EFFECT OF M2 MACROPHAGE-DERIVED SOLUBLE FACTORS ON DIFFERENTIATION OF SH-SY5Y CELLS

Macrophages play a key role in triggering and regulation of neuroregeneration. The characteristic feature of macrophages is pronounced plasticity, which manifests itself in the ability of macrophages to change their functional phenotype depending on the micromilieu. Apoptotic cell clearance (efferocytosis) is an important inducer of a macrophage polarization to M2 phenotype under pathological settings. Previously, we have developed an original protocol for the generation of M2-like macrophages, polarized by efferocytosis under serum-deprived conditions (M2 (LS), Low Serum). The present study was aimed to assess a neuroregenerative potential of M2 (LS) macrophages. We studied their effect on the differentiation of SH-SY5Y cells in comparison with retinoic acid (RA). As the morphological criteria of differentiation we have assessed the relative content of differentiated cells, i.e., cells with a neurite length exceeding the cell body length, and the average neurite length on days 3, 7, and 13. The ratio of neuron-like (N-type) and epithelial-like (S-type) cells in cultures was also assessed. SH-SY5Y cells were characterized by a low level of spontaneous differentiation, both under standard conditions (10% FBS) and serum deprivation (1% FBS). Upon RA treatment, SH-SY5Y cells stopped proliferating and underwent neuronal differentiation. Cultivation of SH-SY5Y cells in the presence of M2 (LS) conditioned medium also led to a significant increase in the relative content of differentiated cells, the average length of neurite-like processes, as well as a change in the balance of S- and N-type cells towards a pronounced predominance of the latter. The morphological features of differentiation were significantly less pronounced at early stage (day 3) of differentiation as compared with the RA-induced changes and reached the level of positive control only at later stages (day 13) (p < 0.05). In contrast to retinoic acid, M2 (LS) conditioned medium induced neuronal differentiation of SH-SY5Y cells without suppressing their proliferative activity. The data obtained may indicate a high neuroregenerative potential of M2 macrophages in vitro, which is realized through soluble factors and manifests itself in promoting SH-SY5Y differentiation

Improved measurements of the energy and shower maximum of cosmic rays with Tunka-Rex

The Tunka Radio Extension (Tunka-Rex) is an array of 63 antennas located in the Tunka Valley, Siberia. It detects radio pulses in the 30-80 MHz band produced during the air-shower development. As shown by Tunka-Rex, a sparse radio array with about 200 m spacing is able to reconstruct the energy and the depth of the shower maximum with satisfactory precision using simple methods based on parameters of the lateral distribution of amplitudes. The LOFAR experiment has shown that a sophisticated treatment of all individually measured amplitudes of a dense antenna array can make the precision comparable with the resolution of existing optical techniques. We develop these ideas further and present a method based on the treatment of time series of measured signals, i.e. each antenna station provides several points (trace) instead of a single one (amplitude or power). We use the measured shower axis and energy as input for CoREAS simulations: for each measured event we simulate a set of air-showers with proton, helium, nitrogen and iron as primary particle (each primary is simulated about ten times to cover fluctuations in the shower maximum due to the first interaction). Simulated radio pulses are processed with the Tunka-Rex detector response and convoluted with the measured signals. A likelihood fit determines how well the simulated event fits to the measured one. The positions of the shower maxima are defined from the distribution of chi-square values of these fits. When using this improved method instead of the standard one, firstly, the shower maximum of more events can be reconstructed, secondly, the resolution is increased. The performance of the method is demonstrated on the data acquired by the Tunka-Rex detector in 2012-2014.Comment: Proceedings of the 35th ICRC 2017, Busan, Kore

IMMUNOMODULATORY EFFECT OF CIRCULATING BONE MARROW PROGENITORS AS A POSSIBLE MECHANISM OF NEUROPROTECTION IN TRAUMATIC BRAIN INJURY

We have previously shown that acute traumatic brain injury (TBI) is accompanied by increased level of circulating bone marrow progenitors, and favorable outcome is associated with early mobilization of CD34+CD45+ hematopoietic progenitor cells (HP). The present study was aimed at investigating whether patients with early HP mobilization differed from those with mobilization failure by systemic inflammatory reaction and immune parameters. The TBI patients were characterized by increased levels of serum C-reactive protein (CRP), IL-1в, IL-6, IL-8, MCP-1, G-CSF and IL-1ra indicative for presence of systemic inflammatory response. Importantly, patients with lacking mobilization of early HPs were shown to have significantly higher serum levels of CRP, MCP-1, MIP-1в, and G-CSF and a lower level of VEGF. In addition, patients with lack of early HP mobilization differed by significantly lower absolute number of lymphocytes, CD3+ T cells, CD4+ T cells, CD16+ NK cells and proliferative response of mononuclear cells to stimulation with ConA as well as by 4-fold higher rate of infectious complications compared with the opposite group. These data suggest that correlation of early mobilization of CD34+CD45+ cells with a favorable outcome in TBI patients may be partially mediated by anti-inflammatory and immunomodulatory effects of circulating bone marrow progenitors

First analysis of inclined air showers detected by Tunka-Rex

The Tunka Radio Extension (Tunka-Rex) is a digital antenna array for the detection of radio emission from cosmic-ray air showers in the frequency band of 30 to 80 MHz and for primary energies above 100 PeV. The standard analysis of Tunka-Rex includes events with zenith angle of up to 50$^\circ$. This cut is determined by the efficiency of the external trigger. However, due to the air-shower footprint increasing with zenith angle and due to the more efficient generation of radio emission (the magnetic field in the Tunka valley is almost vertical), there are a number of ultra-high-energy inclined events detected by Tunka-Rex. In this work we present a first analysis of a subset of inclined events detected by Tunka-Rex. We estimate the energies of the selected events and test the efficiency of Tunka-Rex antennas for detection of inclined air showers.Comment: ARENA2018 proceeding

Signal recognition and background suppression by matched filters and neural networks for Tunka-Rex

The Tunka Radio Extension (Tunka-Rex) is a digital antenna array, which measures the radio emission of the cosmic-ray air-showers in the frequency band of 30-80 MHz. Tunka-Rex is co-located with TAIGA experiment in Siberia and consists of 63 antennas, 57 of them are in a densely instrumented area of about 1 km\textsuperscript{2}. In the present work we discuss the improvements of the signal reconstruction applied for the Tunka-Rex. At the first stage we implemented matched filtering using averaged signals as template. The simulation study has shown that matched filtering allows one to decrease the threshold of signal detection and increase its purity. However, the maximum performance of matched filtering is achievable only in case of white noise, while in reality the noise is not fully random due to different reasons. To recognize hidden features of the noise and treat them, we decided to use convolutional neural network with autoencoder architecture. Taking the recorded trace as an input, the autoencoder returns denoised trace, i.e. removes all signal-unrelated amplitudes. We present the comparison between standard method of signal reconstruction, matched filtering and autoencoder, and discuss the prospects of application of neural networks for lowering the threshold of digital antenna arrays for cosmic-ray detection.Comment: ARENA2018 proceeding

Large negative velocity gradients in Burgers turbulence

We consider 1D Burgers equation driven by large-scale white-in-time random force. The tails of the velocity gradients probability distribution function (PDF) are analyzed by saddle-point approximation in the path integral describing the velocity statistics. The structure of the saddle-point (instanton), that is velocity field configuration realizing the maximum of probability, is studied numerically in details. The numerical results allow us to find analytical solution for the long-time part of the instanton. Its careful analysis confirms the result of [Phys. Rev. Lett. 78 (8) 1452 (1997) [chao-dyn/9609005]] based on short-time estimations that the left tail of PDF has the form ln P(u_x) \propto -|u_x|^(3/2).Comment: 10 pages, RevTeX, 10 figure

Current Status and New Challenges of The Tunka Radio Extension

The Tunka Radio Extension (Tunka-Rex) is an antenna array spread over an area of about 1~km$^2$. The array is placed at the Tunka Advanced Instrument for cosmic rays and Gamma Astronomy (TAIGA) and detects the radio emission of air showers in the band of 30 to 80~MHz. During the last years it was shown that a sparse array such as Tunka-Rex is capable of reconstructing the parameters of the primary particle as accurate as the modern instruments. Based on these results we continue developing our data analysis. Our next goal is the reconstruction of cosmic-ray energy spectrum observed only by a radio instrument. Taking a step towards it, we develop a model of aperture of our instrument and test it against hybrid TAIGA observations and Monte-Carlo simulations. In the present work we give an overview of the current status and results for the last five years of operation of Tunka-Rex and discuss prospects of the cosmic-ray energy estimation with sparse radio arrays.Comment: Proceedings of E+CRS 201

Consistent alpha-cluster description of the 12C (0^+_2) resonance

The near-threshold 12C (0^+_2) resonance provides unique possibility for fast helium burning in stars, as predicted by Hoyle to explain the observed abundance of elements in the Universe. Properties of this resonance are calculated within the framework of the alpha-cluster model whose two-body and three-body effective potentials are tuned to describe the alpha - alpha scattering data, the energies of the 0^+_1 and 0^+_2 states, and the 0^+_1-state root-mean-square radius. The extremely small width of the 0^+_2 state, the 0_2^+ to 0_1^+ monopole transition matrix element, and transition radius are found in remarkable agreement with the experimental data. The 0^+_2-state structure is described as a system of three alpha-particles oscillating between the ground-state-like configuration and the elongated chain configuration whose probability exceeds 0.9

VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTOR-1 SIGNALING AS A NOVEL MECHANISM OF T CELL SUPPRESSION IN TUMOR NEOANGIOGENESIS

The immunomodulatory activity of vascular endothelial growth factors (VEGFs) reveals a new role of neoangiogenesis in tumor development. Most of VEGF effects on T cells are mediated through the VEGF-R2 receptors. Placental growth factor (PlGF) belongs to the VEGFs family and is a selective ligand for VEGF-R1. In order to study the role of VEGF-R1-signaling in the regulation of T-cell functions, the effect of PlGF on the proliferation of donor T cell has been investigated. PlGF has been shown to inhibit the proliferation of T-lymphocytes in cultures of anti-CD3-stimulated mononuclear cells in a wide dose range, suppressing the proliferative response of both CD4 + and CD8 + T cells. The suppressive effect of PlGF was mediated through the direct interaction with VEGFR-1 on T-cells that was evidenced by the expression of VEGFR-1 by T-lymphocytes (especially after their activation) and by blocking the suppressive effect of PlGF with neutralizing anti-VEGFR-1 antibodies. Given the increased levels of PlGF in many tumors, this factor may play an important role in immunomodulation during tumor growth, mediating its effect through the VEGFR-1 signaling pathway