Search

The article analyzes the psychological basis of fascism. Fascism is interpreted as an ideology not of maximizing power and control, but of absolutization of inequality. The probability of the role of Kant's "categorical imperative" principle in its formation is substantiated. Kant denied the affinity of human consciousness (mind) with the Transcendent. Therefore, the categorical imperative, being the maximalism of self-blind submission to a "duty" arbitrarily set by a person for himself, is a form of self-violence over his mind. Establishing morality for himself, a person inevitably feels his exclusivity, elitism, realizes himself as the creator and owner of morality (and even "God himself"). This attitude is obviously inherent in the fascist personality. At the same time, the lack of reflection and self-criticism leads to self-encapsulation and, consequently, to self-abasement, experiencing oneself as a "Victim". The pseudo-moral experience of being a victim is the hidden core of the fascized personality. The self-pity of the "Victim", without changing its essence, can expand and extend to the collective "I", to "my own". This is how empathy arises, which, spreading to its community: nation, race, and becomes the basis of group egoism. Empathy among adherents of fascism can play a big role, since empathy for "their own" replaces morality as a single moral norm.

The NCCN Guidelines for Hematopoietic Cell Transplantation (HCT) provide an evidence- and consensus-based approach for the use of autologous and allogeneic HCT in the management of malignant diseases in adult patients. HCT is a potentially curative treatment option for patients with certain types of malignancies; however, recurrent malignancy and transplant-related complications often limit the long-term survival of HCT recipients. The purpose of these guidelines is to provide guidance regarding aspects of HCT, including pretransplant recipient evaluation, hematopoietic cell mobilization, and treatment of graft-versus-host disease—a major complication of allogeneic HCT—to enable the patient and clinician to assess management options in the context of an individual patient’s condition. These NCCN Guidelines Insights provide a summary of the important recent updates to the NCCN Guidelines for HCT, including the incorporation of a newly developed section on the Principles of Conditioning for HCT.

In this paper, the elastic state of a sphere is studied, inside which there is a spherical cavity (spherical pore) at an arbitrary distance from the center of the sphere. Expressions for the displacement components, strain, and stress tensors depending on the geometrical parameters of the problem and the pressure values on the surfaces of the outer and inner spheres were obtained.

The study is devoted to revealing the individual and synergistic effects of modifications of the carrier medium of the coal-water slurries (CWS) based on coking coal and carbon-containing flotation wastes of this coal on the effective viscosity and sedimentation stability. Synthetic and natural wetting agents as well as liquid solvents (alcohol, oil, conventional liquid fuel, methyl ethers) and solid organic compounds exemplified by sawdust are used for this. The relationships between the effective viscosity, water separation ratio, and zeta potential for the CWS with the separate addition of a wetting agent and a solvent is established. The categories of fuel compositions are identified according to the “stability” criterion. The synergistic effect of the additions of a wetting agent and a solvent on the sedimentation stability and effective viscosity is demonstrated. The physicochemical model of interaction between the solid particles and the additives in CWSs is proposed.

Many molecular and physiological processes in plants occur at a specific time of day. These daily rhythms are coordinated in part by the circadian clock, a timekeeper that uses daylength and temperature to maintain rhythms of ∼24 h in various clock-regulated phenotypes. The circadian MYB-like transcription factor REVEILLE 8 (RVE8) interacts with its transcriptional coactivators NIGHT LIGHT-INDUCIBLE AND CLOCK-REGULATED 1 (LNK1) and LNK2 to promote the expression of evening-phased clock genes and cold tolerance factors. While genetic approaches have commonly been used to discover connections within the clock and between clock elements and other pathways, here, we used affinity purification coupled with mass spectrometry (APMS) to identify time-of-day–specific protein interactors of the RVE8-LNK1/LNK2 complex in Arabidopsis (Arabidopsis thaliana). Among the interactors of RVE8/LNK1/LNK2 were COLD-REGULATED GENE 27 (COR27) and COR28, which coprecipitated in an evening-specific manner. In addition to COR27 and COR28, we found an enrichment of temperature-related interactors that led us to establish a previously uncharacterized role for LNK1 and LNK2 in temperature entrainment of the clock. We established that RVE8, LNK1, and either COR27 or COR28 form a tripartite complex in yeast (Saccharomyces cerevisiae) and that the effect of this interaction in planta serves to antagonize transcriptional activation of RVE8 target genes, potentially through mediating RVE8 protein degradation in the evening. Together, these results illustrate how a proteomic approach can be used to identify time-of-day–specific protein interactions. Discovery of the RVE8-LNK-COR protein complex indicates a previously unknown regulatory mechanism for circadian and temperature signaling pathways.

The problem of the diffusion evolution of a pore filled with molecular hydrogen in a spherical granule in a hydrogen medium is solved. The initial position of the pore is displaced relative to the center of the granule. A nonlinear system of equations is obtained, which describes the behavior of the size of the gas-filled pore, the amount of gas in it and its position relative to the center of the bounded particle with time. Numerical calculations have shown the existence of two stages of evolution. The first (fast) stage is associated with the equalization of pressure in the pore with the external. The second is the slow diffusion "healing" of the pore, when the amount of gas adjusts to its size and the gas pressure is approximately equal to the external., 10 pages, 4 figures. arXiv admin note: text overlap with arXiv:1910.13956

The subject of the study is the psychological mechanisms that produce a person's character. The classical ideas of character, reflected in its modern definitions and interpretations, are considered. The concepts of "intention" and "attitude" are compared. On this basis, the traditional understanding of character as an expression of the system of human relations to people, objects, etc. is transformed into considering it as an intentional "relief" of the subject. The psychological content of the relationship as a substitute for action (activity) is analyzed. The connection of character with the structure of human activity is substantiated. The idea of the imitation-activity nature of character is put forward. Based on the consideration of the types of intentions and relationships, an attempt is made to develop a basic typology of character. Examples illustrating the imitation-activity nature of character types are given. The advantage of the presented concept of the psychological nature of character is that, unlike existing approaches to character (character as accentuation, social character according to E. Fromm, etc.), it allows you to combine a descriptive approach to character with the possibility of analyzing its internal psychological mechanisms. In addition, since the structure of activity (means, function, etc.) correlates with the fundamental composition of these mechanisms, then our typology of characters is not one of the possible ones, but, as we believe, reflects the basic types of character.

The NCCN Guidelines for Myelodysplastic Syndromes (MDS) provide recommendations for the evaluation, diagnosis, and management of patients with MDS based on a review of clinical evidence that has led to important advances in treatment or has yielded new information on biologic factors that may have prognostic significance in MDS. The multidisciplinary panel of MDS experts meets on an annual basis to update the recommendations. These NCCN Guidelines Insights focus on some of the updates for the 2022 version of the NCCN Guidelines, which include treatment recommendations both for lower-risk and higher-risk MDS, emerging therapies, supportive care recommendations, and genetic familial high-risk assessment for hereditary myeloid malignancy predisposition syndromes.

The energy and velocity distributions of ideal gas particles were first obtained by Boltzmann and Maxwell in the second half of the nineteenth century. In the case of a finite number of particles, the particle energy distribution was obtained by Boltzmann in 1868. However, it appears that this distribution is not valid for all vessels. A round vessel is a special case due to the additional integral of motion, the conservation of the gas angular momentum. This paper is intended to fill this gap, it provides the exact distribution of particle energy for a classical non-rotating ideal gas of a finite number of colliding particles in a round vessel. This previously unknown distribution was obtained analytically from the first principles, it includes the dependence on all the particle masses. The exact mean energies of gas particles are also found to depend on the system parameters, i.e., the distribution of energy over the degrees of freedom is not uniform. Therefore, the usual ideal gas model allows for the uneven energy partitioning, which we study here both theoretically and in simple numerical experiments.

Simon Szántó is known as one of the founders of the Jewish press in Vienna, the editor and main author of the Jewish periodical Die Neuzeit, and an influential educator during the high point of Austrian liberalism between the 1860s and the early 1880s. His enormously rich literary legacy covers issues such as the integration of Jews into the Austrian-Hungarian society, religious reform, gender roles, and particularly education. Szántó’s writings offer a unique opportunity to look at the Viennese liberal period of the second half of the nineteenth century and its challenges through the eyes of a mostly overlooked, but highly significant and influential actor of the time. This article will first introduce Simon Szántó’s cultural and educational background that impacted his ideals and his activities, and go on to discuss one of his main concerns, namely Jewish education. Religious education, confessional schooling, and Jewish upbringing at home bore the burden of responsibility for shaping Austrian Jewish women and men. These Jews were to be integrated in an Austrian culture, while at the same time taught to retain a strong Jewish particularity. Szántó aimed to unite this dichotomous reality through the realization of his ideals of Jewish Bildung.

This article is devoted to creation of the secondary network using base stations of mobile telecommunications operators. General advantages of the secondary networks are discussed. Then we suggest to build a novel network of low-cost small base radars (BSR) by adding the low-power radars to the existent selected base stations’ equipment. This gives a possibility to obtain a high-resolution meteorological information in particular about dangerous weather phenomena in real-time and for any region of mobile network coverage. The applications of the proposing network are not limited by meteorology, but includes also some other fields, for example, traffic monitoring, birds and insects’ migration observations, etc. Статья посвящена созданию вторичной сети с использованием базовых станций операторов мобильной связи. Обсуждаются общие преимущества вторичных сетей. Предлагается построить новую сеть недорогих малых базовых радаров, добавив маломощные радары к существующему оборудованию выбранных базовых станций. Это дает возможность получать метеорологическую информацию высокого разрешения, в частности об опасных погодных явлениях, в реальном времени и для любого региона покрытия мобильной сети. Приложения предлагаемой сети не ограничиваются метеорологией, но включают также некоторые другие области, например, мониторинг движения, наблюдения за миграцией птиц и насекомых и т. д. Статтю присвячено створенню вторинної мережі з використанням базових станцій операторів мобільного зв'язку. Обговорюються загальні переваги вторинних мереж. Пропонується побудувати нову мережу недорогих малих базових радарів, додавши малопотужні радари до наявного обладнання вибраних базових станцій. Це дає можливість отримувати метеорологічну інформацію високої роздільної здатності, зокрема, про небезпечні погодні явища в режимі реального часу та для будь-якого регіону покриття мобільної мережі. Застосування запропонованої мережі не обмежується метеорологією, але включає також деякі інші галузі, наприклад, моніторинг руху, спостереження за міграцією птахів і комах, тощо.

Myotonic dystrophy type 1 (DM1) is an autosomal dominant muscular dystrophy that results from a CTG expansion (50–4000 copies) in the 3′ UTR of the DMPK gene. The disease is classified into four or five somewhat overlapping forms, which incompletely correlate with expansion size in somatic cells of patients. With rare exception, it is affected mothers who transmit the congenital (CDM1) and most severe form of the disease. Why CDM1 is hardly ever transmitted by fathers remains unknown. One model to explain the almost exclusive transmission of CDM1 by affected mothers suggests a selection against hypermethylated large expansions in the germline of male patients. By assessing DNA methylation upstream to the CTG expansion in motile sperm cells of four DM1 patients, together with availability of human embryonic stem cell (hESCs) lines with paternally inherited hypermethylated expansions, we exclude the possibility that DMPK hypermethylation leads to selection against viable sperm cells (as indicated by motility) in DM1 patients.

Belarusian history is woven of a multitude of events and processes that defy unambiguous assessment. First of all, this refers to their political component: the Belarusian lands and population for more than a thousand years belonged to states that had nothing in common with the Belarusian ethnos in their names. However, it was this ethnic community that was a most important component of Ancient Rus, the Grand Duchy of Lithuania, the Polish-Lithuanian Commonwealth, and the Russian Empire. It becomes clear that in the educational and scientific environment, as well as in the general intellectual sphere, the ancestors of Belarusians were somewhat outshadowed, which today motivates them to prove their priorities to their neighbors in the West and the East. It was only in the revolutionary upheavals of early 20th century that the Belarusian statehood began to form. And the most important factor in its approval was the first university – the Belarusian State University. The article is devoted to the consideration of its formation in the conditions of 1917–1921, the transformation of the original idea into a fully functioning educational and scientific organism. On the basis of archival material and little-known facts, an attempt is made to show that the university, as a state project, contributed to the strengthening of the Belarusian state, and its activities fully experienced all political and national demands and outlooks. In support of this, the article quotes examples of strict adherence of the BSU staff to all state guidelines, which primarily aimed at the continuous improvement of the educational process, at the training of professionals for the most important spheres of the national economy of the republic. The university strengthened its human potential, paying special attention to the development of fundamental and applied science (not only physics, mathematics, chemistry, and biology but also philosophy, history, and philology). In the 1920s, its scientists and students were in demand as disseminators of state plans among urban and rural population. A special place in the activities of the university was the policy of Belarusianization, which gave both an obvious positive effect and led to negative consequences. As a result, the author concludes that the two key words of the name of the university initially contained the ideas of its national, ethnic. and state affiliation and mission, which BSU strictly follows at the present time.

Using the promising fuel microemulsions based on diesel fuel (29.41–95.33 vol. %) and the mixture of diesel fuel with the vegetable additive in the form of methyl esters of rapeseed oil (4.80–43.27...

This article is devoted to the analysis of prospect to apply multifunctional adaptive antenna systems for radio monitoring stations. The review of publications done demonstrates that current antennas that are developed and used in radio monitoring systems to control and measure the parameters of electromagnetic radiation should be applicable to conduct accurate measurements in wide frequency range under the condition of interferences. The analysis shows that modern adaptive antenna systems are mostly developed for radar and telecommunications applications. In this context we consider possible ways to solve the problem of adapting radio monitoring devices to a complex electromagnetic environment using antenna systems with primary processing of received signals . It was found that the developers of the antennas, which are based on adaptive interference suppression methods, focus basically on the development and implementation of adaptation processes, limiting themselves only to solving electromagnetic compatibility problems. In such approach, the functions of direction finding and measurement of radiation field parameters important exactly for radio monitoring systems are mostly ignored. Therefore, this research area opens up a wide field for identifying new possibilities for constructing multifunctional antenna systems. Focusing on this direction of research, we consider as an example the constraction of a simple two-element adaptive antenna system, which can be used to measure the parameters of the electromagnetic field in radio monitoring systems. The main relations for the error of determining the direction of arrival of the interference signal with a simple two-element antenna are investigated. The influence of the stability of the antenna array parameters and functional units of signal processing onto the errors is estimated.

Subarctic populations of blue mussels represented by “cryptic” speciesMytilus edulis(ME) andM. trossulus(MT) have been studied less intensively than Arctic and boreal populations. Ecological features ofMEandMTin sympatry are poorly known everywhere. The knowledge about mussels at the northeasternmost boundary of the Atlantic littoral communities on Murman coast of the Barents Sea is based on data obtained 50-100 years ago. Our study provides the first insight into the long-term dynamics of the Barents Sea mussels, the habitat segregation ofMEandMT, and the interannual dynamics of their mixed settlements. The Tyuva Inlet (Kola Bay), which is 3 km long, was used as the study site. Mussels were found everywhere in the littoral and the sublittoral down to a depth of 4 m. Their characteristic habitats were sandbanks, littoral rocks, sublittoral kelp forests and “the habitat of the mussel bed” in the freshened top of the inlet. The main spatial gradients explaining the variability of demographics of the settlements (abundance, age structure, size) were associated with the depth and the distance from the inlet top.MEandMTwere partially segregated by depth:MEdominated in the sublittoral andMT, in the littoral. In addition,MEdominated both in the littoral and in the sublittoral parts of the mussel bed. The ratio of species in the mixed settlements varied over time: between 2004 and 2010 the proportions ofMTdecreased everywhere, by 22 % on average. Historical data indicate that the abundance of the Murman mussels declined sharply between the 1960s and the 1970s, which coincided with the cooling of the Arctic. It seems that the populations have not completely recovered in the abnormally warm recent decades. The habitat distribution of mussels apparently changed with time, too: unlike today, in the 20th century mussels were rarely observed in kelps. We suggest that the spatial and temporal dynamics of subarctic mussels can be partly explained by the competition betweenMEandMTcombined with their differing sensitivity to environmental factors.

Rapid eye movement (REM) sleep in rodents is defined by the presence of theta rhythm in the absence of movement. The amplitude and frequency of theta oscillations have been used to distinguish between tonic and phasic REM sleep. However, tonic REM sleep has not been further subdivided, although characteristics of network oscillations such as cross-frequency coupling between theta and gamma vary within this sub-state. Recently, it has been shown that theta-gamma coupling depends on an optimal breathing rate of ~5 Hz. The frequency of breathing varies strongly throughout REM sleep, and the duration of single REM sleep episodes ranges from several seconds to minutes, whereby short episodes predominate. Here we studied the relation between breathing frequency, accelerometer activity, and the length of REM sleep periods. We found that small movements detected with three-dimensional accelerometry positively correlate with breathing rate. Interestingly, breathing is slow in short REM sleep episodes, while faster respiration regimes exclusively occur after a certain delay in longer REM sleep episodes. Thus, merging REM sleep episodes of different lengths will result in a predominance of slow respiration due to the higher occurrence of short REM sleep periods. Moreover, our results reveal that not only do phasic REM sleep epochs predominantly occur during long REM sleep episodes, but that the long episodes also have faster theta and higher gamma activity. These observations suggest that REM sleep can be further divided from a physiological point of view depending on its duration. Higher levels of arousal during REM sleep, indicated by higher breathing rates, can only be captured in long REM sleep episodes.

Systemic capillary leak syndrome (SCLS) is a rare life-threatening disorder due to profound vascular leak. The trigger and the cause of the disease is currently unknown and there is no specific treatment. Here, we identified a rare heterozygous splice-site variant in theTLN1gene in a familial SCLS case, suggestive of autosomal dominant inheritance with incomplete penetrance. Talin1 has a key role in cell adhesions by activating and linking integrins to the actin cytoskeleton. This variant causes in-frame skipping of exon 54 and is predicted to affect talin’s c-terminal actin binding site (ABS3). Modelling the SCLS-TLN1variant by mimicking the actin-binding disruption inTLN1heterozygous endothelial cells resulted in disorganized endothelial adherens junctions. Mechanistically, we established that disruption of talin’s ABS3 sequestrates talin’s interacting partner, vinculin, at cell-extracellular matrix adhesions, leading to destabilization of the endothelial barrier. We propose that pathogenic variant inTLN1underlie SCLS, providing insight into the molecular mechanism of the disease which can be explored for future therapeutic interventions.SUMMARYSystemic capillary leak syndrome (SCLS) is a rare potentially lethal disease with unknown etiology and non-specific treatment. Here, we established a heterozygous splice variant of talin1, a key cell adhesion protein, as a genetic link to a familial SCLS case.

This paper proposes a new approach to estimating the contour of the coverage zone for a cellular communications base station that takes into account meaningful reflecting objects located out of the considering zone. Based on this approach, the procedure for modeling and designing the cellular system coverage area. Unlike known methods, the developed procedure considers the influence of electromagnetic wave reflection from external details of the relief, in particular essential reflecting objects located outside the considered cell. The effect of the external objects on the formation of the coverage area resulting contour is considered analytically, numerically and experimentally. The proposed solution leads to more accurate designing of the coverage area for each cell. This creates the opportunity for further development of designing techniques to more effective engineering solutions at developing and applying cellular communication systems in real situations and at various scenarios.

Type II diabetes mellitus poses numerous negative factors affecting the course of myocardial infarction, including both metabolic indicators (glycated hemoglobin levels, lipid spectrum indicators) and neurological factors (severity of diabetic polyneuropathy, including cardiac autonomic neuropathy).

Purpose. To establish a liquid chromatography/mass spectrometry method to compare the tissue distribution and metabolism of AN1284 after subcutaneous and oral administration at doses causing maximal reductions in IL-6 in plasma and tissues of mice. Methods. Lipopolysaccharide activated RAW 264.7 macrophages were used to detect the anti-inflammatory activity of AN1284 and its metabolites. Mice were given AN1284 by injection or gavage, 15 min before lipopolysaccharide. The reduction of IL-6 measured after 4h. Results. AN1284 is metabolized to the indole (AN1422), a 7-OH derivative and its glucuronide. AN1422 had weaker anti-inflammatory activity than AN1284 in LPS-activated macrophages and in mice. Maximal reductions in IL-6 in plasma, brain and liver were seen after subcutaneous injection of (0.5 mg/kg). This dose was also most effective in reducing IL-6 in the liver after oral drug administration but 2.5 mg/kg was needed for the same reductions in plasma and brain. Peak concentrations after oral administration of AN1284 (2.5 mg/kg) were 5.5-fold higher in the liver but 7-, 11 and 19-fold lower in plasma, brain and kidneys than after injection of 0.5 mg/kg. Similar concentrations in the liver were achieved by AN1284 (1 mg/kg/day) administered in the drinking fluid, and 2.5 mg/kg/day, via subcutaneously-implanted mini-pumps. Although drug levels were only 12% of the peak seen after acute injection of 0.5 mg/kg, they significantly decreased hepatocellular damage, liver triglycerides and cholesterol in diabetic mice. Conclusion. AN1284 can be given orally to treat chronic liver disease and its preferential concentration in the liver should limit potential adverse effects.

Circadian rhythms enable organisms to anticipate and adjust their physiology to periodic environmental changes. These rhythms are controlled by biological clocks that consist of a set of clock genes that regulate each other expression. Circadian oscillations in mRNA levels require regulation of mRNA production and degradation. While transcription factors controlling clock function have been well characterized from cyanobacteria to humans, the role of factors controlling mRNA decay is largely unknown. Here, we show that mutations in XRN4, the central component of the 5’-3’ mRNA decay pathway, alter clock function in Arabidopsis. We found that xrn4 mutants display long period phenotypes for clock gene expression and for the rhythm of leaf movement. These circadian defects were associated with changes in the circadian phases, but not overall mRNA levels, of several core clock genes. We then used non-invasive transcriptome-wide mRNA stability analysis to identify genes and pathways regulated by XRN4. Among genes affected in the xrn4 mutant at the transcriptional and post-transcriptional level, we found an enrichment in genes involved in auxin, ethylene, ABA signaling, and also circadian rhythmicity, although no significant effects were observed for canonical core-clock genes. Strikingly, the mRNAs of several clock regulated BBX genes were stabilized in xrn4 mutants. Some of these BBX genes are auxiliary factors controlling the pace of the clock and are candidates to mediate XRN4 effects on circadian period. Our results establish that, in Arabidopsis, the control of 5’-3’ mRNA decay by XRN4 constitutes a novel post-transcriptional regulatory layer of the circadian gene network.

Circadian rhythms enable organisms to anticipate and adjust their physiology to periodic environmental changes. These rhythms are controlled by biological clocks that consist of a set of clock genes that regulate each other’s expression. Circadian oscillations in messenger RNA (mRNA) levels require the regulation of mRNA production and degradation. While transcription factors controlling clock function have been well characterized from cyanobacteria to humans, the role of factors controlling mRNA decay is largely unknown. Here, we show that mutations in SM-LIKE PROTEIN 1 (LSM1) and exoribonucleases 4 (XRN4), components of the 5ʹ-3ʹ mRNA decay pathway, alter clock function in Arabidopsis. We found that lsm1 and xrn4 mutants display long-period phenotypes for clock gene expression. In xrn4, these circadian defects were associated with changes in circadian phases of expression, but not overall mRNA levels, of several core-clock genes. We then used noninvasive transcriptome-wide mRNA stability analysis to identify genes and pathways regulated by XRN4. Among genes affected in the xrn4 mutant at the transcriptional and posttranscriptional level, we found an enrichment in genes involved in auxin, ethylene and drought recovery. Large effects were not observed for canonical core-clock genes, although the mRNAs of several auxiliary clock genes that control the pace of the clock were stabilized in xrn4 mutants. Our results establish that the 5ʹ-3ʹ mRNA decay pathway constitutes a novel posttranscriptional regulatory layer of the circadian gene network, which probably acts through a combination of small effects on mRNA stability of several auxiliary and some core-clock genes.

The stability of magnetized flows of a nonuniformly rotating layer of an electrically conducting nanofluid is investigated with regard to the effects of Brownian diffusion and thermophoresis. In the absence of a temperature gradient, new types of magnetorotational instability (MRI) are considered in axial, azimuthal, and helical magnetic fields in thin layers of a nanofluid. The increments and development regions of these instabilities are obtained depending on the angular velocity profile (Rossby number Ro) and the radial wavenumber k. In the presence of temperature and nanoparticle concentration gradients, stationary regimes of nonuniformly rotating convection in axial and helical magnetic fields are studied. Expressions are obtained for the critical Rayleigh numbers Rast, and neutral stability curves are plotted depending on the angular velocity profile, the profile of the external azimuthal magnetic field (the magnetic Rossby number Rb), and the radial wavenumber k. Conditions for stabilization and destabilization of stationary convection in axial and helical magnetic fields are found.

The phenomenon of the ignition delay of a stoichiometric methane-air mixture in a shock tube (ST) installation is investigated. These experiments, in contrast to most other similar experiments, are carried out in incident shock waves. This makes it possible to obtain more reliable results by calculating the parameters from the measured velocity of the incident wave behind its front. The onset of the chemical process and, accordingly, the ignition is determined by the appearance of radiation from the OH• radical. H2 and He are used as driver gases. The ignition delay times are measured in the range of 870 to 4000 μs for the initial mixture temperatures of 800 to 1200 K and pressures 0.8 to 2.4 bar. Data on the ignition delay times at such low pressures have not been found in the literature.

Neuroblastoma (NB), a common solid tumor of children, can adopt a lineage-committed adrenergic (ADRN) or an immature mesenchymal (MES) tumor cell type, which differs in phenotype, epigenetic landscape, transcription factors, and core regulatory circuitries. These cell types can spontaneously interconvert, but the mechanism remains largely unknown. Here, we hypothesize that the tumor-associated macrophages (TAM) and cancer-associated fibroblast (CAF) within the tumor microenvironment contribute to pro-tumorigenic factors production and drive switching from ADRN to MES state in neuroblastoma. We first demonstrate the ADRN and MES lineage identity of NB cell lines by Western blot and compared the control and NB cell lines co-cultured with mesenchymal stromal cells (MSC), the precursor cell of CAF, and monocyte in transwell. Initial experiments demonstrated the morphology of NB cell line CHLA255 and CHLA136 showing increased spreading area and spindle shape in TAM-CAF co-cultures compared to control cells. As compared to control cells, monocytes and MSC-CAF co-culture induced the MES lineage markers SOX9 and Notch1 of NB cell lines that had low basal SOX9 expression, with a reduction in protein levels of ADRN lineage markers PHOX2B, and GATA3. Next, single-cell RNA-sequencing was utilized to analyze the expression of TAM and CAF, and MES- and ADRN-signature genes of NB cells in NB-TAM-CAF co-cultures. Single-cell analyses of TAM-CAF co-cultured CHLA255 and CHLA136 demonstrated enrichment of MES signature over time providing clear evidence of mesenchymal differentiation of NB cells within a TME-rich environment. Pathway enrichment analyses reveal enrichment of pathways associated with extracellular matrix (ECM) deposition and epithelial to mesenchymal of TAM-CAF co-cultured NB cell lines. Our results suggested that the presence of CAF and TAM in the tumor microenvironment drives neuroblastoma ADRN: MES switch akin to that observed in epithelial: mesenchymal switch in adult tumors. ADRN-MES state switching has been shown relevant for tumor relapse and therapy resistance. Our studies point to a therapeutic vulnerability by targeting cells and pathways activated in the NB-TAM-CAF axis. Citation Format: Meng-Hua Lee, Kevin Louault, Krinio Giannikou, Xiangming Ding, Alice Yanovsky, Jin-Seok Park, Yves A. DeClerck, Shahab Asgharzadeh. Mesenchymal stromal cells and tumor-associated macrophages modulate adrenergic to mesenchymal state switching in neuroblastoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3543.

Motivation Genome-wide analysis of alternative splicing has been a very active field of research since the early days of next generation sequencing technologies. Since then, ever-growing data availability and the development of increasingly sophisticated analysis methods have uncovered the complexity of the general splicing repertoire. A large number of splicing analysis methodologies exist, each of them presenting its own strengths and weaknesses. For instance, methods exclusively relying on junction information do not take advantage of the large majority of reads produced in an RNA-seq assay, isoform reconstruction methods might not detect novel intron retention events, some solutions can only handle canonical splicing events, and many existing methods can only perform pairwise comparisons. Results In this contribution, we present ASpli, a computational suite implemented in R statistical language, that allows the identification of changes in both, annotated and novel alternative-splicing events and can deal with simple, multi-factor or paired experimental designs. Our integrative computational workflow, that considers the same GLM model applied to different sets of reads and junctions, allows computation of complementary splicing signals. Analyzing simulated and real data, we found that the consolidation of these signals resulted in a robust proxy of the occurrence of splicing alterations. While the analysis of junctions allowed us to uncover annotated as well as non-annotated events, read coverage signals notably increased recall capabilities at a very competitive performance when compared against other state-of-the-art splicing analysis algorithms. Availability and implementation ASpli is freely available from the Bioconductor project site https://doi.org/doi:10.18129/B9.bioc.ASpli. Supplementary information Supplementary data are available at Bioinformatics online.

Calpainopathies constitute a heterogeneous group of disorders resulting from deficiencies in calpains, calcium-specific proteases that modulate substrates by limited proteolysis. Clinical manifestations depend on tissue-specific expression of the defective calpain and substrate specificity. CAPN15, encoding the Drosophila small optic lobes (sol) homolog, was recently found to cause various eye defects in individuals carrying bi-allelic missense variants. Here we report on two siblings with manifestations reminiscent of Johanson-Blizzard syndrome including failure to thrive, microcephaly, global developmental delay, dysmorphic features, endocrine abnormalities and congenital malformations, in addition to eye abnormalities. Exome sequencing identified a homozygous 47 base-pair deletion in a minimal intron of CAPN15, including the splice donor site. Sequencing of cDNA revealed single exon skipping, resulting in an out-of-frame deletion with a predicted premature termination codon. These findings expand the phenotypic spectrum associated with CAPN15 variants, and suggest that complete loss-of-function is associated with a recognizable syndrome of congenital malformations and developmental delay, overlapping Johanson-Blizzard syndrome and the recently observed brain defects in Capn15 knockout (KO) mice. Moreover, the data highlight the unique opportunity for indel detection in minimal introns.