Tight Localizations of Feedback Sets

The classical NP-hard feedback arc set problem (FASP) and feedback vertex set problem (FVSP) ask for a minimum set of arcs $\varepsilon \subseteq E$ or vertices $\nu \subseteq V$ whose removal $G\setminus \varepsilon$, $G\setminus \nu$ makes a given multi-digraph $G=(V,E)$ acyclic, respectively. Though both problems are known to be APX-hard, approximation algorithms or proofs of inapproximability are unknown. We propose a new $\mathcal{O}(|V||E|^4)$-heuristic for the directed FASP. While a ratio of $r \approx 1.3606$ is known to be a lower bound for the APX-hardness, at least by empirical validation we achieve an approximation of $r \leq 2$. The most relevant applications, such as circuit testing, ask for solving the FASP on large sparse graphs, which can be done efficiently within tight error bounds due to our approach.Comment: manuscript submitted to AC

Mycobacterium bovis BCG increase the selected determinants of monocyte/macrophage activity, which were diminished in response to gastric pathogen Helicobacter pylori

High antibiotic resistance of gastric pathogen Helicobacter pylori (Hp) and the ability to escape the host immune response prompt searching for therapeutic immunomodulators. Bacillus Calmette–Guerin (BCG) vaccine with Mycobacterium bovis (Mb) is a candidate for modulation the activity of immunocompetent cells, and onco-BCG formulation was successfully used in immunotherapy of bladder cancer. We determined the influence of onco-BCG on the phagocytic capacity of human THP-1 monocyte/macrophage cells, using the model of Escherichia coli bioparticles and Hp fluorescently labeled. Deposition of cell integrins CD11b, CD11d, CD18, membrane/soluble lipopolysaccharide (LPS) receptors, CD14 and sCD14, respectively, and the production of macrophage chemotactic protein (MCP)-1 were determined. Furthermore, a global DNA methylation, was also assessed. Human THP-1 monocytes/macrophages (TIB 202) primed or primed and restimulated with onco-BCG or Hp, were used for assessment of phagocytosis towards E. coli or Hp, surface (immunostaining) or soluble activity determinants, and global DNA methylation (ELISA). THP-1 monocytes/macrophages primed/restimulated with BCG showed increased phagocytosis capacity towards E. coli fluorescent particles, elevated expression of CD11b, CD11d, CD18, CD14, sCD14, increased MCP-1 secretion and DNA methylation. Preliminary results indicate that BCG mycobacteria may also induce the phagocytosis of H. pylori by THP-1 monocytes. Priming or priming and restimulation of monocytes/macrophages with BCG resulted in an increased activity of these cells, which was negatively modulated by Hp.This research was financially supported by University of Lodz, Grant Number 15/GNZPA/2022 (B2111001000027.07). Development of chitozan biopolimer with Mycobacterium bovis BCG-onko vaccine mycobacteria, with immunomodulatory properties, to improve immune response towards Helicobacter pylori and Student Research Grants financed by University of Lodz

Ryzyko uzależnienia studentów od mediów społecznościowych na przykładzie Facebooka

This paper is devoted to the issue of behavioral addictions associated with social media. The first part describes the phenomenon which social media. They explained the notion of addiction and behavioral addictions for example Facebook. The second part presents the results of the survey, which aim was to diagnose the risk of dependence on Facebook. The presented results showing that only a few of which may be dependent on this medium.Niniejsze opracowanie jest poświęcone zagadnieniu uzależnienia behawioralnego związanego z mediami społecznościowymi. Pierwsza część opisuje fenomen, jakim są portale społecznościowe. Wyjaśnione zostały również pojęcia uzależnienia oraz uzależnienia behawioralnego na przykładzie Facebooka. Druga część prezentuje wyniki badań ankietowych, których celem była diagnoza ryzyka uzależnienia od Facebooka. Z zaprezentowanych wyników widać, że jedynie kilku badanych studentów może być uzależnionym od tego portalu społecznościowego

Proregenerative Activity of IL-33 in Gastric Tissue Cells Undergoing Helicobacter Pylori-Induced Apoptosis

: Interleukin (IL)-33 is a proinflammatory mediator that alerts the host immune system to disorders in tissue homeostasis. Aim. To understand the role of IL-33 in modulating gastric tissue cell growth affected by Helicobacter pylori (H. pylori). Methods. IL-33 production in guinea pigs (Caviae porcellus) experimentally infected with H. pylori was evaluated by ELISA or immunohistochemical staining. The proregenerative activity of IL-33 was evaluated using gastric epithelial cells and fibroblasts that were naive or transfected with IL-33 siRNA exposed to H. pylori glycine acid extract antigenic complex (GE), as well as by measuring cell migration, proliferation, metabolic activity and apoptosis. Animals infected by H. pylori responded with increased production of IL-33. Also, cells treated in vitro with GE released more IL-33 than cells that were unstimulated. Silencing IL-33 in cells resulted in downregulation of metabolic activity, adhesion, migration and proliferation, especially after treatment with H. pylori GE, as well as upregulation of cells apoptosis associated with caspase 3 increase and Bcl-xL decrease, suggesting proregenerative activity of IL-33. Interestingly, upregulation of cell proliferation by IL-33 was Erk independent. Our results indicate that IL-33 may protect gastric tissue from loss of homeostasis caused by deleterious effects of H. pylori components and the inflammatory response developed during infection

Cryo-EM Structure of Dodecameric Vps4p and Its 2:1 Complex with Vta1p

The type I AAA (ATPase associated with a variety of cellular activities) ATPase Vps4 and its co-factor Vta1p/LIP5 function in membrane remodeling events that accompany cytokinesis, multivesicular body biogenesis, and retrovirus budding, apparently by driving disassembly and recycling of membrane-associated ESCRT (endosomal sorting complex required for transport)-III complexes. Here, we present electron cryomicroscopy reconstructions of dodecameric yeast Vps4p complexes with and without their microtubule interacting and transport (MIT) N-terminal domains and Vta1p co-factors. The ATPase domains of Vps4p form a bowl-like structure composed of stacked hexameric rings. The two rings adopt dramatically different conformations, with the “upper” ring forming an open assembly that defines the sides of the bowl and the lower ring forming a closed assembly that forms the bottom of the bowl. The N-terminal MIT domains of the upper ring localize on the symmetry axis above the cavity of the bowl, and the binding of six extended Vta1p monomers causes additional density to appear both above and below the bowl. The structures suggest models in which Vps4p MIT and Vta1p domains engage ESCRT-III substrates above the bowl and help transfer them into the bowl to be pumped through the center of the dodecameric assembly

Validation of LC/MS/MS method for assessment of the "in vitro" activity of selected rat cytochrome P450 isoenzymes : application to early drug metabolism screening

A sensitive and specific liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for simultaneous determination of seven metabolites of CYP450 model substrates (acetaminophen, 4-hydroxytolbutamide, 4'-hydroxymephenytoin, 1-hydroxybufuralol, 6-hydroxychlorzoxazone. 1'-and 4-hydroxymidazolam) in rat liver microsomes was developed. The assay used Kinetex analytical column and a gradient mobile phase consistent of acetonitrile and water with addition of 0.1\% formic acid. The analysis was performed in selected reaction monitoring (SRM) mode both in positive and negative (for 6-hydroxychlorzoxazone) mode. The method was validated over the concentration ranges of 10-2000 ng/mL for 4-hydroxymephenytoin and 4-hydroxytolbutamide, 50-2000 ng/mL for 1-hydroxybufuralol and 25-2000 ng/mL for the rest of the analytes. The intra- and inter-day precision (2-12%) and accuracy (93-119%) were within the limits set by the FDA and EMA guidelines. The developed method was successfully applied to assess the activity of selected CYP450 isoenzymes in rat liver microsomes after addition of ketoconazole

Validation of LC/MS/MS method for assessment of the "in vitro" activity of the selected rat cytochrome P450 isoenzymes : application to early drug metabolism screening

A sensitive and specific liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for simultaneous determination of seven metabolites of CYP450 model substrates (acetaminophen, 4-hydroxytolbutamide, 4í-hydroxymephenytoin, 1-hydroxybufuralol, 6-hydroxychlorzoxazone, 1í- and 4í-hydroxymidazolam) in rat liver microsomes was developed. The assay used Kinetex analytical column and a gradient mobile phase consistent of acetonitrile and water with addition of 0.1% formic acid. The analysis was performed in selected reaction monitoring (SRM) mode both in positive and negative (for 6-hydroxychlorzoxazone) mode. The method was validated over the concentration ranges of 10-2000 ng/mL for 4í-hydroxymephenytoin and 4-hydroxytolbutamide, 50-2000 ng/mL for 1-hydroxybufuralol and 25-2000 ng/mL for the rest of the analytes. The intra- and inter-day precision (2-12%) and accuracy (93-119%) were within the limits set by the FDA and EMA guidelines. The developed method was successfully applied to assess the activity of selected CYP450 isoenzymes in rat liver microsomes after addition of ketoconazole