ANAIS (annual modulation with NaI scintillators) is a dark matter direct detection experiment consisting of 112.5 kg of NaI(Tl) detectors in operation at the Canfranc Underground Laboratory (LSC), in ...Spain, since August 2017. ANAIS' goal is to confirm or refute in a model independent way the DAMA/LIBRA positive result: an annual modulation in the low-energy detection rate having all the features expected for the signal induced by dark matter particles in a standard galactic halo. This modulation, observed for about 20 years, is in strong tension with the negative results of other very sensitive experiments, but a model-independent comparison is still lacking. By using the same target material, NaI(Tl), such a comparison is more direct and almost independent in dark matter particle and halo models. Here, we present the annual modulation analysis corresponding to three years of ANAIS data (for an effective exposure of 313.95 kg × y ), applying a blind procedure, which updates the one developed for the 1.5 years analysis, and later applied to 2 years. The analysis also improves the background modeling in the fitting of the region of interest rates. We obtain for the best fit in the 1–6 keV (2–6 keV) energy region a modulation amplitude of − 0.0034 ± 0.0042 cpd / kg / keV ( 0.0003 ± 0.0037 cpd / kg / keV ), supporting the absence of modulation in our data, and incompatible with the DAMA/LIBRA result at 3.3 (2.6) σ , for a sensitivity of 2.5 (2.7) σ . Moreover, we include two complementary analyses: a phase-free annual modulation search and the exploration of the possible presence of a periodic signal at other frequencies. Finally, we carry out several consistency checks of our result, and we update the ANAIS-112 projected sensitivity for the scheduled 5 years of operation.
How position-dependent cell fate acquisition occurs during embryogenesis is a central question in developmental biology. To study this process, we developed a defined, high-throughput assay to induce ...peri-gastrulation-associated patterning in geometrically confined human pluripotent stem cell (hPSC) colonies. We observed that, upon BMP4 treatment, phosphorylated SMAD1 (pSMAD1) activity in the colonies organized into a radial gradient. We developed a reaction-diffusion (RD)-based computational model and observed that the self-organization of pSMAD1 signaling was consistent with the RD principle. Consequent fate acquisition occurred as a function of both pSMAD1 signaling strength and duration of induction, consistent with the positional-information (PI) paradigm. We propose that the self-organized peri-gastrulation-like fate patterning in BMP4-treated geometrically confined hPSC colonies arises via a stepwise model of RD followed by PI. This two-step model predicted experimental responses to perturbations of key parameters such as colony size and BMP4 dose. Furthermore, it also predicted experimental conditions that resulted in RD-like periodic patterning in large hPSC colonies, and rescued peri-gastrulation-like patterning in colony sizes previously thought to be reticent to this behavior.
TREX-DM is conceived to look for low-mass Weakly Interacting Massive Particles (WIMPs) using a gas Time Projection Chamber equipped with Micromegas readout planes at the Canfranc Underground ...Laboratory. The detector can hold in the active volume
∼
20
l
of pressurized gas up to 10 bar, corresponding to 0.30 kg of Ar or 0.16 kg of Ne. The Micromegas are read with a self-triggered acquisition, being thresholds below 0.4 keV (electron equivalent) at reach. A low background level in the lowest energy region is another essential requirement. To assess the expected background, all the relevant sources have been considered, including the measured fluxes of gamma radiation, muons and neutrons at the Canfranc Laboratory, together with the activity of most of the components used in the detector and ancillary systems, obtained in a complete assay program. The background contributions have been simulated by means of a dedicated application based on Geant4 and a custom-made code for the detector response. The background model developed for the detector presently installed in Canfranc points to levels from 1 to 10 counts
keV
-
1
kg
-
1
day
-
1
in the region of interest, making TREX-DM competitive in the search for low-mass WIMPs. A roadmap to further decrease it down to 0.1 counts
keV
-
1
kg
-
1
day
-
1
is underway.
Epithelia remove dying or excess cells by extrusion, a process that seamlessly squeezes cells out of the layer without disrupting their barrier function. New studies shed light into the intricate ...relationship between extrusion, tissue mechanics, and development. They emphasize the importance of whole tissue-mechanics, rather than single cell-mechanics in controlling extrusion. Tissue compaction, stiffness, and cell–cell adhesion can impact the efficiency of cell extrusion and mechanisms that drive it, to adapt to different conditions during development or disease.
The 18‐membered macrocycle H2macropa was investigated for 225Ac chelation in targeted alpha therapy (TAT). Radiolabeling studies showed that macropa, at submicromolar concentration, complexed all ...225Ac (26 kBq) in 5 min at RT. 225Ac(macropa)+ remained intact over 7 to 8 days when challenged with either excess La3+ ions or human serum, and did not accumulate in any organ after 5 h in healthy mice. A bifunctional analogue, macropa‐NCS, was conjugated to trastuzumab as well as to the prostate‐specific membrane antigen‐targeting compound RPS‐070. Both constructs rapidly radiolabeled 225Ac in just minutes at RT, and macropa‐Tmab retained >99 % of its 225Ac in human serum after 7 days. In LNCaP xenograft mice, 225Ac‐macropa‐RPS‐070 was selectively targeted to tumors and did not release free 225Ac over 96 h. These findings establish macropa to be a highly promising ligand for 225Ac chelation that will facilitate the clinical development of 225Ac TAT for the treatment of soft‐tissue metastases.
Actinium in action! A macrocyclic ligand exhibits unprecedented radiolabeling efficiency for the large α‐emitting radionuclide 225Ac3+. This ligand is extremely promising for the implementation of 225Ac in targeted alpha therapy for cancer. RCY=radiochemical yield.
Embryonic wounds heal rapidly, in a process driven by coordinated cell movements. Polarization of actin and the molecular motor non-muscle myosin II in the cells adjacent to the wound results in the ...formation of a supracellular cable around the wound that drives repair. In Drosophila embryos, the distribution of actin around wounds is heterogeneous, with regions of high and low actin density, and actin heterogeneity is necessary for rapid repair. Here, we demonstrate that actin and myosin display stochastic patterns around embryonic wounds, and that contractile forces around wounds are heterogeneous. Mathematical modelling suggests that actomyosin heterogeneity favours wound closure if myosin is regulated by tension and strain, a hypothesis that we validate experimentally. We show that inhibition of stretch-activated ion channels disrupts myosin dynamics and tissue repair. Together, our results indicate that staggered contractile events, mechanical signals and force-regulated myosin dynamics coordinate cell behaviours to drive efficient wound closure.
The ANAIS (Annual modulation with NaI(Tl) Scintillators) experiment aims at the confirmation or refutation of the DAMA/LIBRA positive annual modulation signal in the low energy detection rate, using ...the same target and technique, at the Canfranc Underground Laboratory (LSC) in Spain. ANAIS-112, consisting of nine 12.5 kg NaI(Tl) modules produced by Alpha Spectra Inc. in a
3
×
3
matrix configuration, is taking data smoothly in “dark matter search” mode since August, 2017, after a commissioning phase and operation of the first detectors during the last years in various set-ups. A large effort has been carried out within ANAIS to characterize the background of sodium iodide detectors, before unblinding the data and performing the first annual modulation analysis. Here, the background models developed for all the nine ANAIS-112 detectors are presented. Measured spectra from threshold to high energy in different conditions are well described by the models based on quantified activities independently estimated following several approaches. In the region from 1 to
6
keV
ee
the measured, efficiency corrected background level is
3.58
±
0.02
keV
-
1
kg
-
1
day
-
1
; NaI crystal bulk contamination is the dominant background source being
210
Pb
,
40
K
,
22
Na
and
3
H
contributions the most relevant ones. This background level, added to the achieved
1
keV
ee
analysis threshold (thanks to the outstanding light collection and robust filtering procedures developed), allow ANAIS-112 to be sensitive to the modulation amplitude measured by DAMA/LIBRA, and able to explore at three sigma level in 5 years the WIMP parameter region singled out by this experiment.
ANAIS is a direct detection dark matter experiment aiming at the study of the annual modulation expected in the interaction rate. It uses same target and technique as the DAMA/LIBRA experiment, which ...reported a highly significant positive modulation compatible with that expected for dark matter particles distributed in the galactic halo. However, other very sensitive experiments do not find any hint of particles with the required properties, although comparison is model dependent. In 2017, ANAIS-112 experiment was installed at the Canfranc Underground Laboratory (LSC), in Spain, and after the commissioning run for calibration and general assessment, ANAIS-112 started data taking in dark matter mode on August 3rd, 2017. It consists of nine NaI(Tl) modules, amounting 112.5 kg of mass in total. Here we report on the experimental apparatus and detector performance after the first year of data taking. Total live time available amounts to 341.72 days, being the corresponding exposure 105.32 kg
×
year. ANAIS-112 has achieved an analysis energy threshold of 1 keVee and an average background in the region of interest, from 1 to 6 keVee, of 3.6 counts/keVee/kg/day after correcting by the event selection efficiencies. In these conditions, ANAIS-112 will be able to test the DAMA/LIBRA result at three sigma level in five years of data taking.
Metastasis is the main cause of carcinoma-related death, yet we know little about how it initiates due to our inability to visualize stochastic invasion events. Classical models suggest that cells ...accumulate mutations that first drive formation of a primary mass, and then downregulate epithelia-specific genes to cause invasion and metastasis. Here, using transparent zebrafish epidermis to model simple epithelia, we can directly image invasion. We find that KRas-transformation, implicated in early carcinogenesis steps, directly drives cell invasion by hijacking a process epithelia normally use to promote death-cell extrusion. Cells invading by basal cell extrusion simultaneously pinch off their apical epithelial determinants, endowing new plasticity. Following invasion, cells divide, enter the bloodstream, and differentiate into stromal, neuronal-like, and other cell types. Yet, only invading KRas
cells deficient in p53 survive and form internal masses. Together, we demonstrate that KRas-transformation alone causes cell invasion and partial dedifferentiation, independently of mass formation.
The annual modulation measured by the DAMA/LIBRA experiment can be explained by the interaction of dark matter WIMPs in NaI(Tl) scintillator detectors. Other experiments, with different targets or ...techniques, exclude the region of parameters singled out by DAMA/LIBRA, but the comparison of their results relies on several hypotheses regarding the dark matter model. ANAIS-112 is a dark matter search with 112.5 kg of NaI(Tl) scintillators at the Canfranc Underground Laboratory (LSC) to test the DAMA/LIBRA result in a model independent way. We analyze its prospects in terms of the
a priori
critical and detection limits of the experiment. A simple figure of merit has been obtained to compare the different experiments looking for the annual modulation observed by DAMA/LIBRA. We conclude that after 5 years of measurement, ANAIS-112 can detect the annual modulation in the
3
σ
region compatible with the DAMA/LIBRA result.
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