To provide insights into the mode of action for Ni3S2 lung carcinogenicity by examining gene expression changes in target cells after inhalation exposure.
Gene expression changes were determined in ...micro-dissected lung broncho-alveolar cells from Fischer 344 rats following inhalation of Ni3S2 at 0.0, 0.04, 0.08, 0.15, and 0.60mg/m3 (0.03, 0.06, 0.11, and 0.44mgNi/m3) for one and four weeks (6h/day, 5days/week).
Broncho-alveolar lavage fluid evaluation and lung histopathology provided evidence of inflammation only at the two highest concentrations, which were similar to those tested in the 2-year bioassay. The number of statistically significant up- and down-regulated genes decreased markedly from one to four weeks of exposure, suggesting adaptation. Cell signal pathway enrichment at both time-points primarily reflected responses to toxicity, including inflammatory and proliferative signaling. While proliferative signaling was up-regulated at both time points, some inflammatory signaling reversed from down-regulation at 1week to up-regulation at 4weeks.
These results support a mode of action for Ni3S2 carcinogenicity driven by chronic toxicity, inflammation and proliferation, leading to mis-replication, rather than by direct genotoxicity. Benchmark dose (BMD) analysis identified the lowest pathway transcriptional BMD exposure concentration as 0.026mgNi/m3, for apoptosis/survival signaling. When conducted on the basis of lung Ni concentration the lowest pathway BMD was 0.64μgNi/g lung, for immune/inflammatory signaling.
These highly conservative BMDs could be used to derive a point of departure in a nonlinear risk assessment for Ni3S2 toxicity and carcinogenicity.
•The mode of action for lung carcinogenicity of inhaled Ni3S2 was investigated in rats.•Gene expression changes were determined in micro-dissected lung tissue at 1–4weeks.•A non-genotoxic mode of action (toxicity, inflammation, proliferation) was supported.•Analyses of lung lavage fluid and histopathology provided complementary results.•Transcriptional benchmark doses could inform point of departure for risk assessment.
The KamLAND-Zen experiment has provided stringent constraints on the neutrinoless double-beta (0νββ) decay half-life in ^{136}Xe using a xenon-loaded liquid scintillator. We report an improved search ...using an upgraded detector with almost double the amount of xenon and an ultralow radioactivity container, corresponding to an exposure of 970 kg yr of ^{136}Xe. These new data provide valuable insight into backgrounds, especially from cosmic muon spallation of xenon, and have required the use of novel background rejection techniques. We obtain a lower limit for the 0νββ decay half-life of T_{1/2}^{0ν}>2.3×10^{26} yr at 90% C.L., corresponding to upper limits on the effective Majorana neutrino mass of 36-156 meV using commonly adopted nuclear matrix element calculations.
We present an improved search for neutrinoless double-beta (0νββ) decay of ^{136}Xe in the KamLAND-Zen experiment. Owing to purification of the xenon-loaded liquid scintillator, we achieved a ...significant reduction of the ^{110m}Ag contaminant identified in previous searches. Combining the results from the first and second phase, we obtain a lower limit for the 0νββ decay half-life of T_{1/2}^{0ν}>1.07×10^{26} yr at 90% C.L., an almost sixfold improvement over previous limits. Using commonly adopted nuclear matrix element calculations, the corresponding upper limits on the effective Majorana neutrino mass are in the range 61-165 meV. For the most optimistic nuclear matrix elements, this limit reaches the bottom of the quasidegenerate neutrino mass region.
We report the first measurement of coherent elastic neutrino-nucleus scattering (CEvNS) on argon using a liquid argon detector at the Oak Ridge National Laboratory Spallation Neutron Source. Two ...independent analyses prefer CEvNS over the background-only null hypothesis with greater than 3σ significance. The measured cross section, averaged over the incident neutrino flux, is (2.2±0.7)×10^{-39} cm^{2}-consistent with the standard model prediction. The neutron-number dependence of this result, together with that from our previous measurement on CsI, confirms the existence of the CEvNS process and provides improved constraints on nonstandard neutrino interactions.
Abstract
We report on a search for electron antineutrinos (
ν
¯
e
) from astrophysical sources in the neutrino energy range 8.3–30.8 MeV with the KamLAND detector. In an exposure of 6.72 kton-year of ...the liquid scintillator, we observe 18 candidate events via the inverse beta decay reaction. Although there is a large background uncertainty from neutral current atmospheric neutrino interactions, we find no significant excess over background model predictions. Assuming several supernova relic neutrino spectra, we give upper flux limits of 60–110 cm
−2
s
−1
(90% confidence level, CL) in the analysis range and present a model-independent flux. We also set limits on the annihilation rates for light dark matter pairs to neutrino pairs. These data improve on the upper probability limit of
8
B solar neutrinos converting into
ν
¯
e
,
P
ν
e
→
ν
¯
e
<
3.5
×
10
−
5
(90% CL) assuming an undistorted
ν
¯
e
shape. This corresponds to a solar
ν
¯
e
flux of 60 cm
−2
s
−1
(90% CL) in the analysis energy range.
The coherent elastic scattering of neutrinos off nuclei has eluded detection for four decades, even though its predicted cross section is by far the largest of all low-energy neutrino couplings. This ...mode of interaction offers new opportunities to study neutrino properties and leads to a miniaturization of detector size, with potential technological applications. We observed this process at a 6.7σ̃ confidence level, using a low-background, 14.6-kilogram CsINa scintillator exposed to the neutrino emissions from the Spallation Neutron Source at Oak Ridge National Laboratory. Characteristic signatures in energy and time, predicted by the standard model for this process, were observed in high signal-to-background conditions. Improved constraints on nonstandard neutrino interactions with quarks are derived from this initial data set.
The catalytic properties of organophosphate hydrolase (OPH) containing a hexahistidine tag His6 (His6-OPH) and purified to 98% homogeneity were investigated. The pH optimum of enzymatic activity and ...isoelectric point of His6-OPH, which were shown to be 10.5 and 8.5, respectively, are shifted to the alkaline range as compared to the same parameters of the native OPH. The recombinant enzyme possessed improved catalytic activity towards S-containing substrates: the catalytic efficiency of methylparathion hydrolysis by His6-OPH is 4.2 x 10(6) M(-1) x sec(-1), whereas by native OPH it is 3.5 x 10(5) M(-1) x sec(-1).
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