The advanced molybdenum-based rare process experiment (AMoRE) aims to search for neutrinoless double beta decay (
0
ν
β
β
) of
100
Mo with
∼
100
kg
of
100
Mo-enriched molybdenum embedded in cryogenic ...detectors with a dual heat and light readout. At the current, pilot stage of the AMoRE project we employ six calcium molybdate crystals with a total mass of 1.9 kg, produced from
48
Ca-depleted calcium and
100
Mo-enriched molybdenum (
48
depl
Ca
100
MoO
4
). The simultaneous detection of heat (phonon) and scintillation (photon) signals is realized with high resolution metallic magnetic calorimeter sensors that operate at milli-Kelvin temperatures. This stage of the project is carried out in the Yangyang underground laboratory at a depth of 700 m. We report first results from the AMoRE-Pilot
0
ν
β
β
search with a 111 kg day live exposure of
48
depl
Ca
100
MoO
4
crystals. No evidence for
0
ν
β
β
decay of
100
Mo is found, and a upper limit is set for the half-life of
0
ν
β
β
of
100
Mo of
T
1
/
2
0
ν
>
9.5
×
10
22
years
at 90% C.L. This limit corresponds to an effective Majorana neutrino mass limit in the range
⟨
m
β
β
⟩
≤
(
1.2
-
2.1
)
eV
.
Background
Chronic rhinosinusitis (CRS) is an inflammatory process in the nasal cavity and paranasal sinuses, and bacteria have been considered to be a cause. Indeed, recent evidence indicates that ...bacteria‐derived extracellular vesicles (EV) appear to be an important causative agent of inflammatory diseases. Here, we aimed to evaluate the diversity of nasal microbiota and their secreted EV in patients with CRS.
Methods
Nasal lavage (NAL) fluid samples were obtained from five patients with CRS with polyposis, three patients with CRS without polyposis, and three non‐CRS controls. After preparation of bacteria and EV from samples using differential centrifugation, genomic DNA was extracted and 16S‐rDNA amplicons were subjected to high‐throughput pyrosequencing on a Roche 454 GS‐FLX platform.
Results
Metagenomics showed that bacteria composition was positively correlated with EV composition. Samples from patients with CRS had greater bacterial abundance and lower diversity, both from bacteria and the EV portion of samples, compared with non‐CRS samples. At each phylogenetic level, Bacteroidetes decreased while Proteobacteria increased in the CRS group at the phylum level. At the genus level, Prevotella spp. decreased in the CRS group, while Staphylococcus spp. increased from both bacteria and EV. Moreover, Staphylococcus aureus and its secreting EV compositions were higher in samples from CRS with polyps compared with CRS without polyps.
Conclusions
These results suggest that patients with CRS have altered nasal microbiota and decreased diversity in bacterial compositions as well as increased S. aureus abundance in those patients with polyps.
Gliomas are associated with high mortality because of their exceedingly invasive character. As these tumors acquire their invasiveness from low-grade tumors, it is very important to understand the ...detailed molecular mechanisms of invasion onset. Recent evidences suggest the significant role of microRNAs in tumor invasion. Thus, we hypothesized that deregulation of microRNAs may be important for the malignant progression of gliomas. We found that the aberrant expression of miR-21 is responsible for glioma invasion by disrupting the negative feedback circuit of Ras/MAPK signaling, which is mediated by Spry2. Upregulation of miR-21 was triggered by tumor microenvironmental factors such as hyaluronan and growth factors in glioma cells lacking functional phosphatase and tensin homolog (PTEN), but not harboring wild-type PTEN. Consistently with these in vitro results, Spry2 protein levels were significantly decreased in 79.7% of invasive WHO grade II-IV human glioma tissues, but not in non-invasive grade I and normal tissues. The Spry2 protein levels were not correlated with their mRNA levels, but inversely correlated with miR-21 levels. Taken together, these results suggest that the post-transcriptional regulation of Spry2 by miR-21 has an essential role on the malignant progression of human gliomas. Thus, Spry2 may be a novel therapeutic target for treating gliomas.
The recovery of the stratospheric ozone layer relies on the continued decline in the atmospheric concentrations of ozone-depleting gases such as chlorofluorocarbons
. The atmospheric concentration of ...trichlorofluoromethane (CFC-11), the second-most abundant chlorofluorocarbon, has declined substantially since the mid-1990s
. A recently reported slowdown in the decline of the atmospheric concentration of CFC-11 after 2012, however, suggests that global emissions have increased
. A concurrent increase in CFC-11 emissions from eastern Asia contributes to the global emission increase, but the location and magnitude of this regional source are unknown
. Here, using high-frequency atmospheric observations from Gosan, South Korea, and Hateruma, Japan, together with global monitoring data and atmospheric chemical transport model simulations, we investigate regional CFC-11 emissions from eastern Asia. We show that emissions from eastern mainland China are 7.0 ± 3.0 (±1 standard deviation) gigagrams per year higher in 2014-2017 than in 2008-2012, and that the increase in emissions arises primarily around the northeastern provinces of Shandong and Hebei. This increase accounts for a substantial fraction (at least 40 to 60 per cent) of the global rise in CFC-11 emissions. We find no evidence for a significant increase in CFC-11 emissions from any other eastern Asian countries or other regions of the world where there are available data for the detection of regional emissions. The attribution of any remaining fraction of the global CFC-11 emission rise to other regions is limited by the sparsity of long-term measurements of sufficient frequency near potentially emissive regions. Several considerations suggest that the increase in CFC-11 emissions from eastern mainland China is likely to be the result of new production and use, which is inconsistent with the Montreal Protocol agreement to phase out global chlorofluorocarbon production by 2010.
Claudins (CLDNs) are a family of integral membrane proteins central to the formation of tight junctions, structures that are involved in paracellular transport and cellular growth and ...differentiation, and are critical for the maintenance of cellular polarity. Recent studies have provided evidence that CLDNs are aberrantly expressed in diverse types of human cancers, including hepatocellular carcinomas (HCCs). However, little is known about how CLDN expression is involved in cancer progression. In this study, we show that CLDN1 has a causal role in the epithelial-mesenchymal transition (EMT) in human liver cells, and that the c-Abl-Ras-Raf-1-ERK1/2 signaling axis is critical for the induction of malignant progression by CLDN1. Overexpression of CLDN1 induced expression of the EMT-regulating transcription factors Slug and Zeb1, and thereby led to repression of E-cadherin, β-catenin expression, enhanced expression of N-cadherin and Vimentin, a loss of cell adhesion, and increased cell motility in normal liver cells and HCC cells. In line with these findings, inhibition of either c-Abl or ERK clearly attenuated CLDN1-induced EMT, as evidenced by a reversal of N-cadherin and E-cadherin expression patterns, and restored normal motility. Collectively, these results indicate that CLDN1 is necessary for the induction of EMT in human liver cells, and that activation of the c-Abl-Ras-Raf-1-ERK1/2 signaling pathway is required for CLDN1-induced acquisition of the malignant phenotype. The present observations suggest that CLDN1 could be exploited as a biomarker for liver cancer metastasis and might provide a pivotal point for therapeutic intervention in HCC.
Uncovering the mechanisms that govern the maintenance of stem-like cancer cells is critical for developing therapeutic strategies for targeting these cells. Constitutive activation of c-Jun ...N-terminal kinase (JNK) has been reported in gliomas and correlates with histological grade. Here, we found that JNK signaling is crucial for the maintenance of 'stemness' in glioma cells. Sphere-cultured glioma cells showed more phosphorylation of JNK compared with serum-containing monolayer cultures. Importantly, blockade of JNK signaling with SP600125 or small interfering RNAs targeting JNK1 or JNK2 significantly reduced the CD133(+)/Nestin(+) population and suppressed sphere formation, colony formation in soft agar, and expression of stem cell markers in sphere-cultured glioma cells. Intriguingly, sphere-cultured glioma cells exhibited enhanced expression of Notch-2, but not Notch-1, -3 or -4, and JNK inhibition almost completely abrogated this increase. Blocking the phosphoinoside 3-kinase (PI3K)/Akt pathway with LY294002 or si-Akt also suppressed the self-renewal of sphere-cultured glioma cells. PI3K, but not Akt, had a role as an upstream kinase in JNK1/2 activation. In addition, treatment with si-JNK greatly increased etoposide- and ionizing radiation (IR)-induced cell death in glioma spheres. Consistent with glioma cell lines, glioma stem-like cells isolated from primary patient glioma cells also had a higher activity of JNK and Notch-2 expression. Importantly, inhibition of JNK2 led to a decrease of Notch-2 expression and suppressed the CD133(+)/Nestin(+) cell population in patient-derived primary glioma cells. Finally, downregulation of JNK2 almost completely suppressed intracranial tumor formation by glioma cells in nude mice. Taken together, these data demonstrate that JNK signaling is crucial for the maintenance of self-renewal and tumorigenicity of glioma stem-like cells and drug/IR resistance, and can be considered a promising target for eliminating stem-like cancer cells in gliomas.
High catalytic efficiency in metal nanocatalysts is attributed to large surface area to volume ratios and an abundance of under-coordinated atoms that can decrease kinetic barriers. Although overall ...shape or size changes of nanocatalysts have been observed as a result of catalytic processes, structural changes at low-coordination sites such as edges, remain poorly understood. Here, we report high-lattice distortion at edges of Pt nanocrystals during heterogeneous catalytic methane oxidation based on in situ 3D Bragg coherent X-ray diffraction imaging. We directly observe contraction at edges owing to adsorption of oxygen. This strain increases during methane oxidation and it returns to the original state after completing the reaction process. The results are in good agreement with finite element models that incorporate forces, as determined by reactive molecular dynamics simulations. Reaction mechanisms obtained from in situ strain imaging thus provide important insights for improving catalysts and designing future nanostructured catalytic materials.
We present a hierarchical Bayesian method for atmospheric trace gas inversions. This method is used to estimate emissions of trace gases as well as "hyper-parameters" that characterize the ...probability density functions (PDFs) of the a priori emissions and model-measurement covariances. By exploring the space of "uncertainties in uncertainties", we show that the hierarchical method results in a more complete estimation of emissions and their uncertainties than traditional Bayesian inversions, which rely heavily on expert judgment. We present an analysis that shows the effect of including hyper-parameters, which are themselves informed by the data, and show that this method can serve to reduce the effect of errors in assumptions made about the a priori emissions and model-measurement uncertainties. We then apply this method to the estimation of sulfur hexafluoride (SF6) emissions over 2012 for the regions surrounding four Advanced Global Atmospheric Gases Experiment (AGAGE) stations. We find that improper accounting of model representation uncertainties, in particular, can lead to the derivation of emissions and associated uncertainties that are unrealistic and show that those derived using the hierarchical method are likely to be more representative of the true uncertainties in the system. We demonstrate through this SF6 case study that this method is less sensitive to outliers in the data and to subjective assumptions about a priori emissions and model-measurement uncertainties than traditional methods.
We present atmospheric sulfur hexafluoride (SF6 ) mole fractions and emissions estimates from the 1970s to 2008. Measurements were made of archived air samples starting from 1973 in the Northern ...Hemisphere and from 1978 in the Southern Hemisphere, using the Advanced Global Atmospheric Gases Experiment (AGAGE) gas chromatographic-mass spectrometric (GC-MS) systems. These measurements were combined with modern high-frequency GC-MS and GC-electron capture detection (ECD) data from AGAGE monitoring sites, to produce a unique 35-year atmospheric record of this potent greenhouse gas. Atmospheric mole fractions were found to have increased by more than an order of magnitude between 1973 and 2008. The 2008 growth rate was the highest recorded, at 0.29 ± 0.02 pmolmol-1 yr-1 . A three-dimensional chemical transport model and a minimum variance Bayesian inverse method was used to estimate annual emission rates using the measurements, with a priori estimates from the Emissions Database for Global Atmospheric Research (EDGAR, version 4). Consistent with the mole fraction growth rate maximum, global emissions during 2008 were also the highest in the 1973-2008 period, reaching 7.4 ± 0.6 Gg yr-1 (1-σ uncertainties) and surpassing the previous maximum in 1995. The 2008 values follow an increase in emissions of 48 ± 20% since 2001. A second global inversion which also incorporated National Oceanic and Atmospheric Administration (NOAA) flask measurements and in situ monitoring site data agreed well with the emissions derived using AGAGE measurements alone. By estimating continent-scale emissions using all available AGAGE and NOAA surface measurements covering the period 2004-2008, with no pollution filtering, we find that it is likely that much of the global emissions rise during this five-year period originated primarily from Asian developing countries that do not report detailed, annual emissions to the United Nations Framework Convention on Climate Change (UNFCCC). We also find it likely that SF6 emissions reported to the UNFCCC were underestimated between at least 2004 and 2005.
AMoRE is an international project to search for the neutrinoless double beta decay of
100
Mo
using a detection technology consisting of magnetic microcalorimeters (MMCs) and molybdenum-based ...scintillating crystals. Data collection has begun for the current AMORE-I phase of the project, an upgrade from the previous pilot phase. AMoRE-I employs thirteen
48
depl
.
Ca
100
MoO
4
crystals and five
Li
2
100
MoO
4
crystals for a total crystal mass of 6.2 kg. Each detector module contains a scintillating crystal with two MMC channels for heat and light detection. We report the present status of the experiment and the performance of the detector modules.
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