Fluorescent bioprobes are invaluable tools for visualizing live cells and deciphering complex biological processes by targeting intracellular biomarkers without disrupting cellular functions. In addition to protein-binding concepts, fluorescent probes utilize various mechanisms, including membrane, metabolism, and gating-oriented strategies. This study introduces a novel fluorescent mechanism distinct from existing ways. Here, we developed a B-cell selective probe, CDrB, with unique transport mechanisms. Through SLC-CRISPRa screening, we identified two transporters, SLCO1B3 and SLC25A41, by sorting out populations exhibiting higher and lower fluorescence intensities, respectively, demonstrating contrasting activities. We confirmed that SLCO1B3, with comparable expression levels in T and B cells, facilitates the transport of CDrB into cells, while SLC25A41, overexpressed in T lymphocytes, actively exports CDrB. The observation suggests that SLC25A41 plays a crucial role in discriminating between T and B lymphocytes. Furthermore, it reveals the potential for reversible localization of SLC25A41 to demonstrate its distinct activity. This study is the first report to unveil a novel strategy of SLC by exporting the probe. We anticipate that this research will open up new avenues for developing fluorescent probes.

The structural transitions RNAs undergo during trafficking are not well-understood. Here, we used the well-developed yeast Ty1 retrotransposon to provide the first structural model of genome (g) RNA in the nucleus from a retrovirus-like transposon. Through a detailed comparison of nuclear Ty1 gRNA structure with those established in the cytoplasm, virus-like particles (VLPs), and synthesized in vitro, we detected Ty1 gRNA structural alternations that occur during retrotransposition. Full-length Ty1 gRNA serves as the mRNA for Gag and Gag-Pol proteins and as the genome that is reverse transcribed within VLPs. We show that about 60% of base pairs predicted for the nuclear Ty1 gRNA appear in the cytoplasm, and active translation does not account for such structural differences. Most of the shared base pairs are represented by short-range interactions, while the long-distance pairings seem unique for each compartment. Highly structured motifs tend to be preserved after nuclear export of Ty1 gRNA. In addition, our study highlights the important role of Ty1 Gag in mediating critical RNA:RNA interactions required for retrotransposition.

Plant-parasitic nematodes cause expressive annual yield losses to worldwide agricultural production. Most cultivated plants have no known resistance against nematodes and the few bearing a resistance gene can be overcome by certain species. The chemical methods that have been deployed to control nematodes were largely banned from use due to their poor specificity and high toxicity. Hence, there is an urgent need for the development of cleaner and more specific control methods. Recent advances in nematode genomics, including in phytoparasitic species, provide an unprecedented opportunity to identify genes and functions specific to these pests. Using phylogenomics, we compared 61 nematode genomes, including 16 for plant-parasitic species and identified more than 24,000 protein families specific to these parasites. In the genome of Meloidogyne incognita, one of the most devastating plant parasites, we found ca. 10,000 proteins with orthologs restricted only to phytoparasitic species and no further homology in protein databases. Among these phytoparasites-specific proteins, ca. 1,000 shared the same properties as known secreted effectors involved in essential parasitic functions. Of those, 68 were novel and showed strong expression during the endophytic phase of the nematode life cycle, based on both RNA-seq and RT-qPCR analyses. Besides effector candidates, transcription-related and neuro-perception functions were enriched in phytoparasites-specific proteins, revealing interesting targets for nematode control methods. This phylogenomics analysis, constitutes an unprecedented resource for the further understanding of the genetic basis of nematode adaptation to phytoparasitism and for the development of more efficient control methods.

African locust bean (Parkia biglobosa (Jacq.) is a multi-purpose economic tree with genetic potentials in sub-Saharan Africa. Its cultivation and production is declining with increased aging and genetically threatened throughout its natural ranges. Research efforts are needed to change the present scenario to sustainable cultivation and utilization, hence this present study. This study was aimed at evaluating genetic diversity and geographical spread relationships of twenty landraces collected from different ecological zones of Nigeria using simple sequence repeat (SSR) markers. Ten SSR markers were screened and five primers (PbL02, PbL03, PbL04, PbL05 and PbL09) were selected based on clear amplification products and reproducible scorable bands. The SSR primers detected a total of 55 alleles ranged from 10 to 14 alleles with a mean of 11. The percentage polymorphisms were high and ranged from 68.75 % in PbL04 to 84.21 % in PbL05 with a mean of 74.16 %. The polymorphic information content (PIC) was in the range of 0.31 in PbL02 to 0.37 in PbL09. The genetic diversity and heterozygosity values ranged from 0.39 to 0.50 and 0.00 to 0.68 while the average genetic distance for all pair wise comparisons was 0.31.The first five Principal Component (PC) accounted for 70.20 % of the total variation out of which PC1 (31.50%) and PC2 (19.20%) extracted 49.70% molecular similarity. The dendrogram resulted in separation of the 19 landraces into three major clusters based on unweighted pair group method with arithmetic average. Cluster I comprised of five landraces: ABNo130 and BENo023; OYNo11, KANo125 and NiNo262 while cluster II had only one (BANo116). Cluster III was diverse comprising 13 landraces: ZANo188, KNNo162, KENo220, GMNo076 and EbNo260, ADNo64, EdNo164, KANo137, KENo217, KwNo270, NiNo241, OsNo206 and PLNo120. The homogeneity of alleles among the studied landraces suggested suspicion of loss of genetic intra-specific variation among the landraces of P. biglobosa which calls for concerted efforts toward better cultivation, conservation, management, utilization and genetic improvement of the species in Nigeria.

A variety of techniques have been utilized in metal additive manufacturing (AM) for melt pool size management, including modeling and feed-forward approaches. In a few cases, closed-loop control has been demonstrated. In this research, closed-loop melt pool size control for large-scale, laser-wire based Directed Energy Deposition is demonstrated with a novel modification: site-specific changes to the controller set-point were commanded at trigger points, the locations of which were generated by the projection of a secondary geometry onto the primary 3D-printed component geometry. The present work shows that, through this technique, it is possible to print a specific geometry that occurs beyond the actual toolpath of the print head. This is denoted as an extra-toolpath geometry and is fundamentally different from other methods of generating component features in metal AM. A proof-of-principle experiment is presented in which a complex oak leaf geometry was embossed on an otherwise ordinary double-bead wall made from Ti-6Al-4V. The process is introduced and characterized primarily from a controls perspective with reports on the performance of the control system, the melt pool size response, and the resulting geometry. The implications of this capability, which extend beyond localized control of bead geometry to the potential mitigations of defects and functional grading of component properties, are discussed.

The application of thermoelectric generators (TEG) on the nozzle of an aviation jet engine was studied by finite element TEG-simulations. Against the background of system-level requirements of the reference aircraft this work reports the resulting requirements on the TEG design with respect to applied thermoelectric (TE) element lengths and fill factors (F) within the TE modules in order to maintain a positive effect on the specific fuel consumption. Assuming a virtual optimized TE material and varying the convective heat transfer coefficients at the nozzle surfaces this work reports the achievable power output. System-level requirement on the gravimetric power density (> 100 Wkg-1) can only be met for F ≤ 21%. Extrapolating TEG coverage to the full nozzle surface, the power output reaches 1.65 kW per engine. Assessment of further potential is demonstrated by a parametric study on the fill factor, convective heat transfer coefficients, and materials performance. This study confirms a feasible design range for TEG installation on the aircraft nozzle with a positive impact on the fuel consumption. This application translates into a reduction of operational costs, allowing for an economically efficient installation of TEG in consideration of the cost-specific power output of modern thermoelectric materials.

In this paper, the time-resolved model of photoacoustic signal for samples with a complex inner structure is derived including local non-equilibrium of structural elements with multiple degrees of freedom, i.e. structural entropy of the system. The local non-equilibrium is taken into account through the fractional operator. By analyzing the model for two types of time-dependent excitation, a very short pulse and a very long pulse, it is shown that the rates of non-equilibrium relaxations in complex samples can be measured by applying the derived model and time-domain measurements. Limitations of the model and further directions of its development are discussed.

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.

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.

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.

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.

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.

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 assessment of Health-Related Quality of Life (HRQoL) in Thalassemia offers a holistic approach to the disease and facilitates better communication between physicians and patients. This study aimed to evaluate the HRQoL of Transfusion-Dependent Thalassemia (TDT) patients in Greece. This was a multicentre, cross-sectional study conducted in 2017, involving 283 adult TDT patients. All participants completed a set of two QoL questionnaires, the generic SF-36v2 and the disease-specific TranQol. Demographic and clinical characteristics were used to predefine patient subgroups. Significant factors identified in univariate analysis were entered into a multivariate analysis to assess their effect on HRQoL. The SF-36 scores of TDT patients were consistently lower, compared to the general population in Greece. The mean summary score of TranQol was relatively high (71±14%), exceeding levels observed in national surveys in other countries. Employment emerged as the most significant independent factor associated with better HRQoL, whereas age had the most significant negative effect. This study represents the first comprehensive QoL assessment in a representative sample of the TDT population in Greece. The implementation of TranQol allowed for the quantification of HRQoL in Greece, establishing a baseline for future follow-up, and identifying more vulnerable patient subgroups.

A calibrated mathematical model of antiviral immune response to SARS-CoV-2 infection is developed. The model considers the innate and antigen-specific responses to SARS-CoV-2 infection. Recently published data sets from human challenge studies with SARS-CoV-2 were used for parameter estimation. Understanding the regulation of multiple intertwined reaction components of the immune system is necessary for linking the clinical phenotypes of COVID-19 with the kinetics of immune responses. Consideration of multiple immune reaction components in a single calibrated mathematical model allowed us to address some fundamental issues related to pathogenesis of COVID-19, i.e. sensitivity of the peak viral load to parameters characterizing the specific response components, the kinetic coordination of the individual responses, and the factors favoring a prolonged viral persistence. The model provides a tool for predicting the infectivity of patients, i.e. the amount of virus which is transmitted via droplets from the person infected with SARS-CoV-2, depending on the time of infection. The thresholds in the relative unbalance between innate and adaptive response parameters which lead to a prolonged persistence of SARS-CoV-2 due to the loss of a kinetic response synchrony/coordination were identified.

Modules composed of a resistance gene flanked by Xer site-specific recombination sites, the vast majority of which were found in Acinetobacter baumannii, are thought to behave as elements that facilitate horizontal dissemination. The A. baumannii xerC and xerD genes were cloned, and the recombinant clones used to complement the cognate Escherichia coli mutants. The complemented strains supported resolution of plasmid dimers, and, as is the case with E. coli and Klebsiella pneumoniae plasmids, the activity was enhanced when cells were growing in low osmolarity growth medium. Binding experiments showed that partially purified A. baumannii XerC and XerD proteins (XerC_Ab and XerD_Ab) bound synthetic Xer site-specific recombination sites, some of them with a nucleotide sequence deduced from existing A. baumannii plasmids. Incubation with suicide substrates resulted in covalent attachment of DNA to a recombinase, probably XerC_Ab, indicating that the first step in the recombination reaction took place. The results described show that XerC_Ab and XerD_Ab are functional proteins and support the hypothesis that they participate in horizontal dissemination of resistant genes among bacteria.

Increased nutrient withdrawal by rapidly expanding intensive cropping systems, in combination with imbalanced fertilization, is leading to potassium (K) depletion from agricultural soils in Asia. There is an urgent need to better understand the soil K-supplying capacity and K-use efficiency of crops to address this issue. Maize is increasingly being grown in rice-based systems in South Asia, particularly in Bangladesh and North East India. The high nutrient extraction, especially K, however, causes concerns for the sustainability of maize production systems in the region. The present study was designed to estimate, through a plant-based method, the magnitude, and variation in K-supplying capacity of a range of soils from the maize-growing areas and the K-use efficiency of maize in Bangladesh. Eighteen diverse soils were collected from several upazillas (or sub-districts) under 11 agro-ecological zones to examine their K-supplying capacity from the soil reserves and from K fertilization (@ 100 mg K kg-1 soil) for successive seven maize crops grown up to V10-V12 in pots inside a net house. A validation field experiment was conducted with five levels of K (0, 40, 80, 120 and 160 kg ha-1) and two fertilizer recommendations based on “Nutrient Expert for Maize-NEM” and “Maize Crop Manager-MCM” decision support tools (DSSs) in 12 farmers’ fields in Rangpur, Rajshahi and Comilla districts in Bangladesh. Grain yield and yield attributes of maize responded significantly (P < 0.001) to K fertilizer, with grain yield increase from 18 to 79% over control in all locations. Total K uptake by plants not receiving K fertilizer, considered as potential K-supplying capacity of the soil in the pot experiment, followed the order: Modhukhali >Mithapukur >Rangpur Sadar >Dinajpur Sadar >Jhinaidah Sadar >Gangachara >Binerpota >Tarash >Gopalpur >Daudkandi >Paba >Modhupur >Nawabganj Sadar >Shibganj >Birganj >Godagari >Barura >Durgapur. Likewise in the validation field experiment, the K-supplying capacity of soils was 83.5, 60.5 and 57.2 kg ha-1 in Rangpur, Rajshahi, and Comilla, respectively. Further, the order of K-supplying capacity for three sites was similar to the results from pot study confirming the applicability of results to other soils and maize-growing areas in Bangladesh and similar soils and areas across South Asia. Based on the results from pot and field experiments, we conclude that the site-specific K management using the fertilizer DSSs can be the better and more efficient K management strategy for maize.

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.

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.

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.

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.

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

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.

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.

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.

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.

Enzymes reliant on pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B6, hold significant importance in both biology and medicine. They facilitate various biochemical reactions, particularly in amino acid and neurotransmitter metabolisms. Vitamin B6 is absorbed by organisms in its non-phosphorylated form and phosphorylated within cells by pyridoxal kinase (PLK) and pyridox-(am)-ine 5'-phosphate oxidase (PNPOx). The flavin mononucleotide dependent PNPOx enzyme converts pyridoxine 5'-phosphate and pyridoxamine 5'-phosphate into PLP. PNPOx is vital for both biosynthesis and salvage pathways in organisms producing B6 vitamers. However, for those depending on vitamin B6 as nutrient, PNPOx participates only in the salvage pathway. Transferring PLP produced by PNPOx to client apo-enzymes is indispensable for their catalytic function, proper folding and targeting to specific organelles. PNPOx activity deficiencies due to inborn errors lead to severe neurological pathologies, particularly neonatal epileptic encephalopathy. PNPOx enzymes from different organisms maintain PLP homeostasis through highly regulated mechanisms, including structural alterations throughout the catalytic cycle and allosteric PLP binding influencing substrate transformation at the active site. Despite shared features, species-specific regulations are evident among PNPOx enzymes.

This work presents noble composites of AAILs@MCM-48 by functionalizing ordered mesopo-rous silicon MCM-48 with two amino acid-based ionic liquids (AAILs) ([Emim][Gly] and [Em-im][Ala]) to improve carbon capture and selectivity of CO2 over nitrogen. Thermogravimetric and XRD analyses of the composites show that the MCM-48 support's thermal and structural in-tegrity was preserved after the AAILs were encapsulated. An N2 adsorption-desorption study at 77 K also confirms AAIL encapsulation in the porous support. Under post-combustion flue gas conditions, both [Emim][Gly]@MCM-48 and [Emim][Ala]@MCM-48 demonstrated improved CO2 adsorption in comparison to unmodified MCM-48, with a CO2 partial pressure of around 0.15 bar. In terms of maximal CO₂ uptake, the 40wt%-[Emim][Gly] composite outperformed the others at 303K, with values of 0.74 and 0.82 mmol g-1, respectively, at 0.1 and 0.2 bar. These numbers show a 10x and 5x increase, respectively, as compared to the pure MCM-48 under iden-tical conditions. In addition, the selectivity of the composites was improved significantly, at 0.1 bar, the selectivity of composites containing 40wt% [Emim][Ala] increased to 17, compared to 2 for pristine MCM-48.

This article describes a novel electrochemical on-chip biosensor that utilizes anti-PSA antibody (Ab) and silver nanoparticles (AgNPs) to enhance the sensing and detection capability of prostate specific antigen (PSA) in the blood. The AgNPs are prepared, characterized, and applied onto a silicon photonic on-chip biosensing receptor platform designed to enhance the accurate detection of PSA. The AgNPs were synthesized by a chemical reduction method using silver nitrate (AgNO₃) as the precursor. Transmission electron microscopy (TEM), selected area electron diffraction (SAED), energy dispersion X-ray spectroscopy (EDS), small angle X-ray scattering (SAXS), X-ray diffraction (XRD), and light microscopy were among the methods used in the characterization and analysis of the AgNPs. Each stage of the immunosensor fabrication was characterized using cyclic voltammetry. The proposed immunosensor was applied in the detection of PSA, a prostate cancer biomarker, with a high sensitivity and a limit of detection of 0.17 ng/mL over a linear concentration range of 2.5 to 11.0 ng/mL. The immunosensor displayed good stability and was selective in the presence of interfering species like immunoglobulin (Ig) in human serum, ascorbic acid (AA), and diclofenac (Dic). The detectivity and sensitivity are significantly higher than previous reports on similar or related technologies.

This study presents the encapsulation of two amino acid-based ionic liquids (AAILs), 1-Ethyl-3-methylimidazolium glycine [Emim][Gly] and 1-Ethyl-3-methylimidazolium alanine [Emim][Ala], in a highly porous metal organic framework (MOF-177), to generate state-of-the-art composites for post-combustion CO2 capture. The thermogravimetric analysis (TGA) demonstrated a successful encapsulation of the AAILs, consequently dramatically reducing the composites' surface area and pore volume. Both [Emim] [Gly]@MOF-177 and [Emim][Ala]@MOF-177 had close to 3 times the CO2 uptake of MOF-177 at 20 wt.% loading, 0.2 bar, and 303 K. Additionally, 20-[Emim][Gly]@MOF-177 and 20-[Emim] [Ala]@MOF-177 enhanced their CO2/N2 selectivity from 5 (pristine MOF-177) to 13 and 11, respectively.

Optical networks offer a wide range of benefits to the telecommunication sector world- wide with its provision of higher bandwidth which leads to faster data speed, longer transmission distance, and improved latency. Currently, the complexity associated with advancements in optical networks poses problems to network flexibility, reliability, and quality of service. Over the years, many reviews and proposals have been implemented by several literatures to provide solutions for optical networks using software-defined networks and network service orchestrators. This paper reviews the significant challenges in current optical network applications, the various solutions rendered by software-defined networks as well as network service orchestration, the impediments, and gaps in these software – defined networks. This paper will go a step further to look into the various improvements and implementations of software-defined networks tailored to solve specific optical network problems. This paper further proposes a flexible orchestration architecture for software-defined networks for solving flexibility and scalability problems in optical networks. This proposal uses Open Network System (ONOS) SDN controller, leveraging on dockerisation as well as kubernetes clusterisation and orchestration. This solution presents a more flexible, reliable, customable, and higher quality of service which is an improvement upon current solutions in literature.

Pure orbital blowout fractures occur within the confines of the internal orbital wall. Restoration of orbital form and volume is paramount to prevent functional and esthetic impairment. The anatomical peculiarity of the orbit has encouraged surgeons to develop implants with customized features to restore its architecture. This has resulted in worldwide clinical demand for patient-specific implants (PSIs) designed to fit precisely in the patient's unique anatomy. Fused filament fabrication (FFF) three-dimensional (3D) printing technology has enabled the fabrication of implant-grade polymers such as Polyetheretherketone (PEEK), paving the way for a more sophisticated generation of biomaterials. This study evaluates the FFF 3D printed PEEK orbital mesh customized implants with a metric considering the relevant design, biomechanical, and morphological parameters. The performance of the implants is studied as a function of varying thicknesses and porous design constructs through a finite element (FE) based computational model and a decision matrix based statistical approach. The maximum stress values achieved in our results predict the high durability of the implants, and the maximum deformation values were under one-tenth of a millimeter (mm) domain in all the implant profile configurations. The circular patterned implant (0.9 mm) had the best performance score. The study demonstrates that compounding multi-design computational analysis with 3D printing can be beneficial for the optimal restoration of the orbital floor.

Despite the remarkable success of Carnot’s heat engine cycle in founding the discipline of thermodynamics two centuries ago, false viewpoints of his use of the caloric theory in the cycle still linger, limiting his legacy. An action revision of the Carnot cycle can correct this, showing that the heat flow powering external mechanical work is compensated internally with configurational changes in the thermodynamic or Gibbs potential of the working fluid, differing in each stage of the cycle quantified by Carnot as caloric. Action (@) is a property of state having the same physical dimensions as angular momentum (mrv=mr2ω). However, this property is scalar rather than vectorial, including a dimensionless phase angle (@=mr2ωδφ). We have recently confirmed with atmospheric gases that their entropy is a logarithmic function of the relative vibrational, rotational and translational action ratios with Planck’s quantum of action ħ. The Carnot principle shows that the maximum rate of work (puissance motrice) possible from the reversible cycle is controlled by the difference in temperature of the hot source and the cold sink, the colder the better. This temperature difference between the source and the sink also controls the isothermal variations of the Gibbs potential of the working fluid, that Carnot identified as reversible temperature-dependent but unequal exchanges in caloric. Importantly, the engine’s inertia ensures that heat from work performed adiabatically in the expansion phase is all restored to the working fluid during the adiabatic recompression, less the net work performed. This allows both the energy and the thermodynamic potential to return to the same values at the beginning of each cycle, a point strongly emphasized by Carnot. Our action revision equates Carnot’s calorique, or the non-sensible heat later described by Clausius as ‘work-heat’ exclusively to negative Gibbs energy (-G) or quantum field energy. This action field complements the sensible energy or vis-viva heat as molecular kinetic motion and its recognition should have significance for designing more efficient heat engines or better understanding of the heat engine powering the Earth’s climates.

The move to a low carbon economy is very important for enhancing international competitiveness. The eco-innovation is the critical factor of the green paradigm. This study is designed to investigate deeply the determinants of eco-innovation of manufacturing firms in Korea by suggesting anticipated regulations, self-regulations, and industry-specific characteristics as external factors and open information sources as internal factors. The data used in the analysis is 1946 sample firms from Korean Innovation Survey 2010 based on the Oslo Manual. Using the multi-variate probit analysis and the zero-inflated negative binomial (ZINB) regression analysis, we have found out that the anticipated regulations and self-regulations have significant influences both on eco-process innovation and eco-product innovation, while industrial characteristics have no effects. The empirical results also show that the breadth of information sources has a positive effect on businesses in implementing eco-innovations. Our findings show that the Korean government should provide a good platform where firms can better understand the future trends of environmental policies, particularly policies on anticipated and self-regulations. At the same time, Korean firms should establish a voluntary system to control environmental activities so that they can improve eco-innovations through integrating external information.

Fibroblast growth factor 14 (FGF14) is a member of the intracellular FGFs, a group of proteins with roles in neuronal ion channel regulation and synaptic transmission. We have previously demonstrated that a male Fgf14-/- mouse model recapitulates salient endophenotypes of synaptic dysfunction and behaviors associated with schizophrenia (SZ). As the underlying etiology of SZ and its sex-specific onset remain elusive, the Fgf14-/- model provides a valuable tool to interrogate pathways that might be related to the disease mechanism. Here, we performed label free quantitative proteomics and bioinformatics to identify enriched pathways at the proteome level in the male and female hippocampi from Fgf14+/+ and Fgf14-/- mice. We discovered that many differentially expressed proteins in Fgf14-/- animals are associated with SZ. In addition, measured changes in the proteome and signaling pathways were predominantly sex-specific with the male Fgf14-/- being distinctly enriched for pathways associated with neuropsychiatric disorders and addiction and the female exhibiting modest changes. In the male Fgf14-/- mouse the major protein changes that could in part explain the previously described neurotransmission and behavioral phenotype of this model were loss of ALDH1A1 and PRKAR2B. ALDH1A1 has been shown to mediate an alternative pathway for GABA synthesis, while PRKAR2B is essential for dopamine 2 receptor signaling, which is the basis of current antipsychotics. Collectively, our results provide new insights in the role of FGF14 and support the use of the Fgf14-/- mouse as a useful preclinical model of SZ for generating hypothesis on the disease mechanism, sex-specific manifestation and therapy.

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.

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 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.

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.

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.

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 mixing of terrestrial groundwater and seawater creates dynamic reaction zones in intertidal areas, where land-derived Fe(II) is oxidized to Fe(III) and then precipitates as Fe hydroxides at groundwater-seawater interface. These hydrogeochemical processes contribute to the formation of iron curtains beneath soil surface, which in turn influences the evolution of coastal aquifers. This paper provides a comprehensive review of physical and geochemical processes at field scale in coastal areas, explores the impact of mineral precipitation on pore structure at pore scale, and synthesizes reactive transport modeling (RTM) approaches for illustrating continuum-scale soil physio-chemical parameters during the evolution of porous media. Upon this review, knowledge gaps and research needs are identified. Additionally, challenges and opportunities are presented. Therefore, the incorporation of observational data into a comprehensive physico-mathematical model becomes imperative for capturing the pore-scale processes in porous media and their influence on groundwater flow and solute transport at large scales. Furthermore, a synergistic approach integrating pore-scale modeling and non-invasive imaging can provide detailed insights into intricate fluid-pore-solid interactions for future studies, as well as facilitate the development of regional engineering-scale models and physio-chemical coupled models with diverse applications in submarine science and engineering.

This study introduces a specialized Automatic Speech Recognition (ASR) system, leveraging the Whisper Large-v2 model, specifically adapted for radiological applications in French language. Our methodology focused on adapting the model to accurately transcribe medical terminology and diverse accents within the French language context, achieving a notable Word Error Rate (WER) of 17.121%. The research involved extensive data collection and preprocessing, utilizing a wide range of French medical audio content. The results demonstrate the system's effectiveness in transcribing complex radiological data, underscoring its potential to enhance medical documentation efficiency in French-speaking clinical settings. The discussion extends to the broader implications of this technology in healthcare, including its potential integration with Electronic Health Records (EHRs) and its utility in medical education. The study also explores future research directions, such as tailoring ASR systems to specific medical specialties and languages. Overall, this research contributes significantly to the field of medical ASR systems, presenting a robust tool for radiological transcription in the French language and paving the way for advanced technology-enhanced healthcare solutions.

LC-SPIK is a liver cancer-specific isoform of Serine Protease Inhibitor Kazal and has been proposed as a new biomarker for the detection of HCC given its unique 3-D structure which differs from normal pancreatic SPIK. An ELISA technology based on its unique structure was developed to use LC-SPIK as an effective biomarker for the clinical diagnosis of HCC. AFP, the most widely used biomarker for HCC surveillance currently, suffers from poor clinical performance, especially in the detection of early-stage HCC. In one case-control study, which included 164 HCC patients and 324 controls, LC-SPIK had an AUC of 0.87 compared to only 0.70 for AFP in distinguishing HCC from liver disease controls (cirrhosis, HBV/HCV). LC-SPIK also performed significantly better than AFP for the 81 patients with early-stage HCC (BCLC stage 0 and A), with an AUC of 0.85 compared to only 0.61 for AFP. Cirrhosis is the major risk factor for HCC, about 80% of patients with newly diagnosed HCC have preexisting cirrhosis. LC-SPIK’s clinical performance was also studied in HCC patients with viral and non-viral cirrhosis including cirrhosis caused by nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). In a total of 163 viral cirrhosis patients with 93 HCC patients (50 early-stage), LC-SPIK had an AUC of 0.85, while AFP had an AUC of 0.70. For patients with early-stage HCC, LC-SPIK had a similar AUC of 0.83, while AFP had an AUC of only 0.60. For 120 patients with nonviral cirrhosis, including 62 HCC (23 early-stage) patients, LC-SPIK had an AUC of 0.84 while AFP had an AUC of only 0.72. For the 23 patients with early-stage HCC, LC-SPIK had a similar AUC of 0.83, while the AUC for AFP decreased to 0.65. All these results suggest that LC-SPIK has significantly better performance in the detection of HCC than AFP in all etiologies of liver diseases. In addition, LC-SPIK accurately detected the presence of HCC in 71%-91% of HCC patients with false-negative AFP test results in viral associated HCC and non-viral associated HCC.

To better understand how immunity develops against SARS-CoV-2 during the pandemic period of 2020 to 2022, we analyzed the immune response of a small group of university staff and students who were either infected or vaccinated. We investigated the levels of receptor-binding domain (RBD)-specific and nucleocapsid (N)-specific IgG and IgA antibodies in serum and saliva samples taken early (around 10 days after infection or vaccination) and later (around 1 month later), as well as N-specific T-cell responses. One patient who had been infected in 2020 developed serum RBD and N-specific IgG antibodies, but declined 8 months later, then mRNA vaccination in 2021 produced a higher level of anti-RBD IgG than natural infection. In the vaccination of naïve individuals, vaccines induced anti-RBD IgG, but it declined after 6 months. A third vaccination boosted the IgG level again, albeit to a lower level than after the second. In 2022, when the Omicron variant became dominant, familial transmission occurred even among vaccinated people. In infected individuals, the levels of serum anti-RBD IgG antibodies increased later, while anti-N IgG peaked earlier. The N-specific activated T cells expressing IFN- or CD107a were detected early. In saliva, SARS-CoV-2-specific IgG but not IgA was detected. Interestingly, two individuals showed a temporary peak in RBD- and N-specific IgA antibodies in their saliva on the second day after infection. Thus, SARS-CoV-2 infection triggers typical immune responses in humans against acute viral infections, but mucosal immune responses, which are temporarily induced early during infection, may be more important for protection than current intramuscular vaccines.

The Suter curves for Wh and Wm characteristics of collected and the first time presented Four-quadrant (4Q) diagrams of 11 radial pump-turbine models with different specific speeds (nq=24.34, nq=24.8, nq=27, nq=28.6, nq=38, nq=41.6, nq=41.9, nq=43.83, nq=50, nq=56, and nq=64.04) are given in the paper, as well as the Suter curves for 2 pump models (nq=25, and nq=41.8) which were already published in the literature. These 11+2 curves were analyzed to establish a certain universal law of behavior in dependence on the specific speed. For the determination of existing laws in behavior, the fitting procedure using the Regression and Spline methods was used. The paper presents a research plan and structures that include: data collection of four-quadrant diagrams for models of pump-turbines and pumps with different specific speeds (nq), the procedure of recalculation of Four-quadrant diagrams of the models into Suter curves for Wh and Wm characteristics, the definition of the optimal point for the pump and turbine operating mode in pump-turbine models for different specific speeds, and developing numerical models in the MATLAB program to obtain the Universal Equation for the Wh and Wm characteristics. The scientific contribution of this paper is the firstly published original mathematical curve named Universal Equation for the Wh and Wm characteristics for radial pumps and pump-turbines. Application of the equation has been demonstrated at the pumping station where two radial pumps are installed. The calculation of transient processes was performed using the numerical model developed by the authors in the mathematical program MATLAB. Comparison of the transition process results has been made for the two cases - when input data in the numerical model have been firstly used with the values of Suter curves for Wh and Wm characteristics obtained by recalculation from the Four-quadrant operating characteristics (Q11, n11, M11) of model’s specific speed, and then secondly with the values of the Suter curves for Wh and Wm characteristics obtained from the Universal Equation.

Sacroiliac (SI) joint dysfunction can lead to debilitating pain but can be treated with minimally invasive sacroiliac joint fusion (SIJF). This treatment is commonly performed using 2D fluoroscopic guidance. This makes placing the implants without damaging surrounding neural structures challenging. Virtual surgical planning (VSP) using simulated fluoroscopic images may improve perioperative guidance. This article describes a workflow with VSP in SIJF using simulated fluoroscopic images and evaluates achieved implant placement accuracy. Routinely collected survey data on the added value of VSP were also evaluated. Ten interventions were performed on 10 patients by the same surgeon, comprising 30 implants; the median age was 39 years, and all patients were female. The overall mean implant placement accuracy was 4.9 ± 1.26 mm and 4.0 ± 1.44°. There were no malpositioning complications. The VSP helped the surgeon understand the anatomy and determine the optimal position and length of the implants. The average Likert scale score of the survey was 4.7, suggesting a positive role of VSP for SIJF. Planned positions of the implants could be reproduced in surgery with clinically acceptable accuracy and VSP was a valuable asset for the surgeon.

Antibody-mediated targeting is an efficient strategy to enhance the specificity and selectivity of polymer nanomedicines towards the target site, typically a tumor. However, direct covalent coupling of an antibody with a polymer usually results in a partial damage of the antibody binding site accompanied with a compromised biological activity. Here, an original solution based on well-defined non-covalent interactions between tris-nitrilotriacetic acid (trisNTA) and hexahistidine (His-tag) groups, purposefully introduced to the structure of each macromolecule, is described. Specifically, trisNTA groups were attached along the chains of a hydrophilic statistical copolymer based on N-(2-hydroxypropyl)methacrylamide (HPMA), and at the end or along the chains of thermo-responsive di-block copolymers based on N-isopropylmethacrylamide (NIPMAM) and HPMA; His-tag was incorporated to the structure of a recombinant single chain fragment of an anti-GD2 monoclonal antibody (scFv-GD2). Static and dynamic light scattering analyses confirmed that mixing of polymer with scFv-GD2 led to the formation of polymer/scFv-GD2 complexes; those prepared from thermo-responsive polymers formed stable micelles at 37 °C. Flow cytometry and fluorescence microscopy clearly demonstrated antigen-specific binding of the prepared complexes to GD2 positive murine T-cell lymphoma cells EL-4 and human neuroblastoma cells UKF-NB3, while no interaction with GD2 negative murine fibroblast cells NIH-3T3 was observed. These non-covalent polymer protein complexes represent a new generation of highly specific actively targeted polymer therapeutics or diagnostics.

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.

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 2022-2023 Mpox multi-country outbreak, identified in over 110 WHO Member States, revealed a predominant impact on cisgender men, particularly those engaging in sex with men, while less frequently affecting women. This disparity prompted a focused investigation into the gender-specific characteristics of Mpox infections, particularly among women, to address a notable knowledge gap. This review systematically gathers and analyzes scientific literature and case reports concerning Mpox infections in women, covering a broad geographical spectrum including regions such as Buenos Aires, Brazil, Northern California, Colombia, Nigeria, Europe, Vietnam, Spain, Switzerland, and the United States. The analysis delves into various aspects of Mpox in women, including clinical features, epidemiology, psychological impacts, preparedness strategies, and case studies, with particular attention to pregnant women and those with underlying health conditions. Empirical data from multiple studies underscore the unique epidemiological and clinical patterns of Mpox in women. In the United States, a small percentage of Mpox cases were reported among cisgender women, with a notable portion involving non-Hispanic Black or African American, non-Hispanic White, and Hispanic or Latino ethnicities. The primary transmission route was identified as sexual or close intimate contact, with the virus predominantly manifesting on the legs, arms, and genital areas. Further, a study in Spain highlighted significant disparities in diagnosis delays, transmission modes, and clinical manifestations between genders, indicating a different risk profile and disease progression in women. Additionally, a case from Vietnam linked to a new Mpox sublineage in women emphasizes the role of women in the transmission dynamics and the importance of genomic monitoring. This review emphasizes the necessity for inclusive surveillance and research to fully understand Mpox dynamics across diverse population groups, including women. Highlighting gender and sexual orientation in public health responses is crucial for an effective approach to managing the spread and impact of the disease. The findings advocate for a gender-diverse assessment in health services and further research to explore the nuances of Mpox transmission, behavior, and progression among different groups, thereby enhancing the global response to Mpox and similar public health challenges.

The dominant paradigm holds that spontaneous and therapeutically induced anti-tumor responses are mediated mainly by CD8 T cells and directed against tumor-specific antigens (TSAs). The presence of specific TSAs on cancer cells can only be proven by mass spectrometry analyses. Bioinformatic predictions and reverse immunology studies cannot provide this type of conclusive evidence. Most TSAs are coded by unmutated non-canonical transcripts that arise from cancer-specific epigenetic and splicing aberrations. When searching for TSAs, mass spectrometry analyses must therefore interrogate not only the canonical reading frame of annotated exome but all reading frames of the entire translatome. The majority of aberrantly expressed TSAs (aeTSAs) derive from unstable short-lived proteins that are good substrates for direct MHC I presentation but poor substrates for cross-presentation. This is an important caveat because cancer cells are poor antigen-presenting cells and the immune system therefore depends on cross-presentation by dendritic cells (DCs) to detect the presence of TSAs. We therefore postulate that, in the untreated host, most aeTSAs are undetected by the immune system. We present evidence suggesting that vaccines inducing direct aeTSA presentation by DCs represent an attractive strategy for cancer treatment.

Translation is spatiotemporally regulated and ER-associated mRNAs are generally in efficient translation. It is unclear whether the ER-associated mRNAs are deadenylated or degraded on the ER surface in situ or in the cytosol. Here, we showed that ER possessed active deadenylases, particularly the poly(A)-specific ribonuclease (PARN), in common cell lines and mouse tissues. Consistently, purified recombinant PARN exhibited a strong ability to insert into the Langmuir monolayer and liposome. ER-anchored PARN was found to be able to reshape the poly(A) length profile of the ER-associated RNAs by suppressing long poly(A) tails without significantly influencing the cytosolic RNAs. The shortening of long poly(A) tails did not affect global translation efficiency, suggesting that the non-specific action of PARN towards long poly(A) tails was beyond the scope of translation regulation on the ER surface. Transcriptome sequencing analysis indicated that the ER-anchored PARN trigged the degradation of a small subset of ER-enriched transcripts. The ER-anchored PARN modulated the translation of its targets by redistributing ribosomes to heavy polysomes, suggesting that PARN may play a role in dynamic ribosome reallocation. During DNA damage response, MK2 phosphorylated PARN-Ser557 to modulate PARN translocation from the ER to cytosol. By promoting the decay of ER-associated MDM2 transcripts with low ribosome occupancy, the ER-anchored PARN modulated DNA damage response and thereby cell viability. These findings revealed that a highly regulated communication between mRNA degradation rate and translation efficiency is present on the ER surface in situ and that PARN may contribute to this communication by modulating the dynamic ribosome reallocation between transcripts with low and high ribosome occupancies.

Background: Recent developments in our understanding of the interactions between long non-coding RNA (lncRNA) and cellular components have improved treatment approaches for various human diseases including cancer, vascular diseases, and neurological diseases. Although investigation of specific lncRNAs revealed their role in the metabolism of cellular RNA, our understanding of their contribution to post-transcriptional regulation is relatively limited. In this study, we explore the role of lncRNAs in modulating alternative splicing and their impact on downstream protein-RNA interaction networks. Results: Analysis of alternative splicing events across 39 lncRNA wildtype and knockout RNA-sequencing datasets from three human cell lines: HeLa (Cervical Cancer), K562 (Myeloid Leukemia), and U87 (Glioblastoma), resulted in high confidence (fdr < 0.01) identification of 4432 skipped exon events and 2474 retained intron events, implicating 759 genes to be impacted at post-transcriptional level due to the loss of lncRNAs. We observed that a majority of the alternatively spliced genes in a lncRNA knockout were specific to the cell type, in agreement with the finding that genes affected by alternative splicing also displayed enriched functions in a cell type specific manner. To understand the mechanism behind this cell-type specific alternative splicing patterns, we analyzed RNA binding protein (RBP)-RNA interaction profiles across the spliced regions. Conclusions: Despite limited RBP binding data across cell lines, alternatively spliced events detected in lncRNA perturbation experiments were associated with RBPs binding in proximal intron-exon junctions, in a cell type specific manner. The cellular functions affected by alternative splicing were also affected in a cell type specific manner. Based on the RBP binding profiles in HeLa and K562 cells, we hypothesize that several lncRNAs are likely to exhibit a sponge effect in disease contexts, resulting in the functional disruption of RBPs due to altered titration of the RBPs from their target loci. We propose that such lncRNA sponges can extensively rewire the post-transcriptional gene regulatory networks by altering the protein-RNA interaction landscape in a cell-type specific manner.

The spread of fake news poses a serious threat to public trust and informed decision-making. The emergence of AI-generated fake news exacerbates this issue, as it can be produced more rapidly and convincingly than human-generated content. Addressing this issue, our paper introduces a robust approach to detect AI-generated fake news that is applicable across major disinformation domains: Politics and Elections, Health and Medicine, Science and Technology, and Entertainment and Celebrities. Our models differentiate between AI-generated and human-generated news articles while assessing their truthfulness. Utilizing large language models such as ChatGPT, we curated datasets spanning both AI and human generated fake and genuine news. Following extensive data preprocessing and the application of diverse feature extraction techniques, our models were trained using multiple machine learning algorithms. Our results show the feasibility of accurately identifying AI-generated fake news, thereby adding a significant layer of defense in combating misinformation across various sectors. In addition, we have explored the potential utility of transferable machine learning models trained on data from one domain (e.g., politics), when tested on another domain (e.g., health).

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].

Tailings generated by mining account for the largest proportion of global waste from industrial activities. Copper is relatively uncommon world-wide, with low concentrations in sediments and waters, yet is very elevated around mining sites. On the Keweenaw Peninsula of Michigan, USA, jutting out into Lake Superior, 140 mines extracted native copper from the Portage Lake Volcanic Series, part of an intercontinental rift system. Between 1901-1932, two mills at Gay (Mohawk, Wolverine) sluiced 22.7 million metric tonnes (MMT) of copper-rich tailings (stamp sands) into Grand (Big) Traverse Bay. Here we examine: 1) 3D coastal elevation and reef bathymetry, 2) particle dispersal, 3) copper concentrations and leaching, plus 4) shoreline toxicity. About 10 MMT of tailings created a migrating coastal beach that stretches 7 km from the Gay pile to the Traverse River Seawall. Another 10 MMT are moving underwater on the coastal shelf, threatening Buffalo Reef, an important lake trout and whitefish breeding ground. Aerial photos, ALS (plane) LiDAR, and relatively inexpensive UAS (drone) surveys characterize shoreline structure and aid initial remediation. Because sands (natural beach quartz, stamp sand basalt) are silicates of similar density, particle dispersal is similar and challenging. However, stamp sand beaches contrast greatly with natural sand beaches in both physical profile and chemistry. Dispersing particles retain copper, and release toxic concentrations. Leaching is elevated by exposure to high DOC and low pH waters. Field experiments, shoreline seining, and benthic sampling confirm serious impacts on aquatic biota, supporting tailings removal.

Diagnosis and treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in women remain insufficient. Fluctuations of reproductive hormones during the premenstrual period, postpartum period and (peri)menopause are neglected, even though they impact ADHD symptoms and as-sociated mood disorders [1]. Therefore, we created a female-specific treatment group for women with ADHD and premenstrual worsening of ADHD and/or mood symptoms. We describe the group programme and underlying rationale, offering a qualitative analysis of the participants’ evaluation. The 7 two-weekly sessions foreground the menstrual cycle and address several ADHD-specific topics in relation to this cyclical pattern: emotional regulation; impulsivity; setting boundaries, and triggers. Concurrently, women track their menstrual cycle and (fluctuating) ADHD and mood symptoms with an adjusted premenstrual calendar. In total, 18 women (25-47yrs) participated in three consecutive groups. We analysed the evaluation of the last group. Participants experienced the group as a safe and welcoming space. Recognition was valued by all. The topics discussed were deemed valuable and the structure suited them well. Completing the premenstrual calendar augmented awareness and recognition of individual cyclical symptoms. Discussing ADHD throughout the lifespan increased self-understanding. Participants took their menstrual cycle more seriously, prioritising self-acceptance and self-care in the luteal phase of the cycle. Exploring a cyclical approach in a group setting seems to be a positive addition to treatment for female ADHD.

Livestock management is challenging for resource-poor (R-P) farmers due to unavailability of quality feed, limited professional advice and rumor-spreading about animal health condition in a herd. This research seeks to improve animal health in southern Africa by promoting sericea lespedeza (Lespedeza cuneata), a nutraceutical fodder legume. An automated geospatial model for precision agriculture (PA) can identify suitable locations for its cultivation. Additionally, a novel approach of radio frequency identifier (RFID) supported telemetry technology can track animal movement, and the analyses of data using artificial intelligence can determine sickness of small ruminants. This RFID-based system is being connected to a smartphone app (under construction) to alert farmers of potential livestock health issues in real-time so they can take immediate corrective measures. An accompanying Decision Support System (DSS) site is being developed for R-P farmers to obtain all possible support on livestock production, including the designed PA and RFID-based DSS.

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.

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.

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.

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.

Hubei, Hunan and Henan Provinces are located in Central China, a region with extensive transport networks and trade. Bursaphelenchus xylophilus, the causative agent of pine wilt disease, is spreads mainly through human activities. In order to further understand the genetic structure of PWN in Central China, we studied the genetic information of PWN populations in this region and compared the genetic relationship with strains from Guangdong and Jiangsu provinces. We found that the HB (Hubei) 15, HEN (Henan) 20, HN (Hunan) 07, HN08 and HN10 had significantly more SNPs and homozygotes than other strains from Central China, and their most frequent mutant genotypes also differed from other strains. The clustering results indicated that HB15, HEN 20, HN07, HN08 and HN10 were genetically distinct from other strains and closely related to Guangdong strains. We also observed significant genetic variation among strains in Henan province, suggesting that some of them might have different transmission sources than those from Hubei and Hunan provinces. The results provide a basis for tracing the origin and spread of PWD in China.

During the past few years unexpected developments have driven studies in the field of clinical immunology. One driver of immense impact was the outbreak of a pandemic caused by the novel virus SARS-CoV-2. Excellent recent reviews address diverse aspects of immunological re-search into cardiovascular diseases. Here, we specifically focus on selected studies taking ad-vantage of advanced state-of-the-art molecular genetic methods ranging from genome-wide epi/transcriptome mapping and variant scanning to optogenetics and chemogenetics. First, we discuss emerging clinical relevance of advanced diagnostics for cardiovascular diseases - includ-ing those associated with COVID-19 - with a focus on the role of inflammation in cardiomyopa-thies and arrhythmias. Second, we consider newly identified immunological interactions at or-gan and systems level which affect cardiovascular pathogenesis. Thus, studies into immune in-fluences arising from the intestinal system are moving towards therapeutic exploitation. Fur-ther, powerful new research tools have enabled novel insight into brain – immune system inter-actions at unprecedented resolution. This latter line of investigation emphasizes the strength of influence of emotional stress - acting through defined brain regions - upon viral and cardiovas-cular disorders. Several challenges need to be overcome before the full impact of these far-reaching new findings will hit the clinical arena.

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.

(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.

The hospital indoor environment plays a significant role in shaping the microbial exposures that humans encounter. Resistance to antibiotics is one of the mechanisms employed by bacteria to develop resilience against stress in indoor environments. The extensive usage of antibiotics has been a key factor in driving changes in the ecological function of antibiotic resistance genes (ARGs) and their acquisition by pathogenic bacteria. By integrating the 16S rRNA Illumina sequencing and high throughput-qPCR approaches with water and air dust samples across seven departments at Peking University Shenzhen Hospital, China, this study yielded intriguing findings regarding the department-specific variation, transmission, and correlation of bacteria, ARGs and MGEs within the hospital indoor environment. One notable observation was that the seasonal variation played a vital role in shaping the bacterial composition in the overall hospital indoor environment across seven studied departments. Nevertheless, a similar significant seasonal impact was only observed in the blood test room and emergency departments, rather than in the other five departments. Another intriguing finding was the correlation between ARGs and MGEs abundance. This correlation was evident in the overall hospital indoor environment, which was conversely not found in the emergency, pneumology and gynecology departments. Additionally, while there was no significant relationship that occurred between bacterial communities and ARGs/MGEs within the hospital, the gynecology department demonstrated a close link between bacterial communities and the presence of ARGs/MGEs. Notably, the gynecology department also stood out as an important source of bacteria and ARGs/MGEs for other departments. This study underscores the need for careful surveillance and monitoring of antibiotic resistance, particularly in Legionella spp. in man-made water systems. The findings also show the importance of monitoring and understanding the genetic elements such as Tp614 involved in gene transfer and recombination, as well as their impact on antimicrobial treatment efficacy.

Age-related myelination decrease is considered one of the likely mechanisms of cognitive decline. The present study is based on the longitudinal assessment of global and regional myelination of the normal adult human brain using the fast macromolecular fraction (MPF) mapping. Additional markers were age-related changes in white matter (WM) hyperintensities on FLAIR-MRI and the levels of anti-myelin autoantibodies in serum. Eleven healthy subjects (33–60 years in the first study) were scanned twice, 7 years apart. An age-related decrease in MPF was found in global WM, GM, and mixed WM-GM, as well as in 48 out of 82 examined WM and GM regions. The greatest decrease in MPF was observed for the frontal WM (2-5%), genu of the corpus callosum (CC) (4.0%) and caudate nucleus (5.9%). The age-related decrease in MPF significantly correlated with an increase in the level of antibodies against myelin basic protein (MBP) in serum (r = 0.69 and r = 0.63 for global WM and mixed WM-GM, correspondingly). The volume of FLAIR hyperintensities increased with age but did not correlate with MPF changes and the levels of anti-myelin antibodies. MPF mapping showed high sensitivity to age-related changes in brain myelination, providing the feasibility of this method in clinics.

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.

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.

There is a growing concern about climate change being a serious threat to insurance business sustainability. Knowing if climate warming is a cause for claims and losses increase, and how this cause-effect relationship will develop in the future are two open major questions. In this article, we answer both questions by particularizing the geographical area of Spain, and a precise risk, hailstorm in crop insurance in the line of business of wine grapes. We measure climate change thanks to the Spanish Actuarial Climate Index (SACI). We use a database containing all the claims caused by hail risk in Spain from 1990 to 2022. With homogenized data, we consider as dependent variables the monthly number of claims, monthly number of loss costs equal to one, and monthly total losses. The independent variable is the monthly Spanish Actuarial Climate Index (SACI). We try to explain the former through the latter using regression and quantile regression models. Our main finding is that climate change as measured by SACI explains these three dependent variables. We also give an estimation of the increase of the monthly total losses Value at Risk, corresponding to a future increase in climate change measured in units of SACI. Spanish crop insurance managers should carefully incorporate these conclusions into their decision-making process to keep this line of business sustainable in the future.

Whole genome duplication (WGD) or polyploidization can occur at the cellular, tissue, and organismal levels. At the cellular level, tetraploidization has been proposed as a driver of aneuploidy and genome instability, and correlates strongly with cancer progression, metastasis, and development of drugs resistance[1–6]. WGD is also a key developmental strategy for regulating cell size, metabolism, and cellular function[1,7–10]. In specific tissues, WGD is involved in normal development (e.g. organogenesis), tissue homeostasis, wound healing, and regeneration[10–17]. At the organismal level, WGD propels evolutionary processes such as adaptation[18], speciation[19], and crop domestication[20]. An essential strategy to further our understanding of the mechanisms promoting WGD and its effects is to compare isogenic strains that differ only in their ploidy. Caenorhabditis elegans (C. elegans) is emerging as an animal model for these comparisons, in part because relatively stable and fertile tetraploid strains can be produced rapidly from nearly any diploid strain[7]. Here we review the use of Caenorhabditis polyploids as tools to understand important developmental processes (e.g. sex determination, dosage compensation, and allometric relationships)[21–27] and cellular processes (e.g. cell cycle regulation, chromosome dynamics during meiosis)[28–32]. We also discuss how the unique characteristics of the C. elegans WGD model will enable significant advances in our understanding of mechanisms of polyploidization and its role in development and disease.

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.

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.

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.

In Geo Polymer bricks (GPB), fly ash content which is a waste from power plants is converted into bricks by chemical treatment. GPB can be dried by using appropriate curing methods. Conven-tionally electric oven curing is one of the prominent methods. Using solar dryer instead of elec-trical oven gives added advantage of saving high grade electrical energy. So in this work solar dryer with PCM (Phase Change materials) Paraffin Wax and without PCM is used for curing ap-plication. GPB are gaining added advantage when compared to conventional bricks like cement and sand bricks in terms of strength. GPB has been taken as specimen for comparing the com-pressive, tensile split strength and flexural strength by electrical energy based curing and solar energy based curing. It is experimentally observed that solar energy based curing with PCM and without PCM exhibits higher compressive strength, higher tensile split strength and flexural strength when compared to electrical energy based curing. Solar curing with PCM shows higher compressive strength, higher tensile split strength and flexural strength when compared to Solar curing without PCM. Open solar curing is a traditional technique but nowadays aggressive cli-matic conditions can lead to severe damage of Geo polymers. The novelty of this work is to suggest to study the effect of PCM like paraffin wax in solar drying on curing time, mechanical properties of GPB.

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.

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.

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.

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.

Activation of the NLRP3 inflammasome plays a crucial role in innate immune response. During cell division, the NLRP3 inflammasome activation must be strictly controlled. Here, we discovered the anaphase promoting complex subunit 10 (Anapc10, APC10), a substrate recognition protein of the anaphase promoting complex/cyclosome (APC/C), is a critical mediator of the NLRP3 inflammasome activation. APC10 protein interacts with NLRP3, and co-localizes with NLRP3 protein in the cytoplasm. During interphase, APC10 interacts with NLRP3 to promote the NLRP3 inflammasome activation. During mitosis, APC10 disassociates from the NLRP3 inflammasome to inhibit the inflammatory responses. This study reveals a distinct mechanism by which APC10 serves as a switch of the NLRP3 inflammasome activation during cell cycle.

The effects of photon inertia on the determination of its trajectory were verified and the representation of a displacement mass characterized by the flow of the number of wavefronts and the decomposition of photon inertia into parts associated with translation and rotation motions was considered. It was found that with the relativistic increase of the photon's resistance to change its directional properties, it inhibits the relativistic trajectory of the second torque, of Minkowski, in an angular range of incidence. After synchronizations, in the OAM inversions, there are reductions of the inertia associated to the translational part that assumes classical predominance, where the relativistic trajectory is allowed while the photon offers less resistance to changes in its directional properties. The classical-relativistic variability of the photon inertia characterizes the classical or relativistic profile of the energy distribution in forms of motion, where adjustments of the rotational and translational parts can be performed as a function of the refractive index rate, temperature and angle of incidence. It was found that with increasing temperature of the refringent medium, the synchronizations displacement in the sense of the normal incidence. A specific vacuum temperature for the refringent medium was characterized, where the photon exhibits a classical-relativistic synchronization under all angles of incidence, characteristic of its immaterial state in vacuum.

Vibration suppression in a field of frequencies and the creation of band gaps which do not allow the propagation of the waves is studied in this paper by means of microstructures designed through topology optimization. Topology optimization is formulated in frequency domain. Band gap design is based on Floquet-Bloch theory and genetic optimization. The result is appealing in view of modern 3D printing techniques.

Following the coronavirus disease 2019 (COVID-19) pandemic, several studies have examined the possibility of correlating the virulence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, to the climatic conditions of the involved sites; however, inconclusive results have been generally obtained. Although either air temperature or humidity cannot be independently correlated with virus viability, a strong relationship between SARS-CoV-2 virulence and the specific enthalpy of moist air appears to exist, as confirmed by extensive data analysis. Given this framework, the present study involves a detailed investigation based on the first 20–30 days of the epidemic before public health interventions in 30 selected Italian provinces with rather different climates, here assumed as being representative of what happened in the country from North to South, of the relationship between COVID-19 distributions and the climatic conditions recorded at each site before the pandemic outbreak. Accordingly, a correlating equation between the incidence rate of the pandemic and the average specific enthalpy of atmospheric air was developed, and an enthalpy-based seasonal virulence risk scale was proposed as a tool to predict the potential danger of COVID-19 spread due to the persistence of weather conditions favorable to SARS-CoV-2 viability. For practical applications, a conclusive risk chart expressed in terms of coupled temperatures and relative humidity (RH) values was provided, showing that safer conditions occur in case of higher RH at the highest temperatures, and of lower RH at the lowest temperatures. The proposed risk scale was in agreement with the available infectivity data in the literature for a number of cities around the world.

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.

Both SARS-CoV-2 (COVID-19) and SARS coronaviruses (CoVs) are members of the subgenus Sarbecovirus. To understand the origin of SARS-CoV-2, protein sequences from sarbecoviruses were analyzed to identify highly-specific molecular markers consisting of conserved inserts or deletions (termed CSIs) in the spike (S) and nucleocapsid (N) proteins that are specific for either particular clusters/lineages of these viruses or are commonly shared by specific lineages. Three novel CSIs in the N-terminal domain of the spike protein S1-subunit (S1-NTD) are uniquely shared by the SARS-CoV-2, BatCoV-RaTG13 and most pangolin CoVs, distinguishing this cluster of viruses (SARS-CoV-2r) from all others. In the same positions, where these CSIs are found, related CSIs are also present in two other sarbecoviruses (viz. CoVZXC21 and CoVZC45 forming CoVZC cluster), which form an out group of the SARS-CoV-2r cluster. These three CSIs are not found in the SARS-CoVs. However, both SARS and SARS-CoV-2r CoVs contain two large CSIs in the C-terminal domain of S1 (S1-CTD), which binds the human ACE-2 receptor, that are absent in the CoVZC cluster of CoVs. These results indicate that while the S1-NTD of the SARS-CoV-2r viruses possesses the sequence characteristics of the CoVZC cluster of CoVs, their S1-CTD resembles the SARS viruses. Thus, the spike protein of SARS-CoV-2r viruses has likely originated from a recombination event between the S1-NTD of the CoVZC viruses and the S1-CTD of SARS viruses. This inference is also supported by the amino acid sequence similarity of the S1-NTD and S1-CTD from SARS-CoV-2 compared to the CoVZC and SARS CoVs. We also present evidence that one of the pangolin-CoV_MP789, whose receptor-binding domain is most similar to the SARS-CoV-2, is also derived by a recent recombination between the S1-NTD of the CoVZC CoVs and the S1-CTD of a SARS-CoV-2 related virus. Several other identified CSIs are specific for others clusters of sarbecoviruses including a clade consisting of bat SARS-CoVs (BM48-31/BGR/2008 and SARS_BtKY72). Structural mappings studies show that the identified CSIs are located within surface-exposed loops and form distinct patches on the surface of the spike protein. These surface loops/patches are predicted to interact with other host components and play important role in the biology/pathology of SARS-CoV-2 virus. Lastly, the CSIs specific for the SARS-CoV-2r clade provide novel means for development of new diagnostic and therapeutic targets for these viruses.

Air pollution, climate change and global warming show direct linkage. Introduction - Background: Research in the field has proposed and demonstrated their link to increased allergenicity in plants, leading to increased allergic diseases. Allergen patterns are changing in response to climate change. Across Europe, up to 12% of the population suffers from allergic diseases (bronchial asthma and allergic rhinitis) caused by the pollen grains. The medical costs of these types of allergies are enormous and are increasing with the spread of common ragweed - Ambrosia artemisiifolia* in Europe. In practice, more and more patients are turning to allergists. Methods: Based on these data, the research aims to identify safety measures and specific legislation to control and eradicate common ragweed in the countries most affected by the spread of this plant in Europe, increase in population exposure in countries affected by the presence of common ragweed and the socio-economic impact of allergic rhinitis and bronchial asthma at European level.[1][2] Our database search did not reveal any other research that has addressed this topic to date. Results: This research identifies specific legislation to the countries most affected by the spread of this plant pollen grains at European level, changes in allergen patterns and monitoring/safety eradication measures decided by local authorities, and data on the spread of common ragweed over the last two decades, costs per treatment, increased allergic rhinitis and bronchial asthma morbidity in the most affected areas. Conclusions: At European level, there are no universally valid models for eradicating this weed. Various methods can be used to limit the spread of common ragweed and its pollen production (e.g. mowing once or twice a year of overgrown land, ploughing, chemical control, public information, etc.). Local and regional cooperation should be considered essential to promote phytosanitary &amp; safety measures and exchange of information on methods to identify and manage the spread of common ragweed. Unified legislation at European level would help all affected countries; reduce morbidity from respiratory allergic diseases and the costs of treating these diseases.

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.

COVID-19 is one of the deadliest respiratory diseases, and its emergence caught the pharmaceutical industry off guard. While vaccines have been rapidly developed, treatment options for infected people remain scarce, and COVID-19 poses a substantial global threat. This study presents a novel workflow to predict robust druggable targets against emerging RNA viruses using metabolic networks and information of the viral structure and its genome sequence. For this purpose, we implemented pymCADRE and PREDICATE to create tissue-specific metabolic models, construct viral biomass functions and predict host-based antiviral targets from more than one genome. We observed that pymCADRE reduces the computational time of flux variability analysis for internal optimizations. We applied these tools to create a new metabolic network of primary bronchial epithelial cells infected with SARS-CoV-2 and identified enzymatic reactions with inhibitory effects. The most promising reported targets were from the purine metabolism, while targeting the pyrimidine and carbohydrate metabolisms seemed to be promising approaches to enhance viral inhibition. Finally, we computationally tested the robustness of our targets in all known variants of concern, verifying our targets’ inhibitory effects. Since laboratory tests are time-consuming and involve complex readouts to track processes, our workflow focuses on metabolic fluxes within infected cells and is applicable for rapid hypothesis-driven identification of potentially exploitable antivirals concerning various viruses and host cell types.

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.

The investigation by the integrated approach newly introduced for this study indicates that insulin resistance (IR) would develop first preferentially in the muscle tissue with a relatively low cell turnover and then progress in sequence to the subcutaneous adipose tissue, to the visceral adipose tissue, and to the liver with higher cell turnovers. Moreover, metabolic disruptions due to IR vary widely from tissue to tissue, contrary to the conventional notion that IR merely impairs glucose uptake in the whole body. This warrants that IR be divided better into four distinct tissue specific IRs: muscle insulin resistance (MIR), subcutaneous adipose insulin resistance (s-AIR), visceral adipose insulin resistance (v-AIR), and hepatic insulin resistance (HIR). Tissue-specific IRs developing in the order of MIR, s-AIR, v-AIR, and HIR – producing tissue specific metabolic disruptions – would amount to nothing but the whole body insulin resistance (WBIR) evolving in four distinctively insulin resistant stages. The four stage metabolic evolution from rapid weight gain to visceral obesity to rapid weight loss to full blown diabetes not only complies well with the natural development history of diabetes but also resolves most of the controversies regarding obesity or diabetes, including visceral obesity, obesity paradox, and dawn phenomenon that have long remained metabolic puzzles. In addition, the four-stage WBIR evolution model refutes the entrenched notion of the lipid-induced insulin resistance (LIIR) but supports instead the glycation-induced insulin resistance (GIIR) proposed in this study. A speculation is that the glycation reaction activated ever more with WBIR evolving may serve as the common thread connecting each other a cluster of disorders or diseases that are often collectively referred to as the metabolic syndrome, such as obesity, diabetes, cardio/cerebral vasculopathy, nephropathy, neuropathy, and retinopathy.

Although the existing paradigm states that CMV reactivation is under control of cellular immune response, the role of humoral counterpart is underestimated. Anti-CMV positive woman after conditioning with Bu-Flu-ATG underwent stem cell transplantation from fully matched, seronegative sibling donor. In immunodeficient recipient fast and significant decrease of specific immune response was observed but reconstitution of marrow-derived B and NK cells was prior thymic origin T cells. The lowest CMV-IgG(89 U/ml) was observed just before CMV viremia. Noteworthy, the sole and exclusive factor of CMV-specific immune response is a residual recipient antibody class IgG. The CMV-quantiferon increase was observed later, but in the first phase immune reconstitution of the PHA-induced IFNγ release was significantly lower than that CMV-induced. It corresponds with NK cells increase at the top of lymphocyte reconstitution and undetected CMV-specific CD8 cells by pentamer technique. Most of NK cells are CD16+, thus are stimulated by residual IgG. In immunocompetent donor the cellular and humoral immune response increases in parallel manner but symptoms of CMV mononucleosis were observed till the increase of specific IgG. Our observations shed light on a unique host-CMV interaction: indicate that significant decrease of CMV-IgG is a good predictor for CMV reactivation during secondary immunodeficiency.