Search results for: cell membrane integrity

Authors: Alejandra Ben-Aissa, Martina Moreno, Luciano Sappia, Paul Lacharmoise, Ana Moya

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Organ-on-Chip (OoC) stands out as a highly promising approach for drug testing, presenting a cost-effective and ethically superior alternative to conventional in vivo experiments. These cutting-edge devices emerge from the integration of tissue engineering and microfluidic technology, faithfully replicating the physiological conditions of targeted organs. Consequently, they offer a more precise understanding of drug responses without the ethical concerns associated with animal testing. When addressing the limitations of OoC due to conventional and time-consuming techniques, Lab-On-Chip (LoC) emerge as a disruptive technology capable of providing real-time monitoring without compromising sample integrity. This work develops LoC platforms that can be integrated within OoC platforms to monitor essential culture media parameters, including glucose, oxygen, and pH, facilitating the straightforward exchange of sensing units within a dynamic and controlled environment without disrupting cultures. This approach preserves the experimental setup, minimizes the impact on cells, and enables efficient, prolonged measurement. The LoC system is fabricated following the patented methodology protected by EU patent EP4317957A1. One of the key challenges of integrating sensors in a biocompatible, feasible, robust, and scalable manner is addressed through fully printed sensors, ensuring a customized, cost-effective, and scalable solution. With this technique, sensor reliability is enhanced, providing high sensitivity and selectivity for accurate parameter monitoring. In the present study, LoC is validated measuring a complete culture media. The oxygen sensor provided a measurement range from 0 mgO2/L to 6.3 mgO2/L. The pH sensor demonstrated a measurement range spanning 2 pH units to 9.5 pH units. Additionally, the glucose sensor achieved a measurement range from 0 mM to 11 mM. All the measures were performed with the sensors integrated in the LoC. In conclusion, this study showcases the impactful synergy of OoC technology with LoC systems using fully printed sensors, marking a significant step forward in ethical and effective biomedical research, particularly in drug development. This innovation not only meets current demands but also lays the groundwork for future advancements in precision and customization within scientific exploration.

Keywords: organ on chip, lab on chip, real time monitoring, biosensors

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Authors: Mahadehe Hassan

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In most countries manufacturing, trading and distribution of gasoline and diesel fuels belongs to the most important sectors of national economy. For Bangladesh, a robust, well-functioning, secure and smartly managed national fuel distribution chain is an essential precondition for achieving Government top priorities in development and modernization of transportation infrastructure, protection of national environment and population health as well as, very importantly, securing due tax revenue for the State Budget. Bangladesh is a developing country with complex fuel supply network, high fuel taxes incidence and – till now - limited possibilities in application of modern, automated technologies for Government national fuel market control. Such environment allows dishonest physical and legal persons and organized criminals to build and profit from illegal fuel distribution schemes and fuel illicit trade. As a result, the market transparency and the country attractiveness for foreign investments, law-abiding economic operators, national consumers, State Budget and the Government ability to finance development projects, and the country at large suffer significantly. Research shows that over 50% of retail petrol stations in major agglomerations of Bangladesh sell adulterated fuels and/or cheat customers on the real volume of the fuel pumped into their vehicles. Other forms of detected fuel illicit trade practices include misdeclaration of fuel quantitative and qualitative parameters during internal transit and selling of non-declared and smuggled fuels. The aim of the study is to recommend the implementation of a National Fuel Distribution Integrity Program (FDIP) in Bangladesh to address and resolve fuel adulteration and illicit trade problems. The program should be customized according to the specific needs of the country and implemented in partnership with providers of advanced technologies. FDIP should enable and further enhance capacity of respective Bangladesh Government authorities in identification and elimination of all forms of fuel illicit trade swiftly and resolutely. FDIP high-technology, IT and automation systems and secure infrastructures should be aimed at the following areas (1) fuel adulteration, misdeclaration and non-declaration; (2) fuel quality and; (3) fuel volume manipulation at retail level. Furthermore, overall concept of FDIP delivery and its interaction with the reporting and management systems used by the Government shall be aligned with and support objectives of the Vision 2041 and Smart Bangladesh Government programs.

Keywords: fuel adulteration, octane, kerosene, diesel, petrol, pollution, carbon emissions

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Authors: Harris Niavis, Dimitra Politaki

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The manufacturing industry was collecting vast amounts of data for monitoring product quality thanks to the advances in the ICT sector and dedicated IoT infrastructure is deployed to track and trace the production line. However, industries have not yet managed to unleash the full potential of these data due to defective data collection methods and untrusted data storage and sharing. Blockchain is gaining increasing ground as a key technology enabler for Industry 4.0 and the smart manufacturing domain, as it enables the secure storage and exchange of data between stakeholders. On the other hand, AI techniques are more and more used to detect anomalies in batch and time-series data that enable the identification of unusual behaviors. The proposed scheme is based on smart contracts to enable automation and transparency in the data exchange, coupled with anomaly detection algorithms to enable reliable data ingestion in the system. Before sensor measurements are fed to the blockchain component and the smart contracts, the anomaly detection mechanism uniquely combines artificial intelligence models to effectively detect unusual values such as outliers and extreme deviations in data coming from them. Specifically, Autoregressive integrated moving average, Long short-term memory (LSTM) and Dense-based autoencoders, as well as Generative adversarial networks (GAN) models, are used to detect both point and collective anomalies. Towards the goal of preserving the privacy of industries' information, the smart contracts employ techniques to ensure that only anonymized pointers to the actual data are stored on the ledger while sensitive information remains off-chain. In the same spirit, blockchain technology guarantees the security of the data storage through strong cryptography as well as the integrity of the data through the decentralization of the network and the execution of the smart contracts by the majority of the blockchain network actors. The blockchain component of the Data Traceability Software is based on the Hyperledger Fabric framework, which lays the ground for the deployment of smart contracts and APIs to expose the functionality to the end-users. The results of this work demonstrate that such a system can increase the quality of the end-products and the trustworthiness of the monitoring process in the smart manufacturing domain. The proposed AI-enabled data traceability software can be employed by industries to accurately trace and verify records about quality through the entire production chain and take advantage of the multitude of monitoring records in their databases.

Keywords: blockchain, data quality, industry4.0, product quality

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Authors: G. V. Novikov, V. S. Sivozhelezov, S. S. Kolesnikov, K. V. Shaitan

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The study reports about the influence of binding of orthosteric ligands as well as point mutations on the conformational dynamics of β-2-adrenoreceptor. Using molecular dynamics simulation we found that there was a little fraction of active states of the receptor in its apo (ligand free) ensemble corresponded to its constitutive activity. Analysis of MD trajectories indicated that such spontaneous activation of the receptor is accompanied by the motion in intracellular part of its alpha-helices. Thus receptor’s constitutive activity directly results from its conformational dynamics. On the other hand the binding of a full agonist resulted in a significant shift of the initial equilibrium towards its active state. Finally, the binding of the inverse agonist stabilized the receptor in its inactive state. It is likely that the binding of inverse agonists might be a universal way of constitutive activity inhibition in vivo. Our results indicate that ligand binding redistribute pre-existing conformational degrees of freedom (in accordance to the Monod-Wyman-Changeux-Model) of the receptor rather than cause induced fit in it. Therefore, the ensemble of biologically relevant receptor conformations is encoded in its spatial structure, and individual conformations from that ensemble might be used by the cell in conformity with the physiological behaviour.

Keywords: seven-transmembrane receptors, constitutive activity, activation, x-ray crystallography, principal component analysis, molecular dynamics simulation

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Authors: S. O. Ekpo

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Environmental science deals with everyday challenges such as a cell for call for good and safe quality air, water, food and healthy leaving condition which include destruction of biodiversity and how to conserve these natural resources for sustainable development. Biodiversity or species richness is the sum of all the different species of animals, plants, fungi and microorganisms leaving on earth and variety of habitats in which they leave. Human beings leave on plants and animals on daily basis for food, clothing, medicine, housing, research and trade or commerce; besides this, biodiversity serves to purify the air, water and land of contaminant, and recycle useful materials for continual use of man. However, man continual incessant exploitation and exploration has affected biodiversity negatively in many ways such habitant fragmentation and destruction, introduction of invasive species, pollution, overharvesting, prediction and pest control amongst others. Measures such as recycling material, establishing natural parks, sperm bank, limiting the exploitation of renewable resources to sustainable yield and urban and industrial development as well as prohibiting hunting endangered species and release of non native live forms into an area will go a long way towards conserving biodiversity for continues profitable yield.

Keywords: biodiversity, conservation, exploitation and exploration sustainable yield, recycling of materials

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Authors: Sadia Arshad, Yifa Tang, Dumitru Baleanu

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A fractional order mathematical model is proposed that incorporate CD8+ cells, natural killer cells, cytokines and tumor cells. The tumor cells growth in the absence of an immune response is modeled by logistic law as it was the simplest form for which predictions also agreed with the experimental data. Natural Killer Cells are our first line of defense. NK cells directly kill tumor cells through several mechanisms, including the release of cytoplasmic granules containing perforin and granzyme, expression of tumor necrosis factor (TNF) family members. The effect of the NK cells on the tumor cell population is expressed with the product term. Rational form is used to describe interaction between CD8+ cells and tumor cells. A number of cytokines are produced by NKs, including tumor necrosis factor TNF, IFN, and interleukin (IL-10). Source term for cytokines is modeled by Michaelis-Menten form to indicate the saturated effects of the immune response. Stability of the equilibrium points is discussed for biologically significant values of bifurcation parameters. We studied the treatment of fractional order system by investigating analytical conditions of tumor eradication. Numerical simulations are presented to illustrate the analytical results.

Keywords: cancer model, fractional calculus, numerical simulations, stability analysis

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Authors: Daniel Osorio, Andreas Klenk, Stefan Weihe, Andreas Kopp, Frank Rödiger

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Future power plants currently face high design requirements due to worsening climate change and environmental restrictions, which demand high operational flexibility, superior thermal performance, minimal emissions, and higher cyclic capability. The aim of the paper is, therefore, to investigate the creep and thermo-mechanical material behavior of improved materials experimentally and welded joints at component scale under near-to-service operating conditions, which are promising for application in highly efficient and flexible future power plants. These materials promise an increase in flexibility and a reduction in manufacturing costs by providing enhanced creep strength and, therefore, the possibility for wall thickness reduction. At the temperature range between 550°C and 625°C, the investigation focuses on the in-phase thermo-mechanical fatigue behavior of dissimilar welded joints of conventional materials (ferritic and martensitic material T24 and T92) to nickel-based alloys (A617B and HR6W) by means of membrane test panels. The temperature and external load are varied in phase during the test, while the internal pressure remains constant. At the temperature range between 650°C and 750°C, it focuses on the creep behavior under multiaxial stress loading of similar and dissimilar welded joints of high temperature resistant nickel-based alloys (A740H, A617B, and HR6W) by means of a thick-walled-component test. In this case, the temperature, the external axial load, and the internal pressure remain constant during testing. Numerical simulations are used for the estimation of the axial component load in order to induce a meaningful damage evolution without causing a total component failure. Metallographic investigations after testing will provide support for understanding the damage mechanism and the influence of the thermo-mechanical load and multiaxiality on the microstructure change and on the creep and TMF- strength.

Keywords: creep, creep-fatigue, component behaviour, weld joints, high temperature material behaviour, nickel-alloys, high temperature resistant steels

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Authors: Eun Young Choi, So Hui Choe, Jin Yi Hyeon, Ji Young Jin, Bo Ram Keum, Jong Min Lim, Hyung Rae Cho, Kwang Keun Cho, In Soon Choi

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This research analyzed the effect of β-glucan that is expected to alleviate the production of inflammatory mediator in macrophagocyte, which was processed by the lipopolysaccharide (LPS) of Escherichia, a pathogen related to allergy. The incubated layer was used for nitric oxide (NO) analysis. The DNA-binding activation of the small unit of NF-κB was measured using ELISA-based kit. In RAW264.7 cells that were vitalized by E.coli LPS, β-glucan inhibited both the combatant and rendering phases of inducible NO synthase (iNOS)-derived NO. β-glucan increased the expression of heme oxygenase-1 (HO-1) in the cell that was stimulated by E.coli LPS, and HO-1 activation was inhibited by SnPP. This shows that NO production induced by LPS is related to the inhibition effect of β-glucan. The phosphorylation of JNK and p38 induced by LPS were not influenced by β-glucan, and IκB-α decomposition was not influenced either. Instead, β-glucan remarkably inhibited the phosphorylation of STAT1 that was induced by E.coli LPS. Overall, β-glucan inhibited the production of NO in macrophagocyte that was vitalized by E.coli LPS through HO-1 induction and STAT1 pathways inhibition in this research. As the host inflammation reaction control by β-glucan weakens the progress of allergy, β-glucan can be used as an effective treatment method.

Keywords: β-glucan, lipopolysaccharide (LPS), nitric oxide (NO), RAW264.7 cells, STAT1

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Authors: Dimassi Wissem

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In this work, we investigate the effect of combination between the porous silicon (PS) layer passivized with Lithium Bromide (LiBr) and grooving of grain boundaries (GB) in multi crystalline silicon. The grain boundaries were grooved in order to reduce the area of these highly recombining regions. Using optimized conditions, grooved GB's enable deep phosphorus diffusion and deep metallic contacts. We have evaluated the effects of LiBr on the surface properties of porous silicon on the performance of silicon solar cells. The results show a significant improvement of the internal quantum efficiency, which is strongly related to the photo-generated current. We have also shown a reduction of the surface recombination velocity and an improvement of the diffusion length after the LiBr process. As a result, the I–V characteristics under the dark and AM1.5 illumination were improved. It was also observed a reduction of the GB recombination velocity, which was deduced from light-beam-induced-current (LBIC) measurements. Such grooving in multi crystalline silicon enables passivization of GB-related defects. These results are discussed and compared to solar cells based on untreated multi crystalline silicon wafers.

Keywords: Multicrystalline silicon, LiBr, porous silicon, passivation

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Authors: Nicholas Fletcher, Zachary Houston, Yongmei Zhao, Christopher Howard, Kristofer Thurecht

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One promising approach to enhance nanomedicine therapeutic efficacy is to include a targeting agent, such as an antibody, to increase accumulation at the tumor site. However, the application of such targeted nanomedicines remains limited, in part due to difficulties involved with biomolecule conjugation to synthetic nanomaterials. One approach recently developed to overcome this has been to engineer bispecific antibodies (BsAbs) with dual specificity, whereby one portion binds to methoxy polyethyleneglycol (mPEG) epitopes present on synthetic nanomedicines, while the other binds to molecular disease markers of interest. In this way, noncovalent complexes of nanomedicine core, comprising a hyperbranched polymer (HBP) of primarily mPEG, decorated with targeting ligands are able to be produced by simple mixing. Further work in this area has now demonstrated such complexes targeting the breast cancer marker epidermal growth factor receptor (EGFR) to show enhanced binding to tumor cells both in vitro and in vivo. Indeed the enhanced accumulation at the tumor site resulted in improved therapeutic outcomes compared to untargeted nanomedicines and free chemotherapeutics. The current work on these BsAb-HBP conjugates focuses on further probing antibody-nanomaterial interactions and demonstrating broad applicability to a range of cancer types. Herein are reported BsAb-HBP materials targeted towards prostate-specific membrane antigen (PSMA) and study of their behavior in vivo using ⁸⁹Zr positron emission tomography (PET) in a dual-tumor prostate cancer xenograft model. In this model mice bearing both PSMA+ and PSMA- tumors allow for PET imaging to discriminate between nonspecific and targeted uptake in tumors, and better quantify the increased accumulation following BsAb conjugation. Also examined is the potential for formation of these targeted complexes in situ following injection of individual components? The aim of this approach being to avoid undesirable clearance of proteinaceous complexes upon injection limiting available therapeutic. Ultimately these results demonstrate BsAb functionalized nanomaterials as a powerful and versatile approach for producing targeted nanomedicines for a variety of cancers.

Keywords: bioengineering, cancer, nanomedicine, polymer chemistry

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Authors: Mahmoud Fouad, Mervat Badr, Marwa Ibrahim

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Micro-grid system is presently considered a reliable solution for the expected deficiency in the power required from future power systems. Renewable power sources such as wind, solar and hydro offer high potential of benign power for future micro-grid systems. Micro-Grid (MG) is basically a low voltage (LV) or medium voltage (MV) distribution network which consists of a number of called distributed generators (DG’s); micro-sources such as photovoltaic array, fuel cell, wind turbine etc. energy storage systems and loads; operating as a single controllable system, that could be operated in both grid-connected and islanded mode. The capacity of the DG’s is sufficient to support all; or most, of the load connected to the micro-grid. This paper presents a micro-grid system based on wind and solar power sources and addresses issues related to operation, control, and stability of the system. Using Matlab/Simulink, the system is modeled and simulated to identify the relevant technical issues involved in the operation of a micro-grid system based on renewable power generation units.

Keywords: micro-grid system, photovoltaic, wind turbine, energy storage, distributed generation, modeling

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Authors: Sahar El Kasmi, Ayoub Aziz, Saadia Lharti, Mohammed El Janati, Boubker Boukili, Nacer El Motawakil, Mayom Chol Luka Awan

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Two types of geomaterials (Red Triassic clay from the Maaziz region and Yellow Pliocene clay from the Akrach region) were used to create different mixtures for the fabrication of ceramic bricks. This study investigated the influence of the Pliocene clay on the overall composition and mechanical properties of the Triassic clay. The red Triassic clay, sourced from Maaziz, underwent various mechanical processes and treatments to facilitate its transformation into ceramic bricks for construction. The triassic clay was subjected to a drying chamber and a heating chamber at 100°C to remove moisture. Subsequently, the dried clay samples were processed using a Planetary Babs ll Mill to reduce particle size and improve homogeneity. The resulting clay material was sieved, and the fine particles below 100 mm were collected for further analysis. In parallel, the Miocene marl obtained from the Akrach region was fragmented into finer particles and subjected to similar drying, grinding, and sieving procedures as the triassic clay. The two clay samples are then amalgamated and homogenized in different proportions. Precise measurements were taken using a weighing balance, and mixtures of 90%, 80%, and 70% Triassic clay with 10%, 20%, and 30% yellow clay were prepared, respectively. To evaluate the impact of Pliocene marl on the composition, the prepared clay mixtures were spread evenly and treated with a water modifier to enhance plasticity. The clay was then molded using a brick-making machine, and the initial manipulation process was observed. Additional batches were prepared with incremental amounts of Pliocene marl to further investigate its effect on the fracture behavior of the clay, specifically their resistance. The molded clay bricks were subjected to compression tests to measure their strength and resistance to deformation. Additional tests, such as water absorption tests, were also conducted to assess the overall performance of the ceramic bricks fabricated from the different clay mixtures. The results were analyzed to determine the influence of the Pliocene marl on the strength and durability of the Triassic clay bricks. The results indicated that the incorporation of Pliocene clay reduced the fracture of the triassic clay, with a noticeable reduction observed at 10% addition. No fractures were observed when 20% and 30% of yellow clay are added. These findings suggested that yellow clay can enhance the mechanical properties and structural integrity of red clay-based products.

Keywords: triassic clay, pliocene clay, mineralogical composition, geo-materials, ceramics, akach region, maaziz region, morocco.

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Authors: Olayinka Oduwole, Steve Sheard

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The magnetic separation of biological cells using super-magnetic beads has been used widely for various bioassays. These bioassays can further be integrated with other laboratory components to form a biosensor which can be used for cell sorting, mixing, purification, transport, manipulation etc. These bio-sensing applications have also been facilitated by the wide availability of magnetic beads which range in size and magnetic properties produced by different manufacturers. In order to improve the efficiency and separation capabilities of these biosensors, it is important to determine the magnetic force induced velocities and interaction of beads within the magnetic field; this will help biosensor users choose the desired magnetic bead for their specific application. This study presents for the first time the interaction between a pair of different sized super-paramagnetic beads suspended in a static fluid moving within a uniform magnetic field using a modified finite-time-finite-difference scheme. A captured video was used to record the trajectory pattern and a good agreement was obtained between the simulated trajectories and the video data. The model is, therefore, a good approximation for predicting the velocities as well as the interaction between various magnetic particles which differ in size and magnetic properties for bio-sensing applications requiring a low concentration of magnetic beads.

Keywords: biosensor, magnetic field, magnetic separation, super-paramagnetic bead

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Authors: Lin Dong-Yih, Yang S. M., Huang B. W., Lian J. A.

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Super duplex stainless steel has excellent mechanical properties and corrosion resistance. It becomes important structural material as its application has been extended to the fields such as renewable energy and the chemical industry because of its excellent properties. As examples are offshore wind power, solar cell machinery, and pipes in the chemical industry. The mechanical properties and corrosion resistance of super duplex stainless steel can be eliminated by welding due to the precipitation of the hard and brittle σ phase, which is rich of chromium, and molybdenum elements. This paper studies the influence of carbon element on the phase transformation of -ferrite and σ phase in 2507 super duplex stainless steel. The 2507 will be under argon gas protection welded with 316 and 316L extra low carbon stainless steel separately. The microstructural phases of stainless steels before and after welding, in fusion, heat affected zones, and base material will be studied via X-ray, OM, SEM, EPMA i.e. their quantity, size, distribution, and morphology. The influences of diffusion by carbon element will be compared according to the microstructures, hardness, and corrosion tests.

Keywords: complex stainless steel, welding, phase formation, carbon element, sigma phase, delta ferrite

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Authors: Kedar Hardikar, Joe Varghese

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Conductive adhesives have found wide-ranging applications in electronics industry ranging from fixing a defective conductor on printed circuit board (PCB) attaching an electronic component in an assembly to protecting electronics components by the formation of “Faraday Cage.” The reliability requirements for the conductive adhesive vary widely depending on the application and expected product lifetime. While the conductive adhesive is required to maintain the structural integrity, the electrical performance of the associated sub-assembly can be affected by the degradation of conductive adhesive. The degradation of the adhesive is dependent upon the highly varied use case. The conventional approach to assess the reliability of the sub-assembly involves subjecting it to the standard environmental test conditions such as high-temperature high humidity, thermal cycling, high-temperature exposure to name a few. In order to enable projection of test data and observed failures to predict field performance, systematic development of an acceleration factor between the test conditions and field conditions is crucial. Common acceleration factor models such as Arrhenius model are based on rate kinetics and typically rely on an assumption of linear degradation in time for a given condition and test duration. The application of interest in this work involves conductive adhesive used in an electronic circuit of a capacitive sensor. The degradation of conductive adhesive in high temperature and humidity environment is quantified by the capacitance values. Under such conditions, the use of established models such as Hallberg-Peck model or Eyring Model to predict time to failure in the field typically relies on linear degradation rate. In this particular case, it is seen that the degradation is nonlinear in time and exhibits a square root t dependence. It is also shown that for the mechanism of interest, the presence of moisture is essential, and the dominant mechanism driving the degradation is the diffusion of moisture. In this work, a framework is developed to incorporate nonlinear degradation of the conductive adhesive for the development of an acceleration factor. This method can be extended to applications where nonlinearity in degradation rate can be adequately characterized in tests. It is shown that depending on the expected product lifetime, the use of conventional linear degradation approach can overestimate or underestimate the field performance. This work provides guidelines for suitability of linear degradation approximation for such varied applications

Keywords: conductive adhesives, nonlinear degradation, physics of failure, acceleration factor model.

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Authors: Darya O. Prima, Elena V. Vorontsova, Yuri G. Slizhov, Andrey V. Zibarev

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A broad family of carbocycle-fluorinated aza-heterocycles including 1,3-benzodiazoles (benzimidazoles), 1,2,3-benzotriazoles, 2,1,3-benzothia/selenadiazoles and 1,4-benzodiazines (quinoxalines) was synthesized in the unified way and assessed for cytotoxicity towards the Hep2 (laryngeal epidermoid carcinoma, a kind of oral cancer) cells. The diazoles, triazoles and selenadiazoles revealed low medium inhibitory concentrations IC50 = 2.2-26.4 µМ and induced the cells’ apoptosis at low concentrations C = 1-25 µМ. For selenadiazoles, cell death dynamics was observed already in the first hours after the treatment. Replacement of one atom F by group Me2N in some cases enlarged apoptotic activity of the compounds towards the Hep2 cells. In contrast, the archetypal (i.e. non-fluorinated) 1,3-benzodiazole, 1,2,3-benzotriazole and 2,1,3-benzoselenadiazole were low toxic (IC50 > 100 µM) and induced apoptosis only at high concentrations. The chlorinated congeners of the heterocycles under discussion were highly toxic towards the Hep2 cells but revealed insignificant ability to induce their apoptosis. Overall, the findings above suggest that fluorinated 1,3-benzodiazole, 1,2,3-benzotriazole and 2,1,3-benzoselenadiazole derivatives can be considered as potential anticancer drugs. For the laryngeal epidermoid carcinoma (for which, according to available statistics, the five-year survival rate remained ~50% during the past 30 years), it is especially important since surgical treatment is seriously complicated here thus encouraging medicament one.

Keywords: Apoptosis, aza-heterocycles, cytotoxicity, fluorinated, Hep2 cells, synthesis

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Authors: Rafat M. Mohareb

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Several D-ring alkylated estrone analogues display exceptionally high affinity for estrogen receptors. In particular, compounds in which an E-ring is formed are known to be involved in the inhibition of steroidogenic enzymes. Such compounds also have an effect on steroid dehydrogenase activity and the ability to inhibit the detrimental action of the steroid sulfatase enzyme. Generally, E-ring extended steroids have been accessed by modification of the C17-ketone in the D-ring by either arylimine or oximino formation, addition of a carbon nucleophile or hydrazone formation. Other approaches have included ketone reduction, silyl enol ether formation or ring-closing metathesis (giving five- or six-membered E-rings). Chemical modification of the steroid D-ring provides a way to alter the functional groups, sizes and stereochemistry of the D-ring, and numerous structure-activity relationships have been established by such synthetic alterations. Steroids bearing heterocycles fused to the D-ring of the steroid nucleus have been of pharmaceutical interest. In the present paper, we report on the efficient synthesis of estrone possessing pyran, pyrimidine and thiazole ring systems. This study focused on the synthesis and biochemical evaluation of newly synthesized heterocyclic compounds which were then subjected through inhibitory evaluations towards human cancer and normal cell lines.

Keywords: estrone, heterocyclization, cytotoxicity, biomedicine

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Authors: Mohammad Hamed Asosheh

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The development of nanobiomaterials has opened new avenues in the field of biomedical engineering, offering unparalleled possibilities for advanced therapeutic applications. This study explores the synthesis and characterization of a distinct class of nanobiomaterials designed to enhance drug delivery systems and support tissue engineering. By integrating biodegradable polymers with bioactive nanoparticles, we have engineered a multifunctional platform that ensures controlled drug release, targeted delivery, and improved biocompatibility. Our findings demonstrate that these nanobiomaterials not only exhibit excellent mechanical properties but also promote cell proliferation and differentiation, making them ideal candidates for regenerative medicine. Furthermore, in vitro and in vivo assessments reveal that the engineered materials significantly reduce cytotoxicity while enhancing the therapeutic efficacy of encapsulated drugs. This research presents a promising approach to addressing current challenges in drug delivery and tissue regeneration, with the potential to revolutionize the treatment of chronic diseases and injury repair. Future work will focus on optimizing the material composition for specific clinical applications and conducting large-scale studies to evaluate long-term safety and effectiveness.

Keywords: nanobiomaterials, drug delivery systems, therapeutic efficacy, bioactive nanoparticles

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Authors: Gamze Karanfil Celep, Kevser Dincer

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The effects of polymer concentration and electrospinning process parameters on the average diameters of electrospun polyacrylonitrile (PAN) nanofibers were experimentally investigated. Besides, mechanical and thermal properties of PAN nanofibers were examined by tensile test and thermogravimetric analysis (TGA), respectively. For this purpose, the polymer concentration, solution feed rate, supply voltage and tip-to-collector distance were determined as the control factors. To succeed these aims, Taguchi’s L16 orthogonal design (4 parameters, 4 level) was employed for the experimental design. Optimal electrospinning conditions were defined using the signal-to-noise (S/N) ratio that was calculated from diameters of the electrospun PAN nanofibers according to "the-smaller-the-better" approachment. In addition, analysis of variance (ANOVA) was evaluated to conclude the statistical significance of the process parameters. The smallest diameter of PAN nanofibers was observed. According to the S/N ratio response results, the most effective parameter on finding out of nanofiber diameter was determined. Finally, the Taguchi design of experiments method has been found to be an effective method to statistically optimize the critical electrospinning parameters used in nanofiber production. After determining the optimum process parameters of nanofiber production, electrical conductivity and fuel cell performance of electrospun PAN nanofibers on the carbon papers will be evaluated.

Keywords: nanofiber, electrospinning, polyacrylonitrile, Taguchi method

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Authors: Abdul Matin, Salik Nawaz, Suk-Yul Jung

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Balamuthia mandrillaris is well known to cause fatal Balamuthia amoebic encephalitis (BAE). Amoebic transmission into the central nervous system (CNS), haematogenous spread is thought to be the prime step, followed by blood-brain barrier (BBB) dissemination. Macrophages are considered to be the foremost line of defense and present in excessive numbers during amoebic infections. The aim of the present investigation was to evaluate the effects of macrophages alone or primed with cytokines on the biological characteristics of Balamuthia in vitro. Using human brain microvascular endothelial cells (HBMEC), which constitutes the BBB, we have shown that Balamuthia demonstrated > 90% binding and > 70% cytotoxicity to host cells. However, macrophages further increased amoebic binding and Balamuthia-mediated cell cytotoxicity. Furthermore, macrophages exhibited no amoebicidal effect against Balamuthia. Zymography assay demonstrated that macrophages exhibited no inhibitory effect on proteolytic activity of Balamuthia. Overall, to our best knowledge, we have shown for the first time macrophages has no inhibitory effects on the biological properties of Balamuthia in vitro. This also strengthened the concept that how and why Balamuthia can cause infections in both immuno-competent and immuno-compromised individuals.

Keywords: Balamuthia mandrillaris, macrophages, cytokines, human brain microvascular endothelial cells, Balamuthia amoebic encephalitis

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Authors: K. Veluraja

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Glycan of glycolipids and glycoproteins is playing a significant role in living systems particularly in molecular recognition processes. Molecular recognition processes are attributed to their occurrence on the surface of the cell, sequential arrangement and type of sugar molecules present in the oligosaccharide structure and glyosidic linkage diversity (glycoinformatics) and conformational diversity (glycoconformatics). Molecular Dynamics Simulation study is a theoretical-cum-computational tool successfully utilized to establish glycoconformatics of glycan. The study on various oligosaccharides of glycan clearly indicates that oligosaccharides do exist in multiple conformational states and these conformational states arise due to the flexibility associated with a glycosidic torsional angle (φ,ψ) . As an example: a single disaccharide structure NeuNacα(2-3) Gal exists in three different conformational states due to the differences in the preferential value of glycosidic torsional angles (φ,ψ). Hence establishing three dimensional structural and conformational models for glycan (cartesian coordinates of every individual atoms of an oligosaccharide structure in a preferred conformation) is quite crucial to understand various molecular recognition processes such as glycan-toxin interaction and glycan-virus interaction. The gycoconformatics models obtained for various glycan through Molecular Dynamics Simulation stored in our 3DSDSCAR (3DSDSCAR.ORG) a public domain database and its utility value in understanding the molecular recognition processes and in drug design venture will be discussed.

Keywords: glycan, glycoconformatics, molecular dynamics simulation, oligosaccharide

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Authors: Dita Mayasari, Zahrina Mardina, Riki Siswanto, Agresta Ifada, Ova Oktavina, Prihartini Widiyanti

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Heart failure is a serious major health problem with high number of mortality per year. Bypass is one of the solutions that has often been taken. Natural vascular graft (xenograft) as the substitute in bypass is inconvenient due to ethic problems and the risk of infection transmission caused by the usage of another species transgenic vascular. Nowadays, synthetic materials have been fabricated from polymers. The aim of this research is to make a synthetic vascular graft with great physical strength, high biocompatibility, and good affordability. The method of this research was mixing PLGA and collagen by magnetic stirrer. This composite were shaped by spinneret with water as coagulant. Then it was coated by chitosan with 3 variations of weight (1 gram, 2 grams, and 3 grams) to increase hemo and cytocompatibility, proliferation, and cell attachment in order for the vascular graft candidates to be more biocompatible. Mechanical strength for each variation was 5,306 MPa (chitosan 1 gram), 3,433 MPa (chitosan 2 grams) and 3,745 MPa (chitosan 3 grams). All the tensile values were higher than human vascular tensile strength. Toxicity test showed that the living cells in all variations were more than 60% in number, thus the vascular graft is not toxic.

Keywords: chitosan, collagen, PLGA, spinneret

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Authors: Chin-Yuan Hsu, Yu-Lung Chuang

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The expression, concentration, and activity of mitochondrial energy-utilized molecules and cellular energy-regulated molecules decreased with age in the trophocytes and oenocytes of honeybees (Apis mellifera), but those of cellular energy-metabolized molecules is unknown. In this study, the expression, concentration, and activity of cellular energy-metabolized molecules were assayed in the trophocytes and fat cells of young and old worker bees by using the techniques of cell and biochemistry. The results showed that (i) the •-hydroxylacyl-coenzyme A dehydrogenase (HOAD) activity/citrate synthase (CS) activity ratio, non-esterified fatty acids concentrations, the expression of eukaryotic initiation factor 4E, and the expression of phosphorylated eIF4E binding protein 1 decreased with age; (ii) fat and glycogen accumulation increased with age; and (iii) the pyruvate dehydrogenase (PDH) activity/citrate synthase (CS) activity ratio was not correlated with age. These finding indicated that •-oxidation (HOAD/CS) and protein synthsis decreased with age. Glycolysis (PDH/CS) was unchanged with age. The most likely reason is that sugars are the vital food of worker bees. Taken together these data reveal that young workers have higher cellular energy metabolism than old workers and that aging results in a decline in the cellular energy metabolism in worker honeybees.

Keywords: aging, energy, honeybee, metabolism

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Authors: Reynaldo Esquivel, Pedro Hernandez, Aaron Martinez-Higareda, Sergio Tena-Cano, Enrique Alvarez-Ramos, Armando Lucero-Acuna

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Stimuli-responsive nanomaterials play an essential role in loading, transporting and well-distribution of anti-cancer compounds in the cellular surroundings. The outstanding properties as the Lower Critical Solution Temperature (LCST), hydrolytic cleavage and protonation/deprotonation cycle, govern the release and delivery mechanisms of payloads. In this contribution, we experimentally determine the load efficiency and release of antineoplastic Vincristine Sulfate into PNIPAM-Interpenetrated-Chitosan (PIntC) nanoparticles. Structural analysis was performed by Fourier Transform Infrared Spectroscopy (FT-IR) and Proton Nuclear Magnetic Resonance (1HNMR). ζ-Potential (ζ) and Hydrodynamic diameter (DH) measurements were monitored by Electrophoretic Mobility (EM) and Dynamic Light scattering (DLS) respectively. Mathematical analysis of the release pharmacokinetics reveals a three-phase model above LCST, while a monophasic of Vincristine release model was observed at 32 °C. Cytotoxic essays reveal a noticeable enhancement of Vincristine effectiveness at low drug concentration on HeLa cervix cancer and MDA-MB-231 breast cancer.

Keywords: nanoparticles, vincristine, drug delivery, PNIPAM

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Authors: Naif Mohsen Alharbi

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This paper present failure occurred on flexible coupling installed at oil anf gas operation. Also it presents maintenance ideas implemented on the flexible coupling installed to transmit high torque from gearbox to pump. Basically, the machine train is including steam turbine which drives the pump and there is gearbox located in between for speed reduction. investigation are identifying the root causes, solving and developing the technology designs or bad actor. This report provides the study intentionally for continues operation optimization, utilize the advanced opportunity and implement a improvement. Objective: The main objectives of the investigation are identifying the root causes, solving and developing the technology designs or bad actor. Ultimately, fulfilling the operation productivity, also ensuring better technology, quality and design by solutions. This report provides the study intentionally for continues operation optimization, utilize the advanced opportunity and implemet improvement. Method: The method used in this project was a very focused root cause analysis procedure that incorporated engineering analysis and measurements. The analysis method extensively covers the measuring of the complete coupling dimensions. Including the membranes thickness, hubs, bore diameter and total length, dismantle flexible coupling to diagnose how deep the coupling has been affected. Also, defining failure modes, so that the causes could be identified and verified. Moreover, Vibration analysis and metallurgy test. Lastly applying several solutions by advanced tools (will be mentioned in detail). Results and observation: Design capacity: Coupling capacity is an inadequate to fulfil 100% of operating conditions. Therefore, design modification of service factor to be at least 2.07 is crucial to address this issue and prevent recurrence of similar scenario, especially for the new upgrading project. Discharge fluctuation: High torque flexible coupling encountered during the operation. Therefore, discharge valve behaviour, tuning, set point and general conditions revaluated and modified subsequently, it can be used as baseline for upcoming Coupling design project. Metallurgy test: Material of flexible coupling membrane (discs) tested at the lab, for a detailed metallurgical investigation, better material grade has been selected for our operating conditions,

Keywords: high speed machine, reliabilty, flexible coupling, rotating equipment

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Authors: Mari Murakami, Hiromi Kawasaki, Saori Fujimoto, Yoko Ueno

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Background: In Japan, one of the goals of midwifery education is the development of one’s ability to comprehensively support the child-rearing generation in collaboration with professionals from other disciplines. However, in order to prevent the spread of Covid-19, it has become extremely difficult to provide face-to-face support for mothers and children. Early on in the pandemic, we sought help from three parenting midwives as an alternative and attempted an online visit. Since midwives who are raising children respond to the training as both mothers who are care recipients and midwives as care providers. Therefore, we attempted to verify the usefulness of midwives experiencing training as mothers by clarifying the effects on those midwives who are raising children and who have experienced online visit training by students. Methods: The online visitations were conducted in June 2020. The collaborators were three midwives who were devoted to childcare. During the online visit training, we used the feedback records of their questions given by the collaborators (with their permission) to the students. The verbatim record was created from the records. Qualitative descriptive analysis was used, and subcategories and categories were extracted. This study was approved by the Ethical Committee for Epidemiology of Hiroshima University. Results: The average age of the three midwives was 36.3 years, with an average of 12.3 years of experience after graduation. They were each raising multiple children (ranging between a minimum of 2 and a maximum of 4 children). Their youngest infants were 6.7 months old on average for all. Five categories that emerged were: contributing to the development of midwifery students as a senior; the joy of accepting the efforts of a mother while raising children; recalling the humility of beginners through the integrity of midwifery students; learning opportunities about the benefits of online visits; and suggesting further challenges for online visits. Conclusion: The online visit training was an opportunity for midwives who are raising their own children to reinforce an honest and humble approach based on the attitude of the students, for self-improvement, and to reflect on the practice of midwifery from another person’s viewpoint. It was also noted that the midwives contributed to the education of midwifery students. Furthermore, they also agreed with the use of online visitations and considered the advantages and disadvantages of its use from the perspective of mothers and midwives. Online visits were seen to empower midwives on childcare leave, as their child-rearing was accepted and admired. Online visits by students were considered to be an opportunity to not only provide a sense of fulfillment as a recipient of care but also to think concretely about career advancement, during childcare leave, regarding the ideal way for midwifery training and teaching.

Keywords: child-rearing midwife, COVID-19 pandemic, online visit practice, qualitive descriptive study

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Authors: Priya Jaswal, Vivek, S. K. Sinha

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One of the most important and complicated factors influencing the functional performance of unpaved roads is traffic loading. The complexity of traffic loading is caused by the variable magnitude and frequency of load, which causes unpaved roads to fail prematurely. Unpaved roads are low-volume roads, and as peri-urbanization increases, unpaved roads act as a means to boost the rural economy. This has also increased traffic on unpaved roads, intensifying the issue of settlement, rutting, and fatigue failure. This is a major concern for unpaved roads built on poor subgrade soil, as excessive rutting caused by heavy loads can cause driver discomfort, vehicle damage, and an increase in maintenance costs. Some researchers discovered that when a consistent static load is exerted as opposed to a rapidly changing load, the rate of deformation of unpaved roads increases. Previously, some of the most common methods for overcoming the problem of rutting and fatigue failure included chemical stabilisation, fibre reinforcement, and so on. However, due to their high cost, engineers' attention has shifted to geotextiles which are used as reinforcement in unpaved roads. Geotextiles perform the function of filtration, lateral confinement of base material, vertical restraint of subgrade soil, and the tension membrane effect. The use of geotextiles in unpaved roads increases the strength of unpaved roads and is an economically viable method because it reduces the required aggregate thickness, which would need less earthwork, and is thus recommended for unpaved road applications. The majority of geotextiles used previously were polymeric, but with a growing awareness of sustainable development to preserve the environment, researchers' focus has shifted to natural fibres. Coir is one such natural fibre that possesses the advantage of having a higher tensile strength than other bast fibres, being eco-friendly, low in cost, and biodegradable. However, various researchers have discovered that the surface of coir fibre is covered with various impurities, voids, and cracks, which act as a plane of weakness and limit the potential application of coir geotextiles. To overcome this limitation, chemical surface modification of coir geotextiles is widely accepted by researchers because it improves the mechanical properties of coir geotextiles. The current paper reviews the effect of using treated coir geotextiles as reinforcement on the load-deformation behaviour of a two-layered unpaved road model.

Keywords: coir, geotextile, treated, unpaved

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Authors: Elena G. Salina, Vadim A. Makarov

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With the emergence of primary resistance to the current drugs and wide distribution of latent tuberculosis infection, a need for new compounds with a novel mode of action is growing steadily. Copper-mediated innate immunity and antibacterial toxicity propose novel strategies in TB drug discovery and development. Transcriptome of M. tuberculosis was obtained by RNA-seq, intracellular copper content was measured by ISP MS and complexes of 1-hydroxy-2-thiopyridines with copper were detected by HPLC.1-hydroxy-2-thiopyridine derivatives were found to be highly active in vitro against both actively growing and dormant non-culturable M. tuberculosis. Transcriptome response to 1-hydroxy-2-thiopyridines revealed signs of copper toxicity in M. tuberculosis bacilli. Indeed, Cu was found to accumulate inside cells treated with 1-hydroxy-2-thiopyridines. These compounds were found to form stable charged lipophylic complexes with Cu²⁺ ions which transport into mycobacterial cell. Subsequent metabolic destruction of the complex led to transformation of 1-hydroxy-2-thiopyridines into 2-methylmercapto-2-ethoxycarbonylpyridines, which did not possess antitubercular activity and releasing of free Cu²⁺ in the cytoplasm. 1-hydroxy-2-thiopyridines are a potent class of Cu-dependent inhibitors of M. tuberculosis which may control M. tuberculosis infection by impairment of copper homeostasis. Acknowledgment: This work was financially supported by the Ministry of Education and Science of the RussianFederation (Agreement No 14.616.21.0065; unique identifier RFMEFI61616X0065).

Keywords: copper toxicity, drug discovery, M. tuberculosis inhibitors, 2-thiopyridines

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Authors: Junkyeong Kim, Jooyoung Park, Aoqi Zhang, Seunghee Park

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The tensile force of Pre-Stressed Concrete (PSC) girder is the most important factor for evaluating the performance of PSC girder bridges. To measure the tensile force of PSC girder, several NDT methods were studied. However, conventional NDT method cannot be applied to the real-size PSC girder because the PS tendons could not be approached. To measure the tensile force of real-size PSC girder, this study proposed embedded EM sensor based tensile force estimation method. The embedded EM sensor could be installed inside of PSC girder as a sheath joint before the concrete casting. After curing process, the PS tendons were installed, and the tensile force was induced step by step using hydraulic jacking machine. The B-H loop was measured using embedded EM sensor at each tensile force steps and to compare with actual tensile force, the load cell was installed at each end of girder. The magnetization energy loss, that is the closed area of B-H loop, was decreased according to the increase of tensile force with regular pattern. Thus, the tensile force could be estimated by the tracking the change of magnetization energy loss of PS tendons. Through the experimental result, the proposed method can be used to estimate the tensile force of the in-situ real-size PSC girder bridge.

Keywords: tensile force estimation, embedded EM sensor, magnetization energy loss, PSC girder

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Authors: Matthew E. Potter, Daniel J. Stewart, Lindsay M. Armstrong, Pier J. A. Sazio, Robert R. Raja

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Rising CO₂ levels in the atmosphere means that CO₂ is a highly desirable feedstock. This requires specific catalysts to be designed to activate this inert molecule, combining a catalytic site tailored for CO₂ transformations with a support that can readily adsorb CO₂. Metal organic frameworks (MOFs) are regularly used as CO₂ sorbents. The organic nature of the linker molecules, connecting the metal nodes, offers many post-synthesis modifications to introduce catalytic active sites into the frameworks. However, the metal nodes may be coordinatively unsaturated, allowing them to bind to organic moieties. Imidazoles have shown promise catalyzing the formation of cyclic carbonates from epoxides with CO₂. Typically, this synthesis route employs toxic reagents such as phosgene, liberating HCl. Therefore an alternative route with CO₂ is highly appealing. In this work we design active sites for CO₂ activation, by tethering substituted-imidazole organocatalytic species to the available Cr3+ metal nodes of a Cr-MIL-101 MOF, for the first time, to create a tailored species for carbon capture utilization applications. Our tailored design strategy combining a CO₂ sorbent, Cr-MIL-101, with an anchored imidazole results in a highly active and selective multifunctional catalyst, achieving turnover frequencies of over 750 hr-1. These findings demonstrate the synergy between the MOF framework and imidazoles for CO₂ utilization applications. Further, the effect of substrate variation has been explored yielding mechanistic insights into this process. Through characterization, we show that the structural and compositional integrity of the Cr-MIL-101 has been preserved on functionalizing the imidazoles. Further, we show the binding of the imidazoles to the Cr3+ metal nodes. This can be seen through our EPR study, where the distortion of the Cr3+ on binding to the imidazole shows the CO₂ binding site is close to the active imidazole. This has a synergistic effect, improving catalytic performance. We believe the combination of MOF support and organocatalyst allows many possibilities to generate new multifunctional catalysts for CO₂ utilisation. In conclusion, we have validated our design procedure, combining a known CO₂ sorbent, with an active imidazole species to create a unique tailored multifunctional catalyst for CO₂ utilization. This species achieves high activity and selectivity for the formation of cyclic carbonates and offers a sustainable alternative to traditional synthesis methods. This work represents a unique design strategy for CO₂ utilization while offering exciting possibilities for further work in characterization, computational modelling, and post-synthesis modification.

Keywords: carbonate, catalysis, MOF, utilisation

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