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.

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Biological properties of extracellular vesicles and their physiological functions

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.

/pdf/extracellular-vesicles-biology-and-emerging-therapeutic-4wc2updtyj.pdf

Extracellular vesicles: biology and emerging therapeutic opportunities

MicroRNAs in Stress Signaling and Human Disease

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.

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

State-of-the-art on use of insects as animal feed.

Introduction- Re-configurable Field Programmable Gate Arrays: basic concepts- Re-configurable Field Programmable Gate Arrays: failure modes and analysis- Re-configurable Field Programmable Gate Arrays: hardening solutions- Commercial off the shelf FPGAs- Radiation hardened SRAM-based FPGAs- Conclusion

https://static.springer.com/sgw/documents/1029744/application/pdf/news1012_engin.pdf

Reconfigurable Field Programmable Gate Arrays for Mission-Critical Applications

The growing availability of embedded processors inside FPGAs provides unprecedented flexibility for system designers. The use of such devices for space or mission critical applications, however, is being delayed by the lack of effective low cost techniques to mitigate radiation induced errors. In this paper a non invasive approach for the implementation of fault tolerant systems based on COTS processors embedded in FPGAs, using lockstep in conjunction with checkpoint and rollback recovery, is presented. The proposed approach does not require modifications in the processor architecture or in the application software. The experimental validation of this approach through fault injection is described, the corresponding results are discussed, and the addition of a write history table as a means to reduce the performance overhead imposed by previous implementations is proposed and evaluated.

/pdf/new-techniques-for-improving-the-performance-of-the-lockstep-3c54vqsgoq.pdf

New Techniques for Improving the Performance of the Lockstep Architecture for SEEs Mitigation in FPGA Embedded Processors

Reconfigurable hardware is gaining a steadily growing interest in the domain of space applications. The ability to reconfigure the information processing infrastructure at runtime together with the high computational power of today's FPGA architectures at relatively low power makes these devices interesting candidates for data processing in space applications. Partial dynamic reconfiguration of FPGAs enables maximum flexibility and can be utilized for performance optimization, for improving energy efficiency, and for enhanced fault tolerance. To be able to prove the effectiveness of these novel approaches for satellite payload processing, a highly scalable prototyping environment has been developed, combining dynamically reconfigurable FPGAs with the required interfaces such as SpaceWire, MIL-STD-1553B, and SpaceFibre. The developed systems have been enabled to space harsh environments thanks to an analytical analysis of the radiation effects on its most critical reconfigurable components. Aiming at that scope, a new algorithm for the analysis of critical radiation effects, in particular, related to Single Event Upsets (SEUs) and Multiple Event Upsets (MEUs) has been developed to obtain an effective estimation of the radiation impact and enabling the tuning of the component mapping reducing the routing interaction between the reconfigurable placed modules in their different feasible positions. The experimental performance of the system has been evaluated by a proper dynamic reconfiguration scenario, demonstrating a partial reconfiguration at 400 MByte/s, blind and readback scrubbing is supported and the scrub rate can be adapted individually for different parts of the design. The fault tolerance capability has been proven by means of a new analysis algorithm and by fault injection campaigns of SEUs and MCUs into the FPGA configuration memory.

A Novel Fault Tolerant and Runtime Reconfigurable Platform for Satellite Payload Processing

FlexGripPlus: An improved GPGPU model to support reliability analysis

The very high integration levels reached by SRAM-based field programmable gate arrays (FPGAs) lead to high occurrence rate of single event upsets (SEUs) in their configuration memory, which can produce multiple errors affecting routing resources. Based on detailed analysis of this phenomenon, we devised a reliability-oriented place and route algorithm able to significantly improve the reliability of SRAM-based FPGAs with limited costs in terms of performance degradation and resource occupation. To evaluate the effectiveness of the algorithm we performed extensive fault injection experiments.

Luca Sterpone

Papers

Reconfigurable Field Programmable Gate Arrays for Mission-Critical Applications

New Techniques for Improving the Performance of the Lockstep Architecture for SEEs Mitigation in FPGA Embedded Processors

A Novel Fault Tolerant and Runtime Reconfigurable Platform for Satellite Payload Processing

FlexGripPlus: An improved GPGPU model to support reliability analysis

Multiple errors produced by single upsets in FPGA configuration memory: a possible solution