Physical and structural origins of morphotropic phase boundaries (MPBs) in ferroics remain elusive despite decades of study. The leading competing theories employ either low-symmetry bridging phases ...or adaptive phases with nanoscale textures to describe different subsets of the macroscopic data, while the decisive atomic-scale information has so far been missing. Here we report direct atomically resolved mapping of polarization and structure order parameter fields in a Sm-doped BiFeO(3) system and their evolution as the system approaches a MPB. We further show that both the experimental phase diagram and the observed phase evolution can be explained by taking into account the flexoelectric interaction, which renders the effective domain wall energy negative, thus stabilizing modulated phases in the vicinity of the MPB. Our study highlights the importance of local order-parameter mapping at the atomic scale and establishes a hitherto unobserved physical origin of spatially modulated phases existing in the vicinity of the MPB.
Objective and design
The existing biological models of diffuse alveolar damage (DAD) in mice have many shortcomings. To offset these shortcomings, we have proposed a simple, nonsurgical, and ...reproducible method of unilateral total damage of the left lung in ICR mice. This model is based on the intrabronchial administration of a mixture of bacterial lipopolysaccharide (LPS) from the cell wall of S. enterica and α-galactosylceramide (inducing substances) to the left lung.
Methods
Using computer tomography of the lungs with endobronchial administration of contrast material, we have been able to perform an operative intravital verification of the targeted delivery of the inducer. The model presented is characterized by more serious and homogeneous damage of the affected lung compared to the existing models of focal pneumonia; at the same time, our model is characterized by longer animal survival since the right lung remains intact.
Results
The model is also characterized by diffuse alveolar damage of the left lung, animal survival of 100%, abrupt increases in plasma levels of TNFa, INFg, and IL-6, and significant myocardial overload in the right heart. It can be used to assess the efficacy of innovative drugs for the treatment of DAD and ARDS as the clinical manifestations that are developed in patients infected with SARS-CoV-2. Morphological patterns of lungs in the noninfectious (“sterile”) model of DAD induced by LPS simultaneously with α-galactosylceramide (presented here) and in the infectious model of DAD induced by SARS-CoV-2 have been compared.
Conclusion
The DAD model we have proposed can be widely used for studying the efficacy of candidate molecules for the treatment of infectious respiratory diseases, such as viral pneumonias of different etiology, including SARS-CoV-2.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Epitaxial oxide interfaces with broken translational symmetry have emerged as a central paradigm behind the novel behaviors of oxide superlattices. Here, we use scanning transmission electron ...microscopy to demonstrate a direct, quantitative unit-cell-by-unit-cell mapping of lattice parameters and oxygen octahedral rotations across the BiFeO3-La0.7 Sr0.3 MnO3 interface to elucidate how the change of crystal symmetry is accommodated. Combined with low-loss electron energy loss spectroscopy imaging, we demonstrate a mesoscopic antiferrodistortive phase transition near the interface in BiFeO3 and elucidate associated changes in electronic properties in a thin layer directly adjacent to the interface.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Ebola hemorrhagic fever, also known as Ebola virus disease or EVD, is one of the most dangerous viral diseases in humans and animals. In this open-label, dose-escalation clinical trial, we assessed ...the safety, side effects, and immunogenicity of a novel, heterologous prime-boost vaccine against Ebola, which was administered in 2 doses to 84 healthy adults of both sexes between 18 and 55 years. The vaccine consists of live-attenuated recombinant vesicular stomatitis virus (VSV) and adenovirus serotype-5 (Ad5) expressing Ebola envelope glycoprotein. The most common adverse event was pain at the injection site, although no serious adverse events were reported. The vaccine did not significantly impact blood, urine, and immune indices. Seroconversion rate was 100 %. Antigen-specific IgG geometric mean titer at day 42 was 3,277 (95 % confidence interval 2,401-4,473) in volunteers immunized at full dose. Neutralizing antibodies were detected in 93.1 % of volunteers immunized at full dose, with geometric mean titer 20. Antigen-specific response in peripheral blood mononuclear cells was also detected in 100 % of participants, as well as in CD4+ and CD8+ T cells in 82.8 % and 58.6 % of participants vaccinated at full dose, respectively. The data indicate that the vaccine is safe and induces strong humoral and cellular immune response in up to 100 % of healthy adult volunteers, and provide a rationale for testing efficacy in Phase III trials. Indeed, the strong immune response to the vaccine may elicit long-term protection. This trial was registered with grls.rosminzdrav.ru (No. 495*), and with zakupki.gov.ru (No. 0373100043215000055).
Electron microscopy is undergoing a transition; from the model of producing only a few micrographs, through the current state where many images and spectra can be digitally recorded, to a new mode ...where very large volumes of data (movies, ptychographic and multi-dimensional series) can be rapidly obtained. Here, we discuss the application of so-called "big-data" methods to high dimensional microscopy data, using unsupervised multivariate statistical techniques, in order to explore salient image features in a specific example of BiFeO3 domains. Remarkably, k-means clustering reveals domain differentiation despite the fact that the algorithm is purely statistical in nature and does not require any prior information regarding the material, any coexisting phases, or any differentiating structures. While this is a somewhat trivial case, this example signifies the extraction of useful physical and structural information without any prior bias regarding the sample or the instrumental modality. Further interpretation of these types of results may still require human intervention. However, the open nature of this algorithm and its wide availability, enable broad collaborations and exploratory work necessary to enable efficient data analysis in electron microscopy.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
We explore ferroelectric properties of cleaved 2-D flakes of copper indium thiophosphate, CuInP2S6 (CITP), and probe size effects along with limits of ferroelectric phase stability, by ambient and ...ultra high vacuum scanning probe microscopy. CITP belongs to the only material family known to display ferroelectric polarization in a van der Waals, layered crystal at room temperature and above. Our measurements directly reveal stable, ferroelectric polarization as evidenced by domain structures, switchable polarization, and hysteresis loops. We found that at room temperature the domain structure of flakes thicker than 100 nm is similar to the cleaved bulk surfaces, whereas below 50 nm polarization disappears. We ascribe this behavior to a well-known instability of polarization due to depolarization field. Furthermore, polarization switching at high bias is also associated with ionic mobility, as evidenced both by macroscopic measurements and by formation of surface damage under the tip at a bias of 4 Vlikely due to copper reduction. Mobile Cu ions may therefore also contribute to internal screening mechanisms. The existence of stable polarization in a van-der-Waals crystal naturally points toward new strategies for ultimate scaling of polar materials, quasi-2D, and single-layer materials with advanced and nonlinear dielectric properties that are presently not found in any members of the growing “graphene family”.
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IJS, KILJ, NUK, PNG, UL, UM
Introduction. The outbreaks of the Zaire ebolavirus (ZE) disease (ZED) that have arisen in the last decade determine the need to study the infection pathogenesis, the formation of specific immunity ...forming as well as the development of effective preventive and therapeutic means. All stages of fight against the ZED spread require the experimental infection in sensitive laboratory animals, which are rhesus monkeys in case of this disease .The aim of the study is to evaluate the rhesus monkey cellular immunity following the ZE experimental infection by the means of flow cytometry (cytofluorimetry).Material and methods. Male rhesus monkeys were intramuscularly infected by the dose of 15 LD50 (dose of the pathogen that causes 50% mortality of infected animals) of the ZE, the Zaire strain (ZEBOV). Levels of 18 peripheral blood lymphocyte populations of the animals before the ZE experimental infection and at the terminal stage of the disease were assessed using flow cytometry.Results and discussion. The certain changes in the levels of the lymphocyte populations were observed following infection, indicating simultaneous activation and suppression of the immune system during ZED. The increase in content was observed for T-lymphocytes, T-helper and cytotoxic T-lymphocytes expressing the corresponding markers of early activation. The decrease was recorded for T-lymphocytes and double-positive T-lymphocytes expressing corresponding markers of late activation, as well as natural killer cells expressing CD8 (p 0.05).Conclusion. For the first time in the Russian Federation, the rhesus monkey cellular immunity before and after the ZE experimental infection was assessed using flow cytometry.
Cellular immunity plays an important role in the pathogenesis and formation of protective immune defense against the SARS‑CoV‑2 virus.
The aim
of the work was to study the cellular immunity of rhesus ...monkeys applying flow cytometry after experimental infection with the SARS‑CoV‑2 virus.
Materials and methods
. Male rhesus monkeys were intranasally inoculated with the SARS‑CoV‑2 virus, Isolate B strain and hCoV-19/Russia/SP48-1226/2020 strain (abbreviated name U-2), at a dose of 5.0 lg PFU. Using flow cytometry, the levels of 21 populations/subpopulations of mononuclear cells in the peripheral blood of animals were determined before experimental infection with the pathogen and on day 14 after infection. SARS‑CoV‑2 coronavirus RNA was assessed using real-time polymerase chain reaction. Determination of the titer of virus-neutralizing antibodies to the SARS‑CoV‑2 virus in the blood sera of animals was conducted through neutralization test evaluating the ability to suppress negative colonies.
Results and discussion
. Infection with Isolate B strain culture has led to an increase in the relative content of total T-lymphocytes (p˂0.2), cytotoxic T-lymphocytes (p˂0.1), as well as monocytes expressing the early activation marker CD25 (p˂0.2). The decrease in levels has been observed for total B-lymphocytes (p˂0.2) and T-helper cells (p˂0.1). Infection with the U-2 strain culture revealed an increase in the relative content of monocytes expressing the early activation marker CD25 (p˂0.2). Thus, for the first time in the Russian Federation, flow cytometry was used to study the cellular immunity of rhesus monkeys before and after experimental infection with the SARS‑CoV‑2 virus. The obtained information can be used for studying the pathogenesis of SARS‑CoV‑2 infection, course, and outcome of the disease, and developing strategies for vaccination and treatment.
The aim of this work was to estimate the efficacy and safety of single intramuscular introduction of specific heterologous immunoglobulin as prophylactic drug against Ebola hemorrhagic fever. ...Materials and methods. The specific heterologous immunoglobulin was introduced as a special prophylactic drug to 28 patients in epidemic situations, after skin hurt with infectious materials or contact with infectious blood. Clinico-laboratory observation was performed in 24 subjects after single intramuscular introduction of heterologous immunoglobulin Ebola. The samples of blood serum were investigated for immunoglobulin Ebola and antibodies to horse gamma-globulin on the 30th and 60th days after prophylaxis. Results. None of the subjects of the study contracted Ebola fever. There were no anaphylactic reactions after special prophylaxis with specific heterologous immunoglobulin. Among the subjects with normal allergic state 31% responded with local reactions; 13%, with a general reaction (mild case of the serum disease). Almost no reaction was observed in patients with unfavorable allergic state subjected to desensitizing therapy; in the absence of desensitizing therapy, 50% of patients with unfavorable allergic state exhibited local reactions; 17%, mild cases of the serum disease; 33%, moderate cases of the serum disease. In summary, if the tactics of immunoglobulin application was right, the quantity of local allergic reactions was 28%; of wide spread reactions, 6%. Weak serum disease was observed in 11% of the subjects. The prognostic period of resistance to Ebola fever was less than 30 days. Conclusion. The prophylactic use of specific immunoglobulin from horse blood serum against hemorrhagic Ebola fever is effective and relatively safe in patients subjected to desensitizing therapy.
Over the two years that have passed since the WHO announced on March 11, 2020, a pandemic of the new coronavirus disease COVID-19, more than 460 million cases of the disease have been detected in the ...world, of which more than five million have been fatal. During the natural evolution of the COVID-19 pathogen, dominant variants emerge that account for most new infections. The WHO constantly monitors coronavirus mutations that potentially pose an epidemiological danger. Currently, the WHO divides modified variants of the SARS-CoV-2 virus into
variants of concern
(VOC) and
variants of interest
(VOI). The WHO-designated group of variants of concern includes potentially the most dangerous lines, which are characterized by a complex of new properties. This group also includes the
Omicron
variant, which has become the dominant agent of the new wave of the COVID-19 pandemic.
The aim of this work is to analyze the characteristics of the SARS-CoV-2 Omicron strain, the dominant agent of the new wave of the COVID-19 pandemic. The proposed mechanism of origin of the Omicron variant, its geographical distribution, the features of the disease caused by it, and the distinguishing features from diseases caused by the Delta variant and the original Wuhan strain of the SARS-CoV-2 virus, mutations of the Omicron variant compared to the parent strain of the SARS-CoV-2 virus, the genetic variability of the Omicron variant, and the epidemiological characteristics of the disease it causes are considered. Particular attention is paid to evaluation of the preventive and therapeutic effectiveness of the existing medical means of protection against COVID-19 in relation to the Omicron strain.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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