Secure gossiping techniques and components

Gossip protocols have proved to be a viable solution to set-up and manage largescale P2P services or applications in a fully decentralised scenario. The gossip or epidemic communication scheme is heavily based on stochastic behaviors and it is the fundamental idea behind many large-scale P2P protocols. It provides many remarkable features, such as scalability, robustness to failures, emergent load balancing capabilities, fast spreading, and redundancy of information. In some sense, these services or protocols mimic natural system behaviors in order to achieve their goals. The key idea of this work is that the remarkable properties of gossip hold when all the participants follow the rules dictated by the actual protocols. If one or more malicious nodes join the network and start cheating according to some strategy, the result can be catastrophic. In order to study how serious the threat posed by malicious nodes can be and what can be done to prevent attackers from cheating, we focused on a general attack model aimed to defeat a key service in gossip overlay networks (the Peer Sampling Service [JGKvS04]). We also focused on the problem of protecting against forged information exchanged in gossip services. We propose a solution technique for each problem; both techniques are general enough to be applied to distinct service implementations. As gossip protocols, our solutions are based on stochastic behavior and are fully decentralized. In addition, each technique’s behaviour is abstracted by a general primitive function extending the basic gossip scheme; this approach allows the adoptions of our solutions with minimal changes in different scenarios. We provide an extensive experimental evaluation to support the effectiveness of our techniques. Basically, these techniques aim to be building blocks or P2P architecture guidelines in building more resilient and more secure P2P services.

SMO inhibitor specifically targets the Hedgehog Pathway and reverts the drug-resistance of Leukemic Stem Cells

Abnormal Hedgehog signaling is associated with human malignancies. Smo, a key player of that signaling, is the most suitable target to inhibit this pathway. To this aim several molecules, antagonists of Smo, have been synthesized, and some of them have started the phase I in clinical trials. Our hospital participated to one of these studies which investigated the oral administration of a new selective inhibitor of Smo (SMOi). To evaluate ex vivo SMOi efficacy and to identify new potential clinical biomarkers of responsiveness, we separated bone marrow CD34+ cells from 5 acute myeloid leukemia (AML), 1 myelofibrosis (MF), 2 blastic phases chronic myeloid leukemia (CML) patients treated with SMOi by immunomagnetic separation, and we analysed their gene expression profile using Affimetrix HG-U133 Plus 2.0 platform. This analysis, showed differential expression after 28 days start of therapy (p-value ≤ 0.05) of 1,197 genes in CML patients and 589 genes in AML patients. This differential expression is related to Hedgehog pathway with a p-value = 0.003 in CML patients and with a p-value = 0.0002 in AML patients, suggesting that SMOi targets specifically this pathway. Among the genes differentially expressed we observed strong up-regulation of Gas1 and Kif27 genes, which may work as biomarkers of responsiveness of SMOi treatment in CML CD34+ cells whereas Hedgehog target genes (such as Smo, Gli1, Gli2, Gli3), Bcl2 and Abca2 were down-regulated, in both AML and CML CD34+ cells. It has been reported that Bcl-2 expression could be correlated with cancer therapy resistance and that Hedgehog signaling modulate ATP-binding (ABC) cassette transporters, whose expression has been correlated with chemoresistance. Moreover we confirmed that in vitro SMOi treatment targets Hedgehog pathway, down-regulate ABC transporters, Abcg2 and Abcb1 genes, and in combination with tyrosine kinase inhibitors (TKIs) could revert the chemoresistance mechanism in K562 TKIs-resistant cell line.