Carbon Monoxide-Releasing Micelles for Immunotherapy

n/

Progettare chatbot: considerazioni e linee guida

Il lavoro si propone di delineare una serie di linee guida per la progettazione di chatbot e assistenti virtuali a partire dall’analisi degli attuali trend di progettazione e delle esigenze lato utente rilevate da precedenti lavori di rassegna della letteratura esistente. Il presente lavoro è stato svolto nell’ambito del progetto “Cognitive Solution for Intelligent Caring” di TIM.This work is focused on the current trends in designing chatbots and virtual assistants. We start from users’ needs identified in industrial surveys on chatbots. The result is a collection of guidelines and considerations which reflect the state of the art

Helper-dependent adenovirus vectors devoid of all viral genes cause less myocardial inflammation compared with first-generation adenovirus vectors

Abstract. : Background: : First-generation, E1-deleted (ΔE1) adenovirus vectors currently used in cardiovascular gene therapy trials are limited by tissue inflammation, mainly due to immune responses to viral gene products. Recently, helper-dependent (HD; also referred to as "gutless”) adenovirus vectors devoid of all viral coding sequences have been shown to cause low inflammation when injected intravenously or into skeletal muscles. However, HD vectors have not been evaluated in cardiovascular tissues. Methods and results: : HD and ΔE1 vectors containing a cytomegalovirus-driven expression cassette for the green fluorescent protein (GFP) gene were administered intramyocardially to adult rats (n = 54). GFP expression was measured by ELISA at varying time intervals after gene transfer. HD and ΔE1 vectors were equally efficient at transducing the myocardium. Tissue inflammation was assessed by immunostaining for leukocytes and quantitative real-time RT-PCR for cytokine mRNA expression. Monocyte/macrophages, CD4+ and CD8+ lymphocytes infiltrating the myocardium were less abundant with HD than ΔE1 vectors. Transcripts levels for pro-inflammatory cytokines such as IL-1β, tumor necrosis factor-α, and RANTES were decreased with HD vectors. However, both vectors were associated with a decline in GFP expression over time, although low-level expression was occasionally detectable 10 weeks after HD vector administration. The two vectors transduced endothelial cells in rat arteries (n = 11) with comparable efficiencies. Vascular GFP expression was not detectable at 10 weeks. Conclusions: : HD vectors are as efficient as ΔE1 vectors at transducing the myocardium and vascular endothelium, while causing less myocardial inflammation. Thus, HD vectors may be superior to earlier-generation adenovirus vectors for cardiovascular gene therapy application

Association of RANTES G-403A gene polymorphism with increased risk of coronary arteriosclerosis

Aims Polymorphisms in the RANTES (G-403A), monocyte chemoattractant protein-1 (MCP-1; A-2518G), stromal cell-derived factor-1β (SDF-1β; G801A), and C-C chemokine receptor-5 (CCR5; Δ32) genes have been associated with functional effects. These chemokines have been implicated in leucocyte recruitment to arterial lesions. In a case-control study, we explored relations between these polymorphisms and coronary artery disease (CAD), with respect to angiographic abnormalities and acute coronary syndromes (ACS). Methods and Results The LUdwigshafen Risk and Cardiovascular health (LURIC) cohort was genotyped by RFLP-PCR. Based on coronary angiography, individuals were sub-divided into CAD cases \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $(n=2694)$ \end{document} and controls \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $(n=530)$ \end{document}. RANTES-403 genotype frequencies were significantly different in cases and controls \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $({\chi}^{2}=4.17,p=0.041)$ \end{document}, as were A allele carrier frequencies (36.01% vs. 30.19%, OR=1.30 [95%-CI=1.06-1.60], \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $p=0.010$ \end{document}). By multivariate analysis, RANTES A-403 retained significant association with CAD \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $({\chi}^{2}=8.40,p=0.0038)$ \end{document}. RANTES A-403 was associated with increased ACS prevalence (OR=1.36 [95%-CI=1.08-1.71], \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $p=0.0073$ \end{document}). MCP-1 G-2518, SDF-1β A801, and CCR5 Δ32 were not associated with CAD. Conclusions RANTES A-403 was associated with CAD independently from conventional risk factors and CRP or fibrinogen as inflammatory biomarkers. The association was enhanced in smokers and ACS, conditions where platelet activation and inflammation predominate. RANTES A-403 may increase genetic susceptibility to CA

Gene transfer of a soluble IL-1 type 2 receptor-Ig fusion protein improves cardiac allograft survival in rats

Objective: Interleukin-1 (IL-1) mediates ischemia-reperfusion injury and graft inflammation after heart transplantation. IL-1 affects target cells through two distinct types of transmembrane receptors, type-1 receptor (IL-1R1), which transduces the signal, and the non-signaling type-2 receptor (IL-1R2), which acts as a ligand sink that subtracts IL-1β from IL-1R1. We analyzed the efficacy of adenovirus (Ad)-mediated gene transfer of a soluble IL-1R2-Ig fusion protein in delaying cardiac allograft rejection and the mechanisms underlying the protective effect. Methods: IL-1 inhibition by IL-1R2-Ig was tested using an in vitro functional assay whereby endothelial cells preincubated with AdIL-1R2-Ig or control virus were stimulated with recombinant IL-1β or tumor necrosis factor-α (TNF-α), and urokinase-type plasminogen activator (u-PA) induction was measured by zymography. AdIL-1R2-Ig was delivered to F344 rat donor hearts ex vivo, which were placed in the abdominal position in LEW hosts. Intragraft inflammatory cell infiltrates and proinflammatory cytokine expression were analyzed by immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. Results: IL-1R2-Ig specifically inhibited IL-1β-induced u-PA responses in vitro. IL-1R2-Ig gene transfer reduced intragraft monocytes/macrophages and CD4+ cell infiltrates (p≪0.05), TNF-α and transforming growth factor-β (TGF-β) expression (p≪0.05), and prolonged graft survival (15.6±5.7 vs 10.3±2.5 days with control vector and 10.1±2.1 days with buffer alone; p≪0.01). AdIL-1R2-Ig combined with a subtherapeutic regimen of cyclosporin A (CsA) was superior to CsA alone (19.4±3.0 vs 15.9±1.8 days; p≪0.05). Conclusions: Soluble IL-1 type-2 receptor gene transfer attenuates cardiac allograft rejection in a rat model. IL-1 inhibition may be useful as an adjuvant therapy in heart transplantatio

Gene transfer of soluble interleukin-17 receptor prolongs cardiac allograft survival in a rat model

Objective: Interleukin-17 (IL-17), a potent proinflammatory cytokine, has been implicated in allograft rejection. We analyzed the efficacy of an adenoviral vector expressing an IL-17 inhibitor in delaying acute allograft rejection in a rat model of heart transplantation, and the biological mechanisms underlying the protective effect. Methods: We constructed an adenoviral vector expressing a soluble IL-17 receptor-immunoglobulin (IL-17R-Ig) fusion protein. IL-17R-Ig activity was assessed by inhibition of IL-17-induced IL-6 release in HeLa cells preincubated with the vector. Intracoronary vector administration was performed in F344 donor hearts that were placed as vascularized grafts into Lewis hosts. Inflammatory cells infiltrating the graft were analyzed by immunohistology. Cytokine transcripts in the graft were determined by real-time RT-PCR. Results: IL-17R-Ig gene transfer resulted in prolonged allograft survival (16.1 ± 3.1 days vs 10.3 ± 2.5 days with control virus and 10.1 ± 2.1 days with virus dilution buffer alone; p ≪ 0.001). IL-17R-Ig gene transfer reduced inflammatory cell infiltrates, especially monocytes/macrophages and CD4+ T cells (p ≪ 0.05). It also reduced intragraft cytokine transcripts for interferon-γ and transforming growth factor-β (p ≪ 0.05) and, to a lesser extent, IL-1β and tumor necrosis factor-α (p = 0.083). Conclusions: Local expression of soluble IL-17 receptor-immunoglobulin attenuates T helper type 1 (Th1) cytokine responses and leukocyte infiltration in rat cardiac allografts, thereby mediating prolonged graft survival. Intragraft IL-17 inhibition may be useful as an adjuvant therapy to systemic immunosuppression in heart transplantatio

Proceedings of the Fifth Italian Conference on Computational Linguistics CLiC-it 2018

On behalf of the Program Committee, a very warm welcome to the Fifth Italian Conference on Computational Linguistics (CLiC-­‐it 2018). This edition of the conference is held in Torino. The conference is locally organised by the University of Torino and hosted into its prestigious main lecture hall “Cavallerizza Reale”. The CLiC-­‐it conference series is an initiative of the Italian Association for Computational Linguistics (AILC) which, after five years of activity, has clearly established itself as the premier national forum for research and development in the fields of Computational Linguistics and Natural Language Processing, where leading researchers and practitioners from academia and industry meet to share their research results, experiences, and challenges

Once upon a tale. On the foundational role of narrative in constructing linguistic and social experience

This paper illustrates the importance of narrativity as a cognitive and linguistic procedure, and the role of storytelling as a social practice. After examining the structural analogy between the “story frame” and our ways of organizing, representing and understanding the world, it argues for the crucial contribution narrativity gives to our experience of being human. It then analyzes the role played by natural languages as the main semiotic system through which this narrative modality is expressed, and retraces the paths along which meanings emerge as the result of recursive linguistic practices in a shared environment. Being narratively and socially constructed, we will further point out, words and meanings only make sense within a relational frame, and the practice of storytelling itself becomes a privileged way to share them in a certain – necessarily local – cultural context. Both as a received competence and an interactional skill storytelling, we will conclude, has a strongly pragmatic dimension, whose exploration will finally lead us to the concept of “narrative community”