Our results indicate that dataset size and construction as well as model fit The RNA polymerase alternative σ factor RpoS in Borrelia burgdorferi (Bb), the Lyme disease pathogen, is responsible for programmatic-positive and -negative gene regulation essential for the spirochete's dual-host enzootic cycle. RpoS is expressed during tick-to-mammal transmission and throughout mammalian infection. Although the mammalian-phase RpoS regulon is well described, its counterpart during the transmission blood meal is unknown. Here, we used Bb-specific transcript enrichment by tick-borne disease capture sequencing (TBDCapSeq) to compare the transcriptomes of WT and ΔrpoS Bb in engorged nymphs and following mammalian host-adaptation within dialysis membrane chambers. TBDCapSeq revealed dramatic changes in the contours of the RpoS regulon within ticks and mammals and further confirmed that RpoS-mediated repression is specific to the mammalian-phase of Bb's enzootic cycle. We also provide evidence that RpoS-dependent gene regulation, including repression of tick-phase genes, is required for persistence in mice. Comparative transcriptomics of engineered Bb strains revealed that the Borrelia oxidative stress response regulator (BosR), a noncanonical Fur family member, and the cyclic diguanosine monophosphate (c-di-GMP) effector PlzA reciprocally regulate the function of RNA polymerase complexed with RpoS. BosR is required for RpoS-mediated transcription activation and repression in addition to its well-defined role promoting transcription of rpoS by the RNA polymerase alternative σ factor RpoN. During transmission, ligand-bound PlzA antagonizes RpoS-mediated repression, presumably acting through BACKGROUND: Individuals with later bedtimes have an increased risk of difficulties with mood and substances. To investigate the causes and consequences of late bedtimes and other sleep patterns, researchers are exploring social media as a data source. Pioneering studies inferred sleep patterns directly from social media data. While innovative, these efforts are variously unscalable, context dependent, confined to specific sleep parameters, or rest on untested assumptions, and none of the reviewed studies apply to the popular Reddit platform or release software to the research community. vitamin b5 price : This study builds on this prior work. We estimate the bedtimes of Reddit users from the times tamps of their posts, test inference validity against survey data, and release our model as an R package (The R Foundation). METHODS: We included 159 sufficiently active Reddit users with known time zones and known, nonanomalous bedtimes, together with the time stamps of their 1 million posts. The model's form was chosen by visualizing the aggregate distribution of the timing of users' posts relative to their reported bedtimes. The chosen model represents a user's frequency of Reddit posting by time of day, with a flat portion before bedtime and a quadratic depletion that begins near the user's bedtime, with parameters fitted to the data. This model estimates the bedtimes of individual Reddit users from the time stamps of their posts. Model performance is assessed through k-fold cross-validation. We then apply the model to estimate the bedtimes of 51,372 sufficiently active, nonbot Reddit users with known time zones from the time stamps of their 140 million posts. RESULTS: The Pearson correlation between expected and observed Reddit posting frequencies in our model was 997 on aggregate data. On average, posting starts declining 45 minutes before bedtime, reaches a nadir 75 hours after bedtime that is 87% lower than the daytime rate, and returns to baseline 25 hours after bedtime. The Pearson correlation between inferred and reported bedtimes for individual users was 61 (P<.001). In 90 of 159 cases (6%), our estimate was within 1 hour of the reported bedtime; 128 cases (5%) were within 2 hours. There was equivalent accuracy in hold-out sets versus training sets of k-fold cross-validation, arguing against overfitting. The model was more accurate than a random forest approach. vitamin b5 : We uncovered a simple, reproducible relationship between Reddit users' reported bedtimes and the time of day when high daytime posting rates transition to low nighttime posting rates. We captured this relationship in a model that estimates users' bedtimes from the time stamps of their posts. Limitations include applicability only to users who post frequently, the requirement for time zone data, and limits on generalizability. Nonetheless, it is a step forward for inferring the sleep parameters of social media users passively at scale. Our model and precomputed estimated bedtimes of 50,000 Reddit Fernanda C Andrade, Philip Corlett, Mark B Gerstein, Rick H Hoyle. Originally published in JMIR Formative Research, digital mental health company, whose work is unrelated to the contents of this piece, and who did not fund this work. The fight against malaria is a continuum as the epidemic is not abating. For proper deployment of tools in the fight against malaria, an assessment of the situation is necessary. This work assessed the level of antimalarial drug treatment failure in Ebonyi State, Nigeria.
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