Comparative epigenetic analysis of tumour initiating cells and syngeneic EPSC-derived neural stem cells in glioblastoma

Epigenetic mechanisms which play an essential role in normal developmental processes, such as self-renewal and fate specification of neural stem cells (NSC) are also responsible for some of the changes in the glioblastoma (GBM) genome. Here we develop a strategy to compare the epigenetic and transcriptional make-up of primary GBM cells (GIC) with patient-matched expanded potential stem cell (EPSC)-derived NSC (iNSC). Using a comparative analysis of the transcriptome of syngeneic GIC/iNSC pairs, we identify a glycosaminoglycan (GAG)-mediated mechanism of recruitment of regulatory T cells (Tregs) in GBM. Integrated analysis of the transcriptome and DNA methylome of GBM cells identifies druggable target genes and patient-specific prediction of drug response in primary GIC cultures, which is validated in 3D and in vivo models. Taken together, we provide a proof of principle that this experimental pipeline has the potential to identify patient-specific disease mechanisms and druggable targets in GBM

The distortion principle for insurance pricing: properties, identification and robustness

Distortion (Denneberg in ASTIN Bull 20(2):181–190, 1990) is a well known premium calculation principle for insurance contracts. In this paper, we study sensitivity properties of distortion functionals w.r.t. the assumptions for risk aversion as well as robustness w.r.t. ambiguity of the loss distribution. Ambiguity is measured by the Wasserstein distance. We study variances of distances for probability models and identify some worst case distributions. In addition to the direct problem we also investigate the inverse problem, that is how to identify the distortion density on the basis of observations of insurance premia

Advances in Vehicular Ad-hoc Networks (VANETs): challenges and road-map for future development

Recent advances in wireless communication technologies and auto-mobile industry have triggered a significant research interest in the field of vehicular ad-hoc networks (VANETs) over the past few years. A vehicular network consists of vehicle-to-vehicle (V2V) and vehicle-to-infrastructure (V2I) communications supported by wireless access technologies such as IEEE 802.11p. This innovation in wireless communication has been envisaged to improve road safety and motor traffic efficiency in near future through the development of intelligent transportation system (ITS). Hence, governments, auto-mobile industries and academia are heavily partnering through several ongoing research projects to establish standards for VANETs. The typical set of VANET application areas, such as vehicle collision warning and traffic information dissemination have made VANET an interesting field of mobile wireless communication. This paper provides an overview on current research state, challenges, potentials of VANETs as well as the ways forward to achieving the long awaited ITS

Pharmacological hemostatic treatment of hemorrahges related to portal hypertension

La vasopressine a été utilisée pour la première fois pour traiter une hémorragie par rupture de varices oesophagiennes il y a quarante ans. Mais ce n'est que depuis un peu plus de 10 ans que l'emploi des vasoconstricteurs a été rationnalisé à la suite d'études contrôlées comparant leurs effets à ceux d'autres techniques d'hémostase. Parallèlement de nouveau produits sont venus s'ajouter à la vasopressine : terlipressine, somatostatine et octréotide. Des données souvent contradictoires de la littérature, on peut retenir que l'efficacité et la tolérance des différents médicaments disponibles sont comparables. Leur efficacité est établie et comparable à celle de la sclérothérapie et des sondes de tamponnement

Performance Evaluation of a Real Vehicular Delay-Tolerant Network Testbed

Vehicular Delay-Tolerant Networks (VDTNs) are a breakthrough based DTN solution used to provide vehicular communications under challenging scenarios, characterized by long delays and sporadic connections. Using the store-carry-and-forward paradigm, this technology allows in-transit bundles to asynchronously reach the destination hop by hop over traveling vehicles equipped with short-range wireless devices. The VDTN architecture assumes out-of-band signaling with control and data planes separation and follows an IP over VDTN approach. This paper presents a real-world VDTN prototype evaluated through a safety application and a Traffic Jam Information Service. It also demonstrates the real deployment of this new vehicular communication approach. The real testbed is an important contribution since some complex issues presented in vehicular communication systems can be studied more accurately in real-world environments than in a laboratory approach. The results confirm that real deployment of VDTNs is doable and can be seen as a very promising technology for vehicular communications, although it requires appropriated technologies for outline interferences and quality of service support. © 2015 Maicke C. G. Paula et al.This work has been partially supported by Instituto de Telecomunicações, Next Generation Networks and Applications Group (NetGNA), Covilhã Delegation, by national funding from the FCT, Fundação para a Ciência e a Tecnologia, through the Pest-OE/EEI/LA0008/2013 Project, by Government of Russian Federation, Grant 074-U01, and by Fiat Automobile (Product Engineering Department), Brazil, which sponsored the new hardware, laboratories, and cars.</p

Treatment of experimental murine pancreatic peritoneal carcinomatosis with fibroblasts genetically modified to express IL12: a role for peritoneal innate immunity

BACKGROUND: Peritoneal carcinomatosis from pancreatic cancer has a poor prognosis with a median survival of 3.1 months. This is mainly due to lack of effective treatment. Interleukin 12 (IL12) is a proinflammatory cytokine that has a potent antitumoral effect by stimulating innate and adoptive immunity. AIM: To examine the antitumoral effect and toxicity of intraperitoneal delivery of IL12 using an ex vivo gene therapy approach in a murine model of pancreatic peritoneal carcinomatosis. METHODS: Peritoneal carcinomatosis was generated by direct intraperitoneal inoculation of the pancreatic cancer cell line Capan‐1 in athymic mice. Syngenic fibroblasts were genetically modified in vitro to secrete IL12 using a polycistronic TFG murine IL12 retroviral vector coding for both p35 and p40 murine IL12 subunits. Ex vivo gene therapy involved injection of the genetically modified fibroblasts intraperitoneally twice a week for 4 weeks. RESULTS: Treatment of pre‐established peritoneal carcinomatosis with fibroblasts genetically modified to express IL12 induced a marked inhibition of tumour growth as measured by comparison of the weights of the intraperitoneal tumour nodules in the treated and control animals (3.52 (SD 0.47) v 0.93 (SD 0.21) g, p<0.05) and improved survival. This effect was associated with infiltration of the peritoneal tumour nodules with macrophages. Peritoneal lavage confirmed enhancement of the innate peritoneal inflammatory activity, with an increased number of activated macrophages and natural killer cells. Moreover, macrophages harvested from animals with peritoneal carcinomatosis and treated with IL12‐expressing fibroblasts expressed an activated proinflammatory antitumoral M1 phenotype that included strongly enhanced reactive oxygen species and nitric oxide production. There was no treatment‐related toxicity. CONCLUSION: Multiple injections of genetically modified fibroblasts to express IL12 is an effective and well‐tolerated treatment for experimental murine pancreatic peritoneal carcinomatosis via activated innate immunity and in particular activated M1 macrophages