Characterization of Natural Killer cells from patients affected by pleural effusions. Caratterizzazione di cellule Natural Killer in pazienti affetti da versamento pleurico.

Natural killer (NK) cells are large innate lymphocytes involved in tumor recognition and eradication. NK cell activity is impaired in cancer patients and in NSCLC these cells showed a pro-angiogenic phenotype and function. We investigated whether NK cells infiltrating inflammatory or malignant pleural effusions caused by primary or metastatic tumors of different origins (iPE, ptPE and tmPE, respectively) are able to acquire pro-tumor and pro-angiogenic features. PE-NK cells are enriched in CD56bright CD16- NK cells expressing the decidual NK marker CD49a and the activation marker CD69, in addition to a lower expression of the CD57 maturation marker. Furthermore, NK cells derived from tmPE display pro-angiogenic properties: they are predominantly VEGF+ and they are able to induce capillary-like structures in vitro on human endothelial cells. Moreover, NK cells from all patient samples showed lower cytotoxicity against K562 tumor target cells and lower positivity for perforin in comparison to peripheral blood of healthy donors (hPB) NK cells. After 3-day of NK culture with IL-2, PE-NK cells restored their cytotoxicity, whereas in PB-NK cells from patients did not reach a high level of killing capacity. 3-day culture using IL-2 plus TGF\u3b2 or IL-2 added with enriched pleural effusion milieu, only partially restored the cytotoxic potential. Purified hPB NK cells treated for 7 days with IL-15 and pleural effusions acquired a pro-angiogenic phenotype, showing cell polarization towards the CD56bright CD16dim IFN\u3b3low NK cell subset, suggesting that in the PE milieu, diverse soluble factors are able to skew cytotoxic NK cells into pro-tumor, pro-angiogenic NK cells

The impact of technological progress on the labour market

One of the major challenges, if not the crucial one, that politicians and governments will face in the next years is the relationship between technological progress and the social exclusion of those who are neglected by the system of social guarantees that the welfare State is still able to ensure. In this article, I analyse through a critical theory approach how technology becomes a purpose, the impact of technology on the job market and its consequences. I try to provoke some ethical reflection on uncontrolled technological progress and on the role of the man in the next years. The future of the labour market will be changed by a series of factors, some of the most important being shifting demographics, dynamic workforces, the rise of individual choice and especially the technological revolution. Of course, these arguments doesn’t mean that technological progress should stop or that I am against technological progress, especially because there are areas where innovations are lifesaving, or reducing casualties in the battlefield or reducing car incidents. The purpose of this  research is to question what will be the role of man in the world

The effect of weld residual stresses and their re-distribution with crack growth during fatigue under constant amplitude loading

In this work the evolution of the residual stresses in a MIG-welded 2024-T3 aluminium alloy M(T) specimen during in situ fatigue crack growth at constant load amplitude has been measured with neutron diffraction. The plastic relaxation and plasticity-induced residual stresses associated with the fatigue loading were found to be small compared with the stresses arising due to elastic re-distribution of the initial residual stress field. The elastic re-distribution was modelled with a finite element simulation and a good correlation between the experimentally-determined and the modelled stresses was found. A significant mean stress effect on the fatigue crack growth rate was seen and this was also accurately predicted using the measured initial residual stresses

A critical review of resilience in international relations

In the context of evolving challenges, EU member states are faced with vulnerabilities for which they are not prepared such as economic crises, populism, fake news, disinformation campaigns and pandemics, therefore the EU underlines the importance of resilience in countering these threats and achieving its foreign policy objectives. Although used in different areas such as psychology, economy, industry, in International Relations resilience was defined in different terms by various institutions, but the common ground resides in acknowledging resilience as the recovery and adaptation after an adversity such as an economic crisis or natural disaster. Moreover, resilience can be strengthened by preparing the population for better coping with future disasters and crises. Given the differences in understanding resilience between different international organizations, as NATO that approaches the term as the resilience of infrastructures, or the EU that refers mainly to the resilience of partner states but targets to strengthen EU’s resilience for its global ambitions and the lackof readiness in our region, there is the need to foster research on this subject and to operationalise the concept. For the EU, Resilience is the central objective of its development & humanitarian assistance but it is also the response for how to sustain progress in the transformational agenda of the EU, althoughthe EU admits there are not indicators of resilience and nor it specifies how this will be undergone. I attempt to approach the concept from an academic perspective, reviewing the literature on resilience and arguing that the study of political culture named The Civic Culture (1963) written by Gabriel Almond and Sydney Verba offers relevant insights on the study of resilience. Starting from the surveys they conducted in the United States, Britain, Italy, West Germany and Mexico, they aimed to establish in which type of political culture a liberal democracy is most probably to appear and develop and I consider that their indicators are also useful when studying resilience. I will create a working definition and present themain critiques towards the concept, to which I add the one that came into my mind after the Coronavirus pandemic started: is the state after an adversity the same as it was before or not? After a disaster there is only one way through the previous normality or there can also be a new balance? I could exemplify with the Coronavirus pandemic- if individual liberties are limited or social cohesion is broken the new situation is still resilient/normal? In this context, the research question is which type of political culture reflects a resilient society. The purpose of the study is to operationalise the concept of resilience based on the set of indicators derived from Almond and Verba. The objectives of the research are to provide a critical literature review on resilience in International Relations; to operationalize the concept, establishing the dimensions, and indicators. The challenges of this research are related to the fact that there are significant differences among the definitions offered by the existing literature and the use of the concept by different international organisations such as NATO and the EU. The main sources would be the literature on political culture, resilience and official documents such as EU Grand Strategy, the 2012 EU Communication on Resilience, the 2013 Resilience Action Plan, the 2015 Resilience Marker and Compendium, the 2017 Joint Communication of the EP and the Council “A Strategic Approach to Resilience in the EU’s External Action”

Load partitioning and evidence of deformation twinning in dual-phase fine-grained zr-2.5%Nb alloy.

In situ neutron diffraction loading experiments were carried out on a cold-rolled dual-phase (a-phase, '"' 10% b-phase) Zr–2.5%Nb alloy at room temperature. The specimens were cut at different angles from the rolling direction (RD) towards the transverse direction (TD), thus the loading axis changes gradually from the rolling to transverse direction. Due to the strong texture of the studied alloy, and unidirectional nature of deformation twinning, the changing loading direction with respect to initial texture has a significant impact on the collaborative slip-twinning deformation mode in the hexagonal close-packed (hcp) a-phase. The present neutron diffraction results provide direct evidence of {1 - 1.2}/1 - 1. - 1S ‘‘tensile’’ twins in the a-phase of dual-phase Zr–2.5%Nb alloy at room temperature. Additionally, TEM analysis was employed to confirm the presence of ‘‘tensile’’ twins, and determine if other type of twins were present. It is further clear from the neutron diffraction results that applied load is gradually transferred from the plastically softer a-phase to the plastically harder b-phase which acts as a reinforcing phase having a yield strength in the range 750–900 MPa depending on the loading direction

JQ1, a BET Inhibitor, Synergizes with Cisplatin and Induces Apoptosis in Highly Chemoresistant Malignant Pleural Mesothelioma Cells

BACKGROUND: Malignant Pleural Mesothelioma (MPM) is an asbestos-associated tumor with poor prognosis and few therapeutic options. JQ1, a selective antagonist of BRD4, modulates transcription of oncogenes, including MPM chemoresistance-associated c-Myc and Fra-1. OBJECTIVE: We investigated if JQ1 could enhance the efficacy of cisplatin against MPM. METHODS: The antiproliferative activity of cisplatin in combination with JQ1 was assessed on MPM cell lines representative of the cellular phenotypes of this tumor (epithelioid, sarcomatoid and biphasic), and on one cisplatin resistant sub-line. The combination schedule was optimized adopting a 3Dspheroid model. Drug combination effects were correlated with cell cycle distribution and senescence- associated \u3b2-galactosidase positive cells. The expression of c-Myc and Fra-1 proteins and some apoptosis markers was assessed by immunoblotting and RT-qPCR. DNA damage and repair were evaluated by means of alkaline comet assay. RESULTS: JQ1 in combination with cisplatin elicited additive or synergistic (superadditive) antiproliferative effects on MPM cells, depending on the cell line. The combination showed tumor regression on the 3D-spheroid model. It induced increased apoptosis, along with decreased c-Myc and, sometimes, Fra-1 expression. JQ1 decreased cisplatin-induced DNA breaks in all MPM cells and increased senescence even in less proficient cells, thus enhancing the DNA Damage Response (DDR). CONCLUSION: The superadditive effect is due to c-Myc repression. The consequent DDR enhancement triggers to apoptosis induction and/or permanent growth arrest (senescence), depending on the MPM cellular context, leading to tumor regression. Thus, the pharmacological modulation of BET activity could represent a promising tool for future MPM therapy

Epigenetic and antitumor effects of platinum(IV)-octanoato conjugates

We present the anticancer properties of cis, cis, trans-[Pt(IV)(NH3)2Cl2(OA)2] [Pt(IV)diOA] (OA = octanoato), Pt(IV) derivative of cisplatin containing two OA units appended to the axial positions of a six-coordinate Pt(IV) center. Our results demonstrate that Pt(IV)diOA is a potent cytotoxic agent against many cancer cell lines (the IC50 values are approximately two orders of magnitude lower than those of clinically used cisplatin or Pt(IV) derivatives with biologically inactive axial ligands). Importantly, Pt(IV)diOA overcomes resistance to cisplatin, is significantly more potent than its branched Pt(IV) valproato isomer and exhibits promising in vivo antitumor activity. The potency of Pt(IV)diOA is a consequence of several factors including enhanced cellular accumulation correlating with enhanced DNA platination and cytotoxicity. Pt(IV)diOA induces DNA hypermethylation and reduces mitochondrial membrane potential in cancer cells at levels markedly lower than the IC50 value of free OA suggesting the synergistic action of platinum and OA moieties. Collectively, the remarkable antitumor effects of Pt(IV)diOA are a consequence of the enhanced cellular uptake which makes it possible to simultaneously accumulate high levels of both cisplatin and OA in cells. The simultaneous dual action of cisplatin and OA by different mechanisms in tumor cells may result in a markedly enhanced and unique antitumor effects of Pt(IV) prodrugs

Problematic smartphone use and psychological well-being: the role of loneliness and metacognitive beliefs

openL’utilizzo massivo della tecnologia, nel corso degli anni, ha contribuito a modificare la vita quotidiana di ciascun individuo, trasformando non solo le forme di comunicazione, ora globalizzate, ma anche la percezione del mondo e il modo in cui lo stesso viene esperito. La disponibilità degli strumenti digitali, in primis lo smartphone, ha infatti generato una graduale ma repentina “rivoluzione” tecnologica e sociologica. Non sorprende, allora, che uno dei problemi principali della società contemporanea sia la quotidiana iperstimolazione causata dai dispositivi digitali, la quale può sfociare in deficit dell’attenzione, difficoltà di adattamento e comunicazione sociale o ancora isolamento e distress emotivo. Risulta sempre più evidente come un numero elevato di giovani sviluppi un attaccamento ossessivo allo smartphone e come, in generale, stiano aumentando drasticamente gli utenti che presentano un utilizzo problematico dello strumento, il quale interferisce nello sviluppo dell’identità e dell’immagine di sé stessi. Il fine del presente lavoro di ricerca è proprio quello di raccogliere informazioni utili allo sviluppo di interventi e protocolli atti a minimizzare i danni psicofisici, siano essi potenziali o attuali, causati dall’uso disfunzionale dei devices digitali. Assumendo che il pubblico usufruisca dinamicamente dei mezzi di comunicazione per soddisfare determinate necessità, si sono volute indagare le modalità e le preferenze di utilizzo dello smartphone, nonché gli stati interni e le credenze che sostengono tali scelte. I risultati mostrano che esistono correlazioni positive tra l’utilizzo problematico dello smartphone e l’insorgenza di sintomatologia ansiosa e depressiva e come lo specifico tipo di utilizzo contribuisca a definire la portata della compromissione, maggiore nel campione di popolazione giovane. Ulteriori variabili indagate sono la percezione soggettiva di solitudine, con particolare riguardo alla sua componente psicologica, e la presenza di credenze metacognitive negative. Entrambe risultano correlate positivamente alle variabili principali (utilizzo problematico dello smartphone e insorgenza di sintomi ansiosi e depressivi), consentendo una comprensione più approfondita del fenomeno in questione e offendo un’opportunità per raggiungere più agevolmente determinati obiettivi clinici e/o sviluppare nuovi interventi preventivi

As diferenças existentes entre as línguas e sua interferência na aprendizagem de uma língua estrangeira: um estudo de caso na Escola Caetano Bez Batti

Monografia apresentada à Diretoria de Pós-graduação da Universidade do Extremo Sul Catarinense – UNESC, para a obtenção do título de especialista em Língua Inglesa.O objetivo desta pesquisa é discutir sobre as diferenças existentes entre as línguas e sua interferência na aprendizagem de uma língua estrangeira, principalmente para aprendizes iniciantes que estudam em escolas regulares. A ideia é fazer um estudo comparativo entre o português e o inglês, destacando algumas diferenças existentes entre esses dois idiomas e verificando na prática como os estudantes lidam com essas diferenças. Além disso, também se constitui como um objetivo secundário indicar estratégias pedagógicas que o professor de língua estrangeira pode utilizar para ajudar os alunos a superarem as dificuldades que podem surgir. O problema sobre o qual gira esta pesquisa é a dificuldade em aprender uma nova língua devido às diferenças existentes entre a língua materna do aprendiz e a língua estrangeira em estudo. A metodologia adotada consistiu em uma pesquisa bibliográfica seguida de uma pesquisa de campo em uma escola de ensino regular. A etapa prática resumiu-se na aplicação de instrumentos de pesquisa e na observação de algumas aulas. Os resultados obtidos revelaram que muitas dúvidas, dificuldades e erros dos aprendizes são decorrentes da falta de entendimento acerca das diferenças existentes entre as línguas, bem como da interferência da língua materna na aprendizagem da língua estrangeira, visto que os alunos demonstraram uma tendência em aplicar na língua estrangeira as regras de sua língua materna, misturando as estruturas. Além disso, também foi possível constatar que o ensino de língua estrangeira nas escolas regulares não está apresentando resultados muito positivos, pois mesmo após vários anos de estudo, os alunos estão deixando a escola despreparados

On the relevance of large scale pulsed-laser deposition: Evidence of structural heterogeneities in ZnO thin films

Pulsed-laser deposition is known as a well-suited method for growing thin films of oxide compounds presenting a wide range of functional properties. A limitation of this method for industrial process is the very anisotropic expansion dynamics of the plasma plume, which induces difficulties to grow on large scale films with homogeneous thickness and composition. The specific aspect of the crystalline or orientation uniformity has not been investigated, despite its important role on oxide films properties. In this work, the crystalline parameters and the texture of zinc oxide films are studied as a function of position with respect to the central axis of the plasma plume. We demonstrate the existence of large non-uniformities in the films. The stoichiometry, the lattice parameter, and the distribution of crystallites orientations drastically depend on the position with respect to the plume axis, i.e., on the oblique incidence of the ablated species. The origin of these non-uniformities, in particular, the unexpected tilted orientation of the ZnO c-axis may be attributed to the combined effects of the oblique incidence and of the ratio between oxygen and zinc fluxes reaching the surface of the growing film