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.

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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.

/pdf/atheroprotective-communication-between-endothelial-cells-and-2ijakoa7r0.pdf

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

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

A flexible system for SoC co-verification is proposed, built around an Infrastructure Microprocessor (IM), providing improved controllability and observability in a fast self-contained FPGA-based emulation environment. In addition, software debug is supported by enabling observation of critical signals, breakpoint setting and step-by-step execution with total memory accessibility. Experimental results in an industrial case study confirm the effectiveness of the approach for validating and debugging hardware and software.

/pdf/a-low-cost-emulation-system-for-fast-co-verification-and-2ov4ookwdi.pdf

A Low-Cost Emulation System for Fast Co-verification and Debug

Reconfigurable logic devices such as field programmable logic arrays (FPGAs) or programmable array logics are nowadays introducing a new design paradigm over the possible techniques an electronic or computing designer may choose to make the desired hardware chip running. Thanks to the higher design flexibility and the increasing performances supported by these devices on several aspects such as power, frequency, and dependability, programmable logic devices design tools play a central rule among the computer aided design (CAD) tools available. The basic concept behind this success is the possibility of defining the logic functionality of an electronic circuits without having a direct interface with the silicon layout mask of the chip itself. FPGA CAD tools have an increasing impact on the performances offered by current programmable devices. state-of-the-art CAD tools support both the synthesis of optimized logic functions and the implementation of design referring to the manner in which programmable switches and hard-wired interconnections are placed between logic functions. In this article survey of the CAD tools for the programmable devices design phases is presented exploring the variety and particularity offered and analyzing the most influcnt results achieved on this area.


Keywords:

FPGA;
PAL;
implementation;
synthesis;
place and route;
optimization;
dependability

FPGA PAL Design Tools

Gene expression is the fundamental control of the structure and functions of the cellular versatility and adaptability of any organisms. The measurement of gene expressions is performed on images generated by optical inspection of microarray devices which allow the simultaneous analysis of thousands of genes. The images produced by these devices are used to calculate the expression levels of mRNA in order to draw diagnostic information related to human disease. The quality measures are mandatory in genes classification and in the decision-making diagnostic. However, microarrays are characterized by imperfections due to sample contaminations, scratches, precipitation or imperfect gridding and spot detection. The automatic and efficient quality measurement of microarray is needed in order to discriminate faulty gene expression levels. In this paper we present a new method for estimate the quality degree and the data's reliability of a microarray analysis. The efficiency of the proposed approach in terms of genes expression classification has been demonstrated through a clustering supervised analysis performed on a set of three different histological samples related to the Lymphoma's cancer disease.

/pdf/gene-expression-reliability-estimation-through-cluster-based-5cwasjz969.pdf

Gene expression reliability estimation through cluster-based analysis

In this paper, we propose a new placement technique that takes advantage of the multi-tiers feature of 3D technology to increase the reliability of 3D designs. The proposed algorithm performs a transient effect analysis to identify the error-sensitive sequential components of the design. These components are allocated in the inner tier to reduce the soft error susceptibility of the circuit, exploiting the shielding effect of the outer tier on reducing the SEU cross-section of the component of the inner tier and performing an oculate placement to reduce the effect of secondary transient pulses. Experimental analyses performed by simulation on different benchmark circuits demonstrate the reduction in radiation-induced error sensitivity.

A Placement-Oriented Mitigation Technique for Single Event Effect in Monolithic 3D IC

Nowadays SRAM-based FPGAs, already widely used for their advantages in terms of size, flexibility and performances, are becoming even more attractive since they may dynamically change their functionalities based on the elaboration demand, thanks to Dynamic Partial Reconfiguration Feature. In these systems the communication infrastructure represents the major performance bottleneck due to routing congestions and to the needs to guarantee signal integrity at the module boundaries. In this paper we propose an Interface-based communication architecture, which simplify the interaction mechanism and the DRPM architecture, reducing both delay and resources overhead with respect to the state-of-the-art solutions.

Luca Sterpone

Papers

A Low-Cost Emulation System for Fast Co-verification and Debug

FPGA PAL Design Tools

Gene expression reliability estimation through cluster-based analysis

A Placement-Oriented Mitigation Technique for Single Event Effect in Monolithic 3D IC

IbIS: Interface-based Interconnection Structure for Dynamically Reconfigurable FPGAs