105 research outputs found
Multilayered shell model with variable representation of displacements across the thickness
A multilayered zig-zag shellmodel is developed; it has a hierarchic representation of displacementsacross the thickness that a priori fulfils the interfacial stress contact conditions on interlaminar shear and normal stresses. Like for classical models, the functional d.o.f. are the mid-plane displacements and the shear rotations. Characteristic feature, the representation can vary from point to point across the thickness, in order to adapt to the variation of solutions. The coefficients of the higher-order terms are determined as functions of the d.o.f. by enforcing equilibrium conditions at discrete points across the thickness. The Lame's coefficients are expanded up to the second order. As shown by the numerical tests, it accurately predicts the stress fields of thick laminated and sandwich shells with abruptly changing material properties with a lower overall processing time than for the fixed representation, since post-processing is unnecessar
Pneumococcal vaccination in adults: rationale, state of the art and perspectives
Streptococcus pneumoniae (SP) is a leading cause of morbid- ity and mortality worldwide. Despite the availability, since the early 1980s, of a 23-valent pneumococcal polysaccharide vaccine (PPV23), its recommendation and increased use in the last decades, and the indirect benefits against invasive pneumococcal diseases following the pediatric immunization strategies with the 7-valent pneumococcal conjugate vaccine (PCV7), pneumoccal diseases, particularly Community Acquired Pneumonia (CAP), still remain a substantial burden among older adults in Western countries. The recent availability on the market of a second generation of pneumococcal conjugate vaccines, with an enlarged spectrum ofprotection against some serotypes not included in the PCV7 (i.e., the 13-valent pneumococcal conjugate vaccine ? PCV13), opens new interesting perspectives for improving the control of this sig- nificant health-care issue among the entire population.
The most interesting and up-dated epidemiological data regard- ing the impact of SP in adults and the elderly in Western countries, together with the available evidence concerning the efficacy and effectiveness of the PPV23 in the same population, are reported and discussed below.
The full article is free available on www.jpmh.or
TYK2-induced phosphorylation of Y640 suppresses STAT3 transcriptional activity
STAT3 is a pleiotropic transcription factor involved in homeostatic and host defense processes in the human body. It is activated by numerous cytokines and growth factors and generates a series of cellular effects. Of the STAT-mediated signal transduction pathways, STAT3 transcriptional control is best understood. Jak kinase dependent activation of STAT3 relies on Y705 phosphorylation triggering a conformational switch that is stabilized by intermolecular interactions between SH2 domains and the pY705 motif. We here show that a second tyrosine phosphorylation within the SH2 domain at position Y640, induced by Tyk2, negatively controls STAT3 activity. The Y640F mutation leads to stabilization of activated STAT3 homodimers, accelerated nuclear translocation and superior transcriptional activity following IL-6 and LIF stimulation. Moreover, it unlocks type I IFN-dependent STAT3 signalling in cells that are normally refractory to STAT3 transcriptional activation
State of the Art, Unresolved Issues, and Future Research Directions in the Fight against Hepatitis C Virus: Perspectives for Screening, Diagnostics of Resistances, and Immunization
Hepatitis C virus (HCV) still represents a major public health threat, with a dramatic burden from both epidemiological and clinical points of view. New generation of direct-acting antiviral agents (DAAs) has been recently introduced in clinical practice promising to cure HCV and to overcome the issues related to the interferon-based therapies. However, the emergence of drug resistance and the suboptimal activity of DAAs therapies against diverse HCV genotypes have been observed, determining treatment failure and hampering an effective control of HCV spread worldwide. Moreover, these treatments remain poorly accessible, particularly in low-income countries. Finally, effective screening strategy is crucial to early identifying and treating all HCV chronically infected patients. For all these reasons, even though new drugs may contribute to impacting HCV spread worldwide a preventive HCV vaccine remains a cornerstone in the road to significantly reduce the HCV spread globally, with the ultimate goal of its eradication. Advances in molecular vaccinology, together with a strong financial, political, and societal support, will enable reaching this fundamental success in the coming years. In this comprehensive review, the state of the art about these major topics in the fight against HCV and the future of research in these fields are discussed
Heptavalent Pneumococcal Conjugate Vaccine: growing knowledge and its implications for Italy
Introductive note
A wide literature on Streptococcus Pneumoniae (Pn) infections is available, largely published in the recent years, after the introduction of the heptavalent conjugate vaccine in US and in Europe. This review is based on the most up-to-date scientific articles about this pathogen
Performance testing of two new one-step real time PCR assays for detection of human influenza and avian influenza viruses isolated in humans and Respiratory Syncytial Virus
Introduction and Methods. Two real time one-step RT-PCRassays were developed for simultaneous detection and typingof influenza A and B viruses and detection of Respiratory Syncytial Virus (RSV). As regard influenza, primers were designedto amplify specific sequences of gene M of A/H1N1, A/H3N2,A/H5N1, A/H7N7 and A/H9N2 viruses and of gene NP of typeB viruses belonging both Yamagata and Victoria lineage. Specificity, analytical and clinical sensitivity, dynamic range, linearity of the new assays were evaluated.Results. Dynamic ranges for Influenza A and B, and RSV,were at least five logs and linearity was conserved. In orderto evaluate the specificity, 80 nasopharyngeal swabs resulting Influenza and RSV negative by multiplex nested PCR andcell culture, were tested and 79 resulted negative. The detection limits for influenza A and B, calculated by 95% probit,was 0,008 and 0,09 PFU, respectively, resulting more sensible than nested PCR. A total of 75 specimens (10 A/H1N1,
Cross-protection by MF59 TM -adjuvanted influenza vaccine: Neutralizing and haemagglutination-inhibiting antibody activity against A(H3N2) drifted influenza viruses
Summary Adjuvants enhance antibody response against vaccination. We compared the ability of MF59 TM -adjuvanted and non-adjuvanted subunit influenza vaccines, containing A/Wyoming/3/03(H3N2), to confer cross-protection against four consecutive drifted strains in the elderly. Neutralizing and haemagglutination-inhibiting antibody were measured. MF59 TMadjuvanted vaccine induced a stronger booster response against A/Panama/2007/99(H3N2) than non-adjuvanted vaccine. A/Panama/2007/99(H3N2) circulated widely during the previous 5 years and was included in vaccines over four consecutive seasons. Broader serological protection against drifted strains that circulated 1 and 2 years after vaccination with A/Wyoming/3/03(H3N2) was observed with MF59 TM -adjuvanted vaccine. Thus, MF59 TMadjuvanted vaccine confers greater immunogenicity than non-adjuvanted vaccines in vulnerable populations
Hyaluronan preconditioning of monocytes/macrophages affects their angiogenic behavior and regulation of TSG-6 expression in a tumor type-specific manner
Hyaluronan is a glycosaminoglycan normally present in the extracellular matrix in most tissues. Hyaluronan is a crucial player in many processes associated with cancer, such as angiogenesis, invasion and metastasis. However, little has been reported regarding the action of hyaluronan on monocytes/macrophages in tumor angiogenesis and its consequences on tumor development. In the present study, we investigated the effects of hyaluronan of different sizes on human monocytes/macrophages angiogenic behavior in colorectal and breast carcinoma. In vitro, treatment of monocytes/macrophages with lysates and conditioned media from a breast, but not from colorectal, carcinoma cell line plus high molecular weight hyaluronan induced: i) an increased expression of angiogenic factors VEGF, ILâ8, FGFâ2 and MMPâ2, ii) increased endothelial cell migration and iii) a differential expression of hyaluronanâbinding protein TSGâ6. Similar results were observed in monocytes/macrophages derived from breast cancer patients treated with tumor lysates. Besides, macrophages primed with high molecular weight hyaluronan and inoculated in human breast cancer xenograft tumor increased blood vessel formation and diminished TSGâ6 levels. In contrast, the effects triggered by high molecular weight hyaluronan on monocytes/macrophages in breast cancer context were not observed in the context of colorectal carcinoma. Taken together, these results indicate that the effect of high molecular weight hyaluronan as an inductor of the angiogenic behavior of macrophages in breast tumor context is in part consequence of the presence of TSGâ6.Fil: Spinelli, Fiorella Mercedes. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Vitale, Daiana LujĂĄn. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Icardi, Antonella. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Caon, Ilaria. UniversitĂ degli Studi dellâInsubria; ItaliaFil: Brandone, Alejandra. Gobierno de la Provincia de Buenos Aires. Hospital Interzonal General de Agudos Doctor Abraham Felix Piñeyro.; ArgentinaFil: Giannoni, Ana Paula. No especifĂca;Fil: Saturno, Maria Virginia. Universidad Austral. Facultad de Ciencias BiomĂ©dicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Passi, Alberto. UniversitĂ degli Studi dellâInsubria; ItaliaFil: GarcĂa, Mariana. Universidad Austral. Facultad de Ciencias BiomĂ©dicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Sevic, Ina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; ArgentinaFil: Alaniz, Laura Daniela. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires; Argentin
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