Celiac Disease: Role of the Epithelial Barrier

In celiac disease (CD) a T-cell–mediated response to gluten is mounted in genetically predisposed individuals, resulting in a malabsorptive enteropathy histologically highlighted by villous atrophy and crypt hyperplasia. Recent data point to the epithelial layer as an under-rated hot spot in celiac pathophysiology to date. This overview summarizes current functional and genetic evidence on the role of the epithelial barrier in CD, consisting of the cell membranes and the apical junctional complex comprising sealing as well as ion and water channel-forming tight junction proteins and the adherens junction. Moreover, the underlying mechanisms are discussed, including apoptosis of intestinal epithelial cells, biology of intestinal stem cells, alterations in the apical junctional complex, transcytotic uptake of gluten peptides, and possible implications of a defective epithelial polarity. Current research is directed toward new treatment options for CD that are alternatives or complementary therapeutics to a gluten-free diet. Thus, strategies to target an altered epithelial barrier therapeutically also are discussed

Multi-frequency Black Hole Imaging for the Next-Generation Event Horizon Telescope

The Event Horizon Telescope (EHT) has produced images of the plasma flow around the supermassive black holes in Sgr A* and M87* with a resolution comparable to the projected size of their event horizons. Observations with the next-generation Event Horizon Telescope (ngEHT) will have significantly improved Fourier plane coverage and will be conducted at multiple frequency bands (86, 230, and 345 GHz), each with a wide bandwidth. At these frequencies, both Sgr A* and M87* transition from optically thin to optically thick. Resolved spectral index maps in the near-horizon and jet-launching regions of these supermassive black hole sources can constrain properties of the emitting plasma that are degenerate in single-frequency images. In addition, combining information from data obtained at multiple frequencies is a powerful tool for interferometric image reconstruction, since gaps in spatial scales in single-frequency observations can be filled in with information from other frequencies. Here we present a new method of simultaneously reconstructing interferometric images at multiple frequencies along with their spectral index maps. The method is based on existing Regularized Maximum Likelihood (RML) methods commonly used for EHT imaging and is implemented in the eht-imaging Python software library. We show results of this method on simulated ngEHT data sets as well as on real data from the VLBA and ALMA. These examples demonstrate that simultaneous RML multi-frequency image reconstruction produces higher-quality and more scientifically useful results than is possible from combining independent image reconstructions at each frequency.Comment: 25 pages, 15 figures. Accepted to Ap

The 2013 Rim Fire: Implications for Predicting Extreme Fire Spread, Pyroconvection, and Smoke Emissions

Abstract The 2013 Rim Fire, which burned over 104,000 ha, was one of the most severe fire events in California's history, in terms of its rapid growth, intensity, overall size, and persistent smoke plume. At least two large pyrocumulonimbus (pyroCb) events were observed, allowing smoke particles to extend through the upper troposphere over a large portion of the Pacific Northwest. However, the most extreme fire spread was observed on days without pyroCb activity or significant regional convection. A diverse archive of ground, airborne, and satellite data collected during the Rim Fire provides a unique opportunity to examine the conditions required for both extreme spread events and pyroCb development. Results highlight the importance of upper-level and nocturnal meteorology, as well as the limitations of traditional fire weather indices. The Rim Fire dataset also allows for a detailed examination of conflicting hypotheses surrounding the primary source of moisture during pyroCb development. All pyroCbs were associated with conditions very similar to those that produce dry thunderstorms. The current suite of automated forecasting applications predict only general trends in fire behavior, and specifically do not predict 1) extreme fire spread events and 2) injection of smoke to high altitudes. While these two exceptions are related, analysis of the Rim Fire shows that they are not predicted by the same set of conditions and variables. The combination of numerical weather prediction data and satellite observations exhibits great potential for improving automated regional-scale forecasts of fire behavior and smoke emissions

Molecular Basis for Cation Selectivity in Claudin-2–based Paracellular Pores: Identification of an Electrostatic Interaction Site

Paracellular ion transport in epithelia is mediated by pores formed by members of the claudin family. The degree of selectivity and the molecular mechanism of ion permeation through claudin pores are poorly understood. By expressing a high-conductance claudin isoform, claudin-2, in high-resistance Madin-Darby canine kidney cells under the control of an inducible promoter, we were able to quantitate claudin pore permeability. Claudin-2 pores were found to be narrow, fluid filled, and cation selective. Charge selectivity was mediated by the electrostatic interaction of partially dehydrated permeating cations with a negatively charged site within the pore that is formed by the side chain carboxyl group of aspartate-65. Thus, paracellular pores use intrapore electrostatic binding sites to achieve a high conductance with a high degree of charge selectivity

Power Versus Affiliation in Political Ideology

Posited motivational differences between liberals and conservatives have historically been controversial. This motivational interface has recently been bridged, but the vast majority of studies have used self-reports of values or motivation. Instead, the present four studies investigated whether two classic social motive themes—power and affiliation—vary by political ideology in objective linguistic analysis terms. Study 1 found that posts to liberal chat rooms scored higher in standardized affiliation than power, whereas the reverse was true of posts to conservative chat rooms. Study 2 replicated this pattern in the context of materials posted to liberal versus conservative political news websites. Studies 3 and 4, finally, replicated a similar interactive (ideology by motive type) pattern in State of the State and State of the Union addresses. Differences in political ideology, these results suggest, are marked by, and likely reflective of, mind-sets favoring affiliation (liberal) or power (conservative). </jats:p

Impact of August 2017 British Columbia Pyrocumulonimbus Injection Events on Lower Stratospheric Composition

On August 12-13, 2017 large wildfires in the Cariboo region of British Columbia, Canada sparked a series of pyrocumulonimbus events lifting carbonaceous aerosol and other trace gases to the tropopause region (~10-11 km). Over the subsequent days, this plume of trace gas and aerosol species was observed from numerous NASA satellite instruments to rise to over 22 km due to the strong shortwave heating of the carbonaceous aerosol. We will show observations of CO and H2O from the Microwave Limb Sounder (MLS) instrument on Aura satellite demonstrating the clear rise and spread of the plume which can be coherently tracked for at least 2 months. Enhancements in HCN, CH3CN, and methanol (CH3OH) are also evident in MLS measurements with the former two having low vertical resolution. We have also detected a significantly lower concentration of O3 and HNO3 in the plume compared to the surrounding environment, which is consistent with a dynamical perturbation from the rapid diabatic rise of the heated plume from the tropopause through the lower stratosphere. In the weeks and months that followed this plume spread over much of the Northern Hemisphere and the aerosol was observed to be slowly removed by transport back into the troposphere. We will compare and contrast the Aug. 2017 event with the other large event in the MLS record, the Feb. 2009 Australian "Black Saturday" event, and use the Goddard Earth Observing System Chemistry-Climate Model (GEOSCCM) replayed to observed meteorology to understand the effect of the British Columbia event on trace gas species. GEOSCCM helps us to separate the relative roles of dynamics and chemistry on lower stratospheric trace gas composition changes, not only in the rising plume but also the impact of its eventual spread over the Northern Hemisphere during fall and winter of 2017-2018

Studying Black Holes on Horizon Scales with VLBI Ground Arrays

High-resolution imaging of supermassive black holes is now possible, with new applications to testing general relativity and horizon-scale accretion and relativistic jet formation processes. Over the coming decade, the EHT will propose to add new strategically placed VLBI elements operating at 1.3mm and 0.87mm wavelength. In parallel, development of next-generation backend instrumentation, coupled with high throughput correlation architectures, will boost sensitivity, allowing the new stations to be of modest collecting area while still improving imaging fidelity and angular resolution. The goal of these efforts is to move from imaging static horizon scale structure to dynamic reconstructions that capture the processes of accretion and jet launching in near real time