Intrinsic Cellular Susceptibility to Barrett’s Esophagus in Adults Born with Esophageal Atresia

The prevalence of Barrett’s esophagus (BE) in adults born with esophageal atresia (EA) is four times higher than in the general population and presents at a younger age (34 vs. 60 years). This is (partly) a consequence of chronic gastroesophageal reflux. Given the overlap between genes and pathways involved in foregut and BE development, we hypothesized that EA patients have an intrinsic predisposition to develop BE. Transcriptomes of Esophageal biopsies of EA patients with BE (n = 19, EA/BE); EA patients without BE (n = 44, EA-only) and BE patients without EA (n = 10, BE-only) were compared by RNA expression profiling. Subsequently, we simulated a reflux episode by exposing fibroblasts of 3 EA patients and 3 controls to acidic conditions. Transcriptome responses were compared to the differential expressed transcripts in the biopsies. Predisposing single nucleotide polymorphisms, associated with BE, were slightly increased in EA/BE versus BE-only patients. RNA expression profiling and pathway enrichment analysis revealed differences in retinoic acid metabolism and downstream signaling pathways and inflammatory, stress response and oncological processes. There was a similar effect on retinoic acid signaling and immune response in EA patients upon acid exposure. These results indicate that epithelial tissue homeostasis in EA patients is more prone to acidic disturbances

Intrinsic Cellular Susceptibility to Barrett’s Esophagus in Adults Born with Esophageal Atresia

The prevalence of Barrett’s esophagus (BE) in adults born with esophageal atresia (EA) is four times higher than in the general population and presents at a younger age (34 vs. 60 years). This is (partly) a consequence of chronic gastroesophageal reflux. Given the overlap between genes and pathways involved in foregut and BE development, we hypothesized that EA patients have an intrinsic predisposition to develop BE. Transcriptomes of Esophageal biopsies of EA patients with BE (n = 19, EA/BE); EA patients without BE (n = 44, EA-only) and BE patients without EA (n = 10, BE-only) were compared by RNA expression profiling. Subsequently, we simulated a reflux episode by exposing fibroblasts of 3 EA patients and 3 controls to acidic conditions. Transcriptome responses were compared to the differential expressed transcripts in the biopsies. Predisposing single nucleotide polymorphisms, associated with BE, were slightly increased in EA/BE versus BE-only patients. RNA expression profiling and pathway enrichment analysis revealed differences in retinoic acid metabolism and downstream signaling pathways and inflammatory, stress response and oncological processes. There was a similar effect on retinoic acid signaling and immune response in EA patients upon acid exposure. These results indicate that epithelial tissue homeostasis in EA patients is more prone to acidic disturbances

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Two-Dimensional Substitution: Towards a Better Understanding of the Structure-Transport Correlations in the Li-Superionic Thio-LISICONs

A deeper understanding of the relationships among composition‒structure‒transport properties in inorganic solid ionic conductors is of paramount importance to develop highly conductive phases for future employment in solid‒state Li‒ion battery applications. In order to shed light on the mechanisms that regulate these relationships, in this work we perform a “two-dimensional” substitution series in the thio-LISICON family Li4Ge1‒xSnxS4‒ySey. The structural modifications brought up by the elemental substitutions were investigated via Rietveld refinements against high‒resolution neutron diffraction data that allowed a precise characterization of the anionic framework and the lithium substructure. The analyses show that the anionic and cationic substitutions influence the polyhedral and unit cell volumes in different fashions and that the size of the polyanionic groups alone is not enough to describe lattice expansion in these materials. Moreover, we show that the lithium disorder that is crucial to achieve fast ionic mobility may be correlated to the lithium polyhedral volumes. The correlation of these structural modifications with the transport properties, investigated via electrochemical impedance spectroscopy and 7Li nuclear magnetic resonance spin-lattice relaxation measurements, shows a non-monotonic behavior of the ionic conductivity and activation energy against the lithium polyhedral volumes, hinting to an optimal size of the conduction pathways for the ionic diffusion. Ultimately, the results obtained in this work will help to establish new guidelines for the optimization of solid electrolytes and to gain a more profound understanding of the influence of the substituents on the structure and transport properties of Li‒ion conductor

Synthesis-Controlled Cation Solubility in Solid Sodium Ion Conductors Na2+xZr1–xInxCl6Na_{2+x}Zr_{1–x}In_xCl_ 6

Mechanochemically synthesized sodium halide solid solutions with the general formula Na2+xZr1–xMxCl6, as a class of potential catholytes, show promising ionic transport in comparison to their parental materials such as Na3YCl6. However, the influence of subsequent heat treatment protocols on the structure and transport properties of these materials is still not fully understood. In this work, a series of Na2+xZr1–xInxCl6 solid solutions are prepared by ball milling with subsequent annealing at different temperatures. X-ray diffraction analyses show a full indium solubility in Na2+xZr1–xInxCl6 when synthesized at low temperatures and crystallizing in the P21/n phase. In contrast, at higher heat treatment temperatures, exsolution is observed as the indium-rich Na2+xZr1–xInxCl6 compound tends to partially transform to the trigonal P3̅1c phase. By assessing the ionic conductivity of the differently synthesized Na2+xZr1–xInxCl6 series, we can show the synergistic effect of the Na+/vacancy ratio and crystallinity on sodium ion transport in this class of materials

Further Evidence for Energy Landscape Flattening in the Superionic Argyrodites Li6+xP1−xMxS5I (M = Si, Ge, Sn)

All-solid-state batteries are promising candidates for next-generation energy storage devices. Although the list of candidate materials for solid electrolytes has grown in the past decade, there are still many open questions concerning the mechanisms behind ionic migration in materials. In particular, the lithium thiophosphate family of materials has shown very promising properties for solid-state battery applications. Recently, the Ge-substituted Li6PS5I argyrodite was shown to be a very fast Li-ion conductor, despite the poor ionic conductivity of the unsubstituted Li6PS5I. Therein, the conductivity was enhanced by over three orders of magnitude due to the emergence of I−/S2−exchange, i.e.site-disorder, which led to a sudden decrease of the activation barrier with a concurrent flattening of the energy landscapes. Inspired by this work, two series of elemental substitutions in Li6+xP1−xMxS5I (M= Si and Sn) were investigated in this study and compared to the Ge-analogue. A sharp reduction in the activation energy was observed at the same M4+/P5+composition as previously found in the Ge-analogue, suggesting a more general mechanism at play. Furthermore, structural analyses with X-ray and neutron diffraction indicate that similar changes in the Li-sublattice occur despite a significant variation in the size of the substituents, suggesting that in the argyrodites, the lithium substructure is most likely influenced by the occurring Li+– Li+interactions. This work provides further evidence that the energy landscape of ionic conductors can be tailored by inducing local disorder.</p

Exploring Aliovalent Substitutions in the Lithium Halide Superionic Conductor Li3-xIn1-xZrxCl6 (0 ≤ X ≤ 0.5)

In recent years, ternary halides Li3MX6 (M = Y, Er, In; X = Cl, Br, I) have garnered attention as solid electrolytes due to their wide electrochemical stability window and favorable room-temperature conductivities. In this material class, the influences of iso- or aliovalent substitutions are so far rarely studied in-depth, despite this being a common tool for correlating structure and transport properties. In this work, we investigate the impact of Zr substitution on the structure and ionic conductivity of Li3InCl6 (Li3-xIn1-xZrxCl6 with 0 ≤ x ≤ 0.5) using a combination of neutron diffraction, nuclear magnetic resonance and impedance spectroscopy. Analysis of high-resolution diffraction data shows the presence of an additional tetrahedrally coordinated lithium position together with cation site-disorder, both of which have not been reported previously for Li3InCl6. This Li+ position and cation disorder lead to the formation of a three-dimensional lithium ion diffusion channel, instead of the expected two-dimensional diffusion. Upon Zr4+ substitution, the structure exhibits non-uniform volume changes along with an increasing number of vacancies, all of which lead to an increasing ionic conductivity in this series of solid solutions.</p

Correlating Structural Disorder to Li+Li^+ Ion Transport in Li4–xGe1–xSbxS4Li_{4–x}Ge_{1–x}Sb_xS_4 (0 ≤ x ≤ 0.2)

Strong compositional influences are known to affect the ionic transport within the thio-LISICON family, however, a deeper understanding of the resulting structure - transport correlations have up until now been lacking. Employing a combination of high-resolution neutron diffraction, impedance spectroscopy and nuclear magnetic resonance spectroscopy, together with bond valence site energy calculations and the maximum entropy method for determining the underlying Li+ scattering density distribution of a crystal structure, this work assesses the impact of the Li+ substructure and charge carrier density on the ionic transport within the Li4-xGe1-xSbxS4 substitution series. By incorporating Sb5+ into Li4GeS4, an anisometric expansion of the unit cell is observed. An additional Li+ position is found as soon as (SbS4)3− polyhedra are present, leading to a better local polyhedral connectivity and a higher disorder in the Li+ substructure. Here, we are able to relate structural disorder to an increase in configurational entropy, together with a two order-of-magnitude increase in ionic conductivity. This result reinforces the typically believed paradigm that structural disorder leads to improvements in ionic transport

Exploring Aliovalent Substitutions in the Lithium Halide Superionic Conductor Li_{3– x}In_{1– x}Zr_xCl₆ (0 ≤ x ≤ 0.5)

In recent years, ternary halides Li3MX6 (M = Y, Er, In; X = Cl, Br, I) have garnered attention assolid electrolytes due to their wide electrochemical stability window and favorable roomtemperatureconductivities. In this material class, the influences of iso- or aliovalentsubstitutions are so far rarely studied in-depth, despite this being a common tool for correlatingstructure and transport properties. In this work, we investigate the impact of Zr substitution onthe structure and ionic conductivity of Li3InCl6 (Li3-xIn1-xZrxCl6 with 0 ≤ x ≤ 0.5) using acombination of neutron diffraction, nuclear magnetic resonance and impedance spectroscopy.Analysis of high-resolution diffraction data shows the presence of an additional tetrahedrallycoordinated lithium position together with cation site-disorder, both of which have not beenreported previously for Li3InCl6. This Li+ position and cation disorder lead to the formation ofa three-dimensional lithium ion diffusion channel, instead of the expected two-dimensionaldiffusion. Upon Zr4+ substitution, the structure exhibits non-uniform volume changes alongwith an increasing number of vacancies, all of which lead to an increasing ionic conductivity inthis series of solid solution