Optogenetic Activation of Dorsal Raphe Serotonin Neurons Rapidly Inhibits Spontaneous But Not Odor-Evoked Activity in Olfactory Cortex

Serotonin (5-hydroxytriptamine; 5-HT) is implicated in a variety of brain functions including not only the regulation of mood and control of behavior but also the modulation of perception. 5-HT neurons in the dorsal raphe nucleus (DRN) often fire locked to sensory stimuli, but little is known about how 5-HT affects sensory processing, especially on this timescale. Here, we used an optogenetic approach to study the effect of 5-HT on single-unit activity in the mouse primary olfactory (anterior piriform) cortex. We show that activation of DRN 5-HT neurons rapidly inhibits the spontaneous firing of olfactory cortical neurons, acting in a divisive manner, but entirely spares sensory-driven firing. These results identify a new role for serotonergic modulation in dynamically regulating the balance between different sources of neural activity in sensory systems, suggesting a possible role for 5-HT in perceptual inference.info:eu-repo/semantics/publishedVersio

DNA methylation testing with S5 for triage of high-risk HPV positive women

Methylation of host and viral genes is promising for triage of women with high‐risk human papillomavirus infections (hrHPV). Using a population‐based sample of hrHPV positive women with cervical biopsies within 12 months after cervical screening, the clinical value of the S5 methylation classifier (S5), HPV genotyping and cytology were compared as potential triage tests, for outcomes of cervical intraepithelial neoplasia (CIN) grade 3 or greater (CIN3+), CIN2+ and CIN2, and the area under the curve (AUC) calculated. S5 scores increased with histopathology severity (P (trend) < .001). For CIN3+, the AUC was 0.780 suggesting S5 provides good discrimination between <CIN3 and CIN3+. AUCs were significant for all pairwise comparisons of <CIN2, CIN2 and CIN3+ (P < .001). The positive predictive value (PPV) of HPV16/18 genotyping for women with any abnormal cytology was greater than S5 (25.36% vs 20.87%, P = .005) for CIN3+, while sensitivity was substantially greater for S5 (83.33% vs 59.28%, P < .001). Restricting to women with abnormal cytology, but excluding those with high‐grade cytology, both S5 and HPV16/18 provided CIN3+ PPVs high enough to recommend colposcopy. Triage with S5 also appeared useful for hrHPV positive women negative for HPV16/18 (CIN3+ PPV: 7.33%, sensitivity: 57.52%). S5 provided increased sensitivity for CIN3+ compared to HPV16/18 genotyping for hrHPV positive women, overall and when restricted to women with abnormal cytology, suggesting S5 may improve colposcopy referral. S5 also has the ability to distinguish between <CIN2, CIN2 and CIN3+, a finding of importance for managing CIN2, given the complexity and uncertainty associated with this diagnosis

Oxidation of ZrB2 SiC TaSi2 Materials at Ultra High Temperatures

ZrB2 - 20v% SiC - 20v% TaSi2 was oxidized in stagnant air for ten minute cycles for times up to 100 minutes at 1627 C and 1927 C. The sample oxidized at 1627 C showed oxidation resistance better than that of the standard ZrB2 - 20v% SiC. The sample oxidized at 1927 C, however, showed evidence of liquid phase formation and complex oxidation products. The sample exposed at 1927 C was analyzed in detail by scanning electron microprobe and wavelength dispersive spectroscopy to understand the complex oxidation and melting reactions occurring during exposure. The as hot-pressed material shows the formation of a Zr(Ta)B2 phase in addition to the three phases in the nominal composition already noted. After oxidation, the TaSi2 in the matrix was completely reacted to form Ta(Zr)C. The layered oxidation products included SiO2, ZrO2, Ta2O5, and a complex oxide containing both Zr and Ta. Likely reactions are proposed based on thermodynamic phase stability and phase morphology

Weighted Least Squares Techniques for Improved Received Signal Strength Based Localization

The practical deployment of wireless positioning systems requires minimizing the calibration procedures while improving the location estimation accuracy. Received Signal Strength localization techniques using propagation channel models are the simplest alternative, but they are usually designed under the assumption that the radio propagation model is to be perfectly characterized a priori. In practice, this assumption does not hold and the localization results are affected by the inaccuracies of the theoretical, roughly calibrated or just imperfect channel models used to compute location. In this paper, we propose the use of weighted multilateration techniques to gain robustness with respect to these inaccuracies, reducing the dependency of having an optimal channel model. In particular, we propose two weighted least squares techniques based on the standard hyperbolic and circular positioning algorithms that specifically consider the accuracies of the different measurements to obtain a better estimation of the position. These techniques are compared to the standard hyperbolic and circular positioning techniques through both numerical simulations and an exhaustive set of real experiments on different types of wireless networks (a wireless sensor network, a WiFi network and a Bluetooth network). The algorithms not only produce better localization results with a very limited overhead in terms of computational cost but also achieve a greater robustness to inaccuracies in channel modeling

Routine cervical screening with primary HPV testing and cytology triage protocol in a randomised setting

The role of high-risk human papillomavirus (hrHPV) testing in primary cervical screening has not been established. We generated a randomised evaluation design ultimately to clarify whether primary hrHPV testing implemented into routine screening can bring increase in the programme effectiveness. The aim of the present report on first-year results was to assess the cross-sectional relative validity parameters for routine hrHPV screening, in comparison with conventional screening. An equal number of women invited to routine screening was randomly allocated to primary hrHPV screening (n=7060) and to cytological screening (n=7089). In the hrHPV screening arm, after a single positive hrHPV test result, the need of colposcopy referral was determined by a cytological triage test. Compared with the conventional arm, more colposcopy referrals were made in the hrHPV screening arm (relative risk 1.51, confidence interval 95% 1.03–2.22). Specificity of the primary screening with sole hrHPV test (91.5–92.1%) was much lower than that with the cytology triage (98.7–99.3%), which was not quite as specific as screening with conventional cytology (99.2–99.6%). Compared with conventional cytology, primary screening with hrHPV test results in increased cross-sectional relative sensitivity at the level of all positive lesions at the cost of substantial loss in specificity. With cytology triage, the specificity improves to the level of conventional cytology