Identification of SOX2 as a novel glioma-associated antigen and potential target for T cell-based immunotherapy

Prognosis for patients suffering from malignant glioma has not substantially improved. Specific immunotherapy as a novel treatment concept critically depends on target antigens, which are highly overexpressed in the majority of gliomas, but the number of such antigens is still very limited. SOX2 was identified by screening an expression database for transcripts that are overexpressed in malignant glioma, but display minimal expression in normal tissues. Expression of SOX2 mRNA was further investigated in tumour and normal tissues by real-time PCR. Compared to cDNA from pooled normal brain, SOX2 was overexpressed in almost all (9 out of 10) malignant glioma samples, whereas expression in other, non-malignant tissues was almost negligible. SOX2 protein expression in glioma cell lines and tumour tissues was verified by Western blot and immunofluorescence. Immunohistochemistry demonstrated SOX2 protein expression in all malignant glioma tissues investigated ranging from 6 to 66% stained tumour cells. Human leucocyte antigen-A*0201-restricted SOX2-derived peptides were tested for the activation of glioma-reactive CD8+ cytotoxic T lymphocytes (CTLs). Specific CTLs were raised against the peptide TLMKKDKYTL and were capable of lysing glioma cells. The abundant and glioma-restricted overexpression of SOX2 and the generation of SOX2-specific and tumour-reactive CTLs may recommend this antigen as target for T-cell-based immunotherapy of glioma

Twenty Years After the Velvet Revolution: Shifts in Czech Adolescents’ Perceptions of Family, School, and Society

Families and schools are traditionally seen as substantial socialization agents forming adolescents’ social values and their views of society. Special attention is paid to the question whether the relative importance of these influences remains stable in times of major social changes. In this study, two different generations of Czech middle adolescents are compared: (a) the “post-totalitarian” generation that grew up in the last decade of the communist regime and entered adolescence during the time of rapid political and socioeconomic changes (data collected in 1995) and (b) the current generation without personal experience with the communist regime, raised in a stable democratic society (data collected in 2010). Both groups of participants (total N = 2,127, aged from 14 to 17 years) were administered an identical questionnaire. First, we examined the changes in adolescents’ perception and evaluation of the society over the last 15 years. Today’s adolescents perceive society more as a community and their future orientations are more focused on materialistic and less on environmental values. While the emotional relationship between the children and parentsremains the same, adolescents learn a somewhat different message in the family, emphasizing self-reliance. School environment is perceived more as positive and engaging than 15 years ago. Second, we predicted adolescents’ social views and values from their assessment of family and school environment. Our results show that the effect of parental values on adolescents’ value orientations is higher in the current generation. Positive school environment contributes to the development of socially responsible orientations despite the changes in society

Subjectivity in a context of environmental change: opening new dialogues in mental health research

In a period of unstable experimentation with challenges of globalization of associated risks, and disenchantment with ‘enduring injustice’, we bring forward a consideration of subjectivity to the study of environmental change and mental health. We begin by identifying how mainstream climate change and mental health studies are unable to explain the emergent and co-evolutionary pathways of agency. As a means of freeing these studies of their objective dimensions of linear-causation, we argue in favour of a re-positioning of subjectivity within an appreciation of recognition conflicts and beyond the over-deterministic interpretations of power centres—state, market or religion. We draw on one example of scientific research that was conducted in a region undergoing strong environmental, social and cultural changes, in the state of São Paulo/Brazil, with the aim to open mental health research to new dialogues, to which we contribute with the notion of the ‘pluriversal subject’

The 4Cs of adaptation tracking: consistency, comparability, comprehensiveness, coherency

Adaptation tracking seeks to characterize, monitor, and compare general trends in climate change adaptation over time and across nations. Recognized as essential for evaluating adaptation progress, there have been few attempts to develop systematic approaches for tracking adaptation. This is reflected in polarized opinions, contradictory findings, and lack of understanding on the state of adaptation globally. In this paper, we outline key methodological considerations necessary for adaptation tracking research to produce systematic, rigorous, comparable, and usable insights that can capture the current state of adaptation globally, provide the basis for characterizing and evaluating adaptations taking place, facilitate examination of what conditions explain differences in adaptation action across jurisdictions, and can underpin the monitoring of change in adaptation over time. Specifically, we argue that approaches to adaptation tracking need to (i) utilize a consistent and operational conceptualization of adaptation, (ii) focus on comparable units of analysis, (iii) use and develop comprehensive datasets on adaptation action, and (iv) be coherent with our understanding of what constitutes real adaptation. Collectively, these form the 4Cs of adaptation tracking (consistency, comparability, comprehensiveness, and coherency)

Using Simulation to Evaluate Dynamic Systems with Weibull or Lognormal Distributions

© Springer International Publishing Switzerland 2014. Most techniques for quantitatively analysing the temporal fault trees of safety-critical systems are used with the assumption that the systems under study have exponentially distributed component failures. However, it is not impossible for real world systems to have various components with different failure distributions. This paper presents a simulation approach – Monte Carlo – for modelling, simulating and estimating the total system failure of state-of-the-art dynamic systems featuring Weibull or lognormal distributions. The proposed techniques have been formulated using the time-to-failure of these distributions to model temporal behaviours; they can be extended to model systems with other distributions