CRISPR-mediated genome editing of Plasmodium falciparum malaria parasites.

    Science.gov (United States)

    Lee, Marcus Cs; Fidock, David A

    2014-01-01

    The development of the CRISPR-Cas system is revolutionizing genome editing in a variety of organisms. The system has now been used to manipulate the genome of Plasmodium falciparum, the most lethal malaria-causing species. The ability to generate gene deletions or nucleotide substitutions rapidly and economically promises to accelerate the analysis of novel drug targets and to help elucidate the function of specific genes or gene families, while complementing genome-wide association studies.

  10. Editing the Plasmodium vivax Genome, Using Zinc-Finger Nucleases

    OpenAIRE

    Moraes Barros, Roberto R.; Straimer, Judith; Sa, Juliana M; Salzman, Rebecca E.; Melendez-Muniz, Viviana A.; Mu, Jianbing; David A Fidock; Thomas E. Wellems

    2014-01-01

    Plasmodium vivax is a major cause of malaria morbidity worldwide yet has remained genetically intractable. To stably modify this organism, we used zinc-finger nucleases (ZFNs), which take advantage of homology-directed DNA repair mechanisms at the site of nuclease action. Using ZFNs specific to the gene encoding P. vivax dihydrofolate reductase (pvdhfr), we transfected blood specimens from Saimiri boliviensis monkeys infected with the pyrimethamine (Pyr)–susceptible Chesson strain with a ZFN ...

  11. CRISPR-mediated genome editing of Plasmodium falciparum malaria parasites

    OpenAIRE

    Lee, Marcus CS; David A Fidock

    2014-01-01

    The development of the CRISPR-Cas system is revolutionizing genome editing in a variety of organisms. The system has now been used to manipulate the genome of Plasmodium falciparum, the most lethal malaria-causing species. The ability to generate gene deletions or nucleotide substitutions rapidly and economically promises to accelerate the analysis of novel drug targets and to help elucidate the function of specific genes or gene families, while complementing genome-wide association studies.

  12. Artesunate plus pyronaridine for treating uncomplicated Plasmodium falciparum malaria

    OpenAIRE

    Bukirwa, Hasifa; Unnikrishnan, B; Kramer, Christine V; Sinclair, David; Nair, Suma; Tharyan, Prathap

    2014-01-01

    Background The World Health Organization (WHO) recommends that people with uncomplicated Plasmodium falciparum malaria are treated using Artemisinin-based Combination Therapy (ACT). ACT combines three-days of a short-acting artemisinin derivative with a longer-acting antimalarial which has a different mode of action. Pyronaridine has been reported as an effective antimalarial over two decades of use in parts of Asia, and is currently being evaluated as a partner drug for artesunate. Objective...

  13. Subinoculation as a technique in the diagnosis of avian plasmodium

    Science.gov (United States)

    Herman, C.M.; Knisley, J.O.; Snyder, E.L.

    1966-01-01

    In two successive years, 1964 and 1965, blood subinoculated from wild Canada geese, negative for Plasmodium by examination of peripheral blood smears, into 5-day-old domestic geese produced 60 % infection in the recipients. Prepatent and patent periods, as well as intensity of parasitemia showed much variation. Intramuscular inoculation produced the same prevalence as the intravenous route, but longer prepatent periods and less intensity of parasitemia.

  14. Antimalarial activity of Malaysian Plectranthus amboinicus against Plasmodium berghei

    OpenAIRE

    Norazsida Ramli; Pakeer Oothuman Syed Ahamed; Hassan Mohamed Elhady; Muhammad Taher

    2014-01-01

    Context: Malaria is a mosquito-borne disease caused by parasitic protozoa from the genus of Plasmodium. The protozoans have developed resistance against many of current drugs. It is urgent to find an alternative source of new antimalarial agent. In the effort to discover new antimalarial agents, this research has been conducted on Plectranthus amboinicus. Aims: This study was conducted to evaluate the toxicity and antiplasmodial properties of P. amboinicus. Materials and Methods: Acute oral t...

  15. Insulin reduces the requirement for serum in Plasmodium falciparum culture

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Tosta

    1984-03-01

    Full Text Available Insulin added to Plasmodium falciparum cultures (0.2 IU/ml reduced the requirement for human serum from ten to five percent. This represents an obvious advantage by its serum-sparing effect and by reducing the chances of using contaminated serum in cultures. The growth-promoting ability of insulin was observed eitherin culture- adapted P. falciparum or in newly-isolated samples.

  16. World Malaria Report: time to acknowledge Plasmodium knowlesi malaria.

    Science.gov (United States)

    Barber, Bridget E; Rajahram, Giri S; Grigg, Matthew J; William, Timothy; Anstey, Nicholas M

    2017-03-31

    The 2016 World Health Organization (WHO) World Malaria Report documents substantial progress towards control and elimination of malaria. However, major challenges remain. In some regions of Southeast Asia, the simian parasite Plasmodium knowlesi has emerged as an important cause of human malaria, and the authors believe this species warrants regular inclusion in the World Malaria Report. Plasmodium knowlesi is the most common cause of malaria in Malaysia, and cases have also been reported in nearly all countries of Southeast Asia. Outside of Malaysia, P. knowlesi is frequently misdiagnosed by microscopy as Plasmodium falciparum or Plasmodium vivax. Thus, P. knowlesi may be underdiagnosed in affected regions and its true incidence underestimated. Acknowledgement in the World Malaria Report of the regional importance of P. knowlesi will facilitate efforts to improve surveillance of this emerging parasite. Furthermore, increased recognition will likely lead to improved delivery of effective treatment for this potentially fatal infection, as has occurred in Malaysia where P. knowlesi case-fatality rates have fallen despite rising incidence. In a number of knowlesi-endemic countries, substantial progress has been made towards the elimination of P. vivax and P. falciparum. However, efforts to eliminate these human-only species should not preclude efforts to reduce human malaria from P. knowlesi. The regional importance of knowlesi malaria was recognized by the WHO with its recent Evidence Review Group meeting on knowlesi malaria to address strategies for prevention and mitigation. The WHO World Malaria Report has an appropriate focus on falciparum and vivax malaria, the major causes of global mortality and morbidity. However, the authors hope that in future years this important publication will also incorporate data on the progress and challenges in reducing knowlesi malaria in regions where transmission occurs.

  17. Aislamiento y mantenimiento in vitro de Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Blanca Pardave L

    1997-07-01

    Full Text Available Se aislaron 08 cepas de Plasmodium falciparum a partir de 10 pacientes. Luego fueron adaptadas y mantenidas en cultivo in vitro durante 60 días en eritrocitos humanos grupo O, en medio RPMI 1640 enriquecido con plasma humano grupo O, bajo una atmósfera de 5% de CO2, 5% de O2 y 90% de Nitrógeno y luego preservados a -70ºC.

  18. Plasmodium serine hydroxymethyltransferase: indispensability and display of distinct localization

    Directory of Open Access Journals (Sweden)

    Pornthanakasem Wichai

    2012-11-01

    Full Text Available Abstract Background Serine hydroxymethyltransferase (SHMT, a pyridoxal phosphate-dependent enzyme, plays a vital role in the de novo pyrimidine biosynthesis pathway in malaria parasites. Two genes have been identified in Plasmodium spp. encoding a cytosolic SHMT (cSHMT and putative mitochondria SHMT (mSHMT, but their roles have not been fully investigated. Methods The presence of Plasmodium SHMT isoforms in the intra-erythrocytic stage was assessed based on their gene expression using reverse transcription PCR (RT-PCR. Localization studies of Plasmodium SHMT isoforms were performed by transfection of fluorescent-tagged gene constructs into P. falciparum and expressions of fluorescent fusion proteins in parasites were observed using a laser scanning confocal microscope. Genetic targeting through homologous recombination was used to study the essentiality of SHMT in Plasmodium spp. Results Semi-quantitative RT-PCR revealed the expression of these two genes throughout intra-erythrocytic development. Localization studies using P. falciparum expressing fluorescent-tagged SHMT showed that PfcSHMT-red fluorescent fusion protein (PfcSHMT-DsRed is localized in the cytoplasm, while PfmSHMT-green fluorescent fusion protein (PfmSHMT-GFP co-localized with Mitotracker™-labelled mitochondria as predicted. The essentiality of plasmodial cSHMT was inferred from transfection experiments where recovery of viable knock-out parasites was not achieved, unless complemented with a functional equivalent copy of shmt. Conclusions Distinct compartment localizations of PfSHMT were observed between cytoplasmic and mitochondrial isoforms, and evidence was provided for the indispensable role of plasmodial cSHMT indicating it as a valid target for development of novel anti-malarials.

  19. Plasmodium activates the innate immune response of Anopheles gambiae mosquitoes.

    OpenAIRE

    Richman, A M; Dimopoulos, G; Seeley, D; Kafatos, F C

    1997-01-01

    Innate immune-related gene expression in the major disease vector mosquito Anopheles gambiae has been analyzed following infection by the malaria parasite, Plasmodium berghei. Substantially increased levels of mRNAs encoding the antibacterial peptide defensin and a putative Gram-negative bacteria-binding protein (GNBP) are observed 20-30 h after ingestion of an infected blood-meal, at a time which indicates that this induction is a response to parasite invasion of the midgut epithelium. The i...

  20. Caspar controls resistance to Plasmodium falciparum in diverse anopheline species.

    OpenAIRE

    Garver, Lindsey S.; Yuemei Dong; George Dimopoulos

    2009-01-01

    Immune responses mounted by the malaria vector Anopheles gambiae are largely regulated by the Toll and Imd (immune deficiency) pathways via the NF-kappaB transcription factors Rel1 and Rel2, which are controlled by the negative regulators Cactus and Caspar, respectively. Rel1- and Rel2-dependent transcription in A. gambiae has been shown to be particularly critical to the mosquito's ability to manage infection with the rodent malaria parasite Plasmodium berghei. Using RNA interference to depl...

  1. Myocarditis associated with Plasmodium vivax malaria: a case report

    Directory of Open Access Journals (Sweden)

    Ana Maria Revoredo da Silva Ventura

    2014-12-01

    Full Text Available Malaria remains a major public health problem in Brazil where Plasmodium vivax is the predominant species, responsible for 82% of registered cases in 2013. Though benign, P. vivax infection may sometimes evolve with complications and a fatal outcome. Here, we report a severe case of P. vivax malaria in a 35-year-old Brazilian man from a malaria endemic area, who presented with reversible myocarditis.

  2. Malaria risk factor assessment using active and passive surveillance data from Aceh Besar, Indonesia, a low endemic, malaria elimination setting with Plasmodium knowlesi, Plasmodium vivax, and Plasmodium falciparum.

    Science.gov (United States)

    Herdiana, Herdiana; Cotter, Chris; Coutrier, Farah N; Zarlinda, Iska; Zelman, Brittany W; Tirta, Yusrifar Kharisma; Greenhouse, Bryan; Gosling, Roly D; Baker, Peter; Whittaker, Maxine; Hsiang, Michelle S

    2016-09-13

    As malaria transmission declines, it becomes more geographically focused and more likely due to asymptomatic and non-falciparum infections. To inform malaria elimination planning in the context of this changing epidemiology, local assessments on the risk factors for malaria infection are necessary, yet challenging due to the low number of malaria cases. A population-based, cross-sectional study was performed using passive and active surveillance data collected in Aceh Besar District, Indonesia from 2014 to 2015. Malaria infection was defined as symptomatic polymerase chain reaction (PCR)-confirmed infection in index cases reported from health facilities, and asymptomatic or symptomatic PCR-confirmed infection identified in reactive case detection (RACD). Potential risk factors for any infection, species-specific infection, or secondary-case detection in RACD were assessed through questionnaires and evaluated for associations. Nineteen Plasmodium knowlesi, 12 Plasmodium vivax and six Plasmodium falciparum cases were identified passively, and 1495 community members screened in RACD, of which six secondary cases were detected (one P. knowlesi, three P. vivax, and two P. falciparum, with four being asymptomatic). Compared to non-infected subjects screened in RACD, cases identified through passive or active surveillance were more likely to be male (AOR 12.5, 95 % CI 3.0-52.1), adult (AOR 14.0, 95 % CI 2.2-89.6 for age 16-45 years compared to malaria infection in index and RACD identified cases was associated with forest exposure, particularly overnights in the forest for work. In low-transmission settings, utilization of data available through routine passive and active surveillance can support efforts to target individuals at high risk.

  3. Interleukin-10 regulates hepcidin in Plasmodium falciparum malaria

    KAUST Repository

    Huang, Honglei

    2014-02-10

    Background: Acute malarial anemia remains a major public health problem. Hepcidin, the major hormone controlling the availability of iron, is raised during acute and asymptomatic parasitemia. Understanding the role and mechanism of raised hepcidin and so reduced iron availability during infection is critical to establish evidence-based guidelines for management of malaria anemia. Our recent clinical evidence suggests a potential role of IL-10 in the regulation of hepcidin in patients with acute P. falciparum malaria. Methods: We have measured secretion of hepcidin by primary macrophages and the hepatoma cell line HepG2 stimulated with IL-10, IL-6 and Plasmodium falciparum-infected erythrocytes. Findings: We have observed that IL-10 and IL-6 production increased in primary macrophages when these cells were co-cultured with Plasmodium falciparum-infected erythrocytes. We found that IL-10 induced hepcidin secretion in primary macrophages in a dose-dependent manner but not in HepG2 cells. These effects were mediated through signal transducer and activator of transcription (STAT) 3-phosphorylation and completely abrogated by a specific STAT3 inhibitor. Conclusion: IL-10 can directly regulate hepcidin in primary macrophages but not in HepG2 cells. This effect can be modulated by Plasmodium falciparum. The results are consistent with a role for IL-10 in modulating iron metabolism during acute phase of infection. 2014 Huang et al.

  4. Targeting Plasmodium PI(4)K to eliminate malaria

    Science.gov (United States)

    McNamara, Case W.; Lee, Marcus C. S.; Lim, Chek Shik; Lim, Siau Hoi; Roland, Jason; Nagle, Advait; Simon, Oliver; Yeung, Bryan K. S.; Chatterjee, Arnab K.; McCormack, Susan L.; Manary, Micah J.; Zeeman, Anne-Marie; Dechering, Koen J.; Kumar, T. R. Santha; Henrich, Philipp P.; Gagaring, Kerstin; Ibanez, Maureen; Kato, Nobutaka; Kuhen, Kelli L.; Fischli, Christoph; Rottmann, Matthias; Plouffe, David M.; Bursulaya, Badry; Meister, Stephan; Rameh, Lucia; Trappe, Joerg; Haasen, Dorothea; Timmerman, Martijn; Sauerwein, Robert W.; Suwanarusk, Rossarin; Russell, Bruce; Renia, Laurent; Nosten, Francois; Tully, David C.; Kocken, Clemens H. M.; Glynne, Richard J.; Bodenreider, Christophe; Fidock, David A.; Diagana, Thierry T.; Winzeler, Elizabeth A.

    2013-12-01

    Achieving the goal of malaria elimination will depend on targeting Plasmodium pathways essential across all life stages. Here we identify a lipid kinase, phosphatidylinositol-4-OH kinase (PI(4)K), as the target of imidazopyrazines, a new antimalarial compound class that inhibits the intracellular development of multiple Plasmodium species at each stage of infection in the vertebrate host. Imidazopyrazines demonstrate potent preventive, therapeutic, and transmission-blocking activity in rodent malaria models, are active against blood-stage field isolates of the major human pathogens P. falciparum and P. vivax, and inhibit liver-stage hypnozoites in the simian parasite P. cynomolgi. We show that imidazopyrazines exert their effect through inhibitory interaction with the ATP-binding pocket of PI(4)K, altering the intracellular distribution of phosphatidylinositol-4-phosphate. Collectively, our data define PI(4)K as a key Plasmodium vulnerability, opening up new avenues of target-based discovery to identify drugs with an ideal activity profile for the prevention, treatment and elimination of malaria.

  5. [Therapeutic response of Plasmodium vivax to chloroquine in Bolivia].

    Science.gov (United States)

    Añez, Arletta; Navarro-Costa, Dennis; Yucra, Omar; Garnica, Cecilia; Melgar, Viviana; Moscoso, Manuel; Arteaga, Ricardo; Nakao, Gladys

    2012-01-01

    Knowledge of the therapeutic efficacy of chloroquine for Plasmodium vivax infections improves the capacity for surveillance of anti-malarial drug resistance. The therapeutic efficacy of chloroquine as treatment was evaluated for uncomplicated Plasmodium vivax malaria in Bolivia. An in vivo efficacy study of chloroquine was undertaken in three regions of Bolivia--Riberalta, Guayaramerín and Yacuiba. Two hundred and twenty-three patients (84, 80, and 59 in the three regions, respectively) aged over 5 years old were administered with chloroquine (25 mg/kg/three days) and followed for 28 days. Blood levels of chloroquine and desethylchloroquine were measured on day 2 and on the day of reappearance of parasitemia. The cumulative incidence of treatment failure was calculated using the Kaplan and Meier survival analysis. The mean parasitemias (asexual) on day 0 were 6,147 parasites/μl of blood in the Riberalta population, 4,251 in Guayaramerín and 5,214 in Yacuiba. The average blood concentrations of chloroquine-desethylchloroquine during day 2 were 783, 817, and 815 ng/ml, respectively. No treatment failures were observed in Yacuiba, whereas in Riberalta and Guayaramerín, the frequencies of treatment failures were 6.2% and 10%. Blood levels of chloroquine and desethylchloroquine in patients with treatment failure showed values below 70 ng/ml on the day of reappearance of parasitemia. Resistance of Plasmodium vivax to chloroquine was not demonstrated in three regions of Bolivia.

  6. Targeting Plasmodium PI(4)K to eliminate malaria.

    Science.gov (United States)

    McNamara, Case W; Lee, Marcus C S; Lim, Chek Shik; Lim, Siau Hoi; Roland, Jason; Nagle, Advait; Simon, Oliver; Yeung, Bryan K S; Chatterjee, Arnab K; McCormack, Susan L; Manary, Micah J; Zeeman, Anne-Marie; Dechering, Koen J; Kumar, T R Santha; Henrich, Philipp P; Gagaring, Kerstin; Ibanez, Maureen; Kato, Nobutaka; Kuhen, Kelli L; Fischli, Christoph; Rottmann, Matthias; Plouffe, David M; Bursulaya, Badry; Meister, Stephan; Rameh, Lucia; Trappe, Joerg; Haasen, Dorothea; Timmerman, Martijn; Sauerwein, Robert W; Suwanarusk, Rossarin; Russell, Bruce; Renia, Laurent; Nosten, Francois; Tully, David C; Kocken, Clemens H M; Glynne, Richard J; Bodenreider, Christophe; Fidock, David A; Diagana, Thierry T; Winzeler, Elizabeth A

    2013-12-12

    Achieving the goal of malaria elimination will depend on targeting Plasmodium pathways essential across all life stages. Here we identify a lipid kinase, phosphatidylinositol-4-OH kinase (PI(4)K), as the target of imidazopyrazines, a new antimalarial compound class that inhibits the intracellular development of multiple Plasmodium species at each stage of infection in the vertebrate host. Imidazopyrazines demonstrate potent preventive, therapeutic, and transmission-blocking activity in rodent malaria models, are active against blood-stage field isolates of the major human pathogens P. falciparum and P. vivax, and inhibit liver-stage hypnozoites in the simian parasite P. cynomolgi. We show that imidazopyrazines exert their effect through inhibitory interaction with the ATP-binding pocket of PI(4)K, altering the intracellular distribution of phosphatidylinositol-4-phosphate. Collectively, our data define PI(4)K as a key Plasmodium vulnerability, opening up new avenues of target-based discovery to identify drugs with an ideal activity profile for the prevention, treatment and elimination of malaria.

  7. Role and Regulation of Glutathione Metabolism in Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Sylke Müller

    2015-06-01

    Full Text Available Malaria in humans is caused by one of five species of obligate intracellular protozoan parasites of the genus Plasmodium. P. falciparum causes the most severe disease and is responsible for 600,000 deaths annually, primarily in Sub-Saharan Africa. It has long been suggested that during their development, malaria parasites are exposed to environmental and metabolic stresses. One strategy to drug discovery was to increase these stresses by interfering with the parasites’ antioxidant and redox systems, which may be a valuable approach to disease intervention. Plasmodium possesses two redox systems—the thioredoxin and the glutathione system—with overlapping but also distinct functions. Glutathione is the most abundant low molecular weight redox active thiol in the parasites existing primarily in its reduced form representing an excellent thiol redox buffer. This allows for an efficient maintenance of the intracellular reducing environment of the parasite cytoplasm and its organelles. This review will highlight the mechanisms that are responsible for sustaining an adequate concentration of glutathione and maintaining its redox state in Plasmodium. It will provide a summary of the functions of the tripeptide and will discuss the potential of glutathione metabolism for drug discovery against human malaria parasites.

  8. Influences of intermittent preventive treatment and persistent multiclonal Plasmodium falciparum infections on clinical malaria risk.

    Directory of Open Access Journals (Sweden)

    Anne Liljander

    Full Text Available BACKGROUND: Intermittent preventive treatment (IPT of malaria involves administration of curative doses of antimalarials at specified time points to vulnerable populations in endemic areas, regardless whether a subject is known to be infected. The effect of this new intervention on the development and maintenance of protective immunity needs further understanding. We have investigated how seasonal IPT affects the genetic diversity of Plasmodium falciparum infections and the risk of subsequent clinical malaria. MATERIAL AND METHODS: The study included 2227 Ghanaian children (3-59 months who were given sulphadoxine-pyrimethamine (SP bimonthly, artesunate plus amodiaquine (AS+AQ monthly or bimonthly, or placebo monthly for six months spanning the malaria transmission season. Blood samples collected at three post-interventional surveys were analysed by genotyping of the polymorphic merozoite surface protein 2 gene. Malaria morbidity and anaemia was monitored during 12 months follow-up. RESULTS: Monthly IPT with AS+AQ resulted in a marked reduction in number of concurrent clones and only children parasite negative just after the intervention period developed clinical malaria during follow-up. In the placebo group, children without parasites as well as those infected with ≥2 clones had a reduced risk of subsequent malaria. The bimonthly SP or AS+AQ groups had similar number of clones as placebo after intervention; however, diversity and parasite negativity did not predict the risk of malaria. An interaction effect showed that multiclonal infections were only associated with protection in children without intermittent treatment. CONCLUSION: Molecular typing revealed effects of the intervention not detected by ordinary microscopy. Effective seasonal IPT temporarily reduced the prevalence and genetic diversity of P. falciparum infections. The reduced risk of malaria in children with multiclonal infections only seen in untreated children suggests that

  9. Visualizing Concurrency Control Algorithms for Real-Time Database Systems

    Directory of Open Access Journals (Sweden)

    Olusegun Folorunso

    2008-11-01

    Full Text Available This paper describes an approach to visualizing concurrency control (CC algorithms for real-time database systems (RTDBs. This approach is based on the principle of software visualization, which has been applied in related fields. The Model-View-controller (MVC architecture is used to alleviate the black box syndrome associated with the study of algorithm behaviour for RTDBs Concurrency Controls. We propose a Visualization "exploratory" tool that assists the RTDBS designer in understanding the actual behaviour of the concurrency control algorithms of choice and also in evaluating the performance quality of the algorithm. We demonstrate the feasibility of our approach using an optimistic concurrency control model as our case study. The developed tool substantiates the earlier simulation-based performance studies by exposing spikes at some points when visualized dynamically that are not observed using usual static graphs. Eventually this tool helps solve the problem of contradictory assumptions of CC in RTDBs.

  10. A case for evaluating sensor network protocols concurrently

    KAUST Repository

    Gnawali, Omprakash

    2010-01-01

    Researchers typically evaluate and compare protocols on the testbeds by running them one at a time. This methodology ignores the variation in link qualities and wireless environment across these experiments. These variations can introduce significant noise in the results. Evaluating two protocols concurrently, however, suffers from inter-protocol interactions. These interactions can perturb performance even under very light load, especially timing and timing sensitive protocols. We argue that the benefits of running protocols concurrently greatly outweigh the disadvantages. Protocols rarely run in isolation in real networks, and so considering such interactions is valuable. Although the wireless environment is still uncontrolled, concurrent evaluations make comparisons fair and more statistically sound. Through experiments on two testbeds, we make the case for evaluating and comparing low data-rate sensor network protocols by running them concurrently. Copyright 2010 ACM.

  11. Human operant learning under concurrent reinforcement of response variability

    NARCIS (Netherlands)

    Maes, J.H.R.; Goot, M.H. van der

    2006-01-01

    This study asked whether the concurrent reinforcement of behavioral variability facilitates learning to emit a difficult target response. Sixty students repeatedly pressed sequences of keys, with an originally infrequently occurring target sequence consistently being followed by positive feedback. T

  12. Prototyping of concurrent control systems implemented in FPGA devices

    CERN Document Server

    Wiśniewski, Remigiusz

    2017-01-01

    This book focuses on prototyping aspects of concurrent control systems and their further implementation and partial reconfiguration in programmable devices. Further, it lays out a full prototyping flow for concurrent control systems. Based on a given primary specification, a system is described with an interpreted Petri net, which naturally reflects the concurrent and sequential relationships of the design. The book shows that, apart from the traditional option of static configuration of the entire system, the latest programmable devices (especially FPGAs) offer far more sophistication. Partial reconfiguration allows selected parts of the system to be replaced without having to reprogram the entire structure of the device. Approaches to dynamic and static partial reconfiguration of concurrent control systems are presented and described in detail.< The theoretical work is illustrated by examples drawn from various applications, with a milling machine and a traffic-light controller highlighted as representat...

  13. Process Algebra Approach to Reasoning About Concurrent Actions

    Institute of Scientific and Technical Information of China (English)

    YuanFeng; Ming-ShengYing

    2004-01-01

    A reasonable transition rule is proposed for synchronized actions and some equational properties of bisimilarity and weak bisimilarity in the process algebra for reasoning about concurrent actions are presented.

  14. Partial Orders and Fully Abstract Models for Concurrency

    DEFF Research Database (Denmark)

    Engberg, Uffe Henrik

    1990-01-01

    In this thesis sets of labelled partial orders are employed as fundamental mathematical entities for modelling nondeterministic and concurrent processes thereby obtaining so-called noninterleaving semantics. Based on different closures of sets of labelled partial orders, simple algebraic languages...

  15. The Revised UCLA Loneliness Scale: Concurrent and Discriminant Validity Evidence.

    Science.gov (United States)

    Russell, Dan; And Others

    1980-01-01

    Two studies provide methodogical refinement in the measurement of loneliness, using a revised version of the self-report UCLA Loneliness Scale. Investigates response bias, concurrent validity, and correlated measures. (Author/SS)

  16. Finite Element Analysis in Concurrent Processing: Computational Issues

    Science.gov (United States)

    Sobieszczanski-Sobieski, Jaroslaw; Watson, Brian; Vanderplaats, Garrett

    2004-01-01

    The purpose of this research is to investigate the potential application of new methods for solving large-scale static structural problems on concurrent computers. It is well known that traditional single-processor computational speed will be limited by inherent physical limits. The only path to achieve higher computational speeds lies through concurrent processing. Traditional factorization solution methods for sparse matrices are ill suited for concurrent processing because the null entries get filled, leading to high communication and memory requirements. The research reported herein investigates alternatives to factorization that promise a greater potential to achieve high concurrent computing efficiency. Two methods, and their variants, based on direct energy minimization are studied: a) minimization of the strain energy using the displacement method formulation; b) constrained minimization of the complementary strain energy using the force method formulation. Initial results indicated that in the context of the direct energy minimization the displacement formulation experienced convergence and accuracy difficulties while the force formulation showed promising potential.

  17. Service-Oriented Synthesis of Distributed and Concurrent Protocol Specifications

    Directory of Open Access Journals (Sweden)

    Jehad Al Dallal

    2008-01-01

    Full Text Available Several methods have been proposed for synthesizing computer communication protocol specifications from service specifications. Some protocol synthesis methods based on the finite state machine (FSM model assume that primitives in the service specifications cannot be executed simultaneously. Others either handle only controlled primitive concurrency or have tight restrictions on the applicable FSM topologies. As a result, these synthesis methods are not applicable to an interesting variety of inherently concurrent applications, such as the Internet and mobile communication systems. This paper proposes a concurrent-based protocol synthesis method that eliminates the restrictions imposed by the earlier methods. The proposed method uses a synthesis method to obtain a sequential protocol specification (P-SPEC from a given service specification (S-SPEC. The resulting P-SPEC is then remodeled to consider the concurrency behavior specified in the S-SPEC, while guaranteeing that P-SPEC provides the specified service.

  18. Malária por Plasmodium falciparum: estudos proteômicos Plasmodium falciparum malaria: proteomic studies

    Directory of Open Access Journals (Sweden)

    Rodrigo Siqueira-Batista

    2012-12-01

    Full Text Available A despeito dos avanços no tratamento e das campanhas de prevenção e de controle da malária nos distintos continentes nos quais a moléstia grassa, a entidade mórbida permanece com significativa relevância no mundo contemporâneo. O Plasmodium falciparum é o grande responsável pela malária grave, caracterizada por distúrbios em diferentes órgãos e sistemas, com possibilidade de evolução ao óbito. Embora incipientes, os estudos proteômicos na malária têm trazido boas perspectivas para melhor compreensão dos aspectos biológicos do Plasmodium, assim como dos mecanismos fisiopatológicos, diagnósticos, terapêuticos e profiláticos da enfermidade. Desse modo, o objetivo do presente artigo é apresentar uma breve revisão das aplicações da análise proteômica na malária por P. falciparum.Despite advances in treatment and campaigns for prevention and control of malaria on the various continents where it is still rampant, this disease remains significantly relevant to the contemporary world. Plasmodium falciparum is the organism that is mainly responsible for severe malaria, which is characterized by disturbances in different organs and systems, with possibly fatal outcomes. Although incipient, proteomic studies of malaria have yielded favorable prospects for elucidating the biological aspects of Plasmodium as well as the pathophysiological, diagnostic, prophylactic, and therapeutic mechanisms of the disease. Thus, the aim of the present article is to present a brief review of the applications of proteomic analysis in P. falciparum malaria.

  19. Time concurrency/phase-time synchronization in digital communications networks

    Science.gov (United States)

    Kihara, Masami; Imaoka, Atsushi

    1990-01-01

    Digital communications networks have the intrinsic capability of time synchronization which makes it possible for networks to supply time signals to some applications and services. A practical estimation method for the time concurrency on terrestrial networks is presented. By using this method, time concurrency capability of the Nippon Telegraph and Telephone Corporation (NTT) digital communications network is estimated to be better than 300 ns rms at an advanced level, and 20 ns rms at final level.

  20. DFM/CAPP/CAM System in a Concurrent Engineering Environment

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    In this paper the importance of DFM/CAPP/CAM system in Concurrent Engineering (CE) is discussed. Based on the analyses of the character of concurrent product design and manufacturing process design, the workflow of DFM/CAPP/CAM system in CE is given. DFM/CAPP/CAM theories, methods and functions are investigated in a delicate and all-round way, and are implemented in the developed DFM/CAPP/CAM system.