Search

Recent discussions about the origin of the so-called gallium anomaly have motivated a remeasurement of the half-life of Ge71. We have conducted three separate measurements using dedicated planar Ge detectors - one with Fe55 as a standard, one with Co57 as a standard, and one standalone Ge71 measurement. Our results yield a half-life of 11.468±0.008 days, which is consistent with, but significantly more precise than, the currently accepted value. With this experiment, the potential explanation of the gallium anomaly being due to an unexpectedly long Ge71 half-life has been ruled out, leaving the anomaly's origin as an open question.

CUPID is a next-generation bolometric experiment aiming at searching for neutrinoless double-beta decay with ∼250 kg of isotopic mass of 100Mo. It will operate at ∼10 mK in a cryostat currently hosting a similar-scale bolometric array for the CUORE experiment at the Gran Sasso National Laboratory (Italy). CUPID will be based on large-volume scintillating bolometers consisting of 100Mo-enriched Li2MoO4 crystals, facing thin Ge-wafer-based bolometric light detectors. In the CUPID design, the detector structure is novel and needs to be validated. In particular, the CUORE cryostat presents a high level of mechanical vibrations due to the use of pulse tubes and the effect of vibrations on the detector performance must be investigated. In this paper we report the first test of the CUPID-design bolometric light detectors with NTD-Ge sensors in a dilution refrigerator equipped with a pulse tube in an above-ground lab. Light detectors are characterized in terms of sensitivity, energy resolution, pulse time constants, and noise power spectrum. Despite the challenging noisy environment due to pulse-tube-induced vibrations, we demonstrate that all the four tested light detectors comply with the CUPID goal in terms of intrinsic energy resolution of 100 eV RMS baseline noise. Indeed, we have measured 70-90 eV RMS for the four devices, which show an excellent reproducibility. We have also obtained high energy resolutions at the 356 keV line from a 133Ba source, as good as Ge semiconductor γ detectors in this energy range.

An array of twelve 0.28 kg lithium molybdate (LMO) low-temperature bolometers equipped with 16 bolometric Ge light detectors, aiming at optimization of detector structure for CROSS and CUPID double-beta decay experiments, was constructed and tested in a low-background pulse-tube-based cryostat at the Canfranc underground laboratory in Spain. Performance of the scintillating bolometers was studied depending on the size of phonon NTD-Ge sensors glued to both LMO and Ge absorbers, shape of the Ge light detectors (circular vs. square, from two suppliers), in different light collection conditions (with and without reflector, with aluminum coated LMO crystal surface). The scintillating bolometer array was operated over 8 months in the low-background conditions that allowed to probe a very low, μBq/kg, level of the LMO crystals radioactive contamination by 228Th and 226Ra.

CUPID is a next-generation tonne-scale bolometric neutrinoless double beta decay experiment that will probe the Majorana nature of neutrinos and discover lepton number violation in case of observation of this singular process. CUPID will be built on experience, expertise and lessons learned in CUORE and will be installed in the current CUORE infra-structure in the Gran Sasso underground laboratory. The CUPID detector technology, successfully tested in the CUPID-Mo experiment, is based on scintillating bolometers of Li2MoO4 enriched in the isotope of interest 100Mo. In order to achieve its ambitious science goals, the CUPID collaboration aims to reduce the backgrounds in the region of interest by a factor 100 with respect to CUORE. This performance will be achieved by introducing the high efficient α/β discrimination demonstrated by the CUPID-0 and CUPID-Mo experiments, and using a high transition energy double beta decay nucleus such as 100Mo to minimize the impact of the gamma background. CUPID will consist of about 1500 hybrid heat-light detectors for a total isotope mass of 250 kg. The CUPID scientific reach is supported by a detailed and safe background model based on CUORE, CUPID-Mo and CUPID-0 results. The required performances have already been demonstrated and will be presented.

Next-generation experiments searching for rare events must satisfy increasingly stringent requirements on the bulk and surface radioactive contamination of their active and structural materials. The measurement of surface contamination is particularly challenging, as no existing technology is capable of separately measuring parts of the 232Th and 238U decay chains that are commonly found to be out of secular equilibrium. We will present the results obtained with a detector prototype consisting of 8 silicon wafers of 150 mm diameter instrumented as bolometers and operated in a low-background dilution refrigerator at the Gran Sasso Underground Laboratory of INFN, Italy. The prototype was characterized by a baseline energy resolution of few keV and a background

The small Ultra-Red Fluorescent Protein (smURFP) represents a new class of fluorescent protein with exceptional photostability and brightness derived from allophycocyanin in a previous directed evolution. Here, we report the smURFP crystal structure to better understand properties and enable further engineering of improved variants. We compare this structure to the structures of allophycocyanin and smURFP mutants to identify the structural origins of the molecular brightness. We then use a structure-guided approach to develop monomeric smURFP variants that fluoresce with phycocyanobilin but not biliverdin. Furthermore, we measure smURFP photophysical properties necessary for advanced imaging modalities, such as those relevant for two-photon, fluorescence lifetime, and single-molecule imaging. We observe that smURFP has the largest two-photon cross-section measured for a fluorescent protein, and that it produces more photons than organic dyes. Altogether, this study expands our understanding of the smURFP, which will inform future engineering toward optimal FPs compatible with whole organism studies.

CUORE Upgrade with Particle IDentification (CUPID) is a foreseen ton-scale array of Li2MoO4 (LMO) cryogenic calorimeters with double readout of heat and light signals. Its scientific goal is to fully explore the inverted hierarchy of neutrino masses in the search for neutrinoless double beta decay of 100Mo. Pile-up of standard double beta decay of the candidate isotope is a relevant background. We generate pile-up heat events via injection of Joule heater pulses with a programmable waveform generator in a small array of LMO crystals operated underground in the Laboratori Nazionali del Gran Sasso, Italy. This allows to label pile-up pulses and control both time difference and underlying amplitudes of individual heat pulses in the data. We present the performance of supervised learning classifiers on data and the attained pile-up rejection efficiency.

Due to the high information and communication importance and potential of the medical blogosphere in the formation of health literacy of the population, there is the increased need to study the opinions of Russian social media users on the impact of the content of medical blogs on personal and public health. Aim of the study was to find out the opinion of social media users on the extent to which the activities of bloggers specializing in public health and health care topics influence the prevention of major non-communicable and infectious diseases, public and personal health, within the changing boundaries of medical knowledge broadcasting (using sociological methods). Material and methods. The authors conducted a quantitative sociological survey of 178 respondents - users of social media: 55 (30.9 %) women and 123 (69.1 %) men about visiting blogs specializing in public health and healthcare. The collection of information was carried out by e-mailing a questionnaire developed by the authors, and analyzed the answers to questions from active blog users through a Google form in April – May 2023. Results. The study results of the impact of bloggers’ activities on personal and public health, including those related to the quality of medical information disseminated in social media, are described. Respondents believe that medical bloggers have a greater impact on public health than personal health. At the same time, according to the respondents, the spheres of influence in the field of public health do not coincide with the spheres of influence in the field of personal health. Thus, 74.7 % of respondents believe that medical bloggers have an impact on maintaining a healthy lifestyle of the population, prevention (61.8 % of all respondents think so) and treatment of infectious diseases (61.2 %). The requirements for the quality of information provided by bloggers are considered. Based on the analysis of Russian and foreign scientific literature, the authors developed a graphical diagram of the effect of dissemination through the blogosphere of information in the field of health care and disease prevention. Conclusions. The content published on medical blogs affects the health literacy of the population. That is why, medical blogs can be seen as a social determinant of health, because health blogs can be the key to the success of disease prevention and control efforts for public health maintaining. For organizing a communication intervention of medical personnel in social media to inform the population about methods for preventing the risk of developing major non-communicable and infectious diseases and increasing the level of health literacy of the population, medical blogs can and should be used to inform and educate patients as part of general or targeted multimodal educational practices or as a means of delivering electronic content. The risks of publishing inaccurate information in the blogosphere must be considered, whereby patients can easily become misinformed, which can have serious consequences for their health, and even increase their risk of mortality. To make the best use of the blogosphere, it is necessary to solve the problems of content accuracy and increase the level of professionalism of bloggers who write on medical topics. They need to be professionally trained to work for health, contributing to the prevention of the risk of developing major non-communicable and communicable diseases, improving the health of the population through education, and raising the level of health literacy. It makes sense to assess the success of the communicative intervention of doctors in social media and their management of the training of medical bloggers as a personnel determinant of public health, since it will depend on the personnel potential of the healthcare sector.

Far-red and near-infrared (NIR) genetically encoded calcium ion (Ca2+ ) indicators (GECIs) are powerful tools for in vivo and multiplexed imaging of neural activity and cell signaling. Inspired by a previous report to engineer a far-red fluorescent protein (FP) from a biliverdin (BV)-binding NIR FP, we have developed a far-red fluorescent GECI, designated iBB-GECO1, from a previously reported NIR GECI. iBB-GECO1 exhibits a relatively high molecular brightness, an inverse response to Ca2+ with ΔF/Fmin  = -13, and a near-optimal dissociation constant (Kd ) for Ca2+ of 105 nM. We demonstrate the utility of iBB-GECO1 for four-color multiplexed imaging in MIN6 cells and five-color imaging in HEK293T cells. Like other BV-binding GECIs, iBB-GECO1 did not give robust signals during in vivo imaging of neural activity in mice, but did provide promising results that will guide future engineering efforts. SIGNIFICANCE: Genetically encoded calcium ion (Ca2+ ) indicators (GECIs) compatible with common far-red laser lines (~630-640 nm) on commercial microscopes are of critical importance for their widespread application to deep-tissue multiplexed imaging of neural activity. In this study, we engineered a far-red excitable fluorescent GECI, designated iBB-GECO1, that exhibits a range of preferable specifications such as high brightness, large fluorescence response to Ca2+ , and compatibility with multiplexed imaging in mammalian cells.

The Majorana Demonstrator comprises two arrays of high-purity germanium detectors constructed to search for neutrinoless double-beta decay in 76Ge and other physics beyond the Standard Model. Its readout electronics were designed to have low electronic noise, and radioactive backgrounds were minimized by using low-mass components and low-radioactivity materials near the detectors. This paper provides a description of all components of the Majorana Demonstrator readout electronics, spanning the front-end electronics and internal cabling, back-end electronics, digitizer, and power supplies, along with the grounding scheme. The spectroscopic performance achieved with these readout electronics is also demonstrated.

P-type point contact (PPC) HPGe detectors are a leading technology for rare event searches due to their excellent energy resolution, low thresholds, and multi-site event rejection capabilities. We have characterized a PPC detector's response to α particles incident on the sensitive passivated and p + surfaces, a previously poorly-understood source of background. The detector studied is identical to those in the Majorana Demonstrator experiment, a search for neutrinoless double-beta decay ( 0νββ ) in 76 Ge. α decays on most of the passivated surface exhibit significant energy loss due to charge trapping, with waveforms exhibiting a delayed charge recovery (DCR) signature caused by the slow collection of a fraction of the trapped charge. The DCR is found to be complementary to existing methods of α identification, reliably identifying α background events on the passivated surface of the detector. We demonstrate effective rejection of all surface α events (to within statistical uncertainty) with a loss of only 0.2% of bulk events by combining the DCR discriminator with previously-used methods. The DCR discriminator has been used to reduce the background rate in the 0νββ region of interest window by an order of magnitude in the Majorana Demonstrator  and will be used in the upcoming LEGEND-200 experiment.

CUPID will be a next generation experiment searching for the neutrinolessdouble $\beta$ decay, whose discovery would establish the Majorana nature ofthe neutrino. Based on the experience achieved with the CUORE experiment,presently taking data at LNGS, CUPID aims to reach a background freeenvironment by means of scintillating Li$_{2}$$^{100}$MoO$_4$ crystals coupledto light detectors. Indeed, the simultaneous heat and light detection allows usto reject the dominant background of $\alpha$ particles, as proven by theCUPID-0 and CUPID-Mo demonstrators. In this work we present the results of thefirst test of the CUPID baseline module. In particular, we propose a newoptimized detector structure and light sensors design to enhance theengineering and the light collection, respectively. We characterized the heatdetectors, achieving an energy resolution of (5.9 $\pm$ 0.2) keV FWHM at the$Q$-value of $^{100}$Mo (about 3034 keV). We studied the light collection ofthe baseline CUPID design with respect to an alternative configuration whichfeatures gravity-assisted light detectors' mounting. In both cases we obtainedan improvement in the light collection with respect to past measures and wevalidated the particle identification capability of the detector, which ensuresan $\alpha$ particle rejection higher than 99.9%, fully satisfying therequirements for CUPID.

CUPID will be a next generation experiment searching for the neutrinoless double β decay, whose discovery would establish the Majorana nature of the neutrino. Based on the experience achieved with the CUORE experiment, presently taking data at LNGS, CUPID aims to reach a background free environment by means of scintillating Li2100MoO4 crystals coupled to light detectors. Indeed, the simultaneous heat and light detection allows us to reject the dominant background of α particles, as proven by the CUPID-0 and CUPID-Mo demonstrators. In this work we present the results of the first test of the CUPID baseline module. In particular, we propose a new optimized detector structure and light sensors design to enhance the engineering and the light collection, respectively. We characterized the heat detectors, achieving an energy resolution of (5.9 ± 0.2) keV FWHM at the Q-value of 100Mo (about 3034 keV). We studied the light collection of the baseline CUPID design with respect to an alternative configuration which features gravity-assisted light detectors’ mounting. In both cases we obtained an improvement in the light collection with respect to past measures and we validated the particle identification capability of the detector, which ensures an α particle rejection higher than 99.9%, fully satisfying the requirements for CUPID.

The past few decades have seen major developments in the design and operation of cryogenic particle detectors. This technology offers an extremely good energy resolution – comparable to semiconductor detectors – and a wide choice of target materials, making low temperature calorimetric detectors ideal for a variety of particle physics applications. Rare event searches have continued to require ever greater exposures, which has driven them to ever larger cryogenic detectors, with the CUORE experiment being the first to reach a tonne-scale, mK-cooled, experimental mass. CUORE, designed to search for neutrinoless double beta decay, has been operational since 2017 at a temperature of about 10 mK. This result has been attained by the use of an unprecedentedly large cryogenic infrastructure called the CUORE cryostat: conceived, designed and commissioned for this purpose. In this article the main characteristics and features of the cryogenic facility developed for the CUORE experiment are highlighted. A brief introduction of the evolution of the field and of the past cryogenic facilities are given. The motivation behind the design and development of the CUORE cryogenic facility is detailed as are the steps taken toward realization, commissioning, and operation of the CUORE cryostat. The major challenges overcome by the collaboration and the solutions implemented throughout the building of the cryogenic facility will be discussed along with the potential improvements for future facilities. The success of CUORE has opened the door to a new generation of large-scale cryogenic facilities in numerous fields of science. Broader implications of the incredible feat achieved by the CUORE collaboration on the future cryogenic facilities in various fields ranging from neutrino and dark matter experiments to quantum computing will be examined.

CUPID is the next generation experiment which will use scintillating cryogenic calorimeters to search for the neutrinoless double β decay. This unobserved process would shed light on the nature of the neutrino, which up to our knowledge could be a Majorana or a Dirac particle, and would give us an important hint to explain the lack of antimatter in the universe. This ambitious search needs a detector with unique characteristics such as an extremely low background level and an excellent energy resolution. CUPID is now in advanced R&D state to optimize the detector design in order to completely exploit the potentialities of scintillating cryogenic calorimeters. In the following I will describe the test performed at the LNGS (Laboratori Nazionali del Gran Sasso) of a single module of the future CUPID detector. In this contribution we present the performance obtained with a novel assembly concept, proving that it matches the requirements for CUPID.

In the past few years, attention has been drawn to the fact that a precision analysis of two-neutrino double beta decay (2νββ) allows the study of interesting physics cases like the emission of Majoron bosons and possible Lorentz symmetry violation. These processes modify the summed-energy distribution of the two electrons emitted in 2νββ. CUPID is a next-generation experiment aiming to exploit 100Mo-enriched scintillating Li2MoO4 crystals, operating as cryogenic calorimeters. Given the relatively fast half-life of 100Mo 2νββ and the large exposure that can be reached by CUPID, we expect to measure with very high precision the 100Mo 2νββ spectrum shape, reaching great sensitivities in the search for distortions induced by the physics beyond the Standard Model. In this contribution, we present the CUPID exclusion sensitivity for such New Physics processes, as well as the preliminary projected background of CUPID.

Abstract l-Lactate is increasingly appreciated as a key metabolite and signaling molecule in mammals. However, investigations of the inter- and intra-cellular dynamics of l-lactate are currently hampered by the limited selection and performance of l-lactate-specific genetically encoded biosensors. Here we now report a spectrally and functionally orthogonal pair of high-performance genetically encoded biosensors: a green fluorescent extracellular l-lactate biosensor, designated eLACCO2.1, and a red fluorescent intracellular l-lactate biosensor, designated R-iLACCO1. eLACCO2.1 exhibits excellent membrane localization and robust fluorescence response. To the best of our knowledge, R-iLACCO1 and its affinity variants exhibit larger fluorescence responses than any previously reported intracellular l-lactate biosensor. We demonstrate spectrally and spatially multiplexed imaging of l-lactate dynamics by coexpression of eLACCO2.1 and R-iLACCO1 in cultured cells, and in vivo imaging of extracellular and intracellular l-lactate dynamics in mice.

Precise characterization of detector time resolution is of crucial importance for next-generation cryogenic-bolometer experiments searching for neutrinoless double-beta decay, such as CUPID, in order to reject background due to pileup of two-neutrino double-beta decay events. In this paper, we describe a technique developed to study the pileup rejection capability of cryogenic bolometers. Our approach, which consists of producing controlled pileup events with a programmable wave-form generator, has the benefit that we can reliably and reproducibly control the time separation and relative energy of the individual components of the generated pileup events. The resulting data allow us to optimize and benchmark analysis strategies to discriminate between individual and pileup pulses. We describe a test of this technique performed with a small array of detectors at the Laboratori Nazionali del Gran Sasso, in Italy; we obtain a 90% rejection efficiency against pulser-generated pileup events with rise time of ∼15ms down to time separation between the individual events of about 2ms.

Imperfections in analog-to-digital conversion (ADC) cannot be ignored when signal digitization requirements demand both wide dynamic range and high resolution, as is the case for the Majorana Demonstrator 76Ge neutrinoless double-beta decay search. Enabling the experiment's high-resolution spectral analysis and efficient pulse shape discrimination required careful measurement and correction of ADC nonlinearities. A simple measurement protocol was developed that did not require sophisticated equipment or lengthy data-taking campaigns. A slope-dependent hysteresis was observed and characterized. A correction applied to digitized waveforms prior to signal processing reduced the differential and integral nonlinearities by an order of magnitude, eliminating these as dominant contributions to the systematic energy uncertainty at the double-beta decay Q value.

A scintillating bolometer based on a large cubic Li$_{2}$$^{100}$MoO$_4$crystal (45 mm side) and a Ge wafer (scintillation detector) has been operatedin the CROSS cryogenic facility at the Canfranc underground laboratory inSpain. The dual-readout detector is a prototype of the technology that will beused in the next-generation $0\nu2\beta$ experiment CUPID. The measurementswere performed at 18 and 12 mK temperature in a pulse tube dilutionrefrigerator. This setup utilizes the same technology as the CUORE cryostatthat will host CUPID and so represents an accurate estimation of the expectedperformance. The Li$_{2}$$^{100}$MoO$_4$ bolometer shows a high energyresolution of 6 keV FWHM at the 2615 keV $\gamma$ line. The detection ofscintillation light for each event triggered by the Li$_{2}$$^{100}$MoO$_4$bolometer allowed for a full separation ($\sim$8$\sigma$) between$\gamma$($\beta$) and $\alpha$ events above 2 MeV. The Li$_{2}$$^{100}$MoO$_4$crystal also shows a high internal radiopurity with $^{228}$Th and $^{226}$Raactivities of less than 3 and 8 $\mu$Bq/kg, respectively. Taking also intoaccount the advantage of a more compact and massive detector array, which canbe made of cubic-shaped crystals (compared to the cylindrical ones), this testdemonstrates the great potential of cubic Li$_{2}$$^{100}$MoO$_4$ scintillatingbolometers for high-sensitivity searches for the $^{100}$Mo $0\nu2\beta$ decayin CROSS and CUPID projects.

A scintillating bolometer based on a large cubic Li$_{2}$$^{100}$MoO$_4$crystal (45 mm side) and a Ge wafer (scintillation detector) has been operatedin the CROSS cryogenic facility at the Canfranc underground laboratory inSpain. The dual-readout detector is a prototype of the technology that will beused in the next-generation $0u2\beta$ experiment CUPID. The measurementswere performed at 18 and 12 mK temperature in a pulse tube dilutionrefrigerator. This setup utilizes the same technology as the CUORE cryostatthat will host CUPID and so represents an accurate estimation of the expectedperformance. The Li$_{2}$$^{100}$MoO$_4$ bolometer shows a high energyresolution of 6 keV FWHM at the 2615 keV $\gamma$ line. The detection ofscintillation light for each event triggered by the Li$_{2}$$^{100}$MoO$_4$bolometer allowed for a full separation ($\sim$8$\sigma$) between$\gamma$($\beta$) and $\alpha$ events above 2 MeV. The Li$_{2}$$^{100}$MoO$_4$crystal also shows a high internal radiopurity with $^{228}$Th and $^{226}$Raactivities of less than 3 and 8 $\mu$Bq/kg, respectively. Taking also intoaccount the advantage of a more compact and massive detector array, which canbe made of cubic-shaped crystals (compared to the cylindrical ones), this testdemonstrates the great potential of cubic Li$_{2}$$^{100}$MoO$_4$ scintillatingbolometers for high-sensitivity searches for the $^{100}$Mo $0u2\beta$ decayin CROSS and CUPID projects.

A scintillating bolometer based on a large cubic Li2100MoO4 crystal (45 mm side) and a Ge wafer (scintillation detector) has been operated in the CROSS cryogenic facility at the Canfranc underground laboratory in Spain. The dual-readout detector is a prototype of the technology that will be used in the next-generation 0ν2β experiment CUPID . The measurements were performed at 18 and 12 mK temperature in a pulse tube dilution refrigerator. This setup utilizes the same technology as the CUORE cryostat that will host CUPID and so represents an accurate estimation of the expected performance. The Li2100MoO4 bolometer shows a high energy resolution of 6 keV FWHM at the 2615 keV γ line. The detection of scintillation light for each event triggered by the Li2100MoO4 bolometer allowed for a full separation (∼8σ) between γ(β) and α events above 2 MeV . The Li2100MoO4 crystal also shows a high internal radiopurity with 228Th and 226Ra activities of less than 3 and 8 μBq/kg, respectively. Taking also into account the advantage of a more compact and massive detector array, which can be made of cubic-shaped crystals (compared to the cylindrical ones), this test demonstrates the great potential of cubic Li2100MoO4 scintillating bolometers for high-sensitivity searches for the 100Mo 0ν2β decay in CROSS and CUPID projects.

The CUPID Collaboration is designing a tonne-scale, background-free detector to search for double beta decay with sufficient sensitivity to fully explore the parameter space corresponding to the inverted neutrino mass hierarchy scenario. One of the CUPID demonstrators, CUPID-Mo, has proved the potential of enriched Li2100MoO4 crystals as suitable detectors for neutrinoless double beta decay search. In this work, we characterised cubic crystals that, compared to the cylindrical crystals used by CUPID-Mo, are more appealing for the construction of tightly packed arrays. We measured an average energy resolution of (6.7 ± 0.6) keV FWHM in the region of interest, approaching the CUPID target of 5 keV FWHM. We assessed the identification of α particles with and without a reflecting foil that enhances the scintillation light collection efficiency, proving that the baseline design of CUPID already ensures a complete suppression of this α-induced background contribution. We also used the collected data to validate a Monte Carlo simulation modelling the light collection efficiency, which will enable further optimisations of the detector.

The CUPID Collaboration is designing a tonne-scale, background-free detector to search for double beta decay with sufficient sensitivity to fully explore the parameter space corresponding to the inverted neutrino mass hierarchy scenario. One of the CUPID demonstrators, CUPID-Mo, has proved the potential of enriched Li2100MoO4 crystals as suitable detectors for neutrinoless double beta decay search. In this work, we characterised cubic crystals that, compared to the cylindrical crystals used by CUPID-Mo, are more appealing for the construction of tightly packed arrays. We measured an average energy resolution of (6.7 ± 0.6) keV FWHM in the region of interest, approaching the CUPID target of 5 keV FWHM. We assessed the identification of α particles with and without a reflecting foil that enhances the scintillation light collection efficiency, proving that the baseline design of CUPID already ensures a complete suppression of this α-induced background contribution. We also used the collected data to validate a Monte Carlo simulation modelling the light collection efficiency, which will enable further optimisations of the detector.

The majorana demonstrator is a neutrinoless double-β decay search consisting of a low-background modular array of high-purity germanium detectors, ∼2/3 of which are enriched to 88% in Ge76. The experiment is also searching for double-beta decay of Ge76 to excited states (e.s.) in Se76. Ge76 can decay into three daughter states of Se76, with clear event signatures consisting of a ββ-decay followed by the prompt emission of one or two γ rays. This results with high probability in multi-detector coincidences. The granularity of the demonstrator detector array enables powerful discrimination of this event signature from backgrounds. Using 41.9 kg yr of isotopic exposure, the demonstrator has set world leading limits for each e.s. decay of Ge76, with 90% CL lower half-life limits in the range of (0.75-4.0)×1024 yr. In particular, for the 2ν transition to the first 0+ e.s. of Se76, a lower half-life limit of 7.5×1023 yr at 90% CL was achieved.

Genetically encoded probes with red-shifted absorption and fluorescence are highly desirable for imaging applications because they can report from deeper tissue layers with lower background and because they provide additional colors for multicolor imaging. Unfortunately, red and especially far-red fluorescent proteins have very low quantum yields, which undermines their other advantages. Elucidating the mechanism of nonradiative relaxation in red fluorescent proteins (RFPs) could help developing ones with higher quantum yields. Here we consider two possible mechanisms of fast nonradiative relaxation of electronic excitation in RFPs. The first, known as the energy gap law, predicts a steep exponential drop of fluorescence quantum yield with a systematic red shift of fluorescence frequency. In this case the relaxation of excitation occurs in the chromophore without any significant changes of its geometry. The second mechanism is related to a twisted intramolecular charge transfer in the excited state, followed by an ultrafast internal conversion. The chromophore twisting can strongly depend on the local electric field because the field can affect the activation energy. We present a spectroscopic method of evaluating local electric fields experienced by the chromophore in the protein environment. The method is based on linear and two-photon absorption spectroscopy, as well as on quantum-mechanically calculated parameters of the isolated chromophore. Using this method, which is substantiated by our molecular dynamics simulations, we obtain the components of electric field in the chromophore plane for seven different RFPs with the same chromophore structure. We find that in five of these RFPs, the nonradiative relaxation rate increases with the strength of the field along the chromophore axis directed from the center of imidazolinone ring to the center of phenolate ring. Furthermore, this rate depends on the corresponding electrostatic energy change (calculated from the known fields and charge displacements), in quantitative agreement with the Marcus theory of charge transfer. This result supports the dominant role of the twisted intramolecular charge transfer mechanism over the energy gap law for most of the studied RFPs. It provides important guidelines of how to shift the absorption wavelength of an RFP to the red, while keeping its brightness reasonably high.

Protein kinases control nearly every facet of cellular function. These key signaling nodes integrate diverse pathway inputs to regulate complex physiological processes, and aberrant kinase signaling is linked to numerous pathologies. While fluorescent protein-based biosensors have revolutionized the study of kinase signaling by allowing direct, spatiotemporally precise kinase activity measurements in living cells, powerful new molecular tools capable of robustly tracking kinase activity dynamics across diverse experimental contexts are needed to fully dissect the role of kinase signaling in physiology and disease. Here, we report the development of an ultrasensitive, second-generation excitation-ratiometric protein kinase A (PKA) activity reporter (ExRai-AKAR2), obtained via high-throughput linker library screening, that enables sensitive and rapid monitoring of live-cell PKA activity across multiple fluorescence detection modalities, including plate reading, cell sorting and one- or two-photon imaging. Notably, in vivo visual cortex imaging in awake mice reveals highly dynamic neuronal PKA activity rapidly recruited by forced locomotion.

The past few decades have seen major developments in the design and operation of cryogenic particle detectors. This technology offers an extremely good energy resolution – comparable to semiconductor detectors – and a wide choice of target materials, making low temperature calorimetric detectors ideal for a variety of particle physics applications. Rare event searches have continued to require ever greater exposures, which has driven them to ever larger cryogenic detectors, with the CUORE experiment being the first to reach a tonne-scale, mK-cooled, experimental mass. CUORE, designed to search for neutrinoless double beta decay, has been operational since 2017 at a temperature of about 10 mK. This result has been attained by the use of an unprecedentedly large cryogenic infrastructure called the CUORE cryostat: conceived, designed and commissioned for this purpose. In this article the main characteristics and features of the cryogenic facility developed for the CUORE experiment are highlighted. A brief introduction of the evolution of the field and of the past cryogenic facilities are given. The motivation behind the design and development of the CUORE cryogenic facility is detailed as are the steps taken toward realization, commissioning, and operation of the CUORE cryostat. The major challenges overcome by the collaboration and the solutions implemented throughout the building of the cryogenic facility will be discussed along with the potential improvements for future facilities. The success of CUORE has opened the door to a new generation of large-scale cryogenic facilities in numerous fields of science. Broader implications of the incredible feat achieved by the CUORE collaboration on the future cryogenic facilities in various fields ranging from neutrino and dark matter experiments to quantum computing will be examined.

The majorana demonstrator is a neutrinoless double-β decay search consisting of a low-background modular array of high-purity germanium detectors, ∼2/3 of which are enriched to 88% in Ge76. The experiment is also searching for double-beta decay of Ge76 to excited states (e.s.) in Se76. Ge76 can decay into three daughter states of Se76, with clear event signatures consisting of a ββ-decay followed by the prompt emission of one or two γ rays. This results with high probability in multi-detector coincidences. The granularity of the demonstrator detector array enables powerful discrimination of this event signature from backgrounds. Using 41.9 kg yr of isotopic exposure, the demonstrator has set world leading limits for each e.s. decay of Ge76, with 90% CL lower half-life limits in the range of (0.75-4.0)×1024 yr. In particular, for the 2ν transition to the first 0+ e.s. of Se76, a lower half-life limit of 7.5×1023 yr at 90% CL was achieved.