Bovine CD4 T cell memory subsets and immunological markers in Mycobacterium bovis infection and vaccination

Mycobacterium bovis is the causative agent of tuberculosis in cattle. M. bovis is a member of the Mycobacterium tuberculosis complex (Mtbc) which also includes M. tuberculosis, M. caprae, M. microti, M. africanum, M. canetti, M. pinnipedii, M. suricattae, M. mungi, and M. bovis Bacillus Calmette Guerin (BCG) 1-3. Despite what the nomenclature may imply, members of this group are not host species specific. The host range of M. bovis appears to be the broadest of the complex, causing disease in a number of species including humans 4. Great strides have been made over the past century both toward the control of bovine tuberculosis (bTB) in cattle and also limiting the risk to human exposure (e.g., pasteurization of milk for dairy products); however, the disease still has great socioeconomic impact for livestock farmers. It is estimated that over 50 million cattle are currently infected worldwide, costing around $3 billion annually5. The WHO (World Health Organization), in conjunction with FAO (Food and Agriculture Organization of the United Nations) and OIE (Office International des ÃÂpizooties), classify bTB as a neglected zoonosis 6,7. A crucial component of the immune response to TB in humans, cattle and mice is the production of interferon (IFN)-γ by T helper 1 (Th1) CD4 T cells 8-12. Immune deficiencies affecting CD4 T cells [e.g., human immunodeficiency virus (HIV) infection] and IL-12/IFN-γ /STAT1 signaling pathways result in more severe disease upon TB infection in humans 13,14. In fact, IFN-γ release assays (IGRA) and delayed type hypersensitivity (i.e., skin test) responses are markers of infection in cattle and humans (reviewed respectively by Schiller et al. 15 and Walzl et al. 16). Diagnostic IGRAs are measures of ‘ex vivo’ immune responses relying on rapid production of IFN-γ in response to mycobacterial antigen stimulation in short-term (16–24 h) whole blood or peripheral blood mononuclear cell (PBMC) cultures. These ex vivo assays are generally considered a measure of T cell effector responses 12,17. Most protective bTB vaccines elicit ex vivo IFN-γ responses; however, not all vaccines inducing this response are protective 5,18. Cultured assays (i.e., culture of cells for 7-14 days before IFN-γ measurement) are assumed to quantify memory responses, primarily central memory T cells (Tcm) in humans 19-21. In light of the idea that cultured ELISPOT measures Tcm responses, several studies have shown its association with protection against malaria, suppression of viral recrudescence in hepatitis B virus carriers, low virus levels in HIV infection, and favorable outcomes in human TB 22-26. In cattle, responses measured by cultured IFN-γ ELISPOT following vaccination are the best-known positive correlate of protection in vaccine and challenge experiments 27-31. Increasing interest has risen in order to characterize and assess the role of polyfunctionality in both protective and detrimental immune responses in TB. Polyfunctional T cells simultaneously produce two or more cytokines with IFN-γ, IL-2, and tumor necrosis factor-α (TNF-α) being the most commonly measured Th-1 cytokines 32,33. Association between protection and vaccination-induced polyfunctional T cells has been mainly studied in small animal models 34,35. In humans, strong polyfunctional responses are detected in M. tuberculosis-infected individuals, high IL-2 production is associated with a positive clinical status (e.g., latent or treated disease), while a strong IFN-γ/TNF-α response is associated with a poor outcome (i.e., active TB) 36. Human polyfunctional responses to vaccination both prior to TB exposure and in previously exposed individuals (i.e., latent infection) are extremely variable. In cattle, T cell polyfunctionality has only been measured upon ex vivo recall stimulation 26,37.These studies found no association between polyfunctional responses measured before challenge and vaccine success. Instead, polyfunctional responses to infection were associated with increased pathology and poor disease outcome 26. Polyfunctional responses by long-term cultured cells for enrichment of Tcm responses have not been evaluated in spite of the fact that cultured IFN-γ ELISPOT is one of the most promising protection correlates in cattle 27-31. The research included in this thesis had the objective to characterize memory cells phenotype and aspects of their functionality in cattle, specifically in response to bTB infection and vaccination. The discrimination of cell phenotype involved in cytokine production under both cultured and ex vivo conditions may be necessary to identify specific correlates of vaccine efficacy, useful for vaccine candidates selection for costly efficacy trials in biosafety level 3 (BSL-3) facilities

DEVELOPMENT OF THE HISTORICAL AND NATURAL HERITAGE OF THE LAZIO’S COAST: TOURISTIC ROUTES’ CREATION

L’arco costiero della regione Lazio, lungo 350 km, è caratterizzato dalla presenza di emergenze storico-archeologiche e paesaggistiche di gran pregio. Il tentativo di indirizzare i turisti verso il patrimonio culturale ha caratterizzato la gestione del territorio degli ultimi anni, sebbene la vocazione balneare del litorale rimanga comunque prevalente. Il turismo culturale è un aspetto della vocazione territoriale, il cui sfruttamento ben si presta a sostenere la crescita economica locale e regionale. A tale scopo, i GIS e la cartografia tradizionale, integrati in unico ambito di ricerca, possono essere utili strumenti di supporto alle azioni di pianificazione, gestione, salvaguardia e valorizzazione del territorio. L’archiviazione, l’elaborazione, la rappresentazione e l’analisi di un’enorme mole di dati, integrati in un unico sistema informativo, offre la possibilità di evidenziare relazioni e criticità estremamente utili, per intervenire in modo concreto sul litorale. In altre parole, attraverso la realizzazione di un progetto che preveda l’ideazione di percorsi tematici creati con il supporto di GIS, si potrebbe dare un concreto sostegno tecnico, logistico e pratico a quella parte di governo del territorio che punta sulla valorizzazione dei beni culturali e paesaggistici, per incentivare la presenza turistica nelle relative aree di interesse lungo la costa laziale. Inoltre un Sistema Informativo Territoriale permette di far coesistere elementi difficilmente correlabili in altri ambiti, creando l’opportunità di una diversificazione dell’offerta turistica, in grado così di rispondere a utenti di diversa provenienza e interesse. In un contesto in cui è fondamentale il recupero e la salvaguardia della memoria del passato, la conservazione e lo sfruttamento di ciò che è intrinsecamente bello e che rappresenta la formazione della nostra civiltà è, quindi, possibile mediante l’uso di strumenti nuovi, come il GIS, al fine di accrescere il valore del patrimonio culturale, di rafforzare l’identità di gruppo delle comunità locali, di sfruttare al meglio le risorse territoriali e di alimentare processi di sviluppo economico.The coast of Lazio is of 350 km and it’s full of important historical evidences. Nonetheless analyzing the touristic image, it is possible to see how the sea is the strongest factor of attraction, but the places are important for the cultural heritage too. The support of GIS will be useful to improve the economic growth through creation of touristic routes

E-commerce: online consumer, service failures and the service paradox

JEL classification: L81; M19In a world where the online space gains gradually more territory and becomes a central part of people’s lives, it is evident that e-commerce will continue to grow and become a natural form of shopping. Equally to its traditional variant, e-commerce is not free from failures, and has in fact the additional disadvantage of not featuring human physical interactions. That is why it is so important for e-retailers to learn about their consumers’ preferences and shopping behaviors, which will allow them to adapt and improve their services and recovery strategies. After an extensive literature review related to the study’s main subjects, it appeared to be extremely pertinent and valuable to study a Portuguese consumer sample, allowing its characterization. This study provides an understanding of consumers’ behavior regarding their online shopping attitudes, their failure experiences and their recovery preferences. It is therefore a useful tool for service providers who seek to improve their customer service and consumer satisfaction. Results show that delivery service variants play an important role when it comes to the experience of delivery failures and consumer satisfaction. Through this study, it is also possible to see how there are a few indicators that do not exclude the possibility of the existence of the phenomenon called recovery paradox, controversial concept regarding consumer post-failure satisfaction.Num mundo onde o espaço online conquista cada vez mais território e se torna numa parte central da vida das pessoas, é natural que o comércio eletrónico tenha, a curto-prazo, um grande crescimento e se estabeleça como uma forma natural de comércio. Tal como a sua variante tradicional, o retalho eletrónico não está livre de falhas. Tem, na verdade, a desvantagem adicional de não contemplar qualquer interação presencial, que representa muitas vezes uma ferramenta de recuperação de falhas valiosa. Por essa razão, é importante que os retalhistas conheçam as preferências e os comportamentos dos seus consumidores, permitindo-lhes adaptar e melhorar os seus serviços e as suas estratégias de recuperação de falhas. Após uma extensa revisão de literatura relacionada com os temas principais deste estudo, tornou-se claro que seria pertinente estudar uma amostra de consumidores portugueses, com o objetivo de fazer a sua caracterização. Este estudo permite conhecer os consumidores portugueses no que diz respeito ao seu comportamento de compra, à sua experiência de falhas e às suas preferências de recuperação das mesmas. É, por isso, uma ferramenta útil para retalhistas que pretendam melhorar o seu serviço e a satisfação dos seus consumidores. Os resultados indicam que as variantes do serviço de entrega têm influência na experiência de falhas e na satisfação dos consumidores. Foi também possível observar que determinados fatores não excluem a possibilidade de existência do fenómeno paradoxo de recuperação da falha, conceito controverso acerca da satisfação do consumidor após ter experienciado uma falha e a sua consequente recuperação

Exploring the status of the human operator in industry 4.0: a systematic review

Industry 4.0 (I4.0) promises to transform jobs and working conditions through the implementation of unprecedented human-machine interaction modes. As the operator working in these new settings, known as the Operator 4.0, is a relatively recent concept, and although technological developments are expected to support workers and require higher labor skills, the risks and health impacts resulting from these changes remain underexplored. This systematic review aims to (i) systematize literature findings on how workers are perceived and participate in I4.0 work systems; (ii) identify the main technological changes driven by I4.0; and (iii) instigate discussion regarding the impacts these changes may have for workers and the sustainability of work systems. Following a systematic review approach using the PRISMA protocol, the articles were organized into two main analysis axes: the technical changes brought about by I4.0, and the representation of the human worker within these new work settings. The findings reveal that a techno-centered approach still seems to be dominant in guiding the implementation of I4.0 models; secondly, as a consequence, the social dimensions of work tend to remain as residual issues, overshadowed by the promises related with technology (e.g., productivity, efficiency); finally, the representation of the Operator 4.0 remains blurry, as he/she is perceived as gender neutral, skillful, and perfectly fit for work, assuring the functioning (and compensating for the limits) of these systems. While I4.0 promises safer and more productive workplaces, issues related to employment conditions, emerging risks and health impacts become more prominent when analyzed from an activity-centered perspective. In terms of future research, a more heuristic analysis could be achieved through a participatory and work-centered approach and following a gender perspective. This way, visibility could be conferred to another side of I4.0, thus guaranteeing conditions for the sustainable development of these work situations

Il paesaggio della trasformazione industriale: il villaggio operaio di Panzano a Monfalcone

Il lavoro analizza la nascita, lo sviluppo e le caratteristiche del villaggio operaio di Panzano in prossimità dei Cantieri Navali a Monfalcone in provincia di Gorizia nel 1908. L’insediamento presenta alcune caratteristiche simili a quelle dei villaggi operai italiani ed europei dei primi anni del Novecento, ma se ne discosta per alcuni caratteri peculiari come ad esempio la presenza di diffuso sistema di welfare aziendale di tipo paternalistico, la collocazione in una stretegica area del confine nazionale, uno stretto rapporto tra sviluppo urbano e fabbrica fordista

Leggere Koolhass: Bigness, Junkspace e città generica

Il lavoro analizza e rilegge in chiave geografica l'apporto fornito da Rem Khoolas alla luce della sue teorizzazioni sulla città e del cambiamento di prospettiva di analisi proposto. Il contributo si sofferma sulla lettura critica proposta da Khoolas in contrapposizione a quella fornita su i non luoghi da Marc Augé come cambiamento paradigmatico nell'approccio alle dinamiche in ambito urbano

Efficient Generation of Multimodal Fluid Simulation Data

Applying the representational power of machine learning to the prediction of complex fluid dynamics has been a relevant subject of study for years. However, the amount of available fluid simulation data does not match the notoriously high requirements of machine learning methods. Researchers have typically addressed this issue by generating their own datasets, preventing a consistent evaluation of their proposed approaches. Our work introduces a generation procedure for synthetic multi-modal fluid simulations datasets. By leveraging a GPU implementation, our procedure is also efficient enough that no data needs to be exchanged between users, except for configuration files required to reproduce the dataset. Furthermore, our procedure allows multiple modalities (generating both geometry and photorealistic renderings) and is general enough for it to be applied to various tasks in data-driven fluid simulation. We then employ our framework to generate a set of thoughtfully designed benchmark datasets, which attempt to span specific fluid simulation scenarios in a meaningful way. The properties of our contributions are demonstrated by evaluating recently published algorithms for the neural fluid simulation and fluid inverse rendering tasks using our benchmark datasets. Our contribution aims to fulfill the community's need for standardized benchmarks, fostering research that is more reproducible and robust than previous endeavors.Comment: 10 pages, 7 figure