3,617 research outputs found

    The Microbial Ecology of Bacterial Vaginosis: A Fine Scale Resolution Metagenomic Analysis

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    The vaginal microbiota play an important protective role in maintaining the health of women. Disruption of the mutualistic relationship that exists between bacterial communities in the vagina and their hosts can lead to bacterial vaginosis (BV), a condition in which lactic acid producing bacteria are supplanted by a diverse array of strictly anaerobic bacteria. BV has been shown to be an independent risk factor for adverse outcomes including preterm delivery and low infant birth weight, acquisition of sexually transmitted infections and HIV, and development of pelvic inflammatory disease. National surveys indicate the prevalence of BV among U.S. women is 29.2%, and yet, despite considerable effort, the etiology of BV remains unknown. Moreover, there are no broadly effective therapies for the treatment of BV, and reoccurrence is common. In the proposed research we will test the overarching hypothesis that vaginal microbial community dynamics and activities are indicators of risk to BV. To do this, we propose to conduct a high resolution prospective study in which samples collected daily from 200 reproductive-age women over two menstrual cycles are used to capture molecular events that take place before, during, and after the spontaneous remission of BV episodes. We will use modern genomic technologies to obtain the data needed to correlate shifts in vaginal microbial community composition and function, metabolomes, and epidemiological and behavioral metadata with the occurrence of BV to better define the syndrome itself and identify patterns that are predictive of BV. The three specific aims of the research are: (1) Evaluate the association between the dynamics of vaginal microbial communities and risk to BV by characterizing the community composition of vaginal specimens archived from a vaginal douching cessation study in which 33 women self-collected vaginal swabs twice-weekly for 16 weeks; (2) Enroll 135 women in a prospective study in which self-collected vaginal swab samples and secretions are collected daily along with data on the occurrence of BV, vaginal pH, and information on time varying habits and practices; (3) Apply model-based statistical clustering and classification approaches to associate the microbial community composition and function, with metadata and clinical diagnoses of BV. The large body of information generated will facilitate understanding vaginal microbial community dynamics, the etiology of BV, and drive the development of better diagnostic tools for BV. Furthermore, the information will enable a more personalized and effective treatment of BV and ultimately help prevent adverse sequelae associated with this highly prevalent disruption of the vaginal microbiome

    Radio background measurements at the Pierre Auger Observatory

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    Mesures du bruit de fond radio sur le site de l'observatoire Pierre Auge

    A critical analysis of the UV-continuum slopes of high-redshift galaxies; no evidence (yet) for extreme stellar populations at z > 6

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    It has recently been reported that the faintest galaxies at z~6-7 display extremely blue UV continuum slopes, with a UV power-law index beta ~ -3. Such slopes are bluer than previously reported for any other galaxy population, and imply extinction-free, young, very low-metallicity stellar populations with a high ionizing photon escape fraction. Here we undertake a critical study of the evidence for such extreme values of beta, combining three new WFC3/IR-selected samples of galaxies spanning ~2 decades in UV luminosity over the redshift range z~4.5-8. We explore the impact of inclusion/exclusion of less robust high-z candidates, and use the varying depths of the samples to explore the effects of noise and selection bias. Simple data-consistency arguments suggest that artificially blue average values of beta can result when the analysis is extended into the deepest ~ 0.5-mag bin of these WFC3/IR-selected samples, regardless of the actual luminosity or z range probed. By confining attention to robust, well-detected high-z galaxy candidates, we find that the average value of beta is consistent with -2.05 +/- 0.10 for z=5-7, and -22 < M_UV < -18. We create and analyse a set of simulations which demonstrate that a bias towards artifically low/blue average values of beta is indeed expected when the UV slope analysis is extended towards the source detection threshold, and conclude that there is as yet no clear evidence for UV slopes significantly bluer than beta ~ -2, the typical value displayed by the bluest star-forming galaxies at more modest z. A robust measurement of beta for the faintest galaxies at z~7-8 remains a key observational goal, as it provides a fundamental test for high escape fractions from a potentially abundant source of reionizing photons. This goal is achievable with HST, but requires still deeper WFC3/IR imaging in the HUDF.Comment: 12 pages, 10 figures, minor modifications made to make arXiv version match the accepted/published MNRAS versio

    Probing Plasmodium falciparum sexual commitment at the single-cell level

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    Background: Malaria parasites go through major transitions during their complex life cycle, yet the underlying differentiation pathways remain obscure. Here we apply single cell transcriptomics to unravel the program inducing sexual differentiation in Plasmodium falciparum. Parasites have to make this essential life-cycle decision in preparation for human-to-mosquito transmission. Methods: By combining transcriptional profiling with quantitative imaging and genetics, we defined a transcriptional signature in sexually committed cells. Results: We found this transcriptional signature to be distinct from general changes in parasite metabolism that can be observed in response to commitment-inducing conditions. Conclusions: This proof-of-concept study provides a template to capture transcriptional diversity in parasite populations containing complex mixtures of different life-cycle stages and developmental programs, with important implications for our understanding of parasite biology and the ongoing malaria elimination campaign

    Pengaruh Bauran Pemasaran terhadap Keputusan Pembelian Mobil pada PT. Astra International Tbk, Daihatsu Manado

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    Strategi pemasaran menjadi salah satu faktor penentu perkembangan dan pertumbuhan industri otomotif yang sangat pesat khususnya mobil. Hal ini ditandai dengan terus bertambahnya kuantitas kendaraan yang dimiliki masyarakat dan terlihat pada mobilitas kendaraan yang berada di jalan-jalan kota besar seperti Manado. Tujuan penelitian ini untuk mengetahui apakah bauran pemasaran yang terdiri dari produk, harga, distribusi dan promosi berpengaruh secara bersama-sama terhadap keputusan pembelian mobil di Daihatsu Paal 2 Manado. Penelitian ini merupakan penelitian kuantitatif, lokasi penelitian pada Daihatsu Paal 2 Manado. Populasinya adalah keseluruhan konsumen yang melakukan pembelian mobil merek Daihatsu selama penelitian berlangsung dengan menarik sampel penelitian sebanyak 100 orang untuk memperoleh hasil yang akurat. Analisis data berupa uji validitas dan reliabilitas, uji asumsi klasik, koefisien determinasi, regresi linear sederhana. Hasil penelitian yaitu produk, harga, distribusi dan promosi secara simultan berpengaruh signifikan terhadap keputusan pembelian mobil di PT Astra Daihatsu Paal 2 Manado. Saran yaitu PT Astra Daihatsu Paal 2 Manado perlu menerapkan Bauran Pemasaran secara bersama yang pada akhirnya akan mempengaruhi mempengaruhi keputusan pembelian mobil. Perusahaan juga perlu memperhatikan fakor Distribusi yang merupakan variabel yang paling signifikan mempengaruhi Keputusan Pembelian Mobil dalam penelitian ini

    Designer lipid-like peptides

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    A crucial bottleneck in membrane protein studies, particularly G-protein coupled receptors, is the notorious difficulty of finding an optimal detergent that can solubilize them and maintain their stability and function. Here we report rapid production of 12 unique mammalian olfactory receptors using short designer lipid-like peptides as detergents. The peptides were able to solubilize and stabilize each receptor. Circular dichroism showed that the purified olfactory receptors had alpha-helical secondary structures. Microscale thermophoresis suggested that the receptors were functional and bound their odorants. Blot intensity measurements indicated that milligram quantities of each olfactory receptor could be produced with at least one peptide detergent. The peptide detergents' capability was comparable to that of the detergent Brij-35. The ability of 10 peptide detergents to functionally solubilize 12 olfactory receptors demonstrates their usefulness as a new class of detergents for olfactory receptors, and possibly other G-protein coupled receptors and membrane proteins

    Radio Detection of Cosmic Ray Extensive Air Showers: present status of the CODALEMA experiment

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    Data acquisition and analysis for the CODALEMA experiment, in operation for more than one year, has provided improved knowledge of the characteristics of this new device. At the same time, an important effort has been made to develop processing techniques for extracting transient signals from data containing interference.Comment: september 200

    Radiodetection of Cosmic Ray Extensive Air Showers

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    We present the characteristics and performance of a demonstration experiment devoted to the observation of ultra high- energy cosmic ray extensive air showers using a radiodetection technique. In a first step, one antenna narrowed band filtered acting as trigger, with a 4 σ\sigma threshold above sky background-level, was used to tag any radio transient in coincidence on the antenna array. Recently, the addition of 4 particle detectors has allowed us to observe cosmic ray events in coincidence with antennas
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