BACKGROUND: Preclinical drug testing requires in vitro and in vivo assessments that are vital for studying drug pharmacokinetics and toxicity. Distinct factors that play an important role in drug screening, such as hydrophobicity, solubility of the substance and serum protein binding can be challenging by inducing result inconsistencies. Hence, establishing accurate methods to quantify drug concentrations in cell cultures becomes pivotal for reliable and reproducible results important for in vivo dosing predictions. OBJECTIVE: This research focuses on developing an optimized analytical approach via high-pressure liquid chromatography (HPLC) to determine thymoquinone (TQ) levels in monolayer cell cultures. METHODS: The method’s validation adheres to the International Council for Harmonisation (ICH) guideline M10, ensuring its acceptance and applicability. Using an HPLC system with a Diode Array Detector (DAD), the study fine-tuned various parameters to achieve an efficient separation of TQ. Validation covered specificity, sensitivity, matrix effects, linearity, precision, and accuracy, alongside assessing TQ stability in RPMI-1640 medium. RESULTS: The HPLC method exhibited remarkable TQ specificity, free from interfering peaks at the analyte retention. Sensitivity analysis at the lower limit of quantification (LLOQ) revealed 5.68% %CV and 98.37% % mean accuracy. Matrix effect evaluation showcased accuracy within 85–115%. Linearity spanned in the concentration range of 2–10 μ M with a correlation coefficient ( r 2 ) of 0.9993. Precision and accuracy were aligned with acceptance criteria. The proposed method was found to be greener in terms of usage of persistent, bioaccumulative, and toxic chemicals and solvents, corrosive samples, and waste production. CONCLUSION: The developed HPLC-DAD method emerges as specific, accurate, sensitive, and reliable for TQ determination in cell cultures. It ensures robust TQ quantification, enhancing precise in vitro assessments and dependable dosing predictions for in vivo studies. Further research is advocated to investigate TQ’s stability across diverse environmental conditions.
This paper studies the stabilization problem of networked control systems (NCSs) with random packet dropouts caused by stochastic channels. To describe the effects of stochastic channels on the information transmission, the transmission times are assumed to be deterministic, whereas the packet transmission is assumed to be random. We first propose a stochastic scheduling protocol to model random packet dropouts, and address the properties of the proposed stochastic scheduling protocol. The proposed scheduling protocol provides a unified modelling framework for a general class of random packet dropouts due to different stochastic channels. Next, the proposed scheduling protocol is embedded into the closed-loop system, which leads to a stochastic hybrid model for NCSs with random packet dropouts. Based on this stochastic hybrid model, we follow the emulation approach to establish sufficient conditions to guarantee uniform global asymptotical stability in probability. In particular, an upper bound on the maximally allowable transmission interval is derived explicitly for all stochastic protocols satisfying Lyapunov conditions that guarantee uniform global asymptotic stability in probability. Finally, two numerical examples are presented to demonstrate the derived results.
While the topic of sustainable development has been extensively explored, there is a lack of quantitative assessment of economic sustainability in the scientific literature; moreover, the term is often interpreted with excessive attention to the environment but not socio-economic inequality. In addition, university cities are often considered the most sustainable, although the higher education system in the United States is often criticized for the inequality of access to it among different racial and other groups of the population. This paper adds to the debate about how the concepts of sustainability and economic development relate. Many researchers have noted that they come into conflict with each other because their ultimate goals are fundamentally different: a voluntary limitation of production and consumption in the interests of future generations and, conversely, the pursuit of well-being during our lives. We would like to explore the issue of economic sustainability, which, at first glance, may become a compromise between the two approaches outlined above. So, our study is devoted to exploring the ambiguous concept of economic sustainability, which can add some new knowledge to the understanding of how social, economic, and ecological factors relate to each other in the broader framework of sustainability. For this objective, we analyzed the economic sustainability of the town of Amherst, MA. The city’s top employer and core enterprise is the University of Massachusetts Amherst, with over 32,000 students and almost 2000 staff members. Based on a literature review, a hypothesis was put forward that a university city should have a high level of economic sustainability. To assess economic sustainability, the original methodology based on the US Cities Economic Sustainability Index (USCESI) was developed. It evaluates sustainability in three groups of parameters: society, economy, and ecology. The first group includes the level of racial diversity, the level of education of the population, and the access to medical services. The second group consists of the Gini coefficient by income level, the median cost of housing, and the unemployment rate. The environmental situation is assessed according to the Air Quality Index developed by the US Environmental Protection Agency. For comparison, the town of Braintree, MA, was chosen. As a result of the study, the USCESI was calculated for both locations. The analysis showed that both Amherst and Braintree have a high degree of economic sustainability. However, it was revealed that proximity to a significant economic center has a more powerful positive impact on economic sustainability than the location of a large university. In our paper, we proposed a new methodology for measuring economic sustainability with a special focus on inequality as a major problem in American society. The findings provide new knowledge about university cities and debunk the myth that they represent an exception to the general logic of urban development in the United States. A similar approach, with clarification of statistical indicators and a different emphasis, can be applied to other countries where inequality may be the main threat to economic sustainability, not in terms of access to higher education but in other areas.
Background Isoprenaline (ISO), a synthetic catecholamine and a β-adrenoceptor agonist, is widely used to develop an experimental model of myocardial injury (MI) in rats. The leading hypothesis for ISO-induced MI in rats is that it results from catecholamine overstimulation, oxidative stress, inflammatory responses, and development of cardiomyopathy during ISO administration. Folic acid (FA) reduces oxidative stress, improves endothelial function and prevents apoptosis, thereby contributing to cardiovascular protection. This study aimed to investigate the potentially protective effect of FA pretreatment on ISO-induced MI in rats. Methods For 7 days, adult male Wistar albino rats were pretreated with 5 mg/kg/day of FA. On the sixth and seventh days, MI in rats was induced by administering 85 mg/kg/day of ISO. Prooxidant markers in plasma samples, antioxidant capacity in erythrocyte lysates, cardiac damage markers, lipid profile, electrocardiography (ECG) and histopathological analysis were evaluated. Results FA pretreatment significantly alleviated changes induced by ISO; it decreased the homocysteine and high-sensitivity troponin I level. FA moderately decreased the reactive oxygen species (ROS) levels (superoxide anion radical, hydrogen peroxide and thiobarbituric acid reactive substances) and improved the antioxidant activities of catalase, superoxide dismutase and reduced glutathione. ISO reduced the nitrite level and FA significantly alleviated this change. Conclusion It can be concluded that FA, as a mild antioxidant, could be an appropriate cardioprotective substance in the rat model of ISO-induced MI.
Metal additive manufacturing (AM) is gaining traction but raises worker health concerns due to micron‐sized powders, including fine inhalable particles. This study explored particle and surface characteristics, electrochemical properties, metal release in artificial lysosomal fluid (ALF), and potential toxicity of virgin and sieved virgin Fe‐based powders, stainless steel (316L), Fe, and two tooling steels. Virgin particles ranged in size from 1 to 100 µm, while sieved particles were within the respirable size range (<5–10 µm). Surface oxide composition differed from bulk composition. The Fe powder showed low corrosion resistance and high metal release due to a lack of protective surface oxide. Sieved particles of 316L, Fe, and one tooling steel released more metals into ALF than virgin particles, with the opposite was observed for the other tooling steel. Sieved particles had no notable impact on cell viability or micronuclei formation in human bronchial epithelial cells. Inflammatory response in human macrophages was generally low, except for the Fe powder and one tooling steel, which induced increased interleukin‐8 (IL‐8/CXCL‐8) and monocyte chemoattractant protein‐1 (MCP‐1/CCL‐2) secretion. This study underscores distinctions between virgin and sieved Fe‐based powders and suggests relatively low acute toxicity.
Digitalizacija je utjecala na brojne segmente naših života, pa i na naše medijske preferencije. U aktuelnom komunikacijskom univerzumu bilo ko prema bilo kome (eng. any to any), omogućeno nam je da sami “pakujemo svoj medijski paket” i budemo (pro)aktivni učesnik u protoku informacija u javnom prostoru i interakciji sa medijima. S ciljem propitivanja koje medije i ostale informacijsko-komunikacijske tehnologije koriste bosanskohercegovački građani, iz kojih izvora se najčešće informišu, te kakva je njihova interakcija sa medijima u digitalnom dobu, provedeno je istraživanje stavova građana Bosne i Hercegovine (N=937). Istraživanje je pokazalo da medijske publike sve više migriraju u online sferu i da se bosanskohercegovački građani najčešće informišu iz online izvora i medija. Sa druge strane, nisu baš aktivni u interakciji sa medijima, dakle, ne iskorištavaju u dovoljnoj mjeri prednosti koje im se kao recipijentima medijskih sadržaja nude u digitalnom dobu.
We demonstrate a real-time, converged 5G-PON through the Cooperative Transport Interface, synchronising 5G and PON-DBA upstream schedulers. This innovative approach, implemented using 5G and PON open network implementations, significantly enhances network resource allocation, reducing latency.
BACKGROUND AND PURPOSE: Potential utility of flat panel CT perfusion imaging (FPCT-PI) performed immediately after mechanical thrombectomy (MT) is unknown. We aimed to assess whether FPCT-PI obtained directly post-MT could provide additional potentially relevant information on tissue reperfusion status. MATERIALS AND METHODS: This was a single-center analysis of all patients with consecutive acute stroke admitted between June 2019 and March 2021 who underwent MT and postinterventional FPCT-PI (n = 26). A core lab blinded to technical details and clinical data performed TICI grading on postinterventional DSA images and qualitatively assessed reperfusion on time-sensitive FPCT-PI maps. According to agreement between DSA and FPCT-PI, all patients were classified into 4 groups: hypoperfusion findings perfectly matched by location (group 1), hypoperfusion findings mismatched by location (group 2), complete reperfusion on DSA with hypoperfusion on FPCT-PI (group 3), and hypoperfusion on DSA with complete reperfusion on FPCT-PI (group 4). RESULTS: Detection of hypoperfusion (present/absent) concurred in 21/26 patients. Of these, reperfusion findings showed perfect agreement on location and size in 16 patients (group 1), while in 5 patients there was a mismatch by location (group 2). Of the remaining 5 patients with disagreement regarding the presence or absence of hypoperfusion, 3 were classified into group 3 and 2 into group 4. FPCT-PI findings could have avoided TICI overestimation in all false-positive operator-rated TICI 3 cases (10/26). CONCLUSIONS: FPCT-PI may provide additional clinically relevant information in a considerable proportion of patients undergoing MT. Hence, FPCT-PI may complement the evaluation of reperfusion efficacy and potentially inform decision-making in the angiography suite.
Crystal plasticity (CP) model is a vital tool for understanding structure–property relations, but it is computationally expensive. Hence, data-driven models have been used as surrogate. We proposed a Deep Operator Network (DeepONet) to predict polycrystal stress–strain response. It employs a convolutional network to encode microstructure. To account for different material properties and boundary conditions, we proposed using single-crystal responses as inputs to the branch, furnishing a material-response-informed DeepONet. This is the most novel contribution. We demonstrate that our model can be trained on one material and loading and generalized to new conditions via transfer learning. Results show that using single-crystal responses as input outperforms a similar model using material properties and overcomes limitations with changing boundary conditions. The new model achieved a R2\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$R^2$$\end{document} value of above 0.99, and over 95% of predicted stresses have a relative error of ≤\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\le $$\end{document} 5%, indicating superior accuracy. With as few as 20 new data and under 1 min training time, the DeepONet can be fine-tuned to generate accurate predictions on different materials and loadings. The prediction speed is 104\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$10^{4}$$\end{document} times faster than CP simulations. The efficiency and generalizability of DeepONet render it a powerful data-driven surrogate to bridge scale gaps in multi-scale analyses.
We propose a unique topological portal between quantum chromodynamics (QCD) and a dark sector characterized by a global symmetry breaking, which connects three QCD to two dark pions. When gauged, it serves as the leading portal between the two sectors, providing an elegant, self-consistent scenario of light thermal inelastic dark matter. The inherent antisymmetrization leads to diminished annihilations at later times and suppressed direct detection. However, novel collider signatures offer tremendous prospects for discovery at Belle II.
Solvent and substitution effects on the UV/Vis spectroscopic and fluorescence behaviour of seven synthesized 3-substituted 4-hydroxycoumarin derivatives were tested. The tested compounds were dissolved in ethyl acetate, acetonitrile, and dimethyl sulfoxide. Absorption and emission spectra were recorded in the range of 200–800 nm. All tested 4-hydroxycoumarin derivatives showed good absorption in a wide range of 200–550 nm, depending on the properties of the substituents on the benzene ring of the cinnamoyl moiety and the type of solvent. In comparison to the unsubstituted analogue, compounds with an electron-donating group exhibited bathochromically shifted UV/Vis absorption and emission spectra. The highest fluorescence quantum yield was observed for compounds with dimethylamino and acetamido groups as substituents at the benzene ring. Considering that both substitution and solvent affect the absorption and emission spectra of the tested compounds, it can be concluded that judiciously selecting these parameters can improve their absorption and fluorescence properties, making them suitable for various analytical uses.
Tracer testing in reservoir formations is utilised to determine residual oil saturation as part of optimum hydrocarbon production. Here, we present a novel detection method of liquid organic compounds by monodisperse SiO2 nanoparticles (NPs) containing two luminophores, a EuIII:EDTA complex and a newly synthesised fluorophore based on the organic boron-dipyrromethene (BODIPY)-moiety. The particles exhibited stable EuIII PL emission intensity with a long lifetime in aqueous dispersion. The fluorescence of the BODIPY was also preserved in the aqueous environment. The ratiometric PL detection technique was demonstrated by using toluene and 1-octanol as model compounds of crude oil. The optimal synthesis conditions were found to give NPs with a diameter of ~ 100 nm, which is suitable for transport through porous oil reservoir structures. The cytotoxicity of the NPs was confirmed to be very low for human lung cell and fish cell lines. These findings demonstrate the potential of the NPs to replace the hazardous chemicals used to estimate the residual oil saturation. Moreover, the ratiometric PL detection technique is anticipated to be of benefit in other fields, such as biotechnology, medical diagnostics, and environmental monitoring, where a reliable and safe detection of a liquid organic phase is needed.
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