Congruence of intranasal aerodynamics and functional heterogeneity of olfactory epithelium

Zonal organization of the olfactory system is determined not only by peculiarities of the expression of olfactory receptor genes but also by the geometry of nasal passage, where receptors to the most muco-soluble compounds are concentrated in the area with the maximal rate of air flow (dorsal part), while receptors to less volatile compounds are concentrated in ventral part of the nose. An increase in the flow rate in certain areas of nasal cavity, on the one hand, allows acceleration of the perception of odor stimuli by olfactory receptors and, on the other hand, increases the risk of the effect of different pathogens (contained in the air) on this area due to the larger intensity of their precipitation. In this study, we demonstrated by means of manganese- enhanced magnetic resonance imaging (MRI) that a more intensive capture of insoluble particles occurs in ventral part of mouse olfactory epithelium than in dorsal part during intranasal introduction of the colloid solution of manganese oxide nanoparticles (MON, Mn3O4). The joint introduction of MON and specific blockers of cellular transport and endocytosis demonstrated that the particles are captured from the nasal cavity by means of endocytosis and are transported in olfactory bulb cells by means of intracellular transport. The clathrin-dependent type of endocytosis mainly contributes to the capture of MON in the dorsal part of the olfactory epithelium (as opposed to ventral). Thus, it was established that two functional regions of mouse olfactory epithelium differing in the intensities of precipitation of submicron aerosols demonstrate different intensities of the capture of insoluble particles from the nasal cavity and have differences in the mechanisms of their endocytosis. Consequently, the structural and functional organization of mouse nasal cavity completely meets the principle of adaptive congruence, which limits infectious and toxic effects of nanoaerosols on the olfactory epithelium cells and the brain

Cytokine-related genes identified from the RIKEN full-length mouse cDNA data set

To identify novel cytokine-related genes, we searched the set of 60,770 annotated RIKEN mouse cDNA clones (FANTOM2 clones), using keywords such as cytokine itself or cytokine names (such as interferon, interleukin, epidermal growth factor, fibroblast growth factor, and transforming growth factor). This search produced 108 known cytokines and cytokine-related products such as cytokine receptors, cytokine-associated genes, or their products (enhancers, accessory proteins, cytokine-induced genes). We found 15 clusters of FANTOM2 clones that are candidates for novel cytokine-related genes. These encoded products with strong sequence similarity to guanylate-binding protein (GBP-5), interleukin-1 receptor-associated kinase 2 (IRAK-2), interleukin 20 receptor alpha isoform 3, a member of the interferon-inducible proteins of the Ifi 200 cluster, four members of the membrane-associated family 1-8 of interferon-inducible proteins, one p27-like protein, and a hypothetical protein containing a Toll/Interleukin receptor domain. All four clones representing novel candidates of gene products from the family contain a novel highly conserved cross-species domain. Clones similar to growth factor-related products included transforming growth factor beta-inducible early growth response protein 2 (TIEG-2), TGFbeta-induced factor 2, integrin beta-like 1, latent TGF-binding protein 4S, and FGF receptor 4B. We performed a detailed sequence analysis of the candidate novel genes to elucidate their likely functional properties

Null Energy Condition Violation and Classical Stability in the Bianchi I Metric

The stability of isotropic cosmological solutions in the Bianchi I model is considered. We prove that the stability of isotropic solutions in the Bianchi I metric for a positive Hubble parameter follows from their stability in the Friedmann-Robertson-Walker metric. This result is applied to models inspired by string field theory, which violate the null energy condition. Examples of stable isotropic solutions are presented. We also consider the k-essence model and analyse the stability of solutions of the form $\Phi(t)=t$.Comment: 27 pages, references added, accepted for publication in Phys. Rev.

Global solutions of a free boundary problem for selfgravitating scalar fields

The weak cosmic censorship hypothesis can be understood as a statement that there exists a global Cauchy evolution of a selfgravitating system outside an event horizon. The resulting Cauchy problem has a free null-like inner boundary. We study a selfgravitating spherically symmetric nonlinear scalar field. We show the global existence of a spacetime with a null inner boundary that initially is located outside the Schwarzschild radius or, more generally, outside an apparent horizon. The global existence of a patch of a spacetime that is exterior to an event horizon is obtained as a limiting case.Comment: 31 pages, revtex, to appear in the Classical and Quantum Gravit

Особенности подготовки лав, извлекающих подработанный сильвинитовый слой на глубоких горизонтах Старобинского месторождения калийных солей

A study was made of the features of rock pressure manifestation and the deformation nature of development and assembly workings depending on the binding of the roof and its location relative to the longwalls mined by the chamber system for layers 2, 2-3, 3, as well as of the panels mined by the chamber system in the extraction conditions of the worked out fourth sylvinite layer of the Third potash horizon at a depth of more than 600 m. It was established that the service life of newly designed workings depends on their location on the panel, the roof binding and fastening parameters. The longest service life of workings will be noted when they are located in the mined space above the mined longwalls along the lower layers, and the shortest service life will be marked when they are carried out in the central part of the safety intercolumn pillars. Based on the studies performed, the recommendations were made on the selection of locations, roof bindings and on the protection and maintenance of development workings for the sites of the mine fields of the JSC “Belaruskali” mines extracting the worked out fourth sylvinite layer at depths over 600 m. The developed recommendations are aimed at improving the work safety and efficiency when extracting abandoned mineral reserves. Using the study results, the project was developed to conduct development workings of a new panel of the longwall 11-5 that provides the necessary stability of workings for the entire period of winning operations and, ultimately, safe extraction of potash ore in the amount of at least 2 million tons.Выполнено исследование особенностей проявления горного давления и характера деформирования подготовительных и монтажных выработок в зависимости от привязки кровли и ее расположения относительно отработанных столбовой системой по слоям 2, 2-3, 3 лав, а также отработанной камерной системой панели в условиях извлечения подработанного четвертого сильвинитового слоя Третьего калийного горизонта на глубине свыше 600 м. Установлено, что срок службы вновь проектируемых выработок зависит от места их расположения на панели, привязки кровли и параметров крепления. Наибольший срок службы выработок будет отмечаться при их расположении в выработанном пространстве над отработанными лавами по нижним слоям, наименьший - при их проведении в центральной части охранных междустолбовых целиков. На основании выполненных исследований разработаны рекомендации по выбору мест заложения, привязок кровли, охране и поддержанию подготовительных выработок для участков шахтных полей рудников ОАО «Беларуськалий», извлекающих подработанный четвертый сильвинитовый слой на глубинах свыше 600 м. Разработанные рекомендации направлены на повышение безопасности и эффективности работ при выемке оставленных запасов минерального сырья. С использованием результатов исследования разработан проект проведения подготовительных выработок нового выемочного столба лавы 11-5, обеспечивающий необходимую устойчивость выработок на весь период очистных работ и, в конечном итоге, безопасную выемку калийной руды в объеме не менее 2 млн т

Meglumine Sodium Succinate to Correct COVID-19-Associated Coagulopathy: the Feasibility Study

Aim of the study: to evaluate the effect of meglumine sodium succinate (MSS) on the efficacy of anticoagulant therapy in patients with severe COVID-19 infection complicated by bilateral community-acquired pneumonia.Materials and methods. Overall efficacy of treatment was analyzed in 12 patients hospitalized to ICU with the diagnosis of severe confirmed COVID-19 coronavirus infection (U07.1) complicated by bilateral multisegmental pneumonia. All patients received prophylactic anticoagulation with unfractionated heparin. The patients were divided into two groups: 7 of them received a multi-electrolyte solution containing MSS 5 ml/kg daily for the entire ICU stay (3-10 days) as a part of therapy; 5 patients received a similar volume of a conventional multi-electrolyte solution containing no metabolically active substrates and comprised a control group. Coagulation parameters were measured in arterial and venous blood of all patients at the following stages: 1) upon admission to the ICU; 2) 2-4 hours after the first dose of heparin; 3) 8-12 hours after the second dose of heparin; 4) 24 hours after the beginning of intensive therapy. On the 28th day of follow-up, mortality, duration of ICU stay, and incidence of thrombotic complications in the groups were evaluated. Nonparametric methods of statistical analysis were used to assess intragroup changes and intergroup differences.Results. The group of patients administered with MSS had significantly fewer thromboembolic events during 28 days of treatment and shorter ICU stay. These patients responded faster to anticoagulant therapy, which was suggested by more distinct changes in coagulation parameters, i.e. increased APTT, persisting viable thrombocyte population, reduced D-dimer and fibrinogen levels.Conclusion. The metabolic action of succinate possibly increases endothelial resistance to damaging factors and reduces its procoagulant activity. The hypothesis requires testing in a larger clinical study with a design including laboratory evaluation of the efficacy of varying doses of the studied drug as well as aiming at elucidation of the mechanisms of its effect on specific pro- and anticoagulation system components

k-Essence, superluminal propagation, causality and emergent geometry

The k-essence theories admit in general the superluminal propagation of the perturbations on classical backgrounds. We show that in spite of the superluminal propagation the causal paradoxes do not arise in these theories and in this respect they are not less safe than General Relativity.Comment: 34 pages, 5 figure

Epigenetic inactivation of gene SFRP5 at breast cancer

Метилирование генов играет важную роль в развитии опухолевых заболеваний. Одним из количественных методов оценки содержания метилированной ДНК в тканях опухолей может быть пиросеквенирование. Целью данного исследования была разработка пиросеквенирования для оценки метилирования ДНК гена SFRP5 в опухолях рака молочной железы. Анализ метилирования был проведен методом количественного пиросеквенирования с использованием прибора PSQ96 ID фирмы Qiagen. Установлено, что для определения содержания метилированной ДНК гена SFRP5 в образцах ткани аденокарциномы молочной железы можно использовать метод пиросеквенирования. Метод дает количественную оценку содержания метилированной ДНК в пробе ткани рака молочной железы. Содержание метилированной ДНК у больных раком молочной железы составляло (35,96±2,23) %, тогда как в образцах условно нормальной ткани молочной железы — (6,00±1,34) % (р≤0,001).Genes methylation plays an important role in the development of cancer. Pyrosequencing technology is one of the methods of quantitative evaluation of methylated DNA level in the tumor tissue. The aim of this study is to develop pyrosequencing to analyze SFRP5 gene methylation in breast cancer. It was performed by quantitative pyrosequencing using the device PSQ96 ID (Qiagen). It was found that pyrosequencing method may be used to evaluate the level of of SFRP5 gene methlated DNA in the adenocarcinoma samples. The method quantifies the level of methylated DNA in breast cancer samples. The methylation level of SFRP5 gene in breast cancer sample was (35.96±2.23)%, whereas the level of methylated DNA in normal breast tissue (6.0±1.0)% (р≤0.001)

Vaccines against toxoplasma gondii : challenges and opportunities

Development of vaccines against Toxoplasma gondii infection in humans is of high priority, given the high burden of disease in some areas of the world like South America, and the lack of effective drugs with few adverse effects. Rodent models have been used in research on vaccines against T. gondii over the past decades. However, regardless of the vaccine construct, the vaccines have not been able to induce protective immunity when the organism is challenged with T. gondii, either directly or via a vector. Only a few live, attenuated T. gondii strains used for immunization have been able to confer protective immunity, which is measured by a lack of tissue cysts after challenge. Furthermore, challenge with low virulence strains, especially strains with genotype II, will probably be insufficient to provide protection against the more virulent T. gondii strains, such as those with genotypes I or II, or those genotypes from South America not belonging to genotype I, II or III. Future studies should use animal models besides rodents, and challenges should be performed with at least one genotype II T. gondii and one of the more virulent genotypes. Endpoints like maternal-foetal transmission and prevention of eye disease are important in addition to the traditional endpoint of survival or reduction in numbers of brain cysts after challenge