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AbstractZika virus is responsible for causing Zika infections and was declared as a public health emergency of international concern in February 2016. The Zika virus NS3-helicase is a viable drug target for the design of inhibitors due to its essential role in the replication of viral genome. The viral RNA is unwound by the NS3-helicase in order to enable the reproduction of viral genome by the NS5 protein. Zika virus infections in humans are being reported for the last 15 years. We have therefore carried out amino acid mutational analyses of NS3-helicase. NS3-helicase has two crucial binding sites: the ATP and RNA binding sites. The cofactor-ATP based pharmacophore was generated for virtual screening of ZINC database using Pharmit server, that is followed by molecular docking and molecular dynamics simulations of potential hits as probable Zika virus NS3-helicase inhibitors at the cofactor binding site. The drug-like properties of the molecules were analysed and, DFT calculations were performed on the five best molecules to reveal their stability in solvent phase compared to gas phase, the HOMO and LUMO and electrostatic potential maps to analyze the electronic and geometric characteristics. These are significant findings towards the discovery of new inhibitors of Zika virus NS3-helicase, a promising drug target to treat the Zika virus infection.Communicated by Ramaswamy H. Sarma

A hybrid Mg composite filled with micro Al2O3 and nano TiO2 is manufactured through a blend press sinter powder metallurgy route. To appraise the significance of filler incorporation on the mechanical and corrosion strength, the composite is undergoing a series of characterizations. Initially the filler distribution was analyzed through electron microscopes. Static mechanical tests as per ASTM are conducted to measure the influence of fillers on the tensile and compression properties. The corrosion characteristics were studied by immersing the composites into the laboratory synthesized stimulated body fluid (SBF). Through the Tafel Polarization, the corroded surfaces are examined. The corrosion resistance of the composites exhibited a change that closely resembled that of pure magnesium. Based on the experimental findings, it appears that the composite being examined is well-suited for various biomedical applications, particularly in the field of dental implants.

Aqueous solutions of surfactants exhibit remarkable differences in their adsorption properties on metal surfaces. This study evaluates the adsorption of surfactant mixtures on zinc metal surfaces. The adsorption of single surfactants cocamidopropyl betaine (CAPB) and sodium dodecyl benzenesulfonate (SDBS) and their mixtures from aqueous solution at mole fractions of 0.00, 0.25, 0.50, 0.75 and 1.00 on zinc powder at 25 °C was studied. The surface tension of the single and CAPB/SDBS surfactant mixtures was measured in the presence and absence of 2 % zinc powder to determine the adsorption isotherms. The depletion method was employed to carry out the adsorption investigation. The amount of the surfactant adsorbed was also calculated from the shaded area between the surface tension versus concentration curves of these surfactants in the presence and absence of 2 % zinc powder. The highest adsorbed amounts were found to increase with the SDBS content. Furthermore, scanning electron microscope (SEM) images of zinc sheets in solutions containing single or mixed CAPB/SDBS surfactants were taken in the presence and absence of 0.05 M HCl. The micrographs indicated that the CAPB-SDBS surfactant layers formed by precipitation can protect zinc metal from acid corrosion.

This article discusses the quasi-optimality of adaptive nonconforming finite element methods for distributed optimal control problems governed by 𝑚-harmonic operators for m=1,2m=1,2. A variational discretization approach is employed and the state and adjoint variables are discretized using nonconforming finite elements. Error equivalence results at the continuous and discrete levels lead to a priori and a posteriori error estimates for the optimal control problem. The general axiomatic framework that includes stability, reduction, discrete reliability, and quasi-orthogonality establishes the quasi-optimality. Numerical results demonstrate the theoretically predicted orders of convergence and the efficiency of the adaptive estimator.

Thioredoxin reductases (TrxR) activate thioredoxins (Trx) that regulate the activity of diverse target proteins essential to prokaryotic and eukaryotic life. However, very little is understood of TrxR/Trx systems and redox control in methanogenic microbes from the domain Archaea(methanogens), for which genomes are abundant with annotations for ferredoxin:thioredoxin reductases [Fdx/thioredoxin reductase (FTR)] from group 4 of the widespread FTR-like family. Only two from the FTR-like family are characterized: the plant-type FTR from group 1 and FDR from group 6. Herein, the group 4 archetype (AFTR) from Methanosarcina acetivoranswas characterized to advance understanding of the family and TrxR/Trx systems in methanogens. The modeled structure of AFTR, together with EPR and Mössbauer spectroscopies, supports a catalytic mechanism similar to plant-type FTR and FDR, albeit with important exceptions. EPR spectroscopy of reduced AFTR identified a transient [4Fe–4S]1+cluster exhibiting a mixture of S= 7/2 and typical S= 1/2 signals, although rare for proteins containing [4Fe–4S] clusters, it is most likely the on-pathway intermediate in the disulfide reduction. Furthermore, an active site histidine equivalent to residues essential for the activity of plant-type FTR and FDR was found dispensable for AFTR. Finally, a unique thioredoxin system was reconstituted from AFTR, ferredoxin, and Trx2 from M. acetivorans, for which specialized target proteins were identified that are essential for growth and other diverse metabolisms.

Vivaldi tapered slot antenna (VTSA) families are low-cost, lightweight, and have a simple design structure with good electrical performance and consistent impedance over a wide frequency range. It can be fabricated on a fragile substrate to be used for various applications like an aircraft wing or in wearable networks. One biggest issue with this antenna is impedance matching. In this design, an antipodal Tapered slot antenna is used. The proposed antenna’s feed structure used a SIW (Substrate Integrated Waveguide) to microstrip transition. It allows us to design the characteristics of an antenna on a common substrate while maintaining a high-quality factor. The structure is simulated in CSTMWS (CST Microwave Studio) and the equivalent circuit of the transition part is also evaluated using ADS software tools. The operating frequency range of the structure is between 8 and 12 GHz (X band). This band has potential uses in radar, imaging, medical, space communication, and military applications. The whole structure is fabricated on the RO4003c substrate and measurements are taken with a VNA. The simulated and measured results are found to be very close to each other. The designed structure has a 40% percentage bandwidth and the overall dimension is 33 × 14 mm2.

ABSTRACTThe increasing adoption of digital technologies at the workplace demands lifelong learning for the employees by enhancing their digital competence (DC), impacting their basic psychological needs satisfaction (BPNS). This study aims to assess the effect of employees’ DC on flourishing through BPNS factors among working professionals in service industries by proposing the BPNS framework. A usable sample of 289 professionals working in service industries from North America, Europe, and the United Kingdom was collected to provide empirical support for the proposed model using PLS-SEM. Findings suggest that the employees’ DC positively impacts all three factors of BPNS, impacting flourishing. The sense of community as a moderator significantly affects the relationship between the autonomy factor of BPNS and flourishing. Service firms can design interventions that take care of the service employees’ needs satisfaction, thus making them flourish. The study ends with a note on its limitations and future research directions.

Applications of multimodal neuroimaging techniques, including electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) have gained prominence in recent years, and they are widely practiced in brain–computer interface (BCI) and neuro-pathological diagnosis applications. Most existing approaches assume observations are independent and identically distributed (i.i.d.), as shown in the top section of the right figure, yet ignore the difference among subjects. It has been challenging to model subject groups to maintain topological information (e.g., patient graphs) while fusing BCI signals for discriminant feature learning. In this article, we introduce a topology-aware graph-based multimodal fusion (TaGMF) framework to classify amyotrophic lateral sclerosis (ALS) and healthy subjects, illustrated in the lower section of the right image. Our framework is built on graph neural networks (GNNs) but with two unique contributions. First, a novel topology-aware graph (TaG) is proposed to model subject groups by considering: 1) intersubject; 2) intrasubject; and 3) intergroup relations. Second, the learned representation of EEG and fNIRS signals of each subject allows for explorations of different fusion strategies along with the TaGMF optimizations. Our analysis demonstrates the effectiveness of our graph-based fusion approach in multimodal classification by achieving a 22.6% performance improvement over classical approaches.

Background: In addition to being one of the deadliest tumors, breast cancer is also one of the most difficult to cure. Due to the serious side effects of current breast cancer treatments and the rise in drug resistance, current drugs are losing their effectiveness. Potential Natural Bioactives: Bioactive natural compounds target various pathophysiological pathways involved in the development and progression of cancer and hence have the ability to prevent both the growth of breast cancer and the advancement of metastatic disease concurrently. Natural anticancer compounds have been shown to be effective, complementary treatment may be of great assistance in this case. Clinical Outcomes: Nutraceuticals and popular folk remedies may provide benefits over manufactured pharmaceuticals since they have fewer side effects and less toxicity in both in vitro and in vivo studies. A variety of natural compounds have been shown to reduce the aggressiveness of breast cancer, inhibit the growth of malignant cells, and alter the pathways involved in cancer development and progression. Either by directly affecting certain biological targets, such genes, or by indirectly stabilising conjugates that have an impact on metabolic processes, natural compounds called phytochemicals can enhance human health. Mechanistic Pathways: There are many promising bioactive natural products that can be used to treat breast cancer, including those that inhibit aromatase activity, target HIF-1 signaling, inhibit cytoplasmic signaling, modulate epigenetic regulation, modulate estrogen signaling pathways, or work in chemosensitivity/adjuvant therapy (such as resveratrol, epigallocatechin-3-gallate, and eugenol).

The development of mutual prodrugs signifies a pivotal advancement in the optimization of therapeutic profiles for established pharmaceuticals. This study explores the synthesis and evaluation of an innovative mutual prodrug combining the nonsteroidal anti-inflammatory drug (NSAID) Ketoprofen and the skeletal muscle relaxant Chlorzoxazone. Designed to alleviate gastric irritation inherent to NSAIDs while capitalizing on the synergistic benefits of both agents, the synthesized mutual prodrug was characterized and confirmed through extensive physicochemical and spectroscopic studies. Solubility and partition coefficient analyses indicated heightened lipophilicity, enhancing the prodrug's suitability for oral administration compared to its parent drugs. Additionally, protein binding studies revealed a low binding affinity, suggesting improved bioavailability. Subsequent in vitrohydrolysis studies assessed the prodrug's stability across various pH levels (1.2, 3, 5 and 7.4) simulated gastric and intestinal fluids, plasma and rat liver homogenate, with quantitative evaluation performed by high-performance liquid chromatography. The prodrug remained stable and unhydrolyzed in the stomach after absorption, but underwent rapid cleavage by esterase's in blood and rat liver homogenate, releasing the active parent drugs. Our investigation underscores the transformative potential of mutual prodrug design in optimizing the efficacy and safety profile of combining NSAIDs with muscle relaxants. This approach offers a novel therapeutic strategy that enhances patient outcomes while minimizing adverse effects, paving the way for innovative treatments in managing musculoskeletal conditions and improving overall quality of life.

Childhood malnutrition is a major problem in developing countries, particularly in Ethiopia. This study aimed to create nutritious emmer wheat and cowpea extruded porridge with optimal macronutrient levels and sensory quality. Utilizing Design-Expert software, the effects of cowpea blending ratios (10–25 %), barrel temperatures (80–120 °C), and feed moisture content (22–26 %) were analyzed using a three-factor, three-level Box-Behnken design. Significant impacts on nutritional characteristics were observed, leading to the identification of optimal extrusion conditions (cowpea blend: 20.17 %, moisture content: 25.91 %, barrel temperature: 117.20 °C). Blending emmer wheat with cowpea flour significantly enhanced the porridge's color, taste, and aroma. The highest color intensity (4.36 %) was at 10 % cowpea and 22 % moisture processed at 100 °C. The best taste (4.41 %) was with 25 % cowpea and 22 % moisture at 100 °C, while the highest aroma was in blends with 10 % and 25 % cowpea at 100 °C. The control had the best mouthfeel (4.36 %), but a blend with 25 % cowpea, 24 % moisture, and 80 °C barrel temperature had the highest overall acceptability (4.31 %). The study highlighted the potential of these protein-rich porridge products to address protein-energy malnutrition, particularly in Ethiopia, by introducing awareness about the unique nutritional composition of Ethiopian emmer wheat and underutilized cowpea, thus creating a new market for nutritious food options.