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The imaging of individual Ba 2+ ions in high pressure xenon gas is one possible way to attain background-free sensitivity to neutrinoless double beta decay and hence establish the Majorana nature of the neutrino. In this paper we demonstrate selective single Ba 2+ ion imaging inside a high-pressure xenon gas environment. Ba 2+ ions chelated with molecular chemosensors are resolved at the gas-solid interface using a diffraction-limited imaging system with scan area of 1 × 1 cm 2 located inside 10 bar of xenon gas. This form of microscopy represents key ingredient in the development of barium tagging for neutrinoless double beta decay searches in 136 Xe. This also provides a new tool for studying the photophysics of fluorescent molecules and chemosensors at the solid-gas interface to enable bottom-up design of catalysts and sensors. Barium tagging is a key ingredient for future detectors of neutrinoless double beta decay in low-background environments. Here, the authors demonstrate fluorescence imaging of single Ba2+ ions in high pressure Xenon gas, by comparing activity between Ba2+ chelated and unchelated samples of crown-ether chemosensors.

The imaging of individual Ba2+ ions in high pressure xenon gas is one possible way to attain background-free sensitivity to neutrinoless double beta decay and hence establish the Majorana nature of the neutrino. In this paper we demonstrate selective single Ba2+ ion imaging inside a high-pressure xenon gas environment. Ba2+ ions chelated with molecular chemosensors are resolved at the gas-solid interface using a diffraction-limited imaging system with scan area of 1 × 1 cm2 located inside 10 bar of xenon gas. This form of microscopy represents key ingredient in the development of barium tagging for neutrinoless double beta decay searches in 136Xe. This also provides a new tool for studying the photophysics of fluorescent molecules and chemosensors at the solid-gas interface to enable bottom-up design of catalysts and sensors.

The NEXT collaboration is dedicated to the study of double beta decays of \\(^{136}\\)Xe using a high-pressure gas electroluminescent time projection chamber. This advanced technology combines exceptional energy resolution (\\(\\leq 1\\%\\) FWHM at the \\(Q_{\\beta\\beta}\\) value of the neutrinoless double beta decay) and powerful topological event discrimination. Building on the achievements of the NEXT-White detector, the NEXT-100 detector started taking data at the Laboratorio Subterráneo de Canfranc (LSC) in May of 2024. Designed to operate with xenon gas at 13.5 bar, NEXT-100 consists of a time projection chamber where the energy and the spatial pattern of the ionising particles in the detector are precisely retrieved using two sensor planes (one with photo-multiplier tubes and the other with silicon photo-multipliers). The detector has been operating at stable conditions using argon and xenon gases at \\(\\sim\\)4 bar and drift fields of 74 V/cm and 118 V/cm, respectively. Alpha decays from the \\(^{222}\\)Rn chain have been used to test and monitor the stability of the detector, showing a constant electron lifetime in the drift volume. In this paper, in addition to reporting the results of the commissioning run, we provide a detailed description of the NEXT-100 detector, describe its assembly, and present the current estimation of the radiopurity budget.

NEXT-100 is a high-pressure xenon time projection chamber with electroluminescent amplification, designed to operate with up to approximately 70.5 kg at 13.5 bar. It is the most recent detector developed by the NEXT collaboration to search for the neutrinoless double-beta decay (\\(\\beta\\beta 0\\nu\\)) of Xe-136. The NEXT gas TPC technology offers the best energy resolution near the Q-value of the decay (\\(Q_{\\beta\\beta}\\) = 2458 keV) among xenon detectors, which is set by design to be <1% FWHM. We report here the high-energy calibration of the detector using a Th-228 source, demonstrating linear response and an energy resolution of \\((0.90 \\pm 0.02)\\)% FWHM at the Tl-208 photopeak (2615 keV). This performance extrapolates to a resolution at the double-beta decay end-point of \\(R(Q_{\\beta\\beta})\\) = \\((0.93 \\pm 0.02)\\)% FWHM, confirming the detector's capability for precision energy measurement in the search for \\(\\beta\\beta 0\\nu\\).

The NEXT collaboration is investigating the double beta decay of \\(^{136}\\)Xe using high-pressure gas electroluminescent time projection chambers, which provide excellent energy resolution together with a robust topological signature. Operating at the Laboratorio Subterráneo de Canfranc (LSC) and building on the success of the NEXT-White detector, the NEXT-100 apparatus began commissioning in May 2024 and started operation with xenon at a pressure of 4 bar in October 2024. We report here the first results obtained with NEXT-100 using low-energy calibration data from \\(^{83m}\\)Kr decays, which allow mapping of the detector response in the active volume and monitoring of its stability over time. After homogenizing the light response, we achieve an energy resolution of 4.37% FWHM at 41.5 keV for \\(^{83m}\\)Kr point-like energy deposits contained in a radius of 425 mm. In a fiducial region representing the operating conditions of NEXT-100 at 10 bar we obtain an improved energy resolution of 4.16% FWHM. These results are in good agreement with that obtained in NEXT-White, and an \\(E^{-1/2}\\) extrapolation to \\(Q_{\\beta\\beta}\\) yields an energy resolution close to 0.5% FWHM, well below the 1% FWHM design target.

The imaging of individual Ba\\(^{2+}\\) ions in high pressure xenon gas is one possible way to attain background-free sensitivity to neutrinoless double beta decay and hence establish the Majorana nature of the neutrino. In this paper we demonstrate selective single Ba\\(^{2+}\\) ion imaging inside a high-pressure xenon gas environment. Ba\\(^{2+}\\) ions chelated with molecular chemosensors are resolved at the gas-solid interface using a diffraction-limited imaging system with scan area of 1\\(\\times\\)1~cm\\(^2\\) located inside 10~bar of xenon gas. This new form of microscopy represents an important enabling step in the development of barium tagging for neutrinoless double beta decay searches in \\(^{136}\\)Xe, as well as a new tool for studying the photophysics of fluorescent molecules and chemosensors at the solid-gas interface.

Human breast tumors comprise a minor sub-population of tumor-initiating cells (TICs), commonly termed cancer stem cells. TICs are thought to sustain tumor growth and to confer resistance to current anticancer therapies. Hence, targeting TIC may be essential to achieving durable cancer cures. To identify molecular targets in breast TIC, we employed a transgenic mouse model of ERBB2 breast cancer; tumors arising in this model comprise a very high frequency of TIC, which is maintained in tumor cell populations propagated in vitro as non-adherent tumorspheres. The Notch pathway is dysregulated in human breast tumors and overexpression of constitutively active Notch proteins induces mammary tumors in mice. The Notch pathway has also been implicated in stem cell processes including those of mammary epithelial stem cells. Hence, we investigated the potential that the Notch pathway is required for TIC activity. We found that an antagonist of Notch signaling, a gamma (γ)-secretase inhibitor termed MRK-003, inhibited the survival of tumorsphere-derived cells in vitro and eliminated TIC as assessed by cell transplantation into syngeneic mice. Whereas MRK-003 also inhibited the self-renewal and/or proliferation of mammosphere-resident cells, this effect of the inhibitor was reversible thus suggesting that it did not compromise the survival of these cells. MRK-003 administration to tumor-bearing mice eliminated tumor-resident TIC and resulted in rapid and durable tumor regression. MRK-003 inhibited the proliferation of tumor cells, and induced their apoptosis and differentiation. These findings suggest that MRK-003 targets breast TIC and illustrate that eradicating these cells in breast tumors ensures long-term, recurrence-free survival.

Purpose Esophageal injury is a potential complication with radiofrequency ablation in the posterior wall of the left atrium (LA). The “box isolation” method isolates the posterior LA wall including the pulmonary veins without ablation on the posterior LA wall. This study compares the acute and long-term efficacy of the box isolation method with conventional circumferential pulmonary vein isolation (PVI) for catheter ablation of AF. Methods Twenty-nine patients (age 60±9 years, 62% male, 79% paroxysmal) with drug refractory AF underwent catheter ablation. Sixteen of the 29 patients (55%) underwent box isolation. Recurrence of AF was detected by checking the daily recorded rhythm strip on a portable home ECG monitor, irrespective of the symptoms. Mean follow-up duration was 10±2 months. Results Complete isolation of the posterior LA using box isolation lesions was achieved in three of 16 (19%) patients. The other 13 patients underwent creation of additional lesions until all PVs were isolated. Of the 16 patients who underwent box isolation, four patients (25%) had complete success, six patients (38%) had improvement, and the remaining six patients (37%) had failure. Of the 13 patients who underwent the standard PV isolation, two patients (15%) had complete success, eight patients (62%) had improvement, and the remaining three patients (23%) had failure ( p =0.44). Conclusion In this pilot study, the efficacy of box isolation is similar to the circumferential PVI for catheter ablation of AF. Few patients achieved PVI with box method alone. Based on these results, we do not recommend the box isolation strategy.

The GMO Risk Assessment and Communication of Evidence (GRACE; www.grace-fp7.eu) project is funded by the European Commission within the 7th Framework Programme. A key objective of GRACE is to conduct 90-day animal feeding trials, animal studies with an extended time frame as well as analytical, in vitro and in silico studies on genetically modified (GM) maize in order to comparatively evaluate their use in GM plant risk assessment. In the present study, the results of two 90-day feeding trials with two different GM maize MON810 varieties, their near-isogenic non-GM varieties and four additional conventional maize varieties are presented. The feeding trials were performed by taking into account the guidance for such studies published by the EFSA Scientific Committee in 2011 and the OECD Test Guideline 408. The results obtained show that the MON810 maize at a level of up to 33 % in the diet did not induce adverse effects in male and female Wistar Han RCC rats after subchronic exposure, independently of the two different genetic backgrounds of the event.