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We recently identified N-cadherin as a novel receptor for fibrin and localized complementary binding sites within the fibrin βN-domains and the third and fifth extracellular domains (EC3 and EC5) of N-cadherin. We also hypothesized that the His16 and Arg17 residues of the βN-domains and the (Asp/Glu)-X-(Asp/Glu) motifs present in the EC3 and EC5 domains may play roles in the interaction between fibrin and N-cadherin. The primary objectives of this study were to test these hypotheses and to further clarify the structural basis for this interaction. To test our hypotheses, we first mutated His16 and Arg17 in the recombinant (β15–66)2fragment, which mimics the dimeric arrangement of the βN-domains in fibrin, using site-directed mutagenesis. The results revealed that the mutations of both His16 and Arg17 are critical for the interaction. Next, we mutated Asp/Glu residues in the three (Asp/Glu)-X-(Asp/Glu) motifs, M1 (Asp-Phe-Glu), M2 (Glu-Ala-Glu), and M3 (Asp-Tyr-Asp), of the fibrin-binding N-cad(3–5) fragment of N-cadherin. The results showed that Asp292 and Glu294 of M1, and Asp468 and Asp470 of M3, are critical for the interaction. Our molecular modeling of the 3D structure of the EC3-EC4-EC5 domains revealed that these residues are located at the interfaces of EC3-EC4 and EC4-EC5 and that some may also be involved in calcium binding. In conclusion, our study identified amino acid residues in the fibrin βN-domains and the EC3 and EC5 domains of N-cadherin that are critical for the interaction of fibrin with N-cadherin and localized the fibrin-binding residues in the 3D structure of N-cadherin.

Interleukin-23 inhibition is effective in treating ulcerative colitis. Guselkumab is a dual-acting, human IgG1, interleukin-23p19 subunit inhibitor that potently neutralises interleukin-23 and can bind to CD64. We aimed to evaluate the efficacy and safety of guselkumab as induction and maintenance therapy in patients with ulcerative colitis.

Abstract: The article presents new information about the distribution of two alien Asian fish species in the Ural River. The topmouth gudgeon Pseudorasbora parvaobserved for the first time in the river basin was recorded only at several locations along a 300-km section between the mouths of the Kolpachka and Urtaburtya rivers, which apparently is due to its relatively recent invasion. The species could have entered the river from fish farms, in which its appearance was the result of an accidental introduction together with phytophagous fishes. Further, it has been established that the Amur sleeper Perccottus gleniipreviously known to occur only in the upper reaches is now widely distributed in the rivers of the Ural basin located in Russia. For both fish species, the variation in values of their meristic features falls within their spectrum of variability. A comparative description of nutrition is also presented. The spectrum of objects consumed by Amur sleeper is wider and their sizes are larger than for topmouth gudgeon. Among the common species of Chironomidae, benthic organisms (Chironomus plumosus, Glyptotendipes gripekoveni) predominate in the diet of Amur sleeper, while for topmouth gudgeon the diet includes organisms localized on aquatic macrophytes (Cricotopus algarum, C. sylvestris, and Tanytarsus gregarius) as well as swimming larvae (Cloeon dipterum) and crawling larvae (Caenis macrura) from the order of Ephemeroptera. The nutritional similarity of Amur sleeper and topmouth gudgeon, as species with similar biotopes, is characterized as relatively low in the Ural River.

GNE Myopathy is a unique recessive neuromuscular disorder characterized by adult-onset, slowly progressive distal and proximal muscle weakness, caused by mutations in the GNEgene which is a key enzyme in the biosynthesis of sialic acid. To date, the precise pathophysiology of the disease is not well understood and no reliable animal model is available. Gne KO is embryonically lethal in mice. To gain insights into GNE function in muscle, we have generated an inducible muscle Gne KO mouse. To minimize the contribution of the liver to the availability of sialic acid to muscle via the serum, we have also induced combined Gne KO in liver and muscle. A mouse carrying loxp sequences flanking Gne exon3 was generated by Crispr/Cas9 and bred with a human skeletal actin (HSA) promoter driven CreERTmouse. Gne muscle knock out was induced by tamoxifen injection of the resulting homozygote GneloxpEx3loxp/HSA Cre mouse. Liver Gne KO was induced by systemic injection of AAV8 vectors carrying the Cre gene driven by the hepatic specific promoter of the thyroxine binding globulin gene. Characterization of these mice for a 12 months period showed no significant changes in their general behaviour, motor performance, muscle mass and structure in spite of a dramatic reduction in sialic acid content in both muscle and liver. We conclude that post weaning lack of Gne and sialic acid in muscle and liver have no pathologic effect in adult mice. These findings could reflect a strong interspecies versatility, but also raise questions about the loss of function hypothesis in Gne Myopathy. If these findings apply to humans they have a major impact on therapeutic strategies.

Elevation of the homocysteine concentration in the plasma called hyperhomocysteinemia (hHCY) during pregnancy causes a number of pre- and postnatal developmental disorders. The aim of our study was to analyze the effects of H2S donors –NaHS and N-acetylcysteine (NAC) on blood-brain barrier (BBB) permeability in rats with prenatal hHCY. In rats with mild hHCY BBB permeability assessed by Evans Blue extravasation in brain increased markedly throughout life. Administration of NaHS or NAC during pregnancy attenuated hHCY-associated damage and increased endogenous concentrations of sulfides in brain tissues. Acute application of dl-homocysteine thiolactone induced BBB leakage, which was prevented by the NMDA receptor antagonist MK-801 or H2S donors. Rats with hHCY demonstrated high levels of NO metabolite – nitrites and proinflammatory cytokines (IL-1β, TNF-α, IL-6) in brain. Lactate dehydrogenase (LDH) activity in the serum was higher in rats with hHCY. Mitochondrial complex-I activity was lower in brain of hHCY rats. NaHS treatment during pregnancy restored levels of proinflammatory cytokines, nitrites and activity of the respiratory chain complex in brain as well as the LDH activity in serum. Our data suggest that H2S has neuroprotective effects against prenatal hHCY-associated BBB disturbance providing a potential strategy for the prevention of developmental impairments in newborns.

ABSTRACTArganiais a monotypic genus belonging to the family Sapotaceae and comprising the only species Argania spinosa. This taxon, endemic to southern Morocco (northern Africa), is important in arid lands. It has a high pastoral value, numerous traditional uses, and it is an important industrial crop for food and cosmetics. A few chromosome counts are available for the species but to date, there is no information on its genome size. Apart from being a parameter useful in many aspects of plant systematic and evolutionary biology, knowing the nuclear DNA amount is a pre-requisite to any genome-sequencing program. In this paper, we present for the first time data on the nuclear DNA content in Argania spinosa, from two populations, and we confirm its chromosome number. Genome size was estimated as 2C = 1.48 pg (1C = 723.72 Mbp) in both studied accessions, revealing a small genome. The chromosome count (2n = 20) revealed that the species has the lowest basic chromosome number (x = 10) in the Sapotaceae, and suggests a descending dysploidy process in the family. The first morphological characterisation of Argania spinosa’s karyotype is presented here. In addition, fluorochrome banding, performed with chromomycin A3and DAPI, showed the absence of AT-rich regions and the presence of GC-rich regions located in three chromosome pairs, bringing the first molecular cytogenetic data in the genus.

As airborne methane surveys of oil and gas systems continue to discover large emissions that are missing from official estimates1–4, the true scope of methane emissions from energy production has yet to be quantified. We integrate approximately one million aerial site measurements into regional emissions inventories for six regions in the USA, comprising 52% of onshore oil and 29% of gas production over 15 aerial campaigns. We construct complete emissions distributions for each, employing empirically grounded simulations to estimate small emissions. Total estimated emissions range from 0.75% (95% confidence interval (CI) 0.65%, 0.84%) of covered natural gas production in a high-productivity, gas-rich region to 9.63% (95% CI 9.04%, 10.39%) in a rapidly expanding, oil-focused region. The six-region weighted average is 2.95% (95% CI 2.79%, 3.14%), or roughly three times the national government inventory estimate5. Only 0.05–1.66% of well sites contribute the majority (50–79%) of well site emissions in 11 out of 15 surveys. Ancillary midstream facilities, including pipelines, contribute 18–57% of estimated regional emissions, similarly concentrated in a small number of point sources. Together, the emissions quantified here represent an annual loss of roughly US$1 billion in commercial gas value and a US$9.3 billion annual social cost6. Repeated, comprehensive, regional remote-sensing surveys offer a path to detect these low-frequency, high-consequence emissions for rapid mitigation, incorporation into official emissions inventories and a clear-eyed assessment of the most effective emission-finding technologies for a given region.

Based on the high structural homology between vascular endothelial (VE)-cadherin and neural (N)-cadherin, we hypothesized that fibrin, which is known to interact with VE-cadherin and promote angiogenesis through this interaction, may also interact with N-cadherin. To test this hypothesis, we prepared fibrin and its plasmin-produced and recombinant fragments covering practically all parts of the fibrin molecule. We also prepared the soluble extracellular portion of N-cadherin (sN-cadherin), which includes all five extracellular N-cadherin domains, and studied its interaction with fibrinogen, fibrin, and the aforementioned fibrin fragments using two independent methods, ELISA and SPR. The experiments confirmed our hypothesis, revealing that fibrin interacts with sN-cadherin with high affinity. Furthermore, the experiments localized the N-cadherin binding site within the fibrin βN-domains. Notably, the recombinant dimeric (β15–66)2fragment, corresponding to these domains and mimicking their dimeric arrangement in fibrin, preserved the N-cadherin-binding properties of fibrin. To localize the fibrin binding site within N-cadherin, we performed ELISA and SPR experiments with (β15–66)2and recombinant N-cadherin fragments representing its individual extracellular domains and combinations thereof. The results obtained indicate that the interaction of fibrin with N-cadherin occurs through the third and fifth extracellular domains of the latter. This is in contrast to our previous study, which revealed that fibrin interacts only with the third extracellular domain of VE-cadherin. In conclusion, our study identified N-cadherin as a novel receptor for fibrin and localized complementary binding sites within both fibrin and N-cadherin. The pathophysiological role of this interaction remains to be established.

We present the hardware and software implementation of the information technologies for the GNSS service of the Russian-Cuban co-located geodetic station. The service is equipped with geodetic and meteorological instruments with data acquisition and transmission systems and allows to conduct high-precision observations of the GPS and GLONASS global navigation satellite systems (GNSS) as well as meteorological measurements. The coordinates of the station are refined while processing GNSS observations and according to the change in coordinates, the movement of Cuban tectonic plates is estimated. Information technologies of the GNSS service is one of the key elements required for conducting regular automated geodetic and meteorological measurements. Information technologies is a group of computing and networking equipment that provides preliminary processing and transfer of observations to the data processing centre at the Institute of Applied Astronomy in St. Petersburg. It also allows the remote monitoring, control, and maintenance of GNSS service scientific instruments.

This article proposes an event-driven solution to genotype imputation, a technique used to statistically infer missing genetic markers in DNA. The work implements the widely accepted Li and Stephens model, primary contributor to the computational complexity of modern x86 solutions, in an attempt to determine whether further investigation of the application is warranted in the event-driven domain. The model is implemented using graph-based Hidden Markov Modeling and executed as a customized forward/backward dynamic programming algorithm. The solution uses an event-driven paradigm to map the algorithm to thousands of concurrent cores, where events are small messages that carry both control and data within the algorithm. The design of a single processing element is discussed. This is then extended across multiple cores and executed on a custom RISC-V NoC cluster called POETS. Results demonstrate how the algorithm scales over increasing hardware resources and a multi-core run demonstrates a 270X reduction in wall-clock processing time when compared to a single-threaded x86 solution. Optimisation of the algorithm via linear interpolation is then introduced and tested, with results demonstrating a wall-clock reduction time of $\mathtt {\sim }$∼5 orders of magnitude when compared to a similarly optimised x86 solution.

Abstract: Nanodiamonds modified with functional groups are obtained for targeted drug delivery. A set of methods for identifying nanodiamonds in biological material is determined and their localization in human macrophages and mouse lung cells is identified. It is shown that seven days after introduction into the mouse lungs, nanodiamonds are internalized by endotheliocytes and interstitial macrophages. Both in the human macrophage culture and in the lung cells, nanodiamonds are localized in phagosomes/phagolysosomes. The nanodiamonds do not cause pathological changes in human macrophages and mouse lung cells. The results obtained lead us to consider nanodiamonds as a promising carrier platform for drug delivery, first and foremost to macrophages of the interstitium of the respiratory portion of the lung, which is relevant in such a disease as tuberculosis.

The current optical anticounterfeit strategies that rely on multimode luminescence in response to the photon or thermal stimuli have significant importance in the field of anticounterfeiting and information encryption. However, the dependence on light and heat sources might limit their flexibility in practical applications. In this work, Er3+single-doped CaF2phosphors that show multistimuli-responsive luminescence have been successfully prepared. The as-obtained CaF2:Er3+phosphor exhibits green photoluminescence (PL) and color-tunable up-conversation (UC) luminescence from red to green due to the cross-relaxation of Er3+ions. Additionally, as-obtained CaF2:Er3+phosphors also display green mechano-luminescence behavior, which is induced by the contact electrification between the CaF2particles and PDMS polymers, enabling the phosphor to flexibly respond to mechanical stimuli. Moreover, feasible anticounterfeiting schemes with the capability of multistimuli-responsive and flexible decryption have been constructed, further expanding the application of optical materials in the field of advanced anticounterfeiting and information encryption.

X-ray dose detection plays a critical role in various scientific fields, including chemistry, materials, and medicine. However, the current materials used for this purpose face challenges in both immediate and delayed radiation detections. Here, we present a visual X-ray dosimetry method for multienvironment applications, utilizing NaLuF4nanocrystals (NCs) that undergo a color change from green to red upon X-ray irradiation. By adjustment of the concentrations of Ho3+, the emission color of the NCs can be tuned thanks to the cross-relaxation effects. Furthermore, X-ray irradiation induces generation of trapping centers in NaLuF4:Ho3+NCs, endowing the generation of mechanoluminescence (ML) behavior upon mechanical stimulation after X-ray irradiation ceases. The ML intensity shows a linear correlation with the X-ray dose, facilitating the detection of delayed radiation. This breakthrough facilitates X-ray dose inspection in flaw detection, nuclear medicine, customs, and civil protection, thereby enhancing opportunities for radiation monitoring and control.

The tunability of the optical properties of lead halide perovskite nanocrystals makes them highly appealing for applications. Halide anion exchange and quantum confinement enable tailoring of the band gap. For spintronics, the Landé g-factors of electrons and holes are essential. Using empirical tight-binding and k·pmethods, we calculate them for nanocrystals of all-inorganic lead halide perovskites CsPbX3(X= I, Br, Cl). The hole g-factor band gap dependence follows the universal law found for bulk perovskites, while for electrons, a considerable modification is predicted. Based on the k·panalysis, we conclude that this difference arises from the interaction of the bottom conduction band with the spin–orbit split electron states. These predictions are confirmed experimentally for electron and hole g-factors in CsPbI3nanocrystals in a glass matrix, measured by time-resolved Faraday ellipticity in a magnetic field at cryogenic temperatures.

Abstract: This paper provides data on the occurrence of vimba bream (Vimba vimba) in the middle reaches of the Ural River. One of the distinguishing features of this species from the native Caspian vimba (V. persa) is a greater number of scales in the lateral line. In the late 1980s, vimba bream was introduced from the Don River basin into the Volga River basin. Having successfully adapted in the Volgograd Reservoir, the species subsequently colonized the unregulated area of the Lower Volga and the northern and, apparently, middle parts of the Caspian Sea and formed a stable residential population in the Ural River basin.

Inference at-the-edge using embedded machine learning models is associated with challenging trade-offs between resource metrics, such as energy and memory footprint, and the performance metrics, such as computation time and accuracy. In this work, we go beyond the conventional Neural Network based approaches to explore Tsetlin Machine (TM), an emerging machine learning algorithm, that uses learning automata to create propositional logic for classification. We use algorithm-hardware co-design to propose a novel methodology for training and inference of TM. The methodology, called REDRESS, comprises independent TM training and inference techniques to reduce the memory footprint of the resulting automata to target low and ultra-low power applications. The array of Tsetlin Automata (TA) holds learned information in the binary form as bits: $\lbrace 0,1\rbrace${0,1}, called excludes and includes, respectively. REDRESS proposes a lossless TA compression method, called the include-encoding, that stores only the information associated with includes to achieve over 99% compression. This is enabled by a novel computationally minimal training procedure, called the Tsetlin Automata Re-profiling, to improve the accuracy and increase the sparsity of TA to reduce the number of includes, hence, the memory footprint. Finally, REDRESS includes an inherently bit-parallel inference algorithm that operates on the optimally trained TA in the compressed domain, that does not require decompression during runtime, to obtain high speedups when compared with the state-of-the-art Binary Neural Network (BNN) models. In this work, we demonstrate that using REDRESS approach, TM outperforms BNN models on all design metrics for five benchmark datasets viz. MNIST, CIFAR2, KWS6, Fashion-MNIST and Kuzushiji-MNIST. When implemented on an STM32F746G-DISCO microcontroller, REDRESS obtained speedups and energy savings ranging 5-5700× compared with different BNN models.

This paper presents a fast way to predict the noise level of installed propeller on wing. Installing the propeller on wing has not only increased wing lift coefficient, but also greatly changed the noise direction. However, the precise prediction of noise level is a difficult and cumbersome, since the aerodynamic interaction effects are so complicated. But with a series of simplicity, here still can get a concise formulation, which is sufficient to evaluate the noise level of early design of propeller-driven aircraft.

The MSM structures based on high-quality 1.6- $\mu \text{m}$ -thick $\alpha $ -gallium oxide (Ga2O3) films grown by the halide vapor phase epitaxy with Ti/Ni interdigital contacts were developed for the detection of short-wave ultraviolet (UVC) radiation. The spectral dependences of responsivity, external quantum efficiency (EQE), and detectivity of MSM structures based on $\alpha $ -Ga2O3 were studied in the wavelength range of 205–260 nm. The responsivity, the EQE, and the detectivity are $7.19\times104$ A $\times \,\,\text{W}^{-{1}}$ , $3.79\times105$ arb.un., and $1.12\times1018$ Hz $^{\text {0.{5}}} \times $ cm $\times \,\,\text{W}^{-{1}}$ , respectively, for structures with an interelectrode distance of 30 $\mu \text{m}$ at an applied voltage of 10 V and exposure to radiation with a wavelength of 235 nm. The high values of the photoelectric characteristics were caused by the manifestation of an internal gain of the photoresponse due to the self-localization of holes in $\alpha $ -Ga2O3. The prospects of researches to develop UVC radiation detectors for wireless UVC communication were shown.