Methods for the Assessment of NET Formation: From Neutrophil Biology to Translational Research

Several studies have indicated that a neutrophil extracellular trap (NET) formation, apart from its role in host defense, can contribute to or drive pathogenesis in a wide range of inflammatory and thrombotic disorders. Therefore, NETs may serve as a therapeutic target or/and a diagnostic tool. Here, we compare the most commonly used techniques for the assessment of NET formation. Furthermore, we review recent data from the literature on the application of basic laboratory tools for detecting NET release and discuss the challenges and the advantages of these strategies in NET evaluation. Taken together, we provide some important insights into the qualitative and quantitative molecular analysis of NETs in translational medicine today.     

Dose-Dependent Cytotoxicity of Polypropylene Microplastics (PP-MPs) in Two Freshwater Fishes

The massive accumulation of plastics over the decades in the aquatic environment has led to the dispersion of plastic components in aquatic ecosystems, invading the food webs. Plastics fragmented into microplastics can be bioaccumulated by fishes via different exposure routes, causing several adverse effects. In the present study, the dose-dependent cytotoxicity of 8–10 μm polypropylene microplastics (PP-MPs), at concentrations of 1 mg/g (low dose) and 10 mg/g dry food (high dose), was evaluated in the liver and gill tissues of two fish species, the zebrafish (Danio rerio) and the freshwater perch (Perca fluviatilis). According to our results, the inclusion of PP-MPs in the feed of D. rerio and P. fluviatilis hampered the cellular function of the gills and hepatic cells by lipid peroxidation, DNA damage, protein ubiquitination, apoptosis, autophagy, and changes in metabolite concentration, providing evidence that the toxicity of PP-MPs is dose dependent. With regard to the individual assays tested in the present study, the biggest impact was observed in DNA damage, which exhibited a maximum increase of 18.34-fold in the liver of D. rerio. The sensitivity of the two fish species studied differed, while no clear tissue specificity in both fish species was observed. The metabolome of both tissues was altered in both treatments, while tryptophan and nicotinic acid exhibited the greatest decrease among all metabolites in all treatments in comparison to the control. The battery of biomarkers used in the present study as well as metabolomic changes could be suggested as early-warning signals for the assessment of the aquatic environment quality against MPs. In addition, our results contribute to the elucidation of the mechanism induced by nanomaterials on tissues of aquatic organisms, since comprehending the magnitude of their impact on aquatic ecosystems is of great importance.     

Regulation of Metastatic Tumor Dormancy and Emerging Opportunities for Therapeutic Intervention

Cancer recurrence and metastasis, following successful treatment, constitutes a critical threat in clinical oncology and are the leading causes of death amongst cancer patients. This phenomenon is largely attributed to metastatic tumor dormancy, a rate-limiting stage during cancer progression, in which disseminated cancer cells remain in a viable, yet not proliferating state for a prolonged period. Dormant cancer cells are characterized by their entry into cell cycle arrest and survival in a quiescence state to adapt to their new microenvironment through the acquisition of mutations and epigenetic modifications, rendering them resistant to anti-cancer treatment and immune surveillance. Under favorable conditions, disseminated dormant tumor cells ‘re-awake’, resume their proliferation and thus colonize distant sites. Due to their rarity, detection of dormant cells using current diagnostic tools is challenging and, thus, therapeutic targets are hard to be identified. Therefore, unraveling the underlying mechanisms required for keeping disseminating tumor cells dormant, along with signals that stimulate their “re-awakening” are crucial for the discovery of novel pharmacological treatments. In this review, we shed light into the main mechanisms that control dormancy induction and escape as well as emerging therapeutic strategies for the eradication of metastatic dormant cells, including dormancy maintenance, direct targeting of dormant cells and re-awakening dormant cells. Studies on the ability of the metastatic cancer cells to cease proliferation and survive in a quiescent state before re-initiating proliferation and colonization years after successful treatment, will pave the way toward developing innovative therapeutic strategies against dormancy-mediated metastatic outgrowth.     

On the security of AUTH, a provably secure authentication protocol based on the subspace LPN problem

At the 2011 Eurocrypt, Kiltz et al., in their best paper price awarded paper, proposed an ultra-lightweight authentication protocol, called $AUTH$ . While the new protocol is supported by a delicate security proof based on the conjectured hardness of the learning parity with noise problem, this security proof does not include man-in-the-middle attacks. In this paper, we show that $AUTH$ is weak against MIM adversaries by introducing a very efficient key recovery MIM attack that has only linear complexity with respect to the length of the secret key.     

Spin-axis stabilization of symmetric spacecraft with two control torques

It is a well-known fact that a symmetric spacecraft with two control torques supplied by gas jet actuators is not controllable, if the two control torques are along axes that span the two-dimensional plane orthogonal to the axis of symmetry. However, feedback control laws can be derived for a restricted problem corresponding to attitude stabilization about the symmetry axis. In this configuration, the final state of the system is a uniform revolute motion about the symmetry axis. The purpose of this paper is to present a new methodology for constructing feedback control laws for this problem, based on a new formulation for the attitude kinematics.     

Visualizing program dependencies: An experimental study

This paper addresses the problem of visualizing program dependencies (i.e. entities and their relations). A code visualization tool that maintains a repository of structural and functional dependencies for C programs is described. Visualization of such dependencies is accomplished by using a presentation model which combines data and control flow information. Moreover, transformation mechanisms and partitioning techniques used by the tool provide the means for managing large graphical representations. The quantitative results from an experimental study using this tool indicate that the productivity of its users was increased and that the quality of changes made during a program modification exercise was improved. Furthermore, the qualitative results have shown that its presentation model, transformation mechanisms and partitioning techniques constitute a promising platform for the comprehension and maintenance of C programs. Finally, the outcome of an empirical evaluation of the tool and the enhancement of its functionality and user interface are also discussed in this paper.     

Convective heat-transfer measurements in liquid metals under different fluid flow conditions

In this study an experimental method to measure convective heat transfer characteristics in liquid metals is presented. This method involves the immersion into a metal bath of a solid specimen whose melting point is equal to or lower than that of the metal or alloy in the metal bath, and which will not react chemically with the liquid metal or alloys used. The specimen should have a hollow bore whose opening is held above the surface of the liquid metal; immersion continues until such a time as the liquid metal penetrates the hollow bore. The apparent weight of the specimen is monitored to determine the rate at which the net downward force changes. Experimental results are reported for liquid aluminum, liquid copper, and liquid steel. Those experimental results were conducted under different fluid flow conditions. The applicability of this method to liquid slags is also discussed. Formerly Postdoctoral Research Fellow with the Department of Metallurgy and Materials Science, University of Toronto