Background: Leishmaniasis is a significant global public health issue that is caused by parasites from Leishmania genus. With limited treatment options and rising drug resistance, there is a pressing need for new therapeutic approaches. Molecular chaperones, particularly Hsp90, play a crucial role in parasite biology and are emerging as promising targets for drug development. Objective: This study evaluates the efficacy of 17-DMAG in treating BALB/c mice from cutane-ous leishmaniasis through in vitro and in vivo approaches. Materials and Methods: We assessed 17-DMAG cytotoxic effect on bone marrow-derived mac-rophages (BMMΦ) and its effects against L. braziliensis promastigotes and intracellular amastigotes. Additionally, we tested the compound's efficacy in BALB/c mice infected with L. braziliensis via intraperitoneal administration to evaluate the reduction of lesion size and de-crease of parasite load in the ears and lymph nodes of infected animals. Results: 17-DMAG showed selective toxicity [selective index=432) towards Leishmania amastigotes, causing minimal damage to host cells. The treatment significantly reduced lesion sizes in mice and results in parasite clearance from ears and lymph nodes. It also diminished in-flammatory responses and reduced the release of pro-inflammatory cytokines (IL-6, IFN-g, TNF) and the regulatory cytokine, IL-10, underscoring its dual leishmanicidal and anti-inflammatory properties. Conclusion: Our findings confirm the potential of 17-DMAG as a viable treatment for cutaneous leishmaniasis and support further research into its mechanisms and potential applications against other infectious diseases.

This article utilizes the Canny edge extraction algorithm based on contour curvature and the cross-correlation template matching algorithm to extensively study the impact of high-repetition-rate CO2 pulsed Laser on the target extraction and tracking performance of the infrared imaging detector. It establishes a quantified dazzling pattern for lasers on infrared imaging systems. By conducting laser dazzling and damage experiments, a detailed analysis of the normalized correlation between target and dazzling images is performed to quantitatively describe laser dazzling effects. Simultaneously, an evaluation system, including target distance and laser power evaluation factors, is established to determine the dazzling level and whether the target is recognizable. The research results reveal that laser power and target position are crucial factors affecting the detection performance of infrared imaging-guided weapon systems under laser dazzling. Different laser powers are required to successfully interfere with the recognition algorithm of infrared imaging-guided weapons at different distances. And laser dazzling will produce a lot of false edge information, which seriously affects the performance of pattern recognition algorithm. In laser damage experiments, the detector experienced functional damage, with a quarter of the image displaying as completely black. The energy density threshold required for functional damage to the detector is approximately 3 J/cm2. The dazzling assessment conclusions also apply to evaluating damage results. Finally, the proposed evaluation formula aligns with experimental results, objectively reflecting the actual impact of laser dazzling on the target extraction and tracking performance of infrared imaging systems. This study provides an in-depth and accurate analysis for understanding the influence of lasers on the performance of infrared imaging-guided weapons.

Based on the demographic shift and the related challenges resulting from the growing number of elderly and persons with chronic diseases, the idea of smart home that supports its inhabitants in the daily life, gains importance. The purpose of this paper was to examine in a prototypic Ambient Assisted Living environment if users after interaction with different health-supporting applications intend to use such in the future. Two experimental studies exemplary show possible applications of home-integrated technology that can support, assist and accompany the target group in different contexts, and examine to what extent participants are willing to future use such sophisticated technology at home. The results show that people in general, but especially the old and chronically ill ones are quite fascinated of health-supporting ambient technology and the majority intends to use such ambient assistance in the future (study I). Moreover, serious games for healthcare are shown as a hedonic use of technology in smart homes that have a great potential to retain or improve the physical health, mobility and the overall well-being of the inhabitants (study II). The article provides two examples of ambient technology to leverage the demographic change and presents important user factors for facilitating high user acceptance.

Strip steel surface defect recognition research has important research significance in industrial production. Aiming at the problems of defect feature extraction difficulty, slow detection speed and insufficient dataset, YOLOv5 is improved on the basis of YOLOv5, and YOLO-LFPD (Lightweight fine particle detection) model is proposed. By introducing the RepVGG (Re-param VGG) module, the robustness of the model to the surface defect features of strip steel is enhanced, and the expressive ability of the model is improved. FasterNet is used to replace the backbone network, which ensures the accuracy and accelerates the inference speed, making the model more suitable for real-time monitoring. The use of pruning, GA genetic algorithm with OTA loss function method further reduces the model size while better learning the strip steel defect feature information, thus improving the generalisation ability and accuracy of the model. The experimental results show that the introduction of the RepVGG module and the use of FasterNet can well improve the model performance, with a reduction of 48% in the number of parameters, a reduction of 13% in the number of GFLOPs, an inference time of 77% of the original, and an optimal accuracy compared with the network models in recent years. The experimental results on the NEU-DET dataset show that the accuracy of YOLO-LFPD is improved by 3% to 81.2%, which is better than other models, and provides new ideas and references for the lightweight strip steel surface defect detection scenarios and application deployment.

By introducing environmental mediator, for avoiding randomness in selecting indicators and subjectivity in deciding interaction path coefficients to reveal interaction mechanism among forest industry, ecology and environmental capacity, structural Pressure–State–Impact–Response (PSIR) and quantitative Structural Equation Modeling (SEM) are utilized with data on thirty–one provinces of China. We can find that: (i) forest industry has a negative influence on ecology, whereas ecology has a positive influence on industry; (ii) the destructive influence that industry has on ecology is much greater than the positive effect ecology has on industry; and (iii) environmental capacity plays a partial mediating role between industry and ecology. According to these results we can conclude that: (i) forest industry and ecology are not in a symbiotic relationship and have not reached a level of ecological security; (ii) the interaction between industry and ecology is in a period of transition from antagonistic to beneficial; and (iii) industry dominates ecology. However, we prospect the following advice: (i) methods of forest industry should be changed; (ii) new modes of industrial integration and circular economy should be developed; and (iii) the ability of the environment to sustain itself should be enhanced. The level of forest ecological security to discuss the symbiotic mechanism of industry and ecology will propose to be measured in future.

The intelligent morphing wing structure has the characteristics of flexibility, large deformation and adaptive change, which are different from those of the conventional wing. The motion law of the variable-camber leading edge is analysed by the numerical simulation method based on kinematics theory to solve the problem of verifying the motion function and structural strength of the variable camber wing. The driving deformation and aerodynamic load simulation of the variable camber leading edge are realised by designing a follow-up load test apparatus. Based on the numerical simulation of the mechanical boundary, the motion trajectory of the upper and lower wing loading points was predicted, and a multi-point cooperative control system was developed. Multi-sensor iteration was used to ensure the loading accuracy of the test control. The test results show that the average error of the deflection angle is 4.59% in the variable camber leading edge motion test. In the variable camber leading edge strength test, the average error of applied load magnitude and direction is 0.54% and 0.24%, respectively.

The paper presents the problem of damage detection in steel girders. Static displacements at the selected point of the structure play the role of measured variables. Structural response signal decomposition is performed according to the Mallat pyramid algorithm, which is used to perform the discrete wavelet transform (DWT). This procedure allows us to quite well determine the location of structural damage. The geometry and the placement of any defective part of the structure may have a random character. It can be assumed that the random processes occurring in the broadly understood structure mechanics are Gaussian in nature. The first four probabilistic moments are estimated using three approaches independent: semi-analytical (SAM), perturbative (SPT), and Monte-Carlo simulations (MCS). The semi-analytical random approach seems to be the most optimal due to the necessary computation time. The incorporation of the mathematical stochastic apparatus into the classical (deterministic) analysis of the statics of the structure makes it possible to estimate the reliability measures of the analyzed girder.

Effects of oxygen content on microstructure and creep property of FGH96 superalloy were investigated. When oxygen content increased from 135ppm to 341ppm, prior particle boundary (PPB) rose from degree 2 to degree 3, and the size of γ′ phase on PPB enlarged from 1.07μm to 1.27μm, and MC carbide size grew from 77.4nm to 104.0nm. Meanwhile, the steady creep rate accelerated form 4.34×10-3 h-1 to 1.87×10-2 h-1, and the creep rupture life shortened from 176h to 94h, and the creep rupture mode transferred from intergranular and transgranular mixed fracture to along PPB fracture. During creep, the micro-twins formation and gliding will be restrained by ∑3 boundaries. FGH96 superalloy with higher oxygen content contains less ∑3 boundaries and its micro-twins cross slipped instead of single direction slip in lower oxygen content superalloy. Consequently, specimen with higher oxygen content creeped faster and raptured earlier.

This literature review provides an in-depth exploration of the research conducted on the investigation and measurement of residual stress (RS) in Wire Arc Additive Manufacturing (WAAM) products, particularly focusing on how process parameters influence the phenomenon. RS plays a crucial role in determining the mechanical behavior and structural integrity of WAAM components. This review article gives an understanding of the relationship between process parameters and RS to optimize the WAAM processes and ensure the durability of the final products. It also summarizes key findings, measurement techniques, challenges, and future directions in this evolving field. The review also analyzes a measurement of RS in the products of WAAM as a function of process parameters depending on examining various research studies, techniques, and methodologies employed in their studies. Experimental measuring techniques and numerical analysis of RS to determine the impacts of RS in mechanical response in products of WAAM were discussed. By offering a comprehensive overview of current research trends and insights, this review serves as a valuable resource to guide future investigations, fostering the advancement of WAAM as a robust and efficient manufacturing technology.

The superfamily of Acid proteases has two catalytic aspartates for proteolysis of their peptide substrates. Here, we show a minimal structural scaffold, the Structural Catalytic Core (SCC), which packs all conserved substructure elements around the catalytic machinery, and which can be found in all enzymes of the Acid proteases superfamily. The SCC is a dimer of several structural blocks, such as the DD-link, the D-loop and the G-loop, around two catalytic aspartates in each protease subunit or within an individual chain. The dimer of two D-loop/DD-link substructures makes a DD-zone, and the dimer of two D-loop/G-loop substructures makes a psi-loop. These structural markers are useful for protein comparison, structure identification, protein family separation and protein engineering.

The effectiveness of a hybrid technique for identifying seismic damage in planar, multistory, steel X or V-braced frames is demonstrated here through an example of a six-story frame. This proposed technique, referred to as “M and P”, combines the instrumental Monitoring (M) with Pushover analysis (P). According to the methodology, the diagram of stepping eigenfrequencies of the frame in the inelastic region is initially plotted against seismic roof displacement. The fundamental natural frequency detected via the monitoring process is then utilized in this key diagram to reveal the inelastic roof displacement that corresponds to the damage state of the steel braced frame. This displacement is subsequently used as the target in the pushover analysis, facilitating the identification of seismic damage in the existing steel braced frame. Finally, the damage image is correlated with the damage stiffness matrix of the frame at the same inelastic roof displacement. The investigation results indicate that combining instrumental monitoring with pushover analysis enables accurate identification of seismic damage potential in existing steel braced frames.

The paper delves into the critical issue of damage detection within the guy cable of a truss steel mast, a pivotal component in structural integrity. It introduces a model wherein damage manifests as a localized cross-section reduction in a single element of the cable. Employing Discrete Wavelet Transform (DWT), a pioneering methodology, the study scrutinizes the behavior of the affected elements through static structural analyses. Signal decomposition via the Mallat pyramid algorithm facilitates comprehensive examination. Static displacements at the connection point between the cable and the truss mast serve as the measured variables. Through systematic investigation, the paper evaluates the impact of damage size and location, external loading force, and cable tension force on the efficacy of the proposed approach. Utilizing data derived from Finite Element Method (FEM) computations for wavelet analysis the authors substantiate the findings with numerical examples, thus offering valuable insights into damage detection strategies for structural health monitoring and engineering applications.

This study provides an in-depth review of the available literature on metal composite material machining, focusing on traditional machining operations such as turning, milling, shaping, drilling, and grinding. The motivation for the study is that this composite type has emerged as a vital material in applications requiring functionality, resilience, cost-effective operation, low consumption of energy and lightweight. Despite its superior characteristics, the manufacturing complexity and poor machinability of metal matrix composites have been the primary barriers to its adoption. Nevertheless, there is a reduction of exceptional efficiency, increase in surface roughness, tool wear and so on in metal matrix composites throughout machining. As a result, this review gives a comprehensive investigation of metal matrix composite machining and effect on process parameters and procedures. Furthermore, this study distinguishes metal matrix composites towards sustainable manufacturing and the metals employed by the researchers, as well as the gaps discovered for future recommendations in metal-based composites.

The epidemic of obesity has increased worldwide and is associated with comorbidities as diabetes as cardiovascular disease. Strategies that modulate body weight and improves glycemic metabolism has increased, and the bariatric surgeries as Sleeve Gastrectomy (SG) has been highlighted in obesity treatment. However, the mechanism by which SG reduces body weight and improves glycemic control are unknow. C57BL mice were submitted to a 10 weeks high fat-diet protocol and submitted to SG. Food intake, fed/fasted glycemia and hypothalamic anorexigenic and orexigenic gene expression were evaluated. SG reduces body weight, fasting glycemia, insulinemia and leptinemia in obese mice. Moreover, SG reduces food and total calorie intake with no alterations in the expression of anorexigenic and orexigenic gene expression. These data indicates that SG improves obesity associated alterations, at least in part, by reduction on food intake. This effect is not associated with the classic food intake pathway in hypothalamus, indicating the involvement of supplementary pathways in this process.

This paper proposes an enhanced Quantum Key Distribution (QKD) protocol by incorporating a Three-Dimensional Angular Momentum Representation (3D AMR) to address vulnerabilities inherent in traditional two-dimensional polarization states-based systems. The 3D AMR method expands the state space, potentially increasing security against sophisticated quantum attacks. We present a theoretical and computational framework that transitions from the conventional two-dimensional polarization to a three-dimensional angular momentum space, which inherently increases the complexity and security of the quantum states used in QKD.

The review analyzes the studies published mainly in the last 10-15 years, on the synthesis, structure, and sensor properties of semiconductor nanocomposites. Particular attention is paid to the interaction between nanoparticles of the sensitive layer and its effect on the structure, sensitivity, and selectivity of semiconductor sensor systems. Various mechanisms are considered of interaction between nanoparticles in metal oxide composites including incorporation of metal ions of one component into the structure of another, heterocontacts between different nanoparticles, and core-shell systems, as well as their influence on the characteristics of gas sensors. The experimental data and studies on the modeling of charge distribution in semiconductor nanoparticles, which determine the conductivity and sensor effect in one- and two-component systems, are also discussed. It is shown that the model which considers the interactions of nanoparticles best describes the experimental results. Some mechanisms of detection selectivity are considered in the conclusion.

The article reveals distinctive features of the interaction between architectural and structural solutions for the design of tall buildings as well as spotlights the most distinctive cases of expression. In the contemporary world, interaction is turning into the antithesis of the formerly dominant utilitarian attitude and standardization of tall buildings architectural solutions. Meanwhile, the search for rational structural solutions leads to new possibilities of architectural expression. This necessitates the transformation of a structural solution and its adaptation to the need of a modern architect to be exceptional and noticed. Interaction covers the current as well as retrospective and perspective periods. SWOT analysis was used by the authors of the article to assess the interaction between architectural and structural solutions in tall buildings design, select the most important criteria that could be used searching for rational architectural and structural solutions in future by applying multi-criteria decision making methods.

Full depth precast deck panel (FDDP) is one element of the prefabricated bridge element and systems (PBES) that allows for quick un-shored assembly of the bridge deck on-site as part of the accelerated bridge construction (ABC) technology. This paper investigates the structural response of full-depth precast deck panels (FDDPs) constructed with new construction materials and connection details. FDDP is cast with normal strength concrete (NSC) and reinforced with high modulus (HM) glass fiber reinforced polymer (GFRP) ribbed bars. The panel-to-girder V-shape connections use the shear pockets to accommodate the clustering of the shear connectors. A novel transverse connection between panels has been developed, featuring three distinct female-to-female joint configurations, each with 175-mm projected GFRP bars extending from the FDDP into the closure strip, complemented by a female vertical shear key and filled with cementitious materials. The ultra-high performance fiber reinforced concrete (UHPFRC) was selectively used to joint-fill the 200-mm transverse joint between adjacent precast panels and the shear pockets connecting the panels to the supporting girders to ensure full shear interaction. Two actual-size FDDP specimens for each type of the three developed joints were erected to perform fatigue tests under the footprint of the Canadian Highway Bridge Design Code (CHBDC) truck wheel loading. The FDDP had a 200-mm thickness, 2500-mm width, and 2400-mm length in traffic direction; the rest was over braced steel twin girders. Two types of fatigue tests were performed; incremental variable amplitude fatigue (VAF) loading and constant amplitude fatigue (CAF) loading, followed by monotonically loading the slab ultimate-to-collapse. It was observed that fatigue test results showed that the ultimate capacity of the slab under VAF loading or after 4 million cycles of CAF exceeds the factored design wheel load specified into the CHBDC. Also, punching shear failure mode was dominant in all the tested FDDP specimens.

Reliable and precise damage localization in mechanical structures is of high importance in the context of structural health monitoring (SHM). The acoustic emission (AE) method has already shown its excellent suitability for damage localization. However, low signal-to-noise ratios (SNRs) are often prevalent in SHM, thus an increase in localization accuracy and robustness is still in demand. The present study faces this task through the integration of various model knowledge for AE source localization. The basis of the presented algorithm is the consideration of the dispersive behavior of elastic waves in thin-walled structures. The continuous wavelet transform (CWT) is used to obtain time-frequency representations of the signals, where frequency-dependent values for time-of-arrival (TOA) are extracted. Furthermore, the algorithm incorporates the knowledge that all sensors receive signals with the same time and location of origin, as well as the slightly different sensitivity of the theoretically equal sensors. The final localization results are achieved by a two-parameter grid search optimization. The algorithm is experimentally tested on a large aluminum plate with four piezoelectric wafer active sensors (PWASs) arranged in an array of 100 mm × 100 mm. The mean localization error of pencil lead breaks at ten different positions within the sensor array is used as an accuracy measure. It is shown that as more of the described model knowledge is incorporated into the localization, the accuracy increases. With the final algorithm, the mean localization error is more than halved compared to AE localization based on classical TOA estimation. Although the experiment described is conducted under laboratory conditions, the remarkable increase in accuracy suggests that AE source localization may be successful even at low SNR as typical for operational conditions.

In recent years, there has been an increasing interest in adopting novel sensing technologies for the continuous monitoring of structural systems. In this respect, Micro-Electro-Mechanical System (MEMS) sensors are widely used in several applications, including Structural Health Monitoring (SHM). Thanks to their significantly lower cost, ease of installation on the structure, and lower power consumption, they enable extensive, pervasive, and battery-less monitoring systems. This paper presents an innovative high-performance device for SHM applications, based on a low-noise triaxial MEMS accelerometer, providing a guideline and insightful results about the opportunities and capabilities of these devices. Sensor nodes have been designed, developed, and calibrated to meet structural vibration monitoring and modal identification requirements. These components include a protocol for reliable command dissemination through the network and data collection, and improvements to software components for data pipelining, jitter control, and high-frequency sampling. Devices were tested in the lab using shaker excitation. Results demonstrate that MEMS-based accelerometers are a feasible solution to replace expensive piezo-based accelerometers. Deploying MEMS is promising to minimize sensor node energy consumption. Time and frequency domain analysis show that MEMS can correctly detect modal frequencies, useful parameters for damage detection. The acquired data from the test bed were used to examine the functioning of the network, data transmission, and data quality. The proposed architecture has been successfully deployed in a real case study to monitor the structural health of the Marcus Aurelius Exedra Hall within the Capitoline Museum of Rome. The performance robustness was demonstrated and the results showed that the wired sensor network provides dense and accurate vibration data for structural continuous monitoring.

Prompt removal of misfolded membrane proteins and misassembled membrane protein complexes is essential for membrane homeostasis. However, the elimination of these toxic proteins from the hydrophobic membrane environment has high energetic barriers. Transmembrane FtsH is the only known ATP-dependent protease responsible for this task, unlike other well-studied soluble ATP-dependent proteases. The mechanisms by which FtsH recognizes, unfolds, translocates, and proteolyzes its substrates remain unclear. Here, we report the crystal structures of the Thermotoga maritima FtsH periplasmic domain (PD) in an associative trimeric state at a 1.5-1.95 Å resolution. We also describe the pH-dependent oligomerization states of the isolated PD using dynamic light scattering. These observations help us understand how FtsH recognizes membrane-anchored misfolded proteins.

There is a lot of pressures from organizations to continually redesign the business processes and the technology infrastructure to support the organization, but to also help organizations manage competing stakeholder needs, changing objectives and behaviour, and so on. A key part of this is making sure that all their activities in the different components of the business are interconnected and that they are moving in the same direction. Enterprise Architecture (EA) is an effective way of dealing with the challenge of designing business activities and supporting IT. This paper will summarize the organization of EA and look more closely at some major components of EA: governance architecture, business architecture, information architecture and technical architecture and consider the overlap and constructive interaction involved. Enterprise Architecture can be best understood through business process redesign. So, it is useful to briefly review the leading frameworks for business process redesign, including COBIT from ISACA, LEAN from the Toyota Group, TOGAF from the Object-Management Group, and the Capgemini Integrated Architecture Framework (IAF). All these frameworks allow us to more successful transformation, to return to the central idea of this paper.

The neuronal etiology of obesity is centered around diet-induced inflammatory state in the arcuate nucleus of the hypothalamus which impairs the functionality of pro-opiomelanocortine neurons (POMCs) responsible for whole-body energy homeostasis and feeding behavior. Intriguingly, systemic salt inducible kinase 2 (SIK2) knockout mouse demonstrated reduced food intake and energy expenditure along with modestly dysregulated metabolic parameters suggesting a causal link between the absence of SIK2 activity in POMCs and the observed phenotype. To test this hypothesis, we conducted a comparative secretomics study from POMC neurons following pharmacologically induced endoplasmic reticulum (ER) stress induction, a hallmark of metabolic inflammation and POMC dysregulation in diet induced obese (DIO) mice. Our data provide significant in vitro evidence for the POMC specific SIK2 activity in controlling the energy metabolism and feeding in DIO mice by regulating the nature of related POMC secretome. Our data also suggests that under physiological stress conditions SIK2 may act as a gatekeeper for the secreted inflammatory factors and signaling molecules critical for cellular survival and energy homeostasis. On the other hand, in the absence of SIK2 gate opens leading to surge of inflammatory cytokines and apoptotic cues concomitant with the dysregulation of POMC neurons.

This paper investigates, experimentally and numerically, the buckling behavior of innovative sustainable Low-Cost Bamboo Composite (LCBC) structural columns under compressive loading. The LCBC columns are manufactured from bamboo culms in combination with bio-based resins to form composite structural columns. Different LCBC cross-sectional configurations are investigated in this study including the Russian doll (RD), Big Russian doll (BRD), Hawser (HAW), and Scrimber (SCR). Extra-large, large, medium, and small sizes of bamboo are employed to form the proposed configurations. Two bio-based resins including one bio-epoxy and one furan-based resin, in addition to a soft bio-based filler and a synthetic epoxy resin are applied. The bamboo species used as the cast-in-place giant bamboo for all configurations include Moso, Guadua, and Tali. In addition to experimental testing of the slender LCBC short columns, finite element analysis (FEA) software ABAQUS is applied to model the composite columns and predict their behavior. A buckling analysis using static Riks method is carried out to determine the LBCB’s response to axial compressive loading. A model is calibrated using test results with various imperfections, accounting for the variable behavior of each bamboo specimen, to accurately predict the behavior of LCBC columns with different resin contents. Slender LCBC columns showed maximum stress at buckling up to 60 MPa, highlighting the potential of bio-based resins for structural applications. The study found that the samples with bio-epoxy resin (BE2) exhibited enhanced material stiffness when compared to with synthetic epoxy (EPX) and furan-based resin (PF1), while PF1 specimens demonstrated increased ductility. The BE2 samples showed strain hardening in their stress-strain behavior, and the PF1 samples exhibited a long plateau phase before reaching the maximum load. Among the specimens with Moso bamboo and BE2 resin, those with SCR and HAW configurations achieved the highest compressive strengths.

The aim of this study was to examine the oxidation of human serum albumin (HSA) caused by oxidative stress after an exhaustive exercise such as ultra-marathon race. Thus, blood samples from 12 adult runners who underwent a 103 km mountain ultra-marathon race were collected pre- and 24, 48 and 72 h post race. HSA was partially purified using affinity chromatography and then was subjected to Western blot analysis for disulfide dimers determination, indicating oxidation. The results were correlated with those from a previous study in which the same samples were analyzed using different oxidative stress markers and a good correlation with protein carbonyls (PC) at all time points was observed. Moreover there was a significant correlation with static oxidation-reduction potential (sORP) at 24 h, and a negative correlation with capacity oxidation-reduction potential (cORP) at 24 and 48 h. In addition, an individual analysis of albumin dimers exhibited great inter-individual differences. This inter-individual variability in the oxidation of HSA may suggest different interventions (e.g. through diet) in order to confront the effects on athletes’ organism after a strenuous exercise. In conclusion, this study supported the importance of the assessment of albumin dimers as a predictive marker for exercise-induced oxidative stress.

A comprehensive study of the interactions of human serum albumin (HSA) and α-1-acid glycoprotein (AAG) with two isoquinoline alkaloids: allocryptopine (ACP) and protopine (PP) was performed. The UV-Vis spectroscopy, molecular docking, competitive binding assays, and circular dichroism (CD) spectroscopy were used for the investigations. The results showed that ACP and PP form spontaneous and stable complexes with HSA and AAG, with ACP displaying a stronger affinity towards both proteins. Molecular docking studies showed also revealed the preferential binding of ACP and PP to specific sites within HSA, with site 2 (IIIA) being identified as the favored location for both alkaloids. This was supported by competitive binding assays using markers specific to HSA's drug binding sites. Similarly, for AAG, a decrease in fluorescence intensity upon addition of the alkaloids to AAG/ Quinaldine Red (QR) complexes indicated the replacement of the marker by the alkaloids, with ACP showing a greater extent of replacement than PP. CD spectroscopy showed that the proteins’ structures remained largely unchanged suggesting that the formation of complexes did not significantly perturb the overall spatial configuration of these macromolecules. These findings are crucial for advancing the knowledge on the natural products-protein interactions and the future design of isoquinoline alkaloid-based therapeutics.

The interaction of poly(trimethylene carbonate) (PTMC) with alcohols were investigated as a model for polymer blending with polysaccharides. While 1-butanol, 2-butanol, ethylene glycol, 1,2-cyclohexanediol showed almost no detectable interaction with PTMC at both of solution state with 1H NMR and solid states of FT-IR, glucose and cellobiose suggests slight change of spectral pattern in FT-IR analysis. The thermal properties of the blending samples of PTMC and these alcohols were also investigated. Although the blend of PTMC with 1-butanol, 2-butanol, and ethylene glycol did not influence on thermal degradation behaviors due to the low boiling points to maintain the structure at blend sample preparation, however, the blend with PTMC and glucose or cellobiose tend to increase thermal resistances and increase glass transition temperature, hence, showed an existence of interaction through hydrogen bonding.

COVID-19 is characterized by an unprecedented abrupt increase in the viral transmission rate (SARS-CoV-2) relative to its pandemic evolutionary ancestor, SARS-CoV (2003). The complex molecular cascade of events related to the viral pathogenicity is triggered by the Spike protein upon interacting with the ACE2 receptor on human lung cells through its receptor binding domain (RBD_Spike). One potential therapeutic strategy to combat COVID-19 could thus be limiting the infection by blocking this key interaction. In this current study, we adopt a protein design approach to predict and propose non-virulent structural mimics of the RBD_Spike which can potentially serve as its competitive inhibitors in binding to ACE2. The RBD_Spike is an independently foldable protein domain, resilient to conformational changes upon mutations and therefore an attractive target for strategic re-design. Interestingly, in spite of displaying an optimal shape fit between their interacting surfaces (attributed to a consequently high mutual affinity), the RBD_Spike–ACE2 interaction appears to have a quasi-stable character due to a poor electrostatic match at their interface. Structural analyses of homologous protein complexes reveal that the ACE2 binding site of RBD_Spike has an unusually high degree of solvent-exposed hydrophobic residues, attributed to key evolutionary changes, making it inherently ‘reaction-prone’. The designed mimics aimed to block the viral entry by occupying the available binding sites on ACE2, are tested to have signatures of stable high-affinity binding with ACE2 (cross-validated by appropriate free energy estimates), overriding the native quasi-stable feature. The results show the apt of directly adapting natural examples in rational protein design, wherein, homology-based threading coupled with strategic ‘hydrophobic ↔ polar’ mutations serve as a potential breakthrough.

This paper investigates the effect of innovative cross-sectional configurations on Low-Cost Bamboo Composite (LCBC) structural members. The study employs both experimental and numerical methods with different resin matrices and bamboo species. In this study, LCBC short columns are designed with different innovative cross-sectional configurations in an attempt to overcome the costly production processes of engineered bamboo. This approach uses bundles of bamboo, both in culm and strip forms. A compatible, environmentally responsible, and economically justifiable resin matrix is used to fabricate an LCBC member. The production of LCBC members does not necessitate highly advanced technology. This capability enables the production of LCBC members in custom-designed cross-sectional shapes and lengths. This study introduces the Russian doll (RD), Big Russian doll (BRD), Hawser (HAW), and Scrimber (SCR) cross-sectional configurations. Extra-large, large, medium, and small sizes of bamboo are employed. Synthetic Epoxy (EXP), a Bio-based Experimental soft filler (BE1), Bio-Epoxy (BE2), Furan-based (PF1) matrices are applied. Furthermore, Moso, Guadua, Madake, and Tali bamboo species are incorporated. The results of this study reveal that the most efficient cross-sectional configuration for compressive strength is the HAW configuration, closely followed by SCR configuration. LCBC members with bio-resins have shown excellent promise in competing in strength with those made with their synthetic counterparts. The theoretical and numerical modeling of the LCBC members showed excellent correlation with the experimental results which provides the capacity to design LCBC for engineering projects. The LCBC design can be further developed with more bamboo and less resin content.

The application of distributed fiber optic strain and temperature measurement can be utilized to address a multitude of measurement tasks across a diverse range of fields, particularly in the context of structural health monitoring in the domains of building construction, civil engineering, and special foundation engineering. However, a comprehensive understanding of the influences on the measurement method and the sensors is essential to prevent misinterpretations or measurement deviations. In this context, this study investigated the effects of moisture exposure, including various salt solutions and a high pH value, on a distributed strain measurement using Rayleigh backscattering. Three fiber optic sensors with different coating materials and one uncoated fiber were exposed to five different solutions for 24 hours. The study revealed significant discrepancies in deformation between the three coating types depending on the surrounding solution. Furthermore, in contrast to the prevailing literature, which predominantly describes swelling effects, a negative deformation was observed in a magnesium chloride solution. The findings of this study indicate that corresponding effects can impact the precision of measurement, potentially leading to misinterpretations. Conversely, these effects could be used to conduct large-scale monitoring of chemical components using distributed fiber optic sensing.

Snow cover plays a critical role in the global energy and water cycles. Snow cover on the Tibetan Plateau (TP) provides vital water sources in western China and Himalayan regions in addition to its weather and climate significance. The massive high mountain topography of the TP is main conditions for the presence and persistence of snow cover on the plateau at the mid-low latitudes of the Northern Hemisphere (NH). However, how mountain topography controls snow cover distribution on the TP is largely remain unclear and the relationship is not well quantified. Here, the spatial distribution of snow cover and topographic controls on snow cover on the TP are examined based on snow cover frequency (SCF) derived from MODIS snow cover product (MOD10A2 v5) and digital elevation model (DEM). The results show that snow cover on the TP is spatially unevenly distributed and is characterized by rich snow and high SCF on the interior and surrounding high mountain ranges, and less snow and low SCF in inland basins and river valleys. Snow cover on the TP presents elevation dependence with the higher the altitude, the higher the SCF, the longer the snow cover duration and the more stable the intra-annual variation. Annual mean SCF below 3000 m above sea level (masl) is less than 4% and it reaches 77% above 6000 masl. The intra-annual snow cover variation below 4000 masl features a unimodal distribution, while above 4000 masl it presents a bimodal distribution. The mean minimum SCF below 6000 masl occurs in summer, while above 6000 masl it occurs in winter. Because of differences in solar radiation and water vapor sources, mean SCF generally increases with mountain slopes and it is the highest on the north-facing aspect, whereas the lowest is observed on the south-facing aspect.

Helicobacter pylori cytotoxin-associated gene A protein (CagA) has been associated with the increase in virulence and risk of cancer. It has been demonstrated that CagA's translocation is dependent on its interaction with phosphatidylserine. We evaluated the variability of the N-terminal CagA in 127 sequences reported in NCBI, by referring to molecular interaction forces with the Phosphatidylserine and the docking of 3 mutations chosen from variations in specific positions. The major sites of conservation of the residues involved in CagA-Phosphatidylserine interaction were 617, 621 and 626 which had no amino acid variation. Position 636 had the lowest conservation score, so mutations in this position were evaluated to observe the differences in intermolecular forces of the CagA-Phosphatidylserine complex. We evaluated the docking of 3 mutations: K636A, K636R and K636N. The models of the crystal and mutations presented a ΔG of −8.919907, −8.665261, −8.701923, −8.515097 Kcal/mol, respectively, while mutations K636A, K636R, K636N and the crystal structure presented 0, 3, 4 and 1 H-bonds, respectively. Likewise, the bulk effect of the ΔG and amount of H-bonds was estimated in all of the docking models. The type of mutation affected both the ΔG (χ²(1) = 93.82, p-value < 2.2 × 10⁻¹⁶) and the H-bonds (χ²(1) = 91.93, p-value < 2.2 × 10⁻¹⁶). In all the data, 76.9% of the strains that exhibit the K636N mutation produced a severe pathology. The average H-bond count diminished when comparing the mutations with the crystal structure of all the docking models, which means that other molecular forces are involved in the CagA-Phosphatidylserine complex interaction.

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.

In this article, we discuss problems that exist in modern SCADA systems and present a Controls-kt (formerly DataForge-controls) software development kit, that allows both to create a control system from scratch and provide integration with existing systems via Magix specification and connector.

In this paper, we extend the KdVSKR equations in (1+1)-dimension and (2+1)-dimension to fractional KdVSKR equations with modified Riemann-Liouville derivative. The (2+1)-dimensional KdVSKR equation, which is a recent extension of (1+1)-dimensional KdVSKR equation, can model the resonances of solitons in shallow water. By means of the Hirota bilinear method, finite symmetry group method and consistent Riccati expansion method, many new interaction solutions have been derived. Soliton-cnoidal interaction solution of the (1+1)-dimensional fractional KdVSKR equation has been derived for the first time. For the (2+1)-dimensional frac-tional KdVSKR equation, two-wave interaction solutions and three-wave interaction solutions, including dark-soliton-sine interaction solution, bright-soliton-elliptic interaction solution, and lump-hyperbolic-sine interaction solution, have been derived. Impact of the fractional order on the shapes of these solutions has been illustrated by figures. Three-wave interaction solutions of fractional systems have not been reported in the existing references. The research idea in this paper can be applied to other fractional differential equations.

The pressure exerted on the heart and blood vessels because of blood flow is considered as an important parameter for the cardiovascular function. It determines sufficient blood perfusion as well as transportation of nutrition, oxygen and other essential factors to every organ. Pressure in the primary arteries located near the heart and the brain, known as central blood pressure (CBP), while in peripheral arteries, known as peripheral blood pressure (PBP). Normally, CBP and PBP are correlated; however, cardiovascular disorders interfere their regulation and affect the blood flow in vital organs and accessory organs, differently. Therefore, understanding each of them in normal and disease conditions is essential for managing various cardiovascular disorders and increasing their treatment outcomes. In this review, we have described the control systems (neural, hormonal, osmotic and cellular) of the blood pressure and its regulation in hypovolemic shock using centhaquine (Lyfaquin®) as a resuscitative agent.

Proteomics research has become one of the most important topics in the fields of life science and natural science. At present, research on protein–protein interaction networks (PPINs) mainly focuses on detecting protein complexes or function modules. However, existing approaches are either ineffective or incomplete. In this paper, we investigate function module detection mechanisms in PPIN, including open databases, existing detection algorithms and recent solutions. After that, we describe the proposed solution based on simplified swarm optimization (SSO) algorithm and gene ontology knowledge. The proposed solution implements SSO algorithm for clustering proteins with similar function, and imports biological gene ontology knowledge for further identifying function complexes and improving detection accuracy. Furthermore, we use four different categories of species dataset for experiment: Fruitfly, Mouse, Scere, and Human. The testing and analysis result show that the proposed solution is feasible, efficient and could achieve a higher accuracy of prediction than existing approaches.

This paper introduces innovative sensitivity indices based on Cliff's Delta for global sensitivity analysis of structural reliability. These indices build on Sobol's method, using binary outcomes (success or failure), but avoid the need to calculate failure probability Pf and the associated distributional assumptions of resistance R and load F. Cliff's Delta, originally for ordinal data, evaluates the dominance of resistance over load without specific assumptions. The mathematical formulations for computing Cliff's Delta between R and F quantify structural reliability by assessing the random realizations of R > F using a double-nested-loop approach. The derived sensitivity indices, based on the squared value of Cliff's Delta​, exhibit properties analogous to those in Sobol's sensitivity analysis, including first-order, second-order, and higher-order indices. This provides a comprehensive framework for evaluating the contributions of input variables and their interactions on structural reliability. This method is particularly significant for FEM applications, where repeated simulations of R or F are computationally intensive. The double-nested-loop algorithm of Cliff's Delta maximizes the extraction of information about structural reliability from these simulations. However, the high computational demand of Cliff's Delta is a disadvantage. Future research should optimize computational demands, especially for small Pf​, where the inner loop may often be unnecessary.

Serotonin (5-hydroxytryptamine: 5-HT), a neurotransmitter that regulates mood in the brain and signaling in the gut, has receptors throughout the body that serve various functions. Selective serotonin reuptake inhibitors (SSRIs) are used to treat depression, but their efficacy is uncertain. Depression is often associated with early gastrointestinal symptoms. Gut disorders such as functional dyspepsia (FD), irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are linked to elevated serotonin levels. In this review, we would like to discuss the approach of using serotonin as a biomarker for gut-brain and body-wide organ communication may lead to the development of preventive and innovative treatments for gut-brain disorders, offering improved visibility and therapeutic monitoring. It could also be used to gauge stress intensity for self-care and mental health improvement.

The vast array of omics data in microbiology presents significant opportunities for studying bacterial pathogenesis and creating computational tools for predicting pathogenic potential. However, the field lacks a comprehensive, curated resource that catalogs bacterial strains and their ability to cause human infections. Current methods for identifying pathogenicity determinants often introduce biases and miss critical aspects of bacterial pathogenesis.In response to this gap, we introduce BacSPaD (Bacterial Strains’ Pathogenicity Database), a thoroughly curated database focusing on pathogenicity annotations for a wide range of high-quality, complete bacterial genomes. Our rule-based annotation workflow combines metadata from trusted sources with automated keyword matching, extensive manual curation, and detailed literature review. Our analysis classified 5,502 genomes as pathogenic to humans (HP) and 490 as non-pathogenic to humans (NHP), encompassing 532 species, 193 genera, and 96 families. Statistical analysis demonstrated a significant but moderate correlation between virulence factors and HP classification, highlighting the complexity of bacterial pathogenicity and the need for ongoing research. This resource is poised to enhance our understanding of bacterial pathogenicity mechanisms and aid in the development of predictive models. To improve accessibility and provide key visualization statistics, we developed a user-friendly web interface, accessible at https://bacspad.altrabio.com.

Research into lightweight structural concrete using volcanic tuff is of great importance to the construction industry. These materials have excellent thermal insulation properties, which helps improve the energy efficiency of buildings. A three-factor experimental design was used to build the statistical model. The test methods used were methods for determining the crushability of volcanic tuff, determining the average density, compressive strength and thermal conductivity of lightweight structural concrete. The influence of basalt fiber on the properties of lightweight structural concrete has been determined. The optimal compositions of lightweight structural concrete using tuff have been selected. The compressive strength of lightweight structural concrete reached 32.0 MPa. The average density range is 1754.6-2114.0 kg/m³. Good thermal conductivity values ​​were obtained in the range of 0.653-0.818 W/m·K. The article obtained the optimal compositions of lightweight structural concrete using volcanic tuff as a filler.

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.

The term `motor control´ encompasses a wide range of mechanisms thought to be implicated in the organization of movements. Their study, like that of any other scientific field, must use specific notions to get to grips with them. This review is therefore organized along a series of notions that are frequently used in motor control, and we will discuss them with particular emphasis on neurological conditions, which may disrupt normal motor functioning. We will start with a short description of the roles of space and time, in which movements take place. Subsequently we will deal with kinematics and kinetics (dynamics) of movements. Then, we will list the inputs to motoneurons (MNs), which, in different forms, convey signals from the central nervous system (CNS) to skeletal muscles and muscle spindles, including central pattern generators (CPGs), sensory inputs and supraspinal descending fiber systems. Some helpers in movement organization will be introduced, such as internal models and neuronal network models. A relatively brief section on sensory-motor learning will follow because learning abilities are required to endow the sensory-motor system with flexibility and adaptability. The major emphasis is placed on neurological processes, which result from genetic modifications, autoimmune diseases, neurodegenerative diseases, infections in the nervous system as well as vascular and traumatic lesions. These neurological diseases lead to a variety of impairments and symptoms, particularly movement derangements including cerebellar ataxia, spasticity, and (other) movement disorders such as Parkinson’s syndromes. The conclusion is that there is no unique top controller that controls ´motor control`.

The cytoskeleton is a master organizer of cell cortex, organelles positioning and membrane trafficking. Therefore, playing a decisive role in establishment of apico-basal polarity. Septins are critical cytoskeleton components which function in apico-basal polarity remain weakly investigated. Here, using 3D culture system, we demonstrate that septin9 localizes at basolateral membrane (BM). Its depletion induces an inverted polarity phenotype, decreasing -catenin at BM and increasing the expression of the transforming growth factor (TGF) and the epithelial-to-mesenchymal transition (EMT) markers. Similar effects were observed upon deleting its two polybasic domains, and the mutant become cytoplasmic and apical. The cysts with an inverted polarity phenotype display an invasive phenotype, with src and cortactin accumulating at the peripheric membrane. Inhibition of TGF-receptor and RhoA rescues the polarized phenotype. Although the cysts from overexpressed-septin 9, overgrowth and present a filled lumen. Both phenotypes correspond to tumor features. This suggests that septin 9 expression and assembly through the two PB domains are essential for establishing and maintaining apico-basal polarity against tumor development through a mechanism involving TGF-dependent EMT and RhoA activity.

Longitudinal cutting is a most common process in steel structure manufacturing, and the man-hours of the process provide an important basis for enterprises to generate production schedules.However, currently the man-hours in factories are mainly estimated by experts, and the accuracy of this method is relatively low.In this study,we propose a system that predicts man-hours with history data in the manufacturing process and that can be applied in practical structural steel fabrication.The system addresses the data inconsistency problem by one-hot encoding and data normalization techniques,Pearson correlation coefficient for feature selection,and the Random Forest Regression(RFR) for prediction.Compared with the other three Machine Learning(ML) algorithms, the Random Forest algorithm has the best performance.The results demonstrate that the proposed system outperforms the conventional approach and has better forecast accuracy, so that it is suitable for man-hours prediction.

The synthesis of enantiomeric forms of D-amino acids can be achieved by a two-step "hydantoinase process" based on the sequential catalysis of substrates by specific enzymes, D-carbamoylase and D-hydantoinase. In addition to our previously studied D-hydantoinase, we describe here the structural features of D-carbamoylase from Pseudomonas, the encoded gene of which was chemically synthesized and cloned into Escherichia coli. A significant fraction of the overexpressed recombinant protein forms insoluble inclusion bodies, which are partially converted to a soluble state upon treatment with N-lauroylsarcosine or upon incubation of the cells at low temperatures. Analysis of the substrate specificity of the purified His-tag protein showed that D-carbamoylase exhibits the highest activity toward N-carbamoyl-D-alanine and N-carbamoyl-D-tryptophan. Molecular docking analysis revealed the location of the substrate binding site in the three-dimensional structure of D-carbamoylase. Molecular dynamics simulations showed that the binding pocket of the enzyme in complex with N-carbamoyl-D-tryptophan is stabilized within 100 ns. The free energy of binding indicated a possible role of residues Arg176 and Asn173 in the formation of hydrogen bonds between the enzyme and N-carbamoyl-D-tryptophan. The properties of the studied D-carbamoylase and D-hydantoinase support further development of a combined biotechnological process for the production of new drugs and peptide hormones.

Background: many studies, on for example taste-visual dissonance, have shown that the influence of the visual cortex on taste sensation is enormous. The aim of the presented work is to investigate, using fNIRS, whether a taste stimulus, in this case the taste of bitter, also causes stimulation of the visual cortex in fNIR study. Methods: 51 participants (204 examinations, 9 996 records) were examined with fNIRS, which collects signals from whole left hemisphere. Differences between the maximum and minimum changes in oxyHb concentrations (ΔoxyHb) for the areas of the brain cortex considered responsible for recording visual and gustatory signals were analyzed. Protocol I, II, III and IV – activation with distillate water, coffee with lower concentration, reference (no stimulation) and coffee with higher concentration respectively, were used. Results: We recorded high signals for teste activation on channels covered gustatory cortex, which confirms the correctness of the choice of research method. What seems important, and somewhat surprising, is the fact that we also received high signals for the channels 45-49, which cover the visual cortex. The statistical analysis does not show any statistical differences between the protocols I, II and IV (different taste activation – water, coffee A and coffee B) for specific channels. As a results of the analysis of the correlation between the subjective bitterness assessment solutions, and the signal ΔoxyHb height, it was observed that statically important correlation, although weak, occurs only for 14 and gustatory channels, only for coffee with a higher concentration. Additionally we recorded the only statistically significant difference between women and men for protocol I (water), where the ΔoxyHb signal was twice as high for women. Conclusions: In conclusion, we can clearly state that the senses of sight and taste work closely together. Moreover, this cooperation is not one-sided - not only the visual activation affects the perception of taste, but interestingly, the taste stimulus can generate a hemodynamic response - activity in the visual cortex.

The characteristics of response to stressful situations depend on a complex of factors such as personality traits, emotional regulation, health state, features of the nervous system, motor functions and proprioception. In cases of disruption of the brain's dopamine system due to disease or chemotherapy, hormone discharge due to stress, changes in emotions and proprioception may occur. The aim of our study was to find the relationship of stress resilence in verbal test and individual differences performed in proprioceptive test in onco-patients, sportsmen and group of control; as well as to observe the differences between these groups in the verbal stress resistance and individual differences proprioceptive tests. The results showed that onco-patients were less resistant as per verbal stress resistance outcomes for a major part of variables compared to other groups. The sportsmen were superior in verbal Risk and Control dimensions compared to other groups; but less in Positive Affectiveness. The proprioceptive test perfomance revealed the only statistically significant difference in performance in the dimension related to Mood, showing more Pessimism in the sportsmen group, but more Optimism in the oncopatients at temperamental (or intrisinc) level. The obtained results can be used by psychologists, therapists, coach and healthcare when needed to attend the specific needs of public, being pateints or sportsmen, etc.

Using the nematode C. elegans germline as a model system, we previously reported that PUF-8 (a PUF RNA-binding protein) and LIP-1 (a dual-specificity phosphatase) repress sperm fate at 20°C and the dedifferentiation of spermatocytes into mitotic cells (termed "spermatocyte dedifferentiation") at 25°C. Thus, double mutants lacking both PUF-8 and LIP-1 produce excess sperm at 20°C, and their spermatocytes return to mitotically dividing cells via dedifferentiation at 25°C, resulting in germline tumors. To gain insight into the molecular competence for spermatocyte dedifferentiation, we compared the germline phenotypes of three mutant strains – fem-3(q20gf), puf-8(q725; fem-3(q20gf), and puf-8(q725); lip-1(zh15). Both fem-3(q20gf) and puf-8(q725); fem-3(q20gf) mutants produced excess sperm like puf-8(q725); lip-1(zh15) double mutants. Our results show that spermatocyte dedifferentiation was not observed in fem-3(q20gf) mutants, but it was more aggressive in puf-8(q725); lip-1(zh15) than in puf-8(q725); fem-3(q20gf) mutants. These results suggest that MPK-1 (the C. elegans ERK1/2 MAPK ortholog) activation by removing the function of LIP-1 in the absence of PUF-8 promotes spermatocyte dedifferentiation. This idea was confirmed using Resveratrol (RSV), a potential activator of MPK-1 and ERK1/2 in C. elegans and human cells. Notably, spermatocyte dedifferentiation was significantly enhanced by RSV treatment, and its effect was blocked by mpk-1 RNAi. We, therefore, conclude that PUF-8 and MPK-1 are normally required to inhibit spermatocyte dedifferentiation and tumorigenesis. Since these regulators are broadly conserved, we suggest that similar regulatory circuitry may control cellular dedifferentiation and tumorigenesis in other organisms, including humans.

Autism has been described as a gastrointestinal and neurological condition that is represented by impairments in language and social situations. Recently reported increases in the occurrence of Autism Spectrum Disorder (ASD) have resulted in increased research into the environmental differences between areas with a high occurrence, as in the “Western” diet populations, and a more locally derived diet population, wherein the rate appears to be significantly less. Thirty autistic children (USA) ages 6 to 21, were sampled at three different intervals: prior to any intervention, post-xylitol intervention, and post-probiotic intervention. The sampling consisted of buccal swabs for MITOSWAB testing, and saliva for metatranscriptomics to determine the entire range of microorganisms and the metabolome. In addition, a “Blue Zone” subject component that included 30 Colombian children, ages 6-16, and who were healthy and within normal behavior standards, also had buccal swabbing and salivary sampling performed for comparison along with 30 healthy (no history medications, illnesses, or behavior issues) USA children matched for age and gender. Saliva samples were analyzed metatranscriptomically and artificial intelligence was utilized to discern important differences in the microbiome that included bacteria, archaea, fungi, and viruses, and microbial functions. Significant differences were noted, and seen in the temporal data, demonstrating shifts that may have been precipitated by the interventions, with both the probiotics and the polyols. Particular bacterial strains were significantly more prevalent in the autism subject group including a strain that reduces neurotransmitters by enzymatic degradation. This provided supporting evidence to the hypothesis that the occurrence of autism may also be influenced by low Gamma Amino Butyric Acid (GABA) levels during development. Also, of interest was the un-expected finding that verbal skills dramatically increased in 6 of the 30 ASD subjects following xylitol supplementation.

Salinity acts as a critical environmental filter on microbial communities in natural systems, negatively affecting microbial diversity. However, how salinity affects the community assembly remains unclear. This study used Wendeng multi-pond saltern as a model to evaluate the prokaryotic community composition and diversity and quantify the relative importance of ecological processes across salinity gradients. Results showed that low saline salterns (45-80 g/L) exhibited higher bacterial diversity than those in high saline salterns (175-265 g/L). The relative abundance of taxa assigned to Halanaerobiaceae, Haloferacaceae, Desulfohalobiaceae, Phormidiaceae, Rohodobacteraceae, and Nitrococcaceae was higher with increasing salinity. Salinity and pH were the primary environmental factors that directly or indirectly determined the composition and diversity of prokaryotic communities. Microbial co-occurrence network dynamics were more complex in the sediment than in water of salterns. An infer Community Assembly Mechanisms by Phylogenetic-bin-based null model analysis (iCAMP) showed that microbial community assembly in sediment and water differed. Our findings provide more information about microbial community structure and the importance of various ecological processes in controlling microbial community diversity and succession along salinity gradients in water and sediment environments.

Across the global construction industry, fatalities continue to occur from high-risk activities where the risk controls have been defined, however were unreliable. In the mining industry, Critical Control Risk Management has provided positive results in reducing major accidents, which raises the question, could the Critical Control approach reduce the fatality rate in the construction industry? This study analysed 10 years of serious and fatal incident investigation reports from four international construction companies to i) assess the reliability of their Critical Controls (CCs) and ii) assess the factors which affect the reliability of CCs. The results show the reliability of CCs, measured by implementation and effectiveness, averaged just 42%. Human performance factors including risk identification, decision-making and competency together with supervision, job planning, communication organisational factors were identified as affecting the reliability of CCs. The study used bow-tie diagrams with real event data to find the actual CC effectiveness. This gave actionable findings directly related to individual CCs enabling the participating organization to focus resources on improving specific verification processes. The results confirm the applicability of CCs for the Major Accident Event hazards analyzed and highlights further review is required of the factors which need to be considered when implementing a CC program. This paper details our methodology and results, to assist others apply CCs as a risk management tool.

The discrete element method (DEM) coupled with computational dynamics (CFD) has been considered one of the most sensitive ways of studying fluidized beds. This paper presents gas-solid fluidized bed simulations by use of CFD-DEM. The two-phase interaction is calculated in a way of decoupling. Within the effective neighborhood of the particles, the kernel approximation method is used to calculate the local porosity, thereby calculating the drag force on the particles. At the grid scale, the momentum exchange coefficient is calculated using a two fluid model based method, thereby calculating the source term of the phase interaction in the fluid control equation. The simulated form, size and motion process of the big bubble are all consistent with experimental observations. The simulated solid volume fraction and relative pressure averaged in a horizontal plane at 45 mm above the bottom are in reasonable agreement with the experimental data. The fluctuation of the simulated bed height over time is similar to the experimental measurement results. The reproduction of these qualitative and quantitative results indicates that the proposed method effectively improves simulation performance and accuracy.

Background: Studies have tried to identify predictors of functional markers of keratoconus progression, whereas structural outcomes of collagen cross-linking have not been properly investigated. Objective: find and set up a combination of diagnostic modalities and measurements to reliably reflect CXL efficiency. Material and methods: We retrospectively reviewed the medical histories of 107 KC patients (131 eyes) who underwent CXL in a medical center from January 2018 to December 2022. The dataset included preoperative examinations and follow-up results, which provided a total of 796 observations. The cases of other corneal diseases, repeated CXL, pregnancy, and observations without follow-up examinations were excluded. Results: The study findings revealed a significant drop in the central and corneal thickness during 14.01±9.98 months of observations. Linear and polynomial equations suggested different trends in pachymetry change after CXL. The linear model showed corneal thinning, and according to the polynomials, pachymetry findings return to baseline values two years after CXL. Conclusion: The most reliable prognosis of postoperative corneal thickness is achieved with the models trained on keratometry readings and topography indices. BAD indices are also reliable predictors of the corneal thickness after CXL. A combination of the aforementioned structural parameters and their derivatives can reliably predict CXL efficiency.

Leishmaniasis are neglected diseases that affect regions such as South Asia, South Africa and Latin America, less developed regions. Current treatment, for cutaneous, mucocutaneous and visceral leishmaniosis, which are the main forms of the disease, is based on the administration of pentavalent antimonial and amphotericin B. However, these drugs have low efficacy and high toxicity. For this reason, the search for new treatments for this disease is necessary, based on studies of new molecules and their conformations. The research proposed the conformational study of brominated guanidine compounds with potential antileishmanial activity using Nuclear Magnetic Resonance (NMR) and X-ray diffraction (XRD) techniques. The present study involves the bro-minated molecules, LQOF-G2, LQOF-G30, LQOF-G35 and LQOF-G35-Br. The later was synthesized by the reaction of LQOF-G35 with NBS under IR irradiation at 120 Watts of potency and dichloro-methane as solvent by 12-h of exposition. The obtained results demonstrated the efficiency of the bromination method, since two bromines atoms entered the molecule. Furthermore, NMR analysis showed the occurrence of a conformational change from Z to E when compound LQOF-G35 was brominated to LQOF-G35-Br. This feature was well confirmed by comparative DRX study of the LQOF-G35 and LQOF-G35-Br compounds. The antileishmanial activity of LQOF-G2 e LQOF-G35 motivated the synthesis of new brominated compounds LQOF-G30 e LQOF-G35-Br.

This paper details the comprehensive activities conducted in a laboratory setting to assess the Structural Health Monitoring (SHM) of prefabricated building envelopes. Aimed at enhancing the structural evaluation of buildings, the focus of this research lies in employing nondestructive sensors for SHM with the objective to advance in the understanding and assessment of facade conditions. The paper outlines the methodologies employed, starting with a modal analysis to define the structural vibration's modal frequency. Subsequently, tests were defined and executed to validate building envelope compliance in case of stress typical of high-rise building. Throughout these tests, continuous monitoring of the façade was conducted using both conventional (accelerometers, extensimeter washers) and non-conventional sensors (Fiber Optic Sensing) The gathered data underwent thorough processing and analysis to provide an overall perspective on the structure's behavior during the stress test. The investigation aimed to identify whether specific physical phenomena correlate with distinct signals and to evaluate if continuous façade monitoring over the building's lifespan aids in preventing potential structural damage. Moreover, two modal analyses were conducted to compare final data and frequencies with earlier data, enabling the detection of any structural alterations. The results from compliance testing and structural analysis yielded noteworthy insights contributing to the evolving field of structural health monitoring, offering valuable findings that advance our ability to proactively manage and maintain the integrity of building structures.

The study of the tribological behavior of the braking system in auto vehicles requires knowing the characteristics of the material in contact and, in the work process, for the friction pair, brake disc-pads. Materials structural analysis is necessary because the wear process depends on the friction pair chemical composition, and brake disk-pads, respectively on the work process parameters (pressing force, rotational speed, traffic conditions, etc.). The material of the brake discs is generally the same gray cast iron, but the brake pads can be semi-metallic (particles of steel, copper, brass, and graphite, all united with a special resin), organic materials (particles of rubber, glass, and kevlar all joined with the help of a resin), composite materials that contain different constituents and ceramic materials (rarely have small copper particles). Therefore, the purpose of the paper is to know the crystalline structure and the mechanical properties of the brake pad materials, through specific studies and analyses, with important implications on the friction and wear behavior.

It is of great academic significance to understand how the atomic structure of interfaces and boundaries in materials impacts the magnetic coupling nature across the boundaries and encourage development of state-of-the-art magnetic devices. Here, we carry out a systematic investigation of the atomic and electronic structures of twin boundaries (TBs) in LiFe5O8 thin films and determine their concurrent magnetic couplings using atomic-resolution transmission electron microscopy and atomistic first-principles calculations. The results show ferromagnetic or antiferromagnetic coupling can exist across the different TBs in LiFe5O8 (LFO) thin films and electrical structures within a few atomic layers directly rely on the TB atomic core structures. Uncovering one-to-one relationship between the magnetic properties of individual TB and the local atomic structures will clarify a thorough comprehension of numerous fascinating magnetic properties of commonly utilized magnetic materials, which will undoubtedly encourage the progress of sophisticated magnetic materials and devices.

In the modern power grid, characterized by the increased penetration of power electronics and extensive utilization of renewable energy, inverters-based power plants play a pivotal role as the principal interface of renewable energy sources (RESs) and the grid. Considering the stability characteristics of grid-following (GFL) inverters when the grid is relatively weak, the application of grid-forming (GFM) controls becomes imperative to enhance the stability of the entire power plant. Thus, there is an urgent need for suitable and effective models to study the interaction and stability of the paralleled inverters employing GFL and GFM controls. Thus, the small-signal modeling with full-order state space model and eigenvalues analysis is presented in this paper. First, the small-signal state-space model of the individual GFL and GFM inverters is obtained considering the control loop, interaction, reference frame, transmissions, and time delays. Then, the models of the individual inverter are extended to the hybrid inverters to study the effects of the GFM inverters on the small- signal stability of the entire system. And, the impacts of the inertia and damping are analyzed by the eigenvalues of the state-transition matrix. Case comprising three parallel GFL inverters and two GFL inverters with one GFM inverter, respectively, are studied to examine the effectiveness and accuracy of the model. Finally, the stability margin obtained from the eigenvalue analysis of the entire system is verified by time-domain simulations.

The integration of Augmented Reality (AR) into Human-Robot Interaction (HRI) represents a significant advancement in collaborative technologies. This paper provides a comprehensive review of AR applications within HRI, emphasizing their role in enhancing collaboration, trust, and safety. By aggregating findings from numerous studies, this research highlights key challenges, including the need for improved situational awareness, enhanced safety, and more effective communication between humans and robots. A framework developed from the literature is presented, detailing the critical elements of AR necessary for advancing HRI. The framework outlines effective methods for continuously evaluating AR systems for HRI. This structured approach focuses on enhancing collaboration and safety, with a strong emphasis on integrating best practices from Human-Computer Interaction (HCI) centered around user experience and design.

The resilience of towns and cities refers to their ability to adapt and recover when confronted with pressures or challenges. This study employs ten variables as indicators to assess the resilience of urban areas by analyzing official data and constructing a multilevel mixed-effects structural equation model. The empirical findings demonstrate that enhancing resilience significantly influ-ences urban service functions, such as strengthening healthcare systems, stabilizing the real estate market, and addressing socio-economic challenges. Specifically, factors such as healthcare re-sources, housing demand, population structure, and social security exhibit varying levels of resil-ience, which profoundly impact the spatial distribution of these factors and socio-economic de-velopment. Disparities in healthcare resource allocation, demographic aging trends, and shifts in the housing market closely correlate with resilience levels in different regions. Additionally, the study emphasizes that improving resilience not only boosts the reliability and security of urban services but also ensures that communities receive necessary support and protection during times of adversity. Consequently, policymakers should recognize the pivotal role of urban resilience in resource allocation and social equity, devising corresponding strategies to enhance the resilience of these areas.

The conservation of the main protease in viral genomes, combined with the absence of a homologous protease in humans, makes this enzyme family an ideal target for developing broad-spectrum antiviral drugs with minimal host toxicity. GC-376, a peptidomimetic 3CL protease inhibitor, has shown significant efficacy against coronaviruses. Recently, a GC-376-based PROTAC was developed to target and induce the proteosome-mediated degradation of the dimeric SARS-CoV-2 3CLPro protein. Extending this approach, the current study investigates the application of the GC-376 PROTAC to the 3CPro protease of Enteroviruses, specifically characterizing its interaction with CVB3 3CPro through X-ray crystallography, NMR and biophysical techniques. The present structural data show that there are some changes between the binding of CVB3 3CPro and SARS-CoV-2 3CLPro, but the overall similarity is strong. The most notable variation is the orientation of the phenylmethyl ester of GC-376 with the S4 subsite of the proteases. This is linked to the flexibility of the protein structure around the region of the catalytic triad shown by our NMR data. Other structural variations include distinct ligand interactions in subsites S1 and S2, influenced by the presence of Glu71 in CVB3 3CPro. Despite these differences, the GC-376 PROTAC fits well within the binding sites of both proteases, demonstrating its potential as a broad-spectrum antiviral agent.

With challenged early detection came the collapse of a school roof, initiating a storm of public mistrust and hundreds of schools under investigation in the United Kingdom. The culprit is a poorly understood material heavily used in the 1950s to mid-1990s, reinforced autoclaved aerated concrete (RAAC). As a lightweight material with excellent insulation, RAAC was mainly used in roof and floor panels in many parts of the world. However, RAAC has a comparatively weak compressive strength, poor reinforcement anchorage, and high permeability and susceptibility to creep. The uniqueness of RAAC properties is exacerbated by poor manufacturing, negligent construction and maintenance as well as structural deviations from original design intent. Current guidance lacks in specifying RAAC management strategies beyond recommendations for periodic surveying. This paper delivers a state-of-the-art review of the material properties and structural performance of RAAC to recommend improved measures characterised by non-destructive testing methods and digital asset management. The reviewed literature targets understanding the influence of variable environmental exposure conditions, reinforcement condition, operational loading variations, structural deficiencies, and ageing, to predict their effect on the mechanism of RAAC failure. The established risk factors of RAAC are examined to inform of feasible response strategies against specific issues encountered in affected RAAC structures such as inadequate bearings, compromised transverse reinforcement, and environmental conditions.

The interaction forces and mechanical properties of the interaction between melittin (Mel) and lipopolysaccharide (LPS) are considered a crucial driving force for Mel in killing Gram−negative bacteria (GNB). However, how their interaction forces are performed at the single−molecule level and the dissociation kinetic characteristics of the Mel/LPS complex remain poorly understood. In this study, the single−molecule level interaction forces between Mel and LPSs from E. coil K−12, O55:B5, O111:B4, and O128:B12 were explored using atomic force microscopy (AFM) based single−molecule force spectroscopy (SMFS). Further, the AFM−based dynamic force spectroscopy (DFS) and advanced analytical model were employed to investigate the kinetic characteristics of the Mel/LPSs complex dissociation. The results indicated that Mel could interact with both rough (R)−form LPS (E. coli K−12) and smooth (S)−form LPSs (E. coli O55:B5, O111:B4, O128:B12), and the S−form LPSs showed a more robust interaction with Mel than R−form LPS, and a slight difference existed in the interaction forces between Mel and diverse S−form LPSs. The Mel interacts with S−form LPSs showed greater specific and non−specific interaction forces than R−form LPS (p &lt; 0.05), as determined by AFM−based SMFS. However, there was no significant difference in the specific and non−specific interaction forces among the three S−form LPSs (p &gt; 0.05), indicating the variability of O−antigen could not affect the interaction between Mel and LPSs. The DFS result showed that the Mel/S−form LPSs complexes had a lower dissociation rate constant (koff), a shorter energy barrier width (xβ), a longer bond lifetime (τoff), and a higher height of the energy barrier (∆G), demonstrating that Mel could interact with S−form LPSs to form more stable complexes. In conclusion, this study promotes our knowledge of the interaction micromechanics and kinetics characteristics between Mel and LPS at the single−molecule level. Moreover, it can help us design and evaluate new anti−GNB drugs.

Stairs are among the key elements in architectural composition, both aesthetically and spatially. They are also one of the main innovations in architecture and building, allowing pedestrians to bridge considerable height differences with relative efficiency. It is therefore surprising that, in spite of all stair regulations in building codes, stairs are responsible for a huge number of accidents – second only to motorcars. The extent of safety failures suggests that user interaction with stairs is poorly understood by designers and policy makers. This is not unrelated to the lack of research into the design and use of stairs. Templer’s seminal work is the exception but it dates from 1992 and since then little has been done to understand the relation between architectural design and stair performance, including safety. To redress this, we can build on affordance-based analyses of stair climbability, which establish a clear connection between the form of a stair and the perception of action possibilities and dangers by all kinds of users. By doing so affordances establish a comprehensive and consistent framework for the analysis of architectural designs, which utilizes both domain and psychological knowledge, including as a foundation for computational applications.

To better understand anogenital warts (AGW) natural history and dynamic of HPV6/11 infection in regional hairs, 32 newly diagnosed AGW male patients and 32 age-matched healthy controls were closely followed. During enrollment and six follow-up visits (every 2.6 months) 43 AGW tissue and 1,232 anogenital and eyebrow hair samples were collected. This represents the closest longitudinal monitoring of AGW patients to date. Patients were treated according to standard-of-care. HPV6/11 prevalence was 19.9% in patients’ hair samples (HPV6 B1 in 87.5%) and 0% in controls. The highest HPV6/11 prevalence was found in pubic hairs (29.0%) and lowest in eyebrows (7.1%). Odds for HPV6/11-positive hairs increased with smoking, shaving anogenital region and age. A close association between HPV6/11 presence in hairs and clinically visible AGW was observed. The proportion of patients with visible AGW and HPV6/11-positive hairs declined during follow-up with similar trends. No particular HPV6/11 variant was linked with increased AGW recurrence, but sublineage HPV6 B1 showed significantly higher clearance from hairs. Despite treatment, 78.1% and 62.5% of AGW patients experienced one and two/more post-initial AGW episodes, respectively. Patients having HPV6/11-positive hairs or visible AGW at preceding visit demonstrated substantially higher odds for presenting with visible AGW in subsequent visit.

The photosystem I (PSI) of the green alga Chlamydomonas reinhardtii associates with 10 light-harvesting proteins (LHCI) to form the PSI-LHCI complex. Binding of LHCII to PSI may also occur and is controlled by a process called state transitions. Hereby, two LHCII trimers bind to the PSAL, PSAH and PSAO side of PSI to produce the PSI-LHCI-LHCII complex. In this work, we took advantage of chemical crosslinking of proteins in conjunction with mass spectrometry to identify protein-protein interactions between the light-harvesting proteins of PSI and PSII. We detected binding of LHCBM proteins to the LHCA1-PSAG side of PSI and identified protein-protein interactions of LHCSR3 with LHCA5 and LHCA3. Our data indicate that the binding of LHCII to PSI is more versatile as anticipated and reveal that LHCSR3 likely regulates excitation energy transfer to the PSI core via LHCA5/LHCA3.

Parkinson's disease (PD) stands as the most prevalent degenerative movement disorder, characterized by the loss of dopaminergic neurons in the substantia nigra of the midbrain. In this study, we assessed the transcriptome by analyzing post-mortem mRNA extracted from the substantia nigra of individuals with PD and healthy controls. A total of 16,148 transcripts were identified, with 92 mRNAs displaying differential expression between PD and control groups. Specifically, 33 mRNAs were significantly upregulated, while 59 mRNAs were downregulated in PD compared to controls. The identification of statistically significant signaling pathways, with an adjusted p-value threshold of 0.05, unveiled noteworthy insights. Particularly, enriched categories included cardiac muscle contraction (involving genes such as ATPase Na+/K+ transporting subunit beta 2 (ATP1B2), solute carrier family 8 member A1 (SLC8A1), and cytochrome c oxidase subunit II (COX2)), GABAergic synapse (involving GABA type A receptor-associated protein like 1 (GABARAPL1), G protein subunit beta 5 (GNB5), and solute carrier family 38 member 2 (SLC38A2)), autophagy (involving GABARAPL1 and tumor protein p53-inducible nuclear protein 2 (TP53INP2)), and Fc gamma R-mediated phagocytosis (involving amphiphysin (AMPH)). These findings uncover new pathophysiological dimensions underlying PD, including the involvement of cardiac muscle contraction and specific mitochondrial activity. This knowledge not only contributes to better diagnostic precision but also paves the way for the development of new targeted therapies.Keywords: mRNAs; RNA sequencing; Parkinson’s disease; transcriptome analysis; substantia nigra

In the present study, the polysaccharide-hydrolyzing secretomes of Irpex lacteus BCC104, Pycnoporus coccineus BCC310, and Schizophyllum commune BCC632 were analyzed in submerged fermentation conditions to elucidate the effect of chemically and structurally different carbon sources on the expression of cellulases and xylanase. Among polymeric substrates, crystalline cellulose appeared to be the best carbon source providing the highest endoglucanase, total cellulase, and xylanase activities. Mandarin pomace as a growth substrate for S. commune allowed to achieve comparatively high volumetric activities of all target enzymes while wheat straw induced a significant secretion of cellulase and xylanase activities of I. lacteus and P. coccineus. A synergistic effect on the secretion of cellulases and xylanases by the tested fungi was observed when crystalline cellulose was combined with mandarin pomace. In I. lacteus the cellulase and xylanase production is inducible in the presence of cellulose-rich substrates but is suppressed in the presence of an excess of easily metabolizable carbon source. These enzymes are expressed in a coordinated manner under all conditions studied. It was shown that the substitution of glucose in the inoculum medium with Avicel provides accelerated enzyme production by I. lacteus and higher cellulase and xylanase activities of the fungus. These results add new knowledge to the physiology of basidiomycetes to improve cellulase production.

A testable theoretical model is presented, proposing which brain parts and mechanisms are responsible for the nature and the nurture components of all human sexual orientations. The model integrates observations from humans and a wide range of animals. If validated, the model would provide a proximate explanation of the biological substrates of all sexual orientations. The basic assumptions of the model are: (1) Children learn automatically and subconsciously in non-sexual conditioning experiences cues for recognizing sexual mates. That skill emerges at puberty. (2) Adults in the child’s surroundings act as innocuous, unaware role-models that provide the learned cues for recognizing mates. (3) Voices of men and women serve as the innate, primary unconditioned stimuli (US) in that learning process. (4) The hypothalamus is the main area that elicits the signals of the unconditioned responses (UR). Those signals trigger the learning of the associated conditioned stimuli (CS) broadcasted by the role-models. (5) The amygdala, base nuclei of the Stria Terminalis (bnST) and hypothalamus play in humans similar roles to those they play in the other species. (6) The human medial geniculate nucleus (MGN) plays the roles played by the olfactory bulbs in rodents. (7) Detectors of innate primary US and activators of the unconditioned sexual responses (UR) are located in the MGN, Amygdala, bnST and Hypothalamus Axis (MASHA). The learned conditioned stimuli (CS) are recorded in the MASHA and in cortical areas. (8) The innate US-UR connections vary across three groups of children. In the first group, only men’s voices trigger the UR. In the second group, only women’s voices trigger the UR, and in a third group each voice can trigger the UR. That determines the learned cues. The first group will be attracted at puberty only to men, the second only to women, and the third group to both.

Efforts to optimize the design and enhance the efficiency of standing-wave thermoacoustic refrigerators (SWTAR), particularly those with parallel plate stacks, are crucial for achieving rapid and straightforward engineering estimates. This study primarily focuses on optimizing the Coefficient of Performance (COP) by combining the linear thermoacoustic theory (LTT) with the Design of Experiments (DOE) approach. The investigation centers around five key parameters affecting the COP, once the working gas is selected. Then, based on the LLT theory, the COP was estimated numerically, over defined intervals of those five parameters. Moreover, through quantitative and qualitative effect analyses, these five parameters and their interactions are determined. Utilizing a transfer function and surface response analyses based on the COP, the study aims to delineate the best COP value as well as the contribution of the thermoacoustic parameters and their interactions. Furthermore, a comparison between contour and surface responses and several statistical decision approaches applying the Full Factorial Design verify the robustness of the study’s findings. Ultimately, the COP results obtained align with existing literature, underscoring the validity and relevance of the study’s methodologies and conclusions.

Genome-wide association studies (GWAS) have successfully revealed many disease-associated genetic variants. For a case-control study, the adequate power of an association test can be achieved with a large sample size, although genotyping large samples is expensive. A cost‐effective strategy to boost power is to integrate external control samples with publicly available genotyped data. However, the naïve integration of external controls may inflate the type I error rates if ignoring the systematic differences (batch effect) between studies, such as the differences in sequencing platforms, genotype calling procedures, population stratification, and so forth. To account for the batch effect, we propose an approach by integrating External Controls into the Association Test by Regression Calibration (iECAT-RC) in case-control association studies. Extensive simulation studies show that iECAT-RC not only can control type I error rates but also can boost statistical power in all models. We also apply iECAT-RC to the UK Biobank data for M72 Fibroblastic disorders by considering genotype calling as the batch effect. Four SNPs associated with Fibroblastic disorders have been detected by iECAT-RC and the other two comparison methods. However, our method has a higher probability of identifying these significant SNPs in the scenario of an unbalanced case-control association study.

Glioblastoma (GB) is the most frequent malignant brain tumor among adults and currently there is no effective treatment. It is a very aggressive tumor that grows fast and spreads through the brain causing the death of patients in 15 months. GB cells mutate frequently and generate a heterogeneous population of tumoral cells genetically distinct. Thus, the contribution of genes and signaling pathways relevant for GB progression is of great relevance. We use a Drosophila model of GB that reproduces the features of human GB, and describe the upregulation of the circadian gene cry in GB patients and in a Drosophila GB model. We study the contribution of cry to the expansion of GB cells, to the neurodegeneration caused by GB, and to premature death and determine that cry is required for GB progression. Moreover, we analyze the mechanisms that regulate cry expression by the PI3K pathway. Finally, we conclude that cry is necessary and sufficient to regulate myc expression in GB. These results contribute to the understanding of the signals that impulse GB malignancy and lethality and open novel opportunities for the treatment of GB patients.

The effects of CO₂-water-rock interactions on the mechanical properties of shale are essential for estimating the possibility of sequestrating CO₂ in shale reservoirs. In this study, uniaxial compressive strength (UCS) tests together with an acoustic emission (AE) system and SEM & EDS analysis were performed to investigate the mechanical properties and microstructural changes of black shales with different saturation times (10 days, 20 days and 30 days) in water dissoluted with sub-/super-critical CO₂. According to the experimental results, the values of UCS, Young’s modulus and brittleness index decrease gradually with increasing saturation time in water with sub-/super-critical CO₂. Compared to intact samples, 30-days’ saturation causes reductions of 56.43% in UCS and 54.21% in Young’s modulus for sub-critical saturated samples, and 66.05% in UCS and 56.32% in Young’s modulus for super-critical saturated samples, respectively. The brittleness index also decreases drastically from 84.3% for intact samples to 50.9% for samples saturated in water with sub-critical CO₂, to 47.9% for samples saturated in water with super-critical carbon dioxide (SC-CO₂). SC-CO₂ causes a greater reduction of shale’s mechanical properties. The crack propagation results obtained from the AE system show that longer saturation time produces higher peak cumulative AE energy. SEM images show that many pores occur when shale samples are saturated in water with sub-/super-critical CO₂. The EDS results show that CO₂-water-rock interactions increase the percentages of C and Fe and decrease the percentages of Al and K on the surface of saturated samples when compared to intact samples.

Photonic sensors are innovative devices that leverage the principles of light-matter interaction to enable precise and efficient detection of various physical parameters. These sensors operate by exploiting the interaction between photons, the fundamental particles of light, and matter. The light propagates through an optical waveguide, and a portion of the electromagnetic field extends beyond the waveguide surface, forming the evanescent field. This evanescent field interacts with the surrounding medium, allowing for highly sensitive detection of changes in the refractive index or properties of nearby substances. The underlying concept involves the modulation of light properties, such as intensity, wavelength, or phase, when it interacts with a target substance or undergoes changes in the surrounding environment. The advancements in photonic sensor technology have paved the way for enhanced sensitivity, selectivity, and miniaturization, making them invaluable tools in diverse industries. The ability to harness light-matter interactions for sensing purposes not only facilitates highly sensitive measurements but also allows for non-intrusive and remote monitoring, contributing to the evolution of smart and connected systems. In this overview, the material platforms and waveguide structures are explored that can make highly sensitive photonic devices applied to gas and biosensing applications.

Expansion tube is ideal energy absorber which dissipates kinetic energy through plastic deformation and friction. There is an urgent need to understand the influence of key parameter, e.g. semi angle, tube material, and friction coefficient, on the mechanical response and energy absorption characteristics of expansion tube. In the present work, the material properties of the tubes were tested under quasi-static loading condition, and the numerical simulations were carried out by using commercial software ABAQUS. Based on the validated finite element simulation, all the semi angle, tube material, and friction have significant effects on the energy absorption capacity of expansion tube. The expansion tube with high tensile stress of parent material have high energy absorption capacity, while the specific energy absorption is linear with the tensile stress/density of tube material. This work would give a guidance to the structural design and parent materials selection for expansion tubes.

The optimal structural design is imperative to minimize material consumption and reduce the environmental impact of construction. Given the complexity in the formulation of structural design problems, the process of optimization is commonly performed using artificial intelligence (AI) global optimization, such as Genetic Algorithm (GA). However, the integration of AI-based optimization together with visual programming (VP) in building information modeling (BIM) projects warrants further investigation. This study proposes a workflow by combining structure analysis, VP, BIM, and GA to optimize trusses. The methodology encompasses several steps including: (i) generation of parametric trusses in Dynamo VP; (ii) performing the finite element modeling (FEM) using Robot Structural Analysis (RSA); (iii) retrieving and evaluating the FEM results interchangeably between Dynamo and RSA; (iv) finding the best solution using GA; and (v) importing the optimized model into Revit, enabling the user to perform simulations and engineering analysis, such as life cycle assessment (LCA) and quantity surveying. The feasibility of the proposed workflow was tested on benchmark problems and compared with open literature. The outcomes of this study offer insight into the opportunities and limitations of combining VP, GA, FEA, and BIM for structural optimization applications, particularly to enhance structural efficiency and sustainability in construction.

Charles Darwin’s theory of evolution, his note as regards descent with modification, added greatly to the knowledge that we already possess of how species have survived down the ages. It is evident that this does not provide the necessary knowledge about the origin of the life on earth. However, it provides remarkable evidence about how life has survived. Looking fundamentally at the cellular construct of organisms, we arrive at the fact that cells, both unicellular and multicellular, have organelles that enable them communicate with one another. This ability for living organisms, down to the lowest - cellular life - to communicate is what I refer to as Biological interaction. It is necessary that we articulate more about this concept and see how this all comes to bear as regards Homeostasis. In reference to the latter, it is to be made known that every living organism is also intrinsically aimed towards a projected linear motion in its time riddled existence. This is to say that every living organism operates on an foundational process, amongst others, known as Homeostasis. We understand this term to mean balance that the living system strives to maintain. However etymologically speaking it means staying the same. How has this homeostatic process added to the fostering of life via biological interaction? How is biological interaction fundamental to the theory of evolution?

Variable flow emitters are a new type of emitter for underground drip irrigation that are used in locations where soil moisture is difficult to transport to the surface, which leads to crop emer-gence difficulties. The flow channel structure parameters of emitters affect the hydraulic per-formance of the emitter and its anticlogging ability. In this study, the variable flow emitter at the conventional low–flow water supply stage is taken as the research object. A combination of CFD numerical simulation of a two–phase flow of water and sand and clear water testing of test samples is applied to study the influence laws of 10 groups of variable flow emitter structural combinations on the effluent flow rate (q), flow index (x), particle passage rate and flow field inside the flow channel. The results show that the Realizable k–ε turbulence model can be used to simulate the flow field inside the variable flow emitter flow channel. The nRMSE between the measured and simulated values of q is 11.23%, and the relative error between the measured and simulated values of x is 4.66%, which gives a high simulation accuracy. The polar analysis shows that the tooth angle A has the smallest effect on the effluent flow rate q0.1 under 0.1 MPa, x, and particle passage rate of the variable flow emitter. The depth of the flow channel D, the spacing of the teeth B, and the height of the teeth E have a different order of precedence in the influence of the three indices, which are D > B > E > A, B > E > D > A, and E > B > D > A, respectively. The value of particle passage rate is positively correlated with the mean flow velocity (v) and the mean turbulent kinetic energy (k) in the flow channel, and particle passage rate tends to increase and then decrease with the increase of x. The retention time (t) of the particles in the flow channel is closely related to the magnitude of v and k. Three multivariate linear regression equations (R2 = 0.883 ~ 0.995) were constructed for q0.1, x, and particle passage rate versus the flow channel structural parameters. Using the scipy.optimize.minimize function in Python, we de-termined the three optimal combinations of flow channel structural parameters corresponding to better hydraulic performance: q0.1 is 1.5 or 2 L/h (objective function y = min x), better clogging resistance (y = max particle passage rate), and both (y = min (0.5 x - 0.5 particle passage rate)). The research results can provide a ref-erence for the optimal design of variable flow emitters.

In the conservation of monumental heritage, the collection and utilization of information are of primary importance. The Heritage Building Information Modeling (HBIM) procedure harnesses the potential of three-dimensional models, offering significant advantages in accessing documentation, interoperability, multidimensionality of intervention design, cost evaluation and maintenance management. Attention here is focused on the Certosa di Pisa, a large historical complex built in the 14th century as a monastery of the Carthusian order, currently in a state of deterioration and in need of restoration and re-functionalization. The multifaceted nature of this monumental complex, with its intricate interplay of architectural elements spanning different historical periods and featuring diverse techniques, poses a significant challenge for structural safety assessment. This case study presents an opportunity to explore an HBIM approach to streamline the diagnostic process and facilitate the intervention design phase. The goal is achieved by utilizing an accurate 3D model enriched with data from multiple sources and automating certain operations for structural assessment. The usefulness of the HBIM methodology is highlighted as a valuable tool in the realm of Cultural Heritage structures for both technicians and scholars alike.

Chitosan (CS) nanoparticles are under investigation for a wide range of applications in nanomedicine. The structural, molecular and physicochemical properties of chitosan nanoparticles have a direct bearing on their efficacy in drug conjugation and delivery, gene delivery, and tissue engineering. Herein we report on the structural, morphological and molecular properties of chitosan nanoparticles synthesized using the ionic gelation method with the intended purpose of being used for drug delivery. The chitosan nanoparticles (CS-NPs) were prepared in the 0.25 to 1.0% w/v concentration range, whereas separate samples of the 1.0% w/v CS-NPs were also functionalized with polyethylene oxide (PEO) alone and with a diblock copolymer of PEO and polypropylene glycol (PPG). The average size of the CS-NPs was determined from TEM imaging to be in the range of 11.3 to 14.8 nm. The XRD and TEM analyses show that the CS-NPs have semi-crystalline structure with the degree of crystallinity depending upon the nature of synthesis. Our results show that functionalizing the 1.0% w/v CS-NPs with PEO increases the degree of crystallinity whereas functionalizing with the diblock copolymer PEO - PPG results in a significant increase in their degree crystallinity. The CS/TPP concentration (CS:TPP fixed at 1:1 ratio) had no apparent effect on the degree of crystallinity of the CS-NPs. The results from the FTIR analysis confirm incorporation of TPP with CS in the CS-NPs. Additionally, FTIR analysis shows an enhancement of hydrogen bonding that is consistent with the increase in the degree of crystallinity of the CS-NPs.

Semantic segmentation of high-resolution remote sensing images provides detailed and precise feature information, playing a pivotal role in decision-making and analysis in sectors such as water management, agriculture, military, and environmental protection. However, most methods merely combine features from various branches directly, without a mechanism for spatial location feature screening, and treat all extracted features as equally important. To overcome these limitations, we introduce a novel spatially adaptive interaction network (SAINet) for dynamic interaction across different features in remote sensing semantic segmentation task. Specifically, we propose a spatial refined module that leverages local context information to filter spatial locations and extract salient regions. Following this, we introduce an innovative spatial interaction module that uses a spatial adaptive modulation mechanism to dynamically select and allocate spatial position weights. This facilitates interaction between local salient areas and global information, allowing the network to focus more on relevant regions. This flexible approach enables the network to capture more informative features, thereby enhancing segmentation accuracy. Experiments conducted on the DeepGlobe, Vaihingen, and Potsdam public datasets confirm the effectiveness and capability of SAINet. Our code and models will be publicly available

Aging-related disorders pose significant challenges due to their complex interplay of physiological and metabolic factors, including inflammation, oxidative stress, and mitochondrial dysfunction. Curcumin, a natural compound with potent antioxidant and anti-inflammatory properties, has emerged as a promising candidate for mitigating these age-related processes. However, gaps in understanding the precise mechanisms of curcumin's effects and the optimal dosages for different conditions necessitate further investigation. This systematic review synthesizes current evidence on curcumin's potential in addressing age-related disorders, emphasizing its impact on cognitive function, neurodegeneration, and muscle health in older adults. By evaluating the safety, efficacy, and mechanisms of action of curcumin supplementation, this review aims to provide insights into its therapeutic potential for promoting healthy aging. A systematic search across three databases using specific keywords yielded 2,256 documents, leading to the selection of 15 clinical trials for synthesis. Here we highlight the promising potential of curcumin as a multifaceted therapeutic agent in combating age-related disorders. The findings of this review suggest that curcumin could offer a natural and effective approach to enhancing the quality of life of aging individuals. Further research and well-designed clinical trials are essential to validate these findings and optimize the use of curcumin in personalized medicine approaches for age-related conditions.

The well-being and sociability of individuals have always been part of modernity. The development of new technologies that meet these aspirations is receiving increasing attention. Thus, strengthening the desired objectives of these tools and minimizing their undesirable side effects is the subject of a growing commitment. The present contribution aims, in this context, to evaluate and analyze the desired and undesirable effects of the interaction of electromagnetic fields with living tissues in general. This involves routines reinforcing expected functions as well as those controlling and protecting against undesirable effects. First, the interactions of electromagnetic fields with tissues are analyzed, involving their thermal biological effects of desired and undesired exposures. The roles of blood and sap fluids in bio-affected tissues are then analyzed. Secondly, the governing electromagnetic, bio-heat equations, and their coupled solution are studied. Third, the thermal behavior of tissues and the exposure adverse effects are examined. Next, monitoring and defending of the effects of exposures are discussed. This contribution illustrates and discusses mathematical modeling routines based on a generalized interaction of electromagnetic fields with living tissues.

New dimers of selected dipyridothiazines with an m-xylene linker have been designed, synthesized and characterized. Their structure was identified using 1H and 13C NMR as well as 2D NMR techniques (COSY, ROESY, HSQC and HMBC experiments) and HR MS spectrometry. The compounds were subjected to preliminary in silico biological profile tests using the Way2Drug server and analysis of the probable cytotoxic effect on various cancer cell lines. Preliminary in vitro cytotoxicity tests were performed against normal cell lines (HaCaT) and five cancer cell lines (SW480, SW620, MDA-MB-231, A-549, LN-229) showing moderate activity. An analysis of the structure-activity relationship was performed.

Innovative tissue engineering biomimetic hydrogels based on hydrophilic polymers have been investigated for their physical and mechanical properties. 5% to 25% by volume loading PHEMA-nanosilica glassy hybrid samples were equilibrated at 37°C in aqueous physiological isotonic and hypotonic saline solutions (0.15 and 0.05 M NaCl) simulating two limiting possible compositions of physiological extracellular fluids. The glassy and hydrated hybrid materials were characterized both for dynamo-mechanical properties and equilibrium absorptions in the two physiological-like aqueous solutions. Mechanical and the morphological modifications occurring in the samples have been described. The 5% volume nanosilica loading hybrid nanocomposite composition showed mechanical characteristics in the dry and hydrated states that were comparable to those of cortical bone and articular cartilage, respectively, and then chosen for further sorption kinetics characterization. Sorption and swelling kinetics were monitored up to equilibrium. Changes in water activities and osmotic pressures in the water-hybrid systems equilibrated at the two limiting solute molarities of the physiological solutions have been related to the observed anomalous sorption modes using the Flory-Huggins interaction parameter approach. The bulk modulus of the dry and glassy PHEMA-5% nanosilica hybrid at 37°C has been observed to be comparable with the values of the osmotic pressures generated from the sorption of isotonic and hypotonic solutions. The anomalous sorption modes and swelling rates are coherent with the difference between osmotic swelling pressures and hybrid glassy nano-composite bulk modulus: the lower the differences the higher the swelling rate and equilibrium solution uptakes. Bone tissue engineering benefits of use of tuneable biomimetic scaffold biomaterials that can be “designed” to act as biocompatible and biomechanically active hybrid interfaces are discussed.

Triazole derivatives of fluorescein containing N,N-dimethylaminopropyl fragments and their ammonium salts were synthesized with yields of 74 - 85%. The resulting compounds exhibit fluorescent properties in the green region of the visible spectrum. The critical aggregation concentration (CAC) was estimated using a py-rene fluorescent probe corresponding to a range of 0.28 - 1.43 mM, and at concentrations above the CAC the compounds form stable aggregates ranging from 165 to 202 nm. A relative quantum yield of 5-24% has been calculated based on fluorescence and UV spectra. The best value is shown by a derivative containing a tetradecyl substituent. When studying the photocatalytic properties of synthesized compounds through the reaction between N-substituted 1,2,3,4-tetrahydroisoquinoline and malonic ester, the mono-tetradecyl deriva-tive demonstrated the best results. According to gas chromatography-mass spectrometry (GC-MS) data, the conversion of the initial heterocycle reached 95%. Therefore, these resulting compounds have the potential to act as an effective photocatalysts.

The integration of robotic devices into healthcare settings for rehabilitation purposes represents a rapidly advancing field with significant benefits for both therapists and patients. However, standalone robot systems face limitations such as inefficient processing of patient data and logistical challenges for patients, such as travel time to rehabilitation centers. To address these shortcomings, this paper proposes the integration of cyber-physical systems into rehabilitation robotics. Cyber-physical systems leverage network connectivity and real-time data processing to enhance the efficiency and convenience of robot-based rehabilitation. By seamlessly integrating sensors, actuators, and computational algorithms, cyber-physical rehabilitation systems empower therapists to more effectively treat patients by providing actionable insights derived from comprehensive data analysis. This enables therapists to tailor treatment plans precisely to each patient’s unique needs, ultimately leading to improved outcomes. Additionally, cyber-physical rehabilitation systems facilitate remote monitoring and intervention, allowing therapists to oversee patient progress and make timely adjustments to treatment protocols without the need for in-person visits. This not only saves patients valuable time and resources but also ensures continuity of care, particularly for individuals residing in remote or underserved areas. Furthermore, cyber-physical rehabilitation systems enable collaborative decision-making by facilitating communication and information sharing among healthcare professionals, further enhancing the quality and efficacy of rehabilitation services. In summary, integrating cyber-physical systems into rehabilitation robotics represents a significant advancement in leveraging technology to optimize patient care and outcomes, promising to revolutionize rehabilitation therapy.

Lirianthe delavayi has valuable ornamental and medicinal value, is an important economic tree, and has a long history of cultivation. As important regulatory molecules, miRNAs are involved in important physiological processes, such as the plant stress response, organ morphogenesis, hormone secretion, and signaling. In this study, based on miRNA sequencing analysis of wild and cultivated Lirianthe delavayi, we explored the differences in posttranscriptional regulation during the cultivation of Lirianthe delavayi from the aspect of miRNA molecular regulation. The results revealed the following: 1. A total of 365 miRNAs were sequenced and identified, and their first bases had obvious uracil (U) base preferences. Among them, 242 miRNAs were classified into 32 miRNA families; 2. Analysis of miRNA expression differences revealed that 39 miRNAs had significant expression differences between wild and cultivated populations; 3. Bioinformatics target gene prediction and target gene enrichment analysis of significantly differentially expressed miRNAs revealed that the target genes were significantly enriched in plant‒pathogen interactions, sphingolipid metabolism, defense responses, and ADP binding. 4. The plant‒pathogen interaction pathway involves seven differentially expressed miRNAs and 30 miRNA‒target gene regulatory pairs, which are involved mainly in pathogen signature molecule recognition and binding, signal transduction, and the regulation of disease resistance molecules or gene expression; Ath-MIR169g-p3_2ss7AG19GA, ath-MIR169g-p5_2ss7AG19GA, and ath-miR408-3p_L-3 are expressed only in wild population, and it is hypothesized that the domestication process from wild to cultivation species may be accompanied by the loss of disease resistance-related miRNAs. This study provides a reference for exploring the posttranscriptional-level regulatory mechanisms of adaptive changes in Lirianthe delavayi from wild to cultivated.

Despite decreasing anthropogenic mercury (Hg) emissions in Europe and the banning and restriction of many persistent organic pollutants (POPs) under the Stockholm Convention, Mediterranean marine mammals still have one of the highest body burdens of persistent pollutants in the world. Moreover, the Mediterranean basin is one of the most sensitive to climate change, with likely changes in the biogeochemical cycle and bioavailability of Hg, primary productivity, and the length and composition of pelagic food webs. The availability of food resources for marine mammals is also affected by widespread overfishing and the increasing number of alien species colonizing the basin. After reporting the most recent findings on the biogeochemical cycle of Hg in the Mediterranean Sea and the physico-chemical and bio-ecological factors determining its exceptional bioaccumulation in odontocetes, this review discusses possible future changes in the bioavailability of the metal. Recent ocean-atmosphere-land models predict that in mid-latitude seas, water warming (which in the Mediterranean is 20% faster than the global average) is likely to decrease the solubility of Hg and favor the escape of the metal to the atmosphere. However, the basin has been affected for thousands of years by natural and anthropogenic inputs of metals, and climate change with sea level rise (3.6 ± 0.3 mm year-1 in the last two decades) and the frequency of extreme weather events will likely remobilize large amount of legacy Hg from soils, riverine and coastal sediments. Moreover, possible changes in pelagic food webs and food availability could determine dietary shifts and lower growth rates in Mediterranean cetaceans, increasing their Hg body burden. Although adult marine mammals have evolved the ability to detoxify monomethylmercury (MMHg) and store the metal in the liver and other organs as insoluble Hg-Se crystals, in Mediterranean populations more exposed to the metal, this process can deplete the biological pool of Se, increasing their susceptibility to infectious diseases and autoimmune disorders. Mediterranean mammals are also among the most exposed in the world to legacy POPs, micro- and nanoplastics and contaminants of emerging interest. Concomitant exposure to these synthetic chemicals may pose a much more serious threat than the Se depletion. Unfortunately, as shown by literature data summarized in this review, the most exposed populations are those living in the NW basin, the main feeding and reproductive area for most Mediterranean cetaceans, declared a sanctuary for their protection since the 2002. Thus, while emphasizing the adoption of all available approaches to mitigate anthropogenic pressure with fishing and maritime traffic, it is recommended to direct future research efforts towards the assessment of possible biological effects, at individual and population level, of chronic and simultaneous exposure to Hg, legacy POPs, contaminants of emerging interest and microplastics.

In 2018, Iran witnessed approximately 21,000 fatalities resulting from road accidents, ranking it as the fifth leading cause of death across all age groups. These incidents carry substantial economic and social burden for the nation, claiming more than 5% of its GDP. Human behavior emerges as a significant contributing factor to high-risk driving offenses. It has been proposed that by influencing general deterrence, a rigorous defense can be established against such violations. Various theories posit that by reinforcing or diminishing influential factors, general deterrence perception can be molded, presenting a potential avenue for an effective deterrent against traffic infractions. This study examines deterrence perceptions prevailing among the public in Iran regarding the enforcement of traffic laws. Employing Structural Equation Modeling (SEM), we delve into the intricate relationships between variables, allowing for a comprehensive exploration of the factors influencing general deterrence. The study draws on the data derived from a survey comprising 548 questionnaires for modeling purposes. An innovative concept, private sector enforcement, is introduced and incorporated into the questioning and modeling process. The findings reveal that socioeconomic status (p-value&lt;0.01), police enforcement (p-value&lt;0.05), private sector enforcement (p-value&lt;0.05), specific deterrence (p-value&lt;0.01), and the use of technology (p-value&lt;0.01) have direct and indirect impacts on the general deterrence perception of drivers.

The seismic events of 2015 in Nepal exposed the challenges associated with constructing earthquake-resistant 2-story self-built stone masonry structures in high-elevation rural regions, especially post-disaster. The Department of Urban Development and Building Construction (DUDBC) provided designs that failed to preserve the local architectural landscape and craftsmanship while adding unfamiliar knowledge and technology. To address the challenges related to architecture, structure, and socio-economic concerns in designing and implementing post-earthquake houses, a need-based building development framework is required for standardized practice. This study presents a novel framework to assess, design, and implement a self-built house after a disaster, consisting of five stages: 1) post-disaster problem assessment, 2) need identification, 3) material selection, 4) design development, and 5) validation and implementation. Based on this framework, we proposed a novel gabions building construction technology for two-story stone masonry structures that effectively mitigate post-disaster challenges such as logistic, resilience, and socioeconomic aspects while improving disaster resiliency specifically in the high-elevation rural areas of Nepal. The proposed two-story gabion building preserves architectural values, enhances structural integrity, and provides cost-effectiveness when compared with its DUDBC peer models while providing much-needed relief to the vulnerable community. The proposed resilient house, G- 2.1, utilizes locally sourced materials and craftsmanship, and innovative gabion technology that ensures affordability and facilitates knowledge transfer. The contribution of this study includes a development framework and a two-story gabions house that is most suitable for self-built post-disaster reconstruction and resilient to local architecture and socio-economic conditions while providing structural integrity and safety.

Abstract Octreotide is the first synthetic peptide hormone, consisted of eight amino acids, that mimics the activity of somatostatin, a natural hormone in the body. During the past decades, advanced instrumentation and crystallographic software established X-ray Powder Diffraction (XRPD) as a valuable tool for extracting structural information of biological macromolecules. The latter was demonstrated by the successful structural determination of octreotide at a remarkably high d-spacing resolution (1.87 Å) (PDB code: 6vc1). This study focuses on the response of octreotide to different humidity levels and temperatures, with a particular focus on the stability of the polycrystalline sample. XRPD measurements were accomplished employing an Anton Paar MHC-trans humidity-temperature chamber installed within a laboratory X’Pert Pro diffractometer (Malvern Panalytical). The chamber is employed to control and maintain precise humidity and temperature levels of samples during XRPD data collection. Pawley analysis of the collected data sets revealed that the octreotide polycrystalline sample is remarkably stable and no structural transitions were observed. The compound retains its orthorhombic symmetry (space group: P212121, a = 18.57744(4) Å, b = 30.17338(6) Å, c = 39.70590(9) Å, d~ 2.35 Å). However, a characteristic structural evolution in terms of lattice parameters and volume of the unit-cell is reported mainly upon controlled relative humidity variation. In addition, an improvement of signal-to-noise ratio in the XRPD data under a cycle of dehydration/rehydration is reported. These results underline the importance of considering the impact of environmental factors, as humidity and temperature, in the context of structure-based drug design, thereby contributing to the development of more effective and stable pharmaceutical products.

The saphenous vein is the conduit of choice for bypass grafting. Unfortunately, the hemodynamic stress associated with the arterial environment of the bypass vein graft leads to the development of intimal hyperplasia (IH), an excessive cellular growth and collagen deposition that results in restenosis and secondary graft occlusion. Hydrogen sulfide (H2S) is a ubiquitous redox-modifying gasotransmitter that inhibits IH. H2S is produced via the reverse trans-sulfuration pathway by 3 enzymes: cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MST). However, the expression and regulation of these enzymes in the human vasculature remains unclear. Here, we investigated the expression of CSE, CBS and 3-MST in segments of native human saphenous vein and large arteries. Furthermore, we evaluated the regulation of these enzymes in vein segments cultured under static, venous (7 mmHg pressure) or arterial (100 mmHg pressure) pressure. CSE was expressed in the media, neointima and intima of the vessels and was negatively regulated by arterial shear stress. Adenoviral-mediated CSE overexpression or RNA interference-mediated CSE knock-down revealed that CSE inhibited primary human VSMC migration but not proliferation. We propose that high shear stress in arteriovenous bypass grafts inhibits CSE expression in both the media and endothelium, which may contribute to increased VSMC migration in the context of IH.

A new class of nano-cube core-shell heterostructures containing Ag coating on the top of WO₃ was fabricated. Physical vapor deposition was used to produce WO₃ based nano-heterostructures. All kind of wet toxic chemical process was avoided to make the process simple and contaminant free. Sputtering of WO₃ and a subsequent thermal annealing process was done to create nano-cubes of WO₃. After that, sputtering of Ag was performed to form the Ag-WO₃ core-shell nano-heterostructures (CSNH). The CSNHs were characterized using field emission scanning electron microscopy (FESEM), energy dispersive spectroscopy (EDS), X-ray diffraction analysis (XRD) and UV-vis spectroscopy. The morphologies, elemental analysis, interfaces, crystallinity, phases, and chemical compositions were analyzed. The bottom-up growth of WO₃ nanocubes was studied using different time periods at 900°C. Ag coating was also studied before and after annealing. Finally, an optical property (band gap) was also analyzed using Tauc plot derive from absorption spectra. The tailoring the band gap of WO₃ from ~2.9eV to ~ 2.45 eV was observed while Ag-WO₃ CSNH formed.

Structural deformations are one of the most significant factor that affects machine tool (MT) positioning accuracy. These induced errors are complex to be represented by a model, nevertheless they need to be evaluated and predicted in order to increase the machining performance. This paper presents a novel approach to calibrate a machine tool in real-time, analyzing the thermo-mechanical errors through Fibre Bragg Grating (FBG) sensors embedded in the MT frame. The proposed configuration consists of an adaptronic structure of passive materials, Carbon Fibre Reinforced Polymers (CFRP), equipped by FBG sensors that are able to measure in real-time the deformed conditions of the frame. By using a proper thermo-mechanical kinematic model, the displacement of the end effector may be predicted and corrected when it is subjected to external undesired factors. By starting from a set of FE simulations to develop a model able to describe the MT structure stresses, a prototype has been fabricated and tested. The scope was to compare the numerical model with the experimental tests using FBG sensors. The experimental campaign has been performed varying the structure temperature over time and measuring the tool tip point (TTP) positions. The obtained results showed a substantial matching between the real and the predicted position of TTP confirming the effectiveness of the proposed calibration system.

Retinoic acid receptor-related orphan receptor γ (RORγ) is a transcription factor regulating the expression of the pro-inflammatory cytokine IL-17 in human T helper 17 (Th17) cells. Activating RORγ can induce multiple IL-17-mediated autoimmune diseases but may also be useful for anticancer therapy. Its deep immunological functions make RORɣ an attractive drug target. Over 100 crystal structures have been published describing atomic interactions between RORɣ and agonists and inverse agonists. In this review, we focus on the role of dynamic properties and plasticity of the RORɣ orthosteric and allosteric binding sites by examining structural information from crystal structures and simulated models. We discuss the possible influences of allosteric ligands on the orthosteric binding site. We find that high structural plasticity favors the druggability of RORɣ, especially for allosteric ligands.

In addition to the canonical loss-of-function mutations, mutations in proteins may additionally result in gain-of-function through the binary activation of cryptic ‘structural capacitance elements’. Our previous bioinformatic analysis allowed us to propose a new mechanism of protein evolution - structural capacitance – that arises via the generation of new elements of microstructure upon mutations that cause a disorder-to-order (DO) transition in previously disordered regions of proteins. Here we propose that the DO transition is a necessary follow-on from expected early codon-anticodon and tRNA acceptor stem-amino acid usage, via the accumulation of structural capacitance elements - reservoirs of disorder in proteins. We develop this argument further to posit that structural capacitance is an inherent consequence of the evolution of the genetic code.

The production of biomass fly ash has been increasing every year in Europe, reaching 5.5 million tons in 2020. Biomass fly ash is not yet accepted in the standards as a substitute material for cement in mortar and concrete. In a first approach, the substitution limit of biomass fly ash is determined by comparing the mechanical strengths, fresh state properties and hardened properties of mortars produced with biomass fly ash to those of mortars produced with classical coal fly ash. Then, masonry and rendering mortars have been designed with different substitution rates of biomass fly ashes from wood combustion in thermal power plant. Although there is an overall decrease in performance, mortars made with biomass ash retain properties that make them suitable for use in masonry or rendering.

Hepatitis B surface antigen (HBsAg) is not only the biomarker of hepatitis B virus (HBV) infection and expression activity in hepatocytes, but also contributes to viral specific T cell exhaustion and HBV persistent infection. Therefore, anti-HBV therapies targeting HBsAg to achieve HBsAg loss are key approaches for HBV functional cure. In this study, we found that YZH-106, a rupestonic acid derivative, inhibited HBsAg secretion and viral replication. Further investigation demonstrated that YZH-106 promoted the lysosomal degradation of viral L- and M-HBs proteins. Mechanistic study by Biacore and docking analysis revealed that YZH-106 bound directly to PreS2 domain of L- and M-HBsAg, thereby blocking their entry to the endoplasmic reticulum (ER) and promoting their degradation in cytoplasm. Our work thereby provide basis for design of novel compound therapy to target HBsAg against HBV infection.