Discovery and development of Seliciclib. How systems biology approaches can lead to better drug performance

Seliciclib (R-Roscovitine) was identified as an inhibitor of CDKs and has undergone drug development and clinical testing as an anticancer agent. In this review, the authors describe the discovery of Seliciclib and give a brief summary of the biology of the CDKs Seliciclib inhibits. An overview of the published in vitro and in vivo work supporting the development as an anti-cancer agent, from in vitro experiments to animal model studies ending with a summary of the clinical trial results and trials underway is presented. In addition some potential non-oncology applications are explored and the potential mode of action of Seliciclib in these areas is described. Finally the authors argue that optimisation of the therapeutic effects of kinase inhibitors such as Seliciclib could be enhanced using a systems biology approach involving mathematical modelling of the molecular pathways regulating cell growth and division

The impact of the Hippo pathway and cell metabolism on pathological complete response in locally advanced Her2+ breast cancer: the TRISKELE multicenter prospective study

The Hippo pathway and its two key effectors, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), are consistently altered in breast cancer. Pivotal regulators of cell metabolism such as the AMP-activated protein kinase (AMPK), Stearoyl-CoA-desaturase 1 (SCD1), and HMG-CoA reductase (HMGCR) are relevant modulators of TAZ/YAP activity. In this prospective study, we measured the tumor expression of TAZ, YAP, AMPK, SCD1, and HMGCR by immunohistochemistry in 65 Her2+ breast cancer patients who underwent trastuzumab-based neoadjuvant treatment. The aim of the study was to assess the impact of the immunohistochemical expression of the Hippo pathway transducers and cell metabolism regulators on pathological complete response. Low expression of cytoplasmic TAZ, both alone and in the context of a composite signature identified by machine learning including also low nuclear levels of YAP and HMGCR and high cytoplasmic levels of SCD1, was a predictor of residual disease in the univariate logistic regression. This finding was not confirmed in the multivariate model including estrogen receptor > 70% and body mass index > 20. However, our findings were concordant with overall survival data from the TCGA cohort. Our results, possibly affected by the relatively small sample size of this study population, deserve further investigation in adequately sized, ad hoc prospective studies

AcceLerate Innovation in urban wastewater management for Climate changE - ALICE

The overall aim of the project is to accelerate innovation in urban wastewater management to address the future challenges arising from climate change. The project will identify solutions and seek to remove barriers for their implementation. The aim will be achieved through secondments and the transfer of knowledge, creating an effective interdisciplinary and inter-sectoral cooperation among the partners involved

DiTEMP: Digital Transformation and Employability: acquiring transversal competences in curricular education

DiTEMP is a European project co-funded by the Erasmus+ Programme of the European Union. It is a joint effort of four Universities, a University Business Foundation and an SME, aiming to explore the impact of Digital Transformation on field-specific markets. The project will provide a model of intervention, completed with tools, to integrate important and critical aspects of Digital transformation into curricular education in Higher education, promoting this way students\u2019 employability. Digital transformation (DX) is a technology-driven continuous change process affecting companies and the entire society, it is about adopting disruptive technologies to increase productivity, value creation, and social welfare. Automation had and has greatly impacted on the labour market in terms of labour savings. Although this phenomenon has so far affected in particular low skilled workers, new business processes affect job positions for middle and highly skilled professionals, which are typical graduate jobs. Moreover, being an entrepreneur or self-employed in the digital era requires a higher level of digital skills and a sound understanding of digital transformation trends over time, in business and society. The DiTEMP project is bridging this gap and mismatch by developing relevant tools and learning material at two levels: That of the educators, teachers and career consultants to make them aware of the impact of digital transformation in their knowledge and labour-market fields. That of the students, in order to increase their capability to manage the rapid changes in their future career fields, as caused by digital transformation, supporting this way their employability. The project will develop Guidelines for integrating digital transformation competences in further curricula and academic fields in 5 languages (English, Greek, Italian, Romanian and Spanish). The DiTEMP learning provision includes: A framework, demonstrating the learning outcomes related to digital transformation, that can be applied across different study curricula and the most effective teaching methods that go with it. A design model for the participating Universities on how to integrate the framework into their actual curricula, complemented by an open-access, publicly available \u2018How to Guide\u2019. The DiTEMP Toolkit for teachers and educators on how to integrate digital transformation concepts in their regular teaching. A modular learning pack for students to understand what digital transformation is all about and become \u2018digital ready\u2019 in the fields of Psychology, Cultural Heritage and Tourism, Business, and Education. The online learning material is freely accessible in English, Greek, Italian, Romanian and Spanish. The DiTEMP project is running from November 2019 and up to October 2021

Marquer la ville

[…] « Marquer la ville » : on aura d’emblée noté que c’est davantage un processus (et ce processus ne peut être naturellement que politique) qu’une typologie formelle qui rassemble ici les différents auteurs. Reste qu’en tant qu’historiens, nous n’avons guère le choix : il faut bien partir d’une description cartographique des empreintes du pouvoir sur la ville pour tenter de reconstituer le mouvement qui les y a laissé, exactement de la même manière que celle du chasseur qui, se penchant vers les traces de sa proie, en déduit que quelqu’un est passé par là, où comme l’archéologue dont la source ne peut être que « l’empreinte du passé marqué dans la matière ». De l’empreinte du pouvoir évidant le centre de la ville aux itinéraires discrètement réticulées qu’impose une forme urbaine dont les rues ne sont pas nommées, Roland Barthes décrit en somme les deux extrémités d’un arc que l’on ambitionne de parcourir dans son entier. Ainsi peut-on espérer définir une rhétorique de la puissance à partir du marquage de la ville par les pouvoirs urbains, et tenter d’y mesurer les parts respectives de la communication, de la persuasion, de l’intimidation ou de la propagande – que celle-ci soit implicite ou explicite. Il s’agit donc avant tout d’inviter à une histoire matérielle, concrète, tangible, du marquage urbain, en ne présumant pas de la nature institutionnelle du pouvoir qui s’y exprime mais en partant simplement d’une phénoménologie : qu’est-ce qui, en ville, parle du pouvoir, à qui et « sur quel ton commande-t-il ? » ajouterait volontiers Paul Veyne. Cette sémiologie politique des espaces urbains doit pouvoir se lire à différentes échelles : des signes les plus discrets (enseignes, blasons, bornes) aux empreintes les plus massives que sont les manifestations architecturales de l’autorité. Mais si l’on doit varier les échelles, il faut également pouvoir reconnaître les différentes intensités du signal : décrire les effets massifs de sens (l’ombre portée d’une tour sur un quartier, ou du château sur la ville tout entière) qui peuvent entraîner des conflits majeurs dans l’occupation de l’espace, mais aussi les éléments ténus d’une « guérilla sémiologique » plus diffuse et à bas bruit (les marques gravées ou griffées sur la pierre, l’écrit éphémère ou les images peintes, voire le paysage sonore) qui participent aussi de la dispute des lieux. Car nous partons sans doute de l’hypothèse que les expressions du pouvoir les plus véhémentes et les plus démonstratives ne sont pas nécessairement les plus convaincantes

The Museum of Renaissance Music: A History in 100 Exhibits

This book collates 100 exhibits with accompanying essays as an imaginary museum dedicated to the musical cultures of Renaissance Europe, at home and in its global horizons. It is a history through artefacts—materials, tools, instruments, art objects, images, texts, and spaces—and their witness to the priorities and activities of people in the past as they addressed their world through music. The result is a history by collage, revealing overlapping musical practices and meanings—not only those of the elite, but reflecting the everyday cacophony of a diverse culture and its musics. Through the lens of its exhibits, this museum surveys music’s central role in culture and lived experience in fifteenth- and sixteenth-century Europe, offering interest and insights well beyond the strictly musicological field