A
bstract
The
Neutrino Experiment with a Xenon TPC
(NEXT) searches for the neutrinoless double-beta (0
νββ
) decay of
136
Xe using high-pressure xenon gas TPCs with electroluminescent amplification. ...A scaled-up version of this technology with about 1 tonne of enriched xenon could reach in less than 5 years of operation a sensitivity to the half-life of 0
νββ
decay better than 10
27
years, improving the current limits by at least one order of magnitude. This prediction is based on a well-understood background model dominated by radiogenic sources. The detector concept presented here represents a first step on a compelling path towards sensitivity to the parameter space defined by the inverted ordering of neutrino masses, and beyond.
The aim of this work was to improve the knowledge of the role of histamine in breast cancer by assessing the therapeutic efficacy of histamine and histamine H4 receptor (H4R) ligands in a ...triple-negative breast cancer (TNBC) model developed in immunocompetent hosts. By using publicly available genomic data, we further investigated whether histidine decarboxylase (HDC) could be a potential biomarker.
Tumours of 4T1 TNBC cells were orthotopically established in BALB/c mice. Treatments employed (mg kg
): histamine (1 and 5), JNJ28610244 (H4R agonist, 1 and 5) and JNJ7777120 (H4R antagonist, 10).
Increased HDC gene expression is associated with better relapse-free and overall survival in breast cancer patients. Histamine treatment (5 mg kg
) of 4T1 tumour-bearing mice reduced tumour growth and increased apoptosis. Although no immunomodulatory effects were observed in wild-type mice, significant correlations between tumour weight and cytotoxic lymphocyte infiltration were detected in H4R knockout mice. H4R agonist or antagonist differentially modulated tumour growth and immunity in 4T1 tumour-bearing mice.
Histamine plays a complex role and stands out as a promising drug for TNBC treatment, which deserves to be tested in clinical settings. HDC expression level is associated with clinicopathological characteristics, suggesting a prognostic value in breast cancer.
An experiment is conducted in a rectangular channel obstructed by a transverse line of four inclined cylindrical rods. The pressure on the surface of a central rod and the pressure drop through the ...channel are measured varying the inclination angle of the rods. Three assemblies of rods with different diameters are tested. The measurements were analyzed applying momentum conservation principles and semi-empirical considerations. Several invariant dimensionless groups of parameters relating the pressure at key locations of the system with characteristic dimensions of the rods are produced. It was found that the independence principle holds for most of the Euler numbers characterizing the pressure at different locations, that is, the group is independent of the inclination angle provided that the inlet velocity projection normal to the rods is used to non-dimensionalize the pressure. The resulting semi-empirical correlations can be useful for designing similar hydraulic units.
Although the role of histamine H4 receptor (H4R) in immune cells is being extensively investigated, its immunomodulatory function in cancer is completely unknown. This study aimed to investigate the ...role of H4R in antitumour immunity in a model of triple-negative breast cancer.
We evaluated growth parameters, histological characteristics and the composition of tumour, splenic and tumour draining lymph node (TDLN) immune subsets, in a syngeneic model, developed orthotopically with 4T1 cells in H4R knockout (H4R-KO) and wild-type mice.
Mice lacking H4R show reduced tumour size and weight, decreased number of lung metastases and percentage of CD4
tumour-infiltrating T cells, while exhibiting increased infiltration of NK cells and CD19
lymphocytes. Likewise, TDLN of H4R-KO mice show decreased CD4
T cells and T regulatory cells (CD4
CD25
FoxP3
), and increased percentages of NK cells. Finally, H4R-deficient mice show decreased Tregs in spleens and non-draining lymph nodes, and a negative correlation between tumour weight and the percentages of CD4
, CD19
and NK splenic cells, suggesting that H4R also regulates antitumour immunity at a systemic level.
This is the first report that demonstrates the participation of H4R in antitumour immunity, suggesting that H4R could be a target for cancer treatment.
A
bstract
Convolutional neural networks (CNNs) are widely used state-of-the-art computer vision tools that are becoming increasingly popular in high-energy physics. In this paper, we attempt to ...understand the potential of CNNs for event classification in the NEXT experiment, which will search for neutrinoless double-beta decay in
136
Xe. To do so, we demonstrate the usage of CNNs for the identification of electron-positron pair production events, which exhibit a topology similar to that of a neutrinoless double-beta decay event. These events were produced in the NEXT-White high-pressure xenon TPC using 2.6 MeV gamma rays from a
228
Th calibration source. We train a network on Monte Carlo-simulated events and show that, by applying on-the-fly data augmentation, the network can be made robust against differences between simulation and data. The use of CNNs offers significant improvement in signal efficiency and background rejection when compared to previous non-CNN-based analyses.
ABSTRACT
The interaction of volatile species with carbonaceous interstellar dust analogues is of relevance in the chemistry and physics of dense clouds in the interstellar medium. Two deposits of ...hydrogenated amorphous carbon (HAC), with different morphologies and aromatic versus aliphatic ratio in their structure, have been grown to model interstellar dust. The interaction of N2, CO, CH4, and CO2 with these two surfaces has been investigated using thermal programmed desorption (TPD). Desorption energy distributions were obtained by analysing TPD spectra for one monolayer coverage with the Polanyi–Wigner equation. The desorption energies found in this work for N2, CO, and CH4 are larger by 10–20 per cent than those reported in the literature for siliceous or amorphous solid water surfaces. Moreover, the experiments suggest that the interaction of the volatiles with the aromatic substructure of HAC is stronger than that with the aliphatic part. Desorption of CO2 from the HAC surfaces follows zero-order kinetics, reflecting the predominance of CO2–CO2 interactions. A model simulation of the heating of cold cloud cores shows that the volatiles considered in this work would desorb sequentially from carbonaceous dust surfaces with desorption times ranging from hundreds to tens of thousands of years, depending on the molecule and on the mass of the core.
A new method to tag the barium daughter in the double-beta decay of ^{136}Xe is reported. Using the technique of single molecule fluorescent imaging (SMFI), individual barium dication (Ba^{++}) ...resolution at a transparent scanning surface is demonstrated. A single-step photobleach confirms the single ion interpretation. Individual ions are localized with superresolution (∼2 nm), and detected with a statistical significance of 12.9σ over backgrounds. This lays the foundation for a new and potentially background-free neutrinoless double-beta decay technology, based on SMFI coupled to high pressure xenon gas time projection chambers.
Glutamine synthetase is an essential enzyme in ammonium assimilation and glutamine biosynthesis. The
Haloferax mediterranei
genome has two other
glnA
-type genes (
glnA2
and
glnA3
) in addition to ...the glutamine synthetase gene
glnA.
To determine whether the
glnA2
and
glnA3
genes can replace
glnA
in nitrogen metabolism, we generated deletion mutants of
glnA
. The
glnA
deletion mutants could not be generated in a medium without glutamine, and thus,
glnA
is an essential gene in
H. mediterranei
. The
glnA
deletion mutant was achieved by adding 40 mM glutamine to the selective medium. This conditional HM26-Δ
glnA
mutant was characterised with different approaches in the presence of distinct nitrogen sources and nitrogen starvation. Transcriptomic analysis was performed to compare the expression profiles of the strains HM26-Δ
glnA
and HM26 under different growth conditions. The
glnA
deletion did not affect the expression of
glnA2, glnA3
and nitrogen assimilation genes under nitrogen starvation. Moreover, the results showed that
glnA, glnA2
and
glnA3
were not expressed under the same conditions. These results indicated that
glnA
is an essential gene for
H. mediterranei
and, therefore,
glnA2
and
glnA3
cannot replace
glnA
in the conditions analysed.
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