On the governing equations for Poisson and Skellam processes time-changed by inverse subordinators

In the paper we present the governing equations for marginal distributions of Poisson and Skellam processes time-changed by inverse subordinators. The equations are given in terms of convolution-type derivatives

Дослiдження розв’язкiв дисперсiйних рiвнянь старшого порядку з φ-субгауссовими початковими умовами

In this paper, there are studied sample paths properties of stochastic processes representing solutions of higher-order dispersive equations with random initial conditions given by φ-sub-Gaussian harmonizable processes. The main results are the bounds for the rate of growth of such stochastic processes considered over unbounded domains. The class of φ-sub-Gaussian processes with φ(x) = |x|^α/α, 1 < α <= 2, is a natural generalization of Gaussian processes. For such initial conditions the bounds for the distribution of supremum of solutions can be calculated in rather simple form. The bounds for the rate of growth of solution to higher-order partial differential equations with random initial conditions in the case of general φ were obtained in [9], the derivation was based on the sults stated in [1]. Here we use another approach, which allows us, for the particular case φ(x) = |x|^α/α, α є (1, 2], to present the expressions for the bounds in the closed form. Pages of the article in the issue: 78 - 84 Language of the article: EnglishIn this paper, there are studied sample paths properties of stochastic processes representing solutions of higher-order dispersive equations with random initial conditions given by φ-sub-Gaussian harmonizable processes. The main results are the bounds for the rate of growth of such stochastic processes considered over unbounded domains. The class of φ-sub-Gaussian processes with φ(x) = |x|^α/α, 1 < α <= 2, is a natural generalization of Gaussian processes. For such initial conditions the bounds for the distribution of supremum of solutions can be calculated in rather simple form. The bounds for the rate of growth of solution to higher-order partial differential equations with random initial conditions in the case of general φ were obtained in [9], the derivation was based on the sults stated in [1]. Here we use another approach, which allows us, for the particular case φ(x) = |x|^α/α, α є (1, 2], to present the expressions for the bounds in the closed form

Властивостi розв’язкiв лiнiйного рiвняння KdV iз φ-субгауссовими початковими умовами

In this paper, there are studied sample paths properties of stochastic processes representing solutions (in L_2(Ω) sense) to the linear Korteweg–de Vries equation (called also the Airy equation) with random initial conditions given by φ-sub-Gaussian stationary processes. The main results are the bounds for the distributions of the suprema for such stochastic processes considered over bounded domains. Also, there are presented some examples to illustrate the results of the study. Pages of the article in the issue: 11 - 19 Language of the article: EnglishВажливий практичний аспект оцiнювання статистичних властивостей фiзичних систем спирається на ефективне представлення зв’язку мiж розв’язками рiвнянь з частинними похiдними та випадковими початковими умовами. У цiй роботi дослiджуються властивостi траєкторiй випадкових процесiв, що задають розв’язки (в L_2(Ω)) для рiвняння Айрi з φ-субгауссовими стацiонарними випадковими початковими умовами. Властивостi субгауссовостi та φ-субгауссовостi є важливими характеристиками випадкових процесiв, оскiльки вони дають можливiсть оцiнити рiзнi функцiонали вiд цих процесiв, i, зокрема, дослiдити поведiнку їх супремумiв. Основнi результати роботи – це оцiнки для розподiлiв супремумiв випадкових процесiв, що задають розв’язки для рiвняння Айрi, на обмежених множинах. Застосування отриманих результатiв проiлюстровано на прикладах у випадках гауссових початкових умов з рiзними допустимими функцiями та φ-субгауссових початкових умов з певними функцiями φ, зокрема φ(x) = exp{|x|} − |x| − 1, x \in R

Lox-dependent gene expression in transgenic plants obtained via Agrobacterium-mediated transformation

Lox sites of the Cre/lox recombination system from bacteriophage P1 were analyzed for their ability to affect on transgene expression when inserted upstream from a gene coding sequence adjacent to the right border (RB) of T-DNA. Wild and mutated types of lox sites were tested for their effect upon bar gene expression in plants obtained via Agrobacterium-mediated and biolistic transformation methods. Lox-mediated expression of bar gene, recognized by resistance of transgenic plants to PPT, occurred only in plants obtained via Agrobacterium-mediated transformation. RT-PCR analysis confirms that PPT-resistant phenotype of transgenic plants obtained via Agrobacterium-mediated transformation was caused by activation of bar gene. The plasmid with promoterless gus gene together with the lox site adjacent to the RB was constructed and transferred to Nicotiana tabacum as well. Transgenic plants exhibited GUS activity and expression of gus gene was detected in plant leaves. Expression of bar gene from the vectors containing lox site near RB allowed recovery of numerous PPT-resistant transformants of such important crops as Beta vulgaris, Brassica napus, Lactuca sativa and Solanum tuberosum. Our results demonstrate that the lox site sequence adjacent to the RB can be used to control bar gene expression in transgenic plants.Проанализирована способность lox-сайтов Cre/lox системы рекомбинации бактериофага Р1 влиять на экспрессию трансгенов при расположении этой последовательности непосредственно возле правого бордера (RB) перед кодирующей последовательностью гена. Нативная и мутированная последовательность lox-сайта были размещены в векторах для трансформации возле гена bar и проведена генетическая трансформация растений с помощью агробактерии и биолистическим методом. Lox-опосредованная экспрессия гена bar, обусловливающая устойчивость растений к фосфинотрицину, наблюдалась только у растений, которые получены с помощью агробактериальной трансформации. Методом РТ-ПЦР анализа подтверждено, что в трансгенных растениях, устойчивых к фосфинотрицину, происходит транскрипция гена bar. Сконструирован вектор, в котором ген gus и предшествующий ему lox-сайт размещены вблизи правого бордера, и проведена трансформация табака этим вектором. Экспрессия гена gus задетектирована в листьях трансгенных растений. Векторы, у которых последовательность lox-сайта предшествует гену bar возле правого бордера (RB-lox-bar), успешно использованы для получения устойчивых к фосфинотрицину трансгенных растений таких видов, как Beta vulgaris, Brassica napus, Lactuca sativa и Solanum tuberosum. Наши результаты подтверждают возможность использования последовательности lox-сайта возле правого бордера для контроля экспрессии гена bar в трансгенных растениях

Мiжнародна наукова конференцiя “Сучасна стохастика: теорiя та застосування. V” (MSTA-V). 1-4 червня 2021

Pages of the article in the issue: 9 Language of the article: UkrainianPages of the article in the issue: 9 Language of the article: Ukrainia

INTERLEUKIN-10 REGULATES PD-1-B7-H1-MEDIATED CYTOTOXIC ACTIVITY OF DENDRITIC CELLS

In this investigation the phenotypic and functional properties of healthy donor and patient with pulmonary tuberculosis (PT) dendritic cells (DCs) were characterized. We also studied the influence of IL-10 on the phenotype and apoptosis-inducing activity of healthy donor DCs. 60 patients with pulmonary tuberculosis with different proliferative response to antigens of M. tuberculosis (purified protein derivative, PPD) and 40 healthy donors were enrolled in this study. It was revealed that DCs, generated in vitro from PT patient's blood monocytes with GM-CSF+IFN-α, were characterized by increased B7-H1 expression, up-production of IL-10 and reducing of allostimulatory activity in mixed lymphocyte culture (MLC). The endogenous IL-10 production by DCs was correlated with expression of B7-H1 in the general group of persons. It was revealed that addition of IL-10 to semi-mature DCs of healthy donor results in increasing of B7-H1 expression, diminishing of allostimulatory activity and enlargement of pro-apoptogenic activity of DCs

INTRANASAL INHALATIONS OF BIOACTIVE FACTORS PRODUCED BY M2 MACROPHAGES IN THE TREATMENT OF PATIENTS WITH ORGANIC BRAIN SYNDROME

The aim of present study was to evaluate safety and clinical efficacy of inhalatory immunotherapy based on intranasal delivery of bioactive factors produced by M2 macrophages applied for treatment of patients with organic brain syndrome (OBS).Materials and methods. The study under the NCT02957123 protocol (www.ClinicalTrails.gov) included thirty patients with OBS of various genesis (10 men and 20 women aged 18 to 81; Me, 62.5 years). Neurological assessment and the levels of 32 cytokines in the blood serum of patients were evaluated before and 2-3 days after completion of inhalation immunotherapy.Intranasal inhalations of cell-free culture medium of M2 macrophages (2 mL, once a day for 28-30 days) were safe and well tolerated. None of 30 treated patients had severe adverse events and serious treatmentrelated side reactions. One month after starting the inhalations, a positive dynamics in neurological status was noted in all the patients. A marked clinical response was documented in twenty out of thirty patients (67%), which manifested as improvement, according to all scales and questionnaires. The neurological improvement was not reversed over 6 months of follow-up period. In other ten patients (33%), a moderate clinical response was shown as improvement of individual scores. The positive changes were as follows: 1) a 43% decrease in anxiety and depression scores (according to HADS scale, pU = 0.0008); 2) an increase of total motor activity (stability and gait) by 25%, pU = 0.0001); 3) correction of cognitive functions (MoCa test, pU = 0.007); 4) reduced number and intensity of the disease symptoms by 52% (pU = 0.0001). This marked clinical response to immunotherapy is shown to be associated with correction/normalization of serum hepatocyte growth factor (HGF) level.Conclusion. Inhalation immunotherapy based on intranasal delivery of bioactive factors produced by M2 macrophages can improve neurological and functional recovery in patients with organic brain syndrome

Expression of arginase 1 and tyrosine kinase Mer by blood monocytes in the dynamics of physiological pregnancy

During pregnancy, the maternal immune system must maintain tolerance to paternal antigens, at the same time being able to eliminate pathogens, which is achieved by the weakening of adoptive immunity and the activation of innate immunity, in particular, monocytes. However, the question about the functional phenotype of monocytes, having not only pro-inflammatory, but also anti-inflammatory activity, remains open. In the given work, we have investigated the expression of M2-associated suppressive markers Arg1 and MerTK in monocyte subpopulations during uncomplicated pregnancy. Fifty-three pregnant women with uncomplicated gestation were recruited, including 14 pregnant in the 1st trimester, 20 – in the 2nd and 19 – in the third pregnancy trimester. The comparison group consisted of 15 fertile unpregnant women without aggravated somatic anamnesis, with a history of at least one childbirth. The findings showed that in the unpregnant group circulating Mo express Arg1 and MerTK, and the most relative number of Arg1+ and MerTK+ cells is concentrated in intermediate and nonclassic monocytes. During pregnancy the expression of researched molecules in monocytes reliably increases. An increase in MerTK expression is manifested by a simultaneous increase in the number of MerTK+ cells and the mean fluorescence intensity of this marker; it is observed in the 1st and 2nd trimesters and registered in all three monocyte subpopulations. At the same time, an increase in Arg1 expression is manifested either by an enhancement of Arg1+ cells, or an increase in receptor density; it is registered throughout pregnancy, including the 3rd trimester, and is maximally expressed in classic monocytes. There is a direct correlation between the number of Arg1+ and MerTK+ cells in intermediate Mo, which increases with the progression of pregnancy, and in the 3rd trimester is also detected in classical and non-classical Mo. In general, the revealed increase in the expression of Arg1 and MerTK by monocytes indicates an increase in the anti-inflammatory potential of monocytes during pregnancy, and the involvement of monocytes in the regulation of the inflammatory process at the system level. Moreover, the features of Arg1 and MerTK expression in various monocyte subpopulations during pregnancy suggest that monocytes expressing Arg1 and MerTK can mediate different mechanisms of immune adaptation during pregnancy

M-CSF and GM-CSF determinate fibromodulatory activity of polarized human macrophages

GM-CSF and M-CSF, the hematopoietic colony-stimulating factors, induce various phenotypic changes in macrophage lineage populations and promote cell differentiation, respectively, into M1- and M2-like macrophages. The pro- and anti-inflammatory properties of macrophages generated by these colony-stimulating factors are well described, but the contribution of differentiation and polarization signals to the fibromodulatory activity of macrophages remains unexplored. To clarify the differences in the fibrogenesis regulation mechanisms inherent in differently activated macrophages, we studied the effects of macrophage-conditioned media on proliferation and differentiation of dermal fibroblasts. In this study, the human macrophages generated from peripheral blood monocytes were investigated. They were induced for differentiation by M-CSF or GM-CSF, being further polarized in the M1 direction with lipopolysaccharide and, in the M2 direction, with IL-4 or dexamethasone. Proliferative response of the fibroblasts was determined radiometrically by [3H]-thymidine incorporation. Differentiation into myofibroblasts was determined with flow cytometry technique, as expression of a specific marker α-smooth muscle actin (α-SMA). The level of macrophage TGF-β1 production was assessed using an appropriate ELISA kit. The data obtained indicate that the macrophages differentiated under the influence of “homeostatic” M-CSF are characterized by a moderate stimulating effect upon fibroblast proliferation, and the effects of M2 (IL-4) and M2 (Dex) macrophages exceed that of M1 (LPS), but do not differ significantly from each other. The M-CSF-induced M1 (LPS) and M2 (IL-4) macrophages, but not M2 (Dex), enhance the fibroblast differentiation and show similar level of stimulation. In contrast to M-CSF, the macrophages induced by “pro-inflammatory” GM-CSF exhibit a pronounced stimulatory effect on fibroblast proliferation, and the effects of M2 macrophages exceed those of M1 cells, being most pronounced for M2 (Dex). At the same time, only GM-CSF-induced M2 (IL-4) macrophages enhance fibroblast differentiation. Dexamethasone-polarized macrophages do not significantly affect fibroblast differentiation regardless of the CSF used (M-CSF or GM-CSF). The content of TGF-β1 in the supernatants of differently activated macrophages does not correlate with the level of stimulating effect of macrophage-conditioned media upon fibroblast differentiation. In general, the data obtained suggest the involvement of differentiation and polarization signals into modulation of pro- and anti-fibrogenic properties of macrophages

M2-LIKE MACROPHAGES ARE POTENTIAL CANDIDATES FOR BRAIN STROKE OUTCOMES' TREATMENT

The safety and effectiveness of in vitro generated M2-like macrophages for treatment of patients with ischemic and hemorrhagic brain stroke in reparative and residual periods has been evaluated. A single endolumbar administration of autologous M2-like macrophages in the mean dose of 17,9 х 106 cells was conducted in 13 patients with ischemic (n = 10) and hemorrhagic (n = 3) brain stroke. At 6 months after cells administration all the patients had clinical Improvement. NIHS score decreased from 8,6 ± 1,06 to 4,4 ± 0.55 (p = 0,0008), several patients showed the decrease of sensitiveness impairments, improvement of cognitive functions and enhanced quality of life. Thus, we demonstrated an ability of generation M2-like macrophages from patients with brain stroke. Endolumbar administration of these cells was safe andi didn't cause severe adverse effects and complications andi — in preliminary data — improvedi motional and cognitive functions