Precedent Text as a Special Kind of Code in the Internet Communication

Precedent texts should be considered as one of the most complicated and multifaceted phenomena which a) indicate common background knowledge of the interlocutors if they have such knowledge; b) work as a specific code for positive and negative emotions and ways of their expression, especially in the case of communication via Internet. The article highlights the hypothesis concerning complicacy of functions performed by precedent texts, and the changing of their range

Influence of anamnesis indicators on the progression of primary open-angle glaucoma

The article analyzes the influence of anamnesis indicators on the progression of primary open-angle glaucoma in 46 patients diagnosed with primary open-angle glaucoma (POAG) of stage I-II. All patients were followed up for 1 year.В статье проанализированы влияние показателей анамнеза на прогрессирование первичной открытоугольной глаукомы, у 46 пациентов с диагнозом первичная открытоугольная глаукома (ПОУГ) I-II стадии. Всепациентынаблюдалисьвтечение 1 года

Experimental rationale for the manufacture of ceramic inlays using an optical impression by the scanner of russian production

The results of the experimental study are presented, in which cavities under the all-ceramic inserts of the in-ley type were prepared on 20 premolars and molars of both jaws removed medically. Optical impressions were obtained with the help of a domestic VT Dental scanner. The tabs were made using the CAD \ CAM method. After fixing the inserts, longitudinal teeth sections were made to study the accuracy of the attachment of the inserts by scanning electron microscopy. Conclusions: The tightness of the all-ceramic inlays in the cavities, which are made using the VT Dental scanner (Russia), has the same results as the best world analogues of the scanning device.Представлены результаты экспериментального исследования, в котором на 20 удаленных по медицинским показаниям премолярах и молярах обеих челюстей были отпрепарированы полости под цельнокерамические вкладки типа inley. Получены оптические оттиски с помощью сканера отечественного производства VT Dental. Вкладки были изготовлены методом CAD\CAM. После фиксации вкладок, были изготовлены продольные шлифы зубов для изучения точности прилегания вкладок методом сканирующей электронной микроскопии. Выводы: Плотность прилегания цельнокермических вкладок в полости, которые изготовлены с использованием сканера VT Dental (россия) имеет результаты, аналогичные при использовании лучших мировых аналогов сканирующего аппарата

Experimental comparison of the fixing density of allceramic structures on adhesive cements

The article presents the results of an experimental study of the density of fixation of all-ceramic structures on adhesive cements.В статье представлены результаты экспериментального исследования плотности фиксации цельнокерамических конструкций на адгезивные цементы

Analysis of the marginal seal accuracy of the prosthetic restorations based on dental implants

The article presents the results of the study of the prosthetic bridge based on dental implants seal accuracy.В статье представлены результаты исследования точности прилегания мостовидного протеза с опорой на имплантаты с использованием четырех различны типов фиксации

Using Multiple Microenvironments to Find Similar Ligand-Binding Sites: Application to Kinase Inhibitor Binding

The recognition of cryptic small-molecular binding sites in protein structures is important for understanding off-target side effects and for recognizing potential new indications for existing drugs. Current methods focus on the geometry and detailed chemical interactions within putative binding pockets, but may not recognize distant similarities where dynamics or modified interactions allow one ligand to bind apparently divergent binding pockets. In this paper, we introduce an algorithm that seeks similar microenvironments within two binding sites, and assesses overall binding site similarity by the presence of multiple shared microenvironments. The method has relatively weak geometric requirements (to allow for conformational change or dynamics in both the ligand and the pocket) and uses multiple biophysical and biochemical measures to characterize the microenvironments (to allow for diverse modes of ligand binding). We term the algorithm PocketFEATURE, since it focuses on pockets using the FEATURE system for characterizing microenvironments. We validate PocketFEATURE first by showing that it can better discriminate sites that bind similar ligands from those that do not, and by showing that we can recognize FAD-binding sites on a proteome scale with Area Under the Curve (AUC) of 92%. We then apply PocketFEATURE to evolutionarily distant kinases, for which the method recognizes several proven distant relationships, and predicts unexpected shared ligand binding. Using experimental data from ChEMBL and Ambit, we show that at high significance level, 40 kinase pairs are predicted to share ligands. Some of these pairs offer new opportunities for inhibiting two proteins in a single pathway

The flavonoid galangin is an inhibitor of CYP1A1 activity and an agonist/antagonist of the aryl hydrocarbon receptor

The effect of the dietary flavonoid galangin on the metabolism of 7,12-dimethylbenz[a]anthracene (DMBA), the activity of cytochrome P 450 1A1 (CYP1A1), and the expression of CYP1A1 in MCF-7 human breast carcinoma cells was investigated. Galangin inhibited the catabolic breakdown of DMBA, as measured by thin-layer chromatography, in a dose-dependent manner. Galangin also inhibited the formation of DMBA-DNA adducts, and prevented DMBA-induced inhibition of cell growth. Galangin caused a potent, dose-dependent inhibition of CYP1A1 activity, as measured by ethoxyresorufin-O-deethylase activity, in intact cells and in microsomes isolated from DMBA-treated cells. Analysis of the inhibition kinetics by double-reciprocal plot demonstrated that galangin inhibited CYP1A1 activity in a non-competitive manner. Galangin caused an increase in the level of CYP1A1 mRNA, indicating that it may be an agonist of the aryl hydrocarbon receptor, but it inhibited the induction of CYP1A1 mRNA by DMBA or by 2,3,5,7-tetrachlorodibenzo-p-dioxin (TCDD). Galangin also inhibited the DMBA- or TCDD-induced transcription of a reporter vector containing the CYP1A1 promoter. Thus, galangin is a potent inhibitor of DMBA metabolism and an agonist/antagonist of the AhR, and may prove to be an effective chemopreventive agent. © 1999 Cancer Research Campaig

A nuclear role for the respiratory enzyme CLK-1 in regulating mitochondrial stress responses and longevity

The coordinated regulation of mitochondrial and nuclear activities is essential for cellular respiration and its disruption leads to mitochondrial dysfunction, a hallmark of ageing. Mitochondria communicate with nuclei through retrograde signalling pathways that modulate nuclear gene expression to maintain mitochondrial homeostasis. The monooxygenase CLK-1 (human homologue COQ7) was previously reported to be mitochondrial, with a role in respiration and longevity. We have uncovered a distinct nuclear form of CLK-1 that independently regulates lifespan. Nuclear CLK-1 mediates a retrograde signalling pathway that is conserved from Caenorhabditis elegans to humans and is responsive to mitochondrial reactive oxygen species, thus acting as a barometer of oxidative metabolism. We show that, through modulation of gene expression, the pathway regulates both mitochondrial reactive oxygen species metabolism and the mitochondrial unfolded protein response. Our results demonstrate that a respiratory enzyme acts in the nucleus to control mitochondrial stress responses and longevity

Identifying chondroprotective diet-derived bioactives and investigating their synergism

Osteoarthritis (OA) is a multifactorial disease and nutrition is a modifiable factor that may contribute to disease onset or progression. A detailed understanding of mechanisms through which diet-derived bioactive molecules function and interact in OA is needed. We profiled 96 diet-derived, mainly plant-based bioactives using an in vitro model in chondrocytes, selecting four candidates for further study. We aimed to determine synergistic interactions between bioactives that affected the expression of key genes in OA. Selected bioactives, sulforaphane, apigenin, isoliquiritigenin and luteolin, inhibited one or more interleukin-1-induced metalloproteinases implicated in OA (MMP1, MMP13, ADAMTS4, ADAMTS5). Isoliquiritigenin and luteolin showed reactive oxygen species scavenging activity in chondrocytes whereas sulforaphane had no effect and apigenin showed only a weak trend. Sulforaphane inhibited the IL-1/NFκB and Wnt3a/TCF/Lef pathways and increased TGFβ/Smad2/3 and BMP6/Smad1/5/8 signalling. Apigenin showed potent inhibition of the IL-1/NFκB and TGFβ/Smad2/3 pathways, whereas luteolin showed only weak inhibition of the IL-1/NFκB pathway. All four bioactives inhibited cytokine-induced aggrecan loss from cartilage tissue explants. The combination of sulforaphane and isoliquiritigenin was synergistic for inhibiting MMP13 gene expression in chondrocytes. We conclude that dietary-derived bioactives may be important modulators of cartilage homeostasis and synergistic relationships between bioactives may have an anti-inflammatory and chondroprotective role