Search Results (14)

By borrowing the metaphor of the ‘tapestry of existence’ to discuss the matter of fate in Homer’s Iliad, we selected four threads that are interwoven in the warp of each hero’s destiny—that of necessity/fatality, the relations between Zeus and the Moîra, the plots and tricks of the gods, and fate and human actions—with the aim of inviting the reader to appreciate the texture of the work with the passages that most caught our attention, without the intention of exhausting the subject. To do so, we draw upon the origin of the word Moîra in anthropology, as well as some of Heidegger’s ideas and those of other commentators to enrich the discussion. Full article

Digital Twins of the Ocean (DTO) are a rapidly emerging topic that has attracted significant interest from scientists in recent years. The initiative, strongly driven by the EU, aims to create a digital replica of the ocean to better understand and manage marine environments. The Iliad project, funded under the EU Green Deal call, is developing a framework to support multiple interoperable DTO using a federated systems-of-systems approach across various fields of applications and ocean areas, called pilots. This paper presents the results of a Water Quality DTO pilot located in the Trondheim fjord in Norway. This paper details the building blocks of DTO, specific to this environmental monitoring pilot. A crucial aspect of any DTO is data, which can be sourced internally, externally, or through a hybrid approach utilizing both. To realistically twin ocean processes, the Water Quality pilot acquires data from both surface and benthic observatories, as well as from mobile sensor platforms for on-demand data collection. Data ingested into an InfluxDB are made available to users via an API or an interface for interacting with the DTO and setting up alerts or events to support ’what-if’ scenarios. Grafana, an interactive visualization application, is used to visualize and interact with not only time-series data but also more complex data such as video streams, maps, and embedded applications. An additional visualization approach leverages game technology based on Unity and Cesium, utilizing their advanced rendering capabilities and physical computations to integrate and dynamically render real-time data from the pilot and diverse sources. This paper includes two case studies that illustrate the use of particle sensors to detect microplastics and monitor algae blooms in the fjord. Numerical models for particle fate and transport, OpenDrift and DREAM, are used to forecast the evolution of these events, simulating the distribution of observed plankton and microplastics during the forecasting period. Full article

In this study, we assessed the influence of area-based socioeconomic deprivation on the incidence of invasive breast cancer (BC) in France, according to stage at diagnosis. All women from six mainland French departments, aged 15+ years, and diagnosed with a primary invasive breast carcinoma between 2008 and 2015 were included (n = 33,298). Area-based socioeconomic deprivation was determined using the French version of the European Deprivation Index. Age-standardized incidence rates (ASIR) by socioeconomic deprivation and stage at diagnosis were compared estimating incidence rate ratios (IRRs) adjusted for age at diagnosis and rurality of residence. Compared to the most affluent areas, significantly lower IRRs were found in the most deprived areas for all-stages (0.85, 95% CI 0.81–0.89), stage I (0.77, 95% CI 0.72–0.82), and stage II (0.84, 95% CI 0.78–0.90). On the contrary, for stages III–IV, significantly higher IRRs (1.18, 95% CI 1.08–1.29) were found in the most deprived areas. These findings provide a possible explanation to similar or higher mortality rates, despite overall lower incidence rates, observed in women living in more deprived areas when compared to their affluent counterparts. Socioeconomic inequalities in access to healthcare services, including screening, could be plausible explanations for this phenomenon, underlying the need for further research. Full article

Background: Despite encouraging anti-tumour activity in lung cancer, anti-PD-1 therapy has encountered increasing resistance to treatment. Several companion diagnostic assays have been performed to identify patients who may benefit from this immunotherapy and to adapt this therapy in case of acquired resistance. Methods: A large panel of methods was used for the analysis of expression and methylation levels of miRNAs (qPCR, MemiRIP, …), protein/miRNA interactions (CLIP, oligo pull-down, …), and protein–protein interactions (CoIP) in cells and/or blood samples. Results: Our work highlights that the saturation of PD-1 by anti-PD1 therapies induces an immune escape phenomenon due to the overexpression of IGSF11 following adenosine methylation of miR-125a-5p. Mechanistically, we identify METTL3/KHDRBS3 and HuR as two crucial players in the methylation and the loss of the repressive function of this miRNA. Finally, our work shows that the adenosine methylation of miR-125a-5p is analyzable from EVs/exosomes from longitudinal blood samples and that such EVs/exosomes modulate the IGSF11/VSIG3 expression in lung cancer cells to promote an immune escape phenomenon. Conclusions: Our data provide a biomarker (m6A-miR-125a-5p level) and two therapeutic solutions (anti-IGSF11 antibody and METTL3 inhibitor) that could potentially address the anti-PD1 therapy failure in the context of precision and personalized medicine. Full article

Background: Deregulation of DNA methylation/demethylation reactions may be the source of C > T mutation via active deamination of 5-methylcytosine to thymine. Exposome, that is to say, the totality of exposures to which an individual is subjected during their life, can deregulate these reactions. Thus, one may wonder whether the exposome can induce C > T mutations in the breast cancer-predisposing gene PALB2. Methods: Our work is based on the exposure of MCF10A mammary epithelial cells to seven compounds of our exposome (folate, Diuron, glyphosate, PFOA, iron, zinc, and ascorbic acid) alone or in cocktail. The qMSRE and RMS techniques were used to study the impact of these exposures on the level of methylation and mutation of the PALB2 gene. Results: Here, we have found that exposome compounds (nutriments, ions, pollutants) promoting the cytosine methylation and the 5-methylcytosine deamination have the ability to promote a specific C > T mutation in the PALB2 gene. Interestingly, we also noted that the addition of exposome compounds promoting the TET-mediated conversion of 5-methylcytosine (Ascorbic acid and iron) abrogates the presence of C > T mutation in the PALB2 gene. Conclusions: Our study provides a proof of concept supporting the idea that exposomes can generate genetic mutation by affecting DNA methylation/demethylation. Full article

The relationship between women and classical antiquity, its texts, artefacts, and study, has been fraught to say the least; the discipline of Classics has often been defined by the exclusion of women, in terms of their education and their ability to contribute to debates more generally. However, we are currently in the middle of an astonishing period when women are laying more of a claim to the discipline than ever before. This article examines three recent novels by women which take on the cultural weight of the Homeric epics, Iliad and Odyssey, to explore the possibilities of a ‘new song’ that foregrounds female characters. The novels experiment with different narrative voices and are self-conscious about the practices of story-telling and of bardic song. Their awareness of their challenge to and contest with Homeric tradition renders their ‘new songs’ fragile as well as precious. Full article

Current pertussis vaccines protect against disease, but not against colonization by and transmission of Bordetella pertussis, whereas natural infection protects against both. The live attenuated vaccine BPZE1 was developed to mimic immunogenicity of natural infection without causing disease, and in preclinical models protected against pertussis disease and B. pertussis colonization after a single nasal administration. Phase 1 clinical studies showed that BPZE1 is safe and immunogenic in humans when administered as a liquid formulation, stored at ≤−70 °C. Although BPZE1 is stable for two years at ≤−70 °C, a lyophilized formulation stored at ≥5 °C is required for commercialization. The development of a BPZE1 drug product, filled and lyophilized directly in vials, showed that post-lyophilization survival of BPZE1 depended on the time of harvest, the lyophilization buffer, the time between harvest and lyophilization, as well as the lyophilization cycle. The animal component-free process, well defined in terms of harvest, processing and lyophilization, resulted in approximately 20% survival post-lyophilization. The resulting lyophilized drug product was stable for at least two years at −20 °C ± 10 °C, 5 °C ± 3 °C and 22.5 °C ± 2.5 °C and maintained its vaccine potency, as evaluated in a murine protection assay. This manufacturing process thus enables further clinical and commercial development of BPZE1. Full article

The imbalance between BCL-2 homologues and pro-death counterparts frequently noted in cancer cells endows them with a cell autonomous survival advantage. To eradicate ectopic cells, inhibitors of these homologues (BH3 mimetics) were developed to trigger, during anticancer treatment, full activation of the canonical mitochondrial apoptotic pathway and related caspases. Despite efficiency in some clinical settings, these compounds do not completely fulfill their initial promise. We herein put forth that a growing body of evidence indicates that mitochondrial integrity, controlled by BCL-2 family proteins, and downstream caspases regulate other cell death modes and influence extracellular signaling by committed cells. Moreover, intercellular communications play a key role in spreading therapeutic response across cancer cell populations and in engaging an immune response. We thus advocate that BH3 mimetics administration would be more efficient in the long term if it did not induce apoptosis in all sensitive cells at the same time, but if it could instead allow (or trigger) death signal production by non-terminally committed dying cell populations. The development of such a trade-off strategy requires to unravel the effects of BH3 mimetics not only on each individual cancer cell but also on homotypic and heterotypic cell interactions in dynamic tumor ecosystems. Full article

Recent findings suggest that S100A4, a protein involved in communication between stromal cells and cancer cells, could be more involved than previously expected in cancer invasiveness. To investigate its cumulative value in the multistep process of the pathogenesis of malignant mesothelioma (MM), SWATH-MS (sequential window acquisition of all theoretical fragmentation spectra), an advanced and robust technique of quantitative proteomics, was used to analyze a collection of 26 preneoplastic and neoplastic rat mesothelial cell lines and models of MM with increasing invasiveness. Secondly, proteomic and histological analyses were conducted on formalin-fixed paraffin-embedded sections of liver metastases vs. primary tumor, and spleen from tumor-bearing rats vs. controls in the most invasive MM model. We found that S100A4, along with 12 other biomarkers, differentiated neoplastic from preneoplastic mesothelial cell lines, and invasive vs. non-invasive tumor cells in vitro, and MM tumors in vivo. Additionally, S100A4 was the only protein differentiating preneoplastic mesothelial cell lines with sarcomatoid vs. epithelioid morphology in relation to EMT (epithelial-to-mesenchymal transition). Finally, S100A4 was the most significantly increased biomarker in liver metastases vs. primary tumor, and in the spleen colonized by MM cells. Overall, we showed that S100A4 was the only protein that showed increased abundance in all situations, highlighting its crucial role in all stages of MM pathogenesis. Full article

Apoptosis is a highly conserved mechanism enabling the removal of unwanted cells. Mitochondrial apoptosis is governed by the B-cell lymphoma (BCL-2) family, including anti-apoptotic and pro-apoptotic proteins. Apoptosis evasion by dysregulation of anti-apoptotic BCL-2 members (BCL-2, MCL-1, BCL-X_L) is a common hallmark in cancers. To divert this dysregulation into vulnerability, researchers have developed BH3 mimetics, which are small molecules that restore effective apoptosis in neoplastic cells by interfering with anti-apoptotic proteins. Among them, venetoclax is a potent and selective BCL-2 inhibitor, which has demonstrated the strongest clinical activity in mature B-cell malignancies, including chronic lymphoid leukemia, mantle-cell lymphoma, and multiple myeloma. Nevertheless, mechanisms of primary and acquired resistance have been recently described and several features such as cytogenetic abnormalities, BCL-2 family expression, and ex vivo drug testing have to be considered for predicting sensitivity to BH3 mimetics and helping in the identification of patients able to respond. The medical need to overcome resistance to BH3 mimetics supports the evaluation of innovative combination strategies. Novel agents including MCL-1 targeting BH3 mimetics are currently evaluated and may represent new therapeutic options in the field. The present review summarizes the current knowledge regarding venetoclax and other BH3 mimetics for the treatment of mature B-cell malignancies. Full article

The article presents the problem of the empathy felt by the author or authors of the Iliad and Odyssey towards women depicted as victims of war. Understanding of the world in the Homeric poems may be misinterpreted today. Since Homer’s works are a product of oral culture, in order to determine his intentions, it is necessary to look at them from the perspective of the tradition from which they derive. Furthermore, the author of an oral work can be deemed as creative because s/he shapes his/her story through interaction with the listening audience. The different aspects of the relationship of women as victims of war with their oppressors are, therefore, interpreted according to the use of traditional techniques adopted to evoke specific emotions in the audience. Full article

The epic is an intriguing genre, claiming its place in both oral and written systems. Ever since the beginning of folklore studies epic has been in the centre of interest, and monumental attempts at describing its characteristics have been made, in which oral literature was understood mainly as a primitive stage leading up to written literature. With the appearance in 1960 of A. B. Lord’s The Singer of Tales and the introduction of the oral-formulaic theory, the paradigm changed towards considering oral literature a special form of verbal art with its own rules. Fieldworkers have been eagerly studying oral epics all over the world. The growth of material caused that the problems of defining the genre also grew. However, after more than half a century of intensive implementation of the theory an internationally valid sociological model of oral epic is by now established and must be respected in cognate fields such as Homeric scholarship. Here the theory is both a help for readers to guard themselves against anachronistic interpretations and a necessary tool for constructing a social-historic context for the Iliad and the Odyssey. As an example, the hypothesis of a gradual crystallization of these two epics is discussed and rejected. Full article

This article is a Letter to the Editor. The major purpose of this Letter is to highlight the development of a new genetically altered whooping cough vaccine. Recently a baboon model has been used to show that this next generation pertussis vaccine can prevent colonization, as well as disease, and elicit antibodies against major pertussis antigens. Two phase I clinical trials have been performed, showing that this new vaccine is safe in humans, and a phase II trial will be performed in the US in 2018. Full article

This article deals with Greek animal fables, traditionally attributed to a former slave, Aesop, who lived during the sixth century BCE. As a genre, the Aesopic fables, or the Aesopica, has had a significant impact on the Western fable tradition and modern Western children’s literature. The Aesopica owes much to the Mesopotamian fables and has parallels in other Near Eastern cultures. Modern research has concentrated on tracing the oriental roots of the fable tradition and the dating of the different parts of the Aesopica, as well as defining the fable as a genre. The traditional reading of fables has, however, excluded animals qua animals, supposing that fables are mainly allegories of the human condition. The moral of the story (included in the epimythia or promythia) certainly guides one to read the stories anthropocentrically, but the original fables did not necessarily include this positioning element. Many fables address the situation when a prey animal, like a lamb, negotiates with a predator animal, like a wolf, by giving reasons why she should not be killed. In this article, I will concentrate on these fables and analyse them from the point of view of their structure and content. Comparing these fables with some animal similes in Homer’s Iliad, I suggest that these fables deal not only with the ethical problem of ‘might makes right’ as a human condition, but also the broader philosophical question of killing other living creatures and the problem of cruelty. Full article