Tyrosine kinase fibroblast growth factor receptor (FGFR), which is aberrant in various cancer types, is a promising target for cancer therapy. Here we reported the design, synthesis, and biological evaluation of a new series of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazoles derivatives as potent FGFR inhibitors. Compound 10a was first identified as a potent FGFR1 inhibitor, with good enzymatic inhibition. Further structure-based optimization revealed that compound 13a is the most potent FGFR1 inhibitor in this series with the enzyme inhibitory activity about 30.2 nM of IC50 value.

Background: Circulating rare cells participate in breast cancer evolution as systemic components of the disease and thus, are a source of theranostic information. Exploration of cancer-associated rare cells is in its infancy. We determined the validity of a rare-cell detection platform and demonstrated the usefulness of a certain rare cell subset as a novel approach to characterize the breast cancer system. Methods: Linearity of the Rarmax® platform was established using a spike-in approach. The platform includes red blood cell lysis, leukocyte depletion and high-resolution fluorescence image recording. Rare cell analysis was conducted on 28 samples (before and after surgery) from 14 patients with breast cancer, 20 healthy volunteers and 9 non-cancer control volunteers. In-depth identification of rare cells, including circulating tumor cells, endothelial-like cells, erythroblasts and inflammation-associated cells, was performed using a phenotype and morphology-based classification system. Results: The platform performed linearly over a range of 5-950 spiked cells, with an average recovery of 84.6%. Circulating epithelial and endothelial-like cell subsets have been demonstrated to be associated with or independent of cancer with tumor presence. Furthermore, certain cell patterns may be associated with treatment-related adverse effects. The sensitivity in detecting tumor-presence and cancer-associated abnormality before surgery was 50% and 85.7%, respectively and the specificity was 100% and 96.6%, respectively. Conclusion: The present study supports the idea of a cancer-associated rare cell abnormality to represent tumor entities as well as systemic cancer. The latter is independent of the apparent clinical cancer.

In this paper, we introduce a specialized, fully automated experimental arrangement designed for assessing the effectiveness of augmented and virtual reality technologies in healthcare setting and explore its design principles focusing on depth sensor characterization. The main goal of this project is to establish a robust benchtop platform for the quantitative evaluation of extended reality technologies in a controlled environment, emphasizing the practical assessment of augmented reality head-mounted devices. We outline a design concept and considerations for an experimental configuration aimed at creating a realistic testing environment. This apparatus comprises an observation platform mounted on a three-degree-of-freedom motorized system and a test phantom stage. Focusing on real-case scenarios, we utilized a range of sensors, including readily available range-sensing cameras and commercial augmented reality headsets, such as the Intel RealSense L515 LiDAR camera, mounted on the motion control system. The setup enabled automated data collection and facilitates controlled assessments and validation of various facets of augmented reality technologies, including object, hand, and head tracking, as well as static and dynamic image registration. This paper describes the system architecture, the process of automated data collection, and presents several evaluation studies conducted with this setup, providing insights into the quality and temporal noise associated with static or moving objects or observers in augmented reality applications.

Precision metagenomic approaches using Oxford Nanopore Technology (ONT) sequencing has been shown to allow recovery of complete genomes of Escherichia coli O157:H7 from overnight enrichments of agricultural waters. This study tests the applicability of a similar approach for Cronobacter genome recovery from powdered infant formula (PIF) overnight enrichments, where Cronobacter typically dominates the overall microbiome (>90%). In this study, we aimed to test whether using ONT sequencing of overnight PIF enrichments could recover a completely closed Cronobacter genome for further genomic characterization. Ten PIF samples, each inoculated with different Cronobacter strains, covering Cronobacter sakazakii, C. muytjensii, C. dublinensis, C. turicensis, and C. universalis, were processed according to the Bacteriological Analytical Manual (BAM) protocol. qPCR was used for initial screening (detection and quantification) of the overnight enrichments and confirmed that the spiked PIF samples after the overnight enrichment have high levels of Cronobacter (107 to 109 CFU/mL). DNA from overnight PIF enrichments was extracted from the enrichment broth and sequenced using ONT. Results showed that ONT sequencing could accurately identify, characterize, and close the genomes of Cronobacter strains from overnight PIF enrichments in 3 days, much faster than the nearly two weeks required by the current BAM method. Complete genome recovery and species differentiation were achieved. This suggests that combining qPCR with ONT sequencing provides a rapid, cost-effective alternative for detecting and characterizing Cronobacter in PIF, enabling timely corrective actions during outbreaks.

Asymmetric lithium salts, such as Lithium (difluoromethanesulfonyl)(trifluoromethanesulfonyl)imide (LiDFTFSI), have been demonstrated to surpass traditional symmetric lithium salts with improved Li+ conductivity and the capacity to generate stable solid electrolyte interphase (SEI) while maintaining compatibility with aluminum (Al0) current collector. However, the intrinsic reductive mechanism through which LiDFTFSI influences battery performance remains unclear and under debate. Herein, the detailed SEI reactions of LiDFTFSI-based electrolytes were investigated by combining density functional theory and molecular dynamics, aiming to clarify the formation process and atomic structure of SEI. Our results show that asymmetric DFTFSI– weakens the interaction between carbonate solvents and Li+, and substantially alter the solvation structure, exhibiting a well-balanced coordination capacity to bis(trifluoromethanesulfonyl)imide (TFSI–). Nanoseconds hybrid molecular dynamics simulation further reveals that the preferential decomposition of LiDFTFSI produces sufficient LiF and Li2O to facilitate a robust SEI. Moreover, the abundant F– generated from LiDFTFSI decomposition accumulates on the Al surface and subsequently combines with Al3+ from the current collector to form AlF3, potentially inhibiting corrosion of the current collector. Overall, these findings elucidate how LiDFTFSI regulates the solvation sheath and SEI structure, advancing the development of high-performance electrolytes compatible with current collector.

This investigation explores the potential of enhancing aqueous zinc-ion batteries (AZIBs) through the introduction of a novel cathode material, NH4V4O10 (NVO), combined with reduced graphene oxide (rGO). Utilizing Density Functional Theory (DFT), it was hypothesized that the incorpora-tion of rGO would increase the interlayer spacing of NVO and diminish the charge transfer in-teractions, thus promoting enhanced diffusion of Zn2+ ions. These theoretical predictions were substantiated by experimental data acquired from hydrothermal synthesis, which indicated a marked increase in interlayer spacing. Significantly, the NVO-rGO composite exhibits remarkable cyclic durability, maintaining 95% of its initial specific capacity of 507 mAh g−1 after 600 cycles at a current density of 5 A g−1. The electrochemical performance of NVO-rGO not only surpasses that of pristine NVO but also outperforms the majority of existing vanadium oxide cathode materials reported in the literature. This study underscores the effective integration of theoretical insights and experimental validation, contributing to the advancement of high-performance energy storage technologies.

This study explores the enhancement of aqueous zinc-ion batteries (AZIBs) using ammonium-enhanced vanadium oxide cathodes. Density Functional Theory (DFT) calculations reveal that NH₄⁺ incorporation into V₆O₁₆ lattices significantly facilitates Zn²⁺ ion diffusion by reducing electrostatic interactions, acting as a structural lubricant. Subsequent experimental validation using (NH₄)₂V₆O₁₆ cathodes synthesized via a hydrothermal method corroborates the DFT findings, demonstrating remarkable electrochemical stability with a capacity retention of 90% after 2000 cycles at 5 A g⁻¹. These results underscore the potential of NH₄⁺ in improving the performance and longevity of AZIBs, providing a pathway for sustainable energy storage solutions.

The ingestion of ethanol presents a significant global public health challenge. Chronic alcohol consumption is associated with the development of conditions such as cancer, cirrhosis, hepatic diseases, cardiovascular diseases, and diabetes, as well as neurological impairments that may predispose individuals to dementia, schizophrenia, and behavioral disorders such as violence and suicide. Alcohol-related fatalities constitute 5.3% of worldwide deaths annually, totaling approximately 3 million. Notably, alcohol consumption is implicated in 25% of cirrhosis-related deaths and 4.1% of cancer-related deaths. Taurine (2-aminoethanesulfonic acid) is a non-protein β-amino acid essential for cellular homeostasis, possessing antioxidant, anti-inflammatory, and cytoprotective properties crucial for life maintenance. This study aimed to evaluate the effects of taurine administration on hippocampal neurogenesis, neuronal preservation or reverse damage in rats exposed to forced ethanol consumption. Results demonstrated the neuroprotective effects of taurine on ethanol-treated rats, promoting tissue regeneration and suggesting its pivotal role in this process. However, this aminoacid failed to induce neurogenesis in the tissues of healthy rats, implying that its activity may be contingent upon post-injury stimuli.

The emergence of prosumers, who actively participate in designing and producing goods, has generated interest in domestically manufactured products. Factors such as innovation, design methods, component reuse, prototyping, and digital fabrication empower prosumer designers to realize their ideas and enhance products to meet their specific design requirements. This article presents a case that combines bioinspired design methods with prosumer characteristics from the perspective of a designer who uses biological research results acting as a prosumer. By analyzing prosumer needs, bioinspired design, and domestic fabrication requirements, designers define the methods that best suit their possibilities. As a result of using biological information, the geometry of Samara seeds, propeller sizing, wind tunnel tests, and subsequent improvements, the custom design of a bioinspired microgenerator has been refined to the final design of a bicycle flashlight. The aim is to popularize a working approach that facilitates the interaction of design methods and reinforces domestic manufacturing processes. Implementing bioinspired design methods within the prosumer context offers a methodological alternative to transform the current economic model, promoting systemic sustainability and the development of proprietary technologies.

This study presents the synthesis and electrochemical evaluation of nitrogen-doped vanadium oxide (N-V2O3/C) as a cathode material for aqueous zinc-ion batteries (AZIBs), using a hydrothermal method. Compared to undoped V2O3/C, N-V2O3/C exhibits enhanced electrical conductivity, capacity, and electrochemical kinetics, attributed to the incorporation of pyridinic and pyrrolic nitrogen. Initial charge-discharge cycles indicate phase transitions to amorphous vanadium oxides, enhancing conductivity. N-V2O3/C shows a high specific capacity of 168.4 mAh g−1 at 10 A g−1 and remarkable reversibility, highlighted by the transient existence of intermediate species during cycling. Optimal electrochemical performance is achieved with a vanadium to nitrogen molar ratio of 2:3, indicating the significant impact of nitrogen doping concentration on the material’s efficiency. This work underscores the potential of N-V2O3/C as a superior cathode material for AZIBs.

Using density functional theory (DFT), the density of states of NH4V3O8 (NVO) was analyzed pre and post-oxygen defects (Od) formation. The findings revealed a reduced bandgap in NVO after Od introduction, emphasizing the role of Od in enhancing conductivity of the material, thus improving its electrochemical attributes. Through the water bath method, both NVO and its oxygen-deficient counterpart, (NH4)2V10O25⸱8H2O (NVOd), were synthesized as potential cathode materials for aqueous zinc-ion batteries (AZIBs). Experimental outcomes resonated with DFT predictions, highlighting the beneficial role of oxygen defects in boosting electrical conductivity. Notably, the refined material displayed a remarkable capacity of 479.3 mAh g-1 at 0.1 A g-1, underscoring its promise for advanced energy storage solutions.

Classical antibacterial drugs were designed to target specific bacterial properties distinct from host human cells to maximize potency and selectivity. These designs were quite effective as they could be easily derivatized to bear next generation drugs. However, the rapid mutation of bacteria and their associated acquired drug resistance have led to the rise of highly pathogenic superbug bacterial strains for which treatment with first line drugs is no match. More than ever, there is a dire need for antibacterial drug design that goes beyond conventional standards. Taking inspiration by the body’s innate immune response to employ its own supply of labile copper ions in a toxic attack against pathogenic bacteria, which have a very low Cu tolerance, this review article examines the feasibility of Cu-centric strategies for antibacterial preventative and therapeutic applications. Promising results are shown for the use of Cu-containing materials in the hospital setting to minimize patient bacterial infections. Studies directed at disrupting bacterial Cu regulatory pathways elucidate new drug targets that can enable toxic increase of Cu levels and perturb bacterial dependence on iron. Likewise, Cu intracellular chelation/prochelation strategies effectively induce bacterial Cu toxicity. Cu-based small molecules and nanoparticles demonstrate the importance of the Cu ions in their mechanism and display potential synergism with classical drugs.

A dioxomolybdenum catalyst [(MoO2Cl2-O-MoO2Cl2)(L)] (1) (with L (1S,2S)-N,N´-bis(2-pyridinecarboxamide)-1,2-cyclohexane) was prepared and used as catalyst for the desulfurization of a multicomponent model fuel containing the most refractory sulfur compounds in real fuels. This complex showed to have a high efficiency to oxidize the aromatic benzothiophene derivative compounds present in fuels, mainly using a biphasic 1:1 model fuel/MeOH system. This process conciliates catalytic oxidative and extractive desulfurization, occurring the oxidation of the sulfur compounds in the polar organic solvent. The oxidative catalytic performance of (1) showed to be influenced by the presence of water in the system. Using 50% aq. H2O2 it was possible to reuse the catalyst and the extraction solvent MeOH during ten consecutive cycles without loss of desulfurization efficiency.

Histone deacetylases (HDAC) represent promising epigenetic targets for several diseases including different cancer types. The HDAC inhibitors approved to date are pan-HDAC inhibitors and most show a poor selectivity profile, side effects and especially hydroxamic acid based inhibitors lack good pharmacokinetic profiles. Therefore, the development of isoform-selective non-hydroxamic acid HDAC inhibitors is a highly regarded field in medicinal chemistry. In this study, we analyzed different ligand-based and structure-based drug design techniques to predict the binding mode and inhibitory activity of recently developed alkylhydrazide HDAC inhibitors. Alkylhydrazides have recently attracted more attention as they have shown promising effects in various cancer cell lines. In this work, pharmacophore models and atom-based quantitative structure-activity relationship (QSAR) models were generated and evaluated. The binding mode of the studied compounds was determined using molecular docking as well as molecular dynamics simulations and compared with known crystal structures. Calculated free energies of binding were also considered to generate QSAR models. The models created show a good explanation of in vitro data and were used to develop novel HDAC3 inhibitors.

In the last decades, the impacts of urbanization on the hydrological cycle have led to an increase in the frequency and magnitude of urban flooding events, also amplified by the effects of climate change. Sustainable Drainage Systems (SuDS) provide a revolutionary change in this field, improving the sustainability and resilience of cities. This research explores the integration of different SuDS with the aim of significantly reducing both flow volume and celerity of floods in a residual urban catchment area of metropolitan city of Querétaro (Mèxico), where extreme rainfall frequently occurs. This catchment is a representative suburb of urban pressure and environmental degradation problems. Currently, managing storm water under climate uncertainty through a multi-disciplinary approach is a major concern in this urban area. A 1D-2D coupling model of shallow water equations, finite volume method, unstructured meshing method, and hybrid parallel computing application defined the optimal configuration of SuDS at catchment scale to reduce the flood vulnerability in Querétaro. Specifically, in this paper we explore the management issues of the proposed SuDS configuration that acts as a water resource system with multiple purposes. A generic simulation model called MODSIM was applied to simulate the designed urban drainage system under a balanced IPCC future climate scenario in terms of reliability, resilience and vulnerability against water scarcity.

In the dynamic landscape of drug discovery, Computer-rAided Drug Design (CADD) emerges as a transformative force, bridging the realms of biology and technology. This paper overviews CADD's historical evolution, categorization into structure-based and ligand-based approaches, and its crucial role in rationalizing and expediting drug discovery. As CADD advances, incorporating diverse biological data and ensuring data privacy become paramount. Challenges persist, demanding the optimization of algorithms and robust ethical frameworks. Integrating Machine Learning and Artificial Intelligence amplifies CADD's predictive capabilities, yet ethical considerations and scalability challenges linger. Collaborative efforts and global initiatives, exemplified by platforms like Open Source Malaria, underscore the democratization of drug discovery. The convergence of CADD with personalized medicine offers tailored therapeutic solutions, though ethical dilemmas and accessibility concerns must be navigated. Emerging technologies like quantum computing, immersive technologies, and green chemistry promise to redefine the future of CADD. The trajectory of CADD, marked by rapid advancements, anticipates challenges in ensuring accuracy, addressing biases in AI, and incorporating sustainability metrics. The paper concludes by highlighting the need for proactive measures in navigating the ethical, technological, and educational frontiers of CADD to shape a healthier, brighter future in drug discovery.

Additive manufacturing processes offer various options to fabricate metal parts, which show numerous ecological and technological advantages compared to formative and subtractive manufacturing methods. Due to quick availability and high accuracy, they are particularly suitable to produce complex prototypes. Metal fused deposition modeling is a relatively new material extrusion additive manufacturing technique based on the widely used fused filament deposition process. This study focuses on the Inconel 625 metal filament from Markforged Inc., it consists of a mixture of metal powder and a binder system, the latter being removed during washing and sintering. In this article, the mechanical properties of printed and sintered Inconel were investigated using tensile testing specimens with three different infill patterns, solid, triangular, and gyroid, printed in flatwise and upright direction. In addition, investigations into the dimensional accuracy of the printed specimens and the sintering shrinkage were carried out. The results showed that neither the dimensional accuracy nor the sintering shrinkage was significantly influenced by the printing orientation. In the context of lightweight engineering, the structures proofed beneficial especially within the elastic region. Generally, triangular infill patterns resulted in higher stiffness, while gyroids led to more ductile specimens. A mass-related evaluation of tensile testing elucidates that with aid of the infill structures weight savings of 40 % resulted in mechanical performance decreased by only 20 % on average.

A proposed low-temperature forging method aims to enhance stainless steel bearings by creating a martensitic subsurface layer, significantly boosting bearing fatigue life due to increased surface hardness. This technique induces beneficial residual stresses, particularly in axial bearings, streamlining their construction and improving machine elements. Challenges persist, especially with radial bearings, but simplicity in axial bearing forging promotes compact, resource-efficient facility construction. Future research will focus on applying this technique to axial bearing washers, potentially replicating success in other bearing components. Despite the energy ex-penditure for cooling during forging, the substantial increase in bearing fatigue life offsets this, enhancing overall longevity and reliability of critical machine components. Integration of this forging technique into bearing fabrication appears seamless, offering a promising trade-off be-tween energy use and enhanced performance.

Tremor is a prevalent neurological disorder characterized by involuntary shaking or trembling of body parts. This condition impairs fine motor skills and hand coordination to varying degrees and can even affect overall body mobility. As a result, tremors severely disrupt the daily lives and work of those affected, significantly limiting their physical activity space. This study developed an innovative Spatial Augmented Reality (SAR) system aimed at assisting individuals with tremor disorders to overcome their physical limitations and expand their range of activities. The system integrates eye-tracking and Internet of Things (IoT) technologies, enabling users to smoothly control objects in the real world through eye movements. It employs a virtual stabilization algorithm for stable interaction with objects in the real environment. The study comprehensively evaluated the system's performance through three experiments: 1) assessing the effectiveness of the virtual stabilization algorithm in enhancing the system's ability to assist individuals with tremors in stable and efficient interaction with remote objects; 2) evaluating the system's fluidity and stability in performing complex interactive tasks; 3) investigating the precision and efficiency of the system in remote interactions within complex physical environments. The results demonstrate that the system significantly improves the stability and efficiency of interactions between individuals with tremor and remote objects, reduces operational errors, and enhances the accuracy and communication efficiency of interactions.

The multiphase motors due to their reliability find new areas of application in the industry and transportation. Developing of any system with multiphase motors at first requires elaborate model of the system, define control mode and controllers. The model of control system for the six-phase drive is based on its conventional d-q mathematical model and indirect field-oriented control. Simulink model of six-phase drive with indirect field-oriented control and simulated with two types PID and PID fuzzy controllers. The simulation results, reflecting step response and provided speed reference law as well as load application at constant speed, are presented and analyzed. Fuzzy controller with 49 rules is considered and applied. Six-phase electric drive with field-oriented control at well-tuned PID controller has good step response specifications: settling time 0.13 s at starting without load, step response has no overshoot, small about 1 % short time decrease of speed at load of 5 Nm application. The system employing PID fuzzy controller shows slightly better results in response to torque application: the decrease in speed 1 % is eliminated in shorter time. Simulation results indicate the robustness of both systems with six-phase drive to disturbance and provide high quality transient specifications at determined reference speed.

African swine fever virus (ASFV), a highly contagious pathogen characterized by a complex structure and a variety of immunosuppression proteins, causes hemorrhagic, acute, and aggressive infectious disease that severely injure the pork product and industry. However, there is no effective vaccine or treatment. The main reasons are not only the complex mechanisms that lead to immunosuppression, but also the unknown functions of various proteins. This review summarizes the interaction between ASFV and host immune system, along with the involvement of virulence related genes and proteins, as well as the corresponding molecular mechanism of immunosuppression of ASFV, encompassing pathways such as cGAS-STING, NF-κB, JAK/STAT, apoptosis, and other modulation. The aim is to summarize the dynamic process during the ASFV infection and entry into host cell, provide a rational insight into development of vaccine and a better clear knowledge of how ASFV impacts host.

The development of ballistic protection vests (BPVs) has become increasingly significant, particularly in the design of soft panels, which are critical to the overall size and configuration of these vests. Despite their importance, a standardized design process for soft panels is lacking in the literature. This research addresses this gap by creating soft panels tailored to the body types of regional soldiers while adhering to relevant standards. We propose a comprehensive design algorithm and evaluate the applicability of the National Institute of Justice (NIJ) standard 0101.06 test templates for configuring these panels. This study aims to design soft ballistic panels for BPVs that cater to the body type requirements of regional soldiers and comply with NIJ 0101.06 standards. We have developed an algorithm for designing soft panels and analyzed the feasibility of using NIJ test templates for their configuration. The research encompasses a detailed literature review, analysis of existing BPV soft panels, and comparison with NIJ test templates. The panels were designed and scaled using computer-aided design (CAD) systems and evaluated through by physical fitting on mannequins and virtual fitting using the Clo3D program. Our findings indicate that the NIJ standard test templates are only partially applicable to the design of soft panels. The developed methodology includes an algorithm and size specifications tailored to regional covers. A coefficient (K) was identified to calculate the soft panel surface area prior to design, thereby saving time and resources.

Nowadays, microfluidics has become an anarchist interdisciplinary topic with considerable attention in a wide range of biotechnology applications. In this research work, numerical investigation of microfluidic micro-mixer is carried out using hybrid actuation approach with different micropillar shapes and gaps. For this purpose, COMSOL Multiphysics is used with three different physics such as thermoviscous acoustic to solve acoustic governing equations, laminar physics is used to solve fluid flow governing equations and diluted transport species is used to solve mixing governing equations. The simulations were carried out with flow velocity of 200 µm/s at both inlets with an oscillation frequency of 15kHz. The outcomes were in the form of acoustic characteristics such as acoustic pressure, acoustic velocity, acoustic streaming and mixing index. The results revealed that the inclusion of micropillars enhanced the mixing performance and strength of acoustic field resulting in improvement of mixing performance compared to the case without micropillars. In addition, it was also investigated that blade shape micropillars with 0.150 mm gaps deliver best results compared to the other cases with maximum and minimum values of the mixing index 0.95 and 0.72 respectively. The obtained results can be extremely helpful for design and modifications of hybrid microfluidics micro-mixer.

This study reports on the development of bio-based hydrophobic coatings for packaging papers through deposition of polyhydroxybutyrate (PHB) particles in combination with nanofibrillated cellulose (NFC) and plant wax. In a first approach, PHB particles in micrometer range (PHB-MP) were prepared through a phase-separation technique providing internally nanosized structures. The particles were transferred as a coating by dip-coating filter papers in the particle suspension, followed by sizing with a carnauba wax solution. This approach allowed partial to almost full surface coverage of PHB-MP over the paper surface resulting in static water contact angles of 105° to 122° and 129° to 144° after additional wax coating. In a second approach, PHB particles with submicron sizes (PHB-SP) were synthesized by an oil-in-emulsion (o/w) solvent evaporation method, and mixed in aqueous suspensions with 0 to 7 wt% NFC. After dip-coating filter papers in PHB-SP/NFC suspensions and sizing with a carnauba wax solution, static water contact angles of 112° to 152° were obtained. The intrinsic properties of the particles were analyzed by scanning electron microscopy, thermal analysis and infrared spectroscopy, indicating higher crystallinity for PHB-SP than PHB-MP. The chemical interactions between the more amorphous PHB-MP particles and paper fibers were identified as an esterification reaction, while the morphology of the NFC fibrillar network was playing a key role as binding agent in the retention of more crystalline PHB-SP at the paper surface, hence contributing to higher hydrophobicity.

The Energy Performance of Buildings Directive 2010 calls for the Nearly Zero Energy Standard for new buildings from 2021 onwards: Buildings using “almost no energy” are powered by renewable sources or energy produced by the building itself. For residential buildings, this ambitious new standard has already been reached. But for other building types this goal is still far away. The potential of these buildings to meet a Nearly Zero Energy Standard was investigated by analyzing ten case studies representing non-residential buildings with different uses. The analysis shows that the primary characteristics common to critical building types are a dense building context with a very high degree of technical installation (such as hospital, research and laboratory buildings). The large primary energy demand of these types of buildings cannot be compensated by building and property-related energy generation including off-site renewables. If the future Nearly Zero Energy Standard were to be defined with lower requirements because of this, the state related properties of Bavaria suggest that the real potential energy savings available in at least 85% of all new buildings would be insufficiently exploited. Therefore, it would be useful to instead individualize the legal energy verification process for new buildings to distinguish critical building types such as laboratories and hospitals.

Energy harvesting is an emerging topic recently. This harvested energy is used to operate wireless sensors for different industrial monitoring and automation. To maximize the harvested energy in spinning systems, the harvester should vibrate at resonance for different spinning frequencies which can be achieved by active fitting. In this research, a novel methodology was developed by actively customizing the length of vibrating element beam to manipulate its natural frequency according to the spinning frequency. Different models were investigated numerically and experimentally to verify the proposed methodology. COMSOL Multiphysics software V5.1 was used to develop the numerical model, then and tip deformation and voltage difference results were benchmarked. The numerical model was verified experimentally by attaching a piezoelectric MIDE PPA 1021 which its vibrating length was varied by changing the supporting length from 0 mm to 12 mm to a spinning object having variable frequency from 0-200 Hz. It is found that the MIDE PPA 1021 beam vibrated at its resonance throughout the specified spinning frequencies. The proposed harvester can be applied in battery-free sensors being used in automotives, wind-mills blades, and rotating machinery.

Confronting the dual challenges of rapid urbanization and climate change, although extensive research has investigated the influencing factors and practical strategies of urban carbon emissions and urban vibrancy, respectively, the unclear mutual nexus between them and the development strategy of collaborative optimization requires further in-depth analysis. This study explores the delicate balance between urban vibrancy and low-carbon sustainability within the confines of Beijing’s Fifth Ring Road. By integrating OpenStreetMap, land use, population, and building carbon emission data, we have developed a reproducible method to estimate total carbon emission and emission intensity per capita. Furthermore, we have introduced vibrancy index data to distinguish the vibrancy evaluation of residential and non-residential land and applied cross-combinational classification technology to dissect the spatial correlation between urban carbon emissions and urban vibrancy. The results reveal that the four combination typologies show more significant differences and regularity in residential land. Based on the discovery of spatial correlation, this study puts forward corresponding development strategy suggestions for each typology based on geographical location and the requirements of urban development policies of these four combination typologies. In conclusion, our study highlights the importance of integrating carbon emissions and urban vibrancy comprehensively in sustainable urban planning and proposes that various land use combinations need targeted development strategies to achieve this goal, which need to consider population, energy, service facilities, and other diverse aspects.

Intraoperative load sensors have been developed with the aim of balancing the soft tissue in the knee during Total Knee Replacements (TKRs). Literature has shown success in soft tissue bal-ancing however, concerns regarding the accuracy of these sensors remain. For this reason, pre-vious research has attempted to create robust sensors for intraoperative use. The design of the sensor in this research has aimed to address the concerns outlined in the literature to create a new and novel smart-sensor for soft-tissue balancing. This new intraoperative load sensor included design features to increase accuracy while artificial intelligence allowed for comprehensive sensing across the entirety of the sensor, providing unparalleled insight during the operation. Notably, the sensor was designed to withstand loads of at least 450 N, ensuring robust perfor-mance of the sensor. To optimize the design process while minimizing cost, Finite Element Analysis was employed. This approach ensured the design features fulfilled their function while maintaining structural integrity to withstand loads. Moreover, the novelty of using training data from simulated data will reduce the iterative process of the labor-intensive collection of training data for the artificial intelligence while reducing human error associated with it. Results from the evaluation demonstrated the ability of this design to successfully bridge the current gap in the market by fulfilling all essential design criteria established within the literature. This innovative smart-sensing tool will in turn enhance patient outcomes and alleviate financial burdens to pa-tients and the healthcare systems by reducing the need for early revision surgeries associated with improper joint tension.

The assessment of existing bridges constitutes a serious challenge for the researchers since their safety evaluation is a complex task due to several sources of uncertainty affecting the parameters identified in the knowledge process. In particular, a high level of uncertainties may arise in the case of prestressing systems requiring special investigation strategies and experimental technologies. The paper aims to investigate how the knowledge uncertainties influence the safety assessment of existing post-tensioned bridges. The semi-probabilistic approach is used, and uncertainties related to the knowledge process are described considering the number of tests, the confidence level assumed for the estimation of the problem parameters, and the measurement errors of in-situ tests. Results concerning a typical post-tensioned bridge are reported and the variability of the outcomes is discussed and compared with a reference case of “perfect knowledge”. The main results of the study confirm the general robustness of the semi-probabilistic Eurocodes safety format and provide an overview of dispersion due to different choices about the number of tests and confidence level. The measurement errors may lead to significant under-estimation of the computed structural capacity with respect to the reference one.

Delivering nucleic acid therapeutics across cell membranes is a significant challenge. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) show promise for siRNA delivery. To improve siRNA delivery and silencing a model STAT3 gene, we hypothesized that oleyl acylation to CPPs, specifically (WRH)n, would enhance STAT3 silencing efficiency in breast and ovarian cancer cells. Using Fmoc/tBu solid-phase peptide chemistry, we synthesized, purified, and characterized the oleyl-conjugated (WRH)n (n = 1-4) peptides. The peptide:siRNA complexes were non-cytotoxic at N/P 40 (~20 μM) against MDA-MB-231, MCF-7, SK-OV-3, and HEK-293 cells after 72 h incubation. All peptide:siRNA complexes showed serum stability at N/P ≥40. The synthesized conjugates, with a diameter of <100 nm, formed nano complexes with siRNA and exhibited stable range of zeta potential values (13-18 mV at N/P 40). Confocal microscopy and flow cytometry analysis provided qualitative and quantitative evidence of successful cellular internalization of siRNA. Peptides oleyl-(WRH)3 and oleyl-(WRH)4 showed ~60% and ~75% cellular uptake of siRNA, respectively, in both MDA-MB-231 and SK-OV-3 cells. Western blot analysis of oleyl-(WRH)4 demonstrated effective silencing of the STAT-3 gene, with ~75% silencing in MDA-MB-231 cells and ~45% in SK-OV-3 cells.

Autonomous navigation in dynamic environments poses a significant challenge in the field of ro-botics with the primary goals of ensuring both smooth and safe movement. This study introduces control strategy based on an Adaptive Neuro-Fuzzy Inference System (ANFIS) to enhance au-tonomous robot navigation in dynamic environments, emphasizing on collision-free path plan-ning. This strategy employs, a path planning technique to develop a trajectory that allows the ro-bot to navigate smoothly while avoiding collisions with both static and dynamic obstacles. The developed control system incorporates four ANFIS controllers: two are tasked with guiding the robot toward its end point, and the other two are activated for obstacle avoidance. The experi-mental setup conducted in CoppeliaSim involves a mobile robot equipped with ultrasonic sensors navigating in an environment with static and dynamic obstacles. Simulation experiments are conducted to demonstrate the model's capability in ensuring collision-free navigation, employing a path planning algorithm to ascertain the shortest route to the target destination. The simulation results highlight the superiority of the ANFIS-based approach over conventional methods, partic-ularly in terms of computational efficiency and navigational smoothness.

Developing and utilising of underground space is an vital direction for urban growth. Underground commercial streets, as a significant component of underground space accommodating extensive human social activities, and consequently necessitate the creation of human-scale spaces. In the evolution of urban design development towards greater refinement, applying architectural theories and excessively subjective designs has resulted in a deficiency of human-centered design and a disordered spatial environment. This study merges environmental psychology and architectural theory to determine the appropriate length of spatial scale. Two experiments focusing on spatial perception evaluation were conducted using a virtual experimental platform that featured varying dimensions of spatial scale combinations. These quantified combinations were correlated with perception evaluation, and regression analysis was employed to identify appropriate scale ranges, which were superimposed on the range of length selection. Finally, the optimal length and scale combination for underground commercial street spaces were established, providing a reference for the human-centered design of these environments.

One of the primary causes of the mechanical seal failure is rotor vibration. Traditional dynamic seal models often would not be able to fully explaining the failure mechanisms. The seal dynamic models proposed in this paper, including those developed by the authors, prove valuable in predicting seal dynamics during operation in specific turbomachinery and in explaining the causes of seal failure. The single-mass dynamic model is suitable for analyzing contact mechanical seal and simple design dry gas seals dynamics. The two-mass dynamic model is used for investigating operational dynamics processes in classical dry gas seals under complex loading conditions. The three-mass dynamic model is used to study various complex mechanical seal types. This model is able to determine the normal operating condition range and to explain leakage mechanisms in the presence of excessive rotor vibrations.

As a member of smart materials, electrorheological elastomers (EREs) formed by pre-treating active electrorheological particles are attracting more and more attention. In this work, four Mg-doped strontium titanate particles with spherical, dendritic, flake-like and pinecone-like morphorlogies were obtained by hydrothermal and low-temperature co-precipitation. XRD, SEM, Raman and FT-IR were used to characterize the obtained products. The results showed that the sizes of Mg-doped strontium titanates are about 1.5‒2.0 μm, and the phase structure are dominated by cubic crystal. These Mg-doped strontium titanates were dispersed in a hydrogel composite elastic medium. Then, Mg-doped strontium titanate/glycerol/gelatin electrorheological composite hydrophilic elastomers were obtained with or without electric field. The electric field response properties of Mg-doped strontium titanate composite elastomers were investigated. It concluded that dendritic Mg-doped strontium titanate composite elastomers is high-performance EREs. And the maximum value of energy storage modulus of Mg-doped strontium titanate composite elastomers has achieved 8.70 MPa. This high electrorheological performance of the products is helpful for their applications in vibration control, force transducers, smart structures, dampers, and other fields.

This work presents a novel approach for the study of the movement of droplets on inclined surfaces under the influence of gravity and chemical heterogeneities. The developed numerical methodology uses data-driven modeling to extend the applicability limits of an analytically derived reduced-order model for the contact line velocity. More specifically, while the reduced-order model is able to capture the effects of the chemical heterogeneities to a satisfactory degree, it does not account for gravity. To alleviate this shortcoming, datasets generated from direct numerical simulations are used to train a data-driven model for the contact line velocity, which is based on the Fourier neural operator and corrects the reduced-order model predictions to match the reference solutions. This hybrid surrogate model, which comprises of both analytical and data-driven components, is then integrated in time to simulate the droplet movement, offering a speedup of five orders of magnitude compared to direct numerical simulations. The performance of this hybrid model is quantified and assessed in different wetting scenarios, by considering various inclination angles and values for the Bond number, demonstrating the accuracy of the predictions as long as the adopted parameters lie within the ranges considered in the training dataset.

The objective of this study is to determine the relationship between body condition score (BCS) and body carcass fat (BCF) of ewes at two key stages of the production cycle. Data were collected from 88 Coopworth ewes including BCS measurements manually evaluated by the farm manager, BCF measurements determined by computerized tomography (CT) and body parameter measurements automatically determined by an image processing application. Artificial neural network (ANN) statistical analysis method was used to develop a relationship between the body parameters and the BCF with an r2=0.96 and RMSE=1.01 using all top and side variables.

This paper presents an innovative multi-agent, data-driven reinforcement learning (RL) approach to develop and utilize the thermal equivalent network model that represents the motor's thermal dynamics. A multi-agent reinforcement learning is designed and trained to adjust the model parameters using data from several motor driving cycles. To ensure the incoming driving cycle matches the historical data before employing the pre-trained RL agents, offline statistical analysis and clustering techniques are developed and used. Numerical simulations highlighted the RL agent's ability to develop strategies that effectively address the variability of driving cycles. The proposed RL framework showed its capability to accurately reflect the motor's thermal behavior under various driving conditions.

The acoustic environment in learning spaces significantly influences learning effectiveness and occupant well-being. Recent studies have shown that a series of architectural factors within physical learning environments can impact students' educational experiences. This research delves into the relationship between architectural characteristics and the perceived acoustic environment among 467 primary students in 19 learning spaces across 9 schools in Chile. The survey comprises a student questionnaire, a checklist evaluating space characteristics, and acoustic measurements of indoor noise levels during occupied conditions. Examined topics include Indoor Environmental Quality (IEQ) comfort perception, noise annoyance, hearing ability, and acoustic preference. Architectural characteristics considered encompass flexible and acoustic space design parameters. The results indicated that noise discomfort was a common issue, especially in traditional learning spaces without acoustic treatment. The type of learning space (traditional or flexible settings) has a greater impact on acoustic perception particularly concerning noise discomfort and acoustic preference. However, poorly acoustic spaces lacking absorbing materials or exhibiting lower spatial density (m2 per student) contribute to increased indoor noise levels affecting noise annoyance caused by children's talking inside. The study emphasizes the importance of considering both architectural design and acoustic conditioning for optimizing the acoustic experience in educational spaces.

The paper introduces a control hybrid model that is designed on the basis of OOSEM (Object-Oriented Systems Engineering Method), MDA (Model-Driven Architecture) concepts, RealTime UML/SysML (Unified Modeling Language/Systems Modeling Language), and an algorithm based on UKF (Unscented Kalman Filter). This hybrid model enables the implementation of control elements for autonomous underwater vehicles (AUVs) and can be adapted to reuse for most standard AUV platforms. To obtain this goal, the dynamic model of AUV is integrated with the following specializations of OOSEM/MDA, in which the analysis model is clarified via the use-case model definition and then combines with HA (hybrid automata) to precisely define the requirements for control. Next, the designed model is specialized via real-time UML/SysML to get the core control blocks, which describe the behaviors and structures of control parts in detail. This design model is then transformed into the model of implementation with the assistance of round-trip engineering to conveniently realize the controller of AUVs. Based on this new model, an AUV controller for low-cost turtle-shaped AUVs is implemented that performs tracking for a planar trajectory with accepted feasibility.

To improve efficacy and safety of sunscreen emulsions, UV‐filter skin permeation could be kept as low as possible by reducing UV‐filter content or changing emulsion composition. In this work, different lipid phase ratio (12, 14 and 16% w/w) were assessed for their ability to affect the technological and sensory properties of O/W emulsions in which bemotrizinol (BMTZ), a broad spectrum sunscreen agent, was incorporated free or loaded into nanostructured lipid nanocarriers (NLC) to reduce its release from the vehicle and, hence, its skin permeation. The following technological properties were evaluated in vitro by suitable methodologies: spreadability, viscosity, pH, occlusion factor, BMTZ release, sun protection factor (SPF). Sensory attributes were assessed by trained panelists in three different phases: before/during pick‐up, rub‐in, after application. Raising the lipid phase ratio led to an increase of viscosity and to a corresponding drop of spreadability while the incorporation of BMTZ‐loaded NLC determined a decrease of occlusion factor and an increase of SPF. No BMTZ release was observed from all emulsions. Sensory attributes were mainly affected by lipid phase ratio. These results suggest that lipid phase ratio and BMTZ incorporation into NLC could contribute to determine technological and sensory properties of O/W emulsions.

In order to quickly develop a multi ship collaborative collision avoidance plan in multi ship encounter scenarios, a multi ship collision avoidance decision model is proposed in accordance with the requirements of the International Maritime Collision Avoidance Regulations, taking into account the collision avoidance operations in multi ship encounter scenarios. Firstly, the collision risk between ships is determined by the closest encounter distance (DCPA) and closest encounter time (TCPA). Secondly, a decision objective function is established based on rules, degree of ship deviation, and ship risk. Finally, the prediction mechanism is used to calculate the minimum value of the objective function and complete the collision avoidance decision. The simulation results show that in the scenario of multiple ship encounters, the collision avoidance model can achieve safe collision avoidance with a smaller steering frequency and a shorter col-lision avoidance time. The proposed multi ship collision avoidance model can provide reference for collision avoidance decision-making in multi ship encounter scenarios, which helps to im-prove the collision avoidance efficiency in multi ship collision avoidance

Firefighters Protective Clothing consist of several layers of different properties and functions. The layers create barriers against dangerous outer factor. However, they are also barriers to transport of sweat produced by human organism. It causes that very often sweat in the form of vapor is not transferred effectively from the human organism through the FPC to environment. This leads to sweat condensation on the skin of the FPC user causing his discomfort. In order to ensure as good as possible physiological comfort of firefighter while firefighting and other rescue actions it is necessary to take into consideration the transport of condensed sweat in the multilayer textile set creating the FPC. In the presented work four variants of multilayer textile sets for the FPC have been tested in the aspect of liquid moisture transport. Measurement was performed by means of the Moisture Management Tester (MMT290) – innovative instrument manufactured by the SDL Atlas. Obtained results showed that the transfer of sweat in liquid form occurs only in the inner, next to skin layer of the multilayer sets for the FPC.

This paper investigates the effects of various process parameters, specifically the substrate temperature, on weld track geometry in Directed Energy Deposition (DED) processes. A specialized experimental setup integrated within a DED machine facilitates controlled thermal conditioning of sample sheets. Through Design of Experiments (DoE) methods, individual weld marks are generated and analysed to assess geometric characteristics. Regression models are constructed to predict machine parameters for desired weld geometry at different substrate temperatures. Validation experiments confirm the accuracy and reliability of the regression models. Results show a consistent trend towards target geometric features across a broad range of substrate temperatures. Despite deviations in measured values, successful fabrication is achieved, demonstrating robust bonding between weld and substrate. Contact angle predictions exhibit precision within a partial temperature range for proper deposition. The developed model offers insights for optimizing DED process parameters to achieve desired weld characteristics, advancing the capabilities and reliability of additive manufacturing technology. Future work aims to refine the regression model and explore additional mathematical relationships for enhanced accuracy. An implication of this work is the potential to vary the local mechanical properties of parts by controlling the temperature profile while maintaining consistent geometric characteristics. By manipulating the substrate temperature, it may be possible to tailor the microstructure and mechanical properties of fabricated components in the future to meet specific requirements in different regions of the part.

CD44 is a type I transmembrane glycoprotein, which is associated with poor prognosis in various solid tumors. Since CD44 plays critical roles in tumor development by regulating cell adhesion, survival, proliferation, and stemness, it has been considered a target for tumor therapy. Anti-CD44 monoclonal antibodies (mAbs) have been developed and applied to antibody-drug conjugates and chimeric antigen receptor-T cell therapy. We previously developed anti‐pan-CD44 mAbs, C₄₄Mab-5 and C₄₄Mab-46, which can recognize both CD44 standard (CD44s) and variant isoforms. In the present study, a defucosylated mouse IgG_2a version of the anti-pan-CD44 mAbs (5-mG_2a-f and C₄₄Mab-46-mG_2a-f) was generated to evaluate the antitumor activities against CD44-positive cells. Both 5-mG_2a-f and C₄₄Mab-46-mG_2a-f recognized CD44s-overexpressed CHO-K1 (CHO/CD44s) cells and esophageal tumor cell line (KYSE770) in flow cytometry. Furthermore, both 5-mG_2a-f and C₄₄Mab-46-mG_2a-f could activate effector cells in the presence of CHO/CD44s cells and exhibited the complement‐dependent cytotoxicity against both CHO/CD44s and KYSE770 cells. Furthermore, the administration of 5-mG_2a-f and C₄₄Mab-46-mG_2a-f significantly suppressed CHO/CD44s and KYSE770 xenograft tumor development compared with the control defucosylated mouse IgG_2a. These results indicate that 5-mG_2a-f and C₄₄Mab-46-mG_2a-f could exert antitumor activities against CD44-positive cancers and could be a promising therapeutic regimen for tumors.

This paper numerically investigates a 3D mesh independency study of a straight blade horizontal axis tidal turbine modelled using Computational Fluid Dynamics (CFD). The solution was produced by employing two turbulence models, the standard k-ε model and Shear Stress Transport (SST) in ANSYS CFX. Three parameters were investigated: mesh resolution, turbulence model, and power coefficient in the initial CFD, analysis. It was found that the mesh resolution and the turbulence model affect the power coefficient results. The power coefficients obtained from the standard k-ε model are 15% to 20% lower than the accuracy of the SST model. It can also be demonstrated that the torque coefficient increases with the increasing Tip Speed Ratio (TSR), but drops drastically after TSR = 5 and k-ε model failing to capture the non-linearity in the torque coefficient with the increasing TSR.

Dengue virus is a global health problem most prevalent in tropical and subtropical regions. However, after the approval of two vaccines, Dengvaxia, TV003/TV005 of Takeda, for its prevention, problems were reported, like enhanced risks of infection or less efficiency of protection. Since then, more struggles have been in demand for the development of better vaccines. Here, we conducted a new design through an in-silico strategy. Initially, epitopes were chosen based on their antigenicity, immunogenicity, and binding affinity with MHC molecule, while excluded with allergenicity, toxicity and potential risk of antibody dependent enhancement. Subsequently, a core antigen was constructed with selected epitopes and linked with distinct adjuvant proteins to achieve three candidate vaccines, PSDV-1~3. PSDV-2 was chosen for further validation based on their advantage in physicochemical and structural properties. With a panel of simulations, this artificial protein showed tight binding with pattern recognition receptors, good stability, robust immune induction, and ultimately was confirmed as a high quality vaccine candidate. The plasmid for its recombinant expression was then designed accordingly. With our new design, one more choice was obtained for the effective protection from Dengue virus. Further experimental validations are still require to confirm it protection capacity and safety.

Smartwatches are one of the most relevant fitness trends of the past two decades, and they collect increasing amounts of health and movement data. The accuracy of these data may be questionable and requires further investigation. Therefore, the aim of the present study is to validate smartwatches for use in triathlon training. Ten different smartwatches were tested for accuracy in measuring heart rate, distance (via global navigation satellite systems, GNSS), swim stroke rates and the number of swim laps in a 50 m Olympic-size pool. The optical heart rate measurement function of each smartwatch was compared to that of a chest strap. Thirty participants (15 females, 15 males) ran five 3-minute intervals on a motorised treadmill to evaluate the accuracy of the heart rate measurements. Moreover, for each smartwatch, running und cycling distance tracking was tested over six runs of 4,000 m on a 400 m tartan stadium track, six hilly outdoor runs over 3.4 km, and four repetitions of a 36.8 km road bike course, respectively. Three swimming protocols ranging from 200 m to 400 m were performed in triplicate in a 50 m Olympic-size pool, evaluating tracked distance and detected number of strokes. The mean absolute percentage errors (MAPEs) for the average heart rate measurements varied between 3.1% and 8.3%, with the coefficient of determination ranging from 0.22 to 0.79. MAPE results ranged from 0.8% to 12.1% for the 4,000 m run on the 400 m track, from 0.2% to 7.5% for the 3.4 km outdoor run, and from 0.0% to 4.2% for the 36.8 km bike ride. For the swimming tests, in contrast, the deviations from the true distance varied greatly, starting at a 0.0% MAPE for the 400 m freestyle and reaching 91.7% for the 200 m medley with style changes every 25 m. In summary, for some of the smartwatches, the measurement results deviated substantially from the true values. Measurements taken while road cycling over longer distances with only a few curves were in relative terms more accurate than for outdoor runs and even more accurate than for the 400 m track. In the swimming exercises, the accuracy of the measured distances was severely deteriorated by the medley changes among the majority of the smartwatches. Altogether, the results of this study should help in assessing the accuracy and thus suitability of smartwatches for general triathlon training.

One of the G protein-coupled receptors, C-C chemokine receptor 5 (CCR5), is an important regulator for the activation of T and B lymphocytes, dendritic cells, natural killer cells, and macrophages. Upon binding to the ligands, CCR5 activates downstream signaling, which plays critical roles in the innate and adaptive immune response through the promotion of lymphocyte migration and the secretion of pro-inflammatory cytokines. Anti-CCR5 monoclonal antibodies (mAbs) have been developed and evaluated in clinical trials for tumors and inflammatory diseases. In this study, we developed novel mAbs for mouse CCR5 (mCCR5) using the N-terminal peptide immunization. Among the established anti-mCCR5 mAbs, C₅Mab-4 (rat IgG_2a, kappa) and C₅Mab-8 (rat IgG₁, kappa), recognized mCCR5-overexpressed Chinese hamster ovary-K1 (CHO/mCCR5) and an endogenously mCCR5-expressing cell line (L1210) by flow cytometry. The dissociation constant (K_D) values of C₅Mab-4 and C₅Mab-8 for CHO/mCCR5 were determined as 3.5 × 10⁻⁸ M and 7.3 × 10⁻⁹ M, respectively. Furthermore, both C₅Mab-4 and C₅Mab-8 could detect mCCR5 by western blotting. These results indicated that C₅Mab-4 and C₅Mab-8 are useful for detecting mCCR5 by flow cytometry and western blotting and provide a possibility to obtain the proof of concept in preclinical studies.

Receptor–ligand interactions at cell interfaces initiate signaling cascades essential for cellular communication and effector functions. Specifically, T cell receptor (TCR) interactions with pathogen-derived peptides presented by the major histocompatibility complex (pMHC) molecules on antigen-presenting cells are crucial for T cell activation. The binding duration, or dwell time, of TCR–pMHC interactions correlates with downstream signaling efficacy, with strong agonists exhibiting longer lifetimes compared to weak agonists. Traditional surface plasmon resonance (SPR) methods quantify 3D affinity but lack cellular context and fail to account for factors like membrane fluctuations. In the recent years, single-molecule Förster resonance energy transfer (smFRET) has been applied to measure 2D binding kinetics of TCR–pMHC interactions in a cellular context. Here, we introduce a rigorous mathematical model based on survival analysis to determine exponentially distributed receptor–ligand interaction lifetimes, verified through simulated data. Additionally, we developed a comprehensive analysis pipeline to extract interaction lifetimes from raw microscopy images, demonstrating the model’s accuracy and robustness across multiple TCR–pMHC pairs. Our new software suite automates data processing to enhance throughput and reduce bias. This methodology provides a refined tool for investigating T cell activation mechanisms, offering insights into immune response modulation.

Cities are complex systems requiring urban design models that balance order and disorder. Collective creativity initiatives engage citizens in these processes, empowering bottom-up approaches that prioritize people and social well-being within urban development. This paper investigates an 'Urban Laboratory' as a case study, examining the potential of collective creativity to address urban complexity. The successful and ongoing project 'El Campo de Cebada' in Madrid, Spain, demonstrates how a community transformed a vacant lot into a vibrant social hub. The phases of this study include case selection, data collection, data analysis, and presentation of the results. This study identifies key enabling factors, including agents, management, social dynamics, infrastructure, and actions. These insights offer a methodological framework for designing future collaborative, resilient, and inclusive urban spaces, addressing the complex needs of communities within our cities.

C-C motif chemokine receptor-8 (CCR8) belongs to class A of G protein-coupled receptors (GPCRs). CCR8 interacts with the specific chemokine ligand CCL1/I-309 in humans, which is produced by various cells, including tumor-associated macrophages and regulatory T cells (Treg). CCR8 is highly expressed on Treg and T-helper 2 (T_H2) cells recruited to the inflammation site and is implicated in allergy, asthma, and cancer progression. The CCR8⁺Treg has been suggested to be an important regulator in the immunosuppressive tumor microenvironment (TME); therefore, it has been desired to develop sensitive monoclonal antibodies (mAbs) for CCR8. This study developed a specific mAb for human CCR8 (hCCR8), which is useful for flow cytometry by employing the Cell-Based Immunization and Screening (CBIS) method. The established anti-hCCR8 mAb, C₈Mab-21, (mouse IgM, kappa) reacted with hCCR8-overexpressed Chinese hamster ovary-K1 (CHO/hCCR8) cells, TALL-1 (acute T lymphoblastic leukemia), CCRF-HSB2 (human T-lymphoblastic leukemia), and natural killer cells, which express endogenous hCCR8 by flow cytometry. Furthermore, C₈Mab-21 demonstrated a moderate binding affinity for CHO/hCCR8 and TALL-1 with a dissociation constant of 6.5×10^-8 M and 2.0×10^-8 M, respectively. C₈Mab-21, which was established by the CBIS method, could be a useful tool for analyzing the hCCR8-related biological response using flow cytometry.

In this paper, carbon nanotubes modified screen-printed electrode (CNTs/SPE) was prepared and the CNTs/SPE was employed for the electrochemical determination of antioxidant substance Chlorogenic acids (CGAs). A pair of well-defined redox peak of CGA was observed at the CNTs/SPE in 0.10 mol∙L^-1 acetic acid-sodium acetate buffer (pH 6.2) and electrode process is adsorption-controlled. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) method for the determination of CGA were proposed based on the CNTs/SPE. Under the optimal conditions, the proposed method exhibited linear ranges from 4.73×10^-7 to 4.45×10^-5 mol∙L^-1, the linear regression equation was Ipa(µA) = 4.1993 C (mol∙L^-1)+1.1039 (r = 0.9976) and the detection limit for CGA could reach 3.25×10^-6 mol∙L^-1. The recovery of matrine was 94.74~106.65% (RSD = 2.92%) in coffe beans. The proposed method is quick, sensitive, reliable, and can be used for the determination of CGA.

Heptanuclear {GdIII7} (complex 1) and tetradecanuclear {GdIII14} (complex 2) have been synthesized using a Rhodamine 6G ligand HL (Rhodamine 6G salicylaldehyde hydrazone) and characterized. Complex 1 has a rare disc-shaped structure, where the central Gd ion was connected to the peripheral six GdIII ions via CH3O-/μ3-OH- bridges. Complex 2 has an unexpected three-layer double sandwich structure with a rare μ6-O2- ion in the center of the cluster. Magnetic studies revealed that complex 1 exhibits a magnetic entropy change of 17.4 J kg−1 K−1 at 3 K and 5 T. On the other hand, complex 2 shows a higher magnetic entropy change of 22.3 J kg−1 K−1 at 2 K and 5 T.

Researchers have explored primary colour-geometric shape associations since Kandinsky's correspondence theory. However, there is a gap in the literature regarding interior colour applications on surface shapes. To address this gap, an online study was employed to gather data with one hundred participants who were asked to choose their preferred colours for shapes on bedroom walls with follow-up questions on the colour-shape semantic associations, their preference of colours and shapes on bedroom walls independently in addition to their favourite colour, their favourite shape, and colour-shape pairs without interior context. The results revealed that colour-shape preferences in interiors differ from those found in psychology studies, other colour applications on bedroom walls, and other preferences, indicating that colour preference is context-dependent. Interestingly, the most popular colour for surface shapes on bedroom walls is purple, followed by brown and blue. The study contributes to the existing literature by providing colour charts for bedroom applications for professionals in the industry, their clients/users, and future studies.

Environmental estrogen pollution and estrogen effects on the female reproduction system are well-recognized scientifically. Among the estrogens, 17 β-estradiol is a priority in environmental estrogen pollution, and it is also a major contributor to estrogen which regulates the female reproduction system. 17 β-estradiol is carcinogen and has a tumor promotion effect relating to breast cancer, lung cancer and others. It also affects the psychological well-being such as depression, fatigue and others. Thus, a simple method of detection of 17 β-estradiol will be important for both environmental estrogen pollution and women’s health care. This study demonstrates a simple-use, cost effective 17 β-estradiol biosensor system which can be used for both environment and women’s health care applications. The bio-recognition mechanism is based on the influence of the redox couple, K₃Fe (CN) ₆/K₄Fe (CN) ₆ by the interaction between 17 β-estradiol antigen and its α-receptor (ER- α; α-estrogen antibody). The transduction mechanism is an electrochemical analytical technique, differential pulse voltammetry (DPV). The levels of 17 β-estradiol antigen studied was between 2.25 pg/mL to 2,250 pg/mL, Phosphate buffered saline (PBS), tap water from the Cleveland regional water district, and simulate urine were used as the test media covering the potential application areas for 17 β-estradiol detection. An interference study by testosterone which has a similar chemical structure and molecular weight as those of 17 β-estradiol was carried out, and this 17 β-estradiol biosensor showed excellent specificity without any interference by similar chemicals.

Biohydrogen is a versatile energy carrier for the generation of electric energy from renewable sources. Hydrogenases can be used in enzymatic fuel cells to oxidize dihydrogen. The rate of electron transfer (ET) at the anodic side between the [NiFe]-hydrogenase enzyme distal iron-sulfur cluster and the electrode surface can be described by the Marcus equation. All parameters for the Marcus equation are accessible from DFT calculations. The distal cubane FeS-cluster has a three cysteine and one histidine coordination [Fe₄S₄](His)(Cys)₃ first ligation sphere. The reorganization energy (inner- and outer-sphere) is almost unchanged upon a histidine-to-cysteine substitution. Differences in rates of electron transfer between the wild-type enzyme and the all-cysteine mutant can be rationalized by a diminished electronic coupling between the donor and acceptor molecules in the [Fe₄S₄](Cys)₄ case. The fast and efficient electron transfer from the distal iron-sulfur cluster is realized by a fine-tuned protein environment which facilitates the flow of electrons. This study enables the design and control of electron transfer rates and pathways by protein engineering.

Public perception contrasts scientific findings on the depression-related effects of cannabis. However, earlier studies were performed when cannabis was predominantly illegal, its production was mostly uncontrolled, and the idea of medical cannabis was incipient only. We hypothesized that recent changes in attitudes and legislations may have favorably affected research. In addition, publication bias against cannabis may have also decreased. To investigate this hypothesis, we conducted a systematic review of research studies published over the last three years. We found 156 relevant studies. In most cross-sectional studies, depression was higher in those who consumed cannabis than in those who did not. An increase in cannabis consumption was typically followed by an increase in depression, whereas withdrawal from cannabis ameliorated depression in most cases. Albeit medical cannabis reduced depression in most studies, none of these were placebo controlled. In clinical studies published in the same period, placebo also ameliorated depression and in addition, the average effect size of placebo was larger than the average effect size of medical cannabis. We also investigated the plausibility of the antidepressant effects of cannabis by reviewing molecular and pharmacological studies. Taken together, the reviewed findings do not support the antidepressant effects of herbal cannabis.

Intrahepatic cholangiocarcinoma (ICCA) is a malignant epithelial neoplasm characterized by biliary differentiation within the liver. ICCA is molecularly heterogeneous and exhibits a broad spectrum of histopathological features. It is a highly aggressive carcinoma with high mortality and poor survival rates. ICCAs are classified into two main subtypes: small duct type and large duct types. These two tumor types have different cell origins and clinicopathological features. ICCAs are characterized by numerous molecular alterations, including mutations in KRAS, TP53, IDH1/2, ARID1A, BAP1, BRAF, SAMD4, and EGFR, and FGFR2 fusion. Two main molecular subtypes–inflammation and proliferation–have been proposed. Recent advances in high-throughput assays using next-generation sequencing have improved our understanding of ICCA pathogenesis and molecular genetics. The diagnosis of ICCA poses a significant challenge for pathologists because of its varied morphologies and phenotypes. Accurate diagnosis of ICCA is essential for effective patient management and prognostic determination. This article provides an updated overview of ICCA pathology, focusing particularly on molecular features, histological subtypes, and diagnostic approaches.

This paper discusses the design and implementation of a portable IoT station. Communication and data synchronization issues in several installations are addressed here, making possible a detailed analysis of the entire system during its operation. The system proposed is interpreted as an additional tool which can be utilized in several applications, where the system operator requires a synchronized data stream, combining multiple communication protocols into one single time stamp. The hardware selected for the portable IoT station complies with the International Electrotechnical Commission (IEC) industrial standards. A short discussion regarding interface customization shows how easily the hardware can be modified so that it is integrated with almost any system. A Programmable Logic Controller enables the Node-Red to be utilized. This open-source programming tool employs flows to define operations for each global variable nominated in the Modbus register. Two applications are presented and discussed in this paper, each application has a distinct methodology utilized to publish and visualize the acquired data. The portable IoT Station is highly customizable, consisting of a modular structure and providing the best platform for future research and development of dedicated algorithms.

Plasmodium falciparum dihydroorotate dehydrogenase (PfDODH) is one of the enzymes currently explored in the treatment of malaria. Although there is currently no clinically approved drug targeting PfDODH, many of the compounds in clinical trials have [1, 2, 4,] triazolo [1, 5-a] pyrimidin-7-amine backbone structure. This study sought to design new compounds from the fragments of known experimental inhibitors of PfDODH. Nine experimental compounds retrieved from Drug Bank online were downloaded and broken into fragments using Schrodinger power shell; the fragments were recombined to generate new ligand structures using BREED algorithm. The new compounds were docked with PfDODH crystal structure, after which the compounds were filtered with extensive drug-likeness and toxicity parameters. A 2D-QSAR model was built using the multiple linear regression method and externally validated. The compounds electronic behaviours were studied using DFT calculations. Structural investigation of the six designed compounds, which had lower binding energies than the standard inhibitors, showed that five of them had [1, 2, 4,] triazolo [1, 5-a] pyrimidin-7-amine moieties and interacted with essential residues at the PfDODH binding site. In addition to their drug-like and pharmacokinetic properties, they also showed minimal toxicities. The externally validated 2D-QSAR model with R² and Q² values of 0.6852 and 0.6691, confirmed the inhibitory prowess of these compounds against PfDODH. The DFT calculations showed regions of the molecules prone to electrophilic and nucleophilic attack. The current study thus provides insight into the development of a new set of potent PfDODH inhibitors.

In recent years, the AHRS has become an important research area. In order to improve the orientation measurement accuracy of AHRS, this paper first expounds the algorithm principle of the AHRS. Then, aiming at the problem of poor stability of the traditional gradient descent method under high dynamics or large magnetic field interference, a gain-scheduled anti-interference AHRS orientation algorithm is designed. By using the switching architecture designed with this algorithm for gain scheduling, it can ensure stable performance while being subjected to apparent acceleration and ferromagnetic interference. Finally, experimental verification is conducted, and the experimental results show that: in the presence of interference, the roll angle error is 0.0350°, the pitch angle error is 0.0277°, and the yaw angle error is 0.9611°, thereby verifying the strong anti-interference performance of the gain-scheduled AHRS orientation algorithm proposed in this paper.

In this paper we propose the generation of synthetic small and more sophisticated molecule structures that optimize the binding affinity to a target (ASYNT-GAN). To achieve this we leverage on three important achievements in A.I.: Attention, Deep Learning on Graphs and Generative Adversarial Networks. Similar to text generation based on parts of text we are able to generate a molecule architecture based on an existing target. By adopting this approach, we propose a novel way of searching for existing compounds that are suitable candidates. Similar to question and answer Natural Language solutions we are able to find drugs with highest relevance to a target. We are able to identify substructures of the molecular structure that are the most suitable for binding. In addition, we are proposing a novel way of generating the molecule in 3D space in such a way that the binding is optimized. We show that we are able to generate compound structures and protein structures that are optimised for binding to a target.

Vertical Indoor Farming (VIF) with hydroponics offers a promising perspective for sustainable food production. Intelligent control of VIF system components plays a key role in reducing operating costs and increasing crop yields. Modern machine vision (MV) systems use Deep Learning (DL) in combination with camera systems for various tasks in agriculture, such as disease and nutrient deficiency detection, and flower and fruit identification and classification for pollination and harvesting. This study presents the applicability of MV technology with DL modelling to detect the growth stages of chilli plants using YOLOv8 networks. The influence of different bird’s eye and side view datasets and different YOLOv8 architectures was analysed. To generate the image data for training and testing the YOLO models, chilli plants were grown in a hydroponic environment and imaged throughout their life cycle using four camera systems. The growth stages were divided into growing, flowering and fruiting classes. All trained YOLOv8 models showed reliable identification of growth stages with high accuracy. The results indicate that models trained with data from both views show better generalisation. YOLO’s middle architecture achieved the best performance.

As the world population grows, fulfilling the need for biomaterials in the healthcare system becomes increasingly important. Biomaterials, which include metals, polymers, ceramics, and composites, play an important role in the creation of medical devices that improve people's lives. The European Society for Biomaterials described biomaterials as non-biological materials used in medical devices to interact with biological systems. This definition has developed to encompass materials that treat, assess, or replace tissues or bodily functions. Biocompatibility, as defined by the FDA, is a key feature of biomaterials, as is the requirement to fulfil design requirements such as mechanical performance, geometry, and electrical control. Over the last decade, advances in regenerative medicine and tissue engineering have boosted biomaterials' usage in medical applications dramatically. Despite its promise, scientists, engineers, and physicians continue to face significant challenges due to the complexity of biomaterials. Biomaterials have various benefits, including biodegradability, non-toxicity, and biocompatibility, making them extremely useful for replacing, sustaining, or improving biological activities in damaged tissues. They are used in a wide range of applications, including tissue engineering implants, human tissue healing and regeneration, medication delivery systems, and biosensors. This study gives insights into the fundamental characteristics, case studies, and ethical issues associated with the usage and use of biomaterials, further examining their potential and significance in healthcare and medicine.

This paper proposes a product design model for internalising users’ positive experiences through attachment. First, the research commences with a literature review to define the concepts and research status of positive experience design (PED) and product attachment. Subsequently, the design model is constructed, accompanied by relevant formulas for concept generation. Finally, the model’s validity is verified through a workshop, and its effectiveness is evaluated and discussed using the USE questionnaire. This study incorporates the seven factors of product attachment to activate positive states within the user–product relationship and facilitate the cultivation of positive thinking. Grounded in theories of PED and embracing a product attachment perspective, the attachment-driven PED model offers a systematic approach for generating design concepts that are relevant to user experience.

This paper investigates an innovative photovoltaic cell configuration, denoted as “Au/CuSCN/RbGeI3/CdTe/ZnO/TiO2/FTO", using SCAPS-1D simulation. The research focuses on optimizing device performance by analyzing key components, including ZnO as the electron transport layer (ETL), RbGeI3 as the perovskite absorber layer, CuSCN as the hole transport layer (HTL), and CdTe as the active buffer layer. A comparison is made with the standard “Au/CuSCN/CH3NH3SnI3/CdTe/ZnO/TiO2/FTO" configuration under dark and illuminated conditions. Through an in-depth investigation involving temperature effects, generation rate analysis, RbGeI3 absorber layer thickness, Nd level, and interface defect levels, an optimized design for a unit area is achieved. The proposed solar cell demonstrates outstanding performance metrics, including an open circuit voltage (Voc) of 0.94V, a short circuit current density (Jsc) of 34.52mA/cm2, a fill factor (FF) of 77.77%, and an energy conversion efficiency (η) of 25.40%. These values significantly outperform the reference models with energy conversion efficiencies of 10.11% and 21.09%. Real-world applicability is validated by implementing these optimized characteristics in a photovoltaic system for Pakistan’s geographical location using PVSyst software. The suggested solar cell achieves a remarkable performance ratio (PR) of 85.6%, surpassing the PR of the reference basic solar cell model at 83%. The findings of this research offer a promising and superior solar cell design, incorporating innovative materials and optimization techniques to achieve exceptional energy conversion efficiency and overall performance. This study’s outcomes have the potential to advance photovoltaic technology and contribute to sustainable energy solutions worldwide.

In an effort to enhance the efficiency and safety of open-pit mines, this study explores the optimization of end slope road parameters and slope structures, specifically focusing on unmanned driving lanes.A significant aspect of the study is the development of a truck trajectory offset model, which considers the different reaction times between automated sensors and human drivers in adapting to environmental changes. To test these concepts, the study uses numerical simulations to confirm the stability of the proposed end slope designs. Using Victory West Mine No. 1 as a case study, the research determines the optimized width for unmanned driving lanes and the maximum angle for safe steepening of end slopes. The findings indicate that the optimized unmanned lane width for NTE240 mining dump trucks is 1743 mm, allowing for a 2-degree increase in the slope angle at the south end slope. This optimization leads to a steep mining stripping volume of 3.2735 million m³ and a coal output of 2.49628 million tons, maintaining a stripping ratio of 1.31m³/t. These results demonstrate that the unmanned driving road width optimization not only ensures slope safety but also significantly boosts the economic benefits of steep mining in open-pit mines.

Rural landscapes are acknowledged for their potential to restore human health due to their natural characteristics. However, few studies have systematically analysed the impact of naturalness, landscape types, and combinations of landscape elements on restorativeness using both subjective and objective measurements. This study investigated the restorative effects of various rural landscapes in Guangzhou, employing electroencephalography and eye-tracking technologies to record physiological responses and using the Restorative Components Scale and the Perceived Restorativeness and Naturalness Scale to evaluate psychological responses. The results indicated the following: (1) There was a significant positive correlation between perceived naturalness and restorativeness, surpassing the impact of actual naturalness. (2) Different landscape types had a varying impact on mental health at the equal perceived naturalness. Natural forest landscapes and artificial forest landscapes exhibited the most substantial restorative effects among the natural and semi-natural landscapes examined, respectively, while settlement landscapes showed the highest restorative potential among the artificial landscapes. (3) Restorative properties varied across landscape elements, with identical elements yielding different benefits in different environments. Trees and water significantly enhanced restorativeness, whereas constructed elements such as roads and infrastructure reduced it. This study provides a scientific basis for restorative rural landscape design to enhance mental health and well-being.

Intense climate change and rapid urbanization have increased the risk of urban flooding, seriously affecting urban economic and social stability. Enhancing the urban flood resilience (UFR) has required a new solution to cope with urban flood disasters. In this study, taking Yingtan city as an example, a system of indicators for evaluating UFR was constructed, with 17 representative indicators, comprising three subsystems: socio-economic, ecological and infrastructural. A hybrid (FAHP-EWM)-TOPSIS model was applied, to develop an index-based measurement to compare and evaluate UFR, and Gray Relational Analysis (GRA) was used to discover the main factors affecting UFR. In addition, the natural discontinuous method was innovatively used to divide the UFR grade interval into levels, and the grade change was evaluated based on the TOPSIS method. The results showed that (1) from 2010 to 2022, the UFR in Yingtan City increased by 80.69%, and the factors affecting UFR are highly correlated with urban infrastructure development. However, the ecological resilience in the subsystem showed a fluctuating downward trend, because of the influence of the surface area of lakes and rivers. (2) The grades of UFR for Yingtan City increased from Level III (2010 and 2016) to Level IV (2022), with local financial expenditures and the age structure of the population being the main factors currently limiting the development of UFR. The study provides a theoretical basis for the construction of an indicator system for assessing the UFR of Yingtan and proposes practical improvement directions for UFR.

During public health events, Active Mobility (walking and cycling) plays an important role in securing residents' travel. To enhance the resilience of urban transportation, this article integrates the travel environment elements for walking and cycling and constructs a travel environment for Active Mobility evaluation index system. This article uses survey data from the main urban area of Harbin in the context of the COVID-19 pandemic in May 2022, and combines the Gradient Boosting Decision Tree (GBDT) and Impact-Asymmetry Analysis (IAA) methods to analyze the satisfaction of the travel environment for Active Mobility. It proposes strategies for optimizing the travel environment for Active Mobility, ensuring residents' travel during public health events, guiding them to adopt Active Mobility, and improving urban transportation resilience. This research shows that Active Mobility can enhance urban transportation resilience. In addition, there are differences in resident demand for walking and cycling environments in the travel environment for Active Mobility. Residents are more concerned about the comfort of the walking environment, while they prioritize the convenience of the cycling environment.

Alzheimer’s disease (AD) is an age-associated neurodegenerative disorder. A wealth of evidence indicates that the amyloid β (Aβ) aggregates result from dyshomeostasis between Aβ production and clearance, which plays a pivotal role in the pathogenesis of AD. Consequently, therapies targeting Aβ reduction represent a promising strategy of AD intervention. Tetramethylpyrazine nitrone (TBN) is a novel tetramethylpyrazine derivative with the potential for the treatment of AD. Previously, we demonstrated that TBN markedly improved cognitive functions and reduced Aβ, APP, BACE 1 and hyperphosphorylated tau levels in 3 × Tg-AD mice. However, the mechanism by which TBN inhibits Aβ deposition still unclear. In this study, we employed the APP/PS1 mice treated with TBN (60 mg/kg, ig, bid) for six months and N2a/APP695swe cells treated with TBN (300 μM) to explore the mechanism of TBN on the Aβ reduction. Our results indicated that TBN significantly alleviated cognitive impairment and reduced Aβ depositions in APP/PS1 mice. Further investigation of the underlying mechanisms revealed that TBN decreased the expression of APP and BACE1, activated the AMPK/mTOR/ULK1 autophagy pathway and inhibited the PI3K/AKT/mTOR/ULK1 autophagy pathway, as well as decreased the phosphorylation levels of JNK and ERK in APP/PS1 mice. Moreover, TBN was found to significantly reduce the mRNA levels of APP and BACE1, as well as those of SP1, CTCF, TGF-β, and NF-κB, transcription factors involved in regulating gene expression. Additionally, TBN was observed to decrease the level of miR-346 and increase the levels of miR-147 and miR-106a in the N2a/APP695swe cells. These findings indicate that TBN may reduce Aβ levels likely via reducing APP expression by regulating APP gene transcriptional factors and miRNAs, reducing BACE1 expression, and promoting autophagy activities.

This study aimed to evaluate the safety and tolerability of STP1, a combination of ibudilast and bumetanide, tailored for the treatment of a specific subgroup of patients with Autism Spectrum Disorder (ASD), namely ASD Phenotype 1 (ASD-Phen1). We conducted a randomized, double-blind, placebo-controlled, parallel-group phase 1b study with two 14-day treatment phases (registered at clinicaltrials.gov as NCT04644003). Nine ASD-Phen1 patients were administered STP1, while three received a placebo. We assessed safety and tolerability, along with electrophysiological markers, such as EEG, Auditory Habituation, and Auditory Chirp Synchronization, to better understand STP1's mechanism of action. Additionally, we used several clinical scales to measure treatment outcomes. The results showed that STP1 was safe and well-tolerated, with electrophysiological markers indicating a significant and dose-related reduction of gamma power in the whole brain and in brain areas associated with executive function and memory. Treatment with STP1 also increased alpha 2 power in frontal and occipital regions and improved habituation and neural synchronization to auditory chirps. Although numerical improvements were observed in several clinical scales, they did not reach statistical significance. Overall, this study suggests that STP1 is safe and well-tolerated in ASD-Phen1 patients and shows indirect target engagement in ASD brain regions of interest.

Ucuùba fat is fat obtained from a plant found in South America, mainly in Amazonian Brazil. Due to its biocompatibility and bioactivity, the Ucuùba fat was used for production of ketoconazole-loaded nanostructured lipid carriers (NLC) in view of an application for the treatment of onychomycosis and other persistent fungal infections. The development and optimization of the Ucuùba fat based NLC were performed using a Box-Behnken design of experiment. The independent variables were surfactant concentration (% w/v), liquid lipids concentration (% w/v), solid lipids concentration (% w/v), while the outputs of interest were particle size, polydispersity index (PDI) and drug encapsulation efficiency (EE). The Ucuùba fat based NLC were produced and the process optimized determining a predictive mathematical model. Applying the model, two formulations with the pre-required particle size, i.e., 30 and 85 nm, were produced for further evaluation. The optimized formulations were characterized and showed a particle size in agreement to the predicted value, i.e. 33.6 nm and 74.6 nm, respectively. The optimized formulations were also characterized using multiple techniques in order to investigate the solid state of drug and excipients (DSC and XRD), particle morphology (TEM) and interactions between the formulation components (FTIR). Furthermore, particle size and surface charge of the formulations was studied during a one-month stability study and did not evidence any significative modification during storage.

Ensuring precise electric locomotive stopping is pivotal for achieving intelligent and unmanned auxiliary transportation systems. Currently, human drivers' expertise plays a central role in the stopping process, posing challenges for automation and cargo location accuracy, particularly in coal mining. This paper focuses on achieving accurate electric locomotive stopping under diverse conditions by utilizing permanent magnet synchronous motor-driven locomotives. This technique introduces a novel stopping control method that combines a fuzzy Proportional-Integral-Derivative (F-PID) controller and a vector control model for permanent magnet synchronous motors (PMSM). After this, we design the F-PID using the PMSM technique based on the new fuzzy rules for each sub-system. In the end, extensive simulations and real-world experiments are conducted on an electric locomotive stopping test bed, which demonstrate the effectiveness of the proposed control method. From the simulation results, it confirming that the ability to achieve precise stopping under various working conditions.

The recent covid crisis has proven important lessons for academia and industry regarding digital reorganization. Among fascinating lessons from these times is the huge potential of data analytics and artificial intelligence. The crisis exponentially accelerated the adoption of analytics and artificial intelligence, and this momentum is predicted to continue into the 2020s and over. Moreover, drug development is a costly and time-consuming business, and only a minority of approved drugs return the revenue that exceeds the research and development costs. As a result, there is a huge drive to make drug discovery cheaper and faster. With modern algorithms and hardware, it is not too surprising that the new technologies of artificial intelligence and other computational simulation tools can help drug developers. In only two years of covid research, many novel molecules have been designed/identified using artificial intelligence methods with astonishing results in terms of time and effectiveness. This paper will review the most significant research on artificial intelligence in the de novo drug design for COVID-19 pharmaceutical research.

Recently, it was proposed that the thiophene ring is capable of promoting mitochondrial accumulation when linked to fluorescent markers. As a noncharged group, thiophene presents several advantages from a synthetic point of view, making it easier to incorporate such a side moiety into different molecules. Herein, we confirm the general applicability of thiophene group as mitochondrial carrier for drugs and fluorescent markers, based on a new concept of nonprotonable, noncharged transporters. We implemented this concept in a medicinal chemistry application by developing an anti-tumoral, metabolic chimeric drug, based on PDHK inhibitor dichloroacetate (DCA). The promising features of the thiophene moiety as a noncharged carrier for targeting mitochondria may represent a starting point for the design of new metabolism-aimed drugs.

Drug design is used for different applications of bioinformatics tools analyze DNA, genome, and sequence target region of a small organic molecule in order to understand the molecules of disease. Bioinformatics tools are identified a newly wide research field and minimize future risks through web servers and data mining. Clinical sample test performed with the bioinformatics tools as the biomedical detective. A particular structure and configuration of protein obliging in Drug design concluded Bioinformatics. This review bioinformatics tools and webserver will discuss functions of small organic molecules according to clinical pharmacology.

Molecular dynamics(MD) simulations are playing an increasingly important role in structure-based drug discovery (SBDD). Here we review the use of MD for proteins in aqueous solvation, organic/aqueous mixed solvents (MDmix) and with small ligands, to the classic SBDD problems: binding mode and binding free energy predictions. The simulation of proteins in their condensed state reveals the solvent structure and preferential interaction sites (hot spots) on the protein surface. This information is largely transferable across all classes of protein ligands (from water to drugs) and can be used very effectively to understand ligand recognition and improve the predictive capability of well-established methods such as molecular docking. MD simulations for protein and drug or drug-like compounds are now being used but are still computationally expensive and can only be applied to specific cases. On the other hand, MDmix simulations can now be used in SBDD and we will describe the latest developments and implementations. We expect to see an increase in the application of these techniques to a plethora of protein targets to identify new drug candidates with the advent of new tools and faster computers.

Cancer-specific monoclonal antibodies (CasMabs) that recognize cancer-specific antigens with in vivo antitumor efficacy are innovative therapeutic strategies for minimizing the adverse effects. We previously established a cancer-specific anti-human epidermal growth factor receptor 2 (HER2)monoclonal antibody (mAb), H₂Mab-250/H₂CasMab-2. In flow cytometry and immunohistochemistry, H₂Mab-250 reacted with HER2-positive breast cancer cells but did not show the reactivity to normal epithelial cells. In contrast, a clinically approved anti-HER2 mAb, trastuzumab, strongly recognizes both breast cancer and normal epithelial cells in flow cytometry. The human IgG₁ version of H₂Mab-250 (H₂Mab-250-hG₁) possesses compatible in vivo antitumor effects against breast cancer xenografts with trastuzumab despite the lower affinity and effector activation than trastuzumab in vitro. This study compared the antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cellular cytotoxicity (CDC) between H₂Mab-250-hG₁ and trastuzumab. Both H₂Mab-250-hG₁ and trastuzumab showed ADCC activity against CHO/HER2 and breast cancer cell lines (BT-474 and SK-BR-3) in the presence of human natural killer cells. Some tendency was observed that trastuzumab showed a more significant ADCC effect compared to H₂Mab-250-hG₁. Importantly, H₂Mab-250-hG₁ exhibited superior CDC activity in these cells compared to trastuzumab. Similar results were obtained in mouse IgG_2a types of both H₂Mab-250 and trastuzumab. These results suggest the different contributions of ADCC and CDC activities to the antitumor effects of H₂Mab-250-hG₁ and trastuzumab and indicate the future direction for the clinical development of H₂Mab-250-hG₁ against HER2-positive tumors.

Drug repurposing is a valuable tool for combating the slowing rates of novel therapeutic discovery. The Computational Analysis of Novel Drug Opportunities (CANDO) platform performs shotgun repurposing of 2030 indications/diseases using 3733 drugs/compounds to predict interactions with 46,784 proteins and relating them via proteomic interaction signatures. An accuracy is calculated by comparing interaction similarities of drugs approved for the same indications. We performed a unique subset analysis by breaking down the full protein library into smaller subsets and then recombining the best performing subsets into larger supersets. Up to 14% improvement in accuracy is seen upon benchmarking the supersets, representing a 100–1000 fold reduction in the number of proteins considered relative to the full library. Further analysis revealed that libraries comprised of proteins with more equitably diverse ligand interactions are important for describing compound behavior. Using one of these libraries to generate putative drug candidates against malaria results in more drugs that could be validated in the biomedical literature than the list suggested by the full protein library. Our work elucidates the role of particular protein subsets and corresponding ligand interactions that play a role in drug repurposing, with implications for drug design and machine learning approaches to improve the CANDO platform.

This research aims to apply Artificial Intelligence (AI) methods, specifically Artificial Immune Systems (AIS), to design an optimal control strategy for a multivariable control plant. Two specific industrial control approaches are investigated: I-PD (Integral-Proportional Derivative) and PI-D (Proportional-Integral Derivative) control. The motivation for using these variations of PID controllers is that they are functionally implemented in modern industrial controllers, where they provide precise process control. The research results in a novel solution to the control synthesis problem for the industrial system. In particular, the research deals with the synthesis of I-P control for a two-loop system in the technological process of a distillation column. This synthesis is carried out using the AIS algorithm, which is the first application of this technique in this specific context. Methodological approaches are proposed to improve the performance of industrial multivariable control systems by effectively using optimization algorithms and establishing modified quality criteria. The numerical performance index ISE justifies the effectiveness of the AIS-based controllers in comparison with conventional PID controllers (ISE₁ = 1.865, ISE₂ = 1.56). The problem of synthesis of the multi-input multi-output (MIMO) control system is solved, considering the interconnections due to the decoupling procedure.

Among bryophytes, the Plagiochila genus represents a large group of leafy liverworts, with over 500 species. Plagiochilins A-to-X are sesquiterpenoids isolated from Plagiochila species. The lead compound plagiochilin A (Plg-A), endowed with anticancer and anti-parasitic properties, has been characterized as a potent mitosis inhibitor, acting selectively at the late stage of cytokinesis termed abscission. The compound perturbs the dynamic of microtubules, blocking cell cycle progression and triggering the death of malignant cells. Based on the compound mechanism of action and the analogy with other natural products bearing a dihydro-pyrone moiety, we postulated that Plg-A could bind to the pironetin site of α-tubulin. A molecular docking analysis has been performed to compare binding of all 24 plagiochilins to α-tubulin and to establish structure-binding relationships. The identification of Plg-E and Plg-G as the best binders in the series pointed out to the importance of the C13-OH or C=O group for α-tubulin recognition. This observation led to the testing of the natural product ester plagiochilin A-15-yl n-octanoate and the corresponding alcohol (Plg-OH), both identified as robust α-tubulin binders. The study provides a rational to explain potentially the mechanism of action of Plg-A and to guide the design of new derivatives.

For several years, drugs bearing reactive electrophilic appendages have been developed. These units typically confer prolonged residence time of the drugs on their protein targets, and may assist targeting shallow binding sites and/or improving drug-protein target spectrum. Studies on natural electrophilic molecules have indicated that in many instances natural electrophiles use similar mechanisms to alter signaling pathways. However, natural reactive species are also endowed with other important mechanisms to hone signaling properties that are uncommon in drug design. These include ability to be active at low occupancy and elevated inhibitor kinetics. Here we discuss how we have begun to harness these properties in inhibitor design.

The main proteinase (Mpro), or 3CLpro, is a critical enzyme in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lifecycle and is responsible for breaking down and releasing vital functional viral proteins crucial for virus development and transmission. As a catalytically active dimer, its dimerization interface has become an attractive target for antiviral drug development. Recent research has extensively investigated the enzymatic activity of Mpro, focusing on its role in regulating the coronavirus replication complex and its significance in virus maturation and infectivity. Computational investigations have identified four druggable pockets, suggesting potential allosteric sites beyond the substrate-binding region. Empirical validation through site-directed alanine mutagenesis targeted residues in both the active and allosteric regions corroborated these predictions. Structural studies of drug target proteins can inform therapeutic approaches, with metadynamics simulations shedding light on the role of H163 in regulating Mpro function and providing insights into its dynamic equilibrium to the wild-type enzyme. Despite the efficacy of vaccines and drugs in mitigating SARS-CoV-2 spread, ongoing viral evolution, selective pressures, and continued transmission pose challenges, potentially leading to resistance mutations. Phylogenetic analyses indicated the existence of several resistance variations predating drug introduction to the human population, emphasizing the likelihood of drug spread. Hydrogen/deuterium-exchange mass spectrometry reveals the structural influence of the mutation, while clinical trials on 3CLPro inhibitors underscore the clinical significance of reduced enzymatic activity and offer avenues for future therapeutic exploration. Understanding the implications of 3CLPro mutations holds promise for shaping forthcoming therapeutic strategies against COVID-19. This review delves into factors influencing mutation rates and identifies areas warranting further investigation, providing a comprehensive overview of Mpro mutations, their categorization, and terminology. Moreover, we examined their associations with clinical outcomes, illness severity, unresolved issues, and future research prospects, including their impact on vaccine efficacy and potential therapeutic targeting.

The clinical practice implies a research translation that helps the use of scientific data and thera-peutic evidence for patient benefits. This review critically summarizes the potential impact of cannabinoids in concomitance with other drugs in the following chronic diseases as Epilepsy, Au-tism Spectrum Disorders (ASD), Oncology, Multiple Sclerosis, and Chronic Pain. The potential in-teractions can change the predicted clinical outcomes of therapeutic protocols and need to be evaluated. Some of the effects would be additive, synergistic or antagonistic, but can also enroll changes in absorption, distribution, metabolism, particularly via cytochrome P450 (CYP) isoen-zymes (e.g CYP2C9 and CYP3A4) and excretion. For instance, the combination of canna-bis-derived compounds and the antifungal drug ketoconazole, a CYP3A4 inhibitor, increases plasma concentration of Δ-9-tetrahydrocannabinol (THC) and CBD (CBD). Opposable, rifampic-in, a CYP3A4 inducer, stands out for the approximately 20-40% reduction in plasma THC levels and 50% to 60% for CBD. Other CYP3A4 inhibitors and inducers are likely to have a similar effect on plasma concentrations if co-administered. Indeed, pharmacokinetic interactions have been also reported with antiseizure drugs. Moreover, pharmacodynamic interactions between cannabinoids and drugs with sympathomimetic effects (eg tachycardia, hypertension), central nervous system depressants (eg drowsiness, ataxia), and anticholinergics (eg tachycardia and drowsiness) are also expected. Even though pending further studies, there is currently clinical evidence supporting drug interaction with cannabinoids, demanding doctors evaluate the risk of drug combinations with cannabinoids. The tables herein provided were designed to facilitate the identification of bi-orelevant interactions that may compromise therapeutic efficacy and toxicity.

China is experiencing rapid urbanization. The focus on health issues has shifted from the treatment of diseases to passive or active prevention. Diseases caused by the deterioration of the urban environment, such as cardiovascular disease, diabetes, obesity and other chronic diseases and mental illness, have gradually become the main threat to public health. Studies have confirmed that urban green spaces (UGS) can help residents relieve mental stress, improve mood, reduce mental fatigue and restore attention, which has a positive effect on people's physical and mental health. In this study, the relationship between the quantity and quality factors of UGS and the physical and mental health of urban residents in Xihu District of Hangzhou is examined, and on this basis, UGS design strategies are proposed to promote the physical and mental health of residents. This study is of great significance for the future construction of UGS that are beneficial to the health of residents and the promotion of a healthy China and healthy city construction.

Substances that can modify the androgen receptor pathway in humans and animals are entering the environment and food chain with the proven ability to disrupt hormonal systems and leading to toxicity and adverse effects on reproduction, brain development, and prostate cancer, among others. State-of-the-art databases with experimental data of human, chimp, and rat effects by chemicals have been used to build machine learning classifiers and regressors and evaluate these on independent sets. Different featurizations, algorithms, and protein structures lead to dif- ferent results, with deep neural networks (DNNs) on user-defined physicochemically-relevant features developed for this work outperforming graph convolutional, random forest, and large featurizations. The results show that these user-provided structure-, ligand-, and statistically-based features and specific DNNs provided the best results as determined by AUC (0.87), MCC (0.47), and other metrics and by their interpretability and chemical meaning of the descriptors/features. In addition, the same features in the DNN method performed better than in a multivariate logistic model: validation MCC = 0.468 and training MCC = 0.868 for the present work compared to evalu- ation set MCC = 0.2036 and training set MCC = 0.5364 for the multivariate logistic regression on the full, unbalanced set. Techniques of this type may improve AR and toxicity description and predic- tion, improving assessment and design of compounds. Source code and data are available at https://github.com/AlfonsoTGarcia-Sosa/ML

In the present work, we report on a 3D MOF of {[Pb5(3-OH)(3-NO3)3(6-pmdc)3·H2O}n formula (pmdc = pyrimidine-4,6-dicarboxylate) synthesized by an oven-heated solvent-free procedure. The large connectivity afforded by the three ligands in their coordination to lead(II) ions grows cubic building units characterized by a central Pb atom with an unusual coordination index of 12 and six pmdc ligands occupying the faces. These cubic units are linked one another giving rise to a quite condensed structure that represents an unprecedented topology showing the (4.62)6(43)2(45.610)3(45.68.82)6(46.69)6(612.83) point symbol. The crystalline material has been characterized by routine physico-chemical techniques to confirm its purity and its thermal behaviour has been also studied by thermogravimetric and thermodiffractometric analyses. The solid presents greenish blue photoluminescent emission based on pmdc ligands, as revealed time-dependent density-functional theory (TD-DFT) calculations, by that is substantially more intense than in free H2pmdc ligand according to its improved quantum yield. The emissive capacity of the material is further analysed according to decreasing temperature of the polycrystalline sample, finding that sizeable long-lasting phosphorescence is present.

This study investigates the spatial and temporal dynamics of Paomo restaurants in Xi'an's central urban area from 2012 to 2023, leveraging Point of Interest (POI) data through a series of sophisticated analytical techniques. Methods including nearest neighbor distance, kernel density estimation, and band set statistical analysis were employed to thoroughly examine the evolutionary patterns and key drivers influencing the spatial distribution of these eateries. Our results highlight a notable trend of expansion from the central city to the periphery, characterized by significant spatial agglomeration. Initially concentrated in the city center, the distribution of Paomo restaurants has progressively shifted towards multiple distinct cores, reflecting the dual influence of urban policy initiatives and the dynamics of market competition. Furthermore, the research identifies several pivotal factors shaping this spatial distribution, particularly transportation access, residential quality of life, and the availability of commercial services. These findings demonstrate the profound effects of urban spatial reconfiguration and socioeconomic development on the specialized catering industry. The insights gleaned from this analysis offer valuable guidance for urban planners and policymakers, providing strategic recommendations for the spatial planning of specialty catering services to optimize urban layouts and foster sustainable economic progress.

Drugs-drugs interactions(DDI) are entities composed of different chemical substructures (functional groups). In existing methods that predict drug–drug interactions based on the usage of substructures, each node is considered the center of a substructure, and adjacent nodes eventually become centers of similar substructures, resulting in redundancy. Furthermore, the significant differ- ences in structure and properties among compounds can lead to unrelated pairings, making it difficult to integrate information. This heterogeneity negatively affects the prediction results. To address these issues, we propose a drug–drug interaction prediction method based on substructure signature learning (DDI-SSL). This method extracts useful information from local subgraphs surrounding drugs and effectively utilizes substructures to assist in predicting drug side effects. Additionally, a deep clustering algorithm is used to aggregate similar substructures, allowing any individual subgraph to be reconstructed using this set of global signatures. Furthermore, we developed a layer-independent collaborative attention mechanism to model the mutual influence between drugs, generating signal strength scores for each class of drugs to mitigate noise caused by heterogeneity. Finally, we evaluated DDI-SSL on a comprehensive dataset and demonstrated improved performance in DDI prediction compared to state-of-the-art methods.

Ever since Varela and Maturana proposed the concept of autopoiesis as the minimal requirement for life, there has been a focus on cellular systems that erect topological boundaries to separate themselves from their surrounding environment. Here we reconsider whether the existence of such a spatial boundary is strictly necessary for self-producing entities. This work presents a novel computational model of a minimal autopoietic system inspired by dendrites and molecular dynamics simulations in three-dimensional space. A series of simulation experiments where the metabolic pathways of a particular autocatalytic set are successively inhibited until autocatalytic entities that could be considered autopoietic are produced. These entities maintain their distinctness in an environment containing multiple identical instances of the entities without the existence of a topological boundary. This gives rise to the concept of a metabolic boundary which manifests as emergent self-selection criteria for the processes of self-production without any need for unique identifiers. However, the adoption of such a boundary comes at a cost, as these autopoietic entities are less suited to their simulated environment than their autocatalytic counterparts. Finally, this work showcases a generalized metabolism-centered approach to the study of autopoiesis that can be applied to both physical and abstract systems alike.

Of the manifold concepts in drug discovery and design, covalent drugs have re-emerged as one of the most promising over the past 20-or so years. All such drugs harness the ability of a covalent bond to drive an interaction between a target biomolecule, typically a protein, and a small molecule. Formation of a covalent bond necessarily prolongs target engagement, opening avenues to targeting shallower binding sites, protein complexes, and other difficult to drug manifolds, amongst other virtues. This opinion piece discusses frameworks around which to develop covalent drugs. Our argument, based on results from our research program on natural electrophile signaling, is that targeting specific residues innately involved in native signaling programs are ideally poised to be targeted by covalent drugs. We outline ways to identify electrophile-sensing residues, and discuss how studying ramifications of innate signaling by endogenous molecules can provide a means to predict drug mechanism and function and assess on- versus off-target behaviors.

Amid escalating urbanization, devising rational commercial space layouts is a critical challenge. Leveraging machine learning, this study uses a Back-propagation (BP) neural network to optimize commercial spaces in Weinan City's central urban area. The results indicate an increased number of commercial facilities with a trend of multi-centered agglomeration and outward expansion. Based on these findings, we propose a strategic framework for rational commercial space development emphasizing aggregation centers, development axes, and spatial guidelines. This strategy provides valuable insights for urban planners in small and medium-sized cities in the Yellow River Basin and metropolitan areas, ultimately showcasing the power of machine learning in enhancing urban planning.

The recent outbreak of the new virus in Wuhan city, China from the sea food market has led to the identification of a new strain called the corona virus and named as novel corona virus (2019-nCoV) belonging to Coronaviridae family. This has created major havoc and concern due to the mortality of 250 persons and affecting more than 10,000 people. This virus causes sudden fever, pneumonia and also kidney failure. In this study a computational approach is proposed for drug and vaccine design. The spike protein sequences were collected from a protein database and analysed with various bioinformatics tools to identify suitable natural inhibitors for the N-terminal receptor binding domain of spike protein. Also, it is attempted to identify suitable vaccine candidates by identifying B-Cell and T-cell epitopes. In the drug design, the tanshinone Iia and methyl Tanshinonate were identified as natural inhibitors based on the docking score. In the vaccine design, B-cell epitope VLLPLVSSQCVNLTTRTQLPPAYTN was found to have the highest antigenicity. FVFLVLLPL of MHC class-I allele and FVFLVLLPL of MHC class-II allele were identified as best peptides based on a number of alleles and antigencity scores. The present study identifies natural inhibitors and putative antigenic epitopes which may be useful as effective drug and vaccine candidates for the eradication of novel corona virus.

Enclosed public spaces are the hotspots for airborne disease transmission. To measure and maintain indoor air quality in terms of airborne transmission, an open source, low cost and distributed array of Particulate Matter Sensors has been developed and named as Dynamic Aerosol Transport for Indoor Ventilation or DATIV system. This system can use multiple Particulate Matter Sensors (PMS) simultaneously and can be remotely controlled using a Raspberry Pie based operating system. The data acquisition system can be easily operated using the GUI within any common browser installed on a remote device such as a PC or Smartphone with corresponding IP address. The software architecture and validation measurements are presented together with possible future developments.

Contemporary financial systems, despite their inherent complexity and resilience, face significant challenges related to transparency, efficiency, and security. Notable deficiencies in transparency and emerging security vulnerabilities underscore the pressing need for innovative solutions in current financial practices. Hence, this paper introduces a financial distribution system based on a consortium blockchain. Given organizations’ preference for keeping sensitive data private, the partially decentralized nature of consortium blockchains plays a pivotal role in the proposed system’s architecture. Moreover, within this system, the proposed smart contract serves a dual role. It functions not only as a transactional tool but also as a specialized solution designed to improve transactional procedures. Its multifaceted capabilities include ensuring data accuracy, facilitating swift execution, and ensuring adherence to regulatory requirements within the dynamic financial distribution landscape. Through rigorous testing and empirical analysis utilizing the Hyperledger Besu platform, it has been observed that the performance of the proposed system surpasses traditional blockchain frameworks. The results unequivocally demonstrate the proposed system’s proficiency in handling high-frequency financial transactions with minimal computational burden.

Presently, Jordan confronts a double substantial challenge of enhancing energy security and mitigating greenhouse gas emissions. One of the most encouraging avenues to attain the objectives of sustainable development, energy security, and environmental conservation is to enhance the integration of renewable energy into the generation of electricity. In pursuit of this goal, the Jordanian government intends to expand investments in the green energy sector, with solar and wind energy poised to play a key role in satisfying energy demands and cultivating an environmental sustainability. This paper aims to examine the distinctive dynamics, challenges, obstacles, and potential solutions corresponding to the establishment of community solar and wind farms in Jordan suburban areas. It aims to highlight the opportunities and barriers influencing the track of sustainable energy adoption in the country. Through a comprehensive analysis of the Jordanian context, the goal is to extract insights that can guide policies and practices. Additionally, the findings may serve as a valuable benchmark for other regions confronting similar challenges on their pursuit for a sustainable energy future.

This paper presents laboratory devices on which experimental measurements were carried out to prove the validity of the assumption about the reduction of vibrations transmitted to the conveyor belt structure generated by the impact forces of falling material grains in the places of transfer or on the hoppers of conveyor belts. In order to limit damage to the conveyor belts caused by the impact of the sharp edges of material grains, conveyor belts are supported by impact rollers or impact rubber rods in the places of transfers and on the hoppers of belt conveyors. The flattened ends of the impact rollers are inserted into the grooves of steel brackets installed on the supports of the fixed conveyor idlers of a conventional design. In this paper, a special modification of the fixed conveyor idler is presented, which consists of inserting plastic brackets into the structurally modified roller axle holders of the fixed conveyor idler. Measurements were carried out on the first laboratory device, which showed that the specially modified fixed conveyor idler resulted in a higher damping of up to 15% of the impact forces of the falling weight on the rubberized hoop of the impact roller shell compared to the conventional fixed conveyor idler design. Measurements carried out on the second laboratory device show that the effective vibration velocity values detected at the points where the impact roller axis fits into the fixed roller table holder, i.e. points B and D, are higher than when using plastic brackets, up to 6% for a 108 mm diameter roller, compared to steel impact roller brackets.

EphB2 is a member of the Eph family tyrosine kinase receptors. EphB2 binds to ephrin-B1, ephrin-B2, and ephrin-B3, which are critical regulators of vascular and nervous development through controlling cell migration and axon guidance. EphB2 is overexpressed in tumors, including glioma, breast cancer, hepatocellular carcinoma, and malignant mesothelioma, and it functions as a tumor promoter. Therefore, the development of monoclonal antibodies (mAbs) against EphB2 is essential for tumor diagnosis and therapy for EphB2-positive tumors. In this study, we developed novel mAbs for human EphB2 using the Cell-Based Immunization and Screening (CBIS) method. One of the established anti-EphB2 mAbs, Eb2Mab-3 (mouse IgG1, kappa), reacted with EphB2-overexpressed Chinese hamster ovary-K1 (CHO/EphB2) and an endogenously EphB2-expressing cancer cell line (LS174T) by flow cytometry. Using flow cytometry, the dissociation constant (KD) values of Eb2Mab-3 for CHO/EphB2 and LS174T were determined as 1.1 × 10−9 M and 3.6 × 10−10 M, respectively. These results indicated that Eb2Mab-3 possesses a high affinity for detecting EphB2 and could apply to tumor therapy.

Elderly individuals frequently perceive companion robots devoid of warmth, resulting in a reluctance to accept these robots' services. This perception has become a significant barrier to the introduction of companion robots into households. To address this issue, this study employs KE methods to translate the elderly's need for warmth perception from companion robots into elements of modelling design. Initially, 20 pairs of affective words and 22 sample images of companion robots were chosen. The "rational-emotional" and "dim-bright" dimensions were identified as positively influencing the elderly's warmth perception of companion robots through SD method analysis. Subsequently, a hierarchical analysis table was established, with warmth perception as the root layer, modelling style and color matching as the basic layer, "rational-emotional" and "dim-bright" as the expansion layer, and the eight characteristic elements of companion robots as the morphological layer. The link between affective imagery and design elements was then established from the sample robots with higher warmth perception scores. Based on the correlation between the two, various design schemes were formed through random combinations. Finally, the design schemes were evaluated using the warmth perception scale, and the warmth perception scores of each sample model were obtained. This research provides design references for designing companion robots for the elderly with a "sense of warmth".