Independent adaptation mechanisms for numerosity and size perception provide evidence against a common sense of magnitude

Abstract How numerical quantity is processed is a central issue for cognition. On the one hand the “number sense theory” claims that numerosity is perceived directly, and may represent an early precursor for acquisition of mathematical skills. On the other, the “theory of magnitude” notes that numerosity correlates with many continuous properties such as size and density, and may therefore not exist as an independent feature, but be part of a more general system of magnitude. In this study we examined interactions in sensitivity between numerosity and size perception. In a group of children, we measured psychophysically two sensory parameters: perceptual adaptation and discrimination thresholds for both size and numerosity. Neither discrimination thresholds nor adaptation strength for numerosity and size correlated across participants. This clear lack of correlation (confirmed by Bayesian analyses) suggests that numerosity and size interference effects are unlikely to reflect a shared sensory representation. We suggest these small interference effects may rather result from top-down phenomena occurring at late decisional levels rather than a primary “sense of magnitude”

Phonon downconversion to suppress correlated errors in superconducting qubits

Quantum error correction can preserve quantum information in the presence of local errors, but correlated errors are fatal. For superconducting qubits, high-energy particle impacts from background radioactivity produce energetic phonons that travel throughout the substrate and create excitations above the superconducting ground state, known as quasiparticles, which can poison all qubits on the chip. We use normal metal reservoirs on the chip back side to downconvert phonons to low energies where they can no longer poison qubits. We introduce a pump-probe scheme involving controlled injection of pair-breaking phonons into the qubit chips. We examine quasiparticle poisoning on chips with and without back-side metallization and demonstrate a reduction in the flux of pair-breaking phonons by over a factor of 20. We use a Ramsey interferometer scheme to simultaneously monitor quasiparticle parity on three qubits for each chip and observe a two-order of magnitude reduction in correlated poisoning due to background radiation.Comment: 24 pages, 17 figures, 5 table

Immunotherapy and its development for gynecological (Ovarian, endometrial and cervical) tumors: From immune checkpoint inhibitors to chimeric antigen receptor (car)-T cell therapy

Gynecological tumors are malignancies with both high morbidity and mortality. To date, only a few chemotherapeutic agents have shown efficacy against these cancer types (only ovarian cancer responds to several agents, especially platinum-based combinations). Within this context, the discovery of immune checkpoint inhibitors has led to numerous clinical studies being carried out that have also demonstrated their activity in these cancer types. More recently, following the development of chimeric antigen receptor (CAR)-T cell therapy in hematological malignancies, this strategy was also tested in solid tumors, including gynecological cancers. In this article, we focus on the molecular basis of gynecological tumors that makes them potential candidates for immunotherapy. We also provide an overview of the main immunotherapy studies divided by tumor type and report on CAR technology and the studies currently underway in the area of gynecological malignancies

Detection of influenza virus in urban wastewater during the season 2022/2023 in Sicily, Italy

Introduction: Seasonal influenza generally represents an underestimated public health problem with significant socioeconomic implications. Monitoring and detecting influenza epidemics are important tasks that require integrated strategies. Wastewater-based epidemiology (WBE) is an emerging field that uses wastewater data to monitor the spread of disease and assess the health of a community. It can represent an integrative surveillance tool for better understanding the epidemiology of influenza and prevention strategies in public health. Methods: We conducted a study that detected the presence of Influenza virus RNA using a wastewater-based approach. Samples were collected from five wastewater treatment plants in five different municipalities, serving a cumulative population of 555,673 Sicilian inhabitants in Italy. We used the RT-qPCR test to compare the combined weekly average of Influenza A and B viral RNA in wastewater samples with the average weekly incidence of Influenza-like illness (ILI) obtained from the Italian national Influenza surveillance system. We also compared the number of positive Influenza swabs with the viral RNA loads detected from wastewater. Our study investigated 189 wastewater samples. Results: Cumulative ILI cases substantially overlapped with the Influenza RNA load from wastewater samples. Influenza viral RNA trends in wastewater samples were similar to the rise of ILI cases in the population. Therefore, wastewater surveillance confirmed the co-circulation of Influenza A and B viruses during the season 2022/2023, with a similar trend to that reported for the weekly clinically confirmed cases. Conclusion: Wastewater-based epidemiology does not replace traditional epidemiological surveillance methods, such as laboratory testing of samples from infected individuals. However, it can be a valuable complement to obtaining additional information on the incidence of influenza in the population and preventing its spread

Partial correction of immunodeficiency by lentiviral vector gene therapy in mouse models carrying Rag1 hypomorphic mutations

Introduction: Recombination activating genes (RAG) 1 and 2 defects are the most frequent form of severe combined immunodeficiency (SCID). Patients with residual RAG activity have a spectrum of clinical manifestations ranging from Omenn syndrome to delayed-onset combined immunodeficiency, often associated with granulomas and/or autoimmunity (CID-G/AI). Lentiviral vector (LV) gene therapy (GT) has been proposed as an alternative treatment to the standard hematopoietic stem cell transplant and a clinical trial for RAG1 SCID patients recently started. However, GT in patients with hypomorphic RAG mutations poses additional risks, because of the residual endogenous RAG1 expression and the general state of immune dysregulation and associated inflammation.Methods: In this study, we assessed the efficacy of GT in 2 hypomorphic Rag1 murine models (Rag1(F971L/F971L) and Rag1(R972Q/R972Q)), exploiting the same LV used in the clinical trial encoding RAG1 under control of the MND promoter.Results and discussion: Starting 6 weeks after transplant, GT-treated mice showed a decrease in proportion of myeloid cells and a concomitant increase of B, T and total white blood cells. However, counts remained lower than in mice transplanted with WT Lin- cells. At euthanasia, we observed a general redistribution of immune subsets in tissues, with the appearance of mature recirculating B cells in the bone marrow. In the thymus, we demonstrated correction of the block at double negative stage, with a modest improvement in the cortical/medullary ratio. Analysis of antigenspecific IgM and IgG serum levels after in vivo challenge showed an amelioration of antibody responses, suggesting that the partial immune correction could confer a clinical benefit. Notably, no overt signs of autoimmunity were detected, with B-cell activating factor decreasing to normal levels and autoantibodies remaining stable after GT. On the other hand, thymic enlargement was frequently observed, although not due to vector integration and insertional mutagenesis. In conclusion, our work shows that GT could partially alleviate the combined immunodeficiency of hypomorphic RAG1 patients and that extensive efficacy and safety studies with alternative models are required before commencing RAG gene therapy in thesehighly complex patients.Transplantation and immunomodulatio