Search Results (270)

The continuous-flow technologies in organic synthesis for the production of active pharmaceutical ingredients (APIs) are nowadays more and more applied. In-silico process design is a powerful tool able to support organic synthesis in the field of scale-up and process development. Process design feasibility and reliability depend on the availability of a well-defined chemical reaction kinetic scheme, information which is usually derived from experimental datasets collected on purpose. The latter approach is time-consuming and demanding in terms of resources. Different possibilities are here proposed to valorize widely available experimental data from explorative works with different approaches, depending on the nature, richness, and structure of the datasets. The kinetic parameters (i.e., reaction order, kinetic constant, and activation energy) of some interesting organic reactions have been approximately estimated by applying different computational methodologies, thanks to built-in experimental databases. The numerical algebra approach dealing with linear and non-linear regression analysis for the kinetic parameters has been initially considered and related to the database information for oseltamivir synthesis. The Bayesian statistic was applied to the ibuprofen case through the application of the Markov Chain Monte Carlo (MCMC) method for reaction order estimation. At last, a Machine Learning (ML) approach has been applied to the Rolipram and Pregabalin case study. The in-house developed T-ReX experimental kinetic constant database was exploited, with application of the k-Nearest neighbor algorithm for classification and regular expression pattern recognition. Advantages and limitations of the three approaches are discussed. Full article

Background: In 2024, Reddit, an emerging social media platform, saw a 50% increase in monthly users to nearly 100 million. Reddit has also emerged as a significant space for discussions about health conditions, including epilepsy, which affects about 50 million people globally. Purpose: This study aims to explore trends in the volume, timing, themes, emotional tone, and sentiment of posts on the r/Epilepsy subreddit from 1 December 2023 to 31 December 2024. Methods: We collected 25,222 original English-language posts from r/Epilepsy using Reddit’s Application Programming Interface (API). Data extraction was restricted to English-language submissions to ensure compatibility with sentiment and thematic analyses. We analyzed post volume and timing using chi-square tests and Poisson regression. Emotional tone was measured using TextBlob (version 0.19.0), while compound sentiment scores were calculated via VADER (Valence Aware Dictionary and Sentiment Reasoner) (NLTK version 3.9.1). A Pearson correlation assessed agreement between sentiment and emotional tone, with statistical significance set at p < 0.05. Thematic analysis was conducted using a KMeans clustering algorithm (scikit-learn version 1.6.1) to identify recurring discussion topics. Results: Total monthly posts steadily increased, with the highest number (2175) in December 2024. Peak posts in descending order were in December 2024, August 2024, and November 2024. Posts were not evenly distributed across the week, with a significant peak on Mondays (χ² = 86.75, p < 0.001) and Poisson regression confirming higher activity early in the week (p = 0.001). Emotional tones fluctuated, with positive sentiments in January and October 2024, and negative sentiments in March and August 2024. KMeans clustering identified five main themes: treatment experiences, community engagement, personal experiences, solidarity, and subreddit gratitude. Manual validation of a random subset of posts demonstrated moderate concordance between automated sentiment classification and human ratings. Conclusions: This study highlights temporal patterns, sentiment dynamics, and thematic structure in online discussions on epilepsy. Social media may offer valuable, real-time insights into patient-centered concerns and community engagement, which can inform healthcare professionals and advocacy groups in supporting individuals affected by epilepsy. Future studies may compare trends of epilepsy discussions across various social media platforms, such as X and Instagram, to further understand online patient experiences. Full article

The Failure Assessment Diagram (FAD), as a significant method for evaluating the suitability of defective metallic structures, has been subject to considerable debate regarding its applicability in assessing ring welded joints for high-grade steel and large-diameter pipelines. To address this issue, this study first designed and conducted two sets of full-scale pressure-tension tests on large-diameter X80 pipeline ring welded joints, considering factors such as different welding processes, joint configurations, defect dimensions, and locations. Subsequently, three widely adopted failure assessment diagram methodologies—BS 7910, API 579, and API 1104—were selected. Corresponding assessment curves were established based on material performance parameters obtained from the ring weld tests. Finally, predictive outcomes from each assessment method were compared against experimental data to investigate the applicability of failure assessment diagrams for evaluating high-strength, large-diameter, thick-walled ring welds. The research findings indicate that, under the specific material and defect assessment conditions employed in this study, the API 1104 assessment results exhibited significant conservatism (two sets matched). Conversely, the BS 7910 and API 579 assessment results showed a high degree of agreement with the experimental data (eight sets matched), with the BS 7910 assessment providing a relatively higher safety margin compared to API 579. The data from this study provides valuable experimental reference for selecting assessment methods under specific conditions, such as similar materials, defects, and loading patterns. Full article

Canagliflozin (CFZ), a sodium–glucose cotransporter 2 (SGLT2) inhibitor, is extensively utilized in the management of type 2 diabetes. Among its various polymorphic forms, the hemi-hydrate (Hemi-CFZ) has been selected as the active pharmaceutical ingredient (API) for CFZ tablets due to its superior solubility. However, during the production, storage, and transportation of CFZ tablets, Hemi-CFZ can undergo transformations into anhydrous (An-CFZ) and monohydrate (Mono-CFZ) forms under the influence of environmental factors such as temperature, humidity, and pressure, which may adversely impact the bioavailability and clinical efficacy of CFZ tablets. Therefore, it is imperative to develop rapid, accurate, non-destructive, and non-contact methods for quantifying An-CFZ and Mono-CFZ content in CFZ tablets to control polymorphic impurity levels and ensure product quality. This research evaluated the feasibility and reliability of using near-infrared spectroscopy (NIR) combined with partial least squares regression (PLSR) for simultaneous quantitative analysis of An-CFZ and Mono-CFZ in CFZ tablets, elucidating the quantifying mechanisms of the quantitative analysis model. Orthogonal experiments were designed to investigate the effects of different pretreatment methods and ant colony optimization (ACO) algorithms on the performance of quantitative models. An optimal PLSR model for simultaneous quantification of An-CFZ and Mono-CFZ in CFZ tablets was established and validated over a concentration range of 0.0000 to 10.0000 w/w%. The resulting model, Y_{An-CFZ/Mono-CFZ} = 0.0207 + 0.9919 X, achieved an R² value of 0.9919. By analyzing the relationship between the NIR spectral signals selected by the ACO algorithm and the molecular structure information of An-CFZ and Mono-CFZ, we demonstrated the feasibility and reliability of the NIR-PLSR approach for quantifying these polymorphic forms. Additionally, the mechanism of PLSR quantitative analysis was further explained through the variance contribution rates of latent variables (LVs), the correlations between LVs loadings and tablets composition, and the relationships between LV scores and An-CFZ/Mono-CFZ content. This study not only provides a robust method and theoretical foundation for monitoring An-CFZ and Mono-CFZ content in CFZ tablets throughout production, processing, storage, and transportation, but also offers a reliable methodological reference for the simultaneous quantitative analysis and quality control of multiple polymorphic impurities in other similar drugs. Full article

Sustainable oil and gas development demands eco-friendly and cost-effective drilling fluids. Water-based drilling fluids (WBDFs) are preferred over oil-based alternatives for their lower environmental impact, but they often suffer from excessive fluid loss in permeable formations, leading to thick filter cakes, reduced mud weight, and operational delays. Conventional chemical additives mitigate this issue but pose environmental and health risks due to their toxicity and non-biodegradability. This study explores the use of biodegradable additives extracted from avocado seed (AS), rambutan shell (RS), tamarind shell (TS) and banana trunk (BT) biomass in four particle sizes of 300, 150, 75 and 32 μm to improve filtration control in WBDFs. All four materials were crushed by ball milling and characterized by Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM) and Energy-dispersive X-ray (EDX). In accordance with API Spec 13A recommendations, several water-based drilling fluids (WBDFs), including reference fluid and modified fluids formulated with biodegradable additives at a fixed percentage of 3 wt% and varied particle sizes, were prepared. The rheological and filtration properties of the formulated drilling fluids were investigated by conducting industry-standard rheology and filtration tests under LPLT conditions (100 psi, 25 °C) and HPHT conditions (1500 psi, 75 °C). The results show that 32 μm tamarind shell powder delivered the strongest performance, reducing fluid loss by 82.4% under HPHT conditions and producing the thinnest mud cake (0.33 mm); it also reduced fluid loss by 72.8% under LPLT conditions, outperforming the other biodegradable materials. Full article

This paper explores the static and cyclic behaviours exhibited by X-joints fabricated from circular hollow sections (CHS) incorporating curved chords under bending loading. First, a finite element (FE) model of CHS X-joints was established, and the accuracy was validated by the test results. Then, the influence of the geometric parameters on the ultimate capacity of these joints was deeply conducted through variable parameter expansion analysis, including the chord curvature (R)-to-diameter (D) ratio α, brace diameter (d)-to-chord diameter (D) ratio β, and chord diameter (D)-to-double thickness (2T) ratio γ. In addition, the formulae for the in-plane bending bearing capacity of CHS X-joints with curved chords were examined based on the FE results and typical design guides. Finally, the hysteresis performance of the joints was investigated to modify such formulae. The results show that (1) the bending bearing capacity decreases with increasing α when 3 ≤ α ≤ 12 and changes slightly when α > 12. The bending bearing capacity increases with increasing β and decreases with increasing γ. (2) The bending bearing capacity design formula is modified by FEM results on the basis of the formula derived from Eurocode 3. The API-WSD and LRFD design codes do not consider the effect of γ, and the AIJ seems to be overly conservative. (3) In light of the hysteresis analysis, the smaller the magnitude of γ and the larger that of β, the more favourable the bending load-bearing capacity, ductility coefficient and plastic deformation capability of the joints are found to be. The bending bearing capacity under cyclic loading was close to the value under static loading when α ≥ 9, whereas a reduction coefficient of 0.9 was considered when α < 9. Comparison analyses indicated that the adjusted design formula was suitable for engineering design. Full article

The growing need for intelligent educational systems calls for architectures supporting adaptive instruction, while enabling more permanent, long-term personalization and cognitive alignment in the long run. While we have seen progress in adaptive learning technologies at the intersection of Self-Regulated Learning (SRL), Continual Learning (CL), and Meta-Learning, these are generally employed in isolation to provide piecemeal solutions. In this paper, we propose CAMEL, a unified architecture for (1) cognitive modelling based on SRL, (2) continual learning functionalities, and (3) meta-learning to provide adaptive, personalized, and cognitively consistent learning environments. CAMEL includes the following components: (1) A Cognitive State Estimator that estimates learner motivation, attention, and persistence from behavioral traces, (2) A Meta-Learning Engine that allows it rapid adaptation through Model-Agnostic Meta-Learning (MAML), (3) A Continual Learning Memory that preserves knowledge across sessions using Elastic Weight Consolidation (EWC) and Replay, (4) A Pedagogical Decision Engine that makes real-time efficient adjustments of instructional strategies, and (5) A closed-loop that continuously reconciles misalignments between pedagogical actions and predicted cognitive states. Experiments conducted on the xAPI-Edu-Data dataset evaluate the system’s few-shot adaptation capability, knowledge retention, cognitive-state prediction accuracy, and knowledge, as well as cognitive responsiveness to the impending questions. It offers competitive performance in learner-state prediction and long-term performance compared to the baselines, and the improvements are consistent across the different baselines. This paper lays the groundwork for next-generation adaptive and cognition-driven AI-based learning systems. Full article

The primary goal of this study was to improve the rheological properties of water-based drilling mud using a combination of TiO₂-coated ZnO nanoparticles and activated carbon (AC) from banana peels. The TiO₂/ZnO nanocomposites were prepared using polyvinyl alcohol (PVA) as a binder under magnetic stirring and ultrasonic sonication to ensure uniform coating, followed by washing and controlled thermal treatment. NaOH-assisted chemical activation of banana peel produced activated carbon with better porosity and surface functionality than raw banana peel. The base water-based mud used in this study had different concentrations of both additives mixed in, and rheological parameters such as mud density, plastic viscosity (PV), yield point (YP), and gel strength were measured according to standard API methods. X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used for structural and morphological characterization, which proved the successful coating and uniform dispersion of TiO₂ on ZnO nanoparticles. The use of mixed additives resulted in a significant improvement in mud properties, such as viscosity, gel strength, and yield point, proving to be more effective in suspension capacity and overall rheological stability. The use of this hybrid bio-nanocomposite mud system is a very economical and eco-friendly way of enhancing the drilling fluid performance, thus proving to be a supporting factor in conducting drilling operations that are both safe and efficient. Additionally, this study provides a sustainable hybrid TiO₂-ZnO and activated carbon additive that results in synergistic improvement of drilling-mud rheology and stability. Full article

Pyrimethamine (PYR), a drug approved for the treatment of infections caused by protozoan parasites, is a multifunctional API based on 2,4-diaminopyrimidine scaffold. The present study aims toward the development of novel solid forms of PYR, by combining it with three isomeric aminobenzoic acids—2-aminobenzoic acid (2NH₂-BA), 3-aminobenzoic acid (3NH₂-BA), and 4-aminobenzoic acid (4NH₂-BA). Solution crystallization led to the formation of three new solvated salts of PYR (PYR/2NH₂-BA/EtOH/H₂O, PYR/3NH₂-BA/EtOH, and PYR/4NH₂-BA/EtOH/H₂O). The detailed physicochemical properties of the formed compounds were characterized by single-crystal X-ray diffraction (SC-XRD), FTIR, PXRD, thermogravimetry (TG), and differential scanning calorimetry (DSC). Additionally, the pre-crystallization solutions of PYR with 2NH₂-BA, 3NH₂-BA, and 4NH₂-BA were studied by electrospray ionization mass spectrometry technique (ESI-MS), which enabled the observation of peaks corresponding to noncovalently bonded molecules, providing insight into their specific aggregation in a solution/gas phase environment. We identified different non-covalent aggregates, including self-aggregates of aminobenzoic acids and PYR/aminobenzoic acid associates of different stoichiometries. Full article

Nominally weakly coordinating anions are useful for modulating the solubility and chemical properties of metal complexes, but identification and analysis of the systematics of the interactions of anions with cationic metal complexes has not received the attention it deserves. Here, a chemical informatics approach is demonstrated for identifying and quantitatively analyzing the ways that the bis(trifluoromethylsulfonyl)imide anion (TFSI) can interact with metal-containing species. An open access computer program (PyCIFTer) was developed to facilitate large-scale structural analysis of TFSI-containing species by utilization of experimental atomic coordinate data from single-crystal X-ray diffraction (XRD) studies obtained from the Cambridge Structural Database (CSD). PyCIFTer establishes a three-dimensional vector space from the raw atomic coordinates, generating acyclic, undirected graphs that are used to rapidly analyze the structural properties (bond lengths and angles) of TFSI in individual structures in sequential/batch fashion. The structures are sorted by PyCIFTer into groups based on pre-set and chemically sensible criteria, affording a comprehensive and systematic view of TFSI structural chemistry. This approach avoids tedious one-at-a-time interrogation of structures, a prospect unreasonable in this case, and many others of contemporary chemical relevance; there were over 1500 structures in the CSD containing TFSI as of November 2024. The results demonstrate that TFSI only rarely binds to cations in the solid state, favoring the formation of species in which TFSI is found in cations’ outer coordination spheres. The prospect of applying PyCIFTer to other moieties is also discussed. PyCIFTer is also schematically compared to the commercial CSD Python application programming interface (API). Taken together, this work demonstrates the usefulness of modular workflows for sequential/batch analysis of structural data from XRD, an approach that appears poised to accelerate the translation of legacy structural results into new chemical insights and hypotheses. Full article

Continuous cooling transformation (CCT) diagrams for two thermo-mechanically controlled processed (TMCP) steels were produced using a modified Johnson–Mehl–Avrami–Kolmogorov (JMAK) model, which accounted for the simultaneous transformation of multiple phases under non-isothermal conditions. A basin hopping algorithm was used to sequentially optimize the model parameters for each phase. Samples were prepared using a dilatometer which replicated the deformation and cooling rates experienced during TMCP. Scanning electron microscopy (SEM) and electron back-scattered diffraction (EBSD) were used to identify and quantify the phases present in each steel. CCT diagrams illustrating the start and stop temperatures of each phase were constructed for both steel samples. Through inclusion of the stop temperatures of each phase transformation, the utility of the CCT diagrams were expanded. This was done by introducing the possibility of applying the Scheil additive principle with respect to the beginning and end of each phase transformation. With this modification, the CCT diagrams are now more appropriately suited to predict the phase transformations that occur on the ROT, where non-continuous cooling occurs. Full article

In this work, plasma nitriding was carried out to improve the corrosion resistance of API 5L X70 steel. The process was conducted at different treatment times, 4, 6, 8, and 10 h, to determine which one provides greater resistance to corrosion. The conditions under which the nitriding was carried out were as follows: a mixture of 20% N₂ and 80% H₂ at 3 torr pressure, a current of 2.6 × 10⁻⁶ A, a voltage of 360 V, and the temperature inside the plasma chamber was 550 °C. The blank and nitrided materials were characterized using dispersive energy spectroscopy and scanning microscopy to study their morphology and chemical composition. In addition, open potential circuit, electrochemical impedance spectroscopy, and potentiodynamic polarization curves in simulated soil solution were performed to evaluate the materials’ corrosion resistance. The treatment achieved at 10 h presented the greatest corrosion resistance, reducing the corrosion current density up to three orders of magnitude. The thickness reached 678.75 µm for this condition. Full article

This article focuses on developing and characterizing one-part rock-based geopolymer slurries using Brazilian rock precursors for well construction and plugging and abandonment (P&A) applications. The study presents the fluid-state and solid-state properties of these geopolymers, as well as X-ray diffraction (XRD) and Scanning Electron Microscopy (SEM), to understand the microstructure of the precursors and the reaction level. The effect of temperature and pressure on the development of compressive strength was investigated. By altering these parameters, the study aimed to examine the impact of various conditions on the strength development of the geopolymer material. Technological tests were conducted following API RP 10B-2. Compressive strength tests were conducted to determine early strength development and thickening time. Post-curing Rietveld refinement by XRD was performed to examine the microstructure and reactivity. Finally, fluid-state properties were also assessed, including thickening time and viscosity. The strength development of geopolymers is observed to be time- and temperature-dependent, as shown by UCS results. The final product has a dense structure, and its long-term performance will require evaluation to determine its sealing capability and volume change as a barrier material. The results highlight the novelty of employing locally available Brazilian rock precursors in one-part geopolymer formulations and provide a scientific basis for their potential application as sustainable alternatives to conventional cements in well construction and abandonment. Full article

Consistent detection of malicious loaders across varied programming languages and build tools remains a significant cybersecurity challenge. This study empirically measures how compiler and language choices affect the detectability of standard in-memory Windows loaders. We implement functionally equivalent loaders (allocate, copy, protect, execute) in C, C#, Fortran, and COBOL, embedding an identical x64 test payload to isolate behavior. Our results reveal significant detection gaps: loaders compiled in legacy languages (Fortran, COBOL) consistently evade static and dynamic antivirus engines that easily flag their C and C# counterparts. We demonstrate this evasion is not due to behavioral differences, but to compiler-specific static artifacts. These artifacts, such as interleaved zero-bytes in Fortran and fragmented payload-construction logic in COBOL, effectively break common signature matching. These findings indicate that many detection tools are overly sensitive to the static build surface rather than true semantic behavior. We provide actionable guidance favoring behavior-focused analysis, such as tracking API call order and memory protection changes, to address this critical legacy code blind spot. Full article

The laser-directed energy deposition (L-DED) technique, with its excellent environmental adaptability and superior repair capability, shows great potential for the repair of damaged X70 pipeline steel. In this work, the microstructure and mechanical properties of L-DED repaired X70 steel were systematically investigated. The deposited material exhibited inhomogeneity along the building direction. From the bottom to the top, the grains gradually coarsened, and the proportion of polygonal ferrite increased. This was mainly attributed to increasing thermal accumulation with deposition height, which reduced the cooling rate and promoted solid-state transformations at higher temperatures. Meanwhile, the heat accumulation and intrinsic heat treatment reduced the dislocation density and promoted Fe₃C precipitation within grains and along boundaries. Microhardness was highest in the bottom region and decreased along the building direction due to the gradual coarsening of microstructure and decreasing in dislocation density. The L-DED X70 showed lower yield strength (435 MPa) and ultimate tensile strength (513 MPa) compared to the base material and API 5L requirements. The elongation of the L-DED X70 was 42.9%, which was 58% higher than that of the base material, indicating excellent ductility. These results revealed a thermal history-dependent strength–ductility trade-off in the L-DED repaired X70 steel. Therefore, more efforts are needed to control the L-DED thermal process, tailor the microstructure, enhance strength, and meet the service requirements of harsh environments. Full article