254 research outputs found

    On the electron energy distribution function in the high power impulse magnetron sputtering discharge

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    We apply the Ionization Region Model (IRM) and the Orsay Boltzmann equation for ELectrons coupled with Ionization and eXcited states kinetics (OBELIX) model to study the electron kinetics of a high power impulse magnetron sputtering (HiPIMS) discharge. In the IRM the bulk (cold) electrons are assumed to exhibit a Maxwellian energy distribution and the secondary (hot) electrons, emitted from the target surface upon ion bombardment, are treated as a high energy tail, while in the OBELIX the electron energy distribution is calculated self-consistently using an isotropic Boltzmann equation. The two models are merged in the sense that the output from the IRM is used as an input for OBELIX. The temporal evolutions of the particle densities are found to agree very well between the two models. Furthermore, a very good agreement is demonstrated between the bi-Maxwellian electron energy distribution assumed by the IRM and the electron energy distribution calculated by the OBELIX model. It can therefore be concluded that assuming a bi-Maxwellian electron energy distribution, constituting a cold bulk electron group and a hot secondary electron group, is a good approximation for modeling the HiPIMS discharge

    Pandemic Dreams : Network Analysis of Dream Content During the COVID-19 Lockdown

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    We used crowdsourcing (CS) to examine how COVID-19 lockdown affects the content of dreams and nightmares. The CS took place on the sixth week of the lockdown. Over the course of 1 week, 4,275 respondents (mean age 43, SD = 14 years) assessed their sleep, and 811 reported their dream content. Overall, respondents slept substantially more (54.2%) but reported an average increase of awakenings (28.6%) and nightmares (26%) from the pre-pandemic situation. We transcribed the content of the dreams into word lists and performed unsupervised computational network and cluster analysis of word associations, which suggested 33 dream clusters including 20 bad dream clusters, of which 55% were pandemic-specific (e.g., Disease Management, Disregard of Distancing, Elderly in Trouble). The dream-association networks were more accentuated for those who reported an increase in perceived stress. This CS survey on dream-association networks and pandemic stress introduces novel, collectively shared COVID-19 bad dream contentsPeer reviewe

    Snake Venom Disintegrins and Cell Migration

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    Cell migration is a key process for the defense of pluricellular organisms against pathogens, and it involves a set of surface receptors acting in an ordered fashion to contribute directionality to the movement. Among these receptors are the integrins, which connect the cell cytoskeleton to the extracellular matrix components, thus playing a central role in cell migration. Integrin clustering at focal adhesions drives actin polymerization along the cell leading edge, resulting in polarity of cell movement. Therefore, small integrin-binding proteins such as the snake venom disintegrins that inhibit integrin-mediated cell adhesion are expected to inhibit cell migration. Here we review the current knowledge on disintegrin and disintegrin-like protein effects on cell migration and their potential use as pharmacological tools in anti-inflammatory therapy as well as in inhibition of metastatic invasion

    Vicrostatin – An Anti-Invasive Multi-Integrin Targeting Chimeric Disintegrin with Tumor Anti-Angiogenic and Pro-Apoptotic Activities

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    Similar to other integrin-targeting strategies, disintegrins have previously shown good efficacy in animal cancer models with favorable pharmacological attributes and translational potential. Nonetheless, these polypeptides are notoriously difficult to produce recombinantly due to their particular structure requiring the correct pairing of multiple disulfide bonds for biological activity. Here, we show that a sequence-engineered disintegrin (called vicrostatin or VCN) can be reliably produced in large scale amounts directly in the oxidative cytoplasm of Origami B E. coli. Through multiple integrin ligation (i.e., αvβ3, αvβ5, and α5β1), VCN targets both endothelial and cancer cells significantly inhibiting their motility through a reconstituted basement membrane. Interestingly, in a manner distinct from other integrin ligands but reminiscent of some ECM-derived endogenous anti-angiogenic fragments previously described in the literature, VCN profoundly disrupts the actin cytoskeleton of endothelial cells (EC) inducing a rapid disassembly of stress fibers and actin reorganization, ultimately interfering with EC's ability to invade and form tubes (tubulogenesis). Moreover, here we show for the first time that the addition of a disintegrin to tubulogenic EC sandwiched in vitro between two Matrigel layers negatively impacts their survival despite the presence of abundant haptotactic cues. A liposomal formulation of VCN (LVCN) was further evaluated in vivo in two animal cancer models with different growth characteristics. Our data demonstrate that LVCN is well tolerated while exerting a significant delay in tumor growth and an increase in the survival of treated animals. These results can be partially explained by potent tumor anti-angiogenic and pro-apoptotic effects induced by LVCN

    Strategies to inhibit tumour associated integrin receptors: rationale for dual and multi-antagonists

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    YesThe integrins are a family of 24 heterodimeric transmembrane cell surface receptors. Involvement in cell attachment to the extracellular matrix, motility, and proliferation identifies integrins as therapeutic targets in cancer and associated conditions; thrombosis, angiogenesis and osteoporosis. The most reported strategy for drug development is synthesis of an agent that is highly selective for a single integrin receptor. However, the ability of cancer cells to change their integrin repertoire in response to drug treatment renders this approach vulnerable to the development of resistance and paradoxical promotion of tumor growth. Here, we review progress towards development of antagonists targeting two or more members of the RGD-binding integrins, notably αvβ3, αvβ5, αvβ6, αvβ8, α5β1, and αIIbβ3, as anticancer therapeutics
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