We present multi-sensor measurements from satellites, unmanned aerial vehicle, marine radar, thermal profilers and repeated conductivity-temperature-depth casts made in the Kara Gates strait connecting the Barents and the Kara Seas during spring tide in August 2021. Analysis of the field data during an 18-hour period from four stations evidence that a complex sill in the Kara Gates is the site of regular production of intense large-amplitude nonlinear internal waves. Satellite data show a presence of a relatively warm northeastward surface current from the Barents Sea toward the Kara Sea attaining 0.8-0.9 m/s. Triangle-shaped measurements of three thermal profilers revealed pronounced vertical thermocline oscillations up to 40 m associated with propagation of short-period nonlinear internal waves of depression generated by stratified flow passing a system of shallow sills in the strait. The most intense waves were recorded during the ebb tide slackening and reversal when the background flow was predominantly supercritical. Observed internal waves had wavelength of ~100 m and travelled northeastward with phase speeds of 0.8-0.9 m/s. The total internal wave energy per unit crest length for the largest waves was estimated to be equal to 1.0-1.8 MJ/m.

Measurements of temperature and salinity in the Amazon River plume in the open ocean of the western tropical North Atlantic are considered. The measurements were carried out using the AML CTD probe in the upper layer and a flow-through system that measures salinity and turbidity of seawater while the vessel is on the way. Additionally, archive oceanographic data from the WOD18 database, data of satellite altimetry measurements (AVISO), and satellite salinity data from Aquarius and SMOS were used. It is shown that the width of the Amazon plume is about 300–400 km, the depth of desalination is from 50 to 100 m. Surface salinity decreases compared to the background (36 PSU) by 0.5 PSU in February and more than by 3 PSU in September during the period of maximum development of the plume, which is determined from satellite measurements of surface salinity. Lagrangian modeling of the back-in-time advection of passive markers simulating freshwater particles was carried out. It was shown that the source of fresh water in the measurement area is the discharge of the Amazon.

Spatial and temporal variation of the free electron concentration in the ionosphere affects SAR interferograms, in particular at low radar frequencies. In this work the identification, estimation and compensation of ionospheric path delay phases in PALSAR-3 and NISAR-L interferograms is discussed. Both these L-band sensors acquire simultaneously SAR data in a main spectral band and in an additional, spectrally separated, narrower second band to support the mitigation of ionospheric path delays. The methods presented permit separating the dispersive and the non-dispersive phase terms based on the double-difference interferogram between the two available spectral bands and the differential interferogram of the main band. The applicability of the proposed methods is demonstrated using PALSAR-3-like data that was simulated based on PALSAR-2 SM1 mode data.

Rubella infection is typically mild or asymptomatic except when infection occurs during pregnancy. Infection in early pregnancy can cause miscarriage, stillbirth, or congenital rubella syndrome. Only individuals that are still susceptible to rubella infection during child-bearing age are vulnerable to this burden. Rubella containing vaccine (RCV) is safe and effective, providing life-long immunity. However, average age-at-infection increases with increasing vaccination coverage, which could potentially lead to increased disease burden as well, if the absolute risk of infection during child-bearing age increases. Dynamics of rubella transmission were explored using EMOD, a software tool for building stochastic, agent-based infection models. Simulations of pre-vaccine, endemic transmission of rubella virus introduced RCV at varying levels of coverage to determine the expected future trajectories of disease burden. Introducing RCV reduces both rubella virus transmission and disease burden for a period of around 15 years. Increased disease burden is only possible more than a decade post-introduction, and only for contexts with low current burden and high transmission intensity. Low or declining rubella virus transmission intensity is concurrently associated with both greater disease burden and greater vaccine effectiveness. The risk of increasing burden through vaccination only exists for locations with persistently high infectivity, high connectivity, and high fertility. A trade-off between the risk of a small, future burden increase and a large, immediate burden decrease strongly favors RCV introduction.

Luminophores featuring thermally activated delayed fluorescence (TADF luminophores) are the workhorse of the third- and fourth-generation OLEDs. While these compounds had usually been used as dopants embedded in the host, non-doped TADF OLEDs have recently shown significant progress as well reaching the performance comparable to the host-dopant ones. For efficient operation of the non-doped OLEDs, charge transport in neat films and single crystals of TADF luminophores is important; however, this issue was nearly unexplored theoretically. In the current study, we calculated charge mobilities in four TADF single crystals, which have different molecular packing motifs. Specifically, in one of them both donor and acceptor moieties form uniform π-stacks, while in the others donors (acceptors) show alternating lateral shifts along the stacks; the difference in molecular packing results in the difference of transfer integral between the molecules. Reorganization energies differ as well up to four times for the studied crystals. As a result, charge mobilities vary from 0.001 to ~0.3 cm2/(V∙s), the largest being predicted for the crystal of the luminophore consisting of rigid donor and acceptor. We anticipate that the results obtained can be useful for the design of TADF luminophores for non-doped OLEDs, OLETs and other organic light-emitting devices.

The 'big data revolution' has enabled novel types of analyses in the life sciences, facilitated by public sharing and reuse of datasets. Here, we review the prodigious potential of reusing publicly available datasets and the challenges, limitations and risks associated with it. Possible solutions to issues and research integrity considerations are also discussed. Due to the prominence, abundance and wide distribution of sequencing data, we focus on the reuse of publicly available sequence datasets. We define ‘successful reuse’ as the use of previously published data to enable novel scientific findings and use selected examples of such reuse from different disciplines to illustrate the enormous potential of the practice, while acknowledging their respective limitations and risks. A checklist to determine the reuse value and potential of a particular dataset is also provided. The open discussion of data reuse and the establishment of the practice as a norm has the potential to benefit all stakeholders in the life sciences.

Background: Evidence suggests that there is substantial comorbidity between fibromyalgia and Axis II pathology (i.e., personality disorders - PDs). The aim of the current study was to find out the exact cluster (A, B, C) PDs or traits that are more prominent in FM and may be predictors of FM diagnosis. Methods: Data from 86 subjects (53 with FM and 33 controls without FM) was analyzed in an observational, cross-sectional, comparative study. The assessment of categorical PDs and traits was performed independently with the Structured Clinical Interview for Personality Disorders (SCID-II). Binary logistic regression was used to determine FM predictors among PDs traits. Results. Compared with controls, FM patients had higher rate of PDs diagnoses (56.7 vs 18.2%, P<.001). However, the rate was significantly higher only for borderline PD diagnosis (28.3% vs 6.1% P<.05). The binary logistic regression analysis showed that schizotypal and schizoid (cluster A), borderline (cluster B), and dependent (cluster C) personality traits may be significant predictors of fibromyalgia (Nagelkerke R2 = 0.415). Conclusions: Our results may reflect association of FM with personality traits of all three PD clusters: A (eccentric), B (dramatic), C (anxious). However, the most consistent evidence seems to be for borderline PD.

Reliable species identification is critical for detection and monitoring of biological invasions. In this study, we propose four sets of primers for efficient amplification of several loci, including the mitochondrial cytochrome oxidase-c (COI) subunit I gene which is a basis for DNA barcoding. This set of primers gives a shorter product which can be used in high-throughput sequencing systems for metabarcoding purposes. Another mitochondrial locus encoding the large ribosomal subunit (16S) may be useful to study the population structure and as an additional source of information in the metabarcoding of communities. We propose to use a set of primers for the nuclear locus of the small ribosomal subunit (18S) as a positive control and to verify the results of the barcoding. Our proposed sets of primers demonstrate a high amplification efficiency and a high specificity both for freshwater alien and indigenous fishes. The proposed research design makes it possible to carry out extremely cheap studies on the assessment of biological diversity using genetic analysis without expensive equipment, and with the technique for conducting laboratory work and processing of the results available to any researcher. The paper also presents original data on the genetic polymorphism of all mass alien fish species in the Volga-Kama region. High efficiency of DNA identification based on our primers is shown as compared to traditional monitoring of biological invasions.

A closed chain of oscillators can be considered as a model of ring-shaped ecosystems, such as atolls or coastal zones of inland reservoirs. As an oscillator model, we use the logistic map that often referred to as an archetypical example of how complex dynamics can arise from very simple nonlinear equations. We investigate the influence of the model parameters both on the nature of oscillations in the oscillator ring and on the spatial structures that arise in this case. Namely, we demonstrate a variety of emerging spatial structures depending on the initial conditions.

Different organisms, cell types, and even similar cell lines can dramatically differ in resistance to genotoxic stress. This testifies to the wide opportunities for genetic and epigenetic regulation of stress resistance. These opportunities could be used to increas the effectiveness of cancer therapy, develop new varieties of plants and animals, and search for new pharmacological targets to enhance human radioresistance, for example, for -manned deep space expeditions. Based on the comparison of transcriptomic studies in cancer cells, in this review we propose that there is a high diversity of genetic mechanisms of development of genotoxic stress resistance. This review focused onpossibilities and limitations of the proposed regulation of the resistance of normal cells whole organisms to genotoxic and oxidative stress by overexpressing of stress-response genes. Moreover, the existing experimental data on the effect of such overexpression on the resistance of cells and organisms to various genotoxic agents has been analyzed and systematized. We suggest that the recent advances in the development of multiplex and highly customizable gene overexpression technology that utilizes the mutant Cas9 protein and the wealth of available data on gene functions and their signal networks open new opportunities for research in this field.

Shot peening has become a well-established technique for the introduction of beneficial compressive Residual Stresses (RS) into the near-surface layers of metallic materials for the purpose of preventing or suppressing fatigue crack nucleation and growth. Ti-alloys are widely used to fabricate compressor blades of aeroengines. Titanium blades that may be susceptible to different modes of damage under cyclic loading (high cycle fatigue, fretting fatigue) are often subjected to shot peening to extend their safe operating time. The control and monitoring of residual stresses in titanium blades is of great importance to assure the safety of aeroengines. The techniques for residual stress evaluation include mechanical methods (material removal) as well as physical methods such as X-ray diffraction. Perhaps the most common and practically accessible form of the latter is the method. Conventional laboratory X-ray diffractometers typically probe samples to the depths up to ~20 µm that correspond to 1x...5x the average grain size for typical metals and alloys. The limitations of the method have been identified and reviewed in the literature, motivating the use of other semi-destructive approaches to evaluate the residual stresses in deeper layers and at more sharply defined locations. In the present report we present a case study of the comparison between non-destructive and semi-destructive evaluation techniques, namely the X-ray diffraction method against the mechanical and FIB-DIC ring-core drilling applied to the samples of VT6 (Russian designation of Ti-6Al-4V) titanium alloy after shot peening with 1 mm steel balls. Mechanical drilling of circular holes of ~2 mm diameter with laser speckle interferometry monitoring of strains gives a rough spatial resolution of a few millimeters, while the Korsunsky FIB-DIC method of Ga-ion beam micro-ring core milling within FIB-SEM with Digital Image Correlation (DIC) deformation analysis delivers spatial resolution down to a few micrometers. Good agreement has been found between the X-ray and FIB-DIC estimates of RS variation profiles as a function of depth in shot peened titanium alloy samples. Some advances in the FIB-DIC method are presented and discussed in terms of the acceleration of data acquisition and interpretation.

The paper shows that it is possible to obtain reliable information on the dependence of radial distribution of longitudinal birefringence in glass cylindrical elements with radial distribution of refractive index (GRIN lenses) on the basis of transverse polarization tomography data of residual stresses. This does not require complicated procedures of sample preparation, as is necessary in the case of longitudinal translucency measurements. The approach developed was verified in the experiments with a set of different GRIN lenses formed with ion exchange technique, and the closeness of the data obtained from transversal and conventional longitudinal transmission measurements was demonstrated.

The ordered Ca3TaGa3Si2O14 and disordered La3Ga5SiO14 crystals of the lantangallium silicate family were grown by the Czochralski method. The independent coefficients of thermal expansion of crystals αc and αa were determined by X-ray powder diffraction based on the analysis of X-ray diffraction spectra measured in the temperature range of 25÷1000°C. It is shown that in the temperature range of 25÷800°C the thermal expansion coefficients are linear. At temperatures above 800°C there is a nonlinear character of the thermal expansion coefficients associated with a decrease in the Ga content in the crystal lattice of the lantangallium silicate family crystals.

Curcumin attracts a huge attention because of its biological properties: antiproliferative, antioxidant, anti-inflammatory, immunomodulatory and so on. However, its usage has been limited by poor water solubility and low bioavailability. Herein, to solve these problems we developed curcumin-loaded nanoparticles based on end-capped amphiphilic poly(N-vinylpyrrolidone). Nanoparticles were obtained using the suspension method and were characterized by dynamic and electrophoretic light scattering, transmission electron microscopy and atomic force microscopy. The average particle size was 200 nm, and ζ-potential was -4 mV. Curcumin release studies showed that nanoparticles are stable in water solution. In vitro release study showed prolonged action in gastric, intestinal and colonic fluids, consistently and in PBS. In vitro studies on epidermoid carcinoma and human embryonic kidney cells showed that the cells absorbed more curcumin in nanoparticles compared to pure curcumin. Nanoparticles are safe for healthy cells and show high cytotoxicity for glioblastoma cells in cytotoxicity studies in vitro. Median lethal dose was determined in acute toxicity assay on Zebrafish and was 23 μM. Overall, the curcumin-loaded nanoparticles seem promising for cancer treatment.

The adoption of algorithms based on Artificial Intelligence (AI) has been rapidly increasing during the last years. However, some aspects of AI techniques are under heavy scrutiny. For instance, in many use cases, it is not clear whether the decisions of an algorithm are well-informed and conforming to human understanding. Having ways to address these concerns is crucial in many domains, especially whenever humans and intelligent (physical or virtual) agents must cooperate in a shared environment. In this paper, we introduce an application of an explainability method based on the creation of a Policy Graph (PG) based on discrete predicates that represent and explain a trained agent’s behaviour in a multi-agent cooperative environment. We show that from these policy graphs, policies for surrogate interpretable agents can be automatically generated. These policies can be used to measure the reliability of the explanations enabled by the PGs, through a fair behavioural comparison between the original opaque agent and the surrogate one. The contributions of this paper represent the first application of policy graphs in the context of explaining agent behaviour in collaborative multi-agent scenarios and presents experimental results that sets this kind of scenario apart from previous application in single-agent scenarios: when requiring collaborative behaviour, predicates that allow representing observations about the other agents are crucial to replicate the opaque agent’s behaviour and increase the reliability of explanations.

3D-printed aluminium alloy fabrications made by selective laser melting (SLM) offer a promising route for the production of small series of custom-designed heat exchangers with complex geometry and shape and miniature size. Alloy composition and printing parameters need to be optimized to mitigate fabrication defects (pores and microcracks) and enhance the part performance. The deformation response needs to be studied with adequate characterization techniques at relevant dimensional scale capturing the peculiarities of micro-mechanical behavior relevant to the particular article and specimen dimensions. Purposefully designed Al-Si-Mg 3D-printable RS-333 alloy was investigated with a number of microscopy techniques including in situ mechanical testing with a Deben Microtest 1 kN stage integrated and synchronized with Tescan Vega3 SEM to acquire high resolution image datasets for Digital Image Correlation (DIC) analysis. Dog bone specimens were 3D-printed in different orientation of gauge zone cross-section with respect to the fast laser beam scanning and growth directions. This corresponds to varying local conditions of metal solidification and cooling. Specimens show variation in mechanical properties, namely, Young’s modulus (65…78 GPa), yield stress (80–150 MPa), ultimate tensile strength (115–225 MPa) and elongation at break (0,75–1,4 %). Furthermore, the failure localization and character was altered with the change of gauge cross-section orientation. DIC analysis allowed correct strain evaluation that overcame the load frame compliance effect and helped to identify the unevenness of deformation distribution (plasticity waves) that ultimately resulted in exceptionally high strain localization near the ultimate failure crack position.

Background Homologous recombination deficiency (HRD) evolved into a major diagnostic marker in high grade ovarian cancer (HGOC) predicting the response to poly (Adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and also platinum-based therapy. In addition to HRD, the type of peritoneal tumor spread influences treatment response and patient survival; miliary type tumor spread has poorer predicted outcome than non-miliary type tumor spread. Methods Known methods for HRD assessment were adapted for our technical requirements and the Predictive-value Integrated Genomic Instability Score (PIGIS) for HRD assessment evolved as an outcome. PIGIS was validated in HGOC samples from 122 patients. We used PIGIS to analyze whether the type of tumor spread correlated with HRD status and whether this had an impact on survival. Results We demonstrated that PIGIS can discriminate HRD positive from HRD negative samples. Tumors with miliary tumor spread are HRD negative and have a very bad prognosis with a progression free survival (PFS) of 15.6 months and an overall survival (OS) of 3.9 years. However, HRD negative non-miliary spreading tumors in our cohort had a much better prognosis (PFS 35.4 months, OS 8.9 years), similar to HRD positive tumors (PFS 34.7 months, OS 8.9 years). Conclusions Our results indicate that in a predominantly PARPi naïve cohort the type of tumor spread might be a better predictor of response to platinum sensitivity than HRD. It remains to be determined, whether this also applies for sensitivity to PARPi.

Groove pancreatitis represents a chronic focal form of pancreatitis affecting the zone between the pancreatic head and the duodenal „C” loop, known as the groove area. This is a rare condition that affects the pancreatic periampullary part, including the duodenum and the common bile duct, associated usually with long-term alcohol and tobacco misuse and being more frequent in men than in women. The most common clinical symptoms of groove pancreatitis include weight loss, acute abdominal pain, nausea, and jaundice. This report is about a 66 year old woman with a history of heavy smoking, presenting with weight loss, nausea, and upper abdominal pain. Contrast enhanced computed tomography revealed the existence of a chronic pancreatitis as well as the dilatation of the main pancreatic duct, a cyst of the pancreatic head and enlargement of the biliary tract. Conservatory treatment was initiated but with no improvement of symptoms. Since there was no indication for endoscopic retrograde cholangiopancreatography, we decided to perform a pancreatoduodenectomy, as surgery appears to be the single effective treatment.

Abstract: CRISPR/Cas systems are used for genome editing, both in basic science and in bio-technology. At the same time, CRISPR/Cas editors have several limitations, including insufficient specificity leading to "off-targets" and the dependence of activity on chromatin state. A number of highly specific Cas9 variants have been obtained now, but most of them are characterized by reduced activity on eukaryotic chromatin. We identified a spatial cluster of amino acid residues in the PAM-recognizing domain of Streptococcus pyogenes Cas9, whose mutations restore the activity of one of the highly specific forms of SpyCas9 without reducing its activity in Saccharomyces cere-visiae. In addition, one of these new mutations also increases the efficiency of SpyCas9-mediated editing of a site localized on the stable nucleosome. The improved Cas9 variants we obtained, which are capable of editing hard-to-reach regions of the yeast genome, may help in both basic research and yeast biotechnological applications.

CNN-based off-the-shelf features have shown themselves as a good baseline for trademark retrieval. However, in recent years, the computer vision area was transitioning from CNNs to a new architecture – Vision Transformer. In this paper, we investigate the performance of off-the-shelf features extracted with vision transformers and explore the effects of pre, post-processing, and pre-training on big datasets. We propose a method of joint usage of global and local features, which leverages the best aspects of both approaches. Experimental results on METU Trademark Dataset show that off-the-shelf features extracted with ViT-based models outperform off-the-shelf features from CNN-based models. The proposed method achieves the mAP value of 31.23, surpassing previous state-of-the-art results. We assume that the proposed approach for the trademark similarity evaluation will allow one to improve the protection of such data with the help of artificial intelligence methods. Moreover, this approach will allow one to identify cases of unfair use of such data and form an evidence base for litigation.

The article presents several innovative systems developed through student laboratory projects, including two autonomous vehicles, a four-legged walking robot, an active ankle-foot orthosis, a ball on beam balancing mechanism, a ball on plate system, and a manipulator arm—all powered by pneumatic artificial muscles (PAMs). Fluidic muscles offer significant potential in various mechatronic systems, robots, and manipulators due to their flexible, lightweight nature and compliance. Their ability to produce smooth and adaptable motions is particularly beneficial in applications requiring natural and human-like movement, such as rehabilitation and assistive devices. Although PAMs powered control systems face challenges with nonlinear phenomena, their biologically inspired design holds promise for future applications across various industries. These may include innovative applicability in industrial, automotive, and aerospace sectors, as well as use in sports, medical aids, entertainment, and animatronics. Incorporating self-made laboratory systems actuated by PAMs into control systems education offers a comprehensive learning opportunity that combines theoretical concepts with hands-on experience. This approach develops the necessary skills of future engineers, expanding their understanding of technical principles and preparing them for future challenges in engineering practice.

Tick-borne encephalitis virus (TBEV) is a RNA-containing enveloped virus, a member of the Flaviviridae family. Here we describe a detailed analysis of the size and structure of inactivated TBEV (the Sofyin-Chumakov TBEV strain, used in vaccines). Four analytical methods were used to analyze individual TBEV particles—negative staining TEM, cryo-EM, AFM, and NTA. All methods confirmed that the particles were monodisperse, and their mean size was ~50 nm. Cryo-EM data were used to obtain a 3D electron density model of the virus with clearly distinguishable E-proteins. STEM-EELS analysis detected phosphorous in the particles, which was interpreted as the RNA signal. Altogether, the described analytical procedures can be valuable for the further analysis of vaccine inactivated virus samples.

High hopes were associated with the new anti-angiogenic medicament, bevacizumab, which due to the possibility of binding to isoform A of vascular endothelial growth factor (VEGF), inhibited the creation of new blood vessels. However, not only blood vessels are responsible for the tumor cells' spread. During the process of tumor growth, lymphangiogenesis is mediated by other isoforms of the VEGF family, specifically VEGF-C and VEGF-D, which are independent of the bevacizumab action. Therefore, based on the mechanism of bevacizumab action and the processes of angio- and lymphangiogenesis, we formed three hypotheses: 1) if the lymph nodes in the primary ovarian cancers are metastatic, the outcome of bevacizumab treatment is worsened; 2) concerning the second-line treatment, bevacizumab will act in a weakened manner if the recurrence occurs in lymph nodes compared to local recurrences; 3) patients treated by bevacizumab are more likely to have recurrences in lymph nodes. These hypotheses raise the issue of the existing gap of knowledge, which concerns the effect of bevacizumab on the metastatic lymph nodes.

Autoantibodies against type 1 interferons (IFN-I) are highly specific marker for type 1 autoimmune polyglandular syndrome (APS-1). Moreover, determination of antibodies to IFN-ω and IFN-α2 allows a short-term diagnosis in patients with isolated and atypical forms of APS-1. In this study, a comparison of three different methods, namely, multiplex microarray-based, cell-based and enzyme-linked immunosorbent assays for detection of antibodies against omega-interferon and alpha2-interferon was carried out. A total of 206 serum samples from adult patients with APS-1, APS-2, isolated autoimmune endocrine pathologies, non-autoimmune endocrine disorders and healthy individuals were analyzed. In the APS-1 patient cohort (n=18), there was good agreement between the results of anti- IFN-I antibody tests performed by three methods, with 100% specificity and sensitivity for microarray-based assay. Although only the cell-based assay can determine the neutralizing activity of autoantibodies, the microarray-based assay can serve as a highly specific and sensitive screening test to identify anti- IFN-I antibody positive patients.

The Upper Hunter Valley is a major coal mining area containing approximately 40% of the currently identified total coal reserves in New South Wales (NSW), Australia. Due to the ongoing increase of mining activities, PM10 (air-borne particle with an aerodynamic diameter less than 10 micrometres) pollution has become a major air quality concern in local communities. This paper summarises the spatial and temporal variability modes of PM10 pollution in the region, based on long-term multi-site monitoring data and the application of the rotated principal component analysis (RPCA) and wavelet analysis techniques. RPCA identified two distinct air quality clusters/subregions in the valley, one in the west/northwest, the other in the southeast. Wavelet analysis revealed the annual cycle to be most persistent temporal mode of PM10 variability in both subregions, with intermittent signals observed at time scales of around 120, 30~90 and under 30 days. How these variation modes are related to the effects of local PM10 emissions and the influence of meteorology at different time scales deserves further attention in future work. The findings will be used in air quality reporting and forecasting in NSW. The methodology and results can also be useful for air quality research in similar regions elsewhere.

In the investment casting process, the pattern made of wax is obtained in a die for further formation of shell mold. This work investigates commercial pattern waxes fluidity with a newly developed injection fluidity test. A good correlation between wax fluidity and its viscosity is observed, which is different from metallic alloys, where the solidification behavior is more critical. The difference in investigated filled waxes fluidity can be associated with the type and amount of filler.

Chromosomal rearrangements in N. gonorrhoeae and N. meningitidis were studied with the determination of mobile elements and their role in rearrangements. The results of whole-genome sequencing and de novo genome assembly for 50 N. gonorrhoeae isolates collected in Russia were compared with 96 genomes of N. gonorrhoeae and 138 genomes of N. meningitidis from the databases. Rearrangement events with the determination of the coordinates of syntenic blocks were analyzed using the SibeliaZ software, the minimum number of events that allow one genome to pass into another was calculated using the DCJ-indel model using the UniMoG program. Population-level analysis revealed a stronger correlation between changes in the gene order and phylogenetic proximity for N. meningitidis in contrast to N. gonorrhoeae. Mobile elements were identified, including Correa elements, Spencer-Smith elements (in N. gonorrhoeae), Neisserial intergenic mosaic elements, IS elements of IS5, IS30, IS110, IS1595 groups, Nf1-Nf3 prophages, NgoФ1-NgoФ9 prophages, Mu-like prophages Pnm1, Pnm2, MuMenB (in N. meningitidis). More than 44% of the observed rearrangements most likely occurred with the participation of mobile elements, including prophages. No differences were found between the Russian and global N. gonorrhoeae population both in terms of rearrangement events and in the number of transposable elements in genomes.

Ultra high molecular weight polyethylene (UHMWPE) is a thermoplastic high-performance polymer in high demand for biomedicine, ship and machine building, anthropomorphic robots and smart prostheses. Highly oriented UHMWPE fibers possess record specific strength and may also be used for the fabrication of self-reinforced PE-PE composites (SRPEC). The temperature evolution study of the small-angle X-ray scattering (SAXS) signature of the supramolecular structure of UHMWPE can help reveal their important role in the mechanism of the shape memory effect in SRPEC. The laboratory SAXS–WAXS beamline XEUSS 3.0 was used for in situ studies of the nanostructure parameters in unidirectional SRPEC. Namely, the radius of gyration and the dimensionality factor were extracted from 2D SAXS patterns using several fitting algorithms. Significant changes of these parameters occurred in temperature ranges that correspond to the initiation of the shape memory effect and melting. The relationship between the material anisotropy and 2D SAXS patterns are discussed in the context of the supramolecular structure evolution.

The broad emission bump in the electromagnetic spectra observed following the detection of gravitational waves created during the kilonova event of merger of two neutron stars in August 2017, GW170817, has been linked to the heavy elements of lanthanides (Z=57-71), and a new understanding of creation of heavy elements in the r-process. The initial spectral emission bump has a wavelength range of 3000 - 7000 \AA, thus covering the region of ultraviolet (UV) to optical (O) wavelengths, and is similar to those seen for lanthanides. Most lanthanides have large number of closely lying energy levels which introduce extensive sets of radiative transitions which often form broad region of lines of significant strength. The current study explores these broad features through photoabsorption spectroscopy of 25 lanthanides ions, Ho I-III, Er I-IV, Tm I-V, Yb I-VI and Lu I-VII. With excitations only to a few orbitals up beyond the ground configurations, we find most of these ions cover large number of bound levels with open $4f$ orbital and produce tens to about hundred thousands lines that may form one or multiple broad features in X-ray to UV, O, and infrared (IR) regions. Spectrum of each of 25 ions is presented indicating presence, shape and wavelength region of the features. Accuracy of atomic data to interpret the merger spectra has been a outstanding problem. The present study aims at providing improved atomic data for energies and transition parameters obtained using relativistic Breit-Pauli approximation implemented in the atomic structure code SUPERSTRUCTURE. The present data have been benchmarked with available experimental data for energies and transition parameters. The study finds that number of ions under the present study are possible contributors of the emission bump of GW170817. All atomic data will be made available online at NORAD-Atomic-Data database.

The study of the impact of polyQ expansion driven proteotoxicity on cell metabolism has evi-denced NAD molecule as a central player in regulating metabolic response and cell repair in neurodegeneration. The decline in NAD intracellular levels represents a hallmark of ageing aris-ing from a dysregulation between NAD-consuming and biosynthetic enzymatic reactions in which NMNAT plays a key role. By an integrated bioanalytical and proteomic experimental design, the derangement of NAD metabolism deriving from the accumulation of polyQ-Htt protein has been analysed in Saccha-romices cerevisiae harbouring a 103Q-Htt and compared with wild-type Htt, in absence and in presence of a phenolic extract from EVOO, as a source of antioxidant bioactive compounds. Quantification of NAD and its precursors and proteomic analysis of the differential protein ex-pression has been performed by LC-DAD-MS. Chronological lifespan and NAD homeostasis was strongly impaired by proteotoxic polyQ-Htt, eliciting a depletion of NAD levels and accumulation of NaMN. In parallel a downregulation of Sirt2 expression levels has been observed. Phenolic extract administration had no meaningful ef-fects on NAD replenishment to prevent proteotoxicity. NaMN can represent a biomarker of accel-erated aging, and/or a signaling molecule for cell repair.

Neosporosis is an infection caused by the protozoan parasite Neospora caninum and has substantial veterinary hazards. Neosporosis cannot be controlled via vaccination or a chemotherapeutic agent. Thus, accurate diagnosis followed by isolation and culling of infected animals is regarded as the most efficient way of control. In vivo diagnosis often relies on serologic testing of the animals, and milk represents a non-invasive and easy to collect sample matrix. However, ELISAs specifically designed for the antibody detection in milk are sometimes not easily available and it is tempting to use ELISA kits designed for use in serum also for milk samples. Herein, we evaluated a widely used commercial ELISA (ID Screen® Neospora caninum competition Multispecies ELISA (ID. Vet, Grabels, France)), developed for detection of N. caninum antibodies in serum samples, for its performance with milk samples instead. Milk samples from dairy ruminants (cows, buffaloes, sheep, goats; n = 149) were tested in parallel with the serum ELISA and a commercial milk ELISA as a standard test (Neospora caninum Milk Competitive ELISA, ID. Vet, Grabels, France). The detected prevalence rates were 42 (28.2%), 26 (17.4%), and 26 (17.4%) using milk ELISA, serum ELISA, and both ELISAs, respectively. Sensitivity, specificity, positive predictive value, and negative predictive value for the serum ELISA used with milk samples were 61.9%, 100%, 100%, 87%, respectively: Agreement and Kappa value between the two ELISAs were 89.3%, and 0.70, respectively. High values of Pearson correlation coefficient (0.991) and area under ROC curve (0.789) demonstrated a high diagnostic performance of serum ELISA also in milk samples. Also, Bland-Altman plot and Histogram describing the frequency of distribution of ELISA optical densities confirmed the high agreement of both serum and milk ELISAs. The current results revealed a high specificity but moderate sensitivity of the serum ELISA used for milk samples compared with the milk ELISA. However, the excellent positive predictive value of the serum ELISA makes it an alternative option in case of unavailability of milk ELISA. With this study, we provided additional evidence that a widely used serum ELISA test kit may also be used for detection of N. caninum antibodies in milk samples.

Febrile seizures (FS) are a relatively common early-life condition that can cause CNS developmental disorders, but the specific mechanisms of action of FS are poorly understood. In this work, we used hyperthermia-induced FS in 10-day-old rats. By recording local field potentials, we showed that the efficiency of glutamatergic synaptic transmission decreased 15 min after FS. This effect was transient, and after 2 days there were no differences between control and post-FS groups. During early ontogeny, the proportion of calcium-permeable (CP)-AMPA receptors in the synapses of principal cortical and hippocampal neurons is high. Therefore, rapid internalization of CP-AMPA receptors may be one of the mechanisms underlying this phenomenon. Using the whole-cell patch clamp method and the selective CP-AMPA receptor blocker IEM-1460, we tested whether the proportion of CP-AMPA receptors changes. We have demonstrated that FS rapidly reduces synaptic CP-AMPA receptors in both the hippocampus and the entorhinal cortex. This process was accompanied by a sharp decrease in calcium permeability of the membrane of principal neurons, which we revealed in experiments with kainate-induced cobalt uptake. Our experiments show that FSs cause rapid changes in the function of the glutamatergic system, which may have compensatory effects that prevent excessive excitotoxicity and neuronal death.

Crystalline silver thin layers were obtained by high-energy pulsed laser ablation without heating of the deposition substrate. The fluid Plateau-Rayleigh (PRI), Rayleigh – Taylor (RTI) and Richtmyer – Meshkov (RMI) instabilities, as well as crown splash induced during pulsed laser deposition (PLD) in high energy regime, resulting in ring and pearl shaped structures, offer the benefit of increased sorption surface. These morphological structures obtained for the silver thin layers make them of interest for catalytic applications. The study presented with this work addresses both the fundamental and applied issues on the morphological structures obtained for the silver thin layer and their catalytic function in organic processes. In this sense, the catalytic action of the thin silver layer was highlighted by modifications of the Reactive Blue 21 dye (C.I.) in aqueous solution with sodium bicarbonate. Specific investigations and analyzes were carried out by electron microscopy and elemental analysis (SEM-EDX), atomic force microscopy (AFM) and profilometry, mass spectrometry, ablation plasma diagnosis, diffractograms (XRD), as well as IR spectroscopy (FTIR). In addition to the experimental investigation and analyzes, simulation of the ionization energy threshold was conducted in COMSOL for complementary evaluation on the involved processes and phenomena.

“Pecorino” is a typical semi-hard cheese obtained with raw or heat-treated sheep milk using procedures to valorize the raw material's chemical and microbiological properties. In the present study, using a high throughput method of 16S rRNA gene sequencing, we assessed the evolution of the microbiome composition from milk to Pecorino cheese in artisanal processes using milk from Comisana and Lacaune sheep breeds. The comparative analysis of the bacterial com-munity composition revealed significant differences in the presence and abundance of specific taxa in the milk microbiome of the Comisana and Lacaune breeds. NGS analysis also revealed differences in the curd microbiome related to dairy farming practices, which have a relevant effect on the final structure of the Pecorino-cheese microbiome.

Features of nanosecond discharge development in a non-uniform electric field are studied experimentally. High spatial resolution imaging showed that thin luminous tracks of great length with a cross-section of a few microns are observed against the background of discharge glow in air and argon. It has been established that the detected tracks are adjacent to brightly luminous white spots on the electrodes or to the vicinity of these spots, and are associated with the flight of small particles. It is shown that the traces have various shapes and change from pulse to pulse. The particle tracks may look like curvy or straight lines. In some photos, they can change the direction of movement to the opposite. The particle trace was found to abruptly cut off and a bright flash is visible at the trail break point. The color of the tracks differs from that of the spark leaders, while the bands of the second positive nitrogen system dominate in the gap spectra during the existence of a diffuse discharge. Areas of blue light are evident near the electrodes, as well. Development of glow in the gap during its breakdown is revealed using an ICCD camera. Physical reasons for the observed phenomena are discussed.

Recent years witnessed progressive broadening of the practical use of 3D-printed aluminium alloy parts, in particular for specific aerospace applications where weight saving is of great importance. Selective laser melting (SLM) is an intrinsically multi-parametric fabrication technology that offers multiple means of controlling mechanical properties (elastic moduli, yield strength, ductility) through the control over grains size, shape, and orientation. Ultimately, this approach implies that structural elements can be purposefully fabricated to reinforce specific zones and directions where higher mechanical loads are anticipated by design. Targeted control over mechanical properties is achieved through the tuning of 3D-printing parameters and may even obviate the need of heat treatment or mechanical post-processing. Systematic studies of grain structure for different printing orientation with the help of EBSD techniques in combination with mechanical testing at different dimensional levels are the necessary first steps to implement this agenda. Samples of 3D-printable Al-Mg-Si RS-333 alloy were fabricated in 3 orientations with respect to the principal build direction and the fast laser beam scanning direction. Sample structure and proper-ties were investigated using a number of techniques, including EBSD, in situ SEM tensile testing, roughness measurements and nanoindentation. The as-printed samples we found to display strong variation in Young’s modulus values from nanoindentation (from 43 to 66 GPa) and tensile tests (from 54 to 75 GPa), yield stress and ultimate tensile strength (100…195 and 130…220 MPa) in different printing orientations, and almost constant hardness of about 0.8 GPa. A further preliminary study was conducted of the effect of surface finishing on the mechanical performance. Surface polishing appears to reduce Young’s modulus and yield strength, but improves ductility, whereas the influence of sand blasting is more controversial. The experimental results are dis-cussed in connection with the grain morphology and orientation.

DIEP-based breast reconstruction necessitates wide undermining at the abdominal donor-site, creating large wound areas. Flap harvesting is usually conducted using electrosurgical dissection devices. This study sought to compare the clinical outcomes in patients after using the PEAK PlasmaBlade (PPB) versus monopolar electrocautery (MPE). This retrospective cohort study included 128 patients with DIEP-based breast reconstruction. Patient characteristics as well as information on the postoperative course were collected and a comparative evaluation was conducted. The MPE group exhibited significantly (p* = 0.0324) higher abdominal drainage volume (351.11 ± 185.96 ml) compared to the PPB group (279.38 ± 183.38 ml). Subgroup analysis demonstrated that PPB significantly reduced postoperative wound fluid in patients with BMI > 30 kg/m² (p* = 0.0284), without prior neoadjuvant chemotherapy (p** = 0.0041), and among non-smokers (p = 0.0046). Furthermore, postoperative pain was significantly (p**** < 0.0001) lower in the PPB cohort. This study confirms the non-inferiority of the PEAK PlasmaBlade to conventional electrocautery for abdominal flap harvesting. The PPB demonstrated advantages, notably reduced drainage volume and lower postoperative pain levels. Recognizing patient subsets that benefit more from the PPB highlights the importance of personalized device selection based on patient characteristics.

Drosophila melanogaster serves as a important research model both for genetic investigations and for the study of metal toxicity, facilitating the elucidation of physiological mechanisms comparable to those of human organisms. In our research, we evaluated the toxicity effect resulting from exposure to various concentrations of lead and copper on the prolificity rates throughout the life cycle (egg-adult) of four genotypes of Drosophila melanogaster: wild-type (control), white, brown, and white-vestigial. During our study, the prolificity rates were examined across three repetitions under the impact of exposure to concentrations of 0.50, 1.00, 2.00, and 4.00 mM of copper (CuSO₄) and lead (Pb(C₂H₃O₂₎₂). Prolificity rates throughout the life cycle exhibited variations as a direct consequence of genetic factors, the concentration of exposure, and the specific type of metal, either copper or lead. The mutant white-vestigial genotype revealed an IC₅₀ concentration for prolificity inhibition at lower doses of 2.00 mM for copper and 4.00 mM for lead, in contrast to the control genotype (wild-type), which exhibited an inhibition concentration rate >IC₅₀ of 4.00 mM only in the case of copper. Our results concluded that the (i) dose influences the prolificity rate in a directly proportional manner, (ii) comparative analyses between copper and lead revealed that copper displayed toxicity across all genotypes within the concentration range of 0.50 mM to 2.00 mM. In contrast, lead exhibited toxicity within the concentration range of 1.00 mM to 4.00 mM, highlighting a (iii) more acute toxicity characteristic in the case of copper. Thus, the results of this research reflect the importance of using Drosophila melanogaster as a genetic model in the comparative study of the interaction between genetic factors and the toxicity of metals, offering significant insights into monitoring their impact and defining the maximum permissible doses on organisms.

SLM Additive Manufacturing has demonstrated great potential for aerospace applications when structural elements of individual design and/or complex shape need to be promptly supplied. 3D-printable AlSi10Mg (RS-300) alloy is widely used for the fabrication of different structures in aerospace industry. The importance of the evaluation of residual stresses that arise as a result of complex 3D-printing process thermal history is widely discussed in literature, but systematic assessment remains lacking for their magnitude, spatial distribution, and comparative analysis of different evaluation techniques. In this study we report the results of a systematic study of residual stresses in a 3D-printed double tower shaped samples using several approaches: the contour method, blind hole drilling laser speckle interferometry, X-ray diffraction, and Xe pFIB-DIC micro-ring-core milling analysis. We show that a high level of tensile and compressive residual stresses is inherited from SLM 3D-printing and retained for longer than 6 months. The stresses vary over a significant proportion of the material yield stress. All residual stress evaluation techniques considered returned comparable values of residual stresses even regardless of dramatically different dimensional scales from millimeters for the Contour Method down, laser speckle interferometry and XRD and down to small fractions of a mm (70 μm) for Xe pFIB-DIC ring-core drilling. The use of residual stress evaluation is discussed in the context of optimizing the printing strategy to enhance the mechanical performance and long-term durability.

The effects of methyl jasmonate (MeJ) on growth and taxoid formation in the cell culture of Himalayan yew was investigated for elucidate the specifics of the action of phytohormones on dedifferentiated plant cells in vitro. The characteristics of the same suspension culture of Taxus wallichiana was compared in 2017 ("young culture") and in 2022 ("old culture") - 1.5 or 6 years after culture induction, respectively. Cells were grown in flasks and bioreactors, MeJ (100 µM) was added at the exponential growth phase. It was found that cell culture demonstrated good growth (dry weight (DW) accumulation 10–18 g/l, specific growth rate µ = 0.15–0.35 day-1) regardless of "age", cultivation system and MeJ addition. UPLC–ESI-MS analysis showed the presence of C14-hydroxylated taxoids (yunnanxane, taxuyunnanine C, sinenxane C, sinenxane B) in cell biomass in the amounts comparable to plants. The content of C14-OH taxoids during 5 years of cultivation increased by 3-5 times. It was 0.2–1.6 mg/g DW for "young culture” and 0.6-10.1 mg/g for “old culture” depending on cultivation conditions. The ratio of individual compounds changed also: in the "young culture" was predominant yunnanxane, in the "old culture" - sinenxane C. Important that C13-hydroxylated taxoids were found in trace amounts only in the "young culture” (below 0.05 mg/g DW) and were not detected in the "old culture”. The response to MeJ was radically different depending on culture’s «age». In the “young culture”, exogenous MeJ had no effect on the content of C14-OH com-pounds, but significantly (almost 10 times) increased the content of C13-OH compounds. In particular, paclitaxel concentration was elevated up to 0.12–0.19 mg/g DW, which is comparable to its content in the bark of yew trees. By contrast, MeJ added to the "old culture” had minor effect on the synthesis of C13-OH toxoids that appeared in trace amounts only (below 3.5 µg/g DW for paclitaxel) but notably increased the content of C14-OH compounds (1.5–2.0 times in flasks and 5–8 times in bioreactors). These findings suggest that hormonal signaling in dedifferentiated yew cells grown in vitro is different from that in plants and change with culture age. This might be a result of the high level of heterogeneity of cells in vitro and their constant auto-selection for proliferate intensity which leads to predominant formation of C14-OH taxoids versus C13-OH taxoids and modified cell response to exogenous MeJ treatment. These results have both fundamental and practical biotechnological application.

X-ray diffraction (XRD) analysis of complex poly-atomic systems, especially of biomolecules, using ultra-short laser pulses (USP), is currently one of the most important fields of modern physics. The basis for interpreting and "deciphering" experimental data is the well-known theory of X-ray scattering, where the main parameter of USPs - its duration - is not taken into account. In the present work it is shown that for scattering of attosecond USPs on DNA and RNA trinucleotides the pulse length is the most important scattering parameter. In this case the diffraction pattern significantly changes with respect to the previously known scattering theory. The results obtained are extremely important in XRD when using attosecond pulses to study trinucleotides of DNA and RNA because using the previously known scattering theory which does not take into account the duration of USPs one can not correctly interpret and therefore "decode" DNA and RNA structures.

Modification the biodegradable matrix was carried by graft-copolymerization polylactide with methacrylic acid of various concentrations. Ultraviolet irradiation with different exposure times to the samples was chosen as the initiator of copolymerization. In the experiment the effect of ultraviolet light on polylactide and graft copolymerization was investigated: the resulting samples were studied by viscosimetry, gravimetry, FTIR, static cation- exchange capacity analysis . The conditions for obtaining grafted copolymers and the dependence of the characteristics on the reaction conditions are established.

Vegetation indexes help perform precision farming because they provide useful information regarding moisture, nutrient content, and crop health. Primary sources of those indexes are satellites and unmanned aerial vehicles equipped with expensive multispectral sensors. Reducing the price of obtaining such information would increase the availability of precision farming for small farms. Several studies have proposed deep neural network methods to estimate the indexes from RGB color images. However, these methods report relatively large errors for mature plants when highly non-linear relationships of images and vegetation indexes arise. One could apply multilayer random forest-based models (Deep Forests) to solve this problem, but the discriminative power of such models is limited: they cannot catch complex dependencies between image features. In this paper, we propose a method that combines ideas of deep forests, random forests of kernel trees, and global pruning of random forests to tackle the problem. As a result, the method considers the properties of objects with a complex structure: the presence of relationships between groups of features, displacement, and scaling of objects. The experimental results show that the proposed method outperforms neural network-based solutions in several datasets.

The synthesis of additives for thinning mineral suspensions based on sodium polyacrylate was carried out. The effect of molecular weight regulators on the molecular weight characteristics of the polymer and the effect of such polymers on the rheological properties of suspensions was studied. Sodium acrylate polymers are synthesized by free radical polymerization in aqueous solution using molecular weight regulators. The molecular weight characteristics of the polymeric samples were estimated by viscometry using Mark-Houwink-Kuhn-Sakurada (MHKS) equation. Synthesized polymers were used as thinners ceramic slurries, prepared according to the recipe of the enterprises producing ceramic products. The thinning ability of polymer samples with different molecular weights was estimated using an Engler viscometer from the time of the ceramic slurry flow. The influence of the type and amount molecular weight regulator on polyacryates was revealed. It was found that molecular weight synthesized samples was in the range of 21000 - 91000. It was determined that samples with a molecular weight of 28000 - 35000 synthesized using mercaptoethanol (at a dosage of 0.5-1.5% by weight of the monomer) provide optimal fluidity to the ceramic slurry.

Reactions of picolinamides with 1,3-propanesultone in methanol followed by the treatment with ketones led to a series of previously unknown chemical transformations, yielding first pyridinium salts (2a-f) with a protonated endocyclic nitrogen atom and then heterocyclic salts (3a-j) containing a 4-imidazoline ring. The structures of intermediate and final products were determined by IR and 1H, 13C NMR spectroscopy and X-ray study. The effects of the ketone and alcohol structures on the product yield were studied by quantum-chemical calculations. The stability of salts 3a-j towards hydrolysis and alcoholysis makes them excellent candidates for the search of new types of biologically active compounds.

Alkaloid-based urea derivatives were produced with high yield through the reaction of anabasine and cytisine with isoxazolylphenylcarbamates in boiling benzene. Their antitumor ac-tivity in combination with the commonly used six anticancer drugs namely cyclophosphane, fluorouracil, etoposide, cysplatine, ribomustine with different mechanisms of action was investi-gated. Based on the quantum chemical calculations data and molecular docking, hypotheses have been put forward to explain their mutual influence when affecting on the С6 rat glioma model cells.

It is well known that X-ray crystallography is based on X-ray diffraction (XRD) by atoms and molecules. The diffraction pattern arises as a result of scattering of incident radiation, which makes it possible to determine the structure of the scattering substance. With the advent of ultrashort radiation sources, the theory and interpretation of X-ray diffraction analysis remained the same. This work shows that when an attosecond laser pulse is scattered on a DNA molecule, including during its nicking and bending, the pulse duration is an important characteristic of the scattering. In this case, the diffraction pattern changes significantly compared to the previously known scattering theory. The results obtained must be used in XRD theory to study DNA structures, their mutations and damage, since the previously known theory can produce large errors and, therefore, the DNA structure can be “deciphered” incorrectly.

In recent years, different deep learning frameworks were introduced for hyperspectral image (HSI) classification. However, the proposed network models have a higher model complexity and do not provide high classification accuracy if few-shot learning is used. This paper pre-sents an HSI classification method that combines random patches network (RPNet) and re-cursive filtering (RF) to obtain informative deep features. The proposed method first convolves image bands with random patches to extract multi-level deep RPNet features. Thereafter, the RPNet feature set is subjected to dimension reduction through principal component analysis (PCA) and the extracted components are filtered using the RF procedure. Finally, HSI spectral features and the obtained RPNet-RF features are combined to classify the HSI using a support vector machine (SVM) classifier. In order to test the performance of the proposed RPNet-RF method, some experiments were performed on three widely known datasets using a few training samples for each class and classification results were compared with those obtained by other advanced HSI classification methods adopted for small training samples. The comparison showed that the RPNet-RF classification is characterized by higher values of such evaluation metrics as overall accuracy and Kappa coefficient (https://github.com/UchaevD/RPNet-RF).

Current understanding of mechanisms of cellular resistance to genotoxic stress is incomplete but is critical for a variety of medical applications. Recent developments in the CRISPR/Cas technologies open new opportunities for targeted interrogation of resistance genes and pathways. In the present work, we used nuclease dead Cas9 constructs to achieve targeted overexpression of endogenous genes encoding two essential subunits of DNA damage sensor complex, XPC and HR23B, in HEK293T cells. Both individual and simultaneous overexpression of the two genes was achieved and the effects on cellular resistance to ionizing radiation and paraquat was examined. Using the fluorometric microculture cytotoxicity assay, we showed that simultaneous, but not separate overexpression of the two genes lead to a 30% increase in survivability. Irradiated cells that overexpressed both XPC and HR23B genes showed higher clonogenic capacity and proliferation rate compared to the irradiated transfection control as revealed by the clonogenic survival assay. Modulation of the gene expression did not affect cell resistance to paraquat. In summary, our results demonstrate a high potential of CRISPR/dCas9-enabled multiplex overexpression of stress-response genes in functionally justified combinations, exemplified here by the XPC-HR23B complex, for achieving an enhanced cellular radioresistance.

The present study aimed at investigating the in vitro and in vivo susceptibility of malaria parasites to crude extracts and fractions from Polyalthia suaveolens, Uvaria angolensis, and Monodora tenuifolia. The ethanolic extracts were prepared by maceration, and were further partitioned using water, dichloromethane, hexane, and methanol. The most promising fraction was subjected to column chromatography and the sub-fractions tested for activity in vitro. The antiplasmodial effect of extracts and fractions was tested against the Chloroquine resistant (PfK1) strain in 96 wells microtiter plate format using SYBR green florescence assay. The promising fraction was further assessed for cytotoxicity and acute toxicity in Swiss albino mice and subsequently against the rodent malaria parasite, P. berghei. Qualitative phytochemical screening was also performed on the promising fraction. The methanol fractions exerted the overall better effect with that of the twigs of P. suaveolens (PStw(Ace)) showing the highest potency with a IC50 value of 3.24 µg/mL followed by the fractions of leaf of M. tenuifolia (MoTel(Ace), IC50= 3.84 µg/ml) and stem bark of P. suaveolens (IC50= 4.90 µg/ml). The phytochemical screening showed the presence of alkaloids, lactones, and phenols in the more active fraction of P. suaveolens (PStw(Ace)). The chromatographic fractionation of this fraction led to 12 sub-fractions with PS8 sub-fraction being the most active (IC50= 4.42 µg/mL). In vivo, oral administration of 2000 mg/kg b.w of fraction PStw(Ace) in mice showed no signs of toxicity. Also, fraction PStw(Ace) at 400 mg/kg b.w exerted the highest suppressive effect against P. berghei strain B throughout the 4 days experiment (% parasitaemia below 5.2%). Overall, the results achieved supported the use of the three plants in the traditional treatment of malaria in Cameroon. More interestingly, the methanolic fraction of the twigs extract from P. suaveolens might be of interest in future development of an antimalarial phytodrug.

Recently, more and more countries are entering the global race for university competitiveness. On the one hand, global rankings are a convenient tool for quantitative analysis. On the other hand, their indicators are often difficult to quickly calculate, they often contradict each other. We thought about using widely available indicators for a quick analysis of the University's publication strategy. We opted for the normalized citation indicators available in SciVal analytical tool, i.e. Source Normalized Impact per Paper (SNIP) and Field-Weighted Citation Impact (FWCI). We have demonstrated the possibility of applying the correlation analysis to the impact indicators of a document and a journal on the sample of the social and humanitarian fields at Peoples' Friendship University of Russia. Particular attention was paid to the application of the results in practice.

Background: Microscopic examination of acid-fast stained sputum smears for detecting mycobacterial acid-fast bacilli (AFB) remains the most economical and readily available method for laboratory diagnosis of tuberculosis (TB). However, this conventional approach has limitations, including low sensitivity and labor-intensive procedures. Methods: An automated microscopy system incorporating artificial intelligence (AI) and machine learning for AFB identification was evaluated. The study was conducted at an Infectious Disease Hospital in Jiangsu Province, China, utilizing an intelligent microscope system (TB-Scan, Wellgen Medical, Kaohsiung). A total of 1,000 sputum smears were included in the analysis, with the system capturing digital microscopic images and employing an image recognition model to automatically identify and classify AFB. Referee technicians provided the gold standard for discrepant results. Results: The automated system demonstrated an overall accuracy of 95.00% (950/1,000), sensitivity of 91.24% (177/194), and specificity of 95.91% (773/806). Notably, the system identified 21 smears as positive that were previously reported as negative, with referee technicians confirming 17 of these as true positive and retracting the test results accordingly. Recalculating the performance, the accuracy increased to 96.70% (967/1,000), sensitivity to 91.94% (194/211), and specificity to 97.97% (773/789), with a false negative rate of 8.06% (17/211) and a false positive rate of 2.03% (16/789). Conclusions: The incorporation of AI and machine learning into an automated microscopy system demonstrated the potential to enhance the sensitivity and efficiency of AFB detection in sputum smears compared to conventional manual microscopy. This approach holds promise for widespread application in TB diagnostics and potentially other fields requiring labor-intensive microscopic examination.

The majority of investigations on microbial communities from various environments are presently built on culture-independent methods. Many studies point to the pivotal, selective role of primers targeting hypervariable regions of 16S rRNA in the metabarcoding of bacteria, including cyanobacterial communities. The selectivity of primers designed to amplify targeted regions of the 16S rRNA gene, which has been highlighted by many authors, limited effective amplification. Moreover, the type and specificity of the studied material can also negatively influence the results of 16S metabarcoding. Most of the studies of cyanobacterial communities have been performed for planktonic microbial communities that are often represented by common, well-studied species. In this study, we present the results of 16S metabarcoding analysis using three primer pairs - two already well-known and a third designed in this study - that amplify divergent regions of the 16S rRNA gene (V3-V4, V4-V6, V6) for benthic, microbial mat-forming cyanobacteria communities. Such communities can be a source of toxigenic cyanobacterial taxa and should be monitored with adequate primers. The comparison of three primer pairs suggested that those designed within the present study describe the structure and composition of highly heterogeneous cyanobacterial mats’ communities better than the others

In the paper, the results of an investigation into trace elements found in slag sulphides from 14 archaeological Bronze Age settlements of the Cis-Urals, Trans-Urals and North and Central Kazakhstan are presented. The study used Cu-(Fe)-sulphides as indicator minerals. Cu-(Fe)-S minerals in slags are primarily represented by covellite and chalcocite, as well as by rarer bornite and single chalcopyrite grains. Slag sulphides formed relic clasts and neogenic droplets of different shapes and sizes. Supergenic ores in the Bronze Age in Urals and Kazakhstan played a significant role in the mineralogical raw material base. In sulphides, the main indicator elements Fe, Co, Ni, As, Se, Te, Sb, Ag, Pb, and Bi are important markers of copper deposit types. Sulphides from olivine Cr-rich spinel containing slags of Ustye, Turganik, and Kuzminkovskoe 2 are characterised by As-Co-Ni assemblages and confined to copper deposits in ultramafic rocks. Olivine sulphide-containing slags from Kamenny Ambar, Konoplyanka and Sarlybay 3 are characterised by Co-Se-Te assemblage and confined to mafic rocks. Glassy sulphide-containing slags from Katzbakh 6, Turganik, Ordynsky Ovrag, Ivanovskoe, Tokskoe, Bulanovskoe 2, Pokrovskoe, Rodnikovoe, and Taldysay are characterised by Ag-Pb-(Ba)-(Bi) assemblage and confined to cupriferous sandstone deposits. High As, Sb, Sn and Ba contents found in slags can be seen as indicators of alloying or flux components in primary copper smelting. These include samples from Ustye, Katzbakh 6, Rodnikovoe, and Taldysay sites, where high Ba and As slag contents are identified. The compilation of a database with a broad sample of sulphide compositions from Bronze Age slags and mines in the Urals and Kazakhstan will permit the further identification of ore types and raw materials associated with a particular deposit.

This study investigated the influence of single nucleotide polymorphisms (SNPs) in genes asso-ciated with the interferon pathway (IFNAR2 rs2236757), antiviral response (OAS1 rs10774671, OAS3 rs10735079), and viral entry (ACE2 rs2074192) on COVID-19 severity and their association with non-alcoholic fatty liver disease (MAFLD). We did not observe a significant association between the investigated SNPs and COVID-19 severity. While the IFNAR2 rs2236757 A allele correlated with higher creatinine levels upon admission and the G allele with lower band neu-trophils upon discharge, these findings require further investigation. The distribution of OAS gene polymorphisms (rs10774671, rs10735079 did not differ between MAFLD and non-MAFLD patients. Our study population's distribution of ACE2 rs2074192 genotypes and alleles differed from the European reference population. Overall, our findings suggest that these specific SNPs may not be major contributors to COVID-19 severity in our patient population, highlighting the potential role of other genetic factors and environmental influences.

Abstract: The objective of these studies was to determine the dependence of the distribution of the microwave field into a grain layer and the efficiency of energy transfer from the magnetron into the grain layer, via a waveguide, on the moisture content. The subject of the research was a semicircular waveguide with slot radiators that supply a microwave field to the grain surrounding the waveguide. The change in the directional diagram of the microwave field in the longitudinal direction of the waveguide was studied using CST Microwave Studio 2019 software. It was found that the change in the moisture content of the processed grain leads to a significant change in both the radiation and total efficiency values of the waveguide. For instance, the radiation efficiency of the waveguide decreases by 15.1% (from 68.729 dB to 58.294 dB) when the moisture content of the processed grain increases from 14% to 26%. The total radiation efficiency also decreases (from 11.27 dB to 21.7 dB). In this case, not only the value of the radiation efficiency but also the shape of its dependence on the magnetron radiation frequency change. Data were obtained on the change in the Q-factor for resonators in which grain layers are processed, depending on the variation in grain moisture content.

Organisms are adapted to each other and the environment, not as tradition would have it, because natural selection made them that way, but because there is inbuilt striving towards stability and equilibrium. A General Theory of Behaviour connects imagery, affect and action with the central executive system we call Consciousness. The General Theory is founded on the assumption that the primary motivation of all of Consciousness and intentional behaviour is Psychological Homeostasis. Psychological homeostasis is as important to the organisation of mind and behaviour as Physiological Homeostasis is to the organisation of bodily systems. Consciousness processes quasi-perceptual images independently of the input to the retina and sensorium. Consciousness is the “I-Am” control centre for integration and regulation of (my) thoughts, (my) feelings and (my) actions with (my) conscious mental imagery as foundation stones. Imagery vividness, a combination of clarity and liveliness, is essential to imagining, remembering, thinking, predicting, planning and acting. Assessment of vividness using introspective report is validated by objective means such as fMRI. A significant body of work shows that vividness of visual imagery is determined by the similarity of neural responses in imagery to those occurring in perception of actual objects and performance of activities. I am Conscious, therefore I am.

Climate warming is expected to have pronounced effects on Arctic and Subarctic ecosystems, especially regions underlain by discontinuous and relatively warm permafrost. The main goal of this research is to evaluate the vulnerability and dynamics of permafrost under climate warming across the various ecotypes in respect of ecosystem stability, socioeconomic impact, and for better understanding possible future environmental changes. We suggested the new version of the spatially distributed permafrost dynamics model (GIPL2-MPI), which is developed in the Geophysical Institute, University of Alaska Fairbanks. This model is based on the ecosystem approach to simulate the permafrost dynamics, which we are discussing in this paper. We combined ground-based observations and numerical freeze/thaw modeling using climate-ecosystem-permafrost interactions to understand the physical processes and mechanisms controlling permafrost physical state. We predict the changes in permafrost conditions using output from two GCMs (NCAR-CCSM4 and GFDL-CM3) and Five-Model Average Ensemble for the RCP-4.5 and RCP-8.5 scaled down to 1 by 1 km spatial resolution (https://uaf-snap.org/) across entire Alaska. Our result shows that by the end of the current century widespread near-surface permafrost degradation could begin everywhere in Alaska southward of the Brooks Range as well as across some spots at the North Slope Alaska.

Here we present 1. a model for amplicon sequencing 2. a definition of the best assignment of a read to a set of reference sequences 3. strategies and structures for indexing reference sequences and computing the best assign- ments of a set of reads efficiently, based on (ultra)metric spaces and their geometry The models, techniques, and ideas are particularly relevant to scenarios akin to 16S taxonomic profiling, where both the number of reference sequences and the read diversity is considerable.

Predicting the prices of cryptocurrency owing to its volatility, instability, and other factors has been challenging; investors and traders especially in Nigeria have been on a constant look for a more reliable way of knowing market trends and prices and while there has been so many research conducted using deep learning, the results for which has fall short of what investors could called a strong predictor. This research reviewed the results of many works that had been done and proposed two types of recurrent neural network (RNNs) namely Long Short-Term Memory and Gated Recurrent Unit (GRU) for predicting the future prices of two of the most common crypto assets namely Bitcoin (BTC) and Ethereum (ETH), these two were selected based on their popularity, the volume traded and their market capitalization. The experiment was conducted in a GPU Jupyter Notebook environment and the performance of our experiment was evaluated on a test set using root mean square error (RMSE) and based on its values, the LSTM presented a better performance with rsme scores of 654.66, and 80.30 respectively for BTC and ETH as compared to GRU. The paper proceeds further to compare the results of this experiment with other related works and we discovered that its performance is a great improvement.

This work (in two parts) will review the recently developed predictive modeling methodology called “4th-BERRU-PM” and its applicability to energy systems as exemplified by an illustrative application to the Polyethylene-Reflected Plutonium (acronym: PERP) OECD/NEA reactor physics benchmark. The acronym 4th-BERRU-PM designates the “Fourth-Order Best-Estimate Results with Reduced Uncertainties Predictive Modeling” methodology, which yields best-estimate results with reduced uncertainties for the first fourth-order moments (mean values, covariance, skewness, and kurtosis) of the optimally predicted posterior distribution of model results and calibrated model parameters. The 4th-BERRU-PM uses the Maximum Entropy (MaxEnt) principle to incorporate fourth-order experimental and computational information, including fourth (and higher) order sensitivities of computed model responses to model parameters, thus incorporating, as particular cases, the results previously predicted by the second-order predictive modeling methodology 2nd-BERRU-PM, and vastly generalizing the results produced by extant data assimilation and data adjustment procedures. The 4th-BERRU-PM methodology encompasses the scopes of high-order sensitivity analysis (SA), uncertainty quantification (UQ), data assimilation (DA) and model calibration (MC). The application of the 4th-BERRU-PM methodology to energy systems is illustrated by means of the above-mentioned OECD/NEA reactor physics benchmark, which is modeled using the neutron transport Boltzmann equation involving 21976 imprecisely known parameters, the solution of which is representative of “large-scale computations.” The model result (“response”) of interest is the leakage of neutrons through the outer surface of this spherical benchmark, which can be computed numerically and measured experimentally. Part 1 of this work illustrates the impact of high-order sensitivities, in conjunction with parameter standard deviations of various magnitudes, on the determination of the expected value and variance of the computed response in terms of the first four moments of the distribution of the uncertain model parameters. Part 2 of this work will illustrate the capabilities of the 4th-BERRU-PM methodology for combining computational and experimental information, up to and including forth-order sensitivities and distributional moments, for producing best-estimate values for the predicted responses and model parameters while reducing their accompanying uncertainties.

Aluminum, a contentious trace element found in the environment, has been demonstrated to have harmful effects on both humans and animals. In contrast, Sempervivum tectorum, an evergreen plant, has been found to offer numerous beneficial effects for both humans and animals. Therefore, this study aims to assess the protective effect of S. tectorum on certain reproductive biomarkers in male rats exposed to aluminum. Thirty-five Wistar rats were randomly divided into five groups: NTC (no-treatment control) received distilled water; NC (negative control) received drinking water containing 1 mg/L aluminum sulfate (AS); E1 received 1 mg/L AS along with an 8% S. tectorum extract; PC (positive control) received only 8% S. tectorum extract; E2 received 1 mg/L AS for three months followed by 8% extract for one month. The study analyzed testosterone, LH, FSH, body weight, and the histological structure of the testis, epididymis, and prostate, as well as the levels of zinc, manganese, copper, and iron in these organs. Significant decreases in body weight, testis, and epididymis size were observed in the aluminum-exposed groups compared to the control, whereas these decreases were not significant in the S. tectorum-treated groups compared to the control. Aluminum exposure led to significant decreases in testosterone and LH levels, with FSH levels showing a non-significant decrease in males, which were mitigated significantly by the administration of the plant extract. Histological analysis revealed alterations in the testis, epididymis, and prostate of the AS-exposed groups, including necrosis of seminiferous tubule epithelium and Leydig cells in the testis, and basal epithelial necrosis in the epididymis and prostate. Aluminum levels increased in all organs studied, while levels of zinc, copper, iron, and manganese decreased, showing a negative and significant correlation with aluminum levels. The aqueous extract of S. tectorum demonstrated a protective effect on certain studied biomarkers in male rats affected by aluminum exposure.

Abstract: The establishment of a circular economy in the mining sector, taking advantage of innovations in the exploration and development of hydrocarbon reserves, [ ], their [ ], transportation [ ] and subsequent processing [ ] are significant concerns. The issues surrounding the employment of technology targeted at enhancing environmental safety to increase the productivity of the reproduction process of the natural gas and oil resource base are equally important. The paper discusses the use of green seismic technology of survey to determine the oil and gas potential of the subsoil. A methodological toolkit is proposed for carrying out technical and economic calculations to determine indicators of the environmental and economic efficiency of using innovative resource-saving technology for geological survey in areas densely planted with forests. The purpose of the work is to establish the viability of employing resource-saving technology known as Green Seismic to search for promising hydrocarbon objects in forested areas and determine the expected environmental and economic benefits of geological exploration using the suggested enhanced methodology for their evaluation. The tasks set to achieve the goal were solved using methods of geological and economic assessment of the hydrocarbon raw material potential of territories and water areas, environmental assessment of the negative influence of anthropogenic environmental impact on the natural environment, economic and statistical methods of performing technical and economic calculations to determine performance indicators for the implementation of innovative projects in the field of geological exploration. The novelty of the results obtained lies in the proposed improved algorithm for conducting an environmental and economic assessment of geological exploration for hydrocarbon raw materials, a conceptual description of the Green Seismic technology, systematization of technical, economic, and environmental risks, justification of new regional directions for geological exploration using resource-saving seismic exploration technology.

Tumor to stroma ratio is a highly debated prognostic factor in the management of several solid tumors and there is no universal agreement on its practicality. In our study we proposed to confirm or dismiss the hypothesis that a simple measurement of stroma quantity is an easy-to-use and strong prognostic tool. We have included 74 consecutive patients with colorectal cancer who underwent primary curative abdominal surgery. The tumors have been grouped into stroma-poor (stroma &lt;10%), medium-stroma (between 10 and 50%) and stroma-rich (over 50%). The proportion of tumor stroma ranged from 5% to 70% with a median of 25%. Very few, only 6.8% of patients had stroma-rich tumors, 4% stroma-poor tumors and 89.2%tumors with a medium quantity of stroma. The proportion of stroma, at any cut-off, had no statistically significant influence on the disease specific survival. This can be explained by the low proportion of stroma-rich tumors in our patient group and the inverse correlation of stroma proportion with tumor grade. The real-life proportion of stroma-rich tumors and the complex nature of the stroma-tumor interaction has to be further elucidated.

The aim of this work was to classify the business incubators in Spain according to the four phases of startups incubation. Taking into account that the graduation rate implies greater survival and business success of the incubated companies, they have been identified at each stage of the incubation (spread of entrepreneurship, pre-incubation, advanced incubation, and graduation). The activities that present higher impacts on the success of the incubated companies and the activities carried out by the incubator that have a greater relevance on the graduation of the companies have concretely been considered. Principal component (PC) cluster analysis have been applied. All the incubation variables were used simultaneously, reducing their number, and grouping them into factors, finally the cases were grouped according to these latent variables. Principal components analysis reduced dimensionality to 8 factors with a 74 % of explained variance. Factor 1 was positively related to pre-incubation variables, factor 2 was linked to training and collaboration variables within the entrepreneurship diffusion phase. Factor 3 called activity monitoring and control and was related to phase 3 or basic incubation variables. Clusters analysis facilitates the grouping of incubators into three clusters: Group 1 (16 % of the total), incubators with strong deficits in incubation phases 1, 2 and 3. They are small Business Incubators, often located in rural areas or cities and low graduation rate. Group 2 (30 %), business incubators with very high graduation rate, and strongly positive values in factor 1 and 2. Factor 3 although positive is susceptible to improvement. They are the largest incubators and usually located in industrial and technological parks. Group 3 (54 %) is the majority, with values close to cluster 2 and 3.

Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) frequently require primary radiochemotherapy (RCT). Despite intensity-modulation, desired radiation-induced effects observed in HNSCC, may also be observed as side-effects in healthy tissue e.g. the sternocleidomastoideus muscle (SCM). These side-effects (e.g. tissue fibrosis) depend on the interval between completion of RCT and restaging-CT. For salvage surgery, the optimal time window for surgery is currently postulated between 6 and 12 weeks after completion of RCT. Thus, no extensive tissue fibrosis is to be expected. This interval is based on studies exploring surgical complications. Studies directly exploring radiation-induced changes of the SCM in HNSCC-patients are sparse. The present study quantifies tissue alterations in SCM and paravertebral musculature (PVM) after RCT applying radiomics to determine the optimal time window for salvage surgery. Three radiomic key parameters 1) volume, 2) mean positivity of pixels (MPP) and 3) uniformity were extracted with mint lesionTM in the staging-CTs and restaging-CTs of 98 HNSCC-patients. Of these, 25 were female, the mean age was 62 (±9.6) years and 80.9% were UICC Stage IV. The mean restaging-interval was 55 (±28; range29-229) days. Only the mean volume significantly decreased after RCT from 9.0 to 8.4 and 96.5 to 91.9 ml for SCM and PVM, respectively (both p=0.007, both Cohen’s d=0.28). In addition, the mean body mass index (BMI) decreases from 23.9 (±4.2) to 21.0 (±3.6) kg/m² (p<0.001); Cohen's d = 0.9). The mean BMI-decrease significantly correlated with the volume decrease for SCM (r=0.27; p=0.007) and PVM (r=0.41; p<0.001). If t-test p-values were adjusted for the BMI-decrease, no significant change in volumes for SCM and PVM was observed (both p>0.05). The present data supports the postulated optimal interval for salvage surgery of 6 to 12 weeks. Irrespective of the remaining risk-benefit ratio of salvage surgery, the risk of additional surgical complications due to fibrosis is not supported by the present observations.

Keywords: Pain; Nociception; Disorders of Consciousness; Consciousness

The problem of optimal scheduling in a system with parallel queues and a single server has been extensively studied in the queueing theory. However, such systems have mostly been studied by assuming homogeneous attributes of arrival and service processes, or in heterogeneous case a Markov random process was usually assumed. In this paper, we explore the possibility of combining simulation and neural network paradigms for optimal scheduling in a heterogeneous system with an arbitrary inter-arrival and service time distributions. The service of any queue by the server is exhaustive. Further routing of the server after the queue has been emptied is as instructed by the trained neural network. Any change in the queue that currently has a server is accompanied by a switching cost. The simulated annealing optimization algorithm which is used to optimize the parameters of the neural network was adapted for numerically evaluated average cost function. A Markov decision problem was formulated for the corresponding markovian queueing system to verify the results of solving the optimization problem. In addition to comparing the actual values of the average cost, the parameter values of the neural network trained on the optimal control policy of the Markov model are also used to determine the domains of parameters required for the simulated annealing defined on a finite discrete domain. Numerical analysis shows the effectiveness of this approach. Moreover, a comparison of the results for different distributions illustrates the insensitivity of the optimal control policy to the shape of the distributions for the same two first moments. Thus, the optimal control policy for an exponential model can be used as a suboptimal one for the general system.

Shiga toxins (Stxs), and more specifically the Stx2a subtype, are the major virulence factors involved in enterohemorrhagic Escherichia coli (EHEC)-associated hemolytic uremic syndrome (eHUS); a life-threatening disease causing acute kidney injury, especially in children. Cleavage of Stxs A subunit, when followed by reduction, boosts the enzymatic activity causing damage to targeted cells. This cleavage was assumed to be mostly mediated by furin during Stx intracellular trafficking. Cleavage of A subunit, without reduction, changes the binding properties of Stxs for blood components during HUS pathogenesis. To investigate whether the cleavage could occur in the intestine, even prior entering target cells, Stx2a structure was characterized after its exposure to specific host factors present in human stool. The structure of Stx2a A subunit was determined by immunoblotting after electrophoretic separation under reducing conditions. Trypsin and chymotrypsin-like elastase 3B (CELA3B), two serine proteases, were identified as potential candidates that may trigger the extracellular cleavage of Stx2a A subunit directly after its secretion by EHEC in the gut. Whether this observation indeed translates to natural infections and plays a role in eHUS pathogenesis has yet to be determined as well as whether host's protease profile could affect disease development by changing the toxin’s biological features.

HLA class-I (HLA-I) polyreactive monoclonal antibodies (mAbs) reacting to all HLA-I alleles were developed by immunizing HLA-E monomeric heavy chain (HC) (Open Conformers, OCs). Two of the mAbs (TFL-006 and TFL-007) bound to the HC’s coated on a solid matrix. The binding was inhibited by a peptide 117AYDGKDY123, present in all alleles of the six HLA-I isoforms but masked by 2-microglobulin -m) in intact HLA-I trimers (Closed Conformers, CCs). Identical HLA-I polyreactivity is observed in IVIg administered to lower anti-HLA antibodies (Abs) in HLA-sensitized patients, but the mechanism is unknown. We hypothesized that the mAbs that mimic IVIg HLA-I polyreactivity might mimic the immunomodulatory functions of IVIg. We tested the relative binding affinity of the mAbs and IVIg for both OCs- and CCs and compared their effects on (a) the phytohemagglutinin (PHA)-activation T-cells, (b) the production of anti-HLA-II antibody (Ab) by B-memory cells, and anti-HLA-I Ab by immortalized B-cells, and (c) the upregulation of CD4+, CD25+, and Fox P3+ T-regs. The mAbs bound only to OCs, whereas IVIg is bound to both CCs and OCs. The mAbs suppressed blastogenesis and proliferation of PHA-activated T-cells, anti-HLA Ab production by B-cells and expanded the T-regs, better than IVIg. We conclude that a humanized version of the TFL-mAbs could be an ideal therapeutic IVIg-mimetic.

Orthohepadnavirus causes chronic hepatitis in a broad range of mammals, including primates, cats, woodchucks, and bats. Hepatitis B virus (HBV) X protein inhibits type-I interferon (IFN) signaling, promoting HBV escape from the innate immune system to establish persistent infection. However, whether X proteins of Orthohepadnavirus viruses in the other species have similar inhibitory activity remains unknown. Here, we investigated the anti-IFN activity of 17 Orthohepadnavirus X proteins derived from various hosts. We observed conserved activity of Orthohepadnavirus X proteins in inhibiting TIR-domain-containing adaptor protein inducing IFN-β (TRIF)-mediated IFN-β signaling pathway through TRIF degradation. X proteins from domestic cat hepadnavirus (DCH), a novel member of Orthohepadnavirus, inhibited mitochondrial antiviral signaling protein (MAVS)-mediated IFNβ signaling pathway comparable with HBV X. These results indicate that inhibition of IFN signaling is conserved in Orthohepadnavirus X proteins.

Spodoptera frugiperda is an invasive pest that has spread in various parts of the world. These pests have the ability to spread and adapt highly to new habitats. Until now, it is not known with certainty the distribution of these invasive pests in Eastern Indonesia, especially Bali and Nusa Tenggara. This study aims to map the spatial distribution and genetic distribution of S. frugiperda which damages maize in the areas of Bali and Nusa Tenggara. This research was conducted using a survey method from May to September 2022 covering the islands of Bali, Lombok, Sumbawa, Sumba, Flores, and Timor. The results showed that S. frugiperda had spread evenly in Bali and Nusa Tenggara. The results of PCR amplification in the COI gene from 9 sample isolates from all research locations showed the similarity of DNA bands leading to the Spodoptera frugiperda species with a banding pattern length of 683 – 697. These results indicated that the distribution of genetic variants of corn caterpillars in Bali, NTB, and NTT was confirmed as S. frugiperda species. However, the isolated gene S. frugiferda, which was shown by the alignment results of the sequences from Lombok, was confirmed as a different strain from strains from Bali, Sumba, Sumbawa, Flores, and Timor. This incident can be seen from the difference in the protein base composition of S. frugiperda from Bali, Sumba, Sumbawa, Timor, and Flores. The results of phylogenetic analysis in this study confirmed 3 clusters of the genetic closeness of S. frugiperda. Cluster-1 comes from the results of the search for specimens of JB FAW and KB FAW from Bali, SB FAW and SB FAW Sorghum from Sumba, SW FAW from Sumbawa, KP FAW from Timor, and FL FAW from Flores. Cluster-2 is an isolate outside of our species. Cluster-3 comes from the search for LT and LS FAW specimens from Lombok. The genetic distance between cluster-1 and cluster-3 is quite far, which is 0.20 mu.

Breast cancer is the most common cancer in women globally, often necessitating mastectomy and subsequent breast reconstruction. Silicone mammary implants (SMIs) play a pivotal role in breast reconstruction, yet their interaction with the host immune system and microbiome remains poorly understood. This study investigates the impact of SMI surface topography on host antimicrobial responses, wound proteome dynamics, and microbial colonization. Biological samples were col-lected from ten human patients undergoing breast reconstruction with SMIs. Mass spectrometry profiles were analyzed for acute and chronic wound proteomes, revealing a nuanced interplay between topography and antimicrobial respondseproteins. 16S rRNA sequencing assessed mi-crobiome dynamics, unveiling topography-specific variations in microbial composition. Surface topography alterations influenced wound proteome composition. Microbiome analysis revealed heightened diversity around rougher SMIs, emphasizing topography-dependent microbial inva-sion. In vitro experiments confirmed staphylococcal adhesion, growth, and biofilm formation on SMI surfaces, with increased texture correlating positively with bacterial colonization. This comprehensive investigation highlights the intricate interplay between SMI topography, wound proteome dynamics, and microbial transmission. The findings contribute to understanding host-microbe interactions on SMI surfaces, essential for optimizing clinical applications and minimizing complications in breast reconstruction.

A power factor correction (PFC) rectifier is compulsory for any electronic circuitry connected to the electrical grid. The majority of PFCs that are utilized are based on a step-up converter that supplies high DC voltage at its output terminal. Electric vehicle battery voltage varies from a few hundred to almost a thousand volts. Thus, an additional conversion step is obligatory when designing an all-brand universal charger. This paper presents a new type of front-end versatile step up / down three voltage level PFC. The rectifier can operate in continuous conduction mode or discontinuous conduction mode. First, the rectifier’s principle of operation is described, and then an innovative rectifier is analyzed for continuous and discontinuous conduction modes. Finally, the proposed theory is experimentally validated in a multiplier-less dual loop mode at discontinuous conduction modes. It was shown that although there is no multiplier use in the control circuitry, the power factor is near unity. It was revealed that the rectifier could swing the output voltage from 50 V to 900 V while the input voltage was 230 Vrms. The innovative topology suits any standard PFC rectifier, three-level voltage supplement, and dual-stage low-voltage power supply.

Stress urinary incontinence (SUI) influences the quality of life of women. The research applied ICIQ LUTS qol (The International Consultation Incontinence Questionnaire Lower Urinary Tract Symptoms quality of life) as a tool to measure the quality of life (QOL) of patients with stage 1 SUI in many areas. 140 perimenopausal women who participated in a urodynamic test at Department of Gynecology, Endocrinology and Gynecologic Oncology, Pomeranian Medical University, Police, Poland in the years 2013-2015 were enrolled in the study. Patients were divided into two groups: A and B. Two questionnaires were applied: the author’s original questionnaire and the standardized ICIQ LUTS qol. Gymnastic plans were recommended 4 times per week for the period of 3 months. The plan for group A included the exercises of pelvic floor muscles (PFM) with the simultaneous tension of the transverse abdominal muscle (TrA) and for group B included the exercises of PMF without TrA. The evaluation of the quality of life of patients with stage 1 SUI with the use of ICIQ LUTS qol among patients from groups A and B after therapy showed a significant improvement in most areas. More impact is observed in the physiotherapy of both PFM with TrA.

F-type ATP synthases play a key role in oxidative and photophosphorylation processes producing adenosine triphosphate (ATP) for most biochemical reactions in living organisms. In contrast to the mitochondrial FOF1-ATP synthases those of chloroplasts are known to be mostly monomers with approx. 15% fraction of oligomers interacting presumably non-specifically in a thylakoid membrane. To shed light to the nature of this difference we studied interactions of the chloroplast ATP synthases using small-angle X-ray scattering (SAXS) method. Here, we report evidence of I-shaped dimerization of solubilized FOF1-ATP synthases from spinach chloroplasts at different salinity. The structural data were obtained by SAXS and showed dimerization in response to changes in ionic strength. The best model describing SAXS data was two ATP-synthases connected through F1/F1’ parts, presumably via their δ-subunits, forming dimers with the “I” shape. Such I-shaped dimers might possibly connect the neighboring lamellae in thylakoid stacks assuming that the FOF1 monomers comprising such dimers are embedded in different thylakoid membranes. If this type of dimerization exists in nature, it might be one of the pathways of inhibition of chloroplast FOF1-ATP synthase for preventing of ATP hydrolysis in dark, when salinity in plant chloroplasts is rising. Together with a redox switch inserted into a γ-subunit of chloroplast FOF1 and lateral oligomerization, an I-shaped dimerization might comprise a subtle regulatory process of ATP synthesis and stabilize the structure of thylakoid stacks in chloroplasts.

The Solvency II regulatory framework specifies procedures and parameters for determining solvency capital requirements (SCRs) for insurance companies. The proposed standard SCR calculations involve two steps. The Value–at–Risk (VaR) of each risk driver is measured and, in a second step, all components are aggregated to the company’s overall SCR, using the Standard Formula. This formula has two inputs: the VaRs of the individual risk drivers and their correlations. The appropriate calibration of these input parameters has been the purpose of various Quantitative Impact Studies that have been conducted during recent years. This paper demonstrates that the parameter calibration for the equity–risk module—overall, with about 25%, the most significant risk component—is seriously flawed, giving rise to spurious and highly erratic parameter values. As a consequence, an implementation of the Standard Formula with the currently proposed calibration settings for equity–risk is likely to produce inaccurate, biased and, over time, highly erratic capital requirements.

Introduction: Carcinoid heart disease is a rare cause of right-sided valvular dysfunction, an important complication in patients with carcinoid syndrome. Objectives: We aim to present our own experience regarding early myocardial dysfunction in patients with carcinoid syndrome. Methods: 64 patients (35-90 year old, 62,5% female, 37,5% male patients) with carcinoid syndrome were evaluated be-tween October 2017 and June 2021. All patients underwent two-dimensional echocardiography with additional tissue Doppler and speckle-tracking techniques. For all patients there were measured urinary level of 5- hydroxyindolacetic acid, serotonin and NT-proBNP values. Results: The following echocardiographic features: global longitudinal strain of both ventricles, mean systolic velocity of the left ventricle, systolic velocity of the free wall of right ventricle, correlated with high values of specific biomarkers: serotonin, and urinary 5-hydroxyindolacetic acid, and also with the presence of hepatic metastases and poorly differentiated tumors. Discussion: In this study we identified several patients with early myocardial dysfunction due to carcinoid syndrome, representing a predictive model of poor prognosis, requiring further investigations. Conclusion: Echocardiographic assessment based on the measurement of systolic velocities, as well as the global longitudinal strain of both ventricles, together with specific biomarkers may contribute to better recognition of carcinoid heart disease in clinical practice, but this needs validation through further studies enrolling larger number of patients.

Alzheimer's disease (AD) is the most common cause of dementia and affects millions of people around the world. Neuronal death in AD is initiated by the toxic action of oligomeric amyloid-β (Aβ) peptides. The formation of membrane channels by Aβ is a primary molecular action and does not require any other proteins. Channels are formed by short amyloid fragments faster and more frequently than by full-length peptides. The channel formation is dependent on an electrostatic interaction between a positively charged peptide and a negatively charged membrane. Negative membranes can be found in several locations of a cell – the inner leaflet of plasma membrane, mitochondria, and lysosomes, which all are well-known cellular targets in AD. Considering that the amyloid enters a cell by endocytosis and is exposed to lysosomal enzymes, we propose the amyloid degradation toxicity hypothesis. Endopeptidases degrade the endocytosed peptide. Produced fragments form membrane channels, which can transfer various ions (including protons) and even relatively large compounds. The neutralization of lysosomal content inactivates enzymes, which fails the whole system of recycling cellular content, including autophagy. The permeabilization of lysosomes could also lead to cell death through necrotic and apoptotic mechanisms. We discuss several mechanisms that describe how amyloid degradation products reach plasma and mitochondrial membranes, and form membrane channels. The pathogenesis of AD is discussed at various levels in a context of how the primary molecular mechanism of membrane channel formation could progress into the disease state. The discussion starts at the molecular level and extends to why the development of a disease takes years and is closely associated with aging. The proposed hypothesis offers an interpretation to several clinical observations such as the involvement of iron metabolism and an inverse association between developing Alzheimer's disease and cancer. Predictions about potential biomarkers and effectiveness of future treatments are discussed.

Phylostratigraphic analysis is a way to look anew on phylogenetic data in the evolutionary aspect. It allows counting the evolutionary age based on the analysis of genes, their orthologs and finding the last common ancestor. We performed phylostratigraphic analysis of Arabidopsis thaliana genes associated with several types of abiotic stresses (heat, cold, water-related, light, osmotic, salt, and oxidative) determined by the Gene Ontology annotation. Comparison of the distributions of ages of genes associated with stresses of different type has shown the heat stress to involve older genes while the light stress – younger genes. At the same time, all types of stress are characterized by a significantly higher proportion of old genes (common to all eukaryotes) compared to the whole set of A.thaliana genes. This can be explained by the involvement of basic molecular processes in plant cells into the stress response. Reconstruction and graphical analysis of the gene network of the heat stress educed several clusters associated with different response functions. Some of these clusters contain only ancient genes. The results obtained show that the phylostratigraphic analysis reveals the fundamental features of the organization of gene networks and their evolution.

The aim of our study was a comprehensive comparative assessment of the effect of consumption of 1 and 2% cholesterol as part of a standard diet with and without regular moderate physical activity on the main biomarkers of lipid and cholesterol metabolism, as well as the intestinal microbiota of male Wistar rats. The animals were randomly divided into 5 groups according to body weight and Open Field test results: Control (n=10), 1% Chol (n=10), 2% Chol (n=10), 1% Chol + RUN (n=10) and 2% Chol + RUN. The cholesterol was additionally added in the amount of 1g or 2g/100g, respectively, to the diet of animals. The rats of experimental groups 1% Chol + RUN and 2% Chol + RUN were subjected to regular (2 days a week) physical activity on a Treadmill. In rats of four experimental groups, when compared to the Control, a response of 39 indicators was revealed. The largest number of changes in biomarkers - 29 (statistically significant, p

Lyme disease, the leading vector-borne ailment in the U.S., annually affects an estimated 476,000 individuals, predominantly in the Northeast and Upper Midwest. Despite its increasing incidence, the evaluation of risk within U.S. cities, including natural public lands, remains inadequate. This study focuses on blacklegged tick occurrences and Borrelia burgdorferi infection prevalence in 24 Staten Island parks, aiming to assess Lyme disease exposure risk. Monthly acarological risk index (ARI) calculations from 2019 to 2022 revealed elevated values (0.16-0.53) in specific parks, notably Wolfe’s Pond Park, High Rock Park, Clay Pit Pond Park, Clove Lake Park, and Fair View Park. June (0.36) and November (0.21) consistently exhibited heightened ARIs, aligning with peak tick collection months. Despite stable yearly infection rates at 28.97%, tick densities varied significantly between parks and years. Identifying a high transmission risk in specific parks in Staten Island, a highly urbanized part of New York City, emphasizes the continuous necessity for Lyme disease risk management, even within the greenspaces of large cities.

We present an open-source Star Tracker (ST) for Attitude Determination. Our implementation makes use of open source software of common usage in astronomy running on a Raspberry Pi 2 platform. The developed platform is open and available for parties interested in further development. Evaluation of the system showed that the ST is suitable for Cubesats of 2U or larger. The ST platform is capable of solving the Lost-In-Space (LIS) problem. Currently, the average accuracy reached of the algorithm is close to 5 seconds of arc with an average processing time of 75 seconds. However, a average accuracy of about 3 minutes of arc can be reached with 35 seconds in average processing time. We also describe the evaluation procedure, the found conclusions of this procedure, in particular the section of the algorithm where most of the processing time is spent and other possible source of errors not included in this study.

The paper describes the research findings on dynamic and mechanical properties of composite elastomers with high permeability magnetic filling agent capable of rapidly and reversibly changing its properties when exposed to an external magnetic field, which makes it a perspective material for application in a wide range of engineering areas. The research has analyzed the trends in the strength properties of the materials obtained through the use of filling agents of different fineness, content, and structural organization in the final polymer, under different conditions. This allowed to obtain the correlations between the influence of the filler's relative fineness on the dynamic and mechanical properties of composite polymers, and to estimate the trends in the parameters describing the material strength under the complex magnetic and thermal influence. The results obtained by the authors allowed to ground the composition and structural organization of the final material with the best set of dynamic and mechanical properties.

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a human DNA repair protein. It is a member of the phospholipase D family based on the structure similarity. TDP1 is a key enzyme involved in repairing stalled topoisomerase 1 (TOP1)-DNA complexes. Previously we obtained with the CRISPR/Cas9 method HEK293A cells with the homozygous knockout of the Tdp1 gene and used knockout cells as a cellular model for studying the mechanisms of anticancer therapy. In this work we studied for the first time by transcriptomic analysis the effect of Tdp1 gene knockout on genes expression changes in human HEK293A cell line. We received original data that may indicate a role of TDP1 in other process besides repair of DNA-TOP1 complex. The differentially expressed genes (DEGs) analysis revealed that TDP1 could be involved in different processes such as cell adhesion and communication, spermatogenesis, mitochondrial function, neurodegeneration, cytokine response, and MAPK pathway signaling.

In a saline semi-isolated Lagoon on the Cape Zeleny (White Sea), the annual dynamics of the vertical hydrological structure, and the seasonal dynamics of phytoplankton were traced, including species composition, and vertical distribution, abundance, nutrition type,and biomass.293 species and supraspecific taxa of algae and cyanobacteria were found. Most of the identified species are marine, and 38 species are freshwater. Taxonomic composition changed in the Lagoon during the year. Dinoflagellates dominated in winter and early June; unidentified cocci and flagellates in July; diatoms, dinoflagellates and unidentified cells in August; dinoflagellates in September; and unidentified cocci and flagellates in October–November. The abundance of algae also changed in the Lagoon during the year. The integrated biomass in the water column varied from 0.01 g C/m2 in January to 0.78 g C/m2 in early September. According to the abiotic parameters, the water column of the Lagoon is subdivided into several zones with different conditions and corresponding phytoplankton communities. Similarity between the communities of different horizons was 32-46% in summer and 7% in winter. The chemocline layer was the most populous. Almost the entire year it contained a maximum of phytoplankton biomass, 1-2 orders of magnitude higher than that in the overlying horizons. Comparison phytoplankton in the lagoon and in the nearby sea area was carried out. Despite the connection between the Lagoon and the sea phytoplankton structure in the surface water layer in the Lagoon and in the sea differs significantly in composition, quantitative parameters, and seasonal dynamics. The similarity of the communities in the sea and the Lagoon never exceeded 50%. In terms of biomass, the Lagoon lags behind the sea until mid-summer, but, starting from August, it outnumbers it, and the phytoplankton development in the Lagoon lasts longer, until late autumn. The phytoplankton structure and dynamics in the Lagoon and the sea by 24.5% was related to the daylight, water salinity, oxygen content and pH, but did not depend on water T, underwater illuminance, and depth. Oxygen content and pH are defined by PhP activity. Salinity serves as a vector of the vertical sequence of ecological niches. The daylight length seems to be the crucial factor of the seasonal PhP dynamics in the semi-isolated coastal stratified lakes and lagoons.

Currently, obesity is a critical global public health burden. Numerous studies have demonstrated the regulation of the pathogenesis of obesity and metabolic abnormalities by the gut microbiota and microbial factors; however, their involvement in the various degrees of obesity is not yet understood well. Previously, obesity has been shown to be associated with decreased levels of vitamin B12. Considering exclusive microbial production of vitamin B12, we hypothesised that a decrease in cobalamin levels in obese individuals may be at least partially caused by its depleted production in the intestinal tract by the commensal microbiota. In the present study, our aim was to estimate the abundance of enzymes and metabolic pathways for vitamin B12 synthesis in the gut microbiota of mouse models of alimentary and genetically determined obesity, to evaluate the contribution of the obesogenic microbiome to vitamin B12 synthesis in the gut. We have defined a significantly lower representation of enzymes and metabolic pathways for vitamin B12 biosynthesis in obese mice compared to non-obese mice, wherein enzyme depletion was more pronounced in lepr(-/-) (db/db) mice, which developed severe obesity. The representation of enzymes involved in cobalamin synthesis is strongly correlated with representation of several microbes in high-fat diet fed mice, whereas there were almost no correlations in db/db mice. Therefore, the degree of obesity and the composition of the correspondent microbiota are the main contributors to the representation of genes and pathways for cobalamin biosynthesis in the mouse gut.

The peripheral lymphatic system plays a crucial role in the recovery mechanisms after many pathological changes, such as infection, trauma, vascular, or metabolic diseases. The lymphatic clearance of different tissues from waste products, viruses, bacteria and toxic proteins significantly contributes to the correspondent recovery processes. However, understanding of the meningeal lymphatics functions is a challenging problem. The exploration of mechanisms of lymphatic communication with brain fluids as well as the role of the lymphatic system in the brain drainage, clearance and recovery are still in its infancy. Here we review novel concepts on the anatomy and physiology of the lymphatics in the brain, which warrant a substantial revision of our knowledge about the role of lymphatics in the rehabilitation of the brain functions after neural pathologies. We discuss a new vision on how to recruit the meningeal lymphatics by the opening of blood-brain barrier as a trigger mechanism of activation of the meningeal lymphatic drainage. This leads to innovative strategies in neurorehabilitation therapy.

The successful vaccination implies the induction of effective specific immune responses. We intend to find biomarkers among various immune cell subpopulations, cytokines and antibodies which could be used to predict the levels of specific antibody- and cell-mediated responses after measles-mumps-rubella vaccination. We measured 59 baseline immune status parameters (frequencies of 42 immune cell subsets, levels of 13 cytokines, immunoglobulins) before vaccination and 13 response variables (specific IgA and IgG, antigen-induced IFN-γ production, CD107a expression on CD8+ T lymphocytes, and cellular proliferation levels by CFSE dilution) 6 weeks after vaccination for 19 individuals. Statistically significant Spearman correlations between some baseline parameters and response variables were found for each response variable (p&lt;0.05). Due to the low number of observations relative to the number of baseline parameters and missing data for some observations, we utilized three feature selection strategies to select potential predictors of the post-vaccination responses among baseline variables: (a) screening of the variables based on the correlation analysis, (b) supervised screening based on the information of changes of baseline variables at day 7, (c) implicit feature selection is performed using regularization-based sparse regression. We identified optimal multivariate liner regression models for predicting the effectiveness of vaccination against measles-mumps-rubella using the baseline immune status parameters. It turned out that the sufficient number of predictor variables ranges from one to five depending on the response variable of interest.

Cuboid diamonds are particularly common in the placers of the northeastern Siberian platform but their origin remains unclear. These crystals usually range in color from dark yellow to orange and more interestingly, are characterized by unusual low aggregated nitrogen impurities (non-aggregated C-center) suggesting a short residence time and/or low temperatures at which they have been stored in the mantle. In order to track possible isotopic signature that could help deciphering cuboid diamond's crystallization processes, δ¹³C values, δ¹⁵N values and nitrogen contents have been determined in-situ in three samples using secondary ion mass spectrometry (SIMS), whereas nitrogen aggregation state have been determined by FTIR spectroscopy. The samples fall out the δ¹³C vs. δ¹⁵N field of canonical mantle composition. Different scale of carbon and nitrogen fractionation may produce the observed variations. Alternatively, mixing of mantle and crustal material would obscure initial co-variations of δ¹³C values with δ¹⁵N or nitrogen content.

The free energy principle (FEP) is a mathematical and scientific principle that describes the relationship between the physical behavior of a dynamical system and the interpretation of such behavior as carrying out inference. It blurs the boundary between the ontological mode of the system of interest and the epistemological significance it acquires through its dynamic interaction with the environment. New materialism (or neo-materialism), despite lacking a single definition, refers to a range of emerging perspectives that attempt to dismantle the long-held divisions between ontology, epistemology, and even ethics, with the aim of achieving a comprehensive transformation of naturalized thinking. In this context, new materialism provides powerful tools to reframe some of the conceptual foundations of the FEP. This paper is the first in a series that aims to systematically construct a neo-materialistic perspective for the FEP, exploring its wide-ranging implications. It serves as an introduction to the series, arguing for the justification of deploying new materialism to reframe the FEP and introducing some essential concepts to be utilized in developing a neo-materialistic account of the FEP.

Rats, including those of the Sprague Dawley strain, may kill mice. Because of this muridical behavior, it is standard practice in many research animal housing facilities to separate mice from rats (i.e., the predators) to minimize stress for the mice. We therefore tested the effect of cohousing on the stress levels of mice from either the C57BL/6J (BL6) or the CD1 strain and Sprague Dawley (SD rat) by determining their fecal corticosterone or cortisol metabolites (FCM) concentration and investigated how cohousing impacts a behavioral assay, i.e., conditioned place preference for intragenus (i.e., mouse-mouse or rat-rat) dyadic social interaction (DSI CPP) that had been shown be sensitive to social factors, especially to handling by humans. We found that the two delivery batches of BL6 mice or SD rats, respectively, had different stress levels at delivery that were statistically significant for the BL6 mice. Even so, the BL6 mice cohoused with rats had significantly increased FCM concentrations, indicative of higher stress levels, as compared to (1) BL6 mice housed alone or (2) BL6 mice at delivery. In contrast to their elevated stress levels, the attractiveness for contextual cues associated with mouse-mouse social interaction (DSI CPP) even increased in rat-cohoused BL6 mice, albeit nonsignificantly. Thus, cohousing BL6 mice and rats did not impair a behavioral assay in BL6 mice that had proved to be sensitive to handling stress by humans in our laboratory. SD rats cohoused with BL6- or CD1 mice and CD1 mice cohoused with SD rats showed DSI CPP that was not different from our previously published data on SD rats and BL6 mice of the Jackson- or NIH substrain obtained in the absence of cohousing. Our findings suggest that the effect of cohousing rats and mice under the conditions described above on their stress levels as opposed to their behavior might be less clearcut than generally assumed and might be overriden by conditions that cannot be controlled, i.e., different deliveries. Our findings can help to use research animal housing resources, which usually are limited, more efficiently.

The etiology of exaggerated fibrous capsule formation around silicone mammary implants (SMI) is multifactorial but primarily induced by immune mechanisms toward the foreign material silicone. The aim of this work was to enlighten the disease progression from implant insertion and immediate tissue damage response reflected in (a) the acute wound proteome, and (b) the adsorption of chronic inflammatory wound proteins at implant surfaces. An intra-individual absolute quantitation TMT-liquid chromatography-tandem mass spectrometry approach was applied to profile wound proteome formed around SMI the first five days post-implantation. Compared to plasma, the acute wound profile resembled a more complex composition comprising plasma-derived and locally differentially expressed proteins (DEPs). DEPs were subjected to functional enrichment analysis, which revealed the dysregulation of signaling pathways mainly involved in immediate inflammation response and ECM turnover. Moreover, we found time-course variations in protein enrichment immediately post-implantation and adsorbed to SMI surfaces after 6-8 months. Characterization of the expander-adhesive proteome by label-free approach uncovered a long-term adsorbed acute wound and the fibrosis-associated proteome. Our findings propose a wound biomarker panel for the early detection and diagnosis of excessive fibrosis that could potentially broaden insights into the characteristics of fibrotic implant encapsulation.

Nanocrystalline silicon oxide (nc-SiOx:H) is a multipurpose material with its varied application in solar cells as a transparent front contact, intermediate reflector, back reflector layer and even tunnel layer for passivating contacts, owing to easy tailoring of its optical properties. In this work, we systematically investigate the influence of gas mixture (SiH4, CO2, PH3 and H2), RF power and process pressure on the optical, structural and passivation properties of thin n-type nc-SiOx:H films prepared in an industrial, high throughput, plasma-enhanced chemical vapor deposition (PECVD) reactor. We provide a detailed description of the n-type nc-SiOx:H material develop-ment using various characterization techniques (SEM, EDX, Raman spectroscopy, and spectro-scopic ellipsometry) with a focus on the relationship between the material properties and the pas-sivation they provide to n-type c-Si wafers characterized by their effective carrier lifetime (τeff). Further, we also outline the parameters to be kept in mind while developing different n-type nc-SiOx:H layers for different solar cell applications. We report a tunable optical gap (1.8 – 2.3 eV) for our n-type nc-SiOx:H films as well as excellent passivation properties with τeff up to 3.5 ms (iVoc ~ 715 mV) before annealing. Oxygen content plays an important role in determining the crystallinity and hence passivation quality of the deposited nanocrystalline silicon oxide films.

The manuscript presents the comprehensive integrative theory of the etiology and pathogenesis of Alzheimer’s disease - the amyloid degradation toxicity hypothesis - and describes the logic that underlies it.The analysis of amyloid biomarkers and stable-isotope label kinetics (SILK) studies suggest that AD diagnosis is associated with higher cellular uptake of beta-amyloid. Uptake of beta-amyloid by cells is needed for its cytotoxicity, so the uptake rate should correlate with the rate of neurodegeneration. Also, the initial step in forming extracellular aggregates cannot occur in the interstitial fluid due to the extremely low concentration of beta-amyloid but can occur intralysosomally. Therefore, the density of extracellular aggregates should positively correlate with the rate of cellular amyloid uptake. The model, which considers that both cytotoxicity and aggregation of beta-amyloid are defined by cellular uptake, successfully reproduces the probability distribution of AD diagnosis in the population. Cellular uptake of beta-amyloid is mediated by endocytosis. Endocytosed beta-amyloid induces lysosomal permeabilization that occurs without plasma membrane damage. Lysosomal permeabilization explains ion disturbances, such as an accumulation of intracellular calcium, caused by cell exposure to extracellular beta-amyloid. Some amyloid fragments, produced from beta-amyloid by lysosomal proteases, can form membrane channels in lysosomal membranes, which are large enough to leak cathepsins to the cytoplasm. Appearance of proteases in the cytoplasm results in necrosis and/or initiation of apoptosis. If the cell survives, the damage of lysosomes leads to autophagy failure and slow recycling of mitochondria, promoting the production of reactive oxygen species and potentiating cell damage.Considering the above, the integrative theory of AD etiology and pathogenesis can be formulated. The etiology of AD is the membrane channel formation by amyloid fragments produced in lysosomes. The pathogenesis includes lysosomal permeabilization by giant membrane channels, which leak lysosomal proteases into the cytoplasm. The correlation between the density of amyloid aggregates and the probability of AD appears because the intensity of cellular uptake defines both aggregation rates in vivo and cytotoxicity of beta-amyloid.The amyloid degradation toxicity hypothesis is the integrative theory of Alzheimer’s disease (AD). It successfully interprets multiple phenomena and paradoxes associated with AD pathobiology at various levels, from molecular and cellular to biomarkers. The hypothesis explains the limitations of currently used biomarkers of AD and proposes etiology-related parameters. These parameters could be measured in humans and become novel diagnostic and prognostic clinical tools. Based on the proposed framework, we foresee the development of effective medications to treat, stall the progression of, or prevent disease development.

Electron can tunnel between cofactor molecules positioned along biological electron transport chains up to the distance of ≃20 Å on the millisecond time scale of enzymatic turnover. This tunneling range mostly determines the design of biological energy chains facilitating cross-membrane transport of electrons. Tunneling distance and cofactors’ redox potentials become main physical parameters of this design. The protein identity, flexibility, or dynamics are missing from this picture assigning universal charge-transport properties to all proteins. This paradigm is challenged by dynamical models of electron transfer showing that the hopping rate is constant within the crossover distance R*≃12 Å, followed with an exponential tunneling falloff at longer distances. In this view, energy chains for electron transport are best designed by placing redox cofactors near the crossover distance R*. Protein flexibility and dynamics affect the magnitude of the maximum hopping rate within the crossover radius. Protein charge transport is not driven by universal parameters anymore and protein identity matters.

In this manuscript, we reassess the data on beta-amyloid-induced changes of intracellular ions concentrations published previously by Abramov et al. (2003, 2004). Their observations made using high-resolution confocal microscopy with fast temporal resolution of images formed by fluorescent ion-sensitive fluorescent probes in living cells represent an unequivocal support for the amyloid channel theory. However, closer look reveals multiple facts which cannot be explained by channel formation in plasma membrane. Recently proposed amyloid degradation toxicity hypothesis provides the interpretation to these facts by considering that channels are formed in the lysosomal membranes.

The current SARS- CoV-2 pandemic underscores the importance of understanding the evolution of RNA genomes. While RNA is subject to the formation of similar lesions as DNA, the evolutionary and physiological impacts RNA lesions have on viral genomes are yet to be characterized. Lesions that may drive the evolution of RNA genomes can induce breaks that are repaired by recombination or can cause base substitution mutagenesis, also known as base editing. Over the past decade or so, base editing mutagenesis of DNA genomes has been subject to many studies, revealing that exposure of ssDNA is subject to hypermutation that is involved in the etiology of cancer. However, base editing of RNA genomes has not been studied to the same extent. Recently hypermutation of single-stranded RNA viral genomes have also been documented though its role in evolution and population dynamics. Here, we will summarize the current knowledge of key mechanisms and causes of RNA genome instability covering areas from the RNA world theory to the SARS- CoV-2 pandemic of today. We will also highlight the key questions that remain as it pertains to RNA genome instability, mutations accumulation, and experimental strategies for addressing these questions.

Background: Mental health has a special relevance in adolescence. Therefore, this study aimed to analyze the possible association between emotional distress and suicidal ideation among adolescents. Methods: The article presents the results of a survey of secondary school students (N=1419) in the city of Tarragona, Spain. The aim of the analysis was to verify the existence of an association between suicidal ideation and risk factors such as emotional distress and low self-esteem. All the data were also analysed to determine the existence of statistically significant differences between girls and boys. Bivariate analyses were performed with chi-square, point-biserial coefficient and non-parametric tests for independent groups. Logistic regression analysis was also performed to calculate the probability of suicidal ideation. Results: These analyses showed that both emotional distress and low self-esteem increase the likelihood of suicidal ideation among adolescents. This was more evident among boys with high levels of emotional distress. Conclusion: Schools should develop suicide ideation prevention programs for adolescents based on situations that cause emotional distress.

The qualitative analysis of nanodiamonds by FTIR spectrometry as photoacoustic (PAS), diffuse-reflectance (DRIFT), and attenuated total reflection (ATR) modalities was evaluated for rapid and nondestructive analysis and comparison of nanodiamonds. The spectra reproducibility and signal-gathering depth was compared. The assignment of characteristic bands showed that only six groups of bands were present in spectra of all the modalities with appropriate sensitivity: 1760 (C=O stretch, isolated carboxyl groups); 1640–1632 (H–O–H bend, liquid water); 1400–1370 (non-carboxyl C–O–H in-plane bend and CH2 deformation); 1103 (non-carboxyl C–O stretch); 1060 (in-plane C–H bend, non-aromatic hydrocarbons and carbohydrates); and 940 cm–1 (out-of-plane carboxyl C–O–H bend). DRIFT provides the maximum number of bands and is capable of measuring hydrogen-bonded bands and CHX groups. ATR provides the good sensitivity for water and C–H/C–C bands in the range 2000–400 cm–1. PAS-FTIR reveals less bands than DRIFT but more intense bands than ATR-FTIR and shows the maximum sensitivity for absorption bands that do not appear in ATR-IR spectra and are expedient for supporting either DRIFT or PAS along with depth-profiling. Thus, all three modalities are required for full characterization of nanodiamonds surface functional groups.