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We report the discovery of new lensed quasar candidates in the imaging data of the Hyper Suprime-Cam Subaru Strategic Program (HSC-SSP) Data Release 4, covering |$1\, 310\deg ^2$| of the sky with median seeing in the i band of ≈0.6 arcsec. In addition to two catalogues of Million Quasars Catalog v7.2 and AllWISE Catalog of Mid-Infra Red Active Galactic Nuclei, containing confirmed and candidate quasars, we preselect quasar sources using colour cuts from the HSC (grizy) and unWISE (W 1 + W 2) photometric data based on SDSS spectroscopic catalogues. We search for the presence of multiple point sources with similar colour through the convolution of the Laplacian of the preselected quasar image cutouts with the Laplacian of the point spread function, resulting in a reduction of lens candidates from 1 652 329 to 121 511 (7.4 per cent). After visual binary classification, we grade 6 199 (0.4 per cent) potential lenses on a scale of 0 to 3, with 3 indicating a lens and 0 indicating a non-lens. Finally we obtain 162 lens candidates with an average grade of ≥2, and among them, we successfully recover 18 known lenses. By fitting the light distribution and removing the known contaminants, we discover that 57 new systems contain at least two point sources and a galaxy in between, including 10 possible quadruply lensed quasars. This new sample exhibits a median separation of 1.26 arcsec and a magnitude limit of i ≈ 22. Spectroscopic or high-resolution imaging follow up on these newly discovered lensed quasar candidates will further allow their natures to be confirmed. [ABSTRACT FROM AUTHOR]

Abstract Current therapeutics of endometriosis focus on hormonal disruption of endometriotic lesions (ectopic endometrium, EcE). Recent findings show higher glycolysis utilization in EcE, suggesting non-hormonal strategy for disease treatment that addresses cellular metabolism. Identifying metabolically altered cell types in EcE is important for targeted metabolic drug therapy without affecting eutopic endometrium (EuE). Here, using single-cell RNA-sequencing, we examine twelve metabolic pathways in paired samples of EuE and EcE from women with confirmed endometriosis. We detect nine major cell types in both EuE and EcE. Metabolic pathways are most differentially regulated in perivascular, stromal, and endothelial cells, with the highest changes in AMPK signaling, HIF-1 signaling, glutathione metabolism, oxidative phosphorylation, and glycolysis. We identify transcriptomic co-activation of glycolytic and oxidative metabolism in perivascular and stromal cells of EcE, indicating a critical role of metabolic reprogramming in maintaining endometriotic lesion growth. Perivascular cells, involved in endometrial stroma repair and angiogenesis, may be potential targets for non-hormonal treatment of endometriosis.

Abstract Tuberculosis (TB) remains one of the top 10 causes of death worldwide and still poses a serious challenge to public health. Recent attention to neutrophils has uncovered unexplored areas demanding further investigation. Therefore, the aim of this study was to determine neutrophil activation and circulatory neutrophil extracellular trap (NET) formation in various types of TB. Sera from TB patients (n = 91) and healthy controls (NHD; n = 38) were analyzed for NE-DNA and MPO–DNA complexes, cell-free DNA (cfDNA), and protease activity (elastase). We show that these NET parameters were increased in TB sera. Importantly, NET formation and NE activity were elevated in TB patients with extensive tissue damage when compared to those with minor damage and in patients with relapse, compared to new cases. We discuss the importance of balancing NET formation to prevent tissue damage or even relapse and argue to analyze circulating NET parameters to monitor the risk of disease relapse. To investigate the tissues for NETs and to find the source of the circulating NET degradation products, we collected sections of granulomas in lung and lymph node biopsies. Samples from other diseases with granulomas, including sarcoidosis (SARC) and apical periodontitis (AP), served as controls. Whereas NET formation characterizes the caseating granulomas, both caseating and non-caseating granulomas harbor DNA with unusual conformation. As TB is associated with hypercoagulation and thromboembolism, we further imaged the pulmonary vessels of TB patients and detected vascular occlusions with neutrophil aggregates. This highlights the dual role of neutrophils in the pathology of TB.

The article presents the application of the time domain reflectometry (TDR) technique for measuring the moisture of porous building materials used in construction. The work is focused on using the potential of artificial intelligence to improve the quality of TDR measurements through a new approach to the interpretation of data obtained from the TDR readings. Machine learning is a data analysis technique, used nowadays in many scientific disciplines. The authors performed a measurement data analysis using the artificial intelligence algorithms to assess moisture of aerated concrete samples tested with a TDR multimeter using two non-invasive sensors which differ in thickness. Data analysis was carried out using supervised machine learning to analyse a series of reflectograms obtained during the measurement. For the data achieved by the classical and machine learning method interpretation, correlation analysis was conducted to confirm the potential of artificial intelligence to improve the quality of TDR measurement. The summary of the work discusses the obtained analytical results and highlights the effectiveness of moisture assessment using the Gaussian Process Regression method, which allowed achieving a level of 0.2 - 0.3% of the RMSE errors value, which is about 10 times lower than the traditional approach.

IntroductionThe identification of significant DNA markers of primary osteoporosis may gain new insights by studying genome regions involved in mechanisms of epigenetic regulation through interactions with microRNAs.MethodsThe authors searched for associations of polymorphic variants of microRNA binding sites of mRNA target genes and polymorphic loci of microRNA genes with primary osteoporosis in a cohort of women and men from the Volga-Ural region of Russia (N = 1.177).ResultsUsing case-control association analysis, the authors found that rs1061947 (COL1A1), rs10793442 (ZNF239), rs6854081 (FGF2), and rs11614913 (miR-196a) were associated with osteoporotic fractures; rs5854 (MMP1) and rs2910164 (miR-146a) were associated with low bone mineral density; and rs10098470 (TPD52), rs11540149 (VDR), rs1042673 (SOX9), rs1054204 (SPARC), and rs1712 (FBXO5) were markers of both fractures and low bone mineral density. Among the identified associations, ethno specific trends were found, as well as sex-specific associations. Prognostic models were developed, among which the model for predicting osteoporosis in general in women (Area Under Curve = 0.909) achieved the highest level of predictive value. Thus, the potential role of polymorphic variants of microRNA binding sites in the development of primary osteoporosis in men and women from the Volga-Ural region of Russia was demonstrated.

The pharmaceutical industry is increasingly embracing laboratory automation to enhance experimental efficiency and operational resilience, particularly through the integration of automated liquid handlers (ALHs). This paper explores the integration of the low-cost Opentrons OT-2 liquid handling robot with F. Hoffmann-La Roche AG's in-house workflow orchestration software, AutoLab, to overcome barriers to lab automation. By leveraging the OT-2′s development-oriented interfaces and AutoLab's modular architecture, we achieved a user-friendly, cost-efficient, and flexible automation solution that aligns with FAIR (findable, accessible, interoperable, reusable) data principles. We demonstrate an advanced workflow development methodology, utilizing the software architecture, that facilitates the creation of two flexible pipetting protocols and medium complexity assays. This deep integration approach diminishes the learning curve for novice users while simultaneously enhancing the overall efficiency and reliability of the experimental workflow. Our findings suggest that such integrations can significantly mitigate the challenges associated with lab automation, including cost, complexity, and adaptability, paving the way for more accessible and robust automated systems in pharmaceutical research.

The relevance of the study lies in the fact that until recently the reaction of various types of perennial grasses to the terms of alienation of herbage in the last cycle of use has not been clarified, which hinders the development and implementation of technology for creating perennial agrophytocoenoses in the continuous pasture system with an extended grazing period for meat livestock in the late autumn period. The purpose of the study was to select the best perennial grasses for late autumn alienation of herbage in the system of an extended continuous pasture for meat breeds of cattle in the Right-Bank Forest-Steppe. The results of long-term research on the features of the development of the yield of aboveground biomass, the chemical composition of feed, the stability of certain types of grasses depending on the time of alienation of aboveground biomass in total for all cycles of use and in the last cycle in the autumn period are presented. The highest productivity (at the level of 0.60-0.95 t/ha of dry weight) of all types of grasses in the last (autumn) cycle of use is provided when the green mass is alienated on October 1. When alienated at a later date, the collection of dry mass from 1 ha decreases, while the quality of feed worsens due to a decrease in the content of crude protein and an increase in the concentration of crude fibre to the limits that do not meet the zootechnical norm of feeding cattle and the requirements of DSTU for green feed. Studies have identified the best single-species agrophytocoenoses of grasses, which include smooth brome, cocksfoot grass, and intermediate wheatgrass. On average, for 2008-2015, in the sum of all three cycles of use, they provide a productivity of 6.52-7.19 t/ha of dry weight when applying N120. The results of these studies can be used in the development of recommendations for the creation of continuous pasture with an extended period of grazing grass with meat livestock in the autumn period, which reduces the cost and increases the competitiveness of livestock products

Abstract Mass transport at surfaces determines the kinetics of processes such as heterogeneous catalysis and thin-film growth, with the diffusivity being controlled by excitation across a translational barrier. Here, we use neutron spectroscopy to follow the nanoscopic motion of triphenylphosphine (P(C6H5)3 or PPh3) adsorbed on exfoliated graphite. Together with force-field molecular dynamics simulations, we show that the motion is similar to that of a molecular motor, i.e. PPh3 rolls over the surface with an almost negligible activation energy for rotations and motion of the phenyl groups and a comparably small activation energy for translation. While rotations and intramolecular motion dominate up to about 300 K, the molecules follow an additional translational jump-motion across the surface from 350-500 K. The unique behaviour of PPh3 is due to its three-point binding with the surface: Along with van der Waals corrected density functional theory calculations, we illustrate that the adsorption energy of PPh3 increases considerably compared to molecules with flat adsorption geometry, yet the effective diffusion barrier for translational motion increases only slightly. We rationalise these results in terms of molecular symmetry, structure and contact angle, illustrating that the molecular degrees of freedom in larger molecules are intimately connected with the diffusivity.

Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor because it does not bind to a known specific receptor on the plasma membrane and functions primarily as an unfolded protein response (UPR) regulator in the endoplasmic reticulum. Data on the effects of CDNF on nonmotor behavior and monoamine metabolism are limited. Here, we performed the intracerebroventricular injection of a recombinant CDNF protein at doses of 3, 10, and 30 μg in C57BL/6 mice. No adverse effects of the CDNF injection on feed and water consumption or locomotor activity were observed for 3 days afterwards. Decreases in body weight and sleep duration were transient. CDNF-treated animals demonstrated improved performance on the operant learning task and a substantial decrease in anxiety and behavioral despair. CDNF in all the doses enhanced serotonin (5-HT) turnover in the murine frontal cortex, hippocampus, and midbrain. This alteration was accompanied by changes in the mRNA levels of the 5-HT1A and 5-HT7 receptors and in monoamine oxidase A mRNA and protein levels. We found that CDNF dramatically increased c-Fos mRNA levels in all investigated brain areas but elevated the phosphorylated-c-Fos level only in the midbrain. Similarly, enhanced CREB phosphorylation was found in the midbrain in experimental animals. Additionally, the upregulation of a spliced transcript of XBP1 (UPR regulator) was detected in the midbrain and frontal cortex. Thus, we can hypothesize that exogenous CDNF modulates the UPR pathway and overall neuronal activation and enhances 5-HT turnover, thereby affecting learning and emotion-related behavior.

The formation of the ferroelectric domain structure as a result of irradiation by focused ion beam of [100]-cut 0.61Pb(Mg[Formula: see text]Nb[Formula: see text]O3–0.39PbTiO3 (PMN–PT) single crystals covered by surface artificial dielectric layer and with free surface was investigated. The dot irradiation resulted in formation of the wedge-like domains grown along [00[Formula: see text]] direction. For irradiation of the free surface, the domains are mainly located under the surface, while at the irradiated surface with an artificial dielectric layer the domains are located at the surface. It was shown that the subsurface wedge-shaped part of the domain is unstable and completely disappears after a month due to spontaneous backswitching under the action of the residual depolarization field. The revealed nonlinear dose dependence of the domain sizes was attributed to the distribution of the electric field using the point charge model. The domain interaction for the distance between irradiated dots below 30[Formula: see text][Formula: see text]m has been revealed in all samples. It was shown that the decrease of the distance between irradiated dots in the created domain row leads to an increase in the length of the central domains, which is explained by the contribution of all injected charges to the switching field.

The paper is devoted to further elaboration of the Method of Matched Sections as a new branch of finite element method in application to the transient 2D temperature problem. The main distinction of MMS from conventional FEM consist in that the conjugation is provided between the adjacent sections rather than in the nodes of the elements. Important feature is that method is based on approximate strong form solution of the governing differential equations called here as the Connection equations. It is assumed that for each small rectangular element the 2D problem can be considered as the combination of two 1D problems – one is x-dependent, and another is y-dependent. Each problem is characterized by two functions – the temperature, , and heat flux . In practical realization for rectangular finite elements the method is reduced to determination of eight unknowns for each element – two unknowns on each side, which are related by the Connection equations, and requirement of the temperature continuity at the center of element. Another salient feature of the paper is an implementation of the original implicit time integration scheme, where the time step became the parameter of shape function within the element, i.e. it determines the behavior of the Connection equations. This method was early proposed by first author for number of 1D problem, and here in first time it is applied for 2D problems. The number of tests for rectangular plate exhibits the remarkable properties of this “embedded” time integration scheme with respect to stability, accuracy, and absence of any restrictions as to increasing of the time step.

The search for the molecular markers of osteoporosis (OP), based on the analysis of differential deoxyribonucleic acid (DNA) methylation in bone cells and peripheral blood cells, is promising for developments in the field of the early diagnosis and targeted therapy of the disease. The Runt-related transcription factor 2 (RUNX2) gene is one of the key genes of bone metabolism, which is of interest in the search for epigenetic signatures and aberrations associated with the risk of developing OP. Based on pyrosequencing, the analysis of the RUNX2 methylation profile from a pool of peripheral blood cells in men and women over 50 years of age of Russian ethnicity from the Volga-Ural region of Russia was carried out. The level of DNA methylation in three CpG sites of the RUNX2 gene was assessed and statistically significant hypomethylation was revealed in all three studied CpG sites in men (U = 746.5, p = 0.004; U = 784, p = 0.01; U = 788.5, p = 0.01, respectively) and in one CpG site in women (U = 537, p = 0.03) with primary OP compared with control. In the general sample, associations were preserved for the first CpG site (U = 2561, p = 0.0001766). The results were obtained for the first time and indicate the existence of potentially new epigenetic signatures of RUNX2 in individuals with OP.

We study quasi-freestanding bilayer graphene on silicon carbide intercalated by calcium. The intercalation, and subsequent changes to the system, were investigated by low-energy electron diffraction, angle-resolved photoemission spectroscopy (ARPES) and density-functional theory (DFT). Calcium is found to intercalate only at the graphene-SiC interface, completely displacing the hydrogen terminating SiC. As a consequence, the system becomes highly n-doped. Comparison to DFT calculations shows that the band dispersion, as determined by ARPES, deviates from the band structure expected for Bernal-stacked bilayer graphene. Instead, the electronic structure closely matches AA-stacked bilayer graphene on calcium-terminated SiC, indicating a spontaneous transition from AB- to AA-stacked bilayer graphene following calcium intercalation of the underlying graphene-SiC interface.

Energy dissipation and the transfer rate of adsorbed molecules do not only determine the rates of chemical reactions but are also a key factor that often dictates the growth of organic thin films. Here, we present a study of the surface dynamical motion of cobalt phthalocyanine (CoPc) on Ag(100) in reciprocal space based on the helium spin-echo technique in comparison with previous scanning tunnelling microscopy studies. It is found that the activation energy for lateral diffusion changes from 150 meV at 45–50 K to ≈100 meV at 250–350 K, and that the process goes from exclusively single jumps at low temperatures to predominantly long jumps at high temperatures. We thus illustrate that while the general diffusion mechanism remains similar, upon comparing the diffusion process over widely divergent time scales, indeed different jump distributions and a decrease of the effective diffusion barrier are found. Hence a precise molecular-level understanding of dynamical processes and thin film formation requires following the dynamics over the entire temperature scale relevant to the process. Furthermore, we determine the diffusion coefficient and the atomic-scale friction of CoPc and establish that the molecular motion on Ag(100) corresponds to a low friction scenario as a consequence of the additional molecular degrees of freedom.

Boronate esters are a class of compounds containing a boron atom bonded to two oxygen atoms in an ester group, often being used as precursors in the synthesis of other materials. The characterization of the structure and properties of esters is usually carried out by UV-visible, infrared, and nuclear magnetic resonance (NMR) spectroscopic techniques. With the aim to better understand our experimental data, in this article, the density functional theory (DFT) is used to analyze the UV-visible and infrared spectra, as well as the isotropic shielding and chemical shifts of the hydrogen atoms 1H, carbon 13C and boron 11B in the compound 4-(4,4,5,5-tetramethyl-1,3,2-dioxoborolan-2-yl)benzaldehyde. Furthermore, this study considers the change in its electronic and spectroscopic properties of this particular ester, when its boron atom is coordinated with a fluoride anion. The calculations were carried out using the LSDA and B3LYP functionals in Gaussian-16, and PBE in CASTEP. The results show that the B3LYP functional gives the best approximation to the experimental data. The formation of a coordinated covalent B–F bond highlights the remarkable sensitivity of the NMR chemical shifts of carbon, oxygen, and boron atoms and their surroundings. Furthermore, this bond also highlights the changes in the electron transitions bands n → π* and π → π* during the absorption and emission of a photon in the UV-vis, and in the stretching bands of the C=C bonds, and bending of BO2 in the infrared spectrum. This study not only contributes to the understanding of the properties of boronate esters but also provides important information on the interactions and responses optoelectronic of the compound when is bonded to a fluorine atom.

Osteoarthritis is a chronic progressive joint disease that clinically debuts at the stage of pronounced morphologic changes, which makes treatment difficult. In this regard, an important task is the study of genetic markers of the disease, which have not been definitively established, due to the clinical and ethnic heterogeneity of the studied populations. To find the genetic markers for the development of knee osteoarthritis (OA) in women from the Volga-Ural region of Russia, we conducted research in two stages using different genotyping methods, such as the restriction fragment length polymorphism (RFLP) measurement, TaqMan technology and competitive allele-specific PCR—KASPTM. In the first stage, we studied polymorphic variants of candidate genes (ACAN, ADAMTS5, CHST11, SOX9, COL1A1) for OA development. The association of the *27 allele of the VNTR locus of the ACAN gene was identified (OR = 1.6). In the second stage, we replicated the GWAS results (ASTN2, ALDH1A2, DVWA, CHST11, GNL3, NCOA3, FILIP/SENP1, MCF2L, GLT8D, DOT1L) for knee OA studies. The association of the *T allele of the rs7639618 locus of the DVWA gene was detected (OR = 1.54). Thus, the VNTR locus of ACAN and the rs7639618 locus of DVWA are risk factors for knee OA in women from the Volga-Ural region of Russia.

We developed a procedure for locating genes on Drosophila melanogaster polytene chromosomes and described three types of chromosome structures (gray bands, black bands, and interbands), which differed markedly in morphological and genetic properties. This was reached through the use of our original methods of molecular and genetic analysis, electron microscopy, and bioinformatics data processing. Analysis of the genome-wide distribution of these properties led us to a bioinformatics model of the Drosophila genome organization, in which the genome was divided into two groups of genes. One was constituted by 65, in which the genome was divided into two groups, 62 genes that are expressed in most cell types during life cycle and perform basic cellular functions (the so-called “housekeeping genes”). The other one was made up of 3162 genes that are expressed only at particular stages of development (“developmental genes”). These two groups of genes are so different that we may state that the genome has two types of genetic organization. Different are the timings of their expression, chromatin packaging levels, the composition of activating and deactivating proteins, the sizes of these genes, the lengths of their introns, the organization of the promoter regions of the genes, the locations of origin recognition complexes (ORCs), and DNA replication timings.

Quantization is a widespread method for reducing the inference time of neural networks on mobile Central Processing Units (CPUs). Eight-bit quantized networks demonstrate similarly high quality as full precision models and perfectly fit the hardware architecture with one-byte coefficients and thirty-two-bit dot product accumulators. Lower precision quantizations usually suffer from noticeable quality loss and require specific computational algorithms to outperform eight-bit quantization. In this paper, we propose a novel 4.6-bit quantization scheme that allows for more efficient use of CPU resources. This scheme has more quantization bins than four-bit quantization and is more accurate while preserving the computational efficiency of the later (it runs only 4% slower). Our multiplication uses a combination of 16- and 32-bit accumulators and avoids multiplication depth limitation, which the previous 4-bit multiplication algorithm had. The experiments with different convolutional neural networks on CIFAR-10 and ImageNet datasets show that 4.6-bit quantized networks are 1.5–1.6 times faster than eight-bit networks on the ARMv8 CPU. Regarding the quality, the results of the 4.6-bit quantized network are close to the mean of four-bit and eight-bit networks of the same architecture. Therefore, 4.6-bit quantization may serve as an intermediate solution between fast and inaccurate low-bit network quantizations and accurate but relatively slow eight-bit ones.

Cancer dependency maps have accelerated the discovery of tumor vulnerabilities that can be exploited as drug targets when translatable to patients. The Cancer Genome Atlas (TCGA) is a compendium of 'maps' detailing the genetic, epigenetic and molecular changes that occur during the pathogenesis of cancer, yet it lacks a dependency map to translate gene essentiality in patient tumors. Here, we used machine learning to build translational dependency maps for patient tumors, which identified tumor vulnerabilities that predict drug responses and disease outcomes. A similar approach was used to map gene tolerability in healthy tissues to prioritize tumor vulnerabilities with the best therapeutic windows. A subset of patient-translatable synthetic lethalities were experimentally tested, including PAPSS1/PAPSS12 and CNOT7/CNOT78, which were validated in vitro and in vivo. Notably, PAPSS1 synthetic lethality was driven by collateral deletion of PAPSS2 with PTEN and was correlated with patient survival. Finally, the translational dependency map is provided as a web-based application for exploring tumor vulnerabilities., (© 2024. The Author(s).)

Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is considered a growing health concern. The majority of NTM-PD cases in Europe are caused by slow-growing mycobacteria (SGM). However, distinct radiological features of different SGM remain largely uninvestigated. We applied a previously described radiological score to a patient cohort consisting of individuals with isolation of different SGM. Correlations between clinical data, species and computed tomography (CT) features were examined by logistic and linear regression analyses, as well as over the course of time. Overall, 135 pulmonary CT scans from 84 patients were included. The isolated NTM-species were mainly Mycobacterium avium complex (MAC, n = 49), as well as 35 patients with non-MAC-species. Patients with isolation of M. intracellulare had more extensive CT findings compared to all other SGM species (coefficient 3.53, 95% Cl - 0.37 to 7.52, p = 0.075) while patients meeting the ATS criteria and not undergoing therapy exhibited an increase in CT scores over time. This study provides insights into differential radiological features of slow-growing NTM. While M. intracellulare exhibited a tendency towards higher overall CT scores, the radiological features were similar across different SGM. The applied CT score might be a useful instrument for monitoring patients and could help to guide antimycobacterial therapy., (© 2024. The Author(s).)