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We analyze the problem of approximating a multivariate function by discrete least-squares projection on a polynomial space starting from random, noise-free observations. An area of possible application of such technique is uncertainty quantification for computational models. We prove an optimal convergence estimate, up to a logarithmic factor, in the univariate case, when the observation points are sampled in a bounded domain from a probability density function bounded away from zero and bounded from above, provided the number of samples scales quadratically with the dimension of the polynomial space. Optimality is meant in the sense that the weighted [L.sup.2] norm of the error committed by the random discrete projection is bounded with high probability from above by the best [L.sup.∞] error achievable in the given polynomial space, up to logarithmic factors. Several numerical tests are presented in both the univariate and multivariate cases, confirming our theoretical estimates. The numerical tests also clarify how the convergence rate depends on the number of sampling points, on the polynomial degree, and on the smoothness of the target function. Keywords Approximation theory * Error analysis * Multivariate polynomial approximation * Nonparametric regression * Noise-free data * Generalized polynomial chaos * Point collocation Mathematical Subject Classification 41A10 * 41A25 * 65N12 * 65N15 * 65N35, 1 Introduction Given a smooth multivariate function φ = φ([Y.sup.1], ..., [Y.sup.d]) depending on d random variables [Y.sup.1], ..., [Y.sup.d] we consider in this work the classical problem of approximating [...]

We analyze the problem of approximating a multivariate function by discrete least-squares projection on a polynomial space starting from random, noise-free observations. An area of possible application of such technique is uncertainty quantification for computational models. We prove an optimal convergence estimate, up to a logarithmic factor, in the univariate case, when the observation points are sampled in a bounded domain from a probability density function bounded away from zero and bounded from above, provided the number of samples scales quadratically with the dimension of the polynomial space. Optimality is meant in the sense that the weighted $$L^2$$ norm of the error committed by the random discrete projection is bounded with high probability from above by the best $$L^\infty $$ error achievable in the given polynomial space, up to logarithmic factors. Several numerical tests are presented in both the univariate and multivariate cases, confirming our theoretical estimates. The numerical tests also clarify how the convergence rate depends on the number of sampling points, on the polynomial degree, and on the smoothness of the target function. [ABSTRACT FROM AUTHOR]

Glucocorticoid hormones (GCH) induce apoptotic cell death in immature thymocytes through an active mechanism, characterized by extensive DNA fragmentation into oligonucleasomal subunits. This requires macromolecular synthesis and is inhibited by protein kinase C (PKC) inhibitors, interleukin-4 (IL-4) and heat shock (hs). We performed experiments to analyse the possible effect of GCH on more differentiated lymphocytes, i.e. mouse natural killer (NK) cells and CD8+ alloreactive cytotoxic T lymphocytes (CTL). The results show that dexamethasone (DEX) induces DNA fragmentation and cell death in NK cells and CTL in vitro. In both NK cells and CTL, DEX-induced apoptosis is inhibited by IL-2 and IL-4 but, unlike that induced in thymocytes, is augmented by mRNA and protein synthesis inhibitors, PKC inhibitors and HS. [ABSTRACT FROM AUTHOR]

Activation of immature thymocytes or transformed T lymphocytes via T-cell receptor (TCR)/CD3 signalling can induce programmed cell death (apoptosis). Recent data indicate that anti-CD3/TCR monoclonal antibodies (mAb) also trigger apoptosis in activated (but not resting) mature peripheral blood T lymphocytes. Here we report that triggering of resting CD4- CD8- TCRαβ+ and/or TCRγδ+ via the alternative CD2-dependent activation pathway is able to induce programmed cell death. A pair of mitogenic anti-CD2 mAb provoked a dramatic rise in [Ca2+]i that was almost entirely sustained by extracellular fluxes, and the inhibition of membrane [Ca2+/ Mg2+] ATPase. The resulting endonuclease activation was able to induce DNA fragmentation, as revealed by propidium iodide staining and gel electrophoresis. Induction of apoptosis was prevented by the presence of interleukin-4 (IL-4) as well as by endonuclease inactivation with 100 μM ZnCl2, but enhanced by the contemporary block of protein kinase C. Thus it seems that in resting T lymphocytes the strong calcium signal delivered by the alternative CD2 activation pathway may act as a negative apoptotic signal in both αβ and γδ T cells with low (non-major histocompatibility complex restricted) antigenic affinity, so limiting the extension of polyclonal T-cell growth. [ABSTRACT FROM AUTHOR]

natural killer (NK) cell activity, as measured against K-562 target cells, was evaluated in 23 untreated and in 11 bromocriptine-treated hyperprolactinemia female patients and in 63 age-matched healthy women using 51Cr-release assay. The NK cell activity was significantly reduced in untreated hyperprolactinemia patients with respect to that of normal subjects, but therapy with bromocriptine restored NK cell function of patients to the levels of normal controls. Moreover, a reduced number of Leu-7+ cells and of large granular lymphocytes in hyperprolactinemia patients, as compared to normal controls and bromocriptine-treated subjects, correlated well with the decreased NK activity. Finally, 'in vitro' incubation with purified human prolactin, did not affect NK cell activity of blood mononuclear cells. The present results demonstrate that pathological hyperprolactinemia, in which a tuberoinfundibular dopaminergic defect has been postulated, is also associated with a reduction in NK cell number and function and indicate a possible interaction between prolactin, neuroendocrine system and NK cell lineage in man. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases (IBD) have a complex, poorly understood pathogenesis and lack long-lasting effective treatments. Recent research suggests that intestinal fungal dysbiosis may play a role in IBD development. This study investigates the effects of the glucocorticoid-induced leucine zipper protein (GILZp)", known for its protective role in gut mucosa, and a yeast extract (Py) with prebiotic properties, either alone or combined, in DSS-induced colitis. Both treatments alleviated symptoms via overlapping or distinct mechanisms. In particular, they reduced the transcription levels of pro-inflammatory cytokines IL-1β and TNF-α, as well as the expression of the tight junction protein Claudin-2. Additionally, GILZp increased MUC2 transcription, while Py reduced IL-12p40 and IL-6 levels. Notably, both treatments were effective in restoring the intestinal burden of clinically important Candida and related species. Intestinal mycobiome analysis revealed that they were able to reduce colitis-associated fungal dysbiosis, and this effect was mainly the result of a decreased abundance of the Meyerozima genus, which was dominant in colitic mice. Overall, our results suggest that combined treatment regimens with GILZp and Py could represent a new strategy for the treatment of IBD by targeting multiple mechanisms, including the fungal dysbiosis.

Over the last decades, the Campania Region in Italy has faced an environmental crisis due to the widespread illegal dumping and burning of waste. This has led to the area being notoriously known as the Land of Fires (Terra dei Fuochi - TdF), sparking serious concerns about public health and threatening the region's agricultural sector, one of its economic mainstays. In such a context, a timely, accurate, and reliable flow of information, aimed both at the population and at stakeholders, is crucial for establishing a proper dialogue between institutions and people, driving the empowerment of citizens. To address this crisis, the Italian Government introduced Law 6 of 2014, establishing a multidisciplinary Working Group tasked with identifying and mapping the sites affected by spills and illegal disposal in the territory. The TdF-WG defined a scientific methodology for classifying these sites in terms of prohibition on the cultivation of specific crops, consequently allowing the adoption of appropriate clean up and restoration measures for the impacted sites. This paper describes the data collection process and the IT platform commissioned by the Government to the IZS-TE and used by the TdF-WG to exchange data, knowledge, and technology, thereby fostering efficient and effective crisis management.

Glucocorticoids (GCs) are commonly used to treat autoimmune and inflammatory diseases, but their clinical effects and long-term use can lead to serious side effects. New drugs that can replace GCs are needed. Glucocorticoid-induced leucine zipper (GILZ) is induced by GCs and mediates many of their anti-inflammatory effects, such as inhibiting the pro-inflammatory molecule NF-κB. The GILZ C-terminal domain (PER region) is responsible for GILZ/p65NF-κB interaction and consequent inhibition of its transcriptional activity. A set of five short peptides spanning different parts of the PER region of GILZ protein was designed, and their anti-inflammatory activity was tested, both in vitro and in vivo. We tested the biological activity of GILZ peptides in human lymphocytic and monocytic cell lines to evaluate their inhibitory effect on the NF-κB-dependent expression of pro-inflammatory cytokines. Among the tested peptides, the peptide named PEP-1 demonstrated the highest efficacy in inhibiting cell activation in vitro. Subsequently, PEP-1 was further evaluated in two in vivo experimental colitis models (chemically induced by DNBS administration and spontaneous colitis induced in IL-10 knock-out (KO) mice (to assess its effectiveness in counteracting inflammation. Results show that PEP-1 reduced disease severity in both colitis models associated with reduced NF-κB pro-inflammatory activity in colon lamina propria lymphocytes. This study explored GILZ-based 'small peptides' potential efficacy in decreasing lymphocyte activation and inflammation associated with experimental inflammatory bowel diseases (IBDs). Small peptides have several advantages over the entire protein, including higher selectivity, better stability, and bioavailability profile, and are easy to synthesize and cost-effective. Thus, identifying active GILZ peptides could represent a new class of drugs for treating IBD patients.

Brucella RB51 is a live modified vaccine. Its use in water buffalo has been proposed using a vaccination protocol different to that used for cattle, but knowledge of the long-term effects of RB51 vaccination in this species remains incomplete. The aim of the study was to evaluate the safety and kinetics of antibody responses in water buffaloes vaccinated according to the protocol described for the bovine species in the WOAH Manual, modified with the use of a triple dose. Water buffaloes were vaccinated with the vaccine RB51. A booster vaccination was administered at 12 months of age. When turning 23-25 months old, female animals were induced to pregnancy. RB51-specific antibodies were detected and quantified using a CFT based on the RB51 antigen. Vaccinated animals showed a positive serological reaction following each vaccine injection, but titers and the duration of the antibody differed among animals. For 36 weeks after booster vaccination, the comparison of CFT values between vaccinated and control groups remained constantly significant. Afterwards, antibody titers decreased. No relevant changes in antibody response were recorded during pregnancy or lactation. In conclusion, results indicated that the vaccination schedule applied is safe and allows for vaccinated and unvaccinated controls to be discriminated between for up to 8 months after booster vaccination.

Comirnaty (BNT162b2) and Spikevax (mRNA-1273) COVID-19 vaccines encode a full-length SARS-CoV-2 Spike (S) protein. To evaluate whether the S-protein expressed following treatment with the two vaccines differs in the real-world context, two cell lines were treated for 24 h with two concentrations of each vaccine, and the expression of the S-protein was evaluated using flow cytometry and ELISA. Vaccines were obtained from three vaccination centers in Perugia (Italy) that provided us with residual vaccines present in vials after administration. Interestingly, the S-protein was detected not only on the cell membrane but also in the supernatant. The expression was dose-dependent only in Spikevax-treated cells. Furthermore, the S-protein expression levels in both cells and supernatant were much higher in Spikewax-than in Comirnaty-treated cells. Differences in S-protein expression levels following vaccine treatment may be attributed to variations in the efficacy of lipid nanoparticles, differences in mRNA translation rates and/or loss of some lipid nanoparticles' properties and mRNA integrity during transport, storage, or dilution, and may contribute to explaining the slight differences in the efficacy and safety observed between the Comirnaty and Spikevax vaccines.

B-acute lymphoblastic leukemia (B-ALL) is one of the most common pediatric cancers, wherein regulatory T cells (Treg) and exhausted CD8 + T cells may be important in its development and maintenance. In this bioinformatics study, we evaluated the expression of 20 Treg/CD8 exhaustion markers and their possible roles in patients with B-ALL. The mRNA expression values of peripheral blood mononuclear cell samples from 25 patients with B-ALL and 93 healthy subjects (HSs) were downloaded from publicly available datasets. Treg/CD8 exhaustion marker expression was normalized with that of the T cell signature and correlated with the expression of Ki-67, regulatory transcription factors (FoxP3, Helios), cytokines (IL-10, TGF-β), CD8 + markers (CD8α chain, CD8β chain), and CD8 + activation markers (Granzyme B, Granulysin). The mean expression level of 19 Treg/CD8 exhaustion markers was higher in the patients than in the HSs. In patients, the expression of five markers (CD39, CTLA-4, TNFR2, TIGIT, and TIM-3) correlated positively with Ki-67, FoxP3, and IL-10 expression. Moreover, the expression of some of them correlated positively with Helios or TGF-β. Our results suggested that Treg/CD8 + T cells expressing CD39, CTLA-4, TNFR2, TIGIT, and TIM-3 favor B-ALL progression, and targeted immunotherapy against these markers could be a promising approach for treating B-ALL.

Ulcerative colitis (UC) and Crohn's Disease (CD) are chronic relapsing inflammatory diseases that are caused by genetic, environmental, and immune factors. Treatment strategies are currently based on symptomatic control by immunosuppression. The glucocorticoid-induced leucine zipper (GILZ), a mediator of several effects of glucocorticoids, was recently found to be secreted by goblet cells and play a role in inflammatory bowel disease (IBD). This study investigates which genes GILZ is associated with in its role in intestinal barrier functions. We examined datasets from the Gene Expression Omnibus (GEO) and ArrayExpress profiles of the gut of healthy subjects (HSs), as well as UC and CD patients. The human colonic epithelial HT29 cell line was used for in vitro validation experiments. GILZ was significantly correlated with MUC2 , TLR2 , and TLR4 . In particular, an inverse correlation was found between the GILZ and MUC2 in HS and patients with IBD, mostly in those with an active disease. Further, direct pairwise correlations for GILZ / TLR2 and GILZ / TLR4 were found in HSs and UC patients, but not in CD patients. Overall, our results reveal the crosstalk at the transcription level between the GILZ , MUC2 , and TLRs in the mucosal barrier through common pathways, and they open up new perspectives in terms of mucosal healing in IBD patients.