Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations ...have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Three-dimensional Bi-chalcogenide topological insulators exhibit surface states populated by massless Dirac fermions that are topologically protected from disorder scattering. Here, we demonstrate ...that these states can be enhanced or destroyed by strain in the vicinity of grain boundaries on the surface of epitaxial Bi2 Se3 (0001) thin films. Using scanning tunnelling and transmission electron microscopy, we show that the low-angle tilt grain boundaries in Bi2 Se3 (0001) films consist of arrays of alternating edge dislocation pairs. Along the boundary, these dislocations introduce periodic in-plane compressive and tensile strains. From tunnelling spectroscopy experiments and first-principles calculations, we find that whereas the energy of the Dirac state shifts in regions under tensile strain, a gap opens in regions under compressive strain, indicative of the destruction of the Dirac states at the surface. These results demonstrate that Dirac states can be tuned by strain at the atomic scale.
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IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
OBJECTIVES: To evaluate the prevalence of malnutrition and its impact on mortality, functional decline and cognitive impairment among elder residents in long-term care settings. DESIGNS: A ...prospective cohort study. SETTINGS: Two veteran homes in Taiwan. PARTICIPANTS: A total of 1,248 male residents aged equal or more than 65 years. MEASUREMENTS: Charlson’s comorbidity index (CCI), Minimum data set (MDS), resident assessment protocols (RAP), Activity of daily living-Hierarchy scale, Cognitive Performance Scale, MDS Social engagement scale. RESULTS: The mean age of participants is 83.1 ± 5.1 years, and the prevalence of malnutrition was 6.1%. Inadequate dietary content (57.9%) and unintentional weight loss (31.6%) account for the majority of malnutrition identified by MDS tool. Higher 18-month mortality rate (25% vs. 14.2%), higher baseline CCI (median 1 vs. 0), and higher baseline sum of RAP triggers (median 8.5 vs. 5) were noted among residents with malnutrition. Furthermore, malnutrition was shown predictive for functional decline (OR: 3.096, 95% CI: 1.715-5.587) and potential cognitive improvement (OR: 2.469, 95% CI: 1.188-5.128) among survivors after adjustment for age, body mass index and CCI. CONCLUSION: Malnutrition among elder men residing in veteran homes was associated with multimoridities and higher care complexity, and was predictive for mortality and functional decline.
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UL, UM, UPCLJ, UPUK, VKSCE, VSZLJ, ZAGLJ, ZRSKP
Magnetotail reconnection plays a crucial role in explosive energy conversion in geospace. Because of the lack of in-situ spacecraft observations, the onset mechanism of magnetotail reconnection, ...however, has been controversial for decades. The key question is whether magnetotail reconnection is externally driven to occur first on electron scales or spontaneously arising from an unstable configuration on ion scales. Here, we show, using spacecraft observations and particle-in-cell (PIC) simulations, that magnetotail reconnection starts from electron reconnection in the presence of a strong external driver. Our PIC simulations show that this electron reconnection then develops into ion reconnection. These results provide direct evidence for magnetotail reconnection onset caused by electron kinetics with a strong external driver.
In this paper, we investigate the sources for Palu Bay tsunamis, which occurred in September 2018 after a M
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7.5 earthquake struck on a strike-slip fault. Previous land-based field studies have ...identified numerous coastal landslides as possible sources for tsunami generation. Here, we present new post-earthquake bathymetry survey data in the bay. We compare the new very detailed nearshore bathymetry with the pre-earthquake data so as to quantify the magnitudes and configurations of coastal landslides and the characteristics of landslide-generated waves. We perform numerical simulations of tsunami propagation, isolating the coastal landslides as the only sources. The results show that, although the landslide-generated waves characteristically have shorter periods than the observed tsunami waves, the combination of the waves is able to produce long waves comparable with those observed, due to the ringing effects of the trapped waves inside the bay. Therefore, we conclude that landslide-generated waves played a significant role in the tsunamis in Palu Bay. Nevertheless, it is likely that the tsunamis were caused by a combination of tectonic and landslide sources.
Delayed single- and few-electron emissions plague dual-phase time projection chambers, limiting their potential to search for light-mass dark matter. This paper examines the origins of these events ...in the XENON1T experiment. Characterization of the intensity of delayed electron backgrounds shows that the resulting emissions are correlated, in time and position, with high-energy events and can effectively be vetoed. In this work we extend previous S2-only analyses down to a single electron. From this analysis, after removing the correlated backgrounds, we observe rates <30 events/(electron×kg×day) in the region of interest spanning 1 to 5 electrons. We derive 90% confidence upper limits for dark matter-electron scattering, first direct limits on the electric dipole, magnetic dipole, and anapole interactions, and bosonic dark matter models, where we exclude new parameter space for dark photons and solar dark photons.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
It has been shown that inhibiting the expression of certain cytokines decreases the rate of tooth movement. Here, we hypothesized that stimulating the expression of inflammatory cytokines, through ...small perforations of cortical bone, increases the rate of bone remodeling and tooth movement. Forty-eight rats were divided into 4 groups: 50-cN force applied to the maxillary first molar (O), force application plus soft tissue flap (OF), force application plus flap plus 3 small perforations of the cortical plate (OFP), and a control group (C). From the 92 cytokines studied, the expression of 37 cytokines increased significantly in all experimental groups, with 21 cytokines showing the highest levels in the OFP group. After 28 days, micro-computed tomography, light and fluorescent microscopy, and immunohistochemistry demonstrated higher numbers of osteoclasts and bone remodeling activity in the OFP group, accompanied by generalized osteoporosity and increased rate of tooth movement.
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CMK, NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
We introduce a two‐phase model for sand transport in sheet flow regime. This model uses a collisional theory and a k – ɛ fluid turbulence closure to respectively model the sediment and fluid phase ...stresses. The sediment stress closure adopts a balance equation of sediment particle fluctuation energy based on kinetic theory that incorporates two‐way interactions between fluid and sediment phases. The fluid turbulence closure also considers the two‐way interaction between fluid turbulence and sand particles. Model‐data comparisons for the sheet layer for oscillatory flows in a U‐tube and for open channel flows demonstrate the model's predictive skill. For steady open channel flows the fluid phase velocity follows closely the law of wall (i.e., the log‐profile) in which the von Karman constant is reduced and the equivalent roughness is increased, compared to the clear fluid flow conditions. The model also provides information in the near‐bed region where the transition from the solid‐like to the fluid‐like behavior of sediment particles is resolved and both the bed load layer thickness and bed load transport rate can be evaluated. For unsteady flows, this model can predict time evolutions for sediment transport throughout the water column.
Previous studies have observed evoked response latency as well as gamma band superior temporal gyrus (STG) auditory abnormalities in individuals with autism spectrum disorders (ASD). A limitation of ...these studies is that associations between these two abnormalities, as well as the full extent of oscillatory phenomena in ASD in terms of frequency and time, have not been examined. Subjects were presented pure tones at 200, 300, 500, and 1,000 Hz while magnetoencephalography assessed activity in STG auditory areas in a sample of 105 children with ASD and 36 typically developing controls (TD). Findings revealed a profile such that auditory STG processes in ASD were characterized by pre-stimulus abnormalities across multiple frequencies, then early high-frequency abnormalities followed by low-frequency abnormalities. Increased pre-stimulus activity was a ‘core’ abnormality, with pre-stimulus activity predicting post-stimulus neural abnormalities, group membership, and clinical symptoms (CELF-4 Core Language Index). Deficits in synaptic integration in the auditory cortex are associated with oscillatory abnormalities in ASD as well as patient symptoms. Increased pre-stimulus activity in ASD likely demonstrates a fundamental signal-to-noise deficit in individuals with ASD, with elevations in oscillatory activity suggesting an inability to maintain an appropriate ‘neural tone’ and an inability to rapidly return to a resting state prior to the next stimulus.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Substantial amounts of secondary organic aerosol (SOA) can be formed from isoprene epoxydiols (IEPOX), which are oxidation products of isoprene mainly under low-NO conditions. Total IEPOX-SOA, which ...may include SOA formed from other parallel isoprene oxidation pathways, was quantified by applying positive matrix factorization (PMF) to aerosol mass spectrometer (AMS) measurements. The IEPOX-SOA fractions of organic aerosol (OA) in multiple field studies across several continents are summarized here and show consistent patterns with the concentration of gas-phase IEPOX simulated by the GEOS-Chem chemical transport model. During the Southern Oxidant and Aerosol Study (SOAS), 78 % of PMF-resolved IEPOX-SOA is accounted by the measured IEPOX-SOA molecular tracers (2-methyltetrols, C5-Triols, and IEPOX-derived organosulfate and its dimers), making it the highest level of molecular identification of an ambient SOA component to our knowledge. An enhanced signal at C5H6O+ (m/z 82) is found in PMF-resolved IEPOX-SOA spectra. To investigate the suitability of this ion as a tracer for IEPOX-SOA, we examine fC5H6O (fC5H6O= C5H6O+/OA) across multiple field, chamber, and source data sets. A background of ~ 1.7 ± 0.1 ‰ (‰ = parts per thousand) is observed in studies strongly influenced by urban, biomass-burning, and other anthropogenic primary organic aerosol (POA). Higher background values of 3.1 ± 0.6 ‰ are found in studies strongly influenced by monoterpene emissions. The average laboratory monoterpene SOA value (5.5 ± 2.0 ‰) is 4 times lower than the average for IEPOX-SOA (22 ± 7 ‰), which leaves some room to separate both contributions to OA. Locations strongly influenced by isoprene emissions under low-NO levels had higher fC5H6O (~ 6.5 ± 2.2 ‰ on average) than other sites, consistent with the expected IEPOX-SOA formation in those studies. fC5H6O in IEPOX-SOA is always elevated (12–40 ‰) but varies substantially between locations, which is shown to reflect large variations in its detailed molecular composition. The low fC5H6O (< 3 ‰) reported in non-IEPOX-derived isoprene-SOA from chamber studies indicates that this tracer ion is specifically enhanced from IEPOX-SOA, and is not a tracer for all SOA from isoprene. We introduce a graphical diagnostic to study the presence and aging of IEPOX-SOA as a triangle plot of fCO2 vs. fC5H6O. Finally, we develop a simplified method to estimate ambient IEPOX-SOA mass concentrations, which is shown to perform well compared to the full PMF method. The uncertainty of the tracer method is up to a factor of ~ 2, if the fC5H6O of the local IEPOX-SOA is not available. When only unit mass-resolution data are available, as with the aerosol chemical speciation monitor (ACSM), all methods may perform less well because of increased interferences from other ions at m/z 82. This study clarifies the strengths and limitations of the different AMS methods for detection of IEPOX-SOA and will enable improved characterization of this OA component.
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