Моторвагонные грузовые электропоезда – альтернатива локомотивной тяге. Сравнение и анализ

The advantages of introduction of modular freight electric trains in comparison with freight trains using locomotive traction are described, the main prerequisites for introduction of a distributed multiple-unit freight traction are indicated. The results of comparison of the technology of transportation with traction by locomotive situated at the head of the train and by the train with self-propelled coaches, as well as the analysis of traction calculations of two types of trains are suggested. The international experience of developing freight trains with distributed traction is described.The main directions of implementation of the concept of accelerating freight transportation on the territory of the Russian Federation are noted. It is concluded that in modern conditions, when speed becomes an economic category, it is necessary to create rolling stock of a new generation (wheel and magnetic suspension), and introduction of freight trains with distributed traction becomes extremely relevant.Описаны преимущества внедрения модульных грузовых электропоездов в сравнении с грузовыми поездами локомотивной тяги, указаны основные предпосылки для внедрения распределённой моторвагонной грузовой тяги. Приведены результаты сравнения технологии перевозок тягой в голове поезда и поездом с моторными вагонами в составе, а также анализ тяговых расчётов двух видов поездов. Описан международный опыт создания грузовых поездов распределённой тяги.Отмечены основные направления реализации концепции ускорения грузовых перевозок по территории Российской Федерации. Делается вывод, что в современных условиях, когда скорость становится экономической категорией, необходимо создавать подвижной состав нового поколения (колёсный и на магнитном подвесе), а вопросы внедрения грузовых поездов распределённой тяги вновь становятся крайне актуальными

Tumor inflating lymphocytes. Purification, expanding and cytotoxicity analisys on primary tumor cultures

Background. Tumor Infiltrating Lymphocytes (TILs) is one of the most promising sources of autologous cytotoxic T-cells for adoptive immunotherapy, which has already shown high efficiency in the treatment of metastatic melanoma. However, the isolation of TILs from solid tumors is technically difficult. A suppressive tumor microenvironment, in particular, a high level of expression of check-point inhibitors PD-1 CTLA4, tissue hypoxia and other factors cause that T cells isolated from the tumor do not proliferate well and do not exhibit cytotoxic properties. Aims. In this study, we isolated TILs from surgical material obtained by resection of solid tumors (primary and metastatic adenocarcinomas of various localization, melanoma, glioblastoma), studied their population composition and developed protocols for the purification expanding, and activation of CD4+, CD8+ cytotoxic antitumor lymphocytes. Methods. An urgent task is the activation of TILs, turning off immunosuppressive mechanisms and increasing their antitumor cytotoxic activity. Various approaches are used for this: activation by a cocktail of cytokines and antibodies, editing the lymphocyte genome by knocking out suppressor genes or, conversely, transduction of activating genes, coincubation with feeder cells, etc. Cells were obtained from samples of resected tumors in 16 patients; in each case we obtain an autologous pair: the primary tumor culture and the TILs culture. Results. We could isolate viable lymphocytes in 100% of cases. Isolated TILs were successfully expanded in our specialized medium using various combinations of IL-2, IL-15, IL-21, IL-7, anti-CD3 and anti-CD28. Immunophenotyping showed that the obtained TILs are a heterogeneous mixture of CD4+, CD8+ cells containing populations of CD3+CD8+CD45+(CTL) CD3+CD4+CD45+ (T-helpers), CD4+CD25+CD127- (Т-regulatory cells), CD3-CD56+CD45+ (NK-cells), CD3+CD56+CD45+ (Т-NK-cells). The initial cultures of TILs were also characterized by a high level of PD1 expression, indicating their low antitumor cytotoxicity. Using different protocols of isolation, expansion, and activation, we obtained a cell preparation containing 80% of CD8+ PD-1- activated TILs in an amount sufficient for adoptive therapy (500106 or more). An in vitro study of the cytotoxicity of obtained TILs in primary cultures of homologous tumors using RTCA Icelligence showed high cytotoxicity, providing almost 100% tumor cell death. Conclusion. Our developed protocol for the production and activation of TILs can be recommended for the phase III clinical trials of adoptive immunotherapy of recurrent, highly metastatic solid tumors

The Repeating Flaring Activity of Blazar AO 0235+164

Context. Blazar AO 0235+164, located at redshift z = 0.94, has undergone several sharp multi-spectral-range flaring episodes during the last decades. In particular, the episodes peaking in 2008 and 2015, that received extensive multi-wavelength coverage, exhibited interesting behavior. Aims. We study the actual origin of these two observed flares by constraining the properties of the observed photo-polarimetric variability, those of the broad-band spectral energy-distribution and the observed time-evolution behavior of the source as seen by ultra-high resolution total-flux and polarimetric Very-long-baseline interferometry (VLBI) imaging. Methods. The analysis of VLBI images allows us to constrain kinematic and geometrical parameters of the 7 mm jet. We use the Discrete Correlation Function to compute the statistical correlation and the delays between emission at different spectral ranges. Multi-epoch modeling of the spectral energy distributions allows us to propose specific models of emission; in particular for the unusual spectral features observed in this source in the X-ray region of the spectrum during strong multi spectral-range flares. Results. We find that these X-ray spectral features can be explained by an emission component originating in a separate particle distribution than the one responsible for the two standard blazar bumps. This is in agreement with the results of our correlation analysis that do not find a strong correlation between the X-rays and the remaining spectral ranges. We find that both external Compton dominated and synchrotron self-Compton dominated models can explain the observed spectral energy distributions. However, synchrotron self-Compton models are strongly favored by the delays and geometrical parameters inferred from the observations

Extreme photometric and polarimetric variability of blazar S4 0954+65 at its maximum optical and γ-ray brightness levels

In 2022 the BL Lac object S4 0954+65 underwent a major variability phase, reaching its historical maximum brightness in the optical and γ -ray bands. We present optical photometric and polarimetric data acquired by the Whole Earth Blazar Telescope (WEBT) Collaboration from 2022 April 6 to July 6. Many episodes of unprecedented fast variability were detected, implying an upper limit to the size of the emitting region as low as 10−4 parsec. The WEBT data show rapid variability in both the degree and angle of polarization. We analyse different models to explain the polarization behaviour in the framework of a twisting jet model, which assumes that the long-term trend of the flux is produced by variations in the emitting region viewing angle. All the models can reproduce the average trend of the polarization degree, and can account for its general anticorrelation with the flux, but the dispersion of the data requires the presence of intrinsic mechanisms, such as turbulence, shocks, or magnetic reconnection. The WEBT optical data are compared to γ -ray data from the Fermi satellite. These are analysed with both fixed and adaptive binning procedures. We show that the strong correlation between optical and γ -ray data without measurable delay assumes different slopes in faint and high brightness states, and this is compatible with a scenario where in faint states we mainly see the imprint of the geometrical effects, while in bright states the synchrotron self-Compton process dominates

The variability patterns of the TeV blazar PG 1553+113 from a decade of MAGIC and multi-band observations

PG 1553+113 is one of the few blazars with a convincing quasi-periodic emission in the gamma-ray band. The source is also a very high-energy (VHE; >100 GeV) gamma-ray emitter. To better understand its properties and identify the underlying physical processes driving its variability, the MAGIC Collaboration initiated a multiyear, multiwavelength monitoring campaign in 2015 involving the OVRO 40-m and Medicina radio telescopes, REM, KVA, and the MAGIC telescopes, Swift and Fermi satellites, and the WEBT network. The analysis presented in this paper uses data until 2017 and focuses on the characterization of the variability. The gamma-ray data show a (hint of a) periodic signal compatible with literature, but the X-ray and VHE gamma-ray data do not show statistical evidence for a periodic signal. In other bands, the data are compatible with the gamma-ray period, but with a relatively high p-value. The complex connection between the low and high-energy emission and the non-monochromatic modulation and changes in flux suggests that a simple one-zone model is unable to explain all the variability. Instead, a model including a periodic component along with multiple emission zones is required.Comment: Accepted for publication in Monthly Notices of the Royal Astronomical Society. 19 pages, 9 figures. Corresponding authors: Elisa Prandini, Antonio Stamerra, Talvikki Hovatt

Multimessenger Characterization of Markarian 501 during Historically Low X-Ray and γ-Ray Activity

We study the broadband emission of Mrk 501 using multiwavelength observations from 2017 to 2020 performed with a multitude of instruments, involving, among others, MAGIC, Fermi's Large Area Telescope (LAT), NuSTAR, Swift, GASP-WEBT, and the Owens Valley Radio Observatory. Mrk 501 showed an extremely low broadband activity, which may help to unravel its baseline emission. Nonetheless, significant flux variations are detected at all wave bands, with the highest occurring at X-rays and very-high-energy (VHE) 3-rays. A significant correlation (>3σ) between X-rays and VHE 3-rays is measured, supporting leptonic scenarios to explain the variable parts of the emission, also during low activity. This is further supported when we extend our data from 2008 to 2020, and identify, for the first time, significant correlations between the Swift X-Ray Telescope and Fermi-LAT. We additionally find correlations between high-energy 3-rays and radio, with the radio lagging by more than 100 days, placing the 3-ray emission zone upstream of the radio-bright regions in the jet. Furthermore, Mrk 501 showed a historically low activity in X-rays and VHE 3-rays from mid-2017 to mid-2019 with a stable VHE flux (>0.2 TeV) of 5% the emission of the Crab Nebula. The broadband spectral energy distribution (SED) of this 2 yr long low state, the potential baseline emission of Mrk 501, can be characterized with one-zone leptonic models, and with (lepto)-hadronic models fulfilling neutrino flux constraints from IceCube. We explore the time evolution of the SED toward the low state, revealing that the stable baseline emission may be ascribed to a standing shock, and the variable emission to an additional expanding or traveling shock. © 2023. The Author(s). Published by the American Astronomical Society

The variability patterns of the TeV blazar PG 1553 + 113 from a decade of MAGIC and multiband observations

PG 1553 + 113 is one of the few blazars with a convincing quasi-periodic emission in the gamma-ray band. The source is also a very high energy (VHE; >100 GeV) gamma-ray emitter. To better understand its properties and identify the underlying physical processes driving its variability, the MAGIC Collaboration initiated a multiyear, multiwavelength monitoring campaign in 2015 involving the OVRO 40-m and Medicina radio telescopes, REM, KVA, and the MAGIC telescopes, Swift and Fermi satellites, and the WEBT network. The analysis presented in this paper uses data until 2017 and focuses on the characterization of the variability. The gamma-ray data show a (hint of a) periodic signal compatible with literature, but the X-ray and VHE gamma-ray data do not show statistical evidence for a periodic signal. In other bands, the data are compatible with the gamma-ray period, but with a relatively high p-value. The complex connection between the low- and high-energy emission and the non-monochromatic modulation and changes in flux suggests that a simple one-zone model is unable to explain all the variability. Instead, a model including a periodic component along with multiple emission zones is required

Multi-year characterisation of the broad-band emission from the intermittent extreme BL Lac 1ES 2344+514

Aims. The BL Lac 1ES 2344+514 is known for temporary extreme properties characterised by a shift of the synchrotron spectral energy distribution (SED) peak energy νsynch;p above 1 keV. While those extreme states have only been observed during high flux levels thus far, additional multi-year observing campaigns are required to achieve a coherent picture. Here, we report the longest investigation of the source from radio to very high energy (VHE) performed so far, focussing on a systematic characterisation of the intermittent extreme states. Methods.We organised a monitoring campaign covering a 3-year period from 2019 to 2021.Morethan ten instruments participated in the observations in order to cover the emission from radio to VHE. In particular, sensitive X-ray measurements by XMM-Newton, NuSTAR, and AstroSat took place simultaneously with multi-hour MAGIC observations, providing an unprecedented constraint of the two SED components for this blazar. Results. While our results confirm that 1ES 2344+514 typically exhibits νsynch;p > 1 keV during elevated flux periods, we also find periods where the extreme state coincides with low flux activity. A strong spectral variability thus happens in the quiescent state, and is likely caused by an increase in the electron acceleration efficiency without a change in the electron injection luminosity. On the other hand, we also report a strong X-ray flare (among the brightest for 1ES 2344+514) without a significant shift of νsynch;p. During this particular flare, the X-ray spectrum is among the softest of the campaign. It unveils complexity in the spectral evolution, where the common harder-when-brighter trend observed in BL Lacs is violated. By combining Swift-XRT and Swift-UVOT measurements during a low and hard X-ray state, we find an excess of the UV flux with respect to an extrapolation of the X-ray spectrum to lower energies. This UV excess implies that at least two regions significantly contribute to the infrared/optical/ultraviolet/X-ray emission. Using the simultaneous MAGIC, XMM-Newton, NuSTAR, and AstroSat observations, we argue that a region possibly associated with the 10 GHz radio core may explain such an excess. Finally, we investigate a VHE flare, showing an absence of simultaneous variability in the 0.3-2 keV band. Using time-dependent leptonic modelling, we show that this behaviour, in contradiction to single-zone scenarios, can instead be explained by a two-component model

Multi-year characterisation of the broad-band emission from the intermittent extreme BL Lac 1ES~2344+514

The BL Lac 1ES 2344+514 is known for temporary extreme properties (e.g., a shift of the synchrotron SED peak energy $\nu_{synch,p}$ above 1keV). While those extreme states were so far observed only during high flux levels, additional multi-year observing campaigns are required to achieve a coherent picture. Here, we report the longest investigation of the source from radio to VHE performed so far, focusing on a systematic characterisation of the intermittent extreme states. While our results confirm that 1ES 2344+514 typically exhibits $\nu_{synch,p}>$1keV during elevated flux periods, we also find periods where the extreme state coincides with low flux activity. A strong spectral variability thus happens in the quiescent state, and is likely caused by an increase of the electron acceleration efficiency without a change in the electron injection luminosity. We also report a strong X-ray flare (among the brightest for 1ES 2344+514) without a significant shift of $\nu_{synch,p}$. During this particular flare, the X-ray spectrum is among the softest of the campaign. It unveils complexity in the spectral evolution, where the common harder-when-brighter trend observed in BL Lacs is violated. During a low and hard X-ray state, we find an excess of the UV flux with respect to an extrapolation of the X-ray spectrum to lower energies. This UV excess implies that at least two regions contribute significantly to the infrared/optical/ultraviolet/X-ray emission. Using the simultaneous MAGIC, XMM-Newton, NuSTAR, and AstroSat observations, we argue that a region possibly associated with the 10 GHz radio core may explain such an excess. Finally, we investigate a VHE flare, showing an absence of simultaneous variability in the 0.3-2keV band. Using a time-dependent leptonic modelling, we show that this behaviour, in contradiction to single-zone scenarios, can instead be explained by a two-component model.Comment: Accepted for publication in Astronomy & Astrophysic

Multi-messenger characterization of Mrk 501 during historically low X-ray and γ\gamma-ray activity

We study the broadband emission of Mrk 501 using multi-wavelength observations from 2017 to 2020 performed with a multitude of instruments, involving, among others, MAGIC, Fermi-LAT, NuSTAR, Swift, GASP-WEBT, and OVRO. Mrk 501 showed an extremely low broadband activity, which may help to unravel its baseline emission. Nonetheless, significant flux variations are detected at all wavebands, with the highest occurring at X-rays and very-high-energy (VHE) $\gamma$-rays. A significant correlation ($>$3$\sigma$) between X-rays and VHE $\gamma$-rays is measured, supporting leptonic scenarios to explain the variable parts of the emission, also during low activity. This is further supported when we extend our data from 2008 to 2020, and identify, for the first time, significant correlations between Swift-XRT and Fermi-LAT. We additionally find correlations between high-energy $\gamma$-rays and radio, with the radio lagging by more than 100 days, placing the $\gamma$-ray emission zone upstream of the radio-bright regions in the jet. Furthermore, Mrk 501 showed a historically low activity in X-rays and VHE $\gamma$-rays from mid-2017 to mid-2019 with a stable VHE flux ($>$0.2 TeV) of 5% the emission of the Crab Nebula. The broadband spectral energy distribution (SED) of this 2-year-long low-state, the potential baseline emission of Mrk 501, can be characterized with one-zone leptonic models, and with (lepto)-hadronic models fulfilling neutrino flux constraints from IceCube. We explore the time evolution of the SED towards the low-state, revealing that the stable baseline emission may be ascribed to a standing shock, and the variable emission to an additional expanding or traveling shock.Comment: 56 pages, 30 figures, 14 tables, submitted. Corresponding authors are L. Heckmann, D. Paneque, S. Gasparyan, M. Cerruti, and N. Sahakya