121 research outputs found
The identification of critical facilities from the position of cybersecurity violation by the example of energy
The article describes methods for identification of critical facilities, being a significant trend in researching critical infrastructures, particularly in the energy sector. The proposed methods are focused on the investigation of the energy object state in relation to the violation of cybersecurity of its information infrastructure. The cyber threats are believed to be important contemporary threats to energy security in Russia. The proposed methods formed the basis of development information-analytical system used for monitoring of cybersecurity violations in energy sector
ISO-1 Binding to the Tautomerase Active Site of MIF Inhibits Its Pro-inflammatory Activity and Increases Survival in Severe Sepsis
MIF is a proinflammatory cytokine that has been implicated in the pathogenesis of sepsis, arthritis, and other inflammatory diseases. Antibodies against MIF are effective in experimental models of inflammation, and there is interest in strategies to inhibit its deleterious cytokine activities. Here we identify a mechanism of inhibiting MIF pro-inflammatory activities by targeting MIF tautomerase activity. We designed small molecules to inhibit this tautomerase activity; a lead molecule, "ISO-1 ((S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester)," significantly inhibits the cytokine activity in vitro. Moreover, ISO-1 inhibits tumor necrosis factor release from macrophages isolated from LPStreated wild type mice but has no effect on cytokine release from MIFdeficient macrophages. The therapeutic importance of the MIF inhibition by ISO-1 is demonstrated by the significant protection from sepsis, induced by cecal ligation and puncture in a clinically relevant time frame. These results identify ISO-1 as the first small molecule inhibitor of MIF proinflammatory activities with therapeutic implications and indicate the potential of the MIF active site as a novel target for therapeutic interventions in human sepsis
Why do people use portable air purifiers? Evidence from occupant surveys and air quality monitoring in homes in three European cities
One of the most widely available technologies to clean the air in homes of particulate matter of less than 2.5 µm in diameter (PM2.5), known to have negative health impacts, are portable home air purifiers (HAPs). This paper presents research which (1) explored the effectiveness of HAPs in real-world conditions in 57 homes in three European cities; (2) examined if HAPs affect users’ perceptions of the indoor air quality (IAQ) at home; and (3) considered the motivations for occupants’ operation of HAPs. Results from this study found that PM2.5 concentrations in bedrooms were reduced by 45% to 69%; perceptions of IAQ were not correlated with measured high PM2.5 levels; occupants reported the HAPs to have a ‘cooling’ effect, which may explain why the predominant driver of HAP use was thermal comfort, rather than IAQ, in all three cities. The latter finding was supported by a statistically significant increase in the probability of HAP use with increasing indoor temperatures. If the operation of HAPs can be managed, or fully automated, to reflect indoor air pollution levels rather than thermal conditions, better pollutant reduction would be feasible and their use to reduce PM2.5 may help mitigate the negative health effects of exposure whilst at home
Rho GTPase function in flies: insights from a developmental and organismal perspective.
Morphogenesis is a key event in the development of a multicellular organism and is reliant on coordinated transcriptional and signal transduction events. To establish the segmented body plan that underlies much of metazoan development, individual cells and groups of cells must respond to exogenous signals with complex movements and shape changes. One class of proteins that plays a pivotal role in the interpretation of extracellular cues into cellular behavior is the Rho family of small GTPases. These molecular switches are essential components of a growing number of signaling pathways, many of which regulate actin cytoskeletal remodeling. Much of our understanding of Rho biology has come from work done in cell culture. More recently, the fruit fly Drosophila melanogaster has emerged as an excellent genetic system for the study of these proteins in a developmental and organismal context. Studies in flies have greatly enhanced our understanding of pathways involving Rho GTPases and their roles in development
Methodological approaches for studying the microbial ecology of drinking water distribution systems
The study of the microbial ecology of drinking water distribution systems (DWDS) has traditionally been based on culturing organisms from bulk water samples. The development and application of molecular methods has supplied new tools for examining the microbial diversity and activity of environmental samples, yielding new insights into the microbial community and its diversity within these engineered ecosystems. In this review, the currently available methods and emerging approaches for characterising microbial communities, including both planktonic and biofilm ways of life, are critically evaluated. The study of biofilms is considered particularly important as it plays a critical role in the processes and interactions occurring at the pipe wall and bulk water interface. The advantages, limitations and usefulness of methods that can be used to detect and assess microbial abundance, community composition and function are discussed in a DWDS context. This review will assist hydraulic engineers and microbial ecologists in choosing the most appropriate tools to assess drinking water microbiology and related aspects
Galectin-1, a gene preferentially expressed at the tumor margin, promotes glioblastoma cell invasion
BACKGROUND: High-grade gliomas, including glioblastomas (GBMs), are recalcitrant to local therapy in part because of their ability to invade the normal brain parenchyma surrounding these tumors. Animal models capable of recapitulating glioblastoma invasion may help identify mediators of this aggressive phenotype. METHODS: Patient-derived glioblastoma lines have been propagated in our laboratories and orthotopically xenografted into the brains of immunocompromized mice. Invasive cells at the tumor periphery were isolated using laser capture microdissection. The mRNA expression profile of these cells was compared to expression at the tumor core, using normal mouse brain to control for host contamination. Galectin-1, a target identified by screening the resulting data, was stably over-expressed in the U87MG cell line. Sub-clones were assayed for attachment, proliferation, migration, invasion, and in vivo tumor phenotype. RESULTS: Expression microarray data identified galectin-1 as the most potent marker (p-value 4.0 x 10(-8)) to identify GBM cells between tumor-brain interface as compared to the tumor core. Over-expression of galectin-1 enhanced migration and invasion in vitro. In vivo, tumors expressing high galectin-1 levels showed enhanced invasion and decreased host survival. CONCLUSIONS: In conclusion, cells at the margin of glioblastoma, in comparison to tumor core cells, have enhanced expression of mediators of invasion. Galectin-1 is likely one such mediator. Previous studies, along with the current one, have proven galectin-1 to be important in the migration and invasion of glioblastoma cells, in GBM neoangiogenesis, and also, potentially, in GBM immune privilege. Targeting this molecule may offer clinical improvement to the current standard of glioblastoma therapy, i.e. radiation, temozolomide, anti-angiogenic therapy, and vaccinotherapy
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