The Modane underground laboratory (LSM) is the deepest operating underground laboratory in Europe. It is located under the Fréjus peak in Savoie Alps in France, with average overburden of 4800 m w. ...e. (water equivalent), providing low-background environment for experiments in nuclear and particle physics, astrophysics and environmental physics. It is crucial to understand individual sources of background such as residual cosmic-ray flux of high-energy muons, muon-induced neutrons and contributions from radionuclides present in the environment. The identified dominant sources of background are radioactive contamination of construction materials of detectors and laboratory walls, radon contamination of the laboratory air, and neutrons produced in the laboratory. The largest neutron contribution has been identified from (α, n) reactions in low Z materials (10−7-10−4 n s−1 Bq−1) and from spontaneous fission of 238U (1.1× 10−6 n s−1 Bq−1).
•Individual background contributions in the Modane underground laboratory are discussed.•Natural radioactive contamination in the detector construction and laboratory environment is the dominant background source.•Neutrons coming from the (α, n) reactions and spontaneous fission have been identified as the dominant neutron background sources.•Muon induced neutrons contribute less than 1% to neutron flux.
IntroductionRecent reports indicate that simultaneous targeting different signalling pathways regulating cell growth with combinations of small molecule inhibitors could be a useful strategy to ...combat cancer and prevent the development of drug resistance. In this study, we identified a dual effect of the pyridinyl imidazoles, widely used p38 MAPK inhibitors, on the growth of malignant melanoma cells bearing BRAF V600E mutation.Material and methodsExperiments were performed in NRAS (Mel-Juso) and BRAF V600E mutant melanoma cells (A375, G361). All cell lines were cultured in RPMI-1640. For the treatment of the cells we used p38 inhibitor BIRB796, MEK inhibitor PD184352, and pyridinyl imidazole compounds SB202190 and SB203580. As pyridinyl imidazoles induce vacuolization of melanoma cells, we used electron and fluorescence microscopy to analyse the origin of the vacuoles. Fluorescent protein-tagged proteins served as markers of the endosomal pathway. We performed western blot analysis to study the effect of pyridinyl imidazoles on the activity of mTOR and ERK pathways. Immunoprecipitations and in-vitro kinase assays were used for the detection of changes in BRAF interacting partners and activity of MEK-ERK signalling, after exposure to pyridinyl imidazoles.Results and discussionsOur study reveals mechanisms, by which the pyridinyl imidazoles affect two critical pro-proliferative pathways, stop cell cycle progression, and decrease the viability of melanoma cells. We found that the compounds can disrupt endocytosis in BRAF-mutant melanoma cells, rather than inhibiting autophagy as previously reported. We show that the resulting accumulation of endocytic vacuoles leads to the deactivation of mTORC1 signalling, that is independent of p38 inhibition. Apart from the effect of these drugs on mTOR activity, they cause a substantial decrease in levels of active ERK kinase. Mechanistically, pyridinyl imidazoles directly bind to the mutated BRAF kinase and inhibit the activation of its downstream targets MEK and ERK.ConclusionThis study identified pyridinyl imidazoles as a class of small molecule compounds capable of dually targeting central proliferative pathways in BRAF-mutant melanoma cells. Our findings could lead to the development of new drugs with anti-melanoma activity.
The Cryogenic Rare Event Search with Superconducting Thermometers (CRESST) experiment aims at the direct detection of dark matter particles via their elastic scattering off nuclei in a scintillating ...CaWO
4
target crystal. The CaWO
4
crystal is operated together with a light detector at mK temperature and read out by a Transition Edge Sensor. For many years, CaWO
4
crystals have successfully been produced in-house at Technical University of Munich (TUM) with a focus on high radiopurity which is crucial to reduce background originating from radioactive contamination. In order to further improve the CaWO
4
crystals, an extensive chemical purification of the raw materials and the synthesised CaWO
4
powder has been performed. In addition, a temperature gradient simulation of the growth process and subsequently an optimisation of the growth furnace with the goal to reduce the intrinsic stress was carried out. We present results on the intrinsic stress in the CaWO
4
crystals and on the CaWO
4
powder radiopurity. A crystal grown from the purified material was installed in the current CRESST set-up. The detector is equipped with an instrumented holder which is used to measure the alpha decay rate of the crystal. We present a preliminary analysis showing a significantly reduced intrinsic background from natural decay chains.
In the current direct dark matter search landscape, the leading experiments in the sub-GeV mass region mostly rely on cryogenic techniques which employ crystalline targets. One attractive type of ...crystals for these experiments is those containing lithium, due to the fact that
7
Li
is an ideal candidate to study spin-dependent dark matter interactions in the low mass region. Furthermore,
6
Li
can absorb neutrons, a challenging background for dark matter experiments, through a distinctive signature which allows the monitoring of the neutron flux directly on site. In this work, we show the results obtained with three different detectors based on
LiAlO
2
, a target crystal never used before in cryogenic experiments.
In this work, a first cryogenic characterization of a scintillating
LiAlO
2
single crystal is presented. The results achieved show that this material holds great potential as a target for direct dark ...matter search experiments. Three different detector modules obtained from one crystal grown at the Leibniz-Institut für Kristallzüchtung (IKZ) have been tested to study different properties at cryogenic temperatures. Firstly, two 2.8 g twin crystals were used to build different detector modules which were operated in an above-ground laboratory at the Max Planck Institute for Physics (MPP) in Munich, Germany. The first detector module was used to study the scintillation properties of
LiAlO
2
at cryogenic temperatures. The second achieved an energy threshold of (
213.02
±
1.48
) eV which allows setting a competitive limit on the spin-dependent dark matter particle-proton scattering cross section for dark matter particle masses between
350
MeV/c
2
and
1.50
GeV/c
2
. Secondly, a detector module with a 373 g
LiAlO
2
crystal as the main absorber was tested in an underground facility at the Laboratori Nazionali del Gran Sasso (LNGS): from this measurement it was possible to determine the radiopurity of the crystal and study the feasibility of using this material as a neutron flux monitor for low-background experiments.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Assessment of radioactive contamination of construction materials used in deep underground experiments has been carried out using ultra-sensitive analytical methods such as radiometrics, inductively ...coupled plasma mass spectrometry (ICPMS), accelerator mass spectrometry (AMS), and neutron activation analysis. The lowest detection limits, < 1 nBq g
−1
, has been obtained with ICPMS and AMS techniques.
Various approaches of determining CO2 fluxes from the soil based on 222Rn calibrated method were tested. It was shown that the exponential fits of CO2 and 222Rn depth profiles led to uncertainties up ...to 50% if the depth profiles of CO2 and 222Rn concentration were not measured at sufficient depths. However, CO2 fluxes determined from linear fits of CO2 and 222Rn concentrations in the surface layer of the soil are lower than the fluxes determined from exponential fits, and have lower uncertainties. The comparison of CO2 fluxes derived from 222Rn calibrated methods with directly measured CO2 fluxes showed that the latter are usually on the order of tens of percent higher than the former. CO2 flux from sandy-clay and uncultivated soil was estimated to be on the level of 3.0 mmol m-2 h-1 in the spring and around 7.0 mmol m-2 h-1 in the summer.
The NEMO-3 results for the double-
β
decay of
150
Nd to the 0
1
+
and 2
1
+
excited states of
150
Sm are reported. The data recorded during 5.25 year with 36.6 g of the isotope
150
Nd are used in the ...analysis. The signal of the
2
ν
β
β
transition to the 0
1
+
excited state is detected with a statistical significance exceeding 5
σ
. The half-life is measured to be
T
1
/
2
2
ν
β
β
(
0
1
+
)
=
1
.
11
-
0.14
+
0.19
stat
-
0.15
+
0.17
syst
×
10
20
year, which is the most precise value that has been measured to date. 90% confidence-level limits are set for the other decay modes. For the
2
ν
β
β
decay to the 2
1
+
level the limit is
T
1
/
2
2
ν
β
β
(
2
1
+
)
>
2.42
×
10
20
year
. The limits on the
0
ν
β
β
decay to the 0
1
+
and 2
1
+
levels of
150
Sm are significantly improved to
T
1
/
2
0
ν
β
β
(
0
1
+
)
>
1.36
×
10
22
year
and
T
1
/
2
0
ν
β
β
(
2
1
+
)
>
1.26
×
10
22
year
.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract The NEMO-3 results for the double- $$\beta $$ β decay of $$^{150}$$ 150 Nd to the 0 $$^+_1$$ 1 + and 2 $$^+_1$$ 1 + excited states of $$^{150}$$ 150 Sm are reported. The data recorded during ...5.25 year with 36.6 g of the isotope $$^{150}$$ 150 Nd are used in the analysis. The signal of the $$2\nu \beta \beta $$ 2 ν β β transition to the 0 $$^+_1$$ 1 + excited state is detected with a statistical significance exceeding 5 $$\sigma $$ σ . The half-life is measured to be $$T_{1/2}^{2\nu \beta \beta }(0^+_1) = \left 1.11 ^{+0.19}_{-0.14} \,\left( \hbox {stat}\right) ^{+0.17}_{-0.15}\,\left( \hbox {syst}\right) \right \times 10^{20}$$ T 1 / 2 2 ν β β ( 0 1 + ) = 1 . 11 - 0.14 + 0.19 stat - 0.15 + 0.17 syst × 10 20 year, which is the most precise value that has been measured to date. 90% confidence-level limits are set for the other decay modes. For the $$2\nu \beta \beta $$ 2 ν β β decay to the 2 $$^+_1$$ 1 + level the limit is $$T^{2\nu \beta \beta }_{1/2}(2^+_1) > 2.42 \times 10^{20}~\hbox {year}$$ T 1 / 2 2 ν β β ( 2 1 + ) > 2.42 × 10 20 year . The limits on the $$0\nu \beta \beta $$ 0 ν β β decay to the 0 $$^+_1$$ 1 + and 2 $$^+_1$$ 1 + levels of $$^{150}$$ 150 Sm are significantly improved to $$T_{1/2}^{0\nu \beta \beta }(0^+_1) > 1.36 \times 10^{22}~\hbox {year}$$ T 1 / 2 0 ν β β ( 0 1 + ) > 1.36 × 10 22 year and $$T_{1/2}^{0\nu \beta \beta }(2^+_1) > 1.26 \times 10^{22}~\hbox {year}$$ T 1 / 2 0 ν β β ( 2 1 + ) > 1.26 × 10 22 year .
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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