Luca Sterpone

Bio: Luca Sterpone is an academic researcher from Polytechnic University of Turin. The author has contributed to research in topic(s): Fault injection & Field-programmable gate array. The author has an hindex of 24, co-authored 222 publication(s) receiving 3125 citation(s). Previous affiliations of Luca Sterpone include Instituto Politécnico Nacional.

Microvesicles Derived from Adult Human Bone Marrow and Tissue Specific Mesenchymal Stem Cells Shuttle Selected Pattern of miRNAs

Abstract: Background: Cell-derived microvesicles (MVs) have been described as a new mechanism of cell-to-cell communication. MVs after internalization within target cells may deliver genetic information. Human bone marrow derived mesenchymal stem cells (MSCs) and liver resident stem cells (HLSCs) were shown to release MVs shuttling functional mRNAs. The aim of the present study was to evaluate whether MVs derived from MSCs and HLSCs contained selected micro-RNAs (miRNAs). Methodology/Principal Findings: MVs were isolated from MSCs and HLSCs. The presence in MVs of selected ribonucleoproteins involved in the traffic and stabilization of RNA was evaluated. We observed that MVs contained TIA, TIAR and HuR multifunctional proteins expressed in nuclei and stress granules, Stau1 and 2 implicated in the transport and stability of mRNA and Ago2 involved in miRNA transport and processing. RNA extracted from MVs and cells of origin was profiled for 365 known human mature miRNAs by real time PCR. Hierarchical clustering and similarity analysis of miRNAs showed 41 co-expressed miRNAs in MVs and cells. Some miRNAs were accumulated within MVs and absent in the cells after MV release; others were retained within the cells and not secreted in MVs. Gene ontology analysis of predicted and validated targets showed that the high expressed miRNAs in cells and MVs could be involved in multi-organ development, cell survival and differentiation. Few selected miRNAs shuttled by MVs were also associated with the immune system regulation. The highly expressed miRNAs in MVs were transferred to target cells after MV incorporation. Conclusions: This study demonstrated that MVs contained ribonucleoproteins involved in the intracellular traffic of RNA and selected pattern of miRNAs, suggesting a dynamic regulation of RNA compartmentalization in MVs. The observation that MV-highly expressed miRNAs were transferred to target cells, rises the possibility that the biological effect of stem cells may, at least in part, depend on MV-shuttled miRNAs. Data generated from this study, stimulate further functional investigations on the predicted target genes and pathways involved in the biological effect of human adult stem cells.

On the Optimal Design of Triple Modular Redundancy Logic for SRAM-based FPGAs

Abstract: Triple modular redundancy (TMR) is a suitable fault tolerant technique for SRAM-based FPGA However, one of the main challenges in achieving 100% robustness in designs protected by TMR running on programmable platforms is to prevent upsets in the routing from provoking undesirable connections between signals from distinct redundant logic parts, which can generate an error in the output This paper investigates the optimal design of the TMR logic (eg, by cleverly inserting voters) to ensure robustness Four different versions of a TMR digital filter were analyzed by fault injection Faults were randomly inserted straight into the bitstream of the FPGA The experimental results presented in this paper demonstrate that the number and placement of voters in the TMR design can directly affect the fault tolerance, ranging from 403% to 098% the number of upsets in the routing able to cause an error in the TMR circuit

A new reliability-oriented place and route algorithm for SRAM-based FPGAs

Abstract: The very high integration levels reached by VLSI technologies for SRAM-based field programmable gate arrays (FPGAs) lead to high occurrence-rate of transient faults induced by single event upsets (SEUs) in FPGAs' configuration memory. Since the configuration memory defines which circuit an SRAM-based FPGA implements, any modification induced by SEUs may dramatically change the implemented circuit. When such devices are used in safety-critical applications, fault-tolerant techniques are needed to mitigate the effects of SEUs in FPGAs' configuration memory. In this paper, we analyze the effects induced by the SEUs in the configuration memory of SRAM-based FPGAs. The reported analysis outlines that SEUs in the FPGA's configuration memory are particularly critical since they are able to escape well-known fault masking techniques such as triple modular redundancy (TMR). We then present a reliability-oriented place and route algorithm that, coupled with TMR, is able to effectively mitigate the effects of the considered faults. The effectiveness of the new reliability-oriented place and route algorithm is demonstrated by extensive fault injection experiments showing that the capability of tolerating SEU effects in the FPGA's configuration memory increases up to 85 times with respect to a standard TMR design technique

A New Partial Reconfiguration-Based Fault-Injection System to Evaluate SEU Effects in SRAM-Based FPGAs

Abstract: Modern SRAM-based field programmable gate array (FPGA) devices offer high capability in implementing complex system. Unfortunately, SRAM-based FPGAs are extremely sensitive to single event upsets (SEUs) induced by radiation particles. In order to successfully deploy safety- or mission-critical applications, designer need to validate the correctness of the obtained designs. In this paper we describe a system based on partial-reconfiguration for running fault-injection experiments within the configuration memory of SRAM-based FPGAs. The proposed fault-injection system uses the internal configuration capabilities that modern FPGAs offer in order to inject SEU within the configuration memory. Detailed experimental results show that the technique is orders of magnitude faster than previously proposed ones.

Analysis of the robustness of the TMR architecture in SRAM-based FPGAs

Abstract: Non radiation-hardened SRAM-based Field Programmable Gate Arrays (FPGAs) are very sensitive to Single Event Upsets (SEUs) affecting their configuration memory and thus suitable hardening techniques are needed when they are intended to be deployed in critical applications. Triple Module Redundancy is a known solution for hardening digital logic against SEUs that is widely adopted for traditional techniques (like ASICs). In this paper we present an analysis of the SEU effects in circuits hardened according to the Triple Module Redundancy to investigate the possibilities of successfully applying TMR to designs mapped on commercial-off-the-shelf SRAM-based FPGAs, which are not radiation hardened. We performed different fault-injection experiments in the FPGA configuration memory implementing TMR designs and we observed that the percentage of SEUs escaping TMR could reach 13%. In this paper we report detailed evaluations of the effects of the observed failure rates, and we proposed a first step toward an improved TMR implementation.

Biological properties of extracellular vesicles and their physiological functions

Abstract: In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.

Extracellular vesicles: biology and emerging therapeutic opportunities

Abstract: Within the past decade, extracellular vesicles have emerged as important mediators of intercellular communication, being involved in the transmission of biological signals between cells in both prokaryotes and higher eukaryotes to regulate a diverse range of biological processes. In addition, pathophysiological roles for extracellular vesicles are beginning to be recognized in diseases including cancer, infectious diseases and neurodegenerative disorders, highlighting potential novel targets for therapeutic intervention. Moreover, both unmodified and engineered extracellular vesicles are likely to have applications in macromolecular drug delivery. Here, we review recent progress in understanding extracellular vesicle biology and the role of extracellular vesicles in disease, discuss emerging therapeutic opportunities and consider the associated challenges.

MicroRNAs in Stress Signaling and Human Disease

Abstract: Disease is often the result of an aberrant or inadequate response to physiologic and pathophysiologic stress. Studies over the last 10 years have uncovered a recurring paradigm in which microRNAs (miRNAs) regulate cellular behavior under these conditions, suggesting an especially significant role for these small RNAs in pathologic settings. Here, we review emerging principles of miRNA regulation of stress signaling pathways and apply these concepts to our understanding of the roles of miRNAs in disease. These discussions further highlight the unique challenges and opportunities associated with the mechanistic dissection of miRNA functions and the development of miRNA-based therapeutics.

Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs.

Abstract: The shear-responsive transcription factor Kruppel-like factor 2 (KLF2) is a critical regulator of endothelial gene expression patterns induced by atheroprotective flow. As microRNAs (miRNAs) post-transcriptionally control gene expression in many pathogenic and physiological processes, we investigated the regulation of miRNAs by KLF2 in endothelial cells. KLF2 binds to the promoter and induces a significant upregulation of the miR-143/145 cluster. Interestingly, miR-143/145 has been shown to control smooth muscle cell (SMC) phenotypes; therefore, we investigated the possibility of transport of these miRNAs between endothelial cells and SMCs. Indeed, extracellular vesicles secreted by KLF2-transduced or shear-stress-stimulated HUVECs are enriched in miR-143/145 and control target gene expression in co-cultured SMCs. Extracellular vesicles derived from KLF2-expressing endothelial cells also reduced atherosclerotic lesion formation in the aorta of ApoE(-/-) mice. Combined, our results show that atheroprotective stimuli induce communication between endothelial cells and SMCs through an miRNA- and extracellular-vesicle-mediated mechanism and that this may comprise a promising strategy to combat atherosclerosis.

Exosomes/microvesicles as a mechanism of cell-to-cell communication

Abstract: Microvesicles (MVs) are circular fragments of membrane released from the endosomal compartment as exosomes or shed from the surface membranes of most cell types. An increasing body of evidence indicates that they play a pivotal role in cell-to-cell communication. Indeed, they may directly stimulate target cells by receptor-mediated interactions or may transfer from the cell of origin to various bioactive molecules including membrane receptors, proteins, mRNAs, microRNAs, and organelles. In this review we discuss the pleiotropic biologic effects of MVs that are relevant for communication among cells in physiological and pathological conditions. In particular, we discuss their potential involvement in inflammation, renal disease, and tumor progression, and the evidence supporting a bidirectional exchange of genetic information between stem and injured cells. The transfer of gene products from injured cells may explain stem cell functional and phenotypic changes without the need of transdifferentiation into tissue cells. On the other hand, transfer of gene products from stem cells may reprogram injured cells to repair damaged tissues.