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High-entropy coatings based on 3D metals have a unique combination of strength and ductility over a wide temperature range and can be obtained using vacuum ion-plasma magnetron sputtering technology. However, the model calculations of the thermomechanical properties of such alloys are complicated by a lack of stable and equilibrium lattices with complete structural information. This article implements prediction of the stability of the phases of an equiatomic high-entropy coating of CrMnFeCoNi by the inverse convex hull method. The thermodynamic and mechanical properties were determined. It was found that, up to room temperature, the medium-entropy, 4-element alloy of composition MnFeCoNi also belongs to the stable phases. [ABSTRACT FROM AUTHOR]

This work discusses the predictable control of plasma-assisted physical vapor deposition (PVD) of coatings. The multiple process parameters and the instability of the nonequilibrium ion plasma system create substantial obstacles to the wide industrial application of promising multicomponent functional coatings. Here we propose a solution to this problem, which includes: creation of a database of diamond-like carbon (DLC) coatings to identify a limited set of adjustable process control parameters, determination of how these parameters affect the coating properties, analysis of the revealed effects using statistical methods and neural network algorithms, and use of the results for the predictable tuning of specified coating properties. The object of research is original DLC coatings whose structure is stabilized with nitrogen instead of conventionally used hydrogen. The experimental database of DLC coatings is created based on our previous studies and includes structural, morphological and architectural characteristics of coatings, various types of substrates, sublayers, physical, mechanical and tribological properties, and various combinations of coating deposition parameters. A specific problem is solved to determine the influence of deposition parameters such as chamber pressure P, stabilizer content (% nitrogen), ion flux rate (coil current λ) and deposition time t on hardness H and elastic modulus E of coatings. Based on the results obtained, the deposition parameters are optimized so as to obtain predictable strength values of the formed carbon coating. The optimization procedure is developed using both classical statistical methods and modern algorithms of ridge regression, randomized trees (ExtraTrees), and a fully connected neural network (multilayer perceptron MLP). [ABSTRACT FROM AUTHOR]

Elements of microfluidic systems created by 3D printing offer numerous advantages, such as rapid manufacturing, low cost, and the ability to create complex 3D channel topologies. Their parameters and performance can be quickly adjusted by editing the model loaded into the printer. However, the mechanical properties of polymers used for printing are often poorly documented and can significantly change over time due to aging, relaxation, or creep effects, leading to unexpected behaviour of 3D-printed devices. To address this issue, we performed a complete mechanical characterization of the samples made by 3D printing, including stress relaxation and creep tests, at different time intervals after printing. The determined properties of the material allowed us to model the mechanical and hydrodynamical performance of the 3D-printed microfluidic device, which we demonstrate using an example of a fully printed check valve specially developed for use in microfluidic systems. This approach allows easy quantitative evaluation of the optimal production cycle and lifetime of 3D-printed microfluidic devices. [ABSTRACT FROM AUTHOR]

In this work, the structure of a CrMnFeCoNiCu high-entropy alloy (HEA) film deposited by magnetron evaporation on a steel substrate is studied. It is established that the phase content of the CrMnFeCoNiCu HEAs is determined by a superposition of contributions from equiatomic simple cubic lattices of the CrMnFeCoNiCu composition (Struct-26 and Struct-278) with space group P1. It is found that the contributions of the diffraction patterns from the reference lattices to the integral intensity are 0.66 and 0.29, respectively. For simple cubic lattices Struct-26 and Struct-278, the full structural information (the lattice parameters, coordinates of atoms, spatial groups, and occupancies) is derived. It is established that the CrMnFeCoNiCu HEA is a stable compound, which is confirmed by calculations of the mixing energy for the convex Hull model. [ABSTRACT FROM AUTHOR]

Underwater Wireless Optical Communication (UWOC) offers a promising alternative to acoustic transmission methods, boasting reduced latency, increased data rates and smaller device sizes, with a focus on leveraging the underwater channel's optical spectra diversity for high-speed data services. Underwater signal propagation encounters absorption, turbulence and scattering, causing misalignment between optical transmitter and receiver due to turbulent water waves, degrading performance. In Point-to-Point UWOC, changes in beam divergence angle at the transmitting node disrupt links between underwater sensor nodes and maximize sensor battery usage. Therefore, this research work introduces the Efficient Deep Spiking Convolutional Neural Network with Graph Attention Layer (EDSCNN-GAL) that serves as a misalignment-robust blind receiver, utilizing convolutional layers, spatial-pooling layers and graph attention layers to extract and process features from received optical signals. Additionally, Multi scale Deep CapsNet (MD CapsNet) optimizes transmission power and beam divergence angle to sustain connections and minimize battery usage in underwater sensors. Enhanced walrus optimization is employed to efficiently optimize MD CapsNet parameters. The introduced model's efficacy is demonstrated through a comparison with state-of-the-art models, achieving better, throughput superior instantaneous signal to noise ratio (24 dB), lower misalignment probability (4%) and less transmission power (6.4 mW). [ABSTRACT FROM AUTHOR]

The opioid epidemic has received considerable attention, but the impact on perinatal opioid-exposed (POE) offspring remains underexplored. This study addresses the emerging public health challenge of understanding and treating POE children. We examined two scenarios using preclinical models: offspring exposed to oxycodone (OXY) in utero (IUO) and acute postnatal OXY (PNO). We hypothesized exposure to OXY during pregnancy primes offspring for neurodevelopmental deficits and severity of deficits is dependent on timing of exposure. Notable findings include reduced head size and brain weight in offspring. Molecular analyses revealed significantly lower levels of inflammasome-specific genes in the prefrontal cortex (PFC). Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) highlighted the enrichment of genes associated with mitochondrial and synapse dysfunction in POE offspring. Western blot analysis validated IPA predictions of mitochondrial dysfunction in PFC-derived synaptosomes. Behavioral studies identified significant social deficits in POE offspring. This study presents the first comparative analysis of acute PNO- and IUO-offspring during early adolescence finding acute PNO-offspring have considerably greater deficits. The striking difference in deficit severity in acute PNO-offspring suggests that exposure to opioids in late pregnancy pose the greatest risk for offspring well-being. [ABSTRACT FROM AUTHOR]

The method for the preparation of 3,6-disubstituted 1,2,4-triazines based on condensation reaction between easily available α-imino esters and isonitrosoacetophenone hydrazones was reported. The significant differences in reaction conditions, ratio of products, and yields between the developed method and the earlier reported approach were demonstrated. The corresponding 2,5-disubstituted pyridines were synthesized from the prepared 1,2,4-triazines, and their photophysical properties were studied. Studies of the photo-physical properties revealed low and moderate luminescence quantum yields, and negligible solvatochromic behavior in case of 4-methoxyphenylpyridine derivative due to the role of donating methoxy group, however, with a low linearity of a Lippert–Mataga plot. Nevertheless, 2,5-disubstituted pyridines are of interest due to simple protocols of synthesis, moderate photophysical properties, and potential applicability in different scientific and industrial areas. [ABSTRACT FROM AUTHOR]

While poly(ethylene glycol) (PEG) hydrogels are generally regarded as biologically inert blank slates, concerns over PEG immunogenicity are growing, and the implications for tissue engineering are unknown. Here, we investigate these implications by immunizing mice against PEG to stimulate anti-PEG antibody production and evaluating bone defect regeneration after treatment with bone morphogenetic protein-2-loaded PEG hydrogels. Quantitative analysis reveals that PEG sensitization increases bone formation compared to naive controls, whereas histological analysis shows that PEG sensitization induces an abnormally porous bone morphology at the defect site, particularly in males. Furthermore, immune cell recruitment is higher in PEG-sensitized mice administered the PEG-based treatment than their naive counterparts. Interestingly, naive controls that were administered a PEG-based treatment also develop anti-PEG antibodies. Sex differences in bone formation and immune cell recruitment are also apparent. Overall, these findings indicate that anti-PEG immune responses can impact tissue engineering efficacy and highlight the need for further investigation. Concerns over the immunogenicity of poly(ethylene glycol) (PEG) are growing, and the implications for tissue engineering are unknown. Here the authors evaluate the impact of anti-PEG antibodies and PEG immunogenicity on the efficacy of a PEG hydrogel-based tissue engineering therapy. [ABSTRACT FROM AUTHOR]

A series of α-cycloamine substituted 2,2'-bipyridines 3ae'-3ce' was obtained via the one-pot approach based on ipso-substitution of a cyano-group in 1,2,4-triazines, followed by aza-Diels–Alder reaction in good yields. Photophysical properties, including fluorosolvatochromism, were studied for 3ae'-3ce' and were compared with α-unsubstituted 2,2'-bipyridines. In addition, dipole moments differences in ground and excited states were calculated by both Lippert-Mataga equation and DFT studies and were compared to each other. The correlation between the size of cycloamine unit and the dipole moments differences value (based on Lippert-Mataga equation) was observed. In addition charge transfer indices (DCT, Λ, H and t) were calculated to demonstrate influence of molecular structure on the intramolecular charge transfer degree. [ABSTRACT FROM AUTHOR]

Magnetic proxy approaches proved to be efficient for potentially toxic elements (PTEs) pollution assessment when targeting forests or areas with a homogenous background where anthropogenic magnetic signals could be easily distinguished. Here, we present a multidisciplinary approach for magnetic susceptibility (x ) and HM assessment in a complex area in the Nile Delta, where geogenic input, land use, and various industries with different fly ash and surface water emissions interfere. Statistical analysis discriminates between the effects of lithologic elements and the concentrations of toxic anthropogenic elements. The studied elements are classified into lithogenic and anthropogenic-related (HMs, Au industry, and fertilizers industry) groups with maximum contamination levels of eight anthropogenic-related and highly toxic PTEs (Cu, Zn, Mo, Cd, Sb, Pb, Hg, and As) in the Akrasha industrial area (pollution load index = 15.84). Considering the whole data set, the numerical correlation of x with most PTE concentrations and the pollution load index (PLI) is weak, while it is moderate to strong with lithogenic elements. However, a comparison of lithogenic elements and PTE concentrations along with x-values in two separate clusters supports the correspondence of lithology with elevated x-values in silt and clay-rich soil samples as well as HM concentration in industrial sandy soils. Correspondence between magnetic maps and chemistry data with land use reflects the potential of magnetic proxy methods for qualitative PTE pollution pre-delineation of the polluted spots, provided that lithological conditions are carefully considered. [ABSTRACT FROM AUTHOR]

One of the options for solving the scientific and applied problem of the predicted formation of ion-plasma coating tribological characteristics is presented. The problem is solved by creating and analyzing a carbon coating database. The object of research in this work is ion-plasma diamond-like coatings (DLCs) deposited on a steel substrate. It is shown that the use of nitrogen instead of hydrogen to stabilize carbon coatings not only ensures stable thicknesses of DLCs at the level of 1.0–1.5 μm, but also serves as an important and convenient technological parameter for regulating the tribological coating characteristics during deposition. Based on the predicted and experimental values of friction coefficient μ and data on sample path length L, the intervals of optimal values of technological parameters %N and λ are determined. The studied ion-plasma DLCs, obtained according to the established optimal application modes, can be recommended for application under friction conditions equivalent to the tribological tests carried out at friction load F ≈ 10 N. [ABSTRACT FROM AUTHOR]

The results of studying the stability of high-entropy NbTiHfVZr alloy on the basis of analysis of (i) the critical Hume-Rothery parameters, (ii) the enthalpy of binary alloys by the Miedema method, and (iii) the mixing entropy of NbTiHfVZr alloy near the melting point are presented. The temperature stability regions extending from the melting point to 1200 K for NbTiHfVZr alloy have been revealed by the method of inverse hull webs. In the case of NbTiHfZr, the temperature stability region extends up to the room temperature. The obtained results evidence that NbTiHfVZr and NbTiHfZr can be classified as high-entropy alloys, whose lattices belong to the class of single-phase one-element solid solutions. It has been established by the Rietveld method on the basis of an experimental X-ray diffraction pattern that the cubic HfNbTiVZr, Hf2Nb2Ti2V2Zr2, NbHfTiZr, and Hf2Nb2Ti2Zr2 lattices found by the USPEX code with space group P1 make a predominant contribution to the integral intensity. In this study, the full structural information including unit cell lattice parameters, atomic coordinates, space group, population of sites, etc. has been established for the HfNbTiVZr, Hf2Nb2Ti2V2Zr2, NbHfTiZr, and Hf2Nb2Ti2Zr2 cubic lattices. The mentioned alloys are stable and characterized by a high bound energy and, according to the found room-temperature elasticity moduli, belong to high-strength materials. The cubic HfNbTiVZr, Hf2Nb2Ti2V2Zr2, NbHfTiZr, and Hf2Nb2Ti2Zr2 lattices can be incorporated into the crystallographic database used to identify the structural state of high-entropy NbTiHfZr and NbTiHfVZr alloys. [ABSTRACT FROM AUTHOR]

The yield of reaction products depends on the interaction between processes on the catalyst surface: adsorption, activation, reaction, desorption, and others. These processes, in turn, depend on the magnitude of the flows of reaction mixtures, temperature, and pressure. Under stationary conditions, active sites on the surface can be poisoned by reaction by-products or blocked by an excess of adsorbed reactant molecules. Dynamic control of reaction parameters takes into account changes in surface properties and adjusts the temperature, flow rates, and other parameters accordingly. A reinforcement learning algorithm was applied to control the oxidation reaction of carbon monoxide CO on the surface of palladium nanoparticles. The algorithm was trained to maximize the rate of carbon dioxide production based on information about the magnitude of CO, O2, and CO2 flows at each time step. A gradient policy algorithm with a continuous action space was chosen, and observations of the flow rates were extended over several successive time steps, which made it possible to obtain a set of non-stationary solutions. The maximum yield of the product is achieved with a periodic change in gas flows, which ensures a balance between the available adsorption sites and the concentration of activated intermediates. This methodology opens up prospects for optimizing catalytic reactions under nonstationary conditions. [ABSTRACT FROM AUTHOR]

The reactions of 5-R-6-aryl-3-(2-pyridyl)-1,2,4-triazines with a 4,5-dimethylaryne intermediate generated in situ, which had not previously been used for this purpose, was studied. The reaction outcome depends on the nature of the substituent at the C5 position of 1,2,4-triazine: the introduction of electron-donating substituents leads to the preferential domino transformation of the 3-(2-pyridyl)-1,2,4-triazine system with the formation of 2,3-dimethyl-10-(1,2,3-triazol-3-yl)pyrido[1,2-a]indoles, and electron-withdrawing ones leads to the formation of the corresponding 6,7-dimethylisoquinolines. The main difference between dimethylaryne and its unsubstituted analogue is a significant increase in the proportion of isoquinolines in the reaction products when 5,6-diaryl-3-(2-pyridyl)-1,2,4-triazines are used as substrates. [ABSTRACT FROM AUTHOR]

This manuscript presents a study of the applicability of machine learning methods for the problem of binding energy approximation of carbon monoxide adsorbates on the surface of a palladium nanoparticle. Machine learning algorithms were trained using a set of structures that represent models of CO interaction with different parts of the Pd55 nanocluster with a variable distance from the molecule to the surface, for which the energy was calculated using the density functional theory methods. For structures that make up a training set, the radial distribution functions were calculated. Using these functions and their segments as descriptors, the effectiveness of various machine learning algorithms, such as "gradient boosting," "ridge regression," "extra trees," and "support vector machines" for calculating the binding energy, was tested. Based on three different metrics, it was found that the error in determining the binding energy was the smallest when using the "support vector machines": the mean absolute error was 0.093 eV. The efficiency of various individual sections of the distribution function used as descriptors was compared. It was found that it is crucial to take into account the part of the radial distribution function from 1.5 to 2.5 Å for a correct approximation of the energy. [ABSTRACT FROM AUTHOR]

Ribosomal protein kinase S6 (S6K1) is one of the key components of the PI3K/mTOR/S6K1-dependent signaling cascade, which plays an important role in the regulation of translation, cell growth, survival, proliferation, and cell migration. Disturbances in the functioning of the PI3K/mTOR/S6K1 signaling cascade, in particular changes in the expression and activity of S6K1, accompany the development of a number of human pathologies, including oncological, neurodegenerative, and cardiovascular diseases; metabolic disorders; and pathologies associated with aging. Recently, in addition to the already known p70 and p85, the existence of a new isoform of the S6K1 kinase, p60, was confirmed. In addition, it was established that a change in the balance in the expression of various S6K1 isoforms towards an increase in p60-S6K1 leads to a multiple increase in the motility of model malignant cells, which is accompanied by significant changes in the expression of molecules involved in cell adhesion and intercellular interaction and may indicate that the cells acquire tumor characteristics important for invasion and metastasis. To find out whether the expression of the p60 isoform of S6K1 correlates with invasion and metastasis at the tumor level, the expression level of S6K1 isoforms was analyzed in three groups of human papillary thyroid carcinoma tumors, namely, without signs of invasion, with signs of invasion, and with lymph node metastases. Conditionally normal tissues adjacent to the tumors were also analyzed at the same time. The analysis was carried out by real-time PCR. A trend towards an increase in the expression level of all S6K1 isoforms, as well as the p60 isoform of S6K1 in tumors with manifestations of invasion and metastasis, was established. However, changes in the ratio of the total expression level of all S6K1 isoforms to p60-S6K 1 in the direction of an increase in the share of the latter in tumors with manifestations of metastasis turned out to be statistically reliable. The obtained results indicate an important role of the p60S6K1 isoform in the maintenance or initiation of invasion and metastasis of thyroid tumors. [ABSTRACT FROM AUTHOR]

Heterometallic FeCo dinuclear complexes on the basis of the redox-active 1,10-phenanthroline-5,6-dione with ancillary bis(pyrazolyl)borate anions and tetradentate N-donor ligands (N,N′-dialkyl-2,11-diaza[3.3]-(2,6)pyridinophane and tris(2-pyridilmethyl)amine derivatives) were studied by the DFT UTPSSh/6–311 + + G(d,p) method in a view to possible spin-crossover (SCO) or valence tautomeric (VT) interconversions. The electronic structures (namely, spin and oxidation states of the electronically labile centers) and magnetic properties of the considered compounds were found to be determined by the position of the outer-sphere PF6– counterion and the type of N-donor base. The most energetically preferred isomers contain a counterion near the cobalt ion. The presence of PF6– next to the iron center stabilizes the ferric state of this metal and the dianionic form of the 1,10-phenanthroline-5,6-dione linker ligand. The variation of the structural peculiarities allowed us revealing the dinuclear complexes prone to exhibit the SCO and VT processes, which makes them promising building blocks of magnetic materials. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum (ER) stress and mitochondrial dysfunction are found in lesions of multiple sclerosis (MS) and animal models of MS such as experimental autoimmune encephalomyelitis (EAE), and may contribute to the neuronal loss that underlies permanent impairment. We investigated whether glatiramer acetate (GA) can reduce these changes in the spinal cords of chronic EAE mice by using routine histology, immunostaining, and electron microscopy. EAE spinal cord tissue exhibited increased inflammation, demyelination, mitochondrial dysfunction, ER stress, downregulation of NAD+ dependent pathways, and increased neuronal death. GA reversed these pathological changes, suggesting that immunomodulating therapy can indirectly induce neuroprotective effects in the CNS by mediating ER stress. [ABSTRACT FROM AUTHOR]

The visualization of microfluidic chips is considered to study the morphology of the microfluidic channel surface and estimate the quality of 3D-printing technology based on digital light processing. Visualization is performed by X-ray microtomography using different iodine-based contrast agents and by scanning electron microscopy. It is shown that X-ray microtomography visualization makes it possible to control the quality of device printing relative to the geometrical parameters of the models specified at the device prototyping stage, as well as to visualize a 3D model of microfluidic channels and surface morphology. The spatial resolution of scanning electron microscopy exceeds the print pixel size and makes it possible to clarify the presence of local defects caused by uneven solidification of the resin during sample washing. [ABSTRACT FROM AUTHOR]

Lithium-ion batteries based on high-voltage cathode materials, such as LiCoPO4, despite being promising in terms of specific power, still suffer from poor cycle life due to the lower stability of common non-aqueous electrolytes at higher voltages. One way to overcome this issue might be decreasing the working potential of the battery by doping LiCoPO4 by Fe, thus reducing electrolyte degradation upon cycling. However, such modification requires a deep understanding of the structural behavior of cathode material upon lithiation/delithiation. Here we used a combination of operando synchrotron-based XRD and XAS to investigate the dynamics of d-metal local atomic structure and charge state upon cycling of LiCo0.5Fe0.5PO4 mixed d-metal olivine cathode material. Principal components analysis (PCA) of XAS data allowed the extraction of spectra of individual phases in the material and their concentrations. For both Co and Fe two components were extracted, they correspond to fully lithiated and delithiated phases of LixMPO4 (where M = Fe, Co). Thus, we were able to track the phase transitions in the material upon charge and discharge and quantitatively analyze the M2+/M3+ electrochemical conversion rate for both Fe and Co. Rietveld's refinement of XRD data allowed us to analyze the changes in the lattice of cathode material and their reversibility upon (de)lithiation during cycling. The calculation of DFT and Bader charge analysis expects the oxygen redox procedure combined with d-metals redox, which supplements iron charge variations and dominates at high voltages when x < 0.75 in LixCoFePO4. [ABSTRACT FROM AUTHOR]

X-ray absorption near-edge structure (XANES) spectra are the fingerprint of the local atomic and electronic structures around the absorbing atom. However, the quantitative analysis of these spectra is not straightforward. Even with the most recent advances in this area, for a given spectrum, it is not clear a priori which structural parameters can be refined and how uncertainties should be estimated. Here, we present an alternative concept for the analysis of XANES spectra, which is based on machine learning algorithms and establishes the relationship between intuitive descriptors of spectra, such as edge position, intensities, positions, and curvatures of minima and maxima on the one hand, and those related to the local atomic and electronic structure which are the coordination numbers, bond distances and angles and oxidation state on the other hand. This approach overcoms the problem of the systematic difference between theoretical and experimental spectra. Furthermore, the numerical relations can be expressed in analytical formulas providing a simple and fast tool to extract structural parameters based on the spectral shape. The methodology was successfully applied to experimental data for the multicomponent Fe:SiO2 system and reference iron compounds, demonstrating the high prediction quality for both the theoretical validation sets and experimental data. [ABSTRACT FROM AUTHOR]

This work rests on our non-viral tissue nanotransfection (TNT) platform to deliver MyoD (TNTMyoD) to injured tissue in vivo. TNTMyoD was performed on skin and successfully induced expression of myogenic factors. TNTMyoD was then used as a therapy 7 days following volumetric muscle loss (VML) of rat tibialis anterior and rescued muscle function. TNTMyoD is promising as VML intervention. [ABSTRACT FROM AUTHOR]

In this paper, we develop a new technique for quantitative analysis of the near region of X-ray absorption spectra that is based on the extraction of spectrum descriptors and machine learning. The use of descriptors (edge position, intensity and curvature of minima and maxima, and tangent of the slope of the absorption edge) allows solution of the problem of systematic differences between theoretical calculations and experimental data, reducing the dimension of the problem and thereby improving the accuracy of machine-learning algorithms. We obtain analytical relations between the spectrum descriptors and the parameters of the local atomic structure of a substance, which extend the range of applicability of the empirical Natoli rule and analysis of the chemical shift of spectra to arbitrary classes of chemical compounds. [ABSTRACT FROM AUTHOR]

Mechanical and tribological properties of the steel surface can be improved by TixAl1–xN multilayer coatings. Their rational design starts from a deep understanding of the functional relation of synthesis parameters, morphology, and crystallinity to final properties of layers. This problem can be described as experimentally intractable as it requires numerous specimens, spectroscopic characteristics, and tribological tests to cover a large multidimensional parameter space. The present paper discusses the possibility of predicting the mechanical and tribological properties of coatings by machine learning methods. The algorithm is trained on a set of theoretical micromechanical calculations. The quality of predictions is determined by comparing between several machine learning methods: ridge regression, random forest, radial basis functions, and neural networks. The machine learning approach is shown to be applicable to reverse engineering. The tandem neural network architecture is used to overcome the ambiguity problem and to predict Young's modulus and Poisson's ratio for each layer depending on the required mechanical parameters of the multilayer coating. The neural network topology is optimized so that the relative error comprises less than 5%. [ABSTRACT FROM AUTHOR]

Rapid development of transcriptome sequencing technologies has resulted in a data revolution and emergence of new approaches to study transcriptomic regulation such as alternative splicing, alternative polyadenylation, CRISPR knockout screening in addition to the regular gene expression. A full characterization of the transcriptional landscape of different groups of cells or tissues holds enormous potential for both basic science as well as clinical applications. Although many methods have been developed in the realm of differential gene expression analysis, they all geared towards a particular type of sequencing data and failed to perform well when applied in different types of transcriptomic data. To fill this gap, we offer a negative beta binomial t-test (NBBt-test). NBBt-test provides multiple functions to perform differential analyses of alternative splicing, polyadenylation, CRISPR knockout screening, and gene expression datasets. Both real and large-scale simulation data show superior performance of NBBt-test with higher efficiency, and lower type I error rate and FDR to identify differential isoforms and differentially expressed genes and differential CRISPR knockout screening genes with different sample sizes when compared against the current very popular statistical methods. An R-package implementing NBBt-test is available for downloading from CRAN (https://CRAN.R-project.org/package=NBBttest). [ABSTRACT FROM AUTHOR]

Physical mechanical stimulation can maintain and even increase bone mass. Here, we report an important role of osteocytic integrin α5 in regulating the anabolic response of bone to mechanical loading using an Itga5 conditional gene knockout (cKO) mouse model. Integrin α5 gene deletion increased apoptotic osteocytes and reduced cortical anabolic responses to tibial compression including decreased endosteal osteoblasts and bone formation, and increased endosteal osteoclasts and bone resorption, contributing to the decreased bone area fraction and biomechanical properties, leading to an enlarged bone marrow area in cKO mice. Similar disruption of anabolic responses to mechanical loading was also detected in cKO trabecular bone. Moreover, integrin α5 deficiency impeded load-induced Cx43 hemichannel opening, and production and release of PGE2, an anabolic factor, resulting in attenuated effects of the loading on catabolic sclerostin (SOST) reduction and anabolic β-catenin increase. Together, this study shows an indispensable role of integrin α5 in osteocytes in the anabolic action of mechanical loading on skeletal tissue through activation of hemichannels and PGE2-evoked gene expression. Integrin α5 could act as a potential new therapeutic target for bone loss, especially in the elderly population with impeded mechanical sensitivity. [ABSTRACT FROM AUTHOR]

Based on machine-learning algorithms, a method is developed for determining the structural parameters of the components of a mixture from X-ray absorption spectra. For each component, a database of spectra is constructed for all possible deformations of its structure. The machine-learning method implemented in the PyFitIt software package allows quick calculation of the spectrum for deformations of structures from the considered family and optimization of the structural parameters of the mixture by fitting the theoretical spectrum to the experimental one. The capabilities of the method are examined by analyzing changes in the structural characteristics and concentrations of the components of the mixture for the bis-dioxolene complex of cobalt with functionalized iminopyridine ligands during its valence-tautomeric interconversion depending on temperature. [ABSTRACT FROM AUTHOR]

The theoretical basis of X-ray absorption spectra beyond the Fe K-edge in the pre-edge region is constructed, and algorithms for using it to quantitatively analyze experimental X-ray near edge spectroscopy (XANES) spectra are described. Within the framework of the ab initio approach of ligand field theory, 60 theoretical spectra or more for Fe with different coordination numbers, oxidation state, and interatomic distances between the central atom and the nearest O atoms are calculated. Various machine learning (ML) methods for solving problems of determining the oxidation state of Fe and coordination number by means of the obtained spectra are used. The quality of the models are estimated using the Leave-One-Out method, the determination accuracy for the oxidation state is 100%; the determination accuracy for the coordination number is 75% in the case of predictions using the entire dataset and 96 and 68% for datasets with fixed oxidation state of Fe +2 and +3, respectively. [ABSTRACT FROM AUTHOR]

Hollow needle array-based tissue nanotransfection (TNT) presents an in vivo transfection approach that directly translocate exogeneous genes to target tissues by using electric pulses. In this work, the gene delivery process of TNT was simulated and experimentally validated. We adopted the asymptotic method and cell-array-based model to investigate the electroporation behaviors of cells within the skin structure. The distribution of nonuniform electric field across the skin results in various electroporation behavior for each cell. Cells underneath the hollow microchannels of the needle exhibited the highest total pore numbers compared to others due to the stronger localized electric field. The percentage of electroporated cells within the skin structure, with pore radius over 10 nm, increases from 25% to 82% as the applied voltage increases from 100 to 150 V/mm. Furthermore, the gene delivery behavior across the skin tissue was investigated through the multilayer-stack-based model. The delivery distance increased nonlinearly as the applied voltage and pulse number increased, which mainly depends on the diffusion characteristics and electric conductivity of each layer. It was also found that the skin is required to be exfoliated prior to the TNT procedure to enhance the delivery depth. This work provides the foundation for transition from the study of murine skin to translation use in large animals and human settings. [ABSTRACT FROM AUTHOR]

Element selectivity and possibilities for in situ and operando applications make X-ray absorption spectroscopy a powerful tool for structural characterization of catalysts. While determination of coordination numbers and interatomic distances from extended spectral region is rather straightforward, analysis of X-ray absorption near-edge structure (XANES) spectra remains a highly debated and topical problem. The latter region of spectra is shaped depending on the local 3D geometry and electronic structure. However, there is no straightforward procedure for the unambiguous extraction of these parameters. This work gives a critical vision on the amount of information that can be practically extracted from Pd K-edge XANES spectra measured under in situ and operando conditions, in which adsorption of reactive molecules at the surface of palladium with further formation of subsurface and bulk palladium carbides are expected. We investigate how particle size, concentration of carbon impurities, and their distribution in the bulk and at the surface of palladium particles affect Pd K-edge XANES features and to which extend they should be implemented in the theoretical model to adequately reproduce experimental data. Then, we show how the step-by-step increasing the complexity of the theoretical model improves the agreement with experiment. Finally, we suggest a set of formal descriptors relevant to possible structural diversity and construct a library of theoretical spectra for machine-learning-based analysis of the experimental data. [ABSTRACT FROM AUTHOR]

1,2,4-Triazines with an unsubstituted (1,2,4-triazol-3-yl)amine residue in the C5 position were synthesized by the solvent-free ipso-amination reaction between 1,2,4-triazine-5-carbonitriles and 3-amino-5H- or 3-amino-5-sulfanyl-1,2,4-triazoles. In the latter case, the reaction is accompanied by desulfurization of the 1,2,4-triazole fragment. [ABSTRACT FROM AUTHOR]

The tribological and wear-resistant behavior of a surface are determined by its morphology, level of defects, degree of crystallinity, and mechanical properties. The surface roughness, crystallite size, dislocations, and point defects are significant parameters on different spatial scales. Advances in methods for supercomputer modeling enable numerical experiments on the atomic level as well as at the nanoscale and microscale. Here, we perform nanoindentation experiments for a system consisting of ~1000 particles, which is the level where precise methods of density functional theory are no longer applicable while empirical potentials are decidedly rough. Defect-formation processes, effects of amorphization on mechanical properties, and irreversible processes of material deformation caused by an indenter are demonstrated at the scale of 2.5 nm. Our results open up new avenues for studying the mechanical and tribological properties of materials by numerical simulations of nanoindentation. [ABSTRACT FROM AUTHOR]

1,2,4-Triazine derivatives containing a 3- or 4-(5-phenyl-1,3,4-oxadiazol-2-yl)anilino group on C5 were synthesized by nucleophilic substitution of the cyano group in 3,6-diaryl-1,2,4-triazine-5-carbonitriles under solvent-free conditions. [ABSTRACT FROM AUTHOR]

The combined antiretroviral therapy era has significantly increased the lifespan of people with HIV (PWH), turning a fatal disease to a chronic one. However, this lower but persistent level of HIV infection increases the susceptibility of HIV-associated neurocognitive disorder (HAND). Therefore, research is currently seeking improved treatment for this complication of HIV. In PWH, low levels of brain derived neurotrophic factor (BDNF) has been associated with worse neurocognitive impairment. Hence, BDNF administration has been gaining relevance as a possible adjunct therapy for HAND. However, systemic administration of BDNF is impractical because of poor pharmacological profile. Therefore, we investigated the neuroprotective effects of BDNF-mimicking 7,8 dihydroxyflavone (DHF), a bioactive high-affinity TrkB agonist, in the memory-involved hippocampus and brain cortex of Tg26 mice, a murine model for HAND. In these brain regions, we observed astrogliosis, increased expression of chemokine HIV-1 coreceptors CXCR4 and CCR5, neuroinflammation, and mitochondrial damage. Hippocampi and cortices of DHF treated mice exhibited a reversal of these pathological changes, suggesting the therapeutic potential of DHF in HAND. Moreover, our data indicates that DHF increases the phosphorylation of TrkB, providing new insights about the role of the TrkB–Akt–NFkB signaling pathway in mediating these pathological hallmarks. These findings guide future research as DHF shows promise as a TrkB agonist treatment for HAND patients in adjunction to the current antiviral therapies. [ABSTRACT FROM AUTHOR]

We have presented the green synthesis and characterization of nano-titania (TiO2 NPs) by using Eucalyptus globulus leaf aqueous extract in a greener approach leading to their utilization as a catalyst in one-pot, three-component A3 coupling reactions. The composition of the as-prepared TiO2 NPs were confirmed by various analytical and spectroscopic techniques such as powder X-ray diffraction, scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, dynamic light scattering analysis and specific surface area measured by Brunauer–Emmett–Teller analysis. TiO2 NPs exhibited a pure anatase phase structure with an average particle size of 12 nm. [ABSTRACT FROM AUTHOR]

Beta-tricalcium phosphate (β-TCP)-based bioinks were developed to support direct-ink 3D printing-based manufacturing of macroporous scaffolds. Binding of the gelatin:β-TCP ink compositions was optimized by adding carboxymethylcellulose (CMC) to maximize the β-TCP content while maintaining printability. Post-sintering, the gelatin:β-TCP:CMC inks resulted in uniform grain size, uniform shrinkage of the printed structure, and included microporosity within the ceramic. The mechanical properties of the inks improved with increasing β-TCP content. The gelatin:β-TCP:CMC ink (25:75 gelatin:β-TCP and 3% CMC) optimized for mechanical strength was used to 3D print several architectures of macroporous scaffolds by varying the print nozzle tip diameter and pore spacing during the 3D printing process (compressive strength of 13.1 ± 2.51 MPa and elastic modulus of 696 ± 108 MPa was achieved). The sintered, macroporous β-TCP scaffolds demonstrated both high porosity and pore size but retained mechanical strength and stiffness compared to macroporous, calcium phosphate ceramic scaffolds manufactured using alternative methods. The high interconnected porosity (45–60%) and fluid conductance (between 1.04 ×10−9 and 2.27 × 10−9 m4s/kg) of the β-TCP scaffolds tested, and the ability to finely tune the architecture using 3D printing, resulted in the development of novel bioink formulations and made available a versatile manufacturing process with broad applicability in producing substrates suitable for biomedical applications. [ABSTRACT FROM AUTHOR]

Comprehensive investigation into ordinary chondrites presented by the species of Markovka (H4 petrological type), Polujamki (H4 type) and Jiddat Al Harasis 055 (L4-5 type) is performed. The element and phase compositions, as well as the oxidation states of iron and nickel in the chondrites, are examined via micro X-ray fluorescence (micro-XRF), Mössbauer spectroscopy and synchrotron-based X-ray absorption spectroscopy. Elemental composition analysis is performed using micro-XRF, allowing one to obtain element distribution maps for the meteorite samples. According to Mössbauer spectroscopy data gathered on iron-containing phases, the chondrites consist mainly of olivine and goethite with a small amount of pyroxene and hematite. A low amount of troilite and kamacite is also observed in the Markovka and Polujamki specimens. The oxidation states of 3d metals in the chondrites are estimated from Fe and Ni K-edge X-ray absorption near-edge structure (XANES) spectra. Most nickel atoms in the meteorites are found to be in the Ni2+ state, while iron has an average oxidation state of +2.4 which is commensurate with the Mössbauer spectroscopy data. Infrared spectroscopy analysis of the chondrites is implemented as well. The results are important from the viewpoint of statistics acquisition on ordinary chondrites, as well as for further understanding of their formation. [ABSTRACT FROM AUTHOR]

LiCoPO4 was synthesized in a short time by a microwave-assisted solvothermal technique at 220°C. The as-prepared samples are characterized as belonging to the Pn21a symmetry group, having poor electrochemical performance, and low specific capacity around 30 mAh/g. Further, activation at 700°C under air and argon increased the specific capacity to 57 mAh/g and 55 mAh/g, respectively. The local atomic and electronic structure of the samples before and after annealing was studied using x-ray absorption spectroscopy (XAS). The activation under air and Ar led to a phase transition from the Pn21a space group to the Pnma space group without changes in the Co oxidation state. Therefore, using myristic acid as a source for carbon coating, we found that there were no specific requirements for the activation atmosphere. [ABSTRACT FROM AUTHOR]

Recent political unrest has highlighted the importance of understanding the short- and long-term effects of gamma-radiation exposure on human health and survivability. In this regard, effective treatment for acute radiation syndrome (ARS) is a necessity in cases of nuclear disasters. Here, we propose 20 therapeutic targets for ARS identified using a systematic approach that integrates gene coexpression networks obtained under radiation treatment in humans and mice, drug databases, disease-gene association, radiation-induced differential gene expression, and literature mining. By selecting gene targets with existing drugs, we identified potential candidates for drug repurposing. Eight of these genes (BRD4, NFKBIA, CDKN1A, TFPI, MMP9, CBR1, ZAP70, IDH3B) were confirmed through literature to have shown radioprotective effect upon perturbation. This study provided a new perspective for the treatment of ARS using systems-level gene associations integrated with multiple biological information. The identified genes might provide high confidence drug target candidates for potential drug repurposing for ARS. [ABSTRACT FROM AUTHOR]

Total energy ab-initio calculations for some SHS products were performed by DFT method using VASP program package. The results of calculations along with XRD results and crystallographic modeling were used to explain specific features of the composition/structure of selected SHS products. [ABSTRACT FROM AUTHOR]

Heart valve disease is a common manifestation of cardiovascular disease and is a significant cause of cardiovascular morbidity and mortality worldwide. The pulmonary valve (PV) is of primary concern because of its involvement in common congenital heart defects, and the PV is usually the site for prosthetic replacement following a Ross operation. Although effects of age on valve matrix components and mechanical properties for aortic and mitral valves have been studied, very little is known about the age-related alterations that occur in the PV. In this study, we isolated PV leaflets from porcine hearts in different age groups (~ 4–6 months, denoted as young versus ~ 2 years, denoted as adult) and studied the effects of age on PV leaflet thickness, extracellular matrix components, and mechanical properties. We also conducted proteomics and RNA sequencing to investigate the global changes of PV leaflets and passage zero PV interstitial cells in their protein and gene levels. We found that the size, thickness, elastic modulus, and ultimate stress in both the radial and circumferential directions and the collagen of PV leaflets increased from young to adult age, while the ultimate strain and amount of glycosaminoglycans decreased when age increased. Young and adult PV had both similar and distinct protein and gene expression patterns that are related to their inherent physiological properties. These findings are important for us to better understand the physiological microenvironments of PV leaflet and valve cells for correctively engineering age-specific heart valve tissues. [ABSTRACT FROM AUTHOR]

Abstract—The enthalpies of formation of γ- and δ-modifications of the TiCu phase were estimated using the density-functional method. The enthalpies of formation are –22 and –12.8 kJ/mol for the γ- and δ-TiCu, respectively. The comparison of X-ray data and quantum-chemical calculations demonstrates that the discrepancy in the experimental values of enthalpy of formation of the TiCu crystals correlates with different content of the γ and δ modifications in the TiCu alloy. [ABSTRACT FROM AUTHOR]

Background: Pain is the most debilitating symptom of recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) and often requires chronic opioids or total pancreatectomy with islet autotransplantation to manage. Pain is a complex experience that can be exacerbated by depression and vice versa. Our aim was to test the hypothesis that depression-associated genes are associated with a constant-severe pain experience in RAP/CP patients. Study: A retrospective study was done using North American Pancreatitis Study II (NAPS2) genotyped RAP and CP patients with completed case report forms (n = 1,357). Subjects were divided based on pattern of pain and pain severity as constant-severe pain (n = 787) versus not constant-severe pain (n = 570) to conduct a nested genome-wide association study. The association between reported antidepressant medication use and depression gene loci was tested. Results: Constant-severe pain was reported in 58% (n = 787) of pancreatitis patients. No differences in sex or alcohol consumption were found based on pain severity. Antidepressant use was reported in 28% (n = 223), and they had lower SF-12 mental quality of life (MCS, p < 2.2 × 10− 16). Fifteen loci associated with constant-severe pain (p < 0.00001) were found to be in or near depression-associated genes including ROBO2, CTNND2, SGCZ, CNTN5 and BAIAP2. Three of these genes respond to antidepressant use (SGCZ, ROBO2, and CTNND2). Conclusion: Depression is a major co-factor in the pain experience. This genetic predisposition to depression may have utility in counseling patients and in instituting early antidepressant therapy for pain management of pancreatitis patients. Prospective randomized trials are warranted. Clinical trials registration: Clinicaltriasl.gov.# NCT01545167 [ABSTRACT FROM AUTHOR]

Background: Volumetric tissue-engineered constructs are limited in development due to the dependence on well-formed vascular networks. Scaffold pore size and the mechanical properties of the matrix dictates cell attachment, proliferation and successive tissue morphogenesis. We hypothesize scaffold pore architecture also controls stromal-vessel interactions during morphogenesis. Methods: The interaction between mesenchymal stem cells (MSCs) seeded on hydroxyapatite scaffolds of 450, 340, and 250 μm pores and microvascular fragments (MVFs) seeded within 20 mg/mL fibrin hydrogels that were cast into the cell-seeded scaffolds, was assessed in vitro over 21 days and compared to the fibrin hydrogels without scaffold but containing both MSCs and MVFs. mRNA sequencing was performed across all groups and a computational mechanics model was developed to validate architecture effects on predicting vascularization driven by stiffer matrix behavior at scaffold surfaces compared to the pore interior. Results: Lectin staining of decalcified scaffolds showed continued vessel growth, branching and network formation at 14 days. The fibrin gel provides no resistance to spread-out capillary networks formation, with greater vessel loops within the 450 μm pores and vessels bridging across 250 μm pores. Vessel growth in the scaffolds was observed to be stimulated by hypoxia and successive angiogenic signaling. Fibrin gels showed linear fold increase in VEGF expression and no change in BMP2. Within scaffolds, there was multiple fold increase in VEGF between days 7 and 14 and early multiple fold increases in BMP2 between days 3 and 7, relative to fibrin. There was evidence of yap/taz based hippo signaling and mechanotransduction in the scaffold groups. The vessel growth models determined by computational modeling matched the trends observed experimentally. Conclusion: The differing nature of hypoxia signaling between scaffold systems and mechano-transduction sensing matrix mechanics were primarily responsible for differences in osteogenic cell and microvessel growth. The computational model implicated scaffold architecture in dictating branching morphology and strain in the hydrogel within pores in dictating vessel lengths. [ABSTRACT FROM AUTHOR]

We report the optical constants of the solid CO2 (dry ice) measured using terahertz time domain spectroscopy. The CO2 ice sample was grown by vapor deposition method. The optical constants were obtained by minimizing the amplitude of the oscillations of refractive index in the spectral domain. We found that the mean refractive index of CO2 ice at 10 K is 1.485 between 0.2 and 1.6 THz with a standard deviation of 0.0137. The experiments were accompanied by first-principles density functional theory calculations using full-potential linear augmented plane wave method. The calculated refractive index is found to be 1.37 which is in reasonable agreement with the experimental value. In addition, the vibrational frequencies of solid CO2 were also studied using density functional perturbation theory, and the corresponding modes were assigned. [ABSTRACT FROM AUTHOR]

The stability of the kappa phase of compounds Me3+xW10–xC3+y (Me = Fe, Co, Ni) is calculated using the density functional theory. Crystal structures with disordered positions are calculated using an additive approach. The crystal structure of the kappa phase is presented as the superposition of four structures: Me3W10C4 (A), Me3W10C3 (B), Me4W9C4 (C), and Me4W9C3 (D). The statistical disorder in the crystals is determined from the relative contributions of these structures. The contribution from each structure is estimated from the calculated enthalpies. The effect 3d-block metal has on the stability of the kappa phase and the character of statistical disorder is studied using the proposed approach. [ABSTRACT FROM AUTHOR]

Selecting a set of valid genetic variants is critical for Mendelian randomization (MR) to correctly infer risk factors causing a disease. We here developed a method for selecting genetic variants as valid instrumental variables for inferring risk factors causing coronary artery disease (CAD). Using this method, we selected two sets of single-nucleotide-polymorphism (SNP) genetic variants (SNP338 and SNP363) associated with each of the three potential risk factors for CAD including low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c) and triglycerides (TG) from two independent GWAS datasets. We performed in-depth multivariate MR (MVMR) analyses and the results from both datasets consistently showed that LDL-c was strongly associated with increased risk for CAD (β = 0.396,OR = 1.486 per 1 SD (equivalent to 38 mg/dL), 95CI = (1.38, 1.59) in SNP338; and β = 0.424, OR = 1.528 per 1 SD, 95%CI = (1.42, 1.65) in SNP363); HDL-c was strongly associated with reduced risk for CAD (β = −0.315, OR = 0.729 per 1 SD (equivalent to 16 mg/dL), 95CI = (0.68, 0.78) in SNP338; and β = −0.319, OR = 0.726 per 1 SD, 95%CI = (0.66, 0.80), in SNP363). In case of TG, when using the full datasets, an increased risk for CAD (β = 0.184, OR = 1.2 per 1 SD (equivalent to 89 mg/dL), 95%CI = (1.12, 1.28) in SNPP338; and β = 0.207, OR = 1.222 per 1 SD, 95%CI = (1.10, 1.36) in SNP363) was observed, while using partial datasets that contain shared and unique SNPs showed that TG is not a risk factor for CAD. From these results, it can be inferred that TG itself is not a causal risk factor for CAD, but it's shown as a risk factor due to pleiotropic effects associated with LDL-c and HDL-c SNPs. Large-scale simulation experiments without pleiotropic effects also corroborated these results. [ABSTRACT FROM AUTHOR]

Plasmonic nanoparticles (NPs) like silver (Ag) strongly absorb the incident light and produce enhanced localized electric field at the localized surface plasmon resonance (LSPR) frequency. Enormous theoretical and experimental research has focused on the plasmonic properties of the metallic nanoparticles with sizes greater than 10 nm. However, such studies on smaller sized NPs in the size range of 3 to 10 nm (quantum-sized regime) are sparse. In this size regime, the conduction band of the metal particles discretizes, thus altering plasmon properties of the NPs from classical to the quantum regime. In this study, plasmonic properties of the spherical Ag NPs in size range of 3 to 20 nm were investigated using both quantum and classical modeling to understand the importance of invoking quantum regime to accurately describing their properties in this size regime. Theoretical calculations using standard Mie theory were carried out to monitor the LSPR peak shift and electric field enhancement as a function of the size of the bare plasmonic nanoparticle and the refractive index (RI) of the surrounding medium. Comparisons were made with and without invoking quantum regime. Also, the optical properties of metallic NPs conjugated with a chemical ligand using multi-layered Mie theory were studied, and interesting trends were observed. [ABSTRACT FROM AUTHOR]