The Temporal Relationship Between Terrestrial Gamma-Ray Flashes and Associated Optical Pulses From Lightning.

We present 221 Terrestrial Gamma-ray Flashes (TGFs) and associated optical pulses observed by the Atmosphere-Space Interactions Monitor (ASIM) on board the International Space Station. The events were detected between the end of March 2019 and November 2020 and consist of X- and gamma-ray energy detections, as well as photometer data (180-230, 337, and 777 nm) and optical camera data (337 and 777 nm). Using the available ASIM data and applying a consistency check based on TGF characteristics and lightning detections from lightning radio atmospherics close in time, we determine the most likely position of the TGFs in relation to the photometer field of view (FoV), and the association to the observed optical pulses. Out of the 221 events we find 72 events where the TGF and optical data are determined to be associated and inside the photometer FoV. Using the measured TGF durations and the time between the onsets of the TGFs and optical pulses we find: (a) That the TGF onsets are always before or at the same time as the optical pulse onsets (taking into account cloud scattering). (b) A tendency for longer duration TGFs to have longer delays between onsets. (c) Two groups of events: (a) where there is a possible overlap between the TGFs and the optical emissions, as the TGFs last longer than the delay between onsets and (b) where the TGFs and optical emissions do not overlap, as there are long delays between the onsets, which cannot be explained by cloud scattering.

Very-high-frequency oscillations in the main peak of a magnetar giant flare.

Magnetars are strongly magnetized, isolated neutron stars1-3 with magnetic fields up to around 1015 gauss, luminosities of approximately 1031-1036 ergs per second and rotation periods of about 0.3-12.0 s. Very energetic giant flares from galactic magnetars (peak luminosities of 1044-1047 ergs per second, lasting approximately 0.1 s) have been detected in hard X-rays and soft γ-rays4, and only one has been detected from outside our galaxy5. During such giant flares, quasi-periodic oscillations (QPOs) with low (less than 150 hertz) and high (greater than 500 hertz) frequencies have been observed6-9, but their statistical significance has been questioned10. High-frequency QPOs have been seen only during the tail phase of the flare9. Here we report the observation of two broad QPOs at approximately 2,132 hertz and 4,250 hertz in the main peak of a giant γ-ray flare11 in the direction of the NGC 253 galaxy12-17, disappearing after 3.5 milliseconds. The flare was detected on 15 April 2020 by the Atmosphere-Space Interactions Monitor instrument18,19 aboard the International Space Station, which was the only instrument that recorded the main burst phase (0.8-3.2 milliseconds) in the full energy range (50 × 103 to 40 × 106 electronvolts) without suffering from saturation effects such as deadtime and pile-up. Along with sudden spectral variations, these extremely high-frequency oscillations in the burst peak are a crucial component that will aid our understanding of magnetar giant flares.

LC-MS/MS analysis of lesional and normally looking psoriatic skin reveals significant changes in protein metabolism and RNA processing.

BACKGROUND: Plaque psoriasis is a chronic autoimmune disorder characterized by the development of red scaly plaques. To date psoriasis lesional skin transcriptome has been extensively studied, whereas only few proteomic studies of psoriatic skin are available. AIM: The aim of this study was to compare protein expression patterns of lesional and normally looking skin of psoriasis patients with skin of the healthy volunteers, reveal differentially expressed proteins and identify changes in cell metabolism caused by the disease. METHODS: Skin samples of normally looking and lesional skin donated by psoriasis patients (n = 5) and samples of healthy skin donated by volunteers (n = 5) were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). After protein identification and data processing, the set of differentially expressed proteins was subjected to protein ontology analysis to characterize changes in biological processes, cell components and molecular functions in the patients' skin compared to skin of the healthy volunteers. The expression of selected differentially expressed proteins was validated by ELISA and immunohistochemistry. RESULTS: The performed analysis identified 405 and 59 differentially expressed proteins in lesional and normally looking psoriatic skin compared to healthy control. In normally looking skin of the patients, we discovered decreased expression of KNG1, APOE, HRG, THBS1 and PLG. Presumably, these changes were needed to protect the epidermis from spontaneous activation of kallikrein-kinin system and delay the following development of inflammatory response. In lesional skin, we identified several large groups of proteins with coordinated expression. Mainly, these proteins were involved in different aspects of protein and RNA metabolism, namely ATP synthesis and consumption; intracellular trafficking of membrane-bound vesicles, pre-RNA processing, translation, chaperoning and degradation in proteasomes/immunoproteasomes. CONCLUSION: Our findings explain the molecular basis of metabolic changes caused by disease in skin lesions, such as faster cell turnover and higher metabolic rate. They also indicate on downregulation of kallikrein-kinin system in normally looking skin of the patients that would be needed to delay exacerbation of the disease. Data are available via ProteomeXchange with identifier PXD021673.

Gamma Ray Glow Observations at 20-km Altitude.

In the spring of 2017 an ER-2 aircraft campaign was undertaken over continental United States to observe energetic radiation from thunderstorms and lightning. The payload consisted of a suite of instruments designed to detect optical signals, electric fields, and gamma rays from lightning. Starting from Georgia, USA, 16 flights were performed, for a total of about 70 flight hours at a cruise altitude of 20 km. Of these, 45 flight hours were over thunderstorm regions. An analysis of two gamma ray glow events that were observed over Colorado at 21:47 UT on 8 May 2017 is presented. We explore the charge structure of the cloud system, as well as possible mechanisms that can produce the gamma ray glows. The thundercloud system we passed during the gamma ray glow observation had strong convection in the core of the cloud system. Electric field measurements combined with radar and radio measurements suggest an inverted charge structure, with an upper negative charge layer and a lower positive charge layer. Based on modeling results, we were not able to unambiguously determine the production mechanism. Possible mechanisms are either an enhancement of cosmic background locally (above or below 20 km) by an electric field below the local threshold or an enhancement of the cosmic background inside the cloud but then with normal polarity and an electric field well above the Relativistic Runaway Electron Avalanche threshold.

Relativistic electrons from sparks in the laboratory.

Discharge experiments were carried out at the Eindhoven University of Technology in 2013. The experimental setup was designed to search for electrons produced in meter-scale sparks using a 1 MV Marx generator. Negative voltage was applied to the high voltage (HV) electrode. Five thin (1 mm) plastic detectors (5 cm2 each) were distributed in various configurations close to the spark gap. Earlier studies have shown (for HV negative) that X-rays are produced when a cloud of streamers is developed 30-60 cm from the negative electrode. This indicates that the electrons producing the X-rays are also accelerated at this location, that could be in the strong electric field from counterstreamers of opposite polarity. Comparing our measurements with modeling results, we find that ∼300 keV electrons produced about 30-60 cm from the negative electrode are the most likely source of our measurements. A statistical analysis of expected detection of photon bursts by these fiber detectors indicates that only 20%-45% of the detected bursts could be from soft (∼10 keV) photons, which further supports that the majority of detected bursts are produced by relativistic electrons.

[Genetically predetermined limitation in the use of HaCaT cells that affects their ability to serve as an experimental model of psoriasis].

Proinflammatory cytokines TNF, IFNG and ILl7 play an important role in eruption of psoriasis. The activation of epidermal keratinocytes with the named cytokines alters their terminal differentiation program and causes their hyperproliferation in the diseased skin. HaCaT cells, which are immortalized human keratinocytes, are often used as a cellular model of psoriasis. The aim of this study was to evaluate changes in gene expression and the proliferation rates in cultured HaCaT cells treated with TNF, IFNG and IL17. We found that HaCaT cells decrease their proliferation rate in response to either IL17 or a combination TNF and IF-NG. The analysis of microarray data discovered a group of 12 genes, which were downregulated in HaCaT after treatments with the named cytokines and upregulated in psoriatic lesional skin. Eight genes were important for DNA replication and they also contributed to two larger networks that regulated cell progression through the cell cycle. We conclude that HaCaT cells have a sufficient limitation as a cellular model of psoriasis due to their treatment with proinflammatory cytokines, namely TNF, IFNG and IL17 does not increase their proliferation rate. Thus, the studies of psoriasis based on HaCaT cells as an experimental model shall take in account this important phenomenon.

[Genetically modified animals as model systems of psoriasis].

Psoriasis is a chronic autoimmune skin disorder. Experimental models of psoriasis can be used to study the disease in controlled conditions. Moreover, the experimental models allow to study a certain aspect of the pathological process. Although none of the multiple mouse models reproduces the human disease precisely, lab animals as model systems can be very helpful because of two reasons. First, introduction of new mutations into animal genome allows to reveal the new genes that may play a certain role in pathogenesis of the disease. Second, the experiments that are carried on the lab animals can be used for testing the new drugs and selection of the most efficient chemical agents from a variety of the proposed experimental preparations. The aim of this paper was to summarize the data on the lab animals that serve as experimental models of psoriasis.

Pharmacological control of receptor of advanced glycation end-products and its biological effects in psoriasis.

Receptor for advanced glycation end-products is implicated in a development of chronic inflammatory response. Aim of this paper is to provide a review on commercial and experimental medicines that can interfere with RAGE and signaling through RAGE. We searched three bibliographical databases (PubMed, Web of Science and MEDLINE) for the publications from 2005 to March 2012 and identified 5 major groups of agents that can interfere with RAGE biological effects. In the first part of this paper, we discuss AGE crosslink breakers. These chemicals destroy advanced glycation end products (AGEs) that are crosslinked to the extracellular matrix proteins and can interact with RAGE as ligands. Then, we describe two non-conventional agents SAGEs and KIOM-79 that abolish certain biological effects of RAGE and have a strong anti-inflammatory potential. In the third part, we evaluate the inhibitors of the signaling cascades that underlie RAGE. Particularly, we discuss two groups of kinase inhibitors tyrphostins and the inhibitors of JAK kinases. Considering RAGE as a potential master regulator of processes that are crucial for the pathogenesis of psoriasis, we propose that these medicins may help in controlling the disease by abolishing the chronic inflammation in skin lesions.

[Role of receptor for advanced glycation end-products in pathgenesis of psoriasis].

This review summarizes the existing knowledge regarding the role of receptor for advanced glycation end products which is a key participant of the inflammatory process, in pathogenesis of psoriasis. By interacting with multiple ligands and activating several signaling mechanisms, receptor for advanced glycation end products regulates gene expression via a group transcription factors, that includes NFKB and AP1. According to the published data the expression of receptor for advanced glycation end products in both immune cells and their targets, a high stability of this receptor in complexes with ligands as well as a positive feedback loop, upregulating the expression of its certain ligands, suggest receptor for advanced glycation end products as a possible principal factor that makes the inflammatory response in psoriasis sustainable. Considering receptor for advanced glycation end products as a potential master regulator of several processes that play a crucial role in development of psoriatic plaques, we believe that further experimental studies are needed to elucidate how exactly this receptor converts a transient inflammatory reaction to a sustainable inflammatory response. These studies are also needed for the development of novel medications that target receptor for advanced glycation end products and signaling mechanisms that this receptor activates.

Three-dimensional model of mouse epidermis for experimental studies of psoriasis.

Three-dimensional models of skin and epidermis imitate the structure of real tissues and provide accurate information about certain skin conditions, such as psoriasis. A three-dimensional model of mouse epidermis was generated from the epidermal keratinocytes of newborn mice and treated with cytokines. The aim of this study was to evaluate this model as an experimental model of psoriasis and to assess the changes occurring in its structure and gene expression after the exposure to proinflammatory cytokines. Treatment of the three-dimensional model with either interleukin 17 or a combination of tumor necrosis factor and interferon γ was shown to produce morphological changes, which were similar to acanthosis in psoriatic skin. The observed changes in gene expression of metalloproteinases and certain psoriasis biomarkers, such as mki67, krt16 and fosl1, were similar to the changes in patients' skin. Notably, changes caused by interleukin 17 were less evident than those caused by the combination of interferon γ and tumor necrosis factor. On the contrary, HaCaT cells exhibited no significant changes in the expression of fosl1 and had decreased levels of mki67 after being treated with a combination of TNF and IFNG. Moreover, treatment with IL17 had no significant effect on krt16 and mki67 expression and even reduced the fosl1 levels. The findings suggest that artificially generated three-dimensional models of murine skin can be used to study psoriasis.

Synthesis of a new element with atomic number Z = 117.

The discovery of a new chemical element with atomic number Z=117 is reported. The isotopes (293)117 and (294)117 were produced in fusion reactions between (48)Ca and (249)Bk. Decay chains involving 11 new nuclei were identified by means of the Dubna gas-filled recoil separator. The measured decay properties show a strong rise of stability for heavier isotopes with Z > or = 111, validating the concept of the long sought island of enhanced stability for superheavy nuclei.

[Closed intrathoracic injury with internal heart rupture and intact bony cage].

A case of a blunt heart trauma in a 21 year-old man (driver) is reported. The man died in a motor-vehicle accident where he sustained aortic valve rupture and a number of non-cardiac injuries including life-threatening ones (hip fracture and left-hand side hemopneumothorax). His ribs remained intact. The fatal outcome was due to tears of papillary muscles in the left and right ventricles and rupture of the right atrial wall that resulted in microthromboembolization of brain vessels.

Studies of the perception of incomplete outline images of different sizes.

The aim of the present work was to assess the range of angular sizes of fragmented images of objects at which perception of the images was scale-independent. Measurements were made of human subjects' recognition thresholds for the shapes of the objects over a wide range of angular sizes (0.19-50 degrees). The experiments used the Gollin test--a method for studying the recognition of fragmented outline images of objects with which the observer is familiar. The results obtained demonstrated that there is a wide range of angular sizes, from 1.0 degrees to 50 degrees, over which the perception thresholds of incomplete outline images do not change with changes in size, along with a narrow range of stimulus sizes, 0.19-1.0 degrees, over which there is a significant size dependence. We suggest that the increase in thresholds and the failure to recognize images of small size occur as a result of an increased contribution of sampling noise at the level of the human retina.

[Investigation of the perception of incomplete contour figures of the various size].

The purpose of the current research was to estimate the range of angular sizes of incomplete images across which the perception of the given images does not depend on scale. We have measured thresholds of recognition of the identities of objects across a wide range of angular sizes from 0.19 to 50 degrees of visual angle. The methodology derived from the Gollin-test which has been used as a method for studying the perception of objects presented as incomplete contour and pattern recognition. Results demonstrated that there is a wide range of angular sizes (from 1 .0 up to 50 degrees of visual angle) across which thresholds perception of incomplete images does not depend on object size. However, there was found a narrow range of small sizes of stimulus (0.19-1.0 degrees of visual angle) at which there was found dependence of performance on object size. We assume that increase of thresholds and occurrence of undistinguished images (when they have small size) depends on increase of the contribution of sampling noise at the observer's eye retina.

[Designing of a liquid serum panel containing or not class IgG antibodies specific to human cytomegalovirus]. / Konstruirovanie zhidkoi paneli syvorotok, soderzhashchikh i ne soderzhashchikh antitela klassa IgG k tsitomegalovirusu cheloveka.

Designing of a liquid serum panel for the determination of class G antibodies specific to human cytomegalovirus (HCMV) is under discussion. Sera were selected by ELISA for antibodies to HCMV and by PCR for CMV DNA. The serum panel comprises samples of positive and negative sera with high and low titers. Sera were stabilized by a stabilization solution. The panel shelf life was evaluated by routine methods and by the "accelerated aging" technique. Sera selected for a standard panel containing or not antibodies to HCMV preserve their properties and stability for as long as 1 year at 4 degrees C.

[Hygienic optimization of the use of chemical protective means on railway transport]. / Gigienicheskaia optimizatsiia ispol'zovaniia sredstv individual'noi zashchity na zheleznodorozhnom transporte.

The paper presents data characterizing the working conditions of railway workers. It shows that there is the greatest levels of noise and vibration, the burden and intensity of work. The worst working conditions are noted in energy supply, car, locomotive services and track facilities. The working conditions determine a significant industrial risk of railway workers since the prevention of health abnormalities by using chemical protective means is a topical problem. The priority lines of hygienic rationale for optimization the choice and use of chemical protective means for workers exposed to occupational hazards are determined.

[Characteristics of blood circulation in the lungs during the early period after blunt multiple trauma]. / Osobennosti gemotsirkuliatsii v legkikh v rannem periode tupoi sochetannoi travmy.

The microscopic and histostereometric examinations of specific features of blood circulation in the lungs (in lethal cases) performed during the early period after combined trauma showed pronounced disturbances of blood circulation in body organs which had a certain sequence in the development of vascular reactions and vascular temporal dynamics. The influence of a preceding alcoholic intoxication and intensive hemorrhage on the circulatory dynamics was demonstrated.

Molecular mechanism of lysosomal sialidase deficiency in galactosialidosis involves its rapid degradation.

Galactosialidosis is an inherited lysosomal storage disease caused by the combined deficiency of lysosomal sialidase and beta-galactosidase secondary to the deficiency of cathepsin A/protective protein, which is associated with sialidase and beta-galactosidase in a high-molecular weight (1.27MDa) complex. Clinical phenotypes of patients as well as the composition of compounds which are stored in patient's tissues implicate sialidase deficiency as the underlying pathogenic defect. The recent cloning and sequencing of lysosomal sialidase [Pshezhetsky, Richard, Michaud, Igdoura, Wang, Elsliger, Qu, Leclerc, Gravel, Dallaire and Potier (1997), Nature Genet. 15, 316-320] allowed us to study the molecular mechanism of sialidase deficiency in galactosialidosis. By Western blotting, using antibodies against the recombinant human enzyme, and by NH2-terminal sequencing, we showed that sialidase is synthesized as a 45.5 kDa precursor and after the cleavage of the 47-amino acid signal peptide and glycosylation becomes a 48.3 kDa mature active enzyme present in the 1.27 kDa complex. Transgenic expression of sialidase in cultured skin fibroblasts from normal controls and from galactosialidosis patients, followed by immunofluorescent and immunoelectron microscopy showed that in both normal and affected cells the expressed sialidase was localized on lysosomal and plasma membranes, but the amount of sialidase found in galactosialidosis cells was approximately 5-fold reduced. Metabolic labelling studies demonstrated that the 48.3 kDa mature active form of sialidase was stable in normal fibroblasts (half-life approximately 2.7 h), whereas in galactosialidosis fibroblasts the enzyme was rapidly converted (half-life approximately 30 min) into 38.7 and 24 kDa catalytically inactive forms. Altogether our data provide evidence that the molecular mechanism of sialidase deficiency in galactosialidosis is associated with abnormal proteolytic cleavage and fast degradation.