Cell fates are determined by specific transcriptional programs. Here we provide evidence that the transcriptional coactivator, Mediator 1 (Med1), is essential for the cell fate determination of ectodermal epithelia. Conditional deletion of Med1 in vivo con

BACKGROUND: While increased levels of circulating inflammatory cytokines in chronologically aged humans have been linked to the development of ageing-associated chronic disorders (e.g., cardiovascular disease, type II diabetes, osteoporosis and Alzheimers disease), approaches that reduce circulating cytokines are not yet available. In chronologically aged mice, we recently demonstrated that epidermal dysfunction largely accounts for age-associated elevations in circulating cytokine levels, and that improving epidermal function reduced circulating cytokine levels. OBJECTIVE: We performed a pilot study to determine whether improving epidermal function reduces circulating pro-inflammatory cytokine levels in aged humans. METHODS: Thirty-three aged humans were topically treated twice-daily for 30 days, with ≈ 3 mL of an emollient, previously shown to improve epidermal function, while untreated, aged humans and a cohort of young volunteers served as controls. Changes in epidermal function and levels of three key, age-related, plasma cytokines (IL-1β, IL-6 and TNFα) were measured at baseline and after treatment, using Luminex 200™ system. RESULTS: We also found significantly higher baseline levels of IL-1β, IL-6 and TNFα in aged vs. young humans (P < 0.001), as previously reported. Topical applications of the barrier repair emollient significantly enhanced epidermal permeability barrier function (P < 0.01) and stratum corneum hydration (P < 0.05). In parallel, circulating levels of IL-1β and IL-6 normalized, while TNFα levels declined substantially. CONCLUSION: The results of this preliminary study suggest that a larger clinical trial should be performed to confirm whether improving epidermal function also can reduce circulating pro-inflammatory cytokine levels in aged humans, while also possibly attenuating the downstream development of chronic inflammatory disorders in the aged humans.

To investigate the fast ion behavior, a fast ion D-alpha (FIDA) diagnostic system has been planned and is presently under development on Experimental Advanced Superconducting Tokamak. The greatest challenges for the design of a FIDA diagnostic are its extremely low intensity levels, which are usually significantly below the continuum radiation level and several orders of magnitude below the bulk-ion thermal charge-exchange feature. Moreover, an overlaying Motional Stark Effect (MSE) feature in exactly the same wavelength range can interfere. The simulation of spectra code is used here to guide the design and evaluate the diagnostic performance. The details for the parameters of design and hardware are presented.

To investigate the fast ion behavior, a fast ion D-alpha (FIDA) diagnostic system has been installed on EAST. Fast ion features can be inferred from the Doppler shifted spectrum of Balmer-alpha light from energetic hydrogenic atoms. This paper will focus on the validation of FIDA measurements performed using MHD-quiescent discharges in 2015 campaign. Two codes have been applied to calculate the D_α spectrum: one is a Monte Carlo code, Fortran 90 version FIDASIM, and the other is an analytical code, Simulation of Spectra (SOS). The predicted SOS fast-ion spectrum agrees well with the measurement; however, the level of fast-ion part from FIDASIM is lower. The discrepancy is possibly due to the difference between FIDASIM and SOS velocity distribution function. The details will be presented in the paper to primarily address comparisons of predicted and observed spectrum shapes/amplitudes.

In the hopes of observing the highest-energy neutrinos (E>1 EeV) populating the Universe, both past (RICE, AURA, ANITA) and current (RNO-G, ARIANNA, ARA and TAROGE-M) polar-sited experiments exploit the impulsive radio emission produced by neutrino interactions. In such experiments, rare single event candidates must be unambiguously identified above backgrounds. Background rejection strategies to date primarily target thermal noise fluctuations and also impulsive radio-frequency signals of anthropogenic origin. In this paper, we consider the possibility that ‘fake’ neutrino signals may also be generated naturally via the ‘triboelectric effect.’ This broadly describes any process in which force applied at a boundary layer results in displacement of surface charge, leading to the production of an electrostatic potential difference ΔV. Wind blowing over granular surfaces such as snow can induce such a potential difference, with subsequent coronal discharge. Discharges over timescales as short as nanoseconds can then lead to radio-frequency emissions at characteristic MHz–GHz frequencies. Using data from various past (RICE, AURA, SATRA, ANITA) and current (RNO-G, ARIANNA and ARA) neutrino experiments, we find evidence for such backgrounds, which are generally characterized by: (a) a threshold wind velocity which likely depends on the experimental trigger criteria and layout; for the experiments considered herein, this value is typically O(10 m/s), (b) frequency spectra generally shifted to the low-end of the frequency regime to which current radio experiments are typically sensitive (100–200 MHz), (c) for the strongest background signals, an apparent preference for discharges from above-surface structures, although the presence of more isotropic, lower amplitude triboelectric discharges cannot be excluded.

The Astropy Project supports and fosters the development of open-source and openly developed Python packages that provide commonly needed functionality to the astronomical community. A key element of the Astropy Project is the core package astropy, which serves as the foundation for more specialized projects and packages. In this article, we provide an overview of the organization of the Astropy project and summarize key features in the core package, as of the recent major release, version 2.0. We then describe the project infrastructure designed to facilitate and support development for a broader ecosystem of interoperable packages. We conclude with a future outlook of planned new features and directions for the broader Astropy Project.