Tumor antigen processing and presentation on MHC Class II molecules for CD4⁺ T cell recognition in health and disease

Animal models have shown that CD4+ T cells are required to achieve effective, long-lasting immunity to cancer. Less is known on the role and functional state in human disease of tumor antigen specific CD4+ T cells. These cells recognise epitopes from tumor antigens presented by MHC-II molecules on professional antigen presenting cells and also directly on tumor cells. MAGE-3 is a tumor specific antigen expressed in tumors of different histology but not healthy tissues and so is an ideal candidate for immunotherapeutic purposes. MAGE-3 CD4 naturally processed epitopes have been described. The aims of the project were to analyse how processing influences the repertoire of MAGE-3 CD4 epitopes formed in different antigen expressing cell types and the role of MAGE-3 epitope specific CD4+ T cells in the natural response of advanced melanoma patients. Formation of epitopes through the exogenous pathway was differently influenced by endosomal proteases. Indeed, depending on the epitope studied cysteine and aspartic proteases lead to epitope formation or destruction affecting the repertoire presented in vivo. No clear data were obtained to understand the processing pathways in tumor cells, as formation of the studied epitope was unaffected by cytosolic proteases and did not require autophagy. Most patients had circulating MAGE-3 specific CD4+ T cells, mainly unpolarized or producing anti-inflammatory cytokines suggesting an impairment of the anti-MAGE-3 CD4+ T cell response in advanced stages of disease. The repertoire of epitopes recognised confirmed the immunodominance of previously described epitopes and correlated well with the results of in vitro processing studies. Collectively, these experiments show that anti-MAGE-3 CD4+ T cell responses develop in vivo and that the repertoire of epitopes formed and recognised is influenced by endosomal proteases. Further studies are needed to investigate factors determining impairment of CD4+ T cell function in advanced stages and ways to overcome this dysfunction.</p

Tumor antigen processing and presentation on MHC Class II molecules for CD4⁺ T cell recognition in health and disease

Animal models have shown that CD4+ T cells are required to achieve effective, long-lasting immunity to cancer. Less is known on the role and functional state in human disease of tumor antigen specific CD4+ T cells. These cells recognise epitopes from tumor antigens presented by MHC-II molecules on professional antigen presenting cells and also directly on tumor cells. MAGE-3 is a tumor specific antigen expressed in tumors of different histology but not healthy tissues and so is an ideal candidate for immunotherapeutic purposes. MAGE-3 CD4 naturally processed epitopes have been described. The aims of the project were to analyse how processing influences the repertoire of MAGE-3 CD4 epitopes formed in different antigen expressing cell types and the role of MAGE-3 epitope specific CD4+ T cells in the natural response of advanced melanoma patients. Formation of epitopes through the exogenous pathway was differently influenced by endosomal proteases. Indeed, depending on the epitope studied cysteine and aspartic proteases lead to epitope formation or destruction affecting the repertoire presented in vivo. No clear data were obtained to understand the processing pathways in tumor cells, as formation of the studied epitope was unaffected by cytosolic proteases and did not require autophagy. Most patients had circulating MAGE-3 specific CD4+ T cells, mainly unpolarized or producing anti-inflammatory cytokines suggesting an impairment of the anti-MAGE-3 CD4+ T cell response in advanced stages of disease. The repertoire of epitopes recognised confirmed the immunodominance of previously described epitopes and correlated well with the results of in vitro processing studies. Collectively, these experiments show that anti-MAGE-3 CD4+ T cell responses develop in vivo and that the repertoire of epitopes formed and recognised is influenced by endosomal proteases. Further studies are needed to investigate factors determining impairment of CD4+ T cell function in advanced stages and ways to overcome this dysfunction.</p

A Debordian Analysis of Facebook

What is the reason for the huge success of Facebook? Facebook, in this very sense, realizes what Guy Debord calls the invasive forces of the \u27spectacle\u27 - a social relation between people that is mediated by images (Debord, 1992).Therefore, Facebook is an alternative tool able to amplify an individual\u27s alienation and narcissism, which, according to Debord are more than an emotive description or an aspect of individual psychology: rather, they are a consequence of the mercantile form of social organization which has reached its climax in capitalism

Virality : notes on a concept crossing disciplines

Virus and virus-related terms were much-abused concepts before the COVID pandemic, and they have become even more so during the pandemic. Such concepts stemming from microbiology are now used in a wide range of areas, such as the media, and even in computing language. In this paper, I map out how these concepts have spread across disciplines

Felt index, source parameters and ground motion evaluation for earthquakes at Mt. Vesuvius

Results of non-instrumental surveys carried out on the recent and past seismicity at Vesuvius fave been retaken in order to propose new analyses regarding source mechanisms and causative faults. We present the results of the October 9, 1999 earthquake, the most intense event since the 1944 eruption

Analysis of historical and present earthquakes at Vesuvius for seismic hazard evaluation

Introduction At Vesuvius about 600,000 people live on the volcano and the risk associated to a large eruption is very high, but its complete evaluation includes also the potential damage due to earthquakes accompanying eruptions. Moreover low-moderate energy earthquakes are also observed in volcanic active areas during quiescent periods. Generally such events are shallow and produce high intensities in the epicentral area. Today at Vesuvius the high housing density and economic value exposed make the area of considerable importance for mitigating seismic risk. To evaluate the effects of the earthquakes at Vesuvius, data are required on the location, source mechanism and damage levels of historical earthquakes, in addition to understanding how Vesuvius works. A damage map of the maximum earthquake recorded is proposed

Felt index, source parameters and ground motion evaluation for earthquakes at Mt. Vesuvius

Results of non-instrumental surveys carried out on the recent and past seismicity at Vesuvius fave been retaken in order to propose new analyses regarding source mechanisms and causative faults. We present the results of the October 9, 1999 earthquake, the most intense event since the 1944 eruption

Analysis of historical and recent earthquakes at Campi Flegrei caldera for seismic hazard evaluation

Introduction At Campi Flegrei about 500,000 people live on caldera and the risk associated to an eruption is very high, but its complete evaluation includes also the potential damage due to earthquakes accompanying eruptions. Moreover low-moderate energy earthquakes are also observed in volcanic active areas during quiescent periods. Generally such events are shallow and produce high intensities in the epicentral area. Today at Campi Flegrei the high housing density and economic value exposed make the area of considerable importance for mitigating seismic risk. To evaluate the effects of the earthquakes at Campi Flegrei, data are required on the location, source mechanism and damage levels of earthquakes, in addition to understanding how dynamic processes occur. A damage map of the maximum earthquake expected is proposed

Digital Natives in a Knowledge Economy: will a new kind of Leadership Emerge?

The aim of this paper is to understand whether digital natives will need a different approach to leadership development. The authors discuss that in knowledge economies extrinsic and explicit knowledge (knowing that) learning approaches are more important than traditional learning methods based on the idea that knowledge has a value per se and it is transferred tacitally (knowing how). In conclusion, authors do acknowledge the importance of extrinsic and explicit knowledge in digital natives learning; but, if they wish to become leaders, digital natives still have not only to turn their explicit knowledge into an implicit one (internalization) in order to intuitively use what they are learning but also natives need to learn more about social skills. Keywords: digital natives, digital immigrants, leadership, knowledge economy, internalization.The aim of this paper is to understand whether digital natives will need a different approach to leadership development. The authors discuss that in knowledge economies extrinsic and explicit knowledge (knowing that) learning approaches are more important than traditional learning methods based on the idea that knowledge has a value per se and it is transferred tacitally (knowing how). In conclusion, authors do acknowledge the importance of extrinsic and explicit knowledge in digital natives learning; but, if they wish to become leaders, digital natives still have not only to turn their explicit knowledge into an implicit one (internalization) in order to intuitively use what they are learning but also natives need to learn more about social skills. Keywords: digital natives, digital immigrants, leadership, knowledge economy, internalization.Uninvited Submission

A representação visual dos géneros: uma análise a partir das revistas de segmento masculino

Este e-working paper integra o debate acerca da diversidade de identidades de género a partir da análise das diferentes formas de representação visual dos corpos veiculadas em algumas das revistas de segmento masculino a circular em Portugal (Maxmen, FHM, Men’s Health e GQ). O trabalho começa por apresentar alguns dados indicativos do surgimento e evolução das vendas das revistas de segmento masculino em Portugal, bem como do perfil dos seus leitores. Posteriormente e a partir das imagens que integram estas publicações desenha-se, então, uma reflexão acerca das diferentes concepções de género associadas às revistas. This e-Working Paper incorporates a debate on the diversity of gender identities through the analysis of different ways of visually representing the body carried in some of the male magazines circulating in Portugal (Maxmen, FHM, Men’s Health and GQ). The work begins by presenting some data regarding the emergence and market evolution of male magazines in Portugal, as well as the reader’s profile. Therefore, through the diversity of images that integrate these publications, there will be a discussion on the different conceptions of gender