1,721,305 research outputs found
Molecular genetic alterations in egfr CA-SSR-1 microsatellite and egfr copy number changes are associated with aggressiveness in thymoma
No full textBackground: The key role of egfr in thymoma pathogenesis has been questioned following the failure in identifying recurrent genetic alterations of egfr coding sequences and relevant egfr amplification rate. We investigated the role of the non-coding egfr CA simple sequence repeat 1 (CA-SSR-1) in a thymoma case series. Methods: We used sequencing and egfr-fluorescence in situ hybridization (FISH) to genotype 43 thymomas; (I) for polymorphisms and somatic loss of heterozygosity of the non-coding egfr CA-SSR-1 microsatellite and (II) for egfr gene copy number changes. Results: We found two prevalent CA-SSR-1 genotypes: A homozygous 16 CA repeat and a heterozygous genotype, bearing alleles with 16 and 20 CA repeats. The average combined allele length was correlated with tumor subtype: Shorter sequences were significantly associated with the more aggressive WHO thymoma subtype group including B2/B3, B3 and B3/C histotypes. Four out of 29 informative cases analysed for somatic CA-SSR-1 loss of heterozygosity showed allelic imbalance (AI), 3/4 with loss of the longer allele. By egfr-FISH analysis, 9 out of 33 cases were FISH positive. Moreover, the two integrated techniques demonstrated that 3 out of 4 CA-SSR-1-AI positive cases with short allele relative prevalence showed significantly low or high chromosome 7 "polysomy"/increased gene copy number by egfr-FISH. Conclusions: Our molecular and genetic and follow up data indicated that CA-SSR-1-allelic imbalance with short allele relative prevalence significantly correlated with EGFR 3+ immunohistochemical score, increased egfr Gene Copy Number, advanced stage and with relapsing/metastatic behaviour in thymomas. © Journal of Thoracic Disease
Prefazione
No full textPrefazione e introduzione ai saggi contenuti nel volume, dedicato a un convento del XVIII secol
Conservare l’eredità di Vittone tra conoscenza storica e progetto di restauro
Full text linkDa una rilettura della storiografia vittoniana emerge la rilevanza della figura di Eugenio Olivero, primo esponente, fra gli studiosi di inizio del XX secolo, a cui si deve il riconoscimento di aver documentato e studiato le architetture di Vittone con passione e curiosità tecnica, ispirando un approccio integrato tra storia e analisi dell’architettura, dei magisteri edilizi e delle tecniche costruttive. Attraverso un esame dell’archivio dell’ studioso, conservato all’Accademia delle Scienze di Torino, il saggio considera l’eredità di Olivero come utile chiave di lettura sia per riflettere sulla carriera e opera di Vittone, sia per ripercorrere le origini di una storia della conservazione dei suoi edifici. Oggi, consolidato l’orientamento metodologico fatto proprio dallo studioso, quale fase propedeutica alla redazione del progetto di restauro, resta aperto il tema della conservazione della autorialità delle architetture vittoniane, individuando in una maggiore interoperabilità dei dati raccolti negli interventi di restauro già eseguiti, la strada per una conservazione e valorizzazione consapevole e coerente, oltre che condivisa, di questo patrimonio
I mulini natanti del Po mantovano
No full textSI INQUADRA LA STORIA DEI MULINI NATANTI IN TERRITORIO MANTOVANO SULLA SCORTA DI DATI ARCHIVISTICI E CARTOGRAFICI INEDIT
IL CAMPANILE VITTONIANO DELL’ANTICA CASA COMUNALE A MONTANARO (To): STUDI PER UNA STORIA DELLA SUA COSTRUZIONE
Full text linkSeismic risk in the chemical process industry: A semi-quantitative methodology for critical equipment identification
No full textNatural events, such as earthquakes, floods, etc., can play a significant role in triggering industrial accidents of various intensities (the so-called Na-Tech risk), so that their inclusion in a comprehensive risk assessment is very important. However, a detailed and comprehensive quantitative approach is often unrealistic, because of the extremely large number of calculations to be carried out and of scenarios to be analysed. A preliminary semi-quantitative methodology is here presented for the characterization of the safety level of the different equipment items located in an industrial site, with respect to seismic hazard. Still based on objective evaluations, the presented approach allows to reduce the calculation burden, rank the equipment items in terms of relative seismic risk, and to identify the most critical items which more urgently need further attention. Along with the proposed methodology, an example of its application to a real industrial case is presented
Beyond DNA repair, the immunological role of PARP-1 and its siblings
No full textADP-ribosylation is the addition of one or more (up to some hundreds) ADP-ribose moieties to acceptor proteins. There are two major families of enzymes that catalyse this reaction: extracellular ADP-ribosyl-transferases (ARTs), which are bound to the cell membrane by a glycosylphosphatidylinositol anchor or are secreted, and poly(ADP-ribose)-polymerases (PARPs), which are present in the cell nucleus and/or cytoplasm. Recent findings revealed a wide immunological role for ADP-ribosylating enzymes. ARTs, by sensing extracellular NAD concentration, can act as danger detectors. PARP-1, the prototypical representative of the PARP family, known to protect cells from genomic instability, is involved in the development of inflammatory responses and several forms of cell death. PARP-1 also plays a role in adaptive immunity by modulating the ability of dendritic cells to stimulate T cells or by directly affecting the differentiation and functions of T and B cells. Both PARP-1 and PARP-14 (CoaSt6) knockout mice were described to display reduced T helper type 2 cell differentiation and allergic responses. Our recent findings showed that PARP-1 is involved in the differentiation of Foxp3+ regulatory T (Treg) cells, suggesting a role for PARP-1 in tolerance induction. Also ARTs regulate Treg cell homeostasis by promoting Treg cell apoptosis during inflammatory responses. PARP inhibitors ameliorate immune-mediated diseases in several experimental models, including rheumatoid arthritis, colitis, experimental autoimmune encephalomyelitis and allergy. Together these findings show that ADP-ribosylating enzymes, in particular PARP-1, play a pivotal role in the regulation of immune responses and may represent a good target for new therapeutic approaches in immune-mediated diseases. © 2013 John Wiley & Sons Ltd
N-glycan engineering of a plant-produced anti-CD20-hIL-2 immunocytokine significantly enhances its effector functions
No full textAnti-CD20 recombinant antibodies are among the most promising therapeutics for the treatment of B-cell malignancies such as non-Hodgkin lymphomas. We recently demonstrated that an immunocytokine (2B8-Fc-hIL2), obtained by fusing an anti-CD20 scFv-Fc antibody derived from C2B8 mAb (rituximab) to the human interleukin 2 (hIL-2), can be efficiently produced in Nicotiana benthamiana plants. The purified immunocytokine (IC) bearing a typical plant protein N-glycosylation profile showed a CD20 binding activity comparable to that of rituximab and was efficient in eliciting antibody-dependent cell-mediated cytotoxicity (ADCC) of human PBMC against Daudi cells, indicating its fuctional integrity. In this work, the immunocytokine devoid of the typical xylose/fucose N-glycosylation plant signature (IC-ΔXF) and the corresponding scFv-Fc-ΔXF antibody not fused to the cytokine, were obtained in a glyco-engineered ΔXylT/FucT N. benthamiana line. Purification yields from agroinfiltrated plants amounted to 20–35 mg/kg of leaf fresh weight. When assayed for interaction with FcγRI and FcγRIIIa, IC-ΔXF exhibited significantly enhanced binding affinities if compared to the counterpart bearing the typical plant protein N-glycosylation profile (IC) and to rituximab. The glyco-engineered recombinant molecules also exhibited a strongly improved ADCC and complement-dependent cytotoxicity (CDC). Notably, our results demonstrate a reduced C1q binding of xylose/fucose carrying IC and scFv-Fc compared to versions that lack these sugar moieties. These results demonstrate that specific N-glycosylation alterations in recombinant products can dramatically affect the effector functions of the immunocytokine, resulting in an overall improvement of the biological functions and consequently of the therapeutic potential. © 2017 Wiley Periodicals, Inc
Vittone under the Looking Glass. An Introduction
Full text linkThe eleven texts gathered in this special collection are characterized
by a certain diversity. They are, indeed, based on different methods
of historical analysis rooted in the various professional paths of their authors (architectural history, the history of art, medieval and early modern history, musicology...). However, one goal is common and has guided the selection: Archistor readers are offered detailed insights on specific aspects of Bernardo Vittone’s work and professional career. By choosing to cast a closer look on specific events, texts and documents, new elements have emerged both from little known episodes in the architects’ career, and from scenarios that were previousy considered as sufficiently investigated. Among the topics that are discussed, are the forbidden books hidden in the inventory of Vittone’s library, the complex web of visual references incorporated in the Istruzioni’s illustrations, the new coordinates to be assigned to Vittone’s education, Vittone’s musical competences, and the sequence of events that explain the dispersion of his graphic legacy in different archival collections. A final essay provides a useful synthesis and an assessment of critical literature. Thanks to these new insights, some of which escape narrow definitions of architectural history, our assessment of Vittone’s role in eighteenth-century Italy, 250 years since his death in 1770, becomes more complex and, hopefully, more contradictory
- …
