The article addresses the issues of extending a category and updating a lexical concept, and determining its reference. Wetry to answer the questions: how can an object seen for the first time extend a category or update a concept? How is itpossible to determine the reference of a concept that represents a behaviour? Firstly, we discuss the learning of inferentiallinguistic competence used to update a concept through an approach based on prototype theory. Secondly, we discuss thelearning of referential linguistic competence used to determine the reference of a concept through an approach based onembodied cognition. Finally, on the basis of the dual dimension of the praxis of rule-following, we show how it is possibleto combine the two approaches into a single model that deals with both the extension of a category and the updating of aconcept, and the determination of the reference.

The suppression of spurious events in the region of interest for neutrinoless double beta decay will play a major role in next generation experiments. The background of detectors based on the technology of cryogenic calorimeters is expected to be dominated by α particles, that could be disentangled from double beta decay signals by exploiting the difference in the emission of the scintillation light. CUPID-0, an array of enriched Zn 82 Se scintillating calorimeters, is the first large mass demonstrator of this technology. The detector started data-taking in 2017 at the Laboratori Nazionali del Gran Sasso with the aim of proving that dual read-out of light and heat allows for an efficient suppression of the α background. In this paper we describe the software tools we developed for the analysis of scintillating calorimeters and we demonstrate that this technology allows to reach an unprecedented background for cryogenic calorimeters.

The R&D activity performed during the last years proved the potential of ZnSe scintillating bolometers to the search for neutrino-less double beta decay, motivating the realization of the first large-mass experiment based on this technology: CUPID-0. The isotopic enrichment in [Formula: see text]Se, the Zn[Formula: see text]Se crystals growth, as well as the light detectors production have been accomplished, and the experiment is now in construction at Laboratori Nazionali del Gran Sasso (Italy). In this paper we present the results obtained testing the first three Zn[Formula: see text]Se crystals operated as scintillating bolometers, and we prove that their performance in terms of energy resolution, background rejection capability and intrinsic radio-purity complies with the requirements of CUPID-0.

Drugs that target human thymidylate synthase (hTS), a dimeric enzyme, are widely used in anticancer therapy. However, treatment with classical substrate-site-directed TS inhibitors induces over-expression of this protein and development of drug resistance. We thus pursued an alternative strategy that led us to the discovery of TS-dimer destabilizers. These compounds bind at the monomer-monomer interface and shift the dimerization equilibrium of both the recombinant and the intracellular protein toward the inactive monomers. A structural, spectroscopic, and kinetic investigation has provided evidence and quantitative information on the effects of the interaction of these small molecules with hTS. Focusing on the best among them, E7, we have shown that it inhibits hTS in cancer cells and accelerates its proteasomal degradation, thus causing a decrease in the enzyme intracellular level. E7 also showed a superior anticancer profile to fluorouracil in a mouse model of human pancreatic and ovarian cancer. Thus, over sixty years after the discovery of the first TS prodrug inhibitor, fluorouracil, E7 breaks the link between TS inhibition and enhanced expression in response, providing a strategy to fight drug-resistant cancers.

Background

Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential.

Methods

To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved.

Results

There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses.

Conclusions

These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk.

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.