Virtual World16: virtual design collaboration for the intersection of academia and industry.

Over the past 13 years, the 'World16'-group has collaborated face-to-face on various challenges that architectural design faces within VR, architecture, urban design, and its delivery to the professional industries. The focus of the collaboration is to foster pathways of academic research and developments to industries and professions. In 2020, due to the restrictions of the pandemic, the group had to rethink and redevelop how to collaborate meaningfully and become resilient: the World16 collaborated akin to the Virtual Design Studios (VDS) of the Nineties for the first time exclusively virtually becoming the 'Virtual World16'. The paper presents the group's various projects that are transformative to the praxis in VR architecture, design and urban design, and critically reflects on the lessons learned from VDS-paradigm

Characterization of the transcriptional and metabolic responses of pediatric high grade gliomas to mTOR-HIF-1α axis inhibition.

Pediatric high grade glioma (pHGGs), including sus-tentorial and diffuse intrinsic pontine gliomas, are known to have a very dismal prognosis. For instance, even an increased knowledge on molecular biology driving this brain tumor entity, there is no treatment able to cure those patients. Therefore, we were focusing on a translational pathway able to increase the cell resistance to treatment and to reprogram metabolically tumor cells, which are, then, adapting easily to a hypoxic microenvironment. To establish, the crucial role of the hypoxic pathways in pHGGs, we, first, assessed their protein and transcriptomic deregulations in a pediatric cohort of pHGGs and in pHGG's cell lines, cultured in both normoxic and hypoxic conditions. Secondly, based on the concept of a bi-therapy targeting in pHGGs mTORC1 (rapamycin) and HIF-1α (irinotecan), we hypothesized that the balanced expressions between RAS/ERK, PI3K/AKT and HIF-1α/HIF-2α/MYC proteins or genes may provide a modulation of the cell response to this double targeting. Finally, we could evidence three protein, genomic and metabolomic profiles of response to rapamycin combined with irinotecan. The pattern of highly sensitive cells to mTOR/HIF-1α targeting was linked to a MYC/ERK/HIF-1α over-expression and the cell resistance to a major hyper-expression of HIF-2α

The translational response of the human mdm2 gene in HEK293T cells exposed to rapamycin: a role for the 5′-UTRs

Polysomal messenger RNA (mRNA) populations change rapidly in response to alterations in the physiological status of the cell. For this reason, translational regulation, mediated principally at the level of initiation, plays a key role in the maintenance of cellular homeostasis. In an earlier translational profiling study, we followed the impact of rapamycin on polysome re-seeding. Despite the overall negative effect on transcript recruitment, we nonetheless observed that some mRNAs were significantly less affected. Consequently, their relative polysomal occupancy increased in the rapamycin-treated cells. The behaviour of one of these genes, mdm2, has been further analysed. Despite the absence of internal ribosome entry site activity we demonstrate, using a dual reporter assay, that both the reported mdm2 5′-UTRs confer resistance to rapamycin relative to the 5′-UTR of β-actin. This relative resistance is responsive to the downstream targets mTORC1 but did not respond to changes in the La protein, a reported factor acting positively on MDM2 translational expression. Furthermore, extended exposure to rapamycin in the presence of serum increased the steady-state level of the endogenous MDM2 protein. However, this response was effectively reversed when serum levels were reduced. Taken globally, these studies suggest that experimental conditions can dramatically modulate the expressional output during rapamycin exposure

Integration of urban development and 5D planning

5D planning is the process of integrating 3D models of buildings or infrastructure projects withconstruction activities and cost planning. The process has been used successfully to rehearse the construction process and indentifying ‘hot spots’ and process clashes prior to site construction activities. Previous research(Dawood, 2008) has concluded that at least 7% of construction time and cost can be reduced if the technology hasbeen deployed at an early stage of construction process. However, construction planning within the context of urbandevelopment not fully exploited and tools and methods for synchronising and rehearing multiple construction planning within urban setting and identify, for example, traffic congestions and other environmental issues that canbe affected with construction processes and nearby sites. In this context, the aim of this paper is to deploy and develop 4D process and technology for urban planning and construction. The objective is to rehearse construction processes for urban construction which can involve a multiple of construction projects, both buildings and infrastructure can be constructed concurrently and can cause massive disruption and congestion at urban scale.Traffic management and flow can be incorporated within the urban simulation and therefore congestions caused bymultiple construction sites can be identified and resolved before construction starts.This paper presents a framework and tools for rehearsing multiple construction projects that was developed toidentify issues and hot spots at urban scale. The paper also present initial results of integrating Uc-win/Road visual urban planning with nDCCIR 5D planning tool. A simple case study was used to demonstrate the technology

Constitutive or Induced HIF-2 Addiction is Involved in Resistance to Anti-EGFR Treatment and Radiation Therapy in HNSCC

International audienceBACKGROUND:management of head and neck squamous cell carcinomas (HNSCC) include anti-Epidermal Growth Factor Receptor (EGFR) antibodies and radiotherapy, but resistance emerges in most patients. RAS mutations lead to primary resistance to EGFR blockade in metastatic colorectal cancer but are infrequent in HNSCC, suggesting that other mechanisms are implicated. Since hypoxia and Hypoxia Inducible Factor-1 (HIF-1) have been associated with treatment failure and tumor progression, we hypothesized that EGFR/mammalian Target Of Rapamycin (mTOR)/HIF-1 axis inhibition could radiosensitize HNSCC.METHODS:We treated the radiosensitive Cal27 used as control, and radioresistant SQ20B and UD-SCC1 cells, in vivo and in vitro, with rapamycin and cetuximab before irradiation and evaluated tumor progression and clonogenic survival.RESULTS:Rapamycin and cetuximab inhibited the mTOR/HIF-1α axis, and sensitized the SQ20B cell line to EGFR-inhibition. However, concomitant delivery of radiation to SQ20B xenografts increased tumor relapse frequency, despite effective HIF-1 inhibition. Treatment failure was associated with the induction of HIF-2α expression by cetuximab and radiotherapy. Strikingly, SQ20B and UD-SCC1 cells clonogenic survival dropped <30% after HIF-2α silencing, suggesting a HIF-2-dependent mechanism of oncogenic addiction.CONCLUSIONS:altogether, our data suggest that resistance to EGFR inhibition combined with radiotherapy in HNSCC may depend on tumor HIF-2 expression and underline the urgent need to develop novel HIF-2 targeted treatments

Bilan des enquêtes 2012, 2013 et 2014 de l’Observatoire national français des centres spécialisés de l’obésité (oNCSO)

International audienceLe Plan obésité a permis la création en France de 37 centres spécialisés de l’Obésité (CSO) en 2012 pour assurer une double mission : la prise en charge pluridisciplinaire de l’obésité sévère ou complexe et l’organisation des filières de soins dans les régions. Ce rapport fait le bilan des trois premières années de fonctionnement des CSO, à partir des données recueillies par l’Observatoire national des CSO (oNCSO), mis en place par la direction générale de l’hospitalisation et de l’offre de soins.Résultats : Le bilan était globalement positif pour l’accès aux examens paracliniques, même si tous les CSO ne disposaient pas d’absorptiomètre biphotonique (DEXA) ni de calorimétrie.Les CSO développaient d’emblée des liens avec les 12 secteurs de prise en charge étudiés par l’oNCSO, avecquelques points faibles, dont la psychiatrie. L’enquête ne permettait pas de faire le point sur les effectifs réels des CSO, auvu du nombre important de données aberrantes. Tous les CSO répondants déclaraient avoir des programmes d’éducationthérapeutique orientés vers les obèses pour les filières médicale, chirurgicale et pédiatrique. L’activité des CSO en médecine, chirurgie, gynécologie–obstétrique et pédiatrie était hétérogène. En 2014, environ 25 à 30 % de l’ensemble desinterventions de chirurgie bariatrique en France étaient pratiquées dans les CSO. En moyenne, les CSO recevaient environ2 500 patients adultes sévèrement obèses, en consultation ou en hospitalisation de jour pour la filière médicale. Les résultatssuggéraient une certaine fragilité des filières de gynécologie–obstétrique et des filières pédiatriques.Conclusion : Cette enquête déclarative, malgré de nombreuses limites, montre cependant que les CSO ont prisd’emblée une place importante dans le système de soins français

Prognostic and Predictive Biomarkers in the Era of Immunotherapy for Lung Cancer

The therapeutic algorithm of lung cancer has recently been revolutionized by the emergence of immune checkpoint inhibitors. However, an objective and durable response rate remains low with those recent therapies and some patients even experience severe adverse events. Prognostic and predictive biomarkers are therefore needed in order to select patients who will respond. Nowadays, the only validated biomarker is the PD-L1 expression, but its predictive value remains imperfect, and it does not offer any certainty of a sustained response to treatment. With recent progresses in molecular biology, genome sequencing techniques, and the understanding of the immune microenvironment of the tumor and its host, new molecular features have been highlighted. There are evidence in favor of the positive predictive value of the tumor mutational burden, as an example. From the expression of molecular interactions within tumor cells to biomarkers circulating in peripheral blood, many markers have been identified as associated with the response to immunotherapy. In this review, we would like to summarize the latest knowledge about predictive and prognostic biomarkers of immune checkpoint inhibitors efficacy in order to go further in the field of precision immuno-oncology