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A determinação de propriedades mecânicas dos materiais com base em campanhas experimentais é de suma importância para as áreas da engenharia e ciência dos materiais, pois é a partir desses indicadores que são realizados os desenvolvimentos dos produtos, elementos estruturais e processos. No entanto, ensaios mecânicos produzem grandezas expressas em valores aproximados, tornando difícil o alcance de valores verdadeiros. Assim sendo, é possível afirmar que os ensaios geram erros e incertezas que são propagados, acarretando a necessidade de aplicar a lei de propagação de incertezas em tais dados experimentais. A estatística de Weibull é uma ferramenta que auxilia no tratamento e análise destas informações, sendo a mais indicada para o estudo de materiais que apresentam tendência dispersiva dos resultados obtidos, como os cerâmicos, por exemplo. Neste contexto, o presente trabalho utilizou técnicas de revisão sistemática da literatura e análise bibliométrica para verificar a aplicação das referidas técnicas relativas ao comportamento mecânico dos materiais, buscando traçar um panorama desse cenário científico. Após a seleção e análise do referencial consultado, foi possível verificar que a lei de propagação de incertezas foi aplicada apenas em um dos artigos pesquisados, demonstrando lacunas no desenvolvimento de publicações neste âmbito científico, indicando um forte nicho de investigação e produção a ser explorado, bem como a estatística de Weibull se mostrou polivalente e eficaz no estabelecimento dos indicadores de tendência.

We here present the first study on the consumed prey by an epigean population of the Italian cave salamander (Speleomantes italicus) from the Republic of San Marino. Using the harmless technique of stomach flushing, we aimed to provide the first data on the diet and on the degree of individual specialization that characterizes the studied population. We performed two-night surveys (one in autumn 2022 and one in spring 2023) in which we opportunistically searched for salamanders in forested areas and dry walls. Captured salamanders were sexed, weighed, photographed, measured and stomach flushed. Overall, we inspected the stomach contents of 67 individuals, recognizing 1,018 prey items belonging to 28 different prey categories. The examined population was mainly composed by generalist individuals, and no differences in number and diversity of prey consumed were observed among salamanders. Contrarily to what has been observed in other Speleomantes species, flying prey provided a minor contribution to the diet of the investigated population. Our study produced the first information on the diet of Speleomantes italicus from the Republic of San Marino, representing the starting point for future assessments on the dietary habits of this specific population.

Very rare cancers in children and adolescents pose a unique challenge for optimal care and research. Due to their rarity and diversity, there is a lack of standardized treatments and limited data to guide clinical decision-making. This paper aims to provide solutions for addressing these challenges through a multidisciplinary approach involving clinicians, researchers, and patient advocates. In recent years, members of the European Cooperative Study Group for Paediatric Rare Tumors (EXPeRT) and members of the European Society of Pediatric Oncology (SIOPE) clinical council worked within the EU Joint Action on Rare Cancers (JARC) and the Paed Can European Reference Network (ERN) on solutions to improve the care and research in the field. This includes a better classification, more financial resources, higher awareness and support by stakeholders, an international database, as well as harmonized diagnostic and therapeutic guidelines. Further research projects in the field of molecular biology, a better collaboration between medical oncologists and pediatricians, and a general strategy to facilitate access to modern therapies are urgently needed.

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.

The CUORE experiment is a large bolometric array searching for the lepton number violating neutrino-less double beta decay (0 νββ) in the isotope 130Te. In this work we present the latest results on two searches for the double beta decay (DBD) of 130Te to the first 02+ excited state of 130Xe : the 0 νββ decay and the Standard Model-allowed two-neutrinos double beta decay (2 νββ). Both searches are based on a 372.5 kg× yr TeO2 exposure. The de-excitation gamma rays emitted by the excited Xe nucleus in the final state yield a unique signature, which can be searched for with low background by studying coincident events in two or more bolometers. The closely packed arrangement of the CUORE crystals constitutes a significant advantage in this regard. The median limit setting sensitivities at 90% Credible Interval (C.I.) of the given searches were estimated as S1/20ν=5.6×1024yr for the 0 νββ decay and S1/22ν=2.1×1024yr for the 2 νββ decay. No significant evidence for either of the decay modes was observed and a Bayesian lower bound at 90 % C.I. on the decay half lives is obtained as: (T1/2)02+0ν>5.9×1024yr for the 0 νββ mode and (T1/2)02+2ν>1.3×1024yr for the 2 νββ mode. These represent the most stringent limits on the DBD of 130Te to excited states and improve by a factor ∼ 5 the previous results on this process.

The CUORE experiment is a large bolometric array searching for the lepton number violating neutrino-less double beta decay (0 νββ) in the isotope 130Te. In this work we present the latest results on two searches for the double beta decay (DBD) of 130Te to the first 02+ excited state of 130Xe : the 0 νββ decay and the Standard Model-allowed two-neutrinos double beta decay (2 νββ). Both searches are based on a 372.5 kg× yr TeO2 exposure. The de-excitation gamma rays emitted by the excited Xe nucleus in the final state yield a unique signature, which can be searched for with low background by studying coincident events in two or more bolometers. The closely packed arrangement of the CUORE crystals constitutes a significant advantage in this regard. The median limit setting sensitivities at 90% Credible Interval (C.I.) of the given searches were estimated as S1/20ν=5.6×1024yr for the 0 νββ decay and S1/22ν=2.1×1024yr for the 2 νββ decay. No significant evidence for either of the decay modes was observed and a Bayesian lower bound at 90 % C.I. on the decay half lives is obtained as: (T1/2)02+0ν>5.9×1024yr for the 0 νββ mode and (T1/2)02+2ν>1.3×1024yr for the 2 νββ mode. These represent the most stringent limits on the DBD of 130Te to excited states and improve by a factor ∼ 5 the previous results on this process.

The CUPID-Mo experiment at the Laboratoire Souterrain de Modane (France) is a demonstrator for CUPID, the next-generation ton-scale bolometric 0νββ experiment. It consists of a 4.2 kg array of 20 enriched Li_{2}^{100}MoO_{4} scintillating bolometers to search for the lepton-number-violating process of 0νββ decay in ^{100}Mo. With more than one year of operation (^{100}Mo exposure of 1.17  kg×yr for physics data), no event in the region of interest and, hence, no evidence for 0νββ is observed. We report a new limit on the half-life of 0νββ decay in ^{100}Mo of T_{1/2}>1.5×10^{24}  yr at 90% C.I. The limit corresponds to an effective Majorana neutrino mass ⟨m_{ββ}⟩

The CUPID-Mo experiment at the Laboratoire Souterrain de Modane (France) is a demonstrator for CUPID, the next-generation ton-scale bolometric 0νββ experiment. It consists of a 4.2 kg array of 20 enriched Li_{2}^{100}MoO_{4} scintillating bolometers to search for the lepton-number-violating process of 0νββ decay in ^{100}Mo. With more than one year of operation (^{100}Mo exposure of 1.17  kg×yr for physics data), no event in the region of interest and, hence, no evidence for 0νββ is observed. We report a new limit on the half-life of 0νββ decay in ^{100}Mo of T_{1/2}>1.5×10^{24}  yr at 90% C.I. The limit corresponds to an effective Majorana neutrino mass ⟨m_{ββ}⟩

We measured two-neutrino double beta decay of ^{130}Te using an exposure of 300.7 kg yr accumulated with the CUORE detector. Using a Bayesian analysis to fit simulated spectra to experimental data, it was possible to disentangle all the major background sources and precisely measure the two-neutrino contribution. The half-life is in agreement with past measurements with a strongly reduced uncertainty: T_{1/2}^{2ν}=7.71_{-0.06}^{+0.08}(stat)_{-0.15}^{+0.12}(syst)×10^{20}  yr. This measurement is the most precise determination of the ^{130}Te 2νββ decay half-life to date.

The Cryogenic Underground Observatory for Rare Events (CUORE) is the first cryogenic experiment searching for neutrinoless double-beta (0vßß) decay that has been able to reach the one-ton scale. The detector, located at the Laboratori Nazionali del Gran Sasso in Italy, consists of an array of 988 TeO2 crystals arranged in a compact cylindrical structure of 19 towers. Following the completion of the detector construction in August 2016, CUORE began its first physics data run in 2017 at a base temperature of about 10 mK. Following multiple optimization campaigns in 2018, CUORE is currently in stable operating mode. In 2019, CUORE released its 2nd result of the search for 0vßß with a TeO2 exposure of 372.5 kg·yr and a median exclusion sensitivity to a 130Te 0vßß decay half-life of 1.7 · 1025 yr. We find no evidence for 0vßß decay and set a 90% C.I. (credibility interval) Bayesian lower limit of 3.2 · 1025 yr on the 130Te 0vßß decay half-life. In this work, we present the current status of CUORE's search for 0vßß, as well as review the detector performance. Finally, we give an update of the CUORE background model and the measurement of the 130Te two neutrino double-beta (2vßß) decay half-life.

Despite being the feeblest and lightest of the known particles, the neutrinois one of the most abundant particles in the Universe and has played a criticalrole in its evolution. Within standard cosmological models, most of theneutrinos were produced in the Big Bang and completely decoupled from matterafter the first second. During that short time it is possible that through theprocess of Leptogenesis neutrinos helped to produce the matter/anti-matterasymmetry that sets the stage for all of the structures that we see in theuniverse today. However, these theories generally require the condition thatthe neutrino is a so-called Majorana particle, acting as its own anti-particle.The search for the extremely rare neutrinoless double-beta $(0\nu\beta\beta)$decay is currently the most practical way to address this question. Here wepresent the results of the first tonne-year exposure search for$0\nu\beta\beta$ decay of $^{130}$Te with CUORE. With a median half-lifeexclusion sensitivity of $2.8\times10^{25}$ yr, this is the most sensitivesearch for $0\nu\beta\beta$ decay in $^{130}$Te to date. We find no evidencefor $0\nu\beta\beta$ decay and set a lower bound of $T_{1/2} >2.2\times10^{25}$ yr at a 90% credibility interval. CUORE is the largest,coldest solid-state detector operating below 100mK in the world. Theachievement of 1 tonne-year of exposure demonstrates the long-term reliabilityand potential of cryogenic technology at this scale, with wide rangingapplications to next-generation rare-event searches, dark matter searches, andeven large-scale quantum computing.

We measured two-neutrino double beta decay of ^{130}Te using an exposure of 300.7 kg yr accumulated with the CUORE detector. Using a Bayesian analysis to fit simulated spectra to experimental data, it was possible to disentangle all the major background sources and precisely measure the two-neutrino contribution. The half-life is in agreement with past measurements with a strongly reduced uncertainty: T_{1/2}^{2ν}=7.71_{-0.06}^{+0.08}(stat)_{-0.15}^{+0.12}(syst)×10^{20}  yr. This measurement is the most precise determination of the ^{130}Te 2νββ decay half-life to date.

CUPID-Mo is a cryogenic detector array designed to search for neutrinoless double-beta decay (0νββ) of 100Mo. It uses 20 scintillating 100Mo-enriched Li2MoO4 bolometers instrumented with Ge light detectors to perform active suppression of α backgrounds, drastically reducing the expected background in the 0νββ signal region. As a result, pileup events and small detector instabilities that mimic normal signals become non-negligible potential backgrounds. These types of events can in principle be eliminated based on their signal shapes, which are different from those of regular bolometric pulses. We show that a purely data-driven principal component analysis based approach is able to filter out these anomalous events, without the aid of detector response simulations.

Abstract Objective To report on a retrospective study of primary DSRCT aiming at characterizing long‐term survivors (LTS). Methods All consecutive patients treated at our institution for a primary DSRCT between 2000 and 2021 were retrospectively identified. Patients received multiagent chemotherapy ± surgery ± hyperthermic intraperitoneal chemotherapy (HIPEC) ± whole abdomino‐pelvic radiotherapy (WAP‐RT) ± high‐dose chemotherapy ± maintenance chemotherapy (MC). Event‐free survival (EFS) and overall survival (OS) were estimated by Kaplan–Meier method. Patients alive, without evidence of disease at ≥36 months from diagnosis, were defined as LTS. Results Thirty‐eight patients were identified. All received multiagent chemotherapy; 27/38 (71%) surgery (7/27 [26%] plus HIPEC), 9/38 (24%) WAP‐RT, 12/38 (32%) MC. At a median‐follow‐up of 37 months (IQR 18–63), overall median‐EFS and median‐OS were 15 and 37 months, respectively. All events occurred within 35 months. In patients who underwent surgery, median‐EFS and median‐OS were 19 and 37 months (23 and 43 months after R0/R1, and 10 and 19 months after R2 resection), respectively. LTS were 5/38 (13%), alive at 37, 39, 53, 64, 209 months. None had liver or extra‐abdominal metastasis at diagnosis, they all received R0/R1 resection, 3/5 had WAP‐RT, 2/5 MC, 1/5 received high‐dose chemotherapy, none HIPEC. Conclusions In our series cure was likely achieved in 13% of DSRCT. LTS had no liver/extra‐abdominal disease, were treated with complete surgery, and possibly WAP‐RT/MC.

Abstract On-shell kinematics for gluon scattering can be parametrized with points on the celestial sphere; in the limit where these points collide, it is known that tree-level gluon scattering amplitudes exhibit an operator product expansion (OPE)-like structure. While it is possible to obtain singular contributions to this celestial OPE, getting regular contributions from both holomorphic and anti-holomorphic sectors is more difficult. In this paper, we use twistor string theory to describe the maximal helicity violating (MHV) sector of tree-level, four-dimensional gluon scattering as an effective 2d conformal field theory on the celestial sphere. By organizing the OPE between vertex operators in this theory in terms of soft gluon descendants, we obtain all-order expressions for the celestial OPE which include all regular contributions in the collinear expansion. This gives new, all-order formulae for the collinear splitting function (in momentum space) and celestial OPE coefficients (in the conformal primary basis) of tree-level MHV gluon scattering. We obtain these results for both positive and negative helicity gluons, and for any incoming/outgoing kinematic configuration within the MHV sector.

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 CUORE experiment is a large bolometric array searching for the leptonnumber violating neutrino-less double beta decay ($0u\beta\beta$) in theisotope $\mathrm{^{130}Te}$. In this work we present the latest results on twosearches for the double beta decay (DBD) of $\mathrm{^{130}Te}$ to the first$0^{+}_2$ excited state of $\mathrm{^{130}Xe}$: the $0u\beta\beta$ decay andthe Standard Model-allowed two-neutrinos double beta decay ($2u\beta\beta$).Both searches are based on a 372.5 kg$\times$yr TeO$_2$ exposure. Thede-excitation gamma rays emitted by the excited Xe nucleus in the final stateyield a unique signature, which can be searched for with low background bystudying coincident events in two or more bolometers. The closely packedarrangement of the CUORE crystals constitutes a significant advantage in thisregard. The median limit setting sensitivities at 90\% Credible Interval (C.I.)of the given searches were estimated as $\mathrm{S^{0u}_{1/2} = 5.6 \times10^{24} \: \mathrm{yr}}$ for the ${0u\beta\beta}$ decay and$\mathrm{S^{2u}_{1/2} = 2.1 \times 10^{24} \: \mathrm{yr}}$ for the${2u\beta\beta}$ decay. No significant evidence for either of the decay modeswas observed and a Bayesian lower bound at $90\%$ C.I. on the decay half livesis obtained as: $\mathrm{(T_{1/2})^{0u}_{0^+_2} > 5.9 \times 10^{24} \:\mathrm{yr}}$ for the $0u\beta\beta$ mode and$\mathrm{(T_{1/2})^{2u}_{0^+_2} > 1.3 \times 10^{24} \: \mathrm{yr}}$ for the$2u\beta\beta$ mode. These represent the most stringent limits on the DBD of$^{130}$Te to excited states and improve by a factor $\sim5$ the previousresults on this process.

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.

IgA is the predominant antibody isotype at intestinal mucosae, where it plays a critical role in homeostasis and provides a first line of immune protection. Dysregulation of IgA production, however, can contribute to immunopathology, particularly in kidneys in which IgA deposition can cause nephropathy. Class-switch DNA recombination (CSR) to IgA is directed by TGF-β signaling, which activates Smad2 and Smad3. Activated Smad2/Smad3 dimers are recruited together with Smad4 to the IgH α locus Iα promoter to activate germline Iα-Cα transcription, the first step in the unfolding of CSR to IgA. Epigenetic factors, such as non-coding RNAs, particularly microRNAs, have been shown to regulate T cells, dendritic cells and other immune elements, as well as modulate the antibody response, including CSR, in a B cell-intrinsic fashion. Here we showed that the most abundant miRNA in resting B cells, miR-146a targets Smad2, Smad3 and Smad4 mRNA 3'UTRs and keeps CSR to IgA in check in resting B cells. Indeed, enforced miR-146a expression in B cells aborted induction of IgA CSR by decreasing Smad levels. By contrast, upon induction of CSR to IgA, as directed by TGF-β, B cells downregulated miR-146a, thereby reversing the silencing of Smad2, Smad3 and Smad4, which, once expressed, led to recruitment of Smad2, Smad3 and Smad4 to the Iα promoter for activation of germline Iα-Cα transcription. Deletion of miR-146a in miR-146a -/- mice significantly increased circulating levels of steady state total IgA, but not IgM, IgG or IgE, and heightened the specific IgA antibody response to OVA. In miR-146a -/- mice, the elevated systemic IgA levels were associated with increased IgA+ B cells in intestinal mucosae, increased amounts of fecal free and bacteria-bound IgA as well as kidney IgA deposition, a hallmark of IgA nephropathy. Increased germline Iα-Cα transcription and CSR to IgA in miR-146a -/- B cells in vitro proved that miR-146a-induced Smad2, Smad3 and Smad4 repression is B cell intrinsic. The B cell-intrinsic role of miR-146a in the modulation of CSR to IgA was formally confirmed in vivo by construction and OVA immunization of mixed bone marrow μMT/miR-146a -/- chimeric mice. Thus, by inhibiting Smad2, Smad3 and Smad4 expression, miR-146a plays an important and B cell intrinsic role in modulation of CSR to IgA and the IgA antibody response.

The Cryogenic Underground Observatory for Rare Events (CUORE) is a tonne-scale cryogenic experiment located at the Laboratori Nazionali del Gran Sasso that exploits bolometric technique to search for neutrinoless double beta decay (0νββ) of 130Te. The detector consists of a segmented array of 988 natural TeO2 cubic crystals arranged in a cylindrical compact structure of 19 towers. The detector construction was completed in August 2016 and data taking started in Spring 2017. In this work, we present a brief description of the bolometric technique for rare events search and the CUORE detector, then we concentrate on the data analysis results. In this respect, we focus on the procedure for data processing and on the first 0νββ results we obtained from a total TeO2 exposure of 86.3kg yr. Next, we illustrate the main background sources and the CUORE background model, from which we obtain the most precise measurement of 130Te 2νββ half-life to date. Finally, we discuss the improvements achieved with 2018 and 2019 detector optimization campaigns and the current perspectives of our experiment.

CUORE is a cryogenic experiment that focuses on the search of neutrinoless double beta decay in 130Te and it is located at the Gran Sasso National Laboratories. Its detector consists of 988 TeO2 crystals operating at a base temperature of ∼10 mK. It is the first ton-scale bolometric experiment ever realized for this purpose. Thanks to its large target mass and ultra-low background, the CUORE detector is also suitable for the search of other rare phenomena. In particular the low energy part of the spectra is interesting for the detection of WIMP-nuclei scattering reactions. One of the most important requirements to perform these studies is represented by the achievement of a stable energy threshold lower than 10 keV. Here, the CUORE capability to accomplish this purpose using a low energy software trigger will be presented and described.

B cell differentiation driven by microbial antigens leads to production of anti-microbial antibodies, such as those neutralizing viruses, bacteria or bacterial toxin, that are class-switched (IgG and IgA) and somatically hypermutated (maturation of the antibody response) as well as secreted in large volume by plasma cells. Similar features characterize pathogenic antibodies to self-antigens in autoimmunity, reflecting the critical role of class switch DNA recombination (CSR), somatic hypermutation (SHM) and plasma cell differentiation in the generation of antibodies to not only foreign antigens but also self-antigens (autoantibodies). Central to CSR/SHM and plasma cell differentiation are AID, a potent DNA cytidine deaminase encoded by Aicda, and Blimp-1, a transcription factor encoded by Prdm1. B cell-intrinsic expression of Aicda and Prdm1 is regulated by epigenetic elements and processes, including DNA methylation, histone post-translational modifications and non-coding RNAs, particularly miRNAs. Here, we will discuss: B cell-intrinsic epigenetic processes that regulate antibody and autoantibody responses; how epigenetic dysregulation alters CSR/SHM and plasma cell differentiation, thereby leading to autoantibody responses, as in systemic lupus; and, how these can be modulated by nutrients, metabolites, and hormones through changes in B cell-intrinsic epigenetic mechanisms, which can provide therapeutic targets in autoimmunity.

The growth in computing capabilities has significantly transformed the realm of data analysis and processing, most notably through the widespread adoption of artificial intelligence (AI) and deep learning technologies [...]

In an increasingly globalized world there is continued debate within educational research about the existence and identity of the global citizen. This article contributes to this exploration by locating the debate within the further education (FE) and skills sector. It is based on the author's MA dissertation and examines the understandings of the global citizen identity as held by adult students from refugee and migrant backgrounds at a large FE college in London. It also investigates the extent to which these students perceive themselves as global citizens in British society. A qualitative study is used to explore these perspectives through student focus groups and the theme of positionality. This article argues that the global citizen identity is largely understood as an aspirational identity that is implicated with orientations of power and that there is an overall absence of a critical approach in relation to understandings of the global citizen identity. Increased criticality is therefore essential in enabling an exploration of this identity as necessarily multifaceted and complex.