4,486 research outputs found

    Visualizing probabilistic models: Intensive Principal Component Analysis

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    Unsupervised learning makes manifest the underlying structure of data without curated training and specific problem definitions. However, the inference of relationships between data points is frustrated by the `curse of dimensionality' in high-dimensions. Inspired by replica theory from statistical mechanics, we consider replicas of the system to tune the dimensionality and take the limit as the number of replicas goes to zero. The result is the intensive embedding, which is not only isometric (preserving local distances) but allows global structure to be more transparently visualized. We develop the Intensive Principal Component Analysis (InPCA) and demonstrate clear improvements in visualizations of the Ising model of magnetic spins, a neural network, and the dark energy cold dark matter ({\Lambda}CDM) model as applied to the Cosmic Microwave Background.Comment: 6 pages, 5 figure

    Surveillance of respiratory viruses among children attending a primary school in rural coastal Kenya

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    Background: Respiratory viruses are primary agents of respiratory tract diseases. Knowledge on the types and frequency of respiratory viruses affecting school-children is important in determining the role of schools in transmission in the community and identifying targets for interventions. Methods: We conducted a one-year (term-time) surveillance of respiratory viruses in a rural primary school in Kilifi County, coastal Kenya between May 2017 and April 2018. A sample of 60 students with symptoms of ARI were targeted for nasopharyngeal swab (NPS) collection weekly. Swabs were screened for 15 respiratory virus targets using real time PCR diagnostics. Data from respiratory virus surveillance at the local primary healthcare facility was used for comparison. Results: Overall, 469 students aged 2-19 years were followed up for 220 days. A total of 1726 samples were collected from 325 symptomatic students; median age of 7 years (IQR 5-11). At least one virus target was detected in 384 (22%) of the samples with a frequency of 288 (16.7%) for rhinovirus, 47 (2.7%) parainfluenza virus, 35 (2.0%) coronavirus, 15 (0.9%) adenovirus, 11 (0.6%) respiratory syncytial virus (RSV) and 5 (0.3%) influenza virus. The proportion of virus positive samples was higher among lower grades compared to upper grades (25.9% vs 17.5% respectively; χ2 = 17.2, P -value <0.001). Individual virus target frequencies did not differ by age, sex, grade, school term or class size. Rhinovirus was predominant in both the school and outpatient setting. Conclusion: Multiple respiratory viruses circulated in this rural school population. Rhinovirus was dominant in both the school and outpatient setting and RSV was of notably low frequency in the school. The role of school children in transmitting viruses to the household setting is still unclear and further studies linking molecular data to contact patterns between the school children and their households are required

    Mapping of bioavailable strontium isotope ratios in France for archaeological provenance studies

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    Strontium isotope ratios (⁸⁷Sr/⁸⁶Sr) of archaeological samples (teeth and bones) can be used to track mobility and migration across geologically distinct landscapes. However, traditional interpolation algorithms and classification approaches used to generate Sr isoscapes are often limited in predicting multiscale ⁸⁷Sr/⁸⁶Sr patterning. Here we investigate the suitability of plant samples and soil leachates from the IRHUM database (www.irhumdatabase.com) to create a bioavailable ⁸⁷Sr/⁸⁶Sr map using a novel geostatistical framework. First, we generated an ⁸⁷Sr/⁸⁶Sr map by classifying ⁸⁷Sr/⁸⁶Sr values into five geologically-representative isotope groups using cluster analysis. The isotope groups were then used as a covariate in kriging to integrate prior geological knowledge of Sr cycling with the information contained in the bioavailable dataset and enhance ⁸⁷Sr/⁸⁶Sr predictions. Our approach couples the strengths of classification and geostatistical methods to generate more accurate ⁸⁷Sr/⁸⁶Sr predictions (Root Mean Squared Error = 0.0029) with an estimate of spatial uncertainty based on lithology and sample density. This bioavailable Sr isoscape is applicable for provenance studies in France, and the method is transferable to other areas with high sampling density. While our method is a step forward in generating accurate ⁸⁷Sr/⁸⁶Sr isoscapes, the remaining uncertainty also demonstrates that fine-modelling of ⁸⁷Sr/⁸⁶Sr variability is challenging and requires more than geological maps for accurately predicting ⁸⁷Sr/⁸⁶Sr variations across the landscape. Future efforts should focus on increasing sampling density and developing predictive models to further quantify and predict the processes that lead to ⁸⁷Sr/⁸⁶Sr variability.Funding was provided by ARC DP110101415 (Grün, Spriggs, Armstrong, Maureille and Falguères) Understanding the migrations of prehistoric populations through direct dating and isotopic tracking of their mobility patterns. Part of this research was supported by the Australian French Association for Science & Technology through the ACT Science Fellowship program (2013) to M. Willme

    Recent sequence variation in probe binding site affected detection of respiratory syncytial virus group B by real-time RT-PCR

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    Background Direct immuno-fluorescence test (IFAT) and multiplex real-time RT-PCR have been central to RSV diagnosis in Kilifi, Kenya. Recently, these two methods showed discrepancies with an increasing number of PCR undetectable RSV-B viruses. Objectives Establish if mismatches in the primer and probe binding sites could have reduced real-time RT-PCR sensitivity. Study design Nucleoprotein (N) and glycoprotein (G) genes were sequenced for real-time RT-PCR positive and negative samples. Primer and probe binding regions in N gene were checked for mismatches and phylogenetic analyses done to determine molecular epidemiology of these viruses. New primers and probe were designed and tested on the previously real-time RT-PCR negative samples. Results N gene sequences revealed 3 different mismatches in the probe target site of PCR negative, IFAT positive viruses. The primers target sites had no mismatches. Phylogenetic analysis of N and G genes showed that real-time RT-PCR positive and negative samples fell into distinct clades. Newly designed primers-probe pair improved detection and recovered previous PCR undetectable viruses. Conclusions An emerging RSV-B variant is undetectable by a quite widely used real-time RT-PCR assay due to polymorphisms that influence probe hybridization affecting PCR accuracy

    SRF-deficient astrocytes provide neuroprotection in mouse models of excitotoxicity and neurodegeneration

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    Reactive astrogliosis is a common pathological hallmark of CNS injury, infection, and neurodegeneration, where reactive astrocytes can be protective or detrimental to normal brain functions. Currently, the mechanisms regulating neuroprotective astrocytes and the extent of neuroprotection are poorly understood. Here, we report that conditional deletion of serum response factor (SRF) in adult astrocytes causes reactive-like hypertrophic astrocytes throughout the mouse brain. Thes

    Differential Regulation of Syngap1 Translation by FMRP Modulates eEF2 Mediated Response on NMDAR Activity

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    SYNGAP1, a Synaptic Ras-GTPase activating protein, regulates synapse maturation during a critical developmental window. Heterozygous mutation in SYNGAP1 (SYNGAP1-/+) has been shown to cause Intellectual Disability (ID) in children. Recent studies have provided evidence for altered neuronal protein synthesis in a mouse model of Syngap1-/+. However, the molecular mechanism behind the same is unclear. Here, we report the reduced expression of a known translation regulator, FMRP, during a specific developmental period in Syngap1-/+ mice. Our results demonstrate that FMRP interacts with and regulates the translation of Syngap1 mRNA. We further show reduced Fmr1 translation leads to decreased FMRP level during development in Syngap1-/+ which results in an increase in Syngap1 translation. These developmental changes are reflected in the altered response of eEF2 phosphorylation downstream of NMDA Receptor (NMDAR)-mediated signaling. In this study, we propose a cross-talk between FMRP and SYNGAP1 mediated signaling which can also explain the compensatory effect of impaired signaling observed in Syngap1-/+ mice
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