While machine learning (ML) has been quite successful in the field of structural health monitoring (SHM), its practical implementation has been limited. This is because ML model training requires data containing a variety of distinct damaged instances captured from a real structure and the experimental generation of such data is challenging. One way to tackle this issue is by generating training data through numerical simulations. However, simulated data cannot capture the bias and variance of experimental uncertainty. To overcome this problem, this work proposes a deep learning-based domain transformation method for transforming simulated data to the experimental domain. Use of this technique has been demonstrated for debonding location and size prediction of stiffened panels using a vibration-based method. The results are satisfactory for both, debonding location and size prediction. This domain transformation method can be used in any field where experimental data for training machine learning models is scarce.

To search for novel thermostable esterase for optimized industrial applications, esterase from a thermophilic eubacterium species, Thermoanaerobacter tengcongensis MB4 was purified and characterised in this work. Sequence analysis of T. tengcongensis esterase with other homologous esterases of the same family revealed an apparent tail at the C-terminal that is not conserved across the esterase family. Hence, it was hypothesized that the tail is unlikely to have an essential structural or catalytic role. However, there is no documented report of any role for this tail region. We probed the role of the C-terminal domain on the catalytic activity and substrate preference of Thermoanaerobacter tengcongensis esterase EstA3 with a view to see how it could be engineered for enhanced properties. To achieve this, we cloned, expressed, and purified the wild-type and the truncated version of the enzyme. In addition, a naturally occurring member of the family (from B. brevis) that lacks the C-terminal tail was also made. In vitro characterization of the purified enzymes showed that the C-terminal domain contributes significantly to the catalytic activity and distinct substrate preference of T. tengcongensis esterase EstA3. All the three recombinant enzymes showed highest preference to paranitrophenyl butyrate (pNPC4), which suggests they are true esterases, not lipases. kinetic data revealed that truncation had a slight effect on the substrate-binding affinity. Thus, the drop in preference towards long-chain substrates might not be a result of substrate binding affinity alone.

This paper presents various procedures for determining the optimal control law for a wing section in compressible flow. The flow regime includes subsonic as well as supersonic flows. For the evolution of the system in the Laplace plane the present method makes use of the exact unsteady aerodynamic forces in the Laplace plane once the control law is established. This is a great advantage against other results previously published, where the unsteady aerodynamics in the Laplace plane are just approximations of the curve-fitted values in the frequency domain (imaginary axis). Different control techniques are investigated like pole-placement, LQR and H-infinity norm. Among these, the H-infinity norm emerges as the optimal choice, exhibiting a norm magnitude approximately two orders of magnitude lower than the LQR case. Furthermore, the H-infinity controller demonstrates lower pole values that those of the pole placement and LQR compensator, showing the advantage of the H-infinity controller in terms of economic efficiency.

Although there are several access control systems in the literature for flexible policy management in multi-authority and multi-domain environments, achieving interoperability & scalability, without relying on strong trust assumptions, is still an open challenge. We present HMBAC, a distributed fine-grained access control model for shared and dynamic multi-authority and multi-domain environments, along with Janus, a practical system for HMBAC policy enforcement. The proposed HMBAC model supports: (a) dynamic trust management between different authorities; (b) flexible access control policy enforcement, defined at domain and cross-domain level; (c) a global source of truth for all entities, supported by an immutable, audit-friendly mechanism. Janus implements the HMBAC model and relies on the effective fusion of two core components. First, a Hierarchical Multi-Blockchain architecture that acts as a single access point that cannot be bypassed by users or authorities. Second, a Multi-Authority Attribute Based Encryption protocol that supports flexible shared multi-owner encryption, where attribute keys from different authorities are combined to decrypt data distributedly stored in different authorities. Our approach was implemented using Hyperledger Fabric as the underlying blockchain, with the system components placed in Kubernetes Docker container pods. We experimentally validated the effectiveness and efficiency of Janus, while fully reproducible artifacts of both our implementation and our measurements are provided.

Understanding the ionic channel network of proton exchange membranes, which dictate fuel cell performance, is crucial when developing proton exchange membrane fuel cells. However, itis difficult to characterize due to complicated nano structure and differing changes to their structure with different amounts of water uptake. Electrostatic force microscopy (EFM) can map surface charge distribution as nano special resolution by measuring the electrostatic force between a vibrating conductive tip and a charged surface under an applied voltage, . In this study, the ionic channel network of a proton exchange membrane is analyzed using EFM. A mathematical approximation model of the ionic channel network is first derived, to explain changes in force gradient on the surface using EFM. The phase lag of dry and wet Nafion under stepwise changes to bias voltage is then measured. Based on the model, variations in the ionic channel network of Nafion with different amounts of water uptake are analyzed numerically. The mean surface charge density of both membranes, which is connected with the ionic channel network, is calculated using the model. The results show that the difference between the mean surface charge of the dry and wet membranes is consistent with the variation in their proton conductivity.

The transnational spread of coronavirus (2019-nCoV) first detected in Wuhan is causing global panic; thus, accelerated research into clinical intervention is of high necessity. The spike glycoprotein structure has been resolved, and its affinity to human angiotensin-converting enzyme 2 (ACE-2) has been experimentally validated. Here, using computational methods, a metastable conformation of 2019-nCoV-RBD/ACE-2 complex has been revealed and FDA-database of approved drugs have been docked into the interface. Darunavir has been discovered as high ligand affinity candidate capable of disrupting communication between 2019-nCoV-RBD and ACE-2. Darunavir, in addition to its previously known anti-HIV protease inhibitor is now repurposeable for the treatment 2019-nCoV disease acting via disruption of cellular recognition, binding and invasion.

SMAD ubiquitination regulatory factor 1 (Smurf1) is a Nedd4 family E3 ubiquitin ligase that regulates cell motility, polarity and TGFβ signaling. Smurf1 contains an N-terminal protein kinase C conserved 2 (C2) domain that targets cell membranes and is required for interactions with membrane-localized substrates such as RhoA. Here we investigated the lipid-binding mechanism of Smurf1 C2, revealing a general affinity for anionic membranes in addition to a selective affinity for phosphoinositides (PIPs). We found that Smurf1 C2 localizes not only to the plasma membrane but also to negatively charged intracellular sites, acting as an anionic charge sensor and selective PIP-binding domain. Site-directed mutagenesis combined with docking/molecular dynamics simulations revealed that the Smurf1 C2 domain loop region primarily interacts with PIPs and cell membranes, as opposed to the β-surface cationic patch employed by other C2 domains. By depleting PIPs from the inner leaflet of the plasma membrane, we found that PIP binding is necessary for plasma membrane localization. Finally, we used a Smurf1 cellular ubiquitination assay to show that the amount of ubiquitin at the plasma membrane interface depends on the lipid-binding properties of Smurf1. This study shows the mechanism by which Smurf1 C2 targets membrane-based substrates and reveals a novel interaction based on PI(4,5)P2 and PIP3 selectivity.

We present a distributed optical-fiber temperature sensor with enhanced sensitivity based on an Al-coated fiber using the Rayleigh backscattering spectra (RBS) shift in optical frequency-domain reflectometry (OFDR). The Al-coated sensing fiber with a higher thermal expansion coefficient compared to silica produces a strain-coupled shift in the RBS under an increase in temperature. This effect leads to an enhanced temperature sensitivity of the distributed measurement scheme. Our results revealed that the temperature sensitivity obtained using the Al-coated fiber in OFDR was ~56% higher relative to that of a single-mode fiber. Moreover, the minimum measurable temperature recorded was 1 °C with a spatial resolution of 5 cm.

A simplified nonlinear dispersive system of BBM-type, initially derived by D. Mitsotakis, is employed here in order to model the generation and propagation of surface water waves over variable bottom. The simplification consists in applying the so-called Boussinesq approximation. Using the finite element method and the FreeFem++ software, we solve numerically this system for three different complexities for the bathymetry function: a flat bottom case, a variable bottom in space, and a variable bottom both in space and in time. The last case is illustrated with the Java 2006 tsunami event. This article is designed rather as a tutorial paper even if it contains the description of completely new adaptation techniques.

Recently, more wind turbine systems are being installed in deep waters far from the coast. Several concepts of floating wind turbine systems (FWTSs) are developed, among which the semisubmersible platform, due to its applicability in different water depths, good hydrodynamic performance, and facility in the installation process, constitutes the most explored technology compared to the others. However, a significant obstacle to the industrialization of this technology is a design of a cost-effective FWTS, which can be achieved by optimizing the geometry, size and weight of the floating platform, along with the mooring system. This is only possible by selecting a method capable of accurately analyzing the FWTS coupled hydro-aero-structural dynamics at each design stage. Accordingly, this paper aims at providing a detailed overview of the most common coupled numerical and physical methods, including their basic assumptions, formulations, limitations, and costs, used for analyzing the dynamics of FWTSs, mainly those supported by a semisubmersible, to assist the choice of the most suitable method at each design phase of FWTSs. Finally, the article discusses possible future research to address challenges in modeling FWTSs dynamics that persist to date.

The origin of neurodegenerative diseases is linked to the abnormal folding of disease-associated proteins. The traditional amyloid hypothesis has been a focal point of research, but recent findings suggest a more complex picture. This review explores the role of physiological conformation of aggregation-prone domain (also known as prion-like low complexity domain) and multiple co-misfolded proteins in neurodegenerative diseases. We highlight the importance of targeting multi-heterotypic misfolded proteins for effective treatments and emphasize the irreversible neurodegeneration stemming from the loss of physiological folding in prion-like disease-causing proteins underscores the criticality of refolding. Additionally, we introduce the concept of ReproFold Therapeutics, a novel approach aimed at restoring the cellular prion-like folding of disease-causing proteins to rebuild normal cross-β interactomes and mitigate neurodegeneration. Baicalein, a potential drug candidate for this approach, shows promise in vitro and in animal models. Moreover, prion-like low complexity domains implicated in neurodegeneration are also associated with other disorders such as diabetes, cancers, and mental illnesses. Understanding the core pathology of neurodegenerative diseases and the broader implications of prion-like LC domains could revolutionize healthcare approaches and policies worldwide.

The reflection and transmission spectra of a metamaterial formed by omega-shaped elements with pre-calculated optimal parameters on a silicon substrate have been recorded in the terahertz range at oblique incidence for the s- and p- polarizations of the incident wave. The spectra were interpreted within the dipole radiation theory of electromagnetic waves. Both measurement results and analysis provide evidence sup-porting the presence of a pronounced polarization anisotropy impact in the reflection and transmission of the metamaterial. The potential of these materials to be utilized in the development of devices that control the polarization properties of THz radiation across a wide spectral range is examined.

Manzamines are complex polycyclic marine-derived β-carboline alkaloids with reported anticancer, immunostimulatory, anti-inflammatory, antibacterial, antiviral, antimalarial, neuritogenic, hyperlipidemia and atherosclerosis suppression bioactivities, putatively associated with inhibition of glycogen synthase kinase-3, cyclin-dependent kinase 5, and vacuolar ATPases. We hypothesized that additional and yet undiscovered molecular targets might be associated with Manzamine A (MZA) reported pharmacological properties. We report herein for the first time to our knowledge that MZA inhibited a 90kDa ribosomal protein kinase S6 (RSK1) when screened against a panel of 30 protein kinases. Furthermore in vitro RSK kinase assays demonstrated a 10-fold selectivity in potency of MZA against RSK1 versus RSK2. MZA’s differential binding and selectivity toward the two isoforms is also supported by computational docking experiments. Specifically, the RSK1-MZA (N- and C-termini) complexes appear to have stronger interactions and preferable energetics contrary to the RSK2-MZA ones. In addition, our computational strategy suggests that MZA binds to the N-terminal kinase domain of RSK1 rather than the C-terminal domain. RSK is a vertebrate family of cytosolic serine-threonine kinases that act downstream of the ras-ERK1/2 (extracellular-signal-regulated kinase 1/2) pathway, which phosphorylates substrates shown to regulate several cellular processes including growth, survival and proliferation. Consequently, our findings have lead us to hypothesize that MZA and the 80 currently known manzamine-type alkaloids isolated from several sponge genera, may have novel pharmacological properties.

Subsurface drainage systems remove excess water from the soil profile thereby improving crop yields in poorly drained farmland. Knowledge of the position of the buried drain lines is important: 1) to improve understanding of leaching and offsite release of nutrients and pesticides, and 2) for the installation of a new set of drain lines between the old ones for enhanced soil water removal efficiency. Traditional methods of drainage mapping involve the use of tile probes and trenching equipment. While these can be effective, they are also time-consuming, labor-intensive, and invasive, thereby entailing an inherent risk of damaging the drainpipes. Non-invasive geophysical soil sensors provide a potential alternative solution. Previous research has focused on the use of time-domain ground penetrating radar (GPR), with variable success depending on local soil and hydrological conditions and the central frequency of the specific equipment employed. The objectives of this study were 1) to test the use of a stepped-frequency continuous wave (SFCW) 3D-GPR (GeoScope Mk IV 3D-Radar with DXG1820 antenna array) for subsurface drainage mapping, and 2) to evaluate the performance of a 3D-GPR with the use of a single-frequency multi-receiver electromagnetic induction (EMI) sensor (DUALEM) in-combination. The 3D-GPR system offers more flexibility for application to different (sub)surface conditions due to the coverage of wide frequency bandwidth. The EMI sensor simultaneously provides information about the apparent electrical conductivity (EC_a) for different soil volumes, corresponding to different depths. This sensor combination was evaluated on twelve different study sites with various soil types with textures ranging from sand to clay till. While the 3-D GPR showed a high success rate in finding the drainpipes at five sites (sandy, sandy loam, loamy sand, and organic topsoils), the results at the other seven sites were less successful due to limited penetration depth (PD) of the 3D-GPR signal. The results suggest that the electrical conductivity estimates produced by the inversion of EC_a data measured by the DUALEM sensor could be a useful proxy to explain the success achieved by the 3D-GPR in finding the drain lines. The high attenuation of electromagnetic waves in highly conductive media limiting the PD of the 3D-GPR can explain the findings obtained in this research.

Recently, there has been considerable research on deepfake detection. However, most existing methods face challenges in adapting to the advancements in new generative models within unknown domains. In addition, the emergence of new generative models capable of producing and editing high-quality images, such as Diffusion, Consistency, and LCM, poses a challenge for traditional deepfake training models. These advancements highlight the need for adapting and evolving existing deepfake detection techniques to effectively counter the threats posed by sophisticated image manipulation technologies. In this paper, our objective is to detect deepfake videos in unknown domains using unlabeled data. Specifically, our proposed approach employs Meta Pseudo Labels (MPL) with Supervised Contrastive Learning, so-called SupCon-MPL, allowing the model to be trained on unlabeled images. MPL involves the simultaneous training of both a Teacher model and a Student model, where the Teacher model generates Pseudo Labels utilized to train the Student model. This method aims to enhance the adaptability and robustness of deepfake detection systems against emerging unknown domains. Supervised Contrastive Learning utilizes labels to compare samples within similar classes more intensively, while encouraging greater distinction from samples in dissimilar classes. This facilitates the learning of features in a diverse set of deepfake images by the model, consequently contributing to the performance of deepfake detection in unknown domains. When utilizing the ResNet50 model as the backbone, SupCon-MPL exhibited an improvement of 1.58% in accuracy compared to traditional MPL in known domain detection. Moreover, in the same generation of unknown domain detection, there was a 1.32% accuracy enhancement, while in the detection of post-generation unknown domains, there was an 8.74% increase in accuracy.

ShK domain-containing proteins are peptides found in different parasitic and venomous organisms. From a previous transcriptomic dataset from Bursaphelenchus xylophilus, a plant-endoparasitic nematode that infects forest tree species, we identified 96 transcripts potentially as ShK domain-containing proteins with unknown function in the nematode genome. This study aimed to characterize and explore the functional role of genes encoding ShK domain-containing proteins in B. xylophilus biology. We selected and functionally analyzed nine candidate genes specific from B. xylophilus. In situ hybridization revealed expression of one B. xylophilus ShK in the pharyngeal gland cells, suggesting their delivery into host cells. Most of the transcripts are highly expressed during infection and showed a significant upregulation in response to peroxide products compared to the nematode catalase enzymes. We reported for the first time, the potential involvement of ShK domain genes in oxidative stress, suggesting that these proteins may have an important role protecting or modulating the reactive oxygen species (ROS) activity of the host plant during parasitism.

This research delves into the impact of complex low-speed wake flow structures on the aerodynamic characteristics of objects downstream. It employs the proper orthogonal decomposition (POD) method and the domain precursor simulation method to compare traditional methods and validate this approach. The study generates several flow structures of parallel dual-cylinder wakes with different scales and spacing. The variations in the aerodynamic coefficient of three downstream objects at various times passing through wakes of varying scales are appropriately compared and analyzed. The study establishes that the wake with a cylinder spacing of G=1.5 has a more compact and concentrated modal structure than that with a cylinder spacing of G=0.35. Smaller objects are more responsive to the wake flow structure with a spacing of G=1.5, whereas larger objects respond more to the flow structure with a spacing of G=0.35. The achieved results also reveal that the aerodynamic force coefficients of objects passing through the wakefield at different times are closely related to the temporal characteristics of the wake flow structure with different scales.

Optical switching is an essential part of photonic integrated circuits and the focus of research at the moment. In this research, an optical switch design working on the phenomenon of the guided-mode resonances in 3D photonic crystals-based structure is reported. The optical-switching mechanism is studied in a dielectric slab-waveguide-based structure operating in the near-infrared range in a telecom window of 1.55 µm. The mechanism is investigated by interference of two signals, i.e., the data signal and the control signal. The data signal is coupled into the optical structure and filtered utilizing guided-mode resonance, whereas, the control signal is index guided in the optical structure. The amplification or de-amplification of the data signal is controlled by tuning the spectral properties of the optical sources and structural parameters of the device. The parameters are optimized first using a single-cell model with periodic boundary conditions and later in a finite 3D-FDTD model of the device. The numerical design is computed in an open-source Finite Difference Time Domain simulation platform. Optical amplification in the range of 13.75 % is achieved in the data signal with a decrease in the linewidth up to 0.0079 µm and a quality factor of 114.58. The proposed device presents great potential in the field of photonic integrated circuits, biomedical technology, and programmable photonics.

The rapid development of digital multimedia has resulted in a massive storm of large-scale data. The data compression method reduces data size and lowers transmission costs. As a result, data-hiding research in the compression domain poses significant challenges to researchers. This paper proposes a highly imperceptible data-hiding scheme for a compressed image of Absolute Moment Block Truncation Coding (AMBTC). The combination theory is implemented to ensure the high imperceptibility of the modified compressed images. By only modifying one pixel in a block to embed secret bits, the experimental results show that the proposed method achieved high imperceptibility and high hiding capacity.

The current study investigated whether a domain-specific intervention targeting maths and executive functions of primary school children with a Roma background would be effective in improving their scholastic performance and executive functioning. In total, 122 students attending Grade 4 of elementary school took part in the project. The study concerned a pretest-intervention-training experimental design with three conditions: the experimental condition, an active and a passive control group. The results suggested that both maths performance and executive functions improved over time, with no significant differences between the three conditions. An additional correlational analysis indicated that pretest performance was not related to posttest performance for the children in the experimental and active control group.

Often, when solving forward, inverse or data assimilation problems, only a part of the solution is needed. As a model, we consider the stationary diffusion problem. We demonstrate an algorithm that can compute only a part or a functional of the solution, without calculating the full inversion operator and the complete solution. It is a well-known fact about partial differential equations that the solution at each discretisation point depends on the solutions at all other discretisation points. Therefore, it is impossible to compute the solution only at one point, without calculating the solution at all other points. The standard numerical methods like a conjugate gradient or Gauss elimination compute the whole solution and/or the complete inverse operator. We suggest a method which can compute the solution of the given partial differential equation 1) at a point; 2) at few points; 3) on an interface; or a functional of the solution, without computing the solution at all points. The required storage cost and computational resources will be lower as in the standard approach. With this new method, we can speed up, for instance, computation of the innovation in filtering or the likelihood distribution, which measures the data misfit (mismatch). Further, we can speed up the solution of the regression, Bayesian inversion, data assimilation, and Kalman filter update problems. Applying additionally the hierarchical matrix approximation, we reduce the cubic computational cost to almost linear $\mathcal{O}(k^2n \log^2 n)$, where $k\ll n$ and $n$ is the number of degrees of freedom. Up to the hierarchical matrix approximation error, the computed solution is exact. One of the disadvantages of this method is the need to modify the existing deterministic solver.

Printed electronic devices are attracting significant interest due to their versatility and low cost; however, quality control during manufacturing is a significant challenge, preventing the widespread adoption of this promising technology. We show that terahertz (THz) radiation can be used for the in situ inspection of printed electronic devices, as confirmed through a comparison with conventional electrical conductivity methods. Our in situ method consists of printing a simple test pattern exhibiting a distinct signature in the THz range that enables the precise characterization of {the static} electrical conductivities of the printed ink. We demonstrate that contactless dual-wavelength THz spectroscopy analysis, which requires only a single THz measurement, is more precise and repeatable than the conventional four-point probe conductivity measurement method. Our results open the door to a simple strategy for performing contactless quality control in real time of printed electronic devices at any stage of its production line.

Purpose: To correlate outflow function and outflow tract vessel diameter changes induced by nitric oxide (NO). Methods: In a porcine anterior segment perfusion model, the effects of a nitric oxide donor (100 µM DETA-NO) on outflow facility were compared to controls (n=8 per group) with trabecular meshwork (TM) and after circumferential ab interno trabeculectomy (AIT). Outflow structures were assessed with spectral domain optical coherence tomography (SD-OCT) before and after NO, or an NO synthase inhibitor (100 µM L-NAME) and the vasoconstrictor, endothelin-1 (100 pg/mL ET-1). Scans were processed with a custom macro script and aligned for automated reslicing and quantification of cross-sectional outflow tract areas (CSA). Results: The facility increased after DETA-NO (0.189±0.081 μL/min·mmHg, p=0.034) and AIT (0.251±0.094 μL/min·mmHg, p=0.009), respectively. Even after AIT, DETA-NO increased the facility by 61.5% (0.190±0.074 μL/min·mmHg, p=0.023) and CSA by 13.9% (p<0.001). L-NAME + ET-1 decreased CSA by -8.6% (p<0.001). NO increased the diameter of focal constrictions 5.0±3.8 fold. Conclusions: NO can dilate vessels of the distal outflow tract and increase outflow facility in a TM-independent fashion. There are short, focally constricting vessel sections that display large diameter changes and may have a substantial impact on outflow.

Thermal Non-destructive Testing and Evaluation (NDT&E) is crucial in ensuring the quality and safety of industrial materials, components, and structures. It serves as a key tool for assessing their operational reliability, thus enhancing safety in a wide range of industries. There is a growing demand for dependable, swift, remote, and secure inspection and assessment techniques to detect hidden flaws, especially for sustainable solutions prompts adjustments in design and manufacturing standards. Hidden defects often emerge during the service life of these materials and structures due to various stress factors, potentially resulting in catastrophic failures. This study delves into the optimal and dependable experimental method for conducting fast, remote, and secure inspections and assessments of carbon fiber reinforced polymer materials using Infrared Imaging (IRI) as part of Thermal Non-Destructive Testing and Evaluation (TNDT&E). Additionally, it examines the post-processing approach associated with this technique. This perspective also sheds light on the current state-of-the-art infrared imaging methods employed in TNDT&E, emphasizing their strengths and weaknesses about their ability to detect subsurface defects present within the material Most of the methods discussed in previous research primarily focus on the thermal differences in specific areas of a sample using processed thermal images, even though these images come from analyzing a series of images captured over time. This study highlights the latest research in thermal/infrared non-destructive testing and evaluation, along with the related post-processing techniques. It aims to not only show hidden subsurface defects through thermal differences also provides information about how these defects change over time.

There is much interest in effective copper chelators to correct copper dyshomeostasis in neurodegenerative and oncological diseases. In this study, a recombinant fusion protein for expression in E. coli cells was constructed from glutathione-S-transferase (GST) and the N-terminal domain (ectodomain) of human high affinity copper transporter CTR1 (hNdCTR1), which has three metal-bound motifs. Several biological properties of the GST-hNdCTR1 fusion protein were assessed. It was demonstrated that in cells, the protein was prone to oligomerization, formed inclusion bodies and displayed no toxicity. Treatment of E. coli cells with copper and silver ions reduced cell viability in a dose- and time-dependent manner. Cells expressing GST-hNdCTR1 protein demonstrated resistance to the metal treatments. These cells accumulated silver ions and formed nanoparticles that contained AgCl and Ag0. In this bacterial population, filamentous bacteria with length about 10 μm were often observed. The possibility for the fusion protein carrying extracellular metal binding motifs to integrate into the cell’s copper metabolism and its chelating properties are discussed.

This paper presents results of the magnetic dynamics study (the microwave power absorptions at the fixed frequencies, during magnetic field sweeping) in samples of Y3Fe5O12 single crystals in the form of plates and spheres of various sizes, at frequencies exceeding 30 GHz, in magnetic fields up to 18 kOe, at room temperature and T=77 K. It was found, that in this case, the inhomogeneity’s of the magnetic state manifested itself in the Y3Fe5O12 samples in as 2D local phase separation regions. These 2D phase separation regions formed inside domain walls representing superlattices with size’s 700 – 900 Å. Landau diamagnetism or de Haas van Alphen oscillations observed in the 2D phase separation regions at room temperature and T=77 K, depending on the shape and size of the studied plates and spheres.

SRC homology 3 (SH3) domains are critical interaction modules that orchestrate the assembly of protein complexes involved in diverse biological processes. They facilitate transient protein-protein interactions by selectively interacting with proline-rich motifs (PRMs). A database search revealed 298 SH3 domains in 221 human proteins. Multiple sequence alignment of human SH3 domains is useful for phylogenetic analysis and determination of their selectivity towards PRM-containing peptides (PRPs). However, a more precise functional classification of SH3 domains is achieved by constructing a phylogenetic tree only from PRM-binding residues and using existing SH3-PRP structures and biochemical data to determine the specificity within each of the 10 families for particular PRPs. In addition, the C-terminal proline-rich domain of the RAS activator SOS1 covers 13 of the 14 recognized proline-rich consensus sequence motifs, encompassing differential PRP pattern selectivity among all SH3 families. To evaluate binding capabilities and affinities, we conducted fluorescence dot blot and polarization experiments using 25 representative SH3 domains and various PRPs derived from SOS1. Our analysis has identified 45 interacting pairs with binding affinities ranging from 0.2 to 125 micromolar out of 300 tested and potential new interactors of SOS1. Furthermore, it establishes a framework to bridge the gap between SH3 and PRP interactions and provides predictive insights into potential interactions of SH3 domains with PRMs based on sequence specifications. This novel framework has the potential to enhance the understanding of protein networks mediated by SH3-PRM interactions and be utilized as a general approach for other domain-peptide interactions.

Ambient vibration energy is widely being harnessed as a source of electrical energy to drive low-power devices. The vibration energy harvester (VEH) of interest employs an electromagnetic transduction mechanism, whereby ambient mechanical vibration is converted to electrical energy. The limitations affecting the performance of VEHs, with an electromagnetic transduction structure, include its operational bandwidth as well as the enclosure-size constraint. In this study, an analysis and design of a nonlinear VEH system is conducted, using the Output Frequency Response Function (OFRF) representations of the actual system model. However, the OFRF representations are determined from the Generalised Associated Linear Equation (GALE) decompositions of the system of interest. The effect of both nonlinear damping and stiffness characteristics, to respectively extend the average power and operational bandwidth of the VEH device, is demonstrated.

The selectivity in selective autophagy pathways is achieved via the selective autophagy receptors (SARs) – proteins that bind a ligand on the substrate to be degraded and the Atg8-family protein on the growing autophagic membrane, phagophore, effectively bridging them. In mammals, the most common ligand of SARs is ubiquitin, a small protein modifier that tags substrates for their preferential degradation by autophagy. Consequently, the most common SARs are the ubiquitin-binding SARs, such as SQSTM1/p62 (sequestosome 1). Surprisingly, there is only one SAR of this type in yeast – Cue5, which acts as a receptor for aggrephagy and proteaphagy – pathways that remove the ubiquitinated protein aggregates and proteasomes, respectively. However, recent studies described the ubiquitin-dependent autophagic pathways that do not require Cue5, e.g. stationary phase lipophagy for intracellular lipid droplets and nitrogen starvation-induced mitophagy for mitochondria. What is the role of ubiquitin in these pathways? Here, we propose that the ubiquitinated lipid droplets and mitochondria are recognized by the alternative ubiquitin-binding SARs. Our analysis identifies the proteins that could potentially fulfill this role in yeast. We think that matching of the ubiquitin-dependent (but Cue5-independent) autophagic pathways with the ubiquitin-and-Atg8-binding proteins enlisted here might uncover the novel ubiquitin-binding SARs in yeast.

Time-domain spectroscopy (TDS) in the Terahertz (THz) frequency range is gaining in importance in nondestructive testing of dielectric materials. One application is the layer thickness measurement of a coating layer. To determine the thickness from the measurement data, the refractive index of the coating layer must be known in the surveyed frequency range. For perpendicular incidence of the radiation, methods exist to extract the refractive index from the measurement data itself without prior knowledge. This paper extends these methods for non-perpendicular incidence, where the polarization of the radiation becomes important. Furthermore, modifications considering effects of surface roughness of the coating are introduced. The new methods are verified using measurement data of a sample of Inconel steel coated with yttria-stabilized zirconia (YSZ) and with COMSOL simulations of the measurement setup. To validate the thickness measurements, scanning electron microscopy (SEM) images of the layer structure are used. The results show good agreement with an average error of 1% for the simulation data and under 4% for the experimental data compared to reference measurements.

Detection of PLA2R and THSD7A among primary membranous glomerulonephritis (MGN) patients transformed the diagnosis, treatment monitoring and prognosis. Anti-PLA2R can be detected in 70-90% of primary MGN patients while anti-THSD7A in 2-3% of anti-PLA2R negative primary MGN patients depending on the technique used. Serum and urine samples are less invasive and non-invasive respectively and can detect the presence of anti-PLA2R and anti-THSD7A with higher sensitivity and specificity, significant in patients’ monitoring and prognosis better than exposing patients to frequent biopsy which is an invasive procedure. Different techniques of detection of PLA2R and THSD7A in patients’ urine and sera were reviewed with the aim of providing newer and alternative techniques. We proposed the use of biomarkers (PLA2R and THSD7A) in making the diagnosis, treatment decision and follow up of patients with primary MGN. We also reviewed other prognostic renal biomarkers like retinol binding protein (RBP) and beta-2 microglobulin in order to detect progression of renal damage for early intervention.

Fine-tuning is an important technique in transfer learning that has achieved significant success in tasks that lack training data. However, as it is difficult to extract effective features for single-source domain fine-tuning when the data distribution difference between the source and the target domain is large, we propose a transfer learning framework based on multi-source domain called adaptive multi-source domain collaborative fine-tuning to address this issue. This approach utilizes multiple source domain models for collaborative fine-tuning, thereby improving the model's feature extraction capability in the target task. Specifically, this approach employs an adaptive multi-source domain layer selection strategy to customize appropriate layer fine-tuning schemes for the target task among multiple source domain models. The objective is to extract more efficient features. Furthermore, a novel multi-source domain collaborative loss function is designed to facilitate the precise extraction of target data features by each source domain model. Simultaneously, it works towards minimizing the output difference among various source domain models, thereby enhancing the adaptability of the source domain model to the target data. In order to validate the effectiveness of the proposed the adaptive multi-source domain collaborative fine-tuning framework, it is analyzed and compared with the most widely used fine-tuning methods by applying them to seven publicly available visual categorization datasets commonly employed in transfer learning. Experimental results demonstrate that, in comparison with the existing fine-tuning approaches, our method not only enhances the accuracy of feature extraction in the model but also provides precise layer fine-tuning schemes for the target task, resulting in state-of-the-art performance.

The unsupervised domain-adaptive vehicle reidentification approach aims to transfer knowledge from a labeled source domain to an unlabeled target domain, however there are knowledge differences between the target domain and the source domain. To reduce domain differences, existing unsupervised domain-adaptive rerecognition methods generally require access to the source domain data to assist in re-training the target domain model. But for security reasons, in many cases, data between different domains cannot communicate. To this end, this paper proposes an unsupervised domain-adaptive vehicle re-identification method based on source-free knowledge transfer. First, by constructing a passive domain knowledge migration module, the target domain is consistent with the source domain model output to train a generator to generate the "source-like samples". Then, it can effectively reduce the model knowledge difference and improve the model generalization performance. According to the experiment and testing of VeRi776 and VehicleID, two mainstream public data sets in this field, the rank-k and mAP indexes obtained are both improved, and are suitable for object re-recognition tasks without source data.

Plasminogen (Plg) is the inactive form of plasmin (Plm) that exists in two major glycoforms, referred to as glycoforms I and II (GI and GII). In the circulation, Plg assumes an activation-resistant 'closed' conformation via interdomain interactions and is mediated by the lysine binding site (LBS) on the kringle (KR) domains. These inter-domain interactions can be readily disrupted when Plg binds to lysine/arginine residues on protein targets or free L-lysine and analogues. This causes Plg to convert into an 'open' form which is crucial for activation by host activators. In this study, we investigated how various ligands affect the kinetics of Plg conformational change using small-angle X-ray scattering (SAXS). We began by examining the open and closed conformations of Plg using size-exclusion chromatography (SEC) coupled with SAXS. Next, we developed a high throughput (HTP) 96-well SAXS assay setup. This method enables us to determine the Kopen value, which is used to compare ligands’ effect on Plg conformation directly. Based on our analysis using Plg GII, we have found that the Kopen for ε-aminocaproic acid (EACA) is approximately three times greater than that of Tranexamic acid (TXA), which is widely recognized as a highly effective ligand. We demonstrated further that Plg undergoes a conformational change when it binds to the C-terminal peptides of the inhibitor α2-antiplasmin and receptor Plg‑RKT. Our findings suggest that, besides the C-terminal lysine, internal lysine(s) are also necessary for the formation of open Plg. Finally, we compared the conformational changes of Plg GI and GII directly and found that the closed form of GI, which has an N-linked glycosylation, is less stable. To summarize, we have successfully determined the response of Plg to various ligand/receptor peptides by directly measuring the kinetics of its conformational changes.

A reduced ability to work with information contained in a text is usually registered in low-achieving students. One important internal factor influencing reading comprehension concerns the child’s executive functioning. The current study investigated whether the domain-specific intervention ExeFun-READ targeting language abilities related to reading comprehension and executive functioning in primary school children would be effective in improving their scholastic performance in their reading domain and executive functioning. ExeFun-READ is designed to address the relations between domain-specific versus thinking-skill-oriented (domain-general) instruction. A child’s active learning is focused on semantic, phonetic, morphological and syntactical comprehension of linguistic material. In total, 151 students attending grade four from seven elementary schools took part in the project. The study concerned a pretest-intervention-posttest experimental design with three conditions: the experimental condition, an active, and a passive control group. To assess the children’s level of EF, the Delis–Kaplan Executive Function System test battery was used; to assess children’s language ability in reading domain, the Cognitive Abilities Test (the verbal battery, Thorndike &amp; Hagan, 1986 [1]), was used. In the current study, the intervention led to improved language abilities related to reading comprehension, but in terms of executive functioning the improvement only extended to switching fluency. Regarding the effects of the ExeFun-READ intervention on children’s reading abilities, specified as language abilities related to reading comprehension, significant improvements were found in vocabulary, completion of sentences, and classification of terms in the group of children that received the ExeFun-READ intervention.

Open domain question answering (OpenQA) tasks have been recently attracting more and more attention from the natural language processing (NLP) community. In this work, we present the first free-form multiple-choice OpenQA dataset for solving medical problems, MedQA, collected from the professional medical board exams. It covers three languages: English, simplified Chinese, and traditional Chinese, and contains 12,723, 34,251, and 14,123 questions for the three languages, respectively. We implement both rule-based and popular neural methods by sequentially combining a document retriever and a machine comprehension model. Through experiments, we find that even the current best method can only achieve 36.7%, 42.0%, and 70.1% of test accuracy on the English, traditional Chinese, and simplified Chinese questions, respectively. We expect MedQA to present great challenges to existing OpenQA systems and hope that it can serve as a platform to promote much stronger OpenQA models from the NLP community in the future.

A SARS-CoV receptor-binding domain (RBD) recombinant protein was developed and manufactured under current good manufacturing practices in 2016. The protein known as RBD219-N1 when formulated on Alhydrogel®, induced high-level neutralizing antibodies and protective immunity with minimal immunopathology in mice after a homologous virus challenge with SARS-CoV (MA15 strain). In this report, we examined published evidence in support of whether the SARS-CoV RBD219-N1 could be repurposed as a heterologous vaccine against Coronavirus Infectious Disease (COVID)-19. Our findings include evidence that convalescent serum from SARS-CoV patients can neutralize SARS-CoV-2. Additionally, a review of published studies using monoclonal antibodies (mAbs) raised against SARS-CoV RBD and that neutralize the SARS-CoV virus in vitro, finds that some of these mAbs bind to the receptor-binding motif (RBM) within the RBD, while others bind to domains outside this region within RBD. This information is relevant and supports the possibility of developing a heterologous SARS-CoV RBD vaccine against COVID-19, especially due to the finding that the overall high amino acid similarity (82%) between SARS-CoV and SARS-CoV-2 spike and RBD domains is not reflected in RBM region (59%). However, the high similarity (94%) in the region outside of RBM offers the potential of conserved neutralizing epitopes between both viruses.

ABC-OCT, Affordable B-scan Camera-based Optical Coherence Tomography, implements Fourier-Domain Optical Coherence Tomography with real-time display using cross-platform C++ and the OpenCV framework. The software can be compiled using current versions of GCC for *nix/Mac and Microsoft^® Visual Studio for Windows. Full functionality of ABC-OCT needs the camera SDK from QHYCCD and a QHYCCD camera to be connected; but the code can be easily modified to support other camera drivers, as is shown by an included demo version which can use any installed webcam. The code is made available under the MIT license. The software is available from GitHub (https://github.com/hn-88/FDOCT).

Accurately predicting electrical signals of three-phase Direct Torque Control (DTC) induction motors is crucial for optimal motor performance and effective condition monitoring. However, multiple DTC motors’ complexity and operating conditions’ variations pose challenges for traditional prediction methods. To overcome these challenges, we propose an innovative approach that combines Fast Fourier Transform (FFT) to transform electrical motor simulation data and a Bi-directional Long Short-Term Memory (Bi-LSTM) network to forecast processed motor data. By transforming the DTC induction motor signals from the time domain to the frequency domain, we enhance the capability of learning models to capture subtle differences and generate various input features. The Bi-LSTM model effectively captures both forward and backward dependencies in time series data, enabling accurate prediction of electrical signals. We evaluate the proposed approach using our simulated dataset and compare the proposed method to a state-of-the-art model, the Gated Recurrent Unit (GRU), demonstrating its effectiveness in improving the accuracy and reliability of induction motor signals forecasting. The finding provides valuable insights for advancing motor control and operation in industrial applications.

Today, the most powerful approach to detect distant homologs of a protein is based on structure prediction and comparison. Yet this approach is still inapplicable to many viral proteins. Therefore, we developed a powerful sequence-based procedure to identify distant homologs of viral proteins. It relies on 3 main principles: 1) Traces of sequence similarity with a protein can persist beyond the significance cutoff of homology detection programs; 2) Candidate homologs can be identified among proteins with weak sequence similarity to the query, by using "contextual" information, e.g. taxonomy or type of host infected; 3) These candidate homologs can be validated using highly sensitive profile-profile comparison.As a test case, we applied our approach to a protein without known homologs, ORF4 of Lake Sinai virus (which infects bees). We discovered that ORF4 is composed of a domain that has homologs in proteins from >20 taxa of viruses infecting arthropods. We called it “Widespread, Intriguing, Versatile” (WIV) domain because it is found in proteins with a wide variety of domain organizations and functions. For example, WIV is encoded by the NSs protein of tospoviruses, a global threat to food security, which infect plants through arthropod vectors; by the protein encoded by RNA2 ORF1 of chronic bee paralysis virus, a widespread virus of bees; and by various proteins of cypoviruses, which infect the silkworm bombyx mori. WIV has a previously unknown structural fold, according to Alphafold predictions. In some viral species, WIV facilitates infection of arthropods, according to bibliographical evidence

The World Health Organization has developed the Integrated Care of Older People (ICOPE) strategy, a program based on the measurement of intrinsic capacity (IC) as “the composite of all physical and mental attributes on which an individual can draw”. Multicomponent interventions appear to be the more effective approach to enhance IC and to prevent frailty and dependence, being adapted physical activity is the preventive intervention that has shown more evidence in the treatment of frailty and risk of falls. The present study aims to describe the development of a multi-domain group-based intervention addressed to frail older people living in the community aimed to improve and/or maintain intrinsic capacity by means of promoting physical activity, healthy nutrition, and psychological wellbeing in frail older people. We used the GUIDED checklist to describe the development process of AMICOPE (Aptitude Multi-domain group-based intervention to improve and/or maintain IC in frail Older PEople). The intervention was built upon the ICOPE framework and it is described with Template for Intervention Description and Replication (TIDieR) guidelines and it includes dietary advice, cognitive stimulation strategies, medication review, goal setting, and activities to strengthen social support and manage depressive symptoms, as well as strength, balance and flexibility exercise using the Vivifrail program. The study represents the first stage of the UK Medical Research Council framework for developing and evaluating a complex intervention. The next step should be carrying out a feasibility study for the AMICOPE intervention, and in a later stage, assessing the effectiveness in a randomized controlled trial.

We address weighted composition operators ψCφ from α-Bloch spaces to Bers-type spaces of bounded holomorphic functions on Y, where Y is a generalized Hua domain of the first kind, and obtain some necessary and sufficient conditions for the boundedness and compactness of those operators.

The aim of this paper is to investigate whether multifractal analysis can be applied to study choroidal blood vessels and help ophthalmologists for the early diagnosis of retinitis pigmentosa (RP). In a case study, we use Spectral Domain Optical Coherence Tomography (SDOCT), which is a non-invasive and highly sensitive imaging technique of the retina and choroid. The image of a choroidal branching pattern can be regarded as a multifractal. Therefore, we calculate generalized Renyi point-centered dimensions, which is considered a measure of inhomogeneity of data, to prove that it increases in the patients with RP with respect to the control group.

The receptor-type protein tyrosine phosphatases (RPTPs) are involved in a wide variety of physiological functions which are mediated via their diverse extracellular regions. They play key roles in cell-cell contacts, bind various ligands and are regulated by dimerization and other processes. Depending on the subgroup they have been described as everything from ‘rigid rods’ to ‘floppy tentacles’. Here we review current experimental structural knowledge on the extracellular region of RPTPs and draw on AlphaFold structural predictions to provide further insights into structure and function of these cellular signalling molecules.

A systematic and comprehensive review of critical applications of Blockchain Technol-ogy with Differential Privacy integration lies within the privacy and security enhancement. This paper aims to highlight the research issues in the e-health domain (e.g., Electronic Medical Rec-ords) and to review the current research directions in Differential Privacy integration with Blockchain Technology.(1) Background: The current state of the art in the e-health domain is identified as follows: (a) healthcare information poses a high level of security and privacy concerns due to its sensitivity; (b) due to vulnerabilities surrounding the healthcare system, a data breach is common and presents a risk for attacks by an adversary; and (c) the current privacy and security apparatus needs further fortification. (2) Methods: The methodology uses a systematic literature review (SLR) to identify and select relevant research papers and academic journals in DP and BT. (3) Results: The results are categorized into: e-Health Record Privacy, Real-Time Health Data, and Health Survey Data Protection to identify inherent issues with Differential Privacy integra-tion with Blockchain and technical challenges.(4) Conclusion: This review thoroughly surveyed and summarized Differential Privacy mechanisms in EMR privacy, real-time health data, and health survey data protection while highlighting challenges.

Detecting, especially locating local degradations at an incipient stage, is very important for mission-critical high voltage rotating machines. One particular challenge of the existing testing techniques is that the characteristic of a local incipient defect is not prominent due to various factors such as averaging with the healthy remainder, attenuation in signal propagation, interference, and varied operating conditions. This paper proposes and investigates the frequency domain reflectometry (FDR) technique based on scattering parameter measurement. The FDR result presents the object length, wave impedance, and reflections due to impedance discontinuity along the measured windings. Experiments were performed on two commercial coils with artificially made defects. These defects include turn-to-turn short, surface creepage, loose coils, and local overheating, which are commonly seen in practice. Two practical water pumps in the field were also selected for investigation. The study outcome shows that the FDR can identify and locate both structure and insulation degradations of both shielded and unshielded objects with good sensitivity. This makes the FDR a comprehensive tool for fault diagnosis and aging assessment.

A microwave-photonics method has been developed for measuring distributed acoustic signals. This method uses microwave-modulated low coherence light as a probe to interrogate distributed in-fiber interferometers, which are used to measure acoustic-induced strain. By sweeping the microwave frequency at a constant rate, the acoustic signals are encoded into the complex microwave spectrum. The microwave spectrum is transformed into the joint time-frequency domain and further processed to obtain the distributed acoustic signals. The method is first evaluated using an intrinsic Fabry Perot interferometer (IFPI). Acoustic signals of frequency up to 15.6 kHz were detected. The method was further demonstrated using an array of in-fiber weak reflectors and an external Michelson interferometer. Two piezo-ceramic cylinders (PCCs) driven at frequencies of 1700 Hz and 3430 Hz were used as acoustic sources. The experiment results show that the sensing system can locate multiple acoustic sources. The system resolves 20 nε when the spatial resolution is 5 cm. The recovered acoustic signals match the excitation signals in frequency, amplitude, and phase, indicating an excellent potential for distributed acoustic sensing (DAS).

Study of RNA-protein interactions and identification of RNA targets are among the key aspects of understanding the RNA biology. Currently, various methods are available to investigate these interactions, in particular, RNA pulldown assay. In the present paper, a method based on the HaloTag technology is presented that is called Halo-RPD (HaloTag RNA PullDown). The proposed protocol uses plants with stable fusion protein expression and the MagneBeads magnetic beads to capture RNA-protein complexes directly from the cytoplasmic lysate of transgenic A. thaliana plants. The key stages described in the paper are as follows: 1) preparation of the magnetic beads 2) tissue homogenization and collection of control samples 3) precipitation and wash of RNA-protein complexes; 4) evaluation of protein binding efficacy; 5) RNA isolation; 6) analysis of the obtained RNA. Recommendations for better NGS assay designs are provided.

Cryonotothenioidea is the main group of fishes that thrive in the extremely cold Antarctic environment, thanks to the acquisition of peculiar morphological, physiological and molecular adaptations. We have previously disclosed that IgM, the main immunoglobulin isotype in teleosts, display typical cold-adapted features. Recently, we have analyzed the gene encoding the heavy chain constant region (CH) of the IgT isotype from the Antarctic teleost Trematomus bernacchii (family Nototheniidae), characterized by the near-complete deletion of the CH2 domain. Here, we aimed to track the loss of the CH2 domain along notothenioid phylogeny and to identify its ancestral origins. To this end, we obtained the IgT gene sequences from several species belonging to the Antarctic families Nototheniidae, Bathydraconidae and Artedidraconidae. All species display a CH2 remnant of variable size, encoded by a short Cτ2 exon, which retains functional splicing sites and therefore is included in the mature transcript. We also considered representative species from the three non-Antarctic families: Eleginopsioidea (Eleginops maclovinus), Pseudaphritioidea (Pseudaphritis urvillii) and Bovichtidae (Bovichtus diacanthus and Cottoperca gobio). Even though only E. maclovinus, the sister taxa of Cryonotothenioidea, shared the partial loss of Cτ2, the other non-Antarctic notothenioid species displayed early molecular signatures of this event. These results shed light on the evolutionary path that underlies the origins of this remarkable gene structural modification.

In E. coli DNA replication forks stall on average once per cell cycle. When this occurs, replisome components disengage from the DNA, exposing an intact, or nearly intact fork. Consequently, the fork structure must be regressed away from the initial impediment so repair can occur. Regression is catalyzed by the powerful, monomeric DNA helicase, RecG. During this reaction, the enzyme couples unwinding of fork arms to rewinding of duplex DNA resulting in the formation of a Holliday junction. RecG works against large opposing forces enabling it to clear the fork of bound proteins. Following subsequent processing of the extruded junction, the PriA helicase mediates reloading of the replicative helicase DnaB leading to the resumption of DNA replication. The single-strand binding protein (SSB) plays a key role in mediating PriA and RecG functions at forks. It binds to each enzyme via linker/OB-fold interactions and controls fork loading sites in a substrate-dependent manner that involves helicase remodeling. Finally, it is displaced by RecG during fork regression. The intimate and dynamic SSB-helicase interactions play key roles in ensuring fork regression and DNA replication restart.

Zika virus (ZIKV) infection and pathogenesis are linked to the disruption of neurogenesis, congenital Zika syndrome and microcephaly by affecting neural progenitor cells. Nonstructural protein 5 (NS5) is the largest product encoded by ZIKV-RNA and is important for replication and immune evasion. Here, we studied the potential effects of NS5 on microtubules (MTs) and autophagy flux, together with the interplay of NS5 with histone deacetylase 6 (HDAC6). Fluorescence microscopy, biochemical cell-fractionation combined with the use of HDAC6 mutants, chemical inhibitors and RNA interference indicated that NS5 accumulates in nuclear structures and strongly promotes the acetylation of MTs that aberrantly reorganize in nested-like structures. Similarly, NS5 accumulates the p62 protein, an autophagic-flux marker. Therefore, NS5 alters events that are under the control of the autophagic tubulin-deacetylase HDAC6. HDAC6 appears to degrade NS5 by autophagy in a deacetylase- and BUZ domain-dependent manner and to control the cytoplasmic expression of NS5. Moreover, NS5 inhibits RNA-mediated RIG-I interferon (IFN) production, resulting in greater activity when autophagy is inhibited (i.e., effect correlated with NS5 stability). Therefore, it is conceivable that NS5 contributes to cell toxicity and pathogenesis, evading the IFN-immune response by overcoming HDAC6 functions. HDAC6 has emerged as an anti-ZIKV factor by targeting NS5.

We evaluated the closure of idiopathic full-thickness macular holes (MHs) the day after surgery in minimizing the burden and maximizing patient outcomes. Herein, 25-gauge pars plana vitrectomy, internal limiting membrane peeling, and fluid-gas (20% sulfur hexafluoride) were performed for the treatment. Patients were instructed to remain in the facedown position until the confirmation of MH closure, and the position was discontinued in cases where the closure was confirmed. In total, 43 eyes of 43 patients, whose average age was 69.7±8.6 years, were enrolled in this study. We used swept-source (SS)-optical coherence tomography (OCT) for the confirmation of MH closure for gas-filled eyes and used spectral domain (SD)-OCT for the reconfirmation of MH closure after the gas volume was reduced to less than half of the vitreous cavity. MH closure was confirmed in 40 eyes (93%, the closure group) on the next day after surgery. The time from surgery to SS-OCT imaging was 24.7 hours. Although facedown positioning was terminated in cases where MH closure was confirmed, there were no cases in which the MH was re-opened afterward. The basal and minimum MH size was significantly larger in the non-closure group than that in the closure group (p = 0.027, p = 0.043, respectively). Therefore, checking with SS-OCT the day after surgery and terminating facedown positioning in cases where MH closure was confirmed would be a useful method, removing great burden for the elderly without sacrificing the MH closure rate.

The application of the sensors optical fiber in the areas of scientific instrumentation and industrial instrumentation is very attractive due to its numerous advantages. In the industry of civil engineering for example, quasi-distributed sensors made with optical fiber are used for reliable strain and temperature measurements. Here, a quasi-distributed sensor in the frequency domain is discussed. The sensor consists of a series of low-finesse Fabry-Perot interferometers where each Fabry-Perot interferometer acts as a local sensor. Fabry-Perot interferometers are formed by pairs of identical low reflective Bragg gratings imprinted in a single mode fiber. All interferometer sensors have different cavity length, provoking the frequency-domain multiplexing. The optical signal represents the superposition of all interference patterns which can be decomposed using the Fourier transform. The frequency spectrum is analyzed and sensor´s properties were defined. Following, a quasi-distributed sensor was numerically simulated. Our sensor simulation considers sensor properties, signal processing, noise system and instrumentation. The numerical results show the behavior of resolution vs. signal-to-noise ratio. From our results, the Fabry-Perot sensor has high resolution and low resolutions. Both resolutions are conceivable because the FDPA algorithm elaborates two evaluations of Bragg wavelength shift

The ability to predict the skin sensitization potential of small organic molecules is of high importance to the development and safe application of cosmetics, drugs and pesticides. One of the most widely accepted methods for predicting this hazard is the rodent local lymph node assay (LLNA). The goal of this work was to develop in silico models for the prediction of the skin sensitization potential of small molecules that go beyond the state of the art, with larger LLNA data sets and, most importantly, a robust and intuitive definition of the applicability domain, paired with additional indicators of the reliability of predictions. We explored a large variety of molecular descriptors and fingerprints in combination with random forest and support vector machine classifiers. The most suitable models were tested on holdout data, on which they yielded competitive performance (Matthews correlation coefficients up to 0.52; accuracies up to 0.76; areas under the receiver operating characteristic curves up to 0.83). The most favorable models are available via a public web service at https://nerdd.zbh.uni-hamburg.de/skinDoctor/ that, in addition to predictions, provides assessments of the applicability domain and indicators of the reliability of the individual predictions.

The evolutionary transition from single-celled to multicellular individuality requires organismal fitness to shift from the cell-level to the cell group. This reorganization of fitness occurs by allocating the two components of fitness, survival and reproduction, between two specialized cell types in the multicellular group – soma and germ, respectively. How does the genetic basis for such fitness reorganization evolve? One possible mechanism is the co-option of life-history genes present in the unicellular ancestors of a multicellular lineage. Single-celled organisms must regulate their investment in survival and reproduction in response to environmental changes, particularly decreasing reproduction to ensure survival when stressed. Such stress response life-history genes can provide the foundation for the genetic basis for cellular differentiation in multicellular lineages. The regA gene family in volvocine green algae provides a model system to study how this co-option occurs. We discuss the origin and evolution of the volvocine regA gene family, including regA – the gene that controls somatic cell development in the model organism Volvox carteri. We hypothesize that the co-option of life history trade-off genes is a general mechanism involved in the transition to multicellular individuality, making volvocine algae and the regA family a useful template for similar investigations in other lineages.

The lactic acid bacteria (LAB) have great potential to produce homoexopolysaccharides (HoPS), have been the subject of extensive research efforts, given their health benefits and physicochemical properties. The HoPS functional properties are determined by structural characteristics of varied molecular weights, types of glycosidic linkages, degrees of branching and chemical composition. The dextransucrases (DSases) are responsible of the synthesis of a kind of HoPS (dextran polymers), which are among the first biopolymers produced at industrial scale with applications in medicine and biotechnology. The concept of glycodiversification opens additional applications for DSases. In that sense the design and characterization of new DSases is of prime importance. Previously, we described the isolation and characterization of a novel extracellular dextransucrase (DSR-F) encoding gene. In this study, from DSR-F, we design a novel chimeric dextransucrase DSR-F-∆SP-∆GBD-CBM2a, where DSR-F-∆SP-∆GBD is fused to the carbohydrate-binding module (CBM2a) of the β-1-4 exoglucanase/xylanase Cex (Xyn10A) of Cellulomonas fimi ATCC 484. This dextransucrase variant is active and without alteration in its specificity. The DSR-F-∆SP-∆GBD-CBM2a is purified by cellulose affinity chromatography for the very first time. Our results indicate that new hybrids and chimeric DSases with novel binding capacity to cellulose can be designed to obtain glyco-biocatalysts from renewable lignocellulosic materials.

The surface enhanced fluorescence（SEF）detection bases by plasmonic nanopillars array with nanoparticles has opened up a new gate in the application of biological imaging and sensing. The fluorescence enhancement of the probe molecule depends on its position in equilibrium, which is close to the hot spot leading to the electromagnetic field enhancement, but not too close to the metal surface resulting in quenching. Here, a large scale SiO₂-Ag-cicada wing SEF substrate was fabricated by magnetron sputtering with correction enhancement factor of 797.6. Thereinto the cicada wing provides the skeleton of the nanopillars array structure, the deposited Ag constructs two kinds of hot spots, and SiO₂ forms a separation layer to prevent quenching. Moreover, the substrate exhibited good reproducibility, high sensitivity with low limits of detection (LOD) and high stability for oxidation resistance. We propose that SEF substrate with modification of SiO₂ can not only improve the enhancement performance, but also expanding its application in the biological investigations.

Giant plasmonic surface enhancement has been observed in gold coated micron sized inverse pyramids entrapping a gold nanoparticle. The amplification of both surface enhanced Raman and photoluminescence signals was found to be dependent on the diameter of trapped gold nanoparticle and around 50-fold enhancement was detected for 250nm diameter sample relatively to the 50nm one. Finite differential time domain simulations, performed to determine the near-field distribution in the structure, showed that when the nanoparticle protrudes into the hotspot zone of the void, coupling of electromagnetic field occurs and the plasmon-related near-field enhancement is concentrated into the close vicinity of the nanoparticle, mainly into the close gaps around the tangential points of the curved sphere and the flat pyramid surface. This results in a more than 15 times increase of the near-field intensity, compared to the empty void.

Diversity-generating retroelements (DGRs) are prokaryotic systems providing rapid modification and adaptation of target proteins. In phages, the main targets of DGRs are receptor-binding proteins that are usually parts of tail structures and the variability of such host-recognizing structures enables phage adaptation to changes on the bacterial host surface. Sometimes, more than one target gene containing a hypermutated variable repeat (VR) can be found in phage DGRs. The role of mutagenesis of two functionally different genes is unclear. In this study, several phage genomes that contain DGRs with two target genes were found in the gut virome of healthy volunteer. Bioinformatics analysis of these genes indicated that they encode proteins with different topology; however, both proteins contain the C-type lectin (C-lec) domain with a hypermutated beta-hairpin on its surface. One of the target proteins belongs to a new family of proteins with a specific topology: N-terminal C-lec domain followed by one or more immunoglobulin domains. Proteins from the new family were named tentaclins after TENTACLe+proteIN. The genes encoding such proteins were found in the genomes of prophages and phages from the gut metagenomes. We hypothesized that tentaclins are involved in binding either to bacterial receptors or intestinal/immune cells.

Intrinsic disorder accounts for the flexibility of protein loops, molecular building blocks that are largely responsible for the processes and molecular functions of the living world. While loops likely represent early structural forms that served as intermediates in the emergence of protein structural domains, their origin and evolution remains poorly understood. Here, we conduct a phylogenomic survey of disorder in loop prototypes sourced from the ArchDB classification. Tracing prototypes associated with protein fold families along an evolutionary chronology revealed ancient prototypes tended to be more disordered than their derived counterparts, with ordered prototypes developing later in evolution. This highlights the central evolutionary role of disorder and flexibility. While mean disorder increased with time, a minority of ordered prototypes exist that emerged early in evolutionary history, possibly driven by the need to preserve specific molecular functions. We also revealed percolation of evolutionary constraints from higher to lower levels of organization. Percolation resulted in trade-offs between flexibility and rigidity that impacted prototype structure and geometry. Our findings provide a deep evolutionary view of the link between structure, disorder, flexibility and function, as well as insights into the evolutionary role of intrinsic disorder in loops and their contribution to protein structure and function.

The Apetala2/ethylene response factor superfamily refers to a group of transcription factors that share a conserved AP2 DNA binding domain. These factors have been found to have different roles in plant responses to both biotic and abiotic stresses. Samples of hexaploid wheat, tetraploid pasta (or durum wheat), and diploid wheat progenitors were selected. The 29 dehydration-responsive element binding transcription factors in these samples were downloaded from NCBI GenBank for six different countries: Iran, China, Italy, France, Afghanistan, and Azerbaijan. The AP2 domain sequences were identified from the dehydration-responsive element binding transcription factors using PROSITE, ProDom, and SMART software. Next, all sequences were aligned using Multalin and Jalview software. The aligned sequences were then analyzed to identify amino acid locations, types, and frequencies. The multiple alignments showed that approximately 76% of the amino acid residues in the AP2 domains are conserved. According to the amino acid analysis, alanine, serine, and glutamic acid are the most abundant amino acids found in three motifs. The performed phylogenetic analysis illustrates the role of geographical effects on the transcription factor sequences of bread wheat in the Middle East. Significant differences were found between Iranian and Chinese transcription factor sequences. Moreover, genetic variation was observed in the transcription factors of Italian sequences found in pasta and wheat progenitors. Motif structures play a critical role in the domain organization of wheat proteins to enhance the characteristics of assorted metabolic pathways. The structure of the AP2 domain was analyzed by several programs, I-TASSER for instance, to identify the α-helix, β-sheets, and the regions of some significant amino acids in the 3-D model.

Since the detection of the first COVID-19 patient, 2 years have passed, during which more than 287,862,000 people fell ill globally, of which about 1.9% died. Implementation of SARS-CoV-2 control programs required efforts from almost all countries. An important direction in the fight against COVID-19 was the formation of herd immunity, the main tool for managing the pandemic. Study goal: to assess the seroprevalence of antibodies (Abs) to SARS-CoV-2 nucleocapsid (Nc) and receptor binding domain (RBD) in the St. Petersburg population during the COVID-19 pandemic. Materials and methods. A longitudinal cohort randomized monitoring study of Ab seroprevalence (SARS-CoV-2 Nc, RBD) was organized and conducted according to a unified methodology developed by Rospotrebnadzor with the participation of the St. Petersburg Pasteur Institute. For this purpose, a cohort of 1000 volunteers was formed who participated in all five stages of seromonitoring. The cohort was divided into 7 age groups: 1-17; 18-29; 30-39; 40-49; 50-59; 60-69; 70; and older (70+) years. Seropositivity levels (Nc, RBD) were assessed by quantitative and qualitative enzyme immunoassays. During the 2nd year of monitoring, some volunteers were vaccinated with the GamCOVIDVac (84%) or EpiVacCorona (11.6%) vaccines approved in Russia. Statistical processing was carried out using the Excel 2010 software package. Confidence intervals for shares and percentages (95% CI) were calculated using the method of A. Wald and J. Wolfowitz with adjustment (A. Agresti, B.A. Coull). The statistical significance of differences was calculated by z-test, using the appropriate online calculator (p<0.05), unless indicated. Results. There was a trend towards: an increase in Nc seropositivity in stages 1-3 of seromonitoring, with a decrease in stages 4-5 among children and adults. The share of RBD seropositive steadily increased during all 5 stages of seromonitoring. The most frequently found were low anti-RBD Abs levels (22.6-220 BAU/ml). High Ab levels were recorded statistically significantly less frequently. Asymptomatic forms were observed in 84-88% of SARS-CoV-2 seropositive volunteers. By the 5th stage of monitoring, this indicator significantly decreased to 69.8% (95% CI: 66.1-73.4). The monitoring revealed a statistically significant increase in anti-RBD Abs, alongside a statistically significant decrease in the proportion of Nc seropositive. This dynamic was especially characteristic of persons vaccinated with GamCOVIDVac. Conclusion. Prior to the use of specific vaccines, a seroprevalence of anti-Nc Abs was noted. After the introduction of the GamCOVIDVac vaccine in adults, a decrease in the level of anti-Nc Abs was noted due to an increase in the proportion of RBD seropositive persons.

Long-span steel structure trusses are widely used in factory buildings, but with the growth of service time and the increase of dynamic load fatigue, a considerable part of the long-span truss with dynamic load appears serious transverse cracks at the bottom of the middle span and oblique deformation of the abdomen in the operation process. The U-shaped cracks at the bottom and belly, as well as the mid-span down deflection of the main truss, reduced the functional function of the factory building truss structure, and had to limit the original crane load, which affected the normal safety and durability of the structure. Therefore, the application principle of the variable axial force cable system in the long-span factory building truss structure and 3D3S software modeling [1] were used. Analyzing and studying the reinforcement method of large-span powerhouse truss can provide practical experience for subsequent similar projects. In view of the above phenomenon, the large-span powerhouse trusses of Hongcheng Powerhouse 1 and No.2 located in Tonglu, Zhejiang Province are used as the research object, and the variable axial force cable method is proposed to strengthen and lift the load. Considering the span of large-span powerhouse truss, the cable system with 22m controlling force of 400kN is proposed to be selected for powerhouse 1, and the cable system with variable axial force of 24m is proposed to be selected for Powerhouse 2. The force model of large-span truss is established by using the finite element method commonly used to analyze the force of truss. Under two working conditions, The influence of reinforcement effect is analyzed and compared from three aspects: stiffness, bearing capacity and stability. And the phenomenon of uneven stress distribution is analyzed. The stress distribution characteristics of each node are understood by simulating the most disadvantageous node plates with the greatest internal force before and after reinforcement.

Group-B enteroviruses (EV-B) are ubiquitous naked single-stranded positive RNA viral pathogens that are responsible for common acute or persistent human infections. Their genome is composed in the 5'end by a non-coding region, which is crucial for the initiation of the viral replication and translation processes. RNA domain-I secondary structures can interact with viral or cellular proteins to form viral ribonucleoprotein (RNP) complexes regulating viral genomic replication, whereas RNA domains-II to -VII (IRES) are known to interact with cellular ribosomal subunits to initiate the viral translation process. Natural 5’ terminally deleted viral forms lacking some genomic RNA domain-I secondary structures have been described in EV-B induced murine or human infections. Recent in vitro studies have evidenced that the loss of some viral RNP complexes in the RNA domain-I can modulate the viral replication and infectivity levels in EV-B infections. Moreover, the disruption of secondary structures of RNA domain-I could impair viral RNA sensing by RIG-I or MDA5 receptors, a way to overcome antiviral innate immune response. Overall, natural 5′ terminally deleted viral genomes resulting in the loss of various structures in the RNA domain-I could be major key players of host-cell interactions driving the development of acute or persistent EV-B infections.

The development of mineral resources in China has gradually entered the stage of deep mining. Rock burst, collapse and other ground pressure disasters caused by deep high stress have become major hidden dangers restricting mine safety production. Microseismic monitoring technology is an important means of ground pressure risk prediction. In this paper, the wavelet coefficient threshold denoising method in time-frequency domain, STA/LTA method, AIC method, Skew and Kurtosis method are studied, and the automatic P-phase onset time picking model based on noise reduction and multiple detection indexes is established. Through the effect analysis of microseismic signals collected by microseismic monitoring system of coral Tungsten Mine in Guangxi, automatic P-phase onset time picking is realized. the reliability of the P-phase onset time picking method proposed in this paper based on noise reduction and multiple detection indexes is verified. The picking accuracy can still be guaranteed under the severe signal interference of background noise, power frequency interference and manual activity underground mine, Which is of great significance to the data processing and analysis of microseismic monitoring.

(1) Background: Adolescent well-being is a multifaceted construct embedded in family, school, and peer socialization contexts. By adopting a social-psychological perspective we test the association between three sources of support (parents, teachers, peers) and specific components of subjective well-being (cognitive, affective, global-and-domain-specific) to determine whether there is a functional specialization of the role that these crucial socialization agents play for adolescents to attain well-being in specific life domains. (2) Methods: Cross-sectional Albanian data from Wave 3 of the Children’s Worlds International Survey (www.isciweb.org) were used, including 2,339 adolescents (age range 9-13; girls = 49.3%). A structural equation model (SEM) was employed to explore associations between supportive relationships with parents, teachers, and peers and adolescent well-being. (3) Results: Findings support a functional specialization hypothesis as parental support was significantly related to global cognitive and affective well-being; teacher support was significantly related with school satisfaction; and significant relations were found between peer support and almost all well-being variables (context-free, domain-based life satisfaction and affective subjective well-being). (4) Conclusions: Findings contribute to a more nuanced understanding of the role of supportive relationships with adults and peers in adolescents’ proximal socialization contexts (family, school, peer groups) and specific components of subjective well-being.

Quantum cryptography revolutionizes secure information transfer, providing defense against both quantum and classical computational attacks. The primary challenge in extending the reach of quantum communication comes from the exponential decay of signals over long distances. Addressing this challenge, we have developed Quantum-protected Control-based Key Distribution (QCKD), overcoming transmission range limitations by monitoring signal leakages and rendering leaked quantum states significantly non-orthogonal. This paper reports on the experiments with the QCKD, conducted over a 1,707 km fiber line. We demonstrate advancements in critical components of the protocol, showing its remarkable scalability and adaptability for extended distances and multi-user configurations.

Through the use of Smart Sensor Networks (SSN), Marine Observatories (MO) provide continuous ocean monitoring. Deployed sensors may not perform as intended due to the heterogeneity of SSN devices’ hardware and software when combined with the Internet. Hence, SSN are regarded as complex distributed systems. As such, SSN designers will encounter challenges throughout the design phase related to time, complexity, sharing diverse domain experiences (viewpoints), and ensuring optimal performance for the deployed SSN. To this end, we describe in this article how we extended our previously proposed ArchiMO meta-model and design tool by extending an Enterprise Architecture Framework based on the ArchiMate Modeling Language. This extension proposes the incorporation of new Underwater Environmental Constraints (UEC) for SSN in ArchiMO which is coupled with the fusion of sensors with Artificial Intelligence. This serves as the basis for generating a new version of our ArchiMO design tool, which incorporates the new added constraints and invokes the AI created Database. To illustrate our proposal, we use the newly generated ArchiMO to create a model in the MO domain. Furthermore, we use our self-developed domain-specific model compiler to produce the relevant simulation code. Throughout the design phase, our approach contributes to handle and control the uncertainties and variances of the provided quality of service that may occur during the performance of the SSN, hence reducing the design activity’s complexity and time. It provides a way to share the different viewpoints of the designers in the domain of SSN.

Abstract: The worldwide spread of SARS-CoV-2 has led to a significant economic and social burden on a global scale. Even though the pandemic has concluded, there remains apprehension regarding the emergence of highly transmissible variants capable of evading immunity induced by either vaccination or prior infection. The success of viral penetration is the specific amino acid residues of the Receptor Binding Motif (RBM) involved in viral attachment. This region interacts with the cellular receptor ACE2, triggering a neutralizing antibody (nAb) response. In this study, we have evaluated the immunogenicity of serum from individuals who received either a single dose or a combination of different vaccines against the original SARS-CoV-2 strain and mutated linear RBM. Despite a modest antibody response to the wild-type SARS-CoV-2 RBM, the Omicron variants exhibit four mutations in the RBM (S477N, T478K, E484A, F486V) that result in even lower antibody titers. The primary immune responses observed were directed towards IgA and IgG. While nAbs typically target the RBD, our investigation has unveiled a reduced seroreactivity within the RBD's crucial subregion, the RBM. This deficiency may have implications for the generation of protective nAbs. Evaluation of S1WT and S2WT RBM peptides binding to nAbs using microscale thermophoresis revealed a higher affinity (35 nM) for the S2WT sequence (GSTPCNGVEGFNCYF), which includes the FNCY patch. Our findings suggest that the linear RBM of SARS-CoV-2 is not an immunodominant region in vaccinated individuals. Comprehending the intricate dynamics of the humoral response, its interplay with viral evolution, and host genetics is crucial for formulating effective vaccination strategies, not only targeting SARS-CoV-2 but also anticipating potential future coronaviruses.

Global economic and social burden was caused by the SARS-CoV-2 spread worldwide. Despite the end of the pandemic, there is a concern about virulent evolving variants of the virus which can bypass the humoral immune response induced by vaccination or infection. Crucial to the viral entrance, amino acid residues in the RBM region, which interacts with cellular receptor ACE2, can elicit neutralizing antibody response. Herein we determine the immunogenicity of one-dose or heterologous dose vaccinated serum against wild-type and mutated RBM region. Despite low antibody response to wild-type SARS-CoV-2 RBM, omicron variants possess four mutations in RBM (S477N, T478K, E484A, F486V) that induce even less antibody titers. The most predominant responses were against IgA and IgG. While neutralizing antibodies (nAbs) predominantly target the RBD, our investigation revealed a diminished seroreactivity within the RBD's crucial region, the receptor-binding motif (RBM), potentially impacting the production of protective nAbs. S1WT and S2WT RBM peptides binding to nAbs were evaluated through microscale thermophoresis, and higher affinity (35 nM) was obtained for sequence S2WT (GSTPCNGVEGFNCYF), containing the FNCY patch. Our data indicates that SARS-CoV-2 RBM is not an immunodominant region in vaccinated individuals. Understanding the intricate dynamics of the humoral response and its interplay with viral evolution and host genetics is essential for the formulation of effective vaccination strategies, not only against SARS-CoV-2 but also for future emerging coronaviruses.

To map Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV 2) spreading and evaluate immune responses variations against this virus, it was essential to locally set up efficient serological tests. The SARS-CoV2 immunogenic proteins were very expensive and not affordable mainly for Low and Middle Income Countries (LMICs). For this purpose, the commonly used antigen, Re-ceptor-Binding Domain (RBD) of Spike S1 protein (S1RBD), was produced using the the Baculovirus Expression Vector System (BEVS) . During the current study, the expression of S1RBD was monitored using western blot under different culture conditions. Different parameters were studied: Multiplicity Of Infection (MOI), cell density at infection and harvest time. Hence, optimal conditions for efficient S1RBD production were identified: MOI 3; cell density at infection 2-3x 106 cells/mL and time post-infection (tpi or harvest time) of 72h and 72-96 h successively for expression in shake-flasks and 7L-bioreactor. A high production yield of S1RBD varying between 4mg and 70 mg per liter of crude cell culture supernatant was achieved, respectively, in shake-flasks and in 7L-bioreactor. Moreover, the produced S1RBD showed an excellent antigenicity potential against COVID-19 patient sera evaluated by western blot. Thus, additional serological assays, such as ELISA, were developed using the purified S1RDB (published by other research groups).

Modeling fluid flow in three-dimensional (3D) Discrete Fracture Networks (DFNs) is of relevance in many engineering applications, such as hydraulic fracturing, oil/gas production, geothermal energy extraction, nuclear waste disposal and CO₂ sequestration. A new Boundary Element Method (BEM) technique with discontinuous quadratic elements and a parallel Domain Decomposition Method (DDM) is presented herein for the simulation of the steady-state fluid flow in 3D DFN systems with wellbores, consisting of planar fractures having arbitrary properties and wellbore trajectories. Numerical examples characterized by DFNs of increasing complexity are investigated to evaluate the accuracy and efficiency of the presented technique. The results show that accurate solutions can be obtained with less nodes than with mesh-based methods (e.g. Finite Element Method). In addition, the DDM algorithm used provides a quite fast convergence. The simulation results of the fluid flow around intersections among traces (linear intersections between fractures), intersections between traces and a fracture boundaries, and wellbore intersections is accurate. Source code is available at : https://github.com/BinWang0213/PyDFN3D.

Controlling functional properties of matter and combine them for engineering a functional device is nowadays a common direction of scientific community. For instance, heterogeneous magnetic nanostructures can make use of different types of geometrical and compositional modulations to achieve the control of the magnetization reversal along with the nano-entities and thus enabling the fabrication of spintronic, magnetic data storage and sensing devices, among others. In this work, diameter modulated FeNi nanowires are fabricated paying special effort to obtain sharp transition regions between two segments of different diameters (from about 450 nm to 120 nm), enabling precise control over the magnetic behavior of the sample. Micromagnetic simulations performed on single bi-segmented nanowires predict a double step magnetization reversal where the wide segment magnetization switches near 200 Oe through a vortex domain wall, while at 500 Oe the magnetization of the narrow one is reversed through a corkscrew like mechanism. Finally, these results are confirmed with magneto-optic Kerr effect measurements at the transition of isolated bi-segmented nanowires. Furthermore, macroscopic vibrating sample magnetometry is used to demonstrate that the magnetic decoupling of nanowire segments is the main phenomenon occurring over the entire fabricated nanowires.

Beginning in 2012, our understanding of human papillomavirus (HPV) subcellular trafficking has undergone a drastic paradigm shift. Work from multiple laboratories has revealed that HPV has evolved a unique means to deliver its viral genome (vDNA) to the cell nucleus, relying on a myriad of host cell proteins and processes. The major breakthrough finding from these recent endeavors was the realization of L2-dependent utilization of cellular sorting factors for the retrograde transport of vDNA away from degradative endo/lysosomal compartments to the Golgi, prior to mitosis-dependent nuclear accumulation of L2/vDNA. An overview of current models of HPV entry, subcellular trafficking, and the role of L2 during initial infection is provided below, highlighting unresolved questions and gaps in knowledge.

The stele concept is one of the oldest enduring concepts in plant biology. This paper reviews the concept and its foundations, and builds an argument for an updated view of steles and their evolution. The history of studies of stelar organization has generated a widely ranging array of definitions of the stele that determine the way we classify steles and construct scenarios about the evolution of stelar architecture. Because at the level of the organism biological evolution proceeds by, and is reflected in, changes in development, concepts of structure need to be grounded in development in order to be relevant in an evolutionary perspective. For the stele, most of the traditional definitions that incorporate development have viewed it as the totality of tissues that either originate from procambium – currently the prevailing view – or are bordered by a boundary layer (e.g., endodermis). A definition of the stele that would bring consensus between these perspectives recasts the stele as a structural entity of dual nature. Here, I review briefly the history of the stele concept, basic terminology related to stelar organization, and traditional classifications of the steles. I then revisit boundary layers from the perspective of histogenesis as a dynamic mosaic of developmental domains. I use classic and recent anatomical and molecular data to reaffirm and explore the importance of boundary layers for stelar organization. Drawing on data from comparative anatomy, developmental regulation, and the fossil record, I offer a model for a stele concept that integrates both the boundary layer and the procambial perspective, consistent with a dual nature of the stele. The dual stele model posits that stelar architecture is determined in the apical meristem by two major cell fate specification events: a first one that specifies a provascular domain and its boundaries, and a second event that specifies a procambial domain (which will mature into conducting tissues) from cell subpopulations of the provascular domain. If the position and extent of the developmental domains defined by the two events are determined by different concentrations of the same morphogen (most likely auxin), then the distribution of this organizer factor in the shoot apical meristem, as modulated by changes in axis size and the effect of lateral organs, can explain the different stelar configurations documented among tracheophytes. This model provides a set of working hypotheses that incorporate assumptions and generate implications that can be tested empirically. The model also offers criteria for an updated classification of steles that is in line with current understanding of plant development. In this classification, steles fall into two major categories determined by the configuration of boundary layers – boundary protosteles and boundary siphonosteles, each with subtypes defined by the architecture of the vascular tissues. Validation the dual stele model and, more generally, in-depth understanding of the regulation of stelar architecture, will necessitate targeted efforts in two areas: (i) the regulation of procambium, vascular tissue, and boundary layer specification in all extant vascular plants, considering that most of the diversity in stelar architecture is hosted by seed-free plants, which are the least explored in terms of developmental regulation; (ii) the configuration of vascular tissues and, especially, boundary layers, in as many extinct species and lineages as possible.

The combination of interstitial hyperthermia treatment (IHT) with high dose rate brachytherapy (HDR-BT) for prostate cancer treatment and has the potential to improve clinical outcome, since it highly enhances the efficiency of cell kill, especially when applied simultaneously. Therefore, we have developed the ThermoBrachy applicators. To effectively apply optimal targeted IHT, treatment planning is considered essential. However, treatment planning in IHT is rarely applied since it is regarded difficult to accurately calculate the deposited energy in the tissue in a short enough time for clinical practice. In this study, we investigated various time-efficient methods for fast computation of the electromagnetic (EM) energy deposition resulting from the ThermoBrachy applicators. Initially, we investigated the use of an electro-quasistatic solver. Next, we extended our investigation to the application of geometric simplifications. Furthermore, we investigated the validity of the superpositioning principle, which can enable adaptive treatment plan optimization without the need for continuous recomputation of the EM field. Finally, we evaluated the accuracy of the methods by comparing them to the golden standard Finite-Difference Time-Domain calculation method using gamma-index analysis. The simplifications considerably reduced the computation time needed, improving from &gt;12 h to a few seconds. All investigated methods showed excellent agreement with the golden standard by showing a &gt;99% passing rate with 1%/0.5 mm Dose Difference and Distance-to-Agreement criteria. These results allow the proposed electromagnetic simulation method to be used for fast and accurate adaptive treatment planning.

Identifying anti-spike antibodies that exhibit strong neutralizing activity against current dominant circulating variants and antibodies that are escaped by these variants have important implications in the development of therapeutic and diagnostic solutions as well as in improving understanding of the humoral response to SARS-CoV-2 infection. We characterized seven anti-RBD monoclonal antibodies for their binding activity, pairing capability and neutralization activity to SARS-CoV-2 and three variant RBDs (UK, SA and BR P.1) via lateral flow immunoassays. The results allowed us to group these antibodies into three distinct epitope bins. Our studies showed that two antibodies had broadly potent neutralizing activity against SARS-CoV-2 and these variant RBDs and that one antibody did not neutralize the SA and BR P.1 RBDs. The antibody escaped by the SA and BR P.1 RBDs retained binding activity to SA and BR P.1 RBDs but was unable to induce neutralization. Further, we demonstrated that the lateral flow immunoassay can be a rapid and effective tool for antibody characterization, including epitope classification and antibody neutralization kinetics. From these studies, the potential contributions of the mutations (N501Y, E484K and K417N/T) contained in these variants’ RBDs on antibody pairing capability, neutralization activity and therapeutic antibody targeting strategy are discussed.

Deep learning heavily relies on statistical correlations to drive artificial intelligence (AI) innovations, particularly in computer vision applications like autonomous driving and robotics. However, despite providing a solid foundation for deep learning, these statistical correlations can be vulnerable to unforeseen and uncontrolled factors. The lack of prior knowledge guidance can result in spurious correlations, introducing confounding factors and affecting the model's robustness. To address this challenge, recent research efforts have focused on integrating causal theory into deep learning methodologies. By modelling the inherent and unbiased causal structure, causal theory can potentially mitigate the impact of spurious correlations effectively. Hence, this paper explores the basics of causal methodologies in image classification.

When using computer-aided translation systems in a typical, professional translation workflow, there are several stages at which there is room for improvement. The SCATE (Smart Computer-Aided Translation Environment) project investigated several of these aspects, both from a human-computer interaction point of view, as well as from a purely technological side. This paper describes the SCATE research with respect to improved fuzzy matching, parallel treebanks, the integration of translation memories with machine translation, quality estimation, terminology extraction from comparable texts, the use of speech recognition in the translation process, and human computer interaction and interface design for the professional translation environment. For each of these topics, we describe the experiments we performed and the conclusions drawn, providing an overview of the highlights of the entire SCATE project.

The cell stress response is an essential system present in every cell for responding and adapting to extracellular environmental stimulations. A major program for stress response is the heat shock factor (HSF)–heat shock protein (HSP) system that maintains proteostasis in cells and promotes cancer progression. However, less is known about how the cell stress response is regulated by alternative transcription factors. Here, we show that the SCAN domain-containing transcription factors (SCAN-TFs) are involved in repressing the stress response in cancer. SCAND1 and SCAND2 are SCAN-TFs that can hetero-oligomerize with SCAN-zinc finger transcription factors, such as MZF1(ZSCAN6), for accessing DNA and transcriptionally co-repressing target genes. We found that heat stress induced the expression of both SCAND1 and MZF1(ZSCAN6) bound to HSP90 gene promoter regions in prostate cancer cells. SCAND1 and MZF1 blocked the heat shock responsiveness of HSP90 in prostate cancer cells. Gene expression of SCAND2, SCAND1 and MZF1 was negatively correlated with HSP90 expression in patients-derived prostate adenocarcinoma. MZF1 and SCAND2 were more highly expressed in paired normal tissues than in tumor tissues in several cancer types. High expression of SCAND2, SCAND1 and MZF1 correlated with enhanced prognoses of pancreatic cancer and head and neck cancers. Additionally, high expression of SCAND2 was correlated with better prognoses of lung adenocarcinoma and sarcoma. In contrast, high expression of HSP90AA1 correlated with poorer prognoses in several cancer types. These data suggest that the stress-inducible SCAN-TFs can function as a feedback system, suppressing excessive stress response and inhibiting cancers.

Non-Linear Simulation by Harmonic Balance Techniques of Load Modulated Power Amplifier Driven by Random Modulated Signals. Comparison with measured results.

The VEMoS AXL system is a new optical biometer based on spectral domain optical coherence tomography (SD-OCT) that has been tested in terms of intrasession repeatability and compared with a swept-source optical coherence tomography biometer (SS-OCT), which is considered the gold standard, for an agreement analysis. A biometric analysis was performed three consecutive times in 120 healthy eyes of 120 patients aged between 18 and 40 years with the SD-OCT system and afterwards a single measurement was obtained with the SS-OCT system. Within-subject standard deviations were 0.004 mm, 4.394 µm and 0.017 mm for axial length (AL), central corneal thickness (CCT), and anterior chamber depth (ACD) measures obtained with the SD-OCT biometer, re-spectively. The agreement between devices was good for AL (Limits of agreement, LoA: -0.04 to 0.03 mm) and CCT (LoA: -4.36 to 14.38 µm), whereas differences between devices were clinically relevant for ACD (LoA: 0.03 to 0.21 mm). In conclusion, the VEMoS AXL system provides consistent measures of anatomical parameters, being most of them interchangeable with those provided by the SS-OCT-based gold standard.

The DNS of film boiling requires strong computational resources that are difficult to obtain for a daily CFD use by the practitioners of the industrial R&amp;D experts. On the other hand, the film boiling experiments are associated with the usage of the expensive and highly sophisticated apparatus, and the research to this end is found to be relatively difficult due to high heat flow rates that are present in the process itself. When combined with a transient heat conduction in a solid, the problem becomes significantly difficult. Therefore, a novel method in computation of conjugate heat transfer during film boiling in a quiescent liquid has been proposed in this paper. The method relies on the solution of mass, momentum and energy conservation equations in a two-fluid framework, supplemented with the appropriate closures. Furthermore, the turbulent flow has been found as an important parameter in obtaining the accurate solution of the temperature field evolution in a solid specimen, via the proper modeling of turbulent kinetic energy (TKE) value, that has been imposed as a constant value, i.e., the frozen turbulence approach. It was found, in addition, that the appropriate TKE value can be obtained by use of Kelvin-Helmholtz instability theory in conjunction with the boundary layer theory. The obtained results show excellent agreement with the experimental data within the first 15 s of the experiment, i.e., the first ca. 10 % of the total duration of the film boiling mode of heat transfer. Furthermore, the heat transfer coefficient has matched the error bands prescribed by the authors of the paper that has presented the correlations, whilst the averaged values are far beyond this band, i.e., are slightly more than 30 % higher. The further inspection has revealed a measure of similarity between the computational result of the volume fraction field distribution and the experiment, thus confirming the capability of the method to obtain realistic interface evolution in time. The method has shown full capability for further pursuing the industrial-scale film boiling problems that involve turbulent flow and the conjugate heat transfer approach.

Background. The course of the COVID-19 epidemic process depends on population immunity which prevents pathogen spread among the population. Aim: to study the evolution of SARS-CoV-2 humoral immunity in the Belarusian population relative to COVID-19 pandemic dynamics. Materials and methods. The work was carried out according to a methodology for assessing population immunity developed by Rospotrebnadzor (Russia) and the Belarusian Ministry of Health with the participation of the St. Petersburg Pasteur Institute (SPPI), taking into account WHO recommendations. The study was approved by the Bioethics Committee of Belarus and the SPPI Bioethics Committee. Participant selection was carried out by questionnaire using a cloud (internet server) service. To monitor population immunity, a cohort of 4,661 people (participating in all stages of seromonitoring) was formed from the overall volunteer group. Volunteers were randomized by age group (1-17, 18-29, 30-39, 40-49, 50-59, 60-69, 70+ years), region, and professional group. For the detection of antibodies (Abs) to nucleocapsid (Nc) and S glycoprotein receptor-binding domain (RBD), corresponding assay systems were used following manufacturer instructions. The study was conducted in 4 stages according to a single scheme. Results. In the 1st stage (pandemic month 15), collective immunity was due mainly to Nc+RBD+ Ab status alone. By the 2nd stage (carried out after 4 months), their share decreased 1.2-fold, while the share of volunteers who had only RBD Abs increased 1.7-fold. In the 3rd and 4th stages (carried out after 9 and 19 months), the share of persons with RBD+Nc‒ compared to the 2nd stage decreased by 3.5%; the proportion of persons with Nc+RBD‒ Abs increased by 1.5-fold. The most important factor in population immunity was vaccination of the population, the coverage of which reached 70% by the 4th stage. Among vaccines, the Sputnik V and Sputnik Light vector designs were used most often. The whole-virion, inactivated BIBP-CorV vaccine was used less often. Conclusion. The evolution of collective SARS-CoV-2 humoral immunity included a set of changes in circulating Ab levels (Nc, RBD). The hybrid immunity formed helped to reduce the incidence to nearly zero.

As SARS-CoV-2 continues to spread among human populations, genetic changes occur and accumulate in the circulating virus. Some of these genetic changes have caused amino acid mutations, including deletions, which may have potential impact on critical SARS-CoV-2 countermeasures, including vaccines, therapeutics, and diagnostics. Considerable efforts have been made to categorize the amino acid mutations of the angiotensin-converting enzyme 2 (ACE2) receptor binding domain (RBD) of the spike (S) protein along with certain mutations in other regions within the S protein as specific variants in an attempt to study the relationship between these mutations and the biological behavior of the virus. However, the currently used whole genome sequencing surveillance technologies can test only a small fraction of the positive specimens with high viral loads and often generate uncertainties in nucleic acid sequencing that needs additional verification for precision determination of mutations. This article introduces a generic protocol to routinely sequence a 437-bp nested RT-PCR cDNA amplicon of the ACE2 RBD and a 490-bp nested RT-PCR cDNA amplicon of the N-terminal domain (NTD) of the S gene for detection of the amino acid mutations needed for accurate determination of all variants of concern and variants of interest according to the definitions published by the U.S. Centers for Disease Control and Prevention. This protocol was able to amplify both nucleic acid targets into cDNA amplicons to be used as templates for Sanger sequencing on all 16 clinical specimens that were positive for SARS-CoV-2.

Large values and gradients of stresses and deformations, triggering concentrations of stresses and deformations, arise in the corner areas of a structure. The action of forced deformations, leading to the finite rupture of the contact between the elements of a structure, also triggers the concentration of stresses, while the rupture reaches an irregular point, a line on the area boundary. The theoretical analysis of the stress-strain state (SSS) of areas with angular cutouts in the boundary under the action of discontinuous forced deformations is reduced to the study of singular solutions to the homogeneous problem of the elasticity theory that has power-related features. The calculation of stress concentration coefficients in the domain of a singular solution to the elastic problem makes no sense. It is experimentally proven that the zone, that is close to the vertex of the angular cutout in the area boundary, has substantial deformations, rotations, and it corresponds to rising values of the first and second derivatives of displacements along the radius in cases of sufficiently small radii in the neighbourhood of the irregular point of the boundary. For such areas, it is necessary to consider the plane problem of the elasticity theory, taking into account the geometric nonlinearity under the action of forced deformations. This will allow analyzing the effect of relations between orders of values of deformations, rotations, and forced deformations on the form of the equation of equilibrium. The purpose of this work is to analyze the effect of relations of deformation orders, rotations, forced deformations on the form of the equilibrium equation in the polar coordinate system for a V-shaped area under the action of forced temperature-induced deformations with regard for the geometrical non-linearity and physical linearity.

C-type lectin CD209/DC-SIGN and CD209L/L-SIGN proteins are distinct cell adhesion and pathogen recognition receptors that mediate cellular interactions and recognize a wide range of pathogens including, viruses such as SARS, SARS-CoV-2, bacteria, fungi and parasites. Pathogens exploit CD209L family proteins to promote infection and evade the immune recognition system. CD209L and CD209 are widely expressed in SARS-CoV-2 target organs and can contribute to infection and pathogenesis. CD209L family receptors are highly susceptible to alternative splicing and genomic polymorphism, which may influence virus tropism and transmission in vivo. The carbohydrate-recognition domain (CRD) and the neck/repeat region represent the key features of CD209L family proteins that are also central to facilitating cellular ligand interactions and pathogen recognition. While, the neck/repeat region is involved in oligomeric dimerization, the CRD recognizes the mannose containing structures present on specific glycoproteins such as those found on the SARS-CoV-2 spike protein. Considering the role of CD209L and related proteins in diverse pathogen recognition, this review article discusses the recent advances in the cellular and biochemical characterization of CD209 and CD209L and their roles in viral uptake, which has important implications in understanding the host-pathogen interaction, the viral pathobiology and driving vaccine development of SARS-CoV-2.

Jingmen viruses are newly described segmented flavi-like viruses that have a worldwide distribution in ticks and have been associated with febrile illnesses in humans. Computational analyses were used to predict that Jingmen flavi-like virus glycoproteins have structural features of class II viral fusion proteins, including an ectodomain consisting of beta-sheets and short alpha-helices, a fusion peptide with interfacial hydrophobicity and a three domain architecture. Jingmen flavi-like virus glycoproteins have a sequence enriched in serine, threonine and proline at the amino terminus, which is a feature of mucin-like domains. Several of the serines and threonines are predicted be modified by the addition of O-linked glycans. Some of the glycoproteins are predicted to have an additional mucin-like domain located prior to the transmembrane anchor, whereas others are predicted to have a stem consisting of two alpha-helices. The flavivirus envelope protein and Jingmen flavi-virus glycoproteins may have diverged from a common class II precursor glycoprotein with a mucin-like domain or domains acquired after divergence.

This study continued the analysis of immunization with the receptor binding domain (RBD) associated with the adjuvants Dimethyldioctadecylammonium bromide (DDA) and Saponin (Sap) (RBD+DDA/Sap) or Aluminum hydroxide (AH) and outer membrane vesicles (OMVs) of Neisseria meningitidis (RBD+AH/OMV); from adult to old age and assessed maternal-fetal transference of antibodies. Outbred Swiss mice were immunized with 2 intramuscular (IM) doses with the antigenic preparations RBD+DDA/Sap, RBD+AH/OMV or RBD alone. The humoral immune response was evaluated using ELISA, avidity-ELISA, Immunoblotting and a Omicron-surrogate-neutralization assay (BA.1), while the cellular immune response was analyzed by ELISpot. Our previous work studied the IgG response; here, we verified that IgM levels were higher right after the immunization doses, but, as IgG, it persisted until 368 days after the immunization. The avidity of IgM increased from low to intermediate-to-high after the booster dose. RBD+DDA/Sap presented neutralizing indexes against Omicron at days 47 and 176, while RBD+AH/OMV showed neutralization on days 21, 47 and 176. Cellular response, measured 465 days after immunization, revealed IFN-Y and IL-4 secretion. The offspring of RBD+DDA/Sap had detectable antibodies, which decreased around 45 days after birth, the last point we analyzed. The results suggested that DDA/Sap is a promising adjuvant mixture to enhance humoral and cellular immune response against SARS-CoV-2, improving maternal-fetal transference of antibodies; cross-reactivity with Omicron variant; and the maintenance of antibodies for a long period.

Current theories of autoimmunity are diverse, sometimes contradictory, and suffer from incompleteness. Although substantial evidence exists that adaptive and innate immunity, sex, genetic predisposition, and the microbiome all play essential roles in autoimmune disease etiologies and pathogenesis, and that antigen processing is altered during disease induction, no existing theory integrates all of these factors through a single, coherent mechanism. In an attempt to focus the field on the need to elucidate such an integrative mechanism, I propose one possibility here that, if nothing else, helps to identify the nature of the problems that need to be addressed. My theory is that autoimmune diseases are induced by normal immunological responses to unique pairs of complementary antigens, at least one of which is a molecular mimic of a host target. Each antigen in the complementary pair induces a complementary immune response (T or B cell); although each immune response is idiotypic in origin, the antigenic complementarity results in what appears to be an idiotype-anti-idiotype relationship between the responses. Additionally, because of the antigenic complementarity, each immune response mimics one of antigens, abrogating the distinction between self and non-self. If at least one of the antigens mimics a host antigen, then the resulting immunological civil war spreads to a host tissue. Complementary antigens also alter antigen processing so that antigens that would normally be proteolytically digested are presented by the major histocompatibility complex (MHC) to T and B cell receptors inducing a cross-reactive immune response. The resulting civil war is supported by the innate immune system due to the complementarity of the initiating antigens.. Complementary antigens stimulate synergistic toll-like receptors (TLR) and/or nucleotide-binding oligomerization receptors (NOD) resulting in up-regulation of cytokine production and further stimulation of the adaptive immune response. Because the immune responses (e.g., antibodies) mimic the initiating antigens, this synergistic activation of innate immunity becomes chronic. Additionally, TLR and NOD function are highly sensitive to sex hormones, some becoming up-regulated and some down-regulated in the presence of either testosterone or estrogens. This sensitivity explains how sex modifies susceptibility to autoimmune diseases. Genetic mutations in TLR, NOD and MHC further alter antigen presentation and the degree to which antigens stimulate an immune response explaining how genetics also modifies susceptibility. Finally, sex hormones also alter the host microbiome, which in turn modulates autoimmune disease risk by shaping the immunological nature of self and by mediating susceptibility to microbial infection. Moreover, it appears that the microbiome camouflages itself from the immune system by mimicking the host antigenic repertoire; the mimicry between the antigens of the microbiome and the host results in selective attacks on microbiome constituents concomitant with any autoimmune attack on host tissues. This antigenic complementarity theory thereby integrates all major elements known to affect, or be affected by, autoimmune diseases and provides a set of testable implications.

Since the come up in the 70´s, various decentralized control methodologies have been developed to deal with the challenge of controlling complex and/or spatially distributed systems with multiple inputs and multiple outputs (MIMO), e.g., chemical plants, power systems, water systems, etc. In general, the use of distributed information and control structures requires to synthesize control laws in a constrained (decentralized) information structure. The article presents another version of the unified frequency domain robust decentralized controller design method [1]. The proposed design procedure is appropriate for uncertain dynamic MIMO systems given as a set of transfer function matrices. Its main framework is provided by the Equivalent Subsystems Method [1, 24] guaranteeing fulfillment of the necessary and sufficient stability condition of the overall closed-loop system if individual closed-loop equivalent subsystems are stable. Generating sets of equivalent subsystems for all transfer function matrices describing the uncertain MIMO plant allows to use the QFT method [19] to independently design local robust SISO controllers that constitute the resulting decentralized controller implemented on true subsystems. The developed design procedure is verified and illustrated on a case study on robust decentralized level controller design for a quadruple tank process [2, 24].

Spinocerebellar ataxia type 2 (SCA2) is caused by polyglutamine expansion in Ataxin-2 (ATXN2). This factor binds RNA/proteins to modify metabolism after stress, and to control calcium (Ca2+) homeostasis after stimuli, thus exerting crucial neuroprotection for cerebellar ataxias and corticospinal motor neuron degeneration. Our Atxn2-CAG100-Knock-In mouse faithfully models features observed in patients at pre-onset, early and terminal stages. Here, its cerebellar global RNA profiling revealed downregulation of signaling cascades to precede motor deficits. Validation work at mRNA/protein level defined alterations that were independent of constant physiological ATXN2 functions, but specific for RNA/aggregation toxicity, and progressive across the short lifespan. Earliest changes were detected at 3 months among Ca2+ channels/transporters (Itpr1, Ryr3, Atp2a2, Atp2a3, Trpc3), IP3 metabolism (Plcg1, Inpp5a, Itpka), and Ca2+-Calmodulin dependent kinases (Camk2a, Camk4). CaMKIV–Sam68 control over alternative splicing of Nrxn1, an adhesion component of glutamatergic synapses between granule and Purkinje neurons, was found affected. Systematic screening of pre/post-synapse components, with dendrite morphology assessment, suggested early impairment of CamKIIα abundance together with weakening of parallel fiber connectivity. These data reveal molecular changes due to ATXN2 pathology, impacting communication and excitability of cerebellar neurons. Discovery of such risk versus progression markers improves the assessment of pre-symptomatic treatments in SCA2 and related disorders.

Chatbots have gained widespread popularity for their task automation capabilities and consistent availability in various domains, including education. However, their ability to adapt to the continuously evolving and dynamic nature of knowledge is limited. This research investigates the implementation of an internet wizard to enhance the knowledge base of an open-domain question-answering chatbot. The proposed approach leverages search engines, particularly Google, and its features, including feature snippets, knowledge graph, and organic search, in conjunction with data science and natural language models. This mechanism empowers the chatbot to dynamically access the extensive and up-to-date knowledge available on the web, enabling the provision of real-time and pertinent answers to user queries sourced from web documents. A pilot study in a higher education context evaluated the chatbot's mechanism and features, confirming its proficiency in generating responses across a broad range of educational and non-educational topics. Positive feedback and high user satisfaction validate these findings. Notably, the chatbot's dynamic feature of retrieving related or follow-up questions from search engines significantly enhances student engagement and facilitates exploration of supplementary information beyond the curriculum.

Nonalcoholic fatty liver disease (NAFLD) is becoming the leading cause of hepatocellular carcinoma (HCC), liver-related mortality, and liver transplantation. There is reasonable epidemiological cohort data to recommend surveillance of patients with NAFLD based upon the incidence of HCC. The American Gastroenterology Association (AGA) expert review published in 2020 recommend that NAFLD patients with cirrhosis or advanced fibrosis estimated by non-invasive tests (NITs) should consider HCC surveillance. NITs include fibrosis-4 (FIB-4) index, the enhanced liver fibrosis (ELF) test, FibroScan, and MR elastography. The recommended surveillance modality is abdominal ultrasound (US) given that it is cost effective and noninvasive with good sensitivity. However, US is limited in obese patients and those with NAFLD. In NAFLD patients with a high likelihood of having an inadequate US or if US is attempted but inadequate, CT or MRI may be utilized. The GALAD score, consisting of age, gender, AFP, lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), and protein induced by vitamin K absence or antagonist-II (PIVKA-II), can help to identify high risk of incident HCC in NAFLD patients. Innovative parameters including Mac-2 binding protein glycated isomer , type IV collagen 7S, free apoptosis inhibitor of macrophage, combination of single nucleoside polymorphisms are expected to be established. Considering a large number of NAFLD population, optimal screening tests must meet several criteria including high sensitivity, cost effectiveness and availability.

Recent studies have indicated that terahertz time-domain spectroscopy (THz-TDS) can stably and efficiently acquire output spectra using an affordable and compact multimode laser diode (MMLD) with delayed optical feedback as the light source. This research focused on a numerical analysis of the optimal conditions for employing an MMLD with delayed optical feedback (chaotic oscillating laser diode) in THz-TDS, utilizing multimode rate equations. The findings revealed that the intermittent chaotic output generated by the MMLD, characterized by concurrent picosecond pulse oscillations lasting several tens of picoseconds, proves to be highly effective for THz-TDS. By appropriately setting the amounts of injection current and optical feedback, and the delay time of optical feedback, intermittent chaotic oscillation can be attained within a considerably broad parameter range. Moreover, both the MMLD output spectrum and the THz-TDS output spectrum exhibit a consistently stable shape at the microsecond scale, demonstrating the attractor properties inherent in an MMLD with delayed optical feedback.

This paper provides a review of an emerging field in the food processing sector, referring to efficient and safe food supply chains, ’from farm to fork’, as enabled by Artificial Intelligence (AI). Recent advances in machine and deep learning are used for effective food production, energy management and food labeling. Appropriate deep neural architectures are adopted and used for this purpose, including Fully Convolutional Networks, Long Short-Term Memories and Recurrent Neural Networks, Auto-Encoders and Attention mechanisms, Latent Variable extraction and clustering, as well as Domain Adaptation. Three experimental studies are presented, illustrating the ability of these AI methodologies to produce state-of-the-art performance in the whole food supply chain. In particular, these concern: (i) predicting plant growth and tomato yield in greenhouses, thus matching food production to market needs and reducing food waste or food unavailability; (ii) optimizing energy consumption across large networks of food retail refrigeration systems, through optimal selection of systems that can get shut-down and through prediction of the respective food de-freezing times, during peaks of power demand load; (iii) optical recognition and verification of food consumption expiry date in automatic inspection of retail packaged food, thus ensuring safety of food and people’s health.

To evaluate whether autologous mesenchymal cells, adipose derived stem cells and platelet-rich plasma, grafted into the supracoroideal space by surgical treatment according to Limoli retinal restoration technique (LRRT), can produce growth factors in order to exert a beneficial effect in retinitis pigmentosa (RP) patients. Twenty-one eyes underwent surgery and divided based on retinal foveal thickness ≤ 190 or >190 µm into group A and group B, respectively. The specific LRRT triad was grafted in a deep scleral pocket above the choroid of each eye. At 6-month follow-up, group B showed an improvement in residual close-up visus and sensitivity at microperimetry compared to group A. After an in-depth review of molecular biology studies concerning degenerative phenomena underlying the etiopathogenesis of RP, it can be confirmed that further research is needed on tapeto-retinal degenerations both from a clinical and molecular point of view to obtain better functional results. In particular, it is necessary to increase the number of patients, extend observation times, and treat subjects in the presence of still trophic retinal tissue to allow adequate biochemical and functional catering.

Over the years, machine learning has emerged as a tool for automated translation and has been studied relentlessly for decades. RBMT, SMT, and NMT models have been used to achieve machine translation and the results have drastically improved from when research in this field first began. Although a few general-purpose translators such as Google Translate or Microsoft Translator have accurate translations compared to that of a human translator, many pieces of text containing highly technical terms or homonyms are often mistranslated completely. When considering the necessity and importance of translating technical patents from different domains, accuracy in translation is not something that can be compromised. This motivates the need to improve the performance of machine translation further. The scope of this paper covers three open-source machine translation models for the purpose of patent documentation translation from English to Japanese, evaluates their performance on patent data, and proposes a methodology that enabled us to improve one of the model’s BLEU score by 41.22%, achieving a BLEU score of 46.18.

Among post-translational modifications of proteins, ADP-ribosylation has been studied for over fifty years, assigning to this PTM a large set of functions, including DNA repair, transcription and cell signaling. This review presents an update on the function of a large set of enzyme writers, the readers that are recruited by the modified targets, and the erasers that reverse the modification to the original amino acid residue, removing the covalent bonds formed. In particular, the review provides details on the involvement of the enzymes performing MAR/PAR cycling in cancers. Of note, there is potential for application of the inhibitors developed for cancer also in the therapy of non-oncological diseases such as the protection against oxidative stress, suppression of inflammatory responses, and the treatment of neurodegenerative diseases. This field of studies is not concluded, since novel enzymes are being discovered at a rapid pace.

Immune checkpoint receptors play a crucial role in steering tumor progression, prompting a focused investigation into the role of TIM3 in breast cancer. Analysis of TCGA BRCA data unveiled diverse correlations between TIM-3 expression and immune cell infiltration across subtypes. In our in-house cohort studied through IHC, significant changes in TIM3 expression with tumor grades were observed. Higher TIM3 expression correlated with increased disease-free survival in pan breast cancer, marking the first revelation of TIM3's positive role in pan BC prognosis. The study indicates that alluring TIM3 response, rather than suppression, may enhance breast cancer prognosis.