Order by Disorder and Energetic Selection of the Ground State in the XY Pyrochlore Antiferromagnet Er2Ti2O7. An Inelastic Neutron Scattering Study

Examples of materials where an "order by disorder" mechanism is at play to select a particular ground state are scarce. It has recently been proposed, however, that the antiferromagnetic XY pyrochlore Er2Ti2O7, reveals a most convincing case of this mechanism. Observation of a spin gap at zone centers has recently been interpreted as a corroboration of this physics. In this paper, we argue, however, that the anisotropy generated by the interaction-induced admixing between the crystal-field ground and excited levels provides for an alternative mechanism. It especially predicts the opening of a spin gap of about 15 micro-eV, which is of the same order of magnitude as the one observed experimentally. We report new high resolution inelastic neutron scattering data which can be well understood within this scenario.Comment: This version corrects a mistake on the numerical values of the exchange couplings $J$ in relation to the published versio

International Space Station Spacecraft Charging Environments: Modeling, Measurement and Implications for Future Human Space Flight Programs

Spacecraft charging analysis and migration is an interdisciplinary subject combining aspects of electrostatics, plasma physics, ionizing radiation, and materials science, as well as electronic system electromagnetic interference and compatibility (EMI/EMC) effects. Spacecraft charging hazards are caused by the accumulation of electrical charge on spacecraft and spacecraft components produced by interactions with space plasmas, energetic charged particles, and solar UV photons as well as spacecraft electrical power and propulsion systems operations. Spacecraft charging hazard effects include both hard and soft avionics and electrical power system anomalies and have led to the partial or complete loss of numerous spacecraft. The International Space Station (ISS) orbital altitude and inclination (~400 km and 51.6o) determined the dominant natural environment factors affecting ISS spacecraft charging; high speed flight through the geomagnetic field and electrical power system interaction with the cold, high-density ionospheric plasma. In addition ISS is exposed to energetic auroral electrons at high latitude. In this paper we present the results of ISS spacecraft charging modeling and measurements and compare the measurements with numerical modeling of ISS charging processes. ISS is a large metallic structure and flight through the geomagnetic field at orbital speed dominates ISS charging. Collection of ionospheric electrons by the large 160V PV arrays is the next largest contributor. Charging by auroral electrons is detectable but makes a relatively minor contribution. Finally we report the observation of short duration (~ 1 sec) rapid charging peaks associated with shunt/un-shunt operations of the 160V PV arrays, a phenomena not predicted before flight. ISS spacecraft charging environments are radically different from those encountered at higher altitudes in Earth?s magnetosphere and in cis-Lunar space. We present a brief review of those charging environments and an assessment of the applicability of ISS spacecraft charging management and experience to future human spaceflight programs beyond LEO

Ampullary cancers harbor ELF3 tumor suppressor gene mutations and exhibit frequent WNT dysregulation

The ampulla of Vater is a complex cellular environment from which adenocarcinomas arise to form a group of histopathologically heterogenous tumors. To evaluate the molecular features of these tumors, 98 ampullary adenocarcinomas were evaluated and compared to 44 distal bile duct and 18 duodenal adenocarcinomas. Genomic analyses revealed mutations in the WNT signaling pathway among half of the patients and in all three adenocarcinomas irrespective of their origin and histological morphology. These tumors were characterized by a high frequency of inactivating mutations of ELF3, a high rate of microsatellite instability, and common focal deletions and amplifications, suggesting common attributes in the molecular pathogenesis are at play in these tumors. The high frequency of WNT pathway activating mutation, coupled with small-molecule inhibitors of β-catenin in clinical trials, suggests future treatment decisions for these patients may be guided by genomic analysis

Multi-laboratory assessment of reproducibility, qualitative and quantitative performance of SWATH-mass spectrometry

Quantitative proteomics employing mass spectrometry is an indispensable tool in life science research. Targeted proteomics has emerged as a powerful approach for reproducible quantification but is limited in the number of proteins quantified. SWATH-mass spectrometry consists of data-independent acquisition and a targeted data analysis strategy that aims to maintain the favorable quantitative characteristics (accuracy, sensitivity, and selectivity) of targeted proteomics at large scale. While previous SWATH-mass spectrometry studies have shown high intra-lab reproducibility, this has not been evaluated between labs. In this multi-laboratory evaluation study including 11 sites worldwide, we demonstrate that using SWATH-mass spectrometry data acquisition we can consistently detect and reproducibly quantify \u3e4000 proteins from HEK293 cells. Using synthetic peptide dilution series, we show that the sensitivity, dynamic range and reproducibility established with SWATH-mass spectrometry are uniformly achieved. This study demonstrates that the acquisition of reproducible quantitative proteomics data by multiple labs is achievable, and broadly serves to increase confidence in SWATH-mass spectrometry data acquisition as a reproducible method for large-scale protein quantification.SWATH-mass spectrometry consists of a data-independent acquisition and a targeted data analysis strategy that aims to maintain the favorable quantitative characteristics on the scale of thousands of proteins. Here, using data generated by eleven groups worldwide, the authors show that SWATH-MS is capable of generating highly reproducible data across different laboratories

Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH -Mutant Molecular Profiles

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance

The MMS22L-TONSL Complex Mediates Recovery from Replication Stress and Homologous Recombination

Genome integrity is jeopardized each time DNA replication forks stall or collapse. Here we report the identification of a complex composed of MMS22L (C6ORF167) and TONSL (NFKBIL2) that participates in the recovery from replication stress. MMS22L and TONSL are homologous to yeast Mms22 and plant Tonsoku/Brushy1, respectively. MMS22L-TONSL accumulates at regions of ssDNA associated with distressed replication forks or at processed DNA breaks, and its depletion results in high levels of endogenous DNA double-strand breaks caused by an inability to complete DNA synthesis after replication fork collapse. Moreover, cells depleted of MMS22L are highly sensitive to camptothecin, a topoisomerase I poison that impairs DNA replication progression. Finally, MMS22L and TONSL are necessary for the efficient formation of RAD51 foci after DNA damage, and their depletion impairs homologous recombination. These results indicate that MMS22L and TONSL are genome caretakers that stimulate the recombination-dependent repair of stalled or collapsed replication forks

Ampullary Cancers Harbor ELF3 Tumor Suppressor Gene Mutations and Exhibit Frequent WNT Dysregulation

The ampulla of Vater is a complex cellular environment from which adenocarcinomas arise to form a group of histopathologically heterogenous tumors. To evaluate the molecular features of these tumors, 98 ampullary adenocarcinomas were evaluated and compared to 44 distal bile duct and 18 duodenal adenocarcinomas. Genomic analyses revealed mutations in the WNT signaling pathway among half of the patients and in all three adenocarcinomas irrespective of their origin and histological morphology. These tumors were characterized by a high frequency of inactivating mutations of ELF3, a high rate of microsatellite instability, and common focal deletions and amplifications, suggesting common attributes in the molecular pathogenesis are at play in these tumors. The high frequency of WNT pathway activating mutation, coupled with small-molecule inhibitors of beta-catenin in clinical trials, suggests future treatment decisions for these patients may be guided by genomic analysis