Soluzioni analitiche per sistemi iperbolici a coefficienti non regolari nel tempo

Il teorema di Cauchy-Kovalevsky afferma che il problema di Cauchy per un sistema kovalevskiano con coefficienti, termine noto e dato iniziale analitici ha una soluzione analitica. E' anche possibile stimare il dominio di esistenza della soluzione, che dipende dai dati. Nel caso dei sistemi iperbolici, si puo’ dimostrare un risultato piu’ forte: il dominio di esistenza della soluzione non dipende dal dato iniziale. In particolare il problema e’ ben posto in opportune classi di funzioni analitiche. In questa tesi analizziamo brevemente i risultati di questo tipo, mostrando inoltre cosa succede se si considerano funzioni analitiche nelle variabili spaziali, ma meno regolari nel tempo. Ampio spazio e’ dedicato ai problemi strettamente iperbolici con coefficienti integrabili nel tempo e analitici nella variabili spaziali. Si studia prima il problema per funzionali analitici reali, e poi, attraverso un procedimento di dualita’, si trasferiscono i risultati al caso delle funzioni analitiche

EVALITA Evaluation of NLP and Speech Tools for Italian - December 17th, 2020

Welcome to EVALITA 2020! EVALITA is the evaluation campaign of Natural Language Processing and Speech Tools for Italian. EVALITA is an initiative of the Italian Association for Computational Linguistics (AILC, http://www.ai-lc.it) and it is endorsed by the Italian Association for Artificial Intelligence (AIxIA, http://www.aixia.it) and the Italian Association for Speech Sciences (AISV, http://www.aisv.it)

Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr

Stereoselectivity of NCS-382 binding to gamma-hydroxybutyrate (GHB) receptor in the rat brain

gamma-Hydroxybutyric acid (GHB), a naturally occurring metabolite of gamma-aminobutyric acid (GABA), has been postulated to act both as a specific agonist of GHB receptors and as a weak GABA(B) receptor agonist. The racemic compound 6,7,8,9-tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylideneacetic acid (RS-NCS-382), the only available antagonist of GHB receptors, has been resolved in two enantiomers, R- and S-; the potency of the latter to displace 4-hydroxy [2-3-H-3] butyric acid ([H-3]GHB) and [H-3]NCS-382 from GHB receptors, on one hand, and [H-3]baclofen from GABA(B) receptors on the other was compared in rat brain homogenates. R-NCS-382 was found to be twice and 60 times more potent than the RS- and S-forms, respectively, in displacing [H-3]GHB and 2 and 14 times, respectively, in displacing [H-3]NCS-382 from GHB binding. Neither RS-NCS-382 nor its enantiomers inhibited [H-3]baclofen binding up to a concentration of 1 mM. Our results demonstrate that R-NCS-382 is the enantiomer of RS-NCS-382 with higher affinity for GHB receptor

Perspectivist approaches to natural language processing:a survey

In Artificial Intelligence research, perspectivism is an approach to machine learning that aims at leveraging data annotated by different individuals in order to model varied perspectives that influence their opinions and world view. We present the first survey of datasets and methods relevant to perspectivism in Natural Language Processing (NLP). We review datasets in which individual annotator labels are preserved, as well as research papers focused on analysing and modelling human perspectives for NLP tasks. Our analysis is based on targeted questions that aim to surface how different perspectives are taken into account, what the novelties and advantages of perspectivist approaches/methods are, and the limitations of these works. Most of the included works have a perspectivist goal, even if some of them do not explicitly discuss perspectivism. A sizeable portion of these works are focused on highly subjective phenomena in natural language where humans show divergent understandings and interpretations, for example in the annotation of toxic and otherwise undesirable language. However, in seemingly objective tasks too, human raters often show systematic disagreement. Through the framework of perspectivism we summarize the solutions proposed to extract and model different points of view, and how to evaluate and explain perspectivist models. Finally, we list the key concepts that emerge from the analysis of the sources and several important observations on the impact of perspectivist approaches on future research in NLP.</p

A CXCR1 haplotype hampers HIV-1 matrix protein p17 biological activity

Design/methods/results: Our results show that Jurkat cells overexpressing CXCR1 or the receptor carrying single polymorphism CXCR1-300 or CXCR1-142 are able to adhere and migrate in response to both IL-8 and p17. On the contrary, Jurkat cells overexpressing CXCR1-300-142 and monocytes of individuals with such CXCR1 polymorphisms lose the capacity to adhere and migrate in response to p17, but not to their physiological ligand IL-8. Surface plasmon resonance (SPR) and multispectral imaging flow cytometry showed that p17 bound with similar affinity to CXCR1 and CXCR1-300-142. Moreover, whereas p17 was able to activate CXCR1, it was incapable of functionally interacting with CXCR1-300-142 by phosphorylating extracellular signal-regulated kinase 1/2, which regulates chemokine-induced cellular responses. Finally, mutagenesis studies showed that, unlike IL-8, p17 does not use Glu-Leu-Arglike motifs to activate CXCR1.Conclusions: Our results, showing the inability of p17 to activate CXCR1-300-142, a receptor found to be expressed on immune cells of patients with a low progression of HIV disease, point to a crucial role of p17 in AIDS pathogenesis. Our findings herein call for an exploration of the therapeutic potential of blocking the p17/CXCR1 axis in HIV infection.Objective: Monocyte inflammatory processes are fundamental events in AIDS pathogenesis. HIV-1 matrix protein p1 7, released from infected cells, was found to exert an interleukin (IL)-8 chemokine-like activity on human monocytes, promoting their trafficking and sustaining inflammatory processes, after binding to CXCR1. A haplotype of the CXCR1 gene(CXCR1-300-142) has been associated with slow HIV disease progression. Here, we determine how CXCR1 genetic variations impact on p17 biological activity

Diabetes-associated myelopoiesis drives stem cell mobilopathy through an OSM-p66Shc signaling pathway

Diabetes impairs the mobilization of hematopoietic stem/progenitor cells (HSPCs) from the bone marrow (BM), which can worsen the outcomes of HSPC transplantation and of diabetic complications. In this study, we examined the oncostatin M (OSM)\u2013p66Shc pathway as a mechanistic link between HSPC mobilopathy and excessive myelopoiesis. We found that streptozotocin-induced diabetes in mice skewed hematopoiesis toward the myeloid lineage via hematopoietic-intrinsic p66Shc. The overexpression of Osm resulting from myelopoiesis prevented HSPC mobilization after granulocyte colony-stimulating factor (G-CSF) stimulation. The intimate link between myelopoiesis and impaired HSPC mobilization after G-CSF stimulation was confirmed in human diabetes. Using cross-transplantation experiments, we found that deletion of p66Shc in the hematopoietic or nonhematopoietic system partially rescued defective HSPC mobilization in diabetes. Additionally, p66Shc mediated the diabetes-induced BM microvasculature remodeling. Ubiquitous or hematopoietic restricted Osm deletion phenocopied p66Shc deletion in preventing diabetes-associated myelopoiesis and mobilopathy. Mechanistically, we discovered that OSM couples myelopoiesis to mobilopathy by inducing Cxcl12 in BM stromal cells via nonmitochondrial p66Shc. Altogether, these data indicate that cell-autonomous activation of the OSM-p66Shc pathway leads to diabetes-associated myelopoiesis, whereas its transcellular hematostromal activation links myelopoiesis to mobilopathy. Targeting the OSM-p66Shc pathway is a novel strategy to disconnect mobilopathy from myelopoiesis and restore normal HSPC mobilization