32 research outputs found

    Genomewide Association Study for Determinants of HIV-1 Acquisition and Viral Set Point in HIV-1 Serodiscordant Couples with Quantified Virus Exposure

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    Host genetic factors may be important determinants of HIV-1 sexual acquisition. We performed a genome-wide association study (GWAS) for host genetic variants modifying HIV-1 acquisition and viral control in the context of a cohort of African HIV-1 serodiscordant heterosexual couples. To minimize misclassification of HIV-1 risk, we quantified HIV-1 exposure, using data including plasma HIV-1 concentrations, gender, and condom use.We matched couples without HIV-1 seroconversion to those with seroconversion by quantified HIV-1 exposure risk. Logistic regression of single nucleotide polymorphisms (SNPs) for 798 samples from 496 HIV-1 infected and 302 HIV-1 exposed, uninfected individuals was performed to identify factors associated with HIV-1 acquisition. In addition, a linear regression analysis was performed using SNP data from a subset (n = 403) of HIV-1 infected individuals to identify factors predicting plasma HIV-1 concentrations.After correcting for multiple comparisons, no SNPs were significantly associated with HIV-1 infection status or plasma HIV-1 concentrations.This GWAS controlling for HIV-1 exposure did not identify common host genotypes influencing HIV-1 acquisition. Alternative strategies, such as large-scale sequencing to identify low frequency variation, should be considered for identifying novel host genetic predictors of HIV-1 acquisition

    Genetic Determination and Linkage Mapping of Plasmodium falciparum Malaria Related Traits in Senegal

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    Plasmodium falciparum malaria episodes may vary considerably in their severity and clinical manifestations. There is good evidence that host genetic factors contribute to this variability. To date, most genetic studies aiming at the identification of these genes have used a case/control study design for severe malaria, exploring specific candidate genes. Here, we performed a family-based genetic study of falciparum malaria related phenotypes in two independent longitudinal survey cohorts, as a first step towards the identification of genes and mechanisms involved in the outcome of infection. We studied two Senegalese villages, Dielmo and Ndiop that differ in ethnicity, malaria transmission and endemicity. We performed genome-scan linkage analysis of several malaria-related phenotypes both during clinical attacks and asymptomatic infection. We show evidence for a strong genetic contribution to both the number of clinical falciparum malaria attacks and the asymptomatic parasite density. The asymptomatic parasite density showed linkage to chromosome 5q31 (LOD = 2.26, empirical p = 0.0014, Dielmo), confirming previous findings in other studies. Suggestive linkage values were also obtained at three additional chromosome regions: the number of clinical malaria attacks on chromosome 5p15 (LOD = 2.57, empirical p = 0.001, Dielmo) and 13q13 (LOD = 2.37, empirical p = 0.0014 Dielmo), and the maximum parasite density during asymptomatic infection on chromosome 12q21 (LOD = 3.1, empirical p<10−4, Ndiop). While regions of linkage show little overlap with genes known to be involved in severe malaria, the four regions appear to overlap with regions linked to asthma or atopy related traits, suggesting that common immune related pathways may be involved

    Étude par co-simulation du principe d'une Interconnexion RF associĂ©e Ă  un multiplexage CDMA

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    National audienceDans ce papier nous dĂ©veloppons de nouvelles interconnexions, de type radiofrĂ©quences, pour remplacer les interconnexions classiques de circuits numĂ©riques. A l'aide d'outils de co simulation, nous avons modĂ©lisĂ© ce principe d'interconnexion associĂ© Ă  un multiplexage numĂ©rique de type CDMA et une modulation d'amplitude. A titre d'exemple, nous prĂ©sentons la rĂ©ponse frĂ©quentielle d'un canal radiofrĂ©quence ainsi que les diffĂ©rents signaux observables le long de la chaine. Cette modĂ©lisation pourra par la suite ĂȘtre utilisĂ©e afin de dĂ©velopper le concept d'interconnexion radiofrĂ©quence

    Study of Proximity-Coupling: Application to new RF-Interconnects

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    International audienceThe new concept of RF Interconnect presented in this paper is aimed at replacing conventional interconnections in digital circuits. The study was, thus, focused on the transmission channel composed of contactless transitions. After a brief recall of the theory, an RF interconnection was modeled through use of multiplexing digital CDMA and amplitude modulation and characterized by using a co-simulation tool. The frequency response of a radiofrequency channel and the signal forms observed along the transmission system are presented to highlight the capabilities of this RF interconnect

    Electromagnetic analysis of RF interconnect

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    International audienceToday, the performances of integrated electronic circuits are limited by global interconnects. To achieve in performance, one needs to consider new solutions to carry the information in the chips or along the system. This communication deals with the study of RF interconnects, which is among the options under discussion within the ITRS [1]. At first, we recall the concept of RF interconnects to further illustrate it in the case of 4-bit transmission. Then, we calculate the transfer function of a complete RF interconnect to identify the parameters to be optimized, in order to increase the gain and obtain relative plane curves over a wide frequency band. Finally, we conduct on electromagnetic study of various coupling options that can be expected when using the available technologies

    Low density parasitaemia, red blood cell polymorphisms and Plasmodium falciparum specific immune responses in a low endemic area in northern Tanzania.

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    BACKGROUND: Low density Plasmodium falciparum infections, below the microscopic detection limit, may play an important role in maintaining malaria transmission in low endemic areas as well as contribute to the maintenance of acquired immunity. Little is known about factors influencing the occurrence of sub-microscopic parasitaemia or the relation with immune responses.We investigated possible associations between the occurrence of sub-microscopic P. falciparum parasite carriage and antibody responses to the asexual stage antigens, G6PD deficiency and alpha+-thalassaemia in 464 subjects from a low endemic area in northern Tanzania. METHODS: We used samples collected from two cross sectional surveys conducted during dry and wet season in 2005. Submicroscopic parasitaemia was detected by using quantitative nucleic acid sequence based amplification (QT-NASBA). Genotyping for G6PD and alpha+-thalassaemia were performed by high throughput PCR; the prevalence and level of total IgG antibodies against MSP-1, MSP-2 and AMA-1 were determined by ELISA. RESULTS: Compared to parasite free individuals, individuals carrying sub-microscopic densities of P. falciparum parasites had significantly higher median antibody levels to MSP-1 (p = 0.042) and MSP-2 (p = 0.034) but not to AMA-1 (p = 0.14) while no clear relation between sub-microscopic parasite carriage and G6PD deficiency or alpha+-thalassaemia was observed. CONCLUSION: Our data suggest a role for sub-microscopic parasite densities in eliciting or maintaining humoral immune responses without evidence for a modulating effect of G6PD deficiency or alpha+-thalassaemia
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