Riflessioni sulla fabbrica di San Simpliciano e le sue trasformazioni medievali a settantacinque anni dalla riscoperta

Il contributo ripercorre la scoperta delle fasi costruttive taroantiche e medievali ella basilica di San Simpliciano Milano alla luce delle ultime indagini condotte sul monumento

Tecniche e materiali da costruzione nella Milano antica e medievale

The city of Milan preserve an amazing historical and architectural heritage, consisting of a high number of ancient churches, in most cases built to the origins of Christianity and transformed into new form during the Romanesque. In the article are synthetically presented the results of the research work of the writer about construction techniques of the most important churches in the city (S. Ambrogio, S. Simpliciano, S. Giovanni alle Fonti, S. Nazaro Maggiore, ...), trying to highlight the main changes between Late Antiquity and Romanesque. A large amount of stone material were used in Roman architecture of Milan and Lombardy, thanks to the geological variety of the territory. The Alps supplied granites, diorites, gneisses and marbles; the Prealps supplied limestones, dolomites, sandstones (Mesozoic) and conglomerates (Quaternary); the Padània alluvial plain supplied pebbles, gravels, sands and clays (Quaternary). Each stone had a local use reaching the nearest towns (Como, Pavia, Milan, Bergamo, Brescia) through waterways; the towns of the plain (Piacenza, Cremona, Mantua) employed bricks made of local clay. Milano, the capital, employed also stones coming from abroad (limestones from Venetia and Friuli). White marbles of Apuanian Alps and coloured marbles of Eastern mediterranean were also diffused in Milan and other Lombard sites despite the laborious supplying. The stones quarried by the Romans were continuously used in the following centuries.La città di Milano conserva un patrimonio storico-architettonico straordinario, costituito da un elevato numero di edifici di culto antichi, nella maggior parte dei casi costruiti alle origini del cristianesimo e trasformati in forme nuove in età romanica. Nel contributo vengono presentati sinteticamente i risultati del lavoro di ricerca, condotto da chi scrive, sulle tecniche costruttive dei principali edifici di culto della città (S. Ambrogio, S. Simpliciano, S. Giovanni alle Fonti, S. Nazaro Maggiore, ...), cercando di mettere in luce le principali trasformazioni tra tardoantico e romanico. Un gran numero di materiali lapidei furono utilizzati nell’architettura romana a Milano e in Lombardia, materiali resi disponibili grazie alla varietà geologica del territorio. Le Alpi fornirono graniti, dioriti, gneiss, marmi; le Prealpi calcari, dolomie, arenarie (Mesozoico) e conglomerati (Quaternario); la pianura Padana ciottoli, ghiaie, sabbie e argille dei depositi alluvionali (Quaternario). Ciascuna pietra fu per lo più usata nelle aree limitrofe alle cave, raggiungendo le città (Comum, Ticinum, Mediolanum, Bergomum, Brixia) attraverso le vie d’acqua; nelle città della pianura (Placentia, Cremona, Mantua) furono privilegiati i laterizi fabbricati con l’argilla locale. A Milano, in quanto città capitale, furono impiegate anche pietre provenienti da maggiore distanza (calcari del Veneto e del Friuli). I marmi bianchi delle Alpi Apuane e i marmi colorati del Mediterraneo orientale, nonostante l’approvvigionamento difficoltoso, ebbero una grande diffusione a Mediolanum e in molti altri siti lombardi. I materiali cavati dai Romani furono continuativamente utilizzati anche nei secoli successivi

Il problema della cronologia del cantiere di San Lorenzo a Milano. Vecchi e nuovi dati a confronto

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Le chiese di Ambrogio e Milano: ambito topografico ed evoluzione costruttiva dal punto di vista archeologico

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Alpha1-acid glycoprotein post-translational modifications: a comparative two dimensional electrophoresis based analysis

Alpha1-acid glycoprotein (AGP) is an immunomodulatory protein expressed by hepatocytes in response to the systemic reaction that follows tissue damage caused by inflammation, infection or trauma. A proteomic approach based on two dimensional electrophoresis, immunoblotting and staining of 2DE gels with dyes specific for post-translational modifications (PTMs) such as glycosylation and phosphorylation has been used to evaluate the differential interspecific protein expression of AGP purified from human, bovine and ovine sera. By means of these techniques, several isoforms have been identified in the investigated species: they have been found to change both with regard to the number of isoforms expressed under physiological condition and with regard to the quality of PTMs (i.e. different oligosaccharidic chains, presence/absence of phosphorilations). In particular, it is suggested that bovine serum AGP may have one of the most complex pattern of PTMs among serum proteins of mammals studied so far

Harnessing NK Cells for Cancer Treatment

In the last years, natural killer (NK) cell-based immunotherapy has emerged as a promising therapeutic approach for solid tumors and hematological malignancies. NK cells are innate lymphocytes with an array of functional competences, including anti-cancer, anti-viral, and anti-graft-vs.-host disease potential. The intriguing idea of harnessing such potent innate immune system effectors for cancer treatment led to the development of clinical trials based on the adoptive therapy of NK cells or on the use of monoclonal antibodies targeting the main NK cell immune checkpoints. Indeed, checkpoint immunotherapy that targets inhibitory receptors of T cells, reversing their functional blocking, marked a breakthrough in anticancer therapy, opening new approaches for cancer immunotherapy and resulted in extensive research on immune checkpoints. However, the clinical efficacy of T cell-based immunotherapy presents a series of limitations, including the inability of T cells to recognize and kill HLA-Ineg tumor cells. For these reasons, new strategies for cancer immunotherapy are now focusing on NK cells. Blockade with NK cell checkpoint inhibitors that reverse their functional block may overcome the limitations of T cell-based immunotherapy, mainly against HLA-Ineg tumor targets. Here, we discuss recent anti-tumor approaches based on mAb-mediated blocking of immune checkpoints (either restricted to NK cells or shared with T cells), used either as a single agent or in combination with other compounds, that have demonstrated promising clinical responses in both solid tumors and hematological malignancie

Post-Transplant Nivolumab Plus Unselected Autologous Lymphocytes in Refractory Hodgkin Lymphoma: A Feasible and Promising Salvage Therapy Associated With Expansion and Maturation of NK Cells

Immune checkpoint inhibitors (CI) have demonstrated clinical activity in Hodgkin Lymphoma (HL) patients relapsing after autologous stem cell transplantation (ASCT), although only 20% complete response (CR) rate was observed. The efficacy of CI is strictly related to the host immune competence, which is impaired in heavily pre-treated HL patients. Here, we aimed to enhance the activity of early post-ASCT CI (nivolumab) administration with the infusion of autologous lymphocytes (ALI). Twelve patients with relapse/refractory (R/R) HL (median age 28.5 years; range 18-65), underwent lymphocyte apheresis after first line chemotherapy and then proceeded to salvage therapy. Subsequently, 9 patients with progressive disease at ASCT received early post-transplant CI supported with four ALI, whereas 3 responding patients received ALI alone, as a control cohort. No severe adverse events were recorded. HL-treated patients achieved negative PET scan CR and 8 are alive and disease-free after a median follow-up of 28 months. Four patients underwent subsequent allogeneic SCT. Phenotypic analysis of circulating cells showed a faster expansion of highly differentiated NK cells in ALI plus nivolumab-treated patients as compared to control patients. Our data show anti-tumor activity with good tolerability of ALI + CI for R/R HL and suggest that this setting may accelerate NK cell development/maturation and favor the expansion of the "adaptive" NK cell compartment in patients with HCMV seropositivity, in the absence of HCMV reactivation

The fading guardian: clinical relevance of TP53 null mutation in high-grade serous ovarian cancers

Backgroundwe evaluated the concordance between immunohistochemical p53 staining and TP53 mutations in a series of HGSOC. Moreover, we searched for prognostic differences between p53 overexpression and null expression groups.Methodspatients affected by HGSOC were included. For each case p53 immunohistochemical staining and molecular assay (Sanger sequencing) were performed. Kaplan-Meier survival analyses were undertaken to determine whether the type of TP53 mutation, or p53 staining pattern influenced overall survival (OS) and progression free survival (PFS).Results34 HGSOC were considered. All cases with a null immunohistochemical p53 expression (n=16) showed TP53 mutations (n=9 nonsense, n=4 in-frame deletion, n=2 splice, n=1 in-frame insertion). 16 out of 18 cases with p53 overexpression showed TP53 missense mutation. Follow up data were available for 33 out of 34 cases (median follow up time 15 month). We observed a significant reduction of OS in p53 null group [HR = 3.64, 95% CI 1.01-13.16].Conclusionimmunohistochemical assay is a reliable surrogate for TP53 mutations in most cases. Despite the small cohort and the limited median follow up, we can infer that HGSOC harboring p53 null mutations are a more aggressive subgroup