Experimental Strategies Research Articles

Computational-Aided Approach for the Optimization of Microfluidic-Based Nanoparticles Manufacturing Process.

In the last few years, the microfluidic production of nanoparticles (NPs) is becoming a promising alternative to conventional industrial approaches (e.g., nanoprecipitation, salting out, and emulsification-diffusion) thanks to the production efficiency, low variability, and high controllability of the production parameters. Nevertheless, the development of new formulations and the switching of the production process toward microfluidic platforms requires expensive and time-consuming number of experiments for the tuning of the formulation to obtain NPs with specific morphological and functional characteristics. In this work, we developed a computational fluid dynamic pipeline, validated through an ad hoc experimental strategy, to reproduce the mixing between the solvent and anti-solvent (i.e., acetonitrile and TRIS-HCl, respectively). Moreover, beyond the classical variables able to describe the mixing performances of the microfluidic chip, novel variables were described in order to assess the region of the NPs formation and the changing of the amplitude of the precipitation region according to different hydraulic conditions. The numerical approach proved to be able to capture a progressive reduction of the nanoprecipitation region due to an increment of the flow rate ratio; in parallel, through the experimental production, a progressive increment of the NPs size heterogeneity was observed with the same fluid dynamic conditions. Hence, the preliminary comparison between numerical and experimental evidence proved the effectiveness of the computational strategy to optimize the NPs manufacturing process.

Quantitative MRI post-processing algorithm and visualization research based on moisture status detection of winter jujube

Quantitative Magnetic Resonance Imaging (qMRI) offers precise measurements of the relaxation characteristics of microstructures, representing a cutting-edge method in non-destructive fruit analysis. This study aims to visualize information on changes in moisture status and distribution at the subcellular level of winter jujube. The 0.5 T nuclear magnetic imaging equipment was utilized to rapidly, non-invasively, and accurately capture the internal relaxation status of the sample with multiple-echo-imaging. By examining the signal and noise data, a simulated dataset was developed to tackle the optimization challenge of estimating parameters for the discrete relaxation model from the multiple-echo-imaging data, especially under conditions of low signal-to-noise ratio (SNR) and in the context of heteroscedastic noise. An optimal weighting factor and the T2NR truncation model have been identified to establish an effective experimental inversion strategy. Subsequently, multiple-echo-imaging can rapidly and stably yielded voxel-level maps under conditions of low signal-to-noise ratio. Utilizing this experimental approach, data from winter jujube was collected and analyzed, facilitating an exploration of water activity (T2 mapping) and associated water content (A2 mapping). Through analyzing winter jujube fruits across two maturity stages, this study elucidates the role of precise quantification and voxel-wise visualization in moisture status detection. The methodology presents an innovative approach for assessing internal moisture distribution in fruits.

The Implementation of Read, Ask, Paraphrase Technique in the News Reading Comprehension

The purpose of this study is to investigate the significance of applying the RAP technique in learning activities in reading classrooms. The researcher employed a quantitative experimental research strategy for this study. The participants in this study were students in classes IX-A and IX-B at SMP Gajah Mada Medan who were in their ninth grade. Selecting samples, researchers used the term cluster random sampling by choosing two classes. There are 60 students total; there are 15 pupils in each class. Two groups of students were formed; the experimental group and the control group. The control group was instructed in traditional ways, whereas the experimental group received therapy (the RAP approach). An exam with multiple choice questions is the tool used to gather data. To assess the data, the t-test formula was used. The data was evaluated using the t-test procedure. The analysis's findings demonstrate that, at a significance level of 0.05 and with 28 degrees of freedom (df), those served exceed the t-table (3.86> 2.44). This indicates that students' learning scores have been positively impacted by the use of the RAP technique in the teaching and learning process, particularly when it comes to the reading of news articles for class.

Adsorption-Driven Deformation and Footprints of the RBD Proteins in SARS-CoV-2 Variants on Biological and Inanimate Surfaces.

Respiratory viruses, carried through airborne microdroplets, frequently adhere to surfaces, including plastics and metals. However, our understanding of the interactions between viruses and materials remains limited, particularly in scenarios involving polarizable surfaces. Here, we investigate the role of the receptor-binding domain (RBD) of the spike protein mutations on the adsorption of SARS-CoV-2 to hydrophobic and hydrophilic surfaces employing molecular simulations. To contextualize our findings, we contrast the interactions on inanimate surfaces with those on native biological interfaces, specifically the angiotensin-converting enzyme 2. Notably, we identify a 2-fold increase in structural deformations for the protein's receptor binding motif (RBM) onto inanimate surfaces, indicative of enhanced shock-absorbing mechanisms. Furthermore, the distribution of adsorbed amino acids (landing footprints) on the inanimate surface reveals a distinct regional asymmetry relative to the biological interface, with roughly half of the adsorbed amino acids arranged in opposite sites. In spite of the H-bonds formed at the hydrophilic substrate, the simulations consistently show a higher number of contacts and interfacial area with the hydrophobic surface, where the wild-type RBD adsorbs more strongly than the Delta or Omicron RBDs. In contrast, the adsorption of Delta and Omicron to hydrophilic surfaces was characterized by a distinctive hopping-pattern. The novel shock-absorbing mechanisms identified in the virus adsorption on inanimate surfaces show the embedded high-deformation capacity of the RBD without losing its secondary structure, which could lead to current experimental strategies in the design of virucidal surfaces.

Determination of Uranium Central-Field Covalency with 3d4f Resonant Inelastic X-ray Scattering.

Understanding the nature of metal-ligand bonding is a major challenge in actinide chemistry. We present a new experimental strategy for addressing this challenge using actinide 3d4f resonant inelastic X-ray scattering (RIXS). Through a systematic study of uranium(IV) halide complexes, [UX6]2-, where X = F, Cl, or Br, we identify RIXS spectral satellites with relative energies and intensities that relate to the extent of uranium-ligand bond covalency. By analyzing the spectra in combination with ligand field density functional theory we find that the sensitivity of the satellites to the nature of metal-ligand bonding is due to the reduction of 5f interelectron repulsion and 4f-5f spin-exchange, caused by metal-ligand orbital mixing and the degree of 5f radial expansion, known as central-field covalency. Thus, this study furthers electronic structure quantification that can be obtained from 3d4f RIXS, demonstrating it as a technique for estimating actinide-ligand covalency.

Structural Optimization of Oxaprozin for Selective Inverse Nurr1 Agonism.

Nuclear receptor related 1 (Nurr1, NR4A2) is a ligand-sensing transcription factor with neuroprotective and anti-inflammatory roles widely distributed in the CNS. Pharmacological Nurr1 modulation is considered a promising experimental strategy in Parkinson's and Alzheimer's disease but target validation is incomplete. While significant progress has been made in Nurr1 agonist development, inverse agonists blocking the receptor's constitutive activity are lacking. Here we report comprehensive structure-activity relationship elucidation of oxaprozin which acts as moderately potent and nonselective inverse Nurr1 agonist and RXR agonist. We identified structural determinants selectively driving RXR agonism or inverse Nurr1 agonism of the scaffold enabling the development of selective inverse Nurr1 agonists with enhanced potency and strong efficacy.

Novel drug design and repurposing: An opportunity to improve translational research in cardiovascular diseases?

Drug repurposing is defined as the use of approved therapeutic drugs for indications different from those for which they were originally designed. Repositioning diminishes both the time and cost for drug development by omitting the discovery stage, the analysis of absorption, distribution, metabolism, and excretion routes, as well as the studies of the biochemical and physiological effects of a new compound. Besides, drug repurposing takes advantage of the increased bioinformatics knowledge and availability of big data biology. There are many examples of drugs with repurposed indications evaluated in in vitro studies, and in pharmacological, preclinical, or retrospective clinical analyses. Here, we briefly review some of the experimental strategies and technical advances that may improve translational research in cardiovascular diseases. We also describe exhaustive research from basic science to clinical studies that culminated in the final approval of new drugs and provide examples of successful drug repurposing in the field of cardiology.

Strategi Dakwah Radio BHASA FM dalam Meningkatkan Pemahaman Keagamaan Masyarakat Situbondo

This article examines Bhasa FM radio's da'wah strategy in increasing the religious understanding of the Situbondo community. Radio has been known for a long time as a medium for conveying information, education and entertainment to the public. However, it is different for Bhasa FM Situbondo radio, a radio whose orientation is not only on these three things but more on the domination of Islamic preaching. Seeing that modern society currently tends to be less interested in religious studies in mosques or prayer rooms, it is hoped that radio can be an alternative in filling and providing religious nutrition for Situbondo Muslims. The research uses field research methods. The researcher looked directly into the field in conducting observations, interviews and documentation studies, to collect complete data and then carry out descriptive analysis to then look for an answer to the focus of this paper. Bhasa FM radio's da'wah strategy uses a sensory da'wah strategy (al-manhaj al-hissy) which is also called an experimental strategy or scientific strategy which is oriented to the five senses and adheres firmly to the results of research and experiments. Bhasa FM Radio invites audiences to join online or off air, apart from that there is also social media such as Twitter, Facebook, YouTube and so on. Apart from that, there is also an external approach, namely data produced by Nielsen surveys, once a month. The aim of this strategy is to find out the age, social and economic status of the listener and all demographic aspects of the listener.

Promising Experimental Treatment in Animal Models and Human Studies of Interstitial Cystitis/Bladder Pain Syndrome.

Interstitial cystitis/bladder pain Syndrome (IC/BPS) remains a mysterious and intricate urological disorder, presenting significant challenges to healthcare providers. Traditional guidelines for IC/BPS follow a hierarchical model based on symptom severity, advocating for conservative interventions as the initial step, followed by oral pharmacotherapy, intravesical treatments, and, in refractory cases, invasive surgical procedures. This approach embraces a multi-tiered strategy. However, the evolving understanding that IC/BPS represents a paroxysmal chronic pain syndrome, often involving extravesical manifestations and different subtypes, calls for a departure from this uniform approach. This review provides insights into recent advancements in experimental strategies in animal models and human studies. The identified therapeutic approaches fall into four categories: (i) anti-inflammation and anti-angiogenesis using monoclonal antibodies or immune modulation, (ii) regenerative medicine, including stem cell therapy, platelet-rich plasma, and low-intensity extracorporeal shock wave therapy, (iii) drug delivery systems leveraging nanotechnology, and (iv) drug delivery systems assisted by energy devices. Future investigations will require a broader range of animal models, studies on human bladder tissues, and well-designed clinical trials to establish the efficacy and safety of these therapeutic interventions.

TEACHING SPEAKING ABILITY OF VOCATIONAL HIGH SCHOOL STUDENTS THROUGH DIRECT NSTRUCTION MODEL

Through the use of oral tests to describe places described in descriptive texts, this study sought to investigate the efficacy of an instruction model combined with a learning model in enhancing the speaking abilities of Vocational High School (SMK) students. The goal of this study was to teach English speaking skills in a classroom setting. An experimental strategy with a pre- and post-test one group design was employed in the research methodology. Tenth grade TKJ students from Vocational High School PGRI Pangkalan Balai academic years 2023/2024 made up the research sample. Speaking exams were used to gather data both before and after the course of treatment. The speaking exam was divided into multiple parts, including fluency, grammar, vocabulary, and pronunciation. With an average pre-test score of 47.23% and an average post-test score of 64.3, the data analysis results demonstrated a considerable improvement in the speaking ability of students who received instruction through a direct instruction paradigm. This result demonstrates how well the learning model with direct instruction worked to enhance the speaking skills of students enrolled in vocational programs.

Evaluating the thermal stability of chemicals and systems: A review

AbstractIn the realm of chemical processing, particularly at the industrial scale, safety is of utmost importance. A predominant factor causing accidents within the chemical industry is runaway phenomena, primarily initiated by uncontrolled exothermic reactions. This review critically examines the often‐overlooked decomposition mechanisms as a significant contributor to thermal energy release, necessitating a comprehensive revision and understanding of both experimental and theoretical strategies for assessing thermal degradation. Key to this discourse is the explication of calorimetry as the principal experimental technique, alongside ab initio quantum chemistry simulations as a robust theoretical framework for quantifying the most relevant properties. However, more than mere cognisance of these methodologies is required for a meticulous thermal stability assessment. The review emphasizes identifying and quantifying fundamental parameters through experimental and theoretical investigations. Only upon acquiring these parameters, including kinetic, thermodynamic, onset, and peak characteristics of the exothermic decomposition reactions, can one effectively mitigate risks and hazards in designing and optimizing chemical processes and apparatus. Furthermore, this review delineates qualitative and quantitative methodologies for hazard assessment, proffering strategies for estimating safe operational conditions and sizing relief devices. The paper culminates in exploring future trajectories in thermal stability assessments, focusing on emerging applications in lithium‐ion batteries, electrolyzers, electrified reactors, ionic liquids, artificial intelligence and machine learning approaches. Thus, the paper underlines the evolving landscape of thermal risk management in contemporary and future chemical industries.

The role of the PI3K/Akt pathway in adenosine’s mechanism of action in osteoporosis with oxidative stress: A wet-dry experimental approach strategy

Adenosine, a nucleoside, regulates various systems, such as the cardiovascular, immune, and nervous systems, by binding to Adenosine receptors. To elucidate the role of Adenosine in Osteoporosis, this study employed an experimental approach involving the stimulation of bone formation in osteoporotic zebrafish and the reduction of reactive oxygen levels in a glucocorticoid-induced zebrafish model of Osteoporosis with oxidative stress. Adenosine significantly promoted the proliferation of MC3T3-E1 cells and increased the activity of alkaline phosphatase (ALP). It also elevated nitric oxide, glutathione, and superoxide dismutase levels while decreasing malondialdehyde. The target of Adenosine’s impact on Osteoporosis with oxidative stress was elucidated through network pharmacology, revealing the PI3K/Akt pathway, a finding corroborated through RT-qPCR analysis. Hence, we present the mechanism through which Adenosine can be utilized to prevent and manage Osteoporosis accompanied by oxidative stress, distinct from the previously identified mode of action of Adenosine in osteoporosis treatment.

Why Conceptions of Scale Matter to Artificity Arguments in SRM Ethics

ABSTRACT Ethicists have raised a variety of concerns about solar radiation management (SRM). This essay investigates the specific worries associated with artificity: Does SRM transform the planet into an artifact? Should experimental SRM strategies be implemented if the consequences are unpredictable? These worries have led some to strongly reject SRM. But the conceptual framework used by environmental scientists to understand the scope of management interventions might offer a way to adequately defuse the perceived ethical concerns about artificity. Concepts from theories of scale, like discontinuity and panarchy, are discussed to demonstrate how the artificity arguments appear to depend on disputable premises.

TopoDoE: a design of experiment strategy for selection and refinement in ensembles of executable gene regulatory networks

BackgroundInference of Gene Regulatory Networks (GRNs) is a difficult and long-standing question in Systems Biology. Numerous approaches have been proposed with the latest methods exploring the richness of single-cell data. One of the current difficulties lies in the fact that many methods of GRN inference do not result in one proposed GRN but in a collection of plausible networks that need to be further refined. In this work, we present a Design of Experiment strategy to use as a second stage after the inference process. It is specifically fitted for identifying the next most informative experiment to perform for deciding between multiple network topologies, in the case where proposed GRNs are executable models. This strategy first performs a topological analysis to reduce the number of perturbations that need to be tested, then predicts the outcome of the retained perturbations by simulation of the GRNs and finally compares predictions with novel experimental data.ResultsWe apply this method to the results of our divide-and-conquer algorithm called WASABI, adapt its gene expression model to produce perturbations and compare our predictions with experimental results. We show that our networks were able to produce in silico predictions on the outcome of a gene knock-out, which were qualitatively validated for 48 out of 49 genes. Finally, we eliminate as many as two thirds of the candidate networks for which we could identify an incorrect topology, thus greatly improving the accuracy of our predictions.ConclusionThese results both confirm the inference accuracy of WASABI and show how executable gene expression models can be leveraged to further refine the topology of inferred GRNs. We hope this strategy will help systems biologists further explore their data and encourage the development of more executable GRN models.

Uncover the Unusual Near‐Infrared Luminescence in Stannates – Interplay of Cr3 + with Codopants

AbstractThe unintentional incorporation of various unknown trace amounts of impurities poses challenges and controversies in identifying luminescent mechanisms of certain systems. A common approach to confirm or exclude the involvement of a certain activation center is to monitor the changes in luminescence by intentionally doping the inferred species into the crystal. Here, an intriguing luminescent phenomenon resulting from the hidden interplay between the dopants and trace impurities, is presented. In alkaline‐earth stannate perovskites, near‐infrared luminescence is observed. By combining density‐functional calculations with the well‐designed doping and codoping experimental strategies, the mechanisms behind this anomaly is successfully uncovered. It originates from the stabilization of Cr3 + by codopants such as Bi and rare‐earth (RE) ions, acting as electron donors. The luminescence is almost unobservable when chromium is doped alone, and thus the traditional identification method does't work. This work emphasizes the important role of trace impurity in materials, especially the subtle change of valence state of trace impurity upon doping, which provides enlightening insights and prompts reassessments of numerous reported anomalous luminescent phenomena.

Searching for axion forces with spin precession in atoms and molecules

We propose to use atoms and molecules as quantum sensors of axion-mediated monopole-dipole forces. We show that electron spin precession experiments using atomic and molecular beams are well-suited for axion searches thanks to the presence of co-magnetometer states and single-shot temporal resolution. Experimental strategies to detect axion gradients from localised sources and the earth are presented, taking ACME III as a prototype example. Other possibilities including atomic beams, and laser-cooled atoms and molecules are discussed.

Identification of Babesia microti immunoreactive antigens by phage display cDNA screen.

Human babesiosis is a malaria-like illness caused by protozoan parasites of the genus Babesia. Babesia microti is responsible for most cases of human babesiosis in the United States, particularly in the Northeast and the Upper Midwest. Babesia microti is primarily transmitted to humans through the bite of infected deer ticks but also through the transfusion of blood components, particularly red blood cells. There is a high risk of severe and even fatal disease in immunocompromised patients. To date, serology testing relies on an indirect immunofluorescence assay that uses the whole Babesia microti antigen. Here, we report the construction of phage display cDNA libraries from Babesia microti-infected erythrocytes as well as human reticulocytes obtained from donors with hereditary hemochromatosis. Plasma samples were obtained from patients who were or had been infected with Babesia microti. The non-specific antibody reactivity of these plasma samples was minimized by pre-exposure to the human reticulocyte library. Using this novel experimental strategy, immunoreactive segments were identified in three Babesia microti antigens termed BmSA1 (also called BMN1-9; BmGPI12), BMN1-20 (BMN1-17; Bm32), and BM4.12 (N1-15). Moreover, our findings indicate that the major immunoreactive segment of BmSA1 does not overlap with the segment that mediates BmSA1 binding to mature erythrocytes. When used in combination, the three immunoreactive segments form the basis of a sensitive and comprehensive diagnostic immunoassay for human babesiosis, with implications for vaccine development.

Optimization of biotransformation processes of Camarosporium laburnicola to improve production yields of potent telomerase activators

BackgroundTelomerase activators are promising agents for the healthy aging process and the treatment/prevention of short telomere-related and age-related diseases. The discovery of new telomerase activators and later optimizing their activities through chemical and biological transformations are crucial for the pharmaceutical sector. In our previous studies, several potent telomerase activators were discovered via fungal biotransformation, which in turn necessitated optimization of their production. It is practical to improve the production processes by implementing the design of experiment (DoE) strategy, leading to increased yield and productivity. In this study, we focused on optimizing biotransformation conditions utilizing Camarosporium laburnicola, a recently discovered filamentous fungus, to afford the target telomerase activators (E-CG-01, E-AG-01, and E-AG-02).ResultsDoE approaches were used to optimize the microbial biotransformation processes of C. laburnicola. Nine parameters were screened by Plackett-Burman Design, and three significant parameters (biotransformation time, temperature, shaking speed) were optimized using Central Composite Design. After conducting validation experiments, we were able to further enhance the production yield of target metabolites through scale-up studies in shake flasks (55.3-fold for E-AG-01, 13-fold for E-AG-02, and 1.96-fold for E-CG-01).ConclusionFollowing a process optimization study using C. laburnicola, a significant increase was achieved in the production yields. Thus, the present study demonstrates a promising methodology to increase the production yield of potent telomerase activators. Furthermore, C. laburnicola is identified as a potential biocatalyst for further industrial utilization.

Development of a MIMO fuzzy inference system—PI controller for a closed‐circuit grinding ball mill circuit

AbstractThis article aims to study the implementation of classical proportional‐integrative (PI) controllers and their coupling with the fuzzy inference systems (FISs) in the act of closed‐circuit grinding (CCG) ball mill system. The system was formed for a multiple‐input multiple‐output (MIMO) system, with two inputs, the feed rate (WF) and speed classifier rotor (VR), and two outputs, a sieve fraction 45 μm (P45) and the amount of material by a weight inside the drum (hold up [HU]). The model was simulated based on experimental processes and control strategies. The fuzzy‐PI controllers were developed on the software, and the data from this process were used to build the database and the necessary knowledge to construct the FIS controllers (with fuzzy rules base 3 × 3 and 5 × 5). Their implementation decreases the error criteria integral of time multiplied by the absolute error (ITAE) and integral of the absolute magnitude of the error (IAE) by 35% and 65%, respectively. Although, applying fuzzy‐PI systems with a smaller rule‐based outcome gives the benefits of implementing the fuzzy logic (FL) but with a smaller oscillatory performance and a minor negative effect on HU control.

Research on abnormal wear mechanism of the coupler system in heavy-haul trains

Abnormal wear issues of the coupler system exist in heavy-haul trains and are rarely studied before. In this paper, we thoroughly report and investigate the abnormal wear phenomenon of the coupler using theoretical and experimental strategies. Firstly, the operational conditions of the trains with worn couplers are analyzed through field tests. Then, the causes of the coupler abnormal wear are theoretically analyzed according to structural characteristics. Next, A refined dynamic model of coupler considering the coupler components is developed and validated. The key influencing factors of abnormal wear are studied, including the wear depth of the component and the friction coefficient of the follower. Experiments and simulations prove that multiple braking of trains will lead to upward movements of the follower and then induce contact between the follower and the coupler yoke, further resulting in abnormal wear. Finally, countermeasures are proposed to mitigate the abnormal wear of the coupler system.