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A two-dimensional steady-state model problem on a half-plane with a semi-infinite crack propagating at constant speed parallel to the boundary of the half-plane is considered. The crack faces are subjected to normal and tangential loads, while the boundary of the half-plane is free of traction. The problem is formulated as an order-2 vector Riemann–Hilbert problem and then reduced to a system of singular integral equations in a semi-infinite segment with respect to the derivatives of the displacement jumps. The solution to the system of integral equations is represented in a series form in terms of an orthonormal basis of the associated Hilbert space, the orthonormal Jacobi polynomials. The coefficients of the expansions solve an infinite system of linear algebraic equations of the second kind. The stress intensity factors and the weight functions are determined and computed. The Griffith energy criterion is applied to derive a crack growth criterion in terms of the KI- and KII-stress intensity factors, the crack speed, the shear and dilatational waves speeds and the Griffith material constant. [ABSTRACT FROM PUBLISHER]

The SMC protein family, including cohesin and condensin I/II, plays a pivotal role in maintaining the topological structure of chromosomes and influences many cellular processes, notably the repair of double-stranded DNA breaks (DSBs). The cohesin complex impacts DSB repair by spreading γH2AX signal and containing DNA ends in close proximity by loop extrusion. Cohesin supports DNA stability by sister chromatid cohesion during the S/G2 phase, which limits DNA end mobility. Cohesin knockdown was recently shown to stimulate frequencies of genomic deletions produced by distant paired DSBs, but does not affect DNA repair of a single or close DSBs. We examined how auxin-inducible protein degradation of Rad21 (cohesin) or Smc2 (condensins I+II) changes the frequencies of rearrangements between paired distant DSBs in mouse embryonic stem cells (mESCs). We used Cas9 RNP nucleofection to generate deletions and inversions with high efficiency without additional selection. We determined optimal Neon settings and deletion appearance timings. Two strategies for auxin addition were tested (4 independent experiments in total). We examined deletion/inversion frequencies for two regions spanning 3.5 and 3.9 kbp in size. Contrary to expectations, in our setting, Rad21 depletion did not increase deletion/inversion frequencies, not even for the region with an active Ctcf boundary. We actually observed a 12 % decrease in deletions (but not inversions). At the same time, double condensin depletion (Smc2 degron line) demonstrated high biological variability between experiments, complicating the analysis, and requires additional examination in the future. TIDE analysis revealed that editing frequency was consistent (30-50 %) for most experiments with a minor decrease after auxin addition. In the end, we discuss the Neon/ddPCR method for deletion generation and detection in mESCs., Competing Interests: The authors declare no conflict of interest., (Copyright © AUTHORS.)

Chromatin is not randomly distributed within the nucleus, but organized in a three-dimensional structure that plays a critical role in genome functions. Сohesin and condensins are conserved multi-subunit protein complexes that participate in mammalian genome organization by extruding chromatin loops. The fine temporal regulation of these complexes is facilitated by a number of other proteins, one of which is microcephalin (Mcph1). Mcph1 prevents condensin II from associating with chromatin through interphase. Loss of Mcph1 induces chromosome hypercondensation; it is not clear to what extent this reorganization affects gene expression. In this study, we generated several mouse embryonic stem cell (mESC) lines with knockout of the Mcph1 gene and analyzed their gene expression profile. Gene Ontology analyses of differentially expressed genes (DEGs) after Mcph1 knockout revealed gene categories related to general metabolism and olfactory receptor function but not to cell cycle control previously described for Mcph1. We did not find a correlation between the DEGs and their frequency of lamina association. Thus, this evidence questions the hypothesis that Mcph1 knockout-mediated chromatin reorganization governs gene expression in mESCs. Among the negative effects of Mcph1 knockout, we observed numerous chromosomal aberrations, including micronucleus formation and chromosome fusion. This confirms the role of Mcph1 in maintaining genome integrity described previously. In our opinion, dysfunction of Mcph1 may be a kind of "Rosetta stone" for deciphering the function of condensin II in the interphase nucleus. Thus, the cell lines with knocked-out Mcph1 can be used to further study the influence of chromatin structural proteins on gene expression., Competing Interests: The authors declare no conflict of interest., (Copyright © AUTHORS.)

The objective of the study was to analyze whether axial psoriatic arthritis (axPsA) patients meet classification criteria for axial spondyloarthritis (axSpA) and ankylosing spondylitis (AS). A total of 104 patients (66 men and 38 women) with PsA according to CASPAR criteria were examined, all patients had back pain. Patients were evaluated for presence of inflammatory back pain (IBP) by ASAS criteria. Back pain not meeting the ASAS criteria was taken to be chronic back pain (chrBP). Patients underwent hands, feet and pelvis, cervical spine and lumbar spine X-rays. Erosions, osteolysis, and juxta-articular new bone formation were evaluated. Definite radiographic sacroiliitis (d-rSI) was defined as bilateral grade ≥ 2 or unilateral grade ≥ 3. Nineteen patients without d-rSI underwent sacroiliac joints MRI. Ninety-three patients underwent HLA B27 examination. The number of patients who met the criteria for axSpA (ASAS) and the modified New York (mNY) criteria for AS was determined. IBP was identified in 67 (64.4%) patients; chrBP, in 37 (35.6%) patients; 31 (29.8%) patient were of older age (over 40) at the onset of IBP/chrBP; 57 (58.8%) patients had d-rSI; 6 (31.6%) patients had MRI-SI; syndesmophytes were detected in 57 (58.8%) cases. Among 40 patients without d-rSI, 19 (47.5%) had syndesmophytes. In 38/97 (39.2%) patients d-rSI was detected along with syndesmophytes, while 19/97 (19.6%) patients had isolated d-rSI without spondylitis, and 19/97 (19.6%) patients had isolated syndesmophytes without d-rSI. HLA B27 was present in 28 (30.1%) cases. 51 (55.4%) patients met criteria for axSpA. Forty-one (44.6%) patients did not meet criteria for axSpA; however, 27 (65.9%) of them had syndesmophytes. Forty-eight (48.5%) PsA patients met mNY criteria for AS. Among these patients, a set of specific features was revealed: 18 (37.5%) had no IBP, 18 (37.5%) were of older age (over 40) at the onset of IBP/chrBP, 34 (70.8%) had dactylitis, 38 (79.2%) had erosive polyarthritis, 23 (48.8%) had juxta-articular new bone formation, 14 (30.2%) had osteolysis, 23 (48.9%) had "chunky" non-marginal syndesmophytes, and 40 (82.6%) had nail psoriasis; 28 (66.6%) patients were HLA-B27 negative. Forty-five percent of axPsA patients do not meet criteria for axSpA. Characteristic features have been identified to differentiate axPsA from AS., (© 2024. Pleiades Publishing, Ltd.)

The COVID-19 pandemic has uncovered the high genetic variability of the SARS-CoV-2 virus and its ability to evade the immune responses that were induced by earlier viral variants. Only a few monoclonal antibodies that have been reported to date are capable of neutralizing a broad spectrum of SARS-CoV-2 variants. Here, we report the isolation of a new broadly neutralizing human monoclonal antibody, iC1. The antibody was identified through sorting the SARS-CoV-1 RBD-stained individual B cells that were isolated from the blood of a vaccinated donor following a breakthrough infection. In vitro , iC1 potently neutralizes pseudoviruses expressing a wide range of SARS-CoV-2 Spike variants, including those of the XBB sublineage. In an hACE2-transgenic mouse model, iC1 provided effective protection against the Wuhan strain of the virus as well as the BA.5 and XBB.1.5 variants. Therefore, iC1 can be considered as a potential component of the broadly neutralizing antibody cocktails resisting the SARS-CoV-2 mutation escape., Competing Interests: Patent applications are being filed for the iC1 antibody. KB, LM, OV, AN, NC, and AT are employees of IMGEN+, LLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from IMGEN+ LLC. The funder had the following involvement in the study: collection of data., (Copyright © 2024 Guselnikov, Baranov, Kulemzin, Belovezhets, Chikaev, Murasheva, Volkova, Mechetina, Najakshin, Chikaev, Solodkov, Sergeeva, Smirnov, Serova, Serov, Markhaev, Kononova, Alekseev, Gulyaeva, Danilenko, Battulin, Shestopalov and Taranin.)

We compute the potential-photon contributions to the classical relativistic scattering angle of two charged nonspinning bodies in electrodynamics through fifth order in the coupling. We use the scattering amplitudes framework, effective field theory, and multiloop integration techniques based on integration by parts and differential equations. At fifth order, the result is expressed in terms of cyclotomic polylogarithms. Our calculation demonstrates the feasibility of the corresponding calculations in general relativity, including the evaluation of the encountered four-loop integrals.

Compound L-36, a new derivative of 6H-1,3,4-thiadiazine, was studied in in vitro and in vivo experiments. This compound exhibits high antiplatelet and antithrombogenic activity. In in vitro experiments, compound L-36 by its antiplatelet activity (by IC 50 ) was superior to acetylsalicylic acid by 9.4 times. In in vivo experiments, compound L-36 by its ED 50 value was close to the comparison drug. On the model of pulmonary artery thrombosis, compound L-36 ensured better survival of experimental animals than acetylsalicylic acid. Morphological studies showed that compound L-36 effectively attenuated the thrombosis processes in the pulmonary tissue induced by intravenous injection of a thrombogenic mixture (epinephrine and collagen)., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

Samples of the holothurian Eupentactafraudatrix (Djakonov & Baranova in Djakonov, Baranova & Saveljeva, 1958) from the Sea of Japan were studied and the relationships of the genera Eupentacta and Sclerodactyla , as well as related taxa, were evaluated on the basis of phylogenetic analysis of the mitochondrial DNA COI and 16S rRNA genes. Using three methods, phylogenetic trees were constructed, and the degree of reliability of topological reconstructions was estimated by means of a nonparametric bootstrap test for the neighbor joining (NJ) and maximum likelihood (ML) techniques, as well as by a posteriori probability for Bayesian inference (BI) analysis. Genetic data confirm the validity of the assignment of Cucumariafraudatrix to the genus Eupentacta Deichmann, 1938. The study of sequences obtained from the holothurian specimens collected in Russian waters, near the city of Vladivostok, and determined by morphological characters clearly indicate that these specimens belong to the genus Eupentacta and are assigned as E.fraudatrix . The specimens from China in GenBank named as Sclerodactylamultipes and used in the present study, were likely misidentified, and after re-examination they may be assigned to the genus Eupentacta , either as E.fraudatrix or another taxon. Analyses of morphological characters of S.multipes unequivocally affirm that this species must be excluded from Sclerodactyla Ayres, 1851 and is provisionally assigned to the genus Sclerothyone Thandar, 1989 based on the external morphological characters and the body wall ossicles., Competing Interests: The authors have declared that no competing interests exist., (Sergei V. Turanov, Alexey V. Smirnov, Yuri Ph. Kartavtsev.)

One of the most productive strategies for finding the functions of proteins is to study the consequences of loss of protein function. For this purpose, cells or organisms with a knockout of the gene encoding the protein of interest are obtained. However, many proteins perform important functions and cells or organisms could suddenly lose fitness when the function of a protein is lost. For such proteins, the most productive strategy is to use inducible protein degradation systems. A system of auxin-dependent protein degradation is often implemented. To use this system, it is sufficient to introduce a transgene encoding a plant-derived auxin-dependent ubiquitin ligase into mammalian cells and insert a sequence encoding a degron domain into the gene of interest. A crucial aspect of development of cell lines engineered for inducible protein depletion is the selection of cell clones with efficient auxin-dependent degradation of the protein of interest. To select clones induced by depletion of the architectural chromatin proteins RAD21 (a component of the cohesin complex) and SMC2 (a component of the condensin complex), we propose to use the morphology of metaphase chromosomes as a convenient functional test. In this work, we obtained a series of clones of human HAP1 cells carrying the necessary genetic constructs for inducible depletion of RAD21 and SMC2. The degradation efficiency of the protein of interest was assessed by flow cytometry, Western blotting and metaphase chromosome morphology test. Based on our tests, we showed that the clones we established with the SMC2 degron effectively and completely lose protein function when induced by auxin. However, none of the HAP1 clones we created with the RAD21 degron showed complete loss of RAD21 function upon induction of degradation by auxin. In addition, some clones showed evidence of loss of RAD21 function even in the absence of induction. The chromosome morphology test turned out to be a convenient and informative method for clone selection. The results of this test are in good agreement with flow cytometry analysis and Western blotting data., Competing Interests: The authors declare no conflict of interest., (Copyright © AUTHORS.)

Mucormycosis is a disease caused by fungi of the Mucorales family, widespread in the environment, with pronounced angiotropism and the ability to angioinvasion, leading to thrombosis with surrounding necrosis. The main triggers for the development of mucormycosis are: immunodeficiency states, use of glucocorticosteroid drugs, decompensation of diabetes mellitus, concomitant diseases, age > 65 years. We present a clinical case of rhinocerebral mucormycosis in a 79-year-old patient against the background of uncontrolled type 2 diabetes mellitus with ketoacidosis, a condition after previous glucocorticosteroid therapy for COVID-19 (according to the severity of the disease). After suffering a new coronavirus infection caused by the SARS-CoV-2 virus, she was admitted to the hospital with complaints characteristic of mucormycosis. On the 5 th day of hospital stay, the patient's condition worsened significantly, despite the correction of the therapy, and on the 12 th day the patient died. According to the results of the autopsy, it was established that the rhinocerebral mucormycosis was complicated by thrombosis of the anterior and posterior left cerebral arteries with subsequent infarctions in the frontal lobe and parieto-occipital region of the brain left hemisphere, cerebral edema, which was the immediate cause of death.

Cohen syndrome is an autosomal recessive disorder caused by VPS13B ( COH1 ) gene mutations. This syndrome is significantly underdiagnosed and is characterized by intellectual disability, microcephaly, autistic symptoms, hypotension, myopia, retinal dystrophy, neutropenia, and obesity. VPS13B regulates intracellular membrane transport and supports the Golgi apparatus structure, which is critical for neuron formation. We generated induced pluripotent stem cells from two patients with pronounced manifestations of Cohen syndrome and differentiated them into neural stem cells and neurons. Using transmission electron microscopy, we documented multiple new ultrastructural changes associated with Cohen syndrome in the neuronal cells. We discovered considerable disturbances in the structure of some organelles: Golgi apparatus fragmentation and swelling, endoplasmic reticulum structural reorganization, mitochondrial defects, and the accumulation of large autophagosomes with undigested contents. These abnormalities underline the ultrastructural similarity of Cohen syndrome to many neurodegenerative diseases. The cell models that we developed based on patient-specific induced pluripotent stem cells can serve to uncover not only neurodegenerative processes, but the causes of intellectual disability in general.

Analytical devices for bacterial detection are an integral part of modern laboratory medicine, as they permit the early diagnosis of diseases and their timely treatment. Therefore, special attention is directed to the development of and improvements in monitoring and diagnostic methods, including biosensor-based ones. A promising direction in the development of bacterial detection methods is optical sensor systems based on colorimetric and fluorescence techniques, the surface plasmon resonance, and the measurement of orientational effects. This review shows the detecting capabilities of these systems and the promise of electro-optical analysis for bacterial detection. It also discusses the advantages and disadvantages of optical sensor systems and the prospects for their further improvement.

Amoebae of the genus Leptomyxa have variable morphologies and can only be reliably identified using molecular data. However, species distinction based on the 18S rRNA gene sequence is difficult due to the very low level of sequence divergence among morphologically different species. The database for other genes is much smaller, and genomic data on Leptomyxa is almost absent. In this study, we describe two new terrestrial species of the genus Leptomyxa isolated from Northwestern Russia, Leptomyxa botanica n. sp. and Leptomyxa monrepos n. sp. Both species easily adopt an expanded fan-shaped form and have a complex structure of the nucleolar material. Phylogenetic analyses show a derived status of these two species. They form a clade with Leptomyxa valladaresi. Our tree confirms that the 18S rRNA gene sequences of Leptomyxa species are split into two large clades. The morphological synapomorphies of these clades are not obvious. This analysis is complicated by the lack of reliable morphological data on many sequenced strains and probable misidentification of some isolates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Fibrodysplasia ossificans progressive (FOP) is an ultra-rare genetic disorder that is caused by a mutation in the ACVR1 gene and provokes severe heterotopic ossification. Since flares of the disease are associated with inflammation, it is assumed that JAK inhibitors can control active FOP due to blocking multiple signaling pathways., (© 2023. BioMed Central Ltd., part of Springer Nature.)

This study presents data on the growth rate and frequency of induction of the solid form of Ehrlich's ascites carcinoma (EAC) in mice in the short and long term after inoculation of ascitic cells irradiated ex vivo with a proton beam in the dose range of 30-150 Gy. It was shown that the growth rate of solid tumors after inoculation of irradiated cells ex vivo coincided with the growth of tumors in the control group. The frequency of tumor induction in mice after inoculation of EAC cells irradiated at a dose of 30 Gy was 80%, 60 Gy-60%, 90 Gy-25%, and 120 Gy-10%; at irradiation at a dose of 150 Gy, no tumors appeared during the entire observation period. Thus, we determined the dose of proton radiation required to eliminate tumor cells and/or signaling factors that can lead to the induction of tumor growth of EAC in mice., (© 2023. Pleiades Publishing, Ltd.)

An antibody-detecting sensor is described that is based on a microwave electrodynamic resonator. A polystyrene film with immobilized bacteria deposited on a lithium niobate plate was placed at one end of the resonator and was used as the sensing element. The second end was electrically shorted. The frequency and depth of the reflection coefficient S 11 for three resonances in the range 6.5-8.5 GHz were used as an analytical signal to examine antibody interactions with bacteria and determine the time required for cell immobilization. The sensor distinguished between situations in which bacteria interacted with specific antibodies and those in which no such interaction occurred (control). Although the cell-antibody interaction changed the frequency and depth of the second and third resonance peaks, the parameters of the first resonance peak did not change. The interaction of cells with nonspecific antibodies did not change the parameters of any of the peaks. These results are promising for use in the design of methods to detect specific antibodies, which can supplement the existing methods of antibody analysis., Competing Interests: Declaration of competing interest There is no conflict of interest about this article. Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Interstitial electron density ρ_{o} is offered as a direct metric for maximum strength in metals, arising from universal properties derived from an electron gas. ρ_{o} sets the exchange-correlation parameter r_{s} in density-functional theory. It holds also for maximum shear strength τ_{max} in polycrystals [M. Chandross and N. Argibay, Phys. Rev. Lett. 124, 125501 (2020)PRLTAO0031-900710.1103/PhysRevLett.124.125501]. Elastic moduli and τ_{max} for polycrystalline (amorphous) metals are linear with ρ_{o} and melting T_{m} (glass-transition T_{g}) temperature. ρ_{o} or r_{s}, even with rule-of-mixture estimate, predicts relative strength for rapid, reliable selection of high-strength alloys with ductility, as confirmed for elements to steels to complex solid solutions, and validated experimentally.

This paper presents the design, prototype engineering, and initial testing of a relatively low-voltage, high aspect ratio electron gun for versatile pulsed power applications. The sheet beam, diode electron gun is designed for (23-25) kV voltage and 6 µA/V1.5, as is required for x-band klystron, as a part of a compact Klylac delivering electron beam energy in the MeV range. The gun prototype was engineered, built, and tested using a Scandinova M1-0.5 modulator. Beam loss on the anode aperture is evaluated from transient waveforms and equivalent circuit modeling., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Objectives: Netakimab is a humanised camelid-derived monoclonal antibody targeting interleukin-17A. Here, we report the results of post-hoc analysis of the ASTERA phase 3 study (NCT03447704, February 27, 2018) in patients with active radiographic axial spondyloarthritis (r-axSpA) grouped by baseline C-reactive protein (CRP), baseline sacroiliac joint (SIJ) inflammation through magnetic resonance imaging (MRI) or presence of peripheral arthritis (PA)., Methods: In this double-blinded, multicentre, randomised, placebo-controlled, phase 3 ASTERA study, 228 adult patients with active r-axSpA received 120 mg of subcutaneous netakimab or placebo at weeks 0, 1, 2, and thereafter every other week. For the subanalysis, 16-week data of 114 netakimab-treated patients with the available baseline CRP and SIJ MRI were grouped by normal (<5 mg/L) or abnormal (≥5 mg/L) CRP, by the grade of sacroiliitis (SI) based on the SPARCC MRI score <2 (MRI-SI-) or ≥2 (MRI-SI+), or by the presence of PA. ASAS-recommended activity, spinal mobility, and function endpoints for r-axSpA were analysed., Results: At week 16, an improvement in all the outcomes was similar for MRI-SI- and MRI-SI+ patients, except for a change in ASspi-MRI-a which was significantly greater in MRI-SI+. Netakimab was effective regardless of baseline CRP and PA. For patients with CRP ≥5 mg/L, a more pronounced decline in r-axSpA activity was observed with a trend towards the most prominent improvement in ASDAS-CRP and BASDAI for patients with CRP >20 mg/L., Conclusions: Subcutaneous netakimab is effective in patients with r-axSpA irrespective of baseline CRP and inflammation on SIJ MRI. The benefit in patients with high CRP (>20 mg/L) was more pronounced.

Metchnikovellids (Microsporidia: Metchnikovellida) are poorly studied hyperparasitic microsporidia that live in gregarines inhabiting the intestines of marine invertebrates, mostly polychaetes. Our recent studies showed that diversity of metchnikovellids might be significantly higher than previously thought, even within a single host. Four species of metchnikovellids were found in the gregarines inhabiting the gut of the polychaete Pygospio elegans from littoral populations of the White and Barents Seas: the eugregarine Polyrhabdina pygospionis is the host for Metchnikovella incurvata and M. spiralis, while the archigregarine Selenidium pygospionis is the host for M. dogieli and M. dobrovolskiji. The most common species in the White Sea is M. incurvata, while M. dobrovolskiji prevails in the Barents Sea. Gregarines within a single worm could be infected with different metchnikovellid species. However, co-infection of one and the same gregarine with several species of metchnikovellids has never been observed. The difference in prevalence and intensity of metchnikovellid invasion apparently depends on the features of the life cycle and on the development strategies of individual species., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

The influence of the method of applying the activating additive ammonium chloride and its concentration on the density and microstructure of zinc oxide ceramic obtained by cold sintering at 244 °C was investigated. The activating agent was applied by two methods: impregnation and subsequent autoclave treatment. When the powder was activated by the impregnation method, the crystal sizes remained at the initial level of 0.17-0.19 μm. After the autoclave treatment, the crystal sizes increased to 0.31-0.53 μm. Samples of cold sintering ZnO with relative density up to 0.96 and average grain sizes 0.29-0.86 μm were obtained. ZnO powders and ceramic samples were analyzed using SEM, TGA/DSC, and XRD to reveal the effect of the powder activation method and cold sintering conditions on the material microstructure. The effect of ammonium chloride concentration on grain growth and microstructure of ceramic samples is shown. It was found that the average grain size of ceramic samples with an increase in additive concentration passes through a minimum. In cold sintering of the autoclave activated powder, the effect of reducing the average grain size was observed. The results of this work are discussed on the basis of the idea of the solid-phase mobility of the crystal structure arising when interacting with an aqueous medium.