Background. Coronary artery disease (CAD) with extensive stenosis presents significant clinical challenges. This case report details the management and outcomes of a 61-year-old male with a notable history of CAD, initially treated with coronary artery bypass grafting (CABG), followed by an innovative intravenous hydrogen and oxygen nanobubble therapy due to recurrent symptoms.Case Presentation. Mr. BH was diagnosed with significant stenosis in the left anterior descending (LAD) artery and left circumflex (LCx) artery, initially managed by CABG. Recurring symptoms led to the adoption of a novel treatment involving hydrogen and oxygen nanobubbles. Following treatment initiation, Mr. BH experienced substantial improvements in physical capacity and symptomatic relief, with an ability to climb 22 flights of stairs and resolution of previous symptoms such as dyspnea and cough. Despite these improvements, subsequent imaging revealed in-stent restenosis and progression of graft disease.Discussion. The application of hydrogen and oxygen nanobubbles as a therapy in CAD is explored, highlighting potential mechanisms such as reduction of oxidative stress and improvement in endothelial function. This case contrasts the effects of conventional surgical and pharmaceutical interventions with the novel nanobubble therapy, illustrating both the benefits and complexities of managing advanced CAD with innovative treatments.Conclusion. While Mr. BH showed clinical improvement with nanobubble therapy, the development of new severe stenosis and restenosis underscores the need for further research to understand the long-term efficacy and mechanisms of nanobubble therapy in complex CAD cases. This case suggests that while innovative therapies may provide symptomatic relief and functional improvement, they do not obviate the need for ongoing surveillance and possibly further intervention.

Background. Chronic kidney disease (CKD) is a progressive condition with limited treatment options that often lead to significant morbidity. Recent studies suggest that oxyhydrogen nanobubbles (HHOnb) may offer therapeutic benefits due to their antioxidative and anti-inflammatory properties. This case series examines the effects of intravenous HHOnb therapy on three patients with varying stages of CKD.Methods. Three patients with CKD underwent a series of ten HHOnb infusions over a period of two to three months. The patients, aged 43 to 70, presented with additional comorbidities including hypertension, diabetes mellitus, and polycystic kidney disease. Clinical parameters, including glomerular filtration rate (GFR), serum creatinine, blood pressure, and uric acid levels, were monitored alongside subjective health improvements.Results. Patient A. A 70-year-old woman with CKD grade 3a experienced a reduction in serum creatinine from 0.98 mg/dL to 0.82 mg/dL and an improvement in GFR from 59 mL/min/1.73 m² to 73.2 mL/min/1.73 m². She reported reduced leg swelling and increased vitality. Patient B. A 52-year-old man with CKD grade 4 and class III obesity showed a decrease in serum creatinine from 3.0 mg/dL to 2.86 mg/dL, an increase in GFR from 23 mL/min/1.73 m² to 24.4 mL/min/1.73 m², and improved sleep quality. Blood pressure reduced from 167/82 mmHg to 145/85 mmHg. Patient C. A 43-year-old man with CKD grade 4 and massive polycystic kidney disease reported reduced fatigue and normalized urination. His serum creatinine decreased from 3.26 mg/dL to 3.09 mg/dL, and his GFR improved from 22 mL/min/1.73 m² to 23.6 mL/min/1.73 m².Conclusion. Intravenous HHOnb therapy demonstrated potential benefits in improving renal function and overall health in CKD patients. These findings suggest that HHOnb could be a promising complementary treatment for CKD, though larger, controlled studies are needed to confirm its efficacy and safety.

Coal gasification with carbon dioxide is a process for generating clean gaseous fuels and relieving greenhouse effect. Zhundong coal has high alkali and alkali earth metals (AAEMs) content, medium volatile and low ash in nature. Isothermal CO₂ gasification of char derived from Zhundong coal (R-char) and char from acid washing R-char (AR-char) are performed in thermo-gravimetric analyzer (TGA). The effect of AAEMs is investigated on the gasification behavior in the range of temperatures 1073 K to 1273 K. The carbon conversion increases rapidly with increasing reaction temperature and CO₂ concentration. R-char has high gasification rate and carbon conversion compared with AR-char. The accuracy of the free-model approach for calculating activation energy at different conversions is validated by compared with different kinetic models (volume reaction model, distributed activation energy model). Moreover, R-char gasification with CO₂ shows a compensation effect as the Arrhenius parameters (EA and k0) increase or decrease simultaneously.

This article describes techniques employed in the production of a synthetic dataset of driver telematics emulated from a similar real insurance dataset. The synthetic dataset generated has 100,000 policies that included observations about driver’s claims experience together with associated classical risk variables and telematics-related variables. This work is aimed to produce a resource that can be used to advance models to assess risks for usage-based insurance. It follows a three-stage process using machine learning algorithms. The first stage is simulating values for the number of claims as multiple binary classifications applying feedforward neural networks. The second stage is simulating values for aggregated amount of claims as regression using feedforward neural networks, with number of claims included in the set of feature variables. In the final stage, a synthetic portfolio of the space of feature variables is generated applying an extended SMOTE algorithm. The resulting dataset is evaluated by comparing the synthetic and real datasets when Poisson and gamma regression models are fitted to the respective data. Other visualization and data summarization produce remarkable similar statistics between the two datasets. We hope that researchers interested in obtaining telematics datasets to calibrate models or learning algorithms will find our work valuable.

Three kinds of inorganic alkali are introduced into tetraethylenepentamine (TPEA) and polyethyleneimine (PEI) modified MCM-41 as the CO2 adsorbents. FT-IR and TGA are used to characterize the surface groups and the thermal stability of adsorbents. Chemical titration method is used to measure the alkali amounts of adsorbents. Thermo-gravimetric analysis with 10%CO2/N2 as the simulated flue gas is used to test the CO2 adsorption performance of adsorbents. The results show that all three kinds of inorganic alkali containing adsorbents exhibit promoted CO2 adsorption capability than traditional TPEA and PEI modified samples. Ca(OH)2 and PEI modified samples exhibit the highest adsorption capacity and stable regeneration property. The introduction of inorganic alkali changes the chemical adsorption mechanism between CO2 and increases the effective alkali amounts due to its hydroxyl groups. The CO2 adsorption capacities have a linear dependence relation with the alkali amounts of adsorbents, indicating that alkali amount is a critical factor for novel adsorbents exploring.

This article develops a multi-perspective view on motivations and methods for tobamovirus purification through the ages, and presents a novel efficient, easy-to-use approach that can be well-adapted to different species of native and functionalized virions. We survey the various driving forces prompting researchers to enrich tobamoviruses: from the search for the causative agents of mosaic diseases in plants to their increasing recognition as versatile nanocarriers in biomedical and engineering applications. Best practice and also rarely applied options for the serial processing steps required for successful isolation of tobamoviruses are then reviewed. Adaptations for distinct particle species, pitfalls and 'forgotten' or underrepresented technologies are considered as well. The article is topped off with our own development of a method for virion preparation, rooted in historical protocols. It combines selective re-solubilization of polyethylene glycol (PEG) virion raw precipitates with density step gradient centrifugation in biocompatible iodixanol formulations, yielding ready-to-use particle suspensions. This newly established protocol and some considerations for perhaps worthwile further developments could serve as putative stepping stones towards preparation procedures appropriate for routine practical uses of the multivalent soft-matter nanorods.

Industrial Control Systems (ICS) are integral to managing and optimizing processes in various industries, including manufacturing, power generation, and more. However, the scarcity of widely adopted ICS datasets hampers research efforts in areas like optimization and security. This scarcity arises due to the substantial cost and technical expertise required to create physical ICS environments. In response to these challenges, this paper presents a groundbreaking approach to generating synthetic ICS data through a data-driven ICS network simulation. We circumvent the need for expensive hardware by recreating the entire ICS environment in software. Moreover, rather than manually replicating the control logic of ICS components, we leverage existing data to autonomously generate control logic. The core of our method involves the stochastic setting of setpoints, which introduces randomness into the generated data. Setpoints serve as target values for controlling the operation of the ICS process. This approach enables us to augment existing ICS datasets and cater to the data requirements of machine learning-based ICS intrusion detection systems and other data-driven applications. Our simulated ICS environment employs virtualized containers to mimic the behavior of real-world PLCs and SCADA systems, while control logic is deduced from publicly available ICS datasets. Setpoints are generated probabilistically to ensure data diversity. Experimental results validate the fidelity of our synthetic data, emphasizing its ability to closely replicate temporal and statistical characteristics of real-world ICS networks. In conclusion, this innovative data-driven ICS network simulation offers a cost-effective and scalable solution for generating synthetic ICS data. It empowers researchers in the field of ICS optimization and security with diverse, realistic datasets, furthering advancements in this critical domain. Future work may involve refining the simulation model and exploring additional applications for synthetic ICS data.

CT scans are currently the most common imaging modality used for suspected stroke patients due to their short acquisition time and wide availability. However, MRI offers superior tissue contrast and image quality. In this study, eight deep learning models are developed, trained, and tested using a dataset of 181 CT/MR pairs from stroke patients. The resultant synthetic MRIs generated by these models are compared through a variety of qualitative and quantitative methods. The synthetic MRIs generated by a 3D UNet model consistently demonstrated superior performance across all methods of evaluation. Overall, the generation of synthetic MRIs from CT scans using the methods described in this paper produces realistic MRIs that can guide the registration of CT scans to MRI atlases. The synthetic MRIs enable the segmentation of white matter, gray matter, and cerebrospinal fluid using algorithms designed for MRIs, exhibiting a high degree of similarity to true MRIs.

Civic participation is of great significance to urban management decision-making. In order to facilitate citizens to participate in city management decision-making, this paper proposes a large-scale group decision-making (LSGDM) method based on multi-granular probabilistic linguistic preference relations (MG-PLPRs). First, each decision maker selects a language terms set from the multi-granularity language terms set to represent individual preference relations and the MG-PLPRs are obtained by statistical calculation to represent sub-group’s preferences information. Then, an optimization model based on the expected consistency of PLPR and consensus measure of groups is established to achieving consensus reaching processes, which can ensure satisfactory individual consistency and group consensus. Finally, the validity and applicability of the proposed method is verified by a case of a city "shared garden" site selection with the participation of citizens.

This paper provides a methodology for the production of synthetic images for training neural networks to recognise shapes and objects. There are many scenarios in which it is difficult, expensive and even dangerous to produce a set of images that is satisfactory for the training of a neural network. The development of 3D modelling software has nowadays reached such a level of realism and ease of use that it seemed natural to explore this innovative path and to give an answer regarding the reliability of this method that bases the training of the neural network on synthetic images. The results obtained in the two proposed use cases, that of the recognition of a pictorial style and that of the recognition of migrants at sea, leads us to support the validity of the approach, provided that the work is conducted in a very scrupulous and rigorous manner, exploiting the full potential of the modelling software. The code produced, which automatically generates the transformations necessary for the data augmentation of each image, and the generation of random environmental conditions in the case of Blender and Unity3D software, is available under the GPL licence on GitHub. The results obtained lead us to affirm that through the good practices presented in the article, we have defined a simple, reliable, economic and safe method to feed the training phase of a neural network dedicated to the recognition of objects and features, to be applied to various contexts.

2019-n-CoV is the seventh coronavirus known to infect humans and cause serious illness, and due to its lethality there was a worldwide mobilization for the development of new drugs and new vaccines for Covid-19. Therefore, the present work aims to carry out a virtual screening of terpenes with potential anti SARS-CoV-2 activity. To perform the ligand-based virtual, a model was constructed regarding the compounds which already showed inhibitory activity of the SARS-CoV-2. The test series corresponded to terpenes isolated in the Fabaceae Family. The compounds that were most likely to activity were subjected to Molecular Docking and the best poses obtained were subjected to Molecular Dynamics (MD) simulations carried. The molecules under study were submitted to in vitro evaluation to assess inhibitory activity of compounds against SARS-CoV-2 in a phenotypic screening model of the virus. The compounds selected by in silico screening corresponded to triterpenoids from the lupane series. In the in vitro test, both demonstrated activity against the SARS-CoV-2 virus. The virtual screening performed managed to identify the compounds with the highest probability of activity, as well as the most stable compounds, and the method used was validated by the in vitro study carried out.

The Dph1•Dph2 heterodimer from yeast is a radical SAM (RS) enzyme that generates the 3-amino-3-carboxy-propyl (ACP) precursor for diphthamide, a clinically relevant modification on eukaryotic elongation factor 2 (eEF2). ACP formation requires SAM cleavage and atypical Cys-bound Fe-S clusters in each Dph1 and Dph2 subunit. Intriguingly, the first Cys residue in each motif locates next to another, ill-defined cysteine that we show in-here is conserved across eukaryotes. As judged from structural modeling, the orientation of these tandem cysteine motifs (TCM) suggests a candidate Fe-S cluster ligand role. Hence, we generated by site-directed DPH1 and DPH2 mutagenesis, Dph1•Dph2 variants with cysteines from each TCM replaced individually or in combination by serines. Assays diagnostic for diphthamide formation in vivo reveal that while single substitutions in the TCM of Dph2 cause mild defects, double mutations almost entirely inactivate the RS enzyme. Based on enhanced Dph1 and Dph2 subunit instability in response to cycloheximide chases, the variants with Cys substitutions in their cofactor motifs are particularly prone to protein degradation. In sum, we identify a fourth functionally cooperative Cys residue within the Fe-S motif of Dph2 and show that the Cys-based cofactor binding motifs in Dph1 and Dph2 are critical for the structural integrity of the dimeric RS enzyme in vivo.

In addressing the challenges of data scarcity in biometrics, this study explores the generation of synthetic palmprint images as an efficient, cost effective, and privacy preserving alternative to real-world data reliance. Traditional methods for synthetic biometric image creation primarily involve orientation modifications and filter applications, with no established method specific to palmprints. We introduced the utilization of the “Style-based generator”, StyleGAN2-ADA, from the StyleGAN series, renowned for generating high-quality images. Furthermore, we explore the capabilities of its successor, StyleGAN3, which boasts enhanced image generation, facilitating smooth and realistic transitions. By comparing the performance of StyleGAN3 on public dataset, we aim to establish the most efficient generative model for this purpose. Evaluations were conducted using the SIFT (Scale-Invariant Feature Transform) algorithm into our evaluation framework. Preliminary findings suggest that StyleGAN3 offers superior generative capabilities, enhancing equivariance in synthetic palmprint generation.

Facial recognition systems are widely used systems around the globe. Their applications in real world scenarios like law enforcement, surveillance, ID card identification, information security, access control and many more has made them very important in today’s world. These systems have shown promising results and excellent performance; however, these systems need tremendous number of facial images for training before they are implemented in the real-world scenarios. The problem arises when we face lack of training images due to which the performance of such systems decreases exponentially. The problem becomes even worse when there is only one image per subject for training our facial recognition system, the probe image might contain variation like illumination, expression and disguise which are hard to be accurately recognized. Generative models have achieved great success for handling the lack of training data by generating synthetic data that resembles the original data. We have created a new method by fine tuning the basic Conditional Generative Adversarial Network (CGAN) to generate synthetic facial images provided only single image per subject. These synthetic facial images contain six variations that are smile, anger, stare, illumination and disguise. We increased the size of the dataset and then applied a convolutional neural network for facial recognition, which improved the accuracy of our system from 0.76 to 0.99.

A common reactor type in the chemical and process industry is the fixed-bed reactor. Accurate modeling can be achieved with particle-resolved Computational Fluid Dynamic (CFD) simulations. However, the underlying bed morphology plays a paramount role. Synthetic bed-generation methods are much more flexible and faster than image-based approaches. In this study, we look critically at the two different bed generation methods: Discrete Element Method (DEM) (in the commercial software STAR-CCM+) and the rigid-body model (in the open-source software Blender). The two approaches are compared in terms of synthetically generated beds with experimental data of overall and radial porosity, particle orientation, as well as radial velocities. Both models show accurate agreement for the porosity. However, only Blender shows similar particle orientation than the experimental results. The main drawback of the DEM is the long calculation time and the shape approximation with composite particles.

The analysis of microscopy images has always been an important yet time consuming process in in materials science. Convolutional Neural Networks (CNNs) have been very successfully used for a number of tasks, such as image segmentation. However, training a CNN requires a large amount of hand annotated data, which can be a problem for material science data. We present a procedure to generate synthetic data based on ad-hoc parametric data modelling for enhancing generalization of trained neural network models. Especially for situations where it is not possible to gather a lot of data, such an approach is beneficial and may enable to train a neural network reasonably. Furthermore, we show that targeted data generation by adaptively sampling the parameter space of the generative models gives superior results compared to generating random data points.

Breast cancer is the second most common cancer worldwide, primarily affecting women, while histopathological image analysis is one of the possibilities used to determine tumor malignancy. Regarding image analysis, the application of deep learning has become increasingly prevalent in recent years. However, a significant issue is the unbalanced nature of available datasets, with some classes having more images than others, which may impact the performance of the models due to poorer generalisability. A possible strategy to avoid this problem is downsampling the class with the most images to create a balanced dataset. Nevertheless, this approach is not recommended for small datasets as it can lead to poor model performance. Instead, techniques such as data augmentation are traditionally used to address this issue. These techniques apply simple transformations, such as translation or rotation, to the images to increase variability in the dataset. Recently, Generative Adversarial Networks (GANs) have emerged, which can generate images from a relatively small training set. This work aims to enhance the model’s performance in classifying histopathological images by applying data augmentation using GANs instead of traditional techniques.

Continuous glucose monitoring devices allow diabetes condition management. However, when limited data is available, one option is to increase their size by generating synthetic samples. From a homemade wearable prototype was created a real dataset with 18 instances and 53 attributes that capture characteristics of capillary and venous blood glucose, oxygen concentration, pulse rate, skin temperature, and 24 modules and 24 phases related to bio-impedance. The objective of this article is to generate synthetic datasets, and also it investigates the ideal features subset and optimal model for non-invasive diabetes prediction. Gaussian-Copulas (GC), conditional generative adversarial networks (CG), variational autoencoders, and Copula-GAN techniques' were used to generate five synthetic datasets. Experiments show that GC1 and GC2 datasets follow min/max boundaries and are not copies of the original data. Multilayer perceptron regressor outperformed (train and test) with 2.17, 2.51 in MAE; 9.29, 13.59 in MSE; 3.05, 3.69 in RMSE, and 0.95, 0.92 in R2 in GC1, and 2.64, 3.02 in MAE; 11.43, 15.11 in MSE; 3.38, 3.89 in RMSE, and 0.94, 0.92 in R2 in GC2 with eight features. Future work is necessary to explore autoencoder and generative architectures, datasets with diverse characteristics, and the effect of the number of features.

Autonomous aircraft are the key enablers of future urban services, such as postal and transportation systems. Digital Twins (DT) are promising cutting-edge technologies that can transform the future transport ecosystem into an autonomous and resilient system. However, since DT is a data-driven solution based on AI, proper data management is essential in implementing DT as a Service (DTaaS). One of the challenges in DT development is the availability of real-life data, particularly for training algorithms and verifying the functionality of DT. The current article focuses on data augmentation through synthetic data generation. This approach can facilitate the development of DT in case the developers do not have enough data to train the Machine Learning (ML) algorithm. The current twinning approach provides a prospective ideal state of the engine used for proactive monitoring of the engine’s health as an anomaly detection service. In line with the track of Unmanned Aircraft Vehicles (UAV) for Urban Air Mobility in Smart Cities applications, this paper focuses specifically on the common Hybrid turbo-shaft in drones/helicopters. However, there is a significant gap in real-life similar synthetic data generation in the UAV domain literature. Therefore, Rolling Linear Regression and Kalman Filter algorithms were implemented on noise-added data, which simulate the data measured from the engine in a real-life operational lifecycle. For both thermal and hybrid models, the corresponding DT model has shown high efficiency in noise filtration and a certain amount of predictions with a lower error rate on all engine parameters, except the engine torque.

: Schizophrenia and schizoaffective disorder are generally treated with second-generation antipsychotic drugs. These drugs are mostly D2 and 5-HT2A antagonists. They improve positive schizophrenia symptoms sufficiently well; however, they ameliorate negative schizophrenia symptoms and cognitive functions to a small extent. We review novel antipsychotic drugs exerting a partial agonism at dopaminergic and serotonergic receptors such as cariprazine, brexipiprazole and lumateperone. Besides, the mechanisms of actions of non-anti-dopaminergic antipsychotic drugs are pointed out. Updated neural networks are used to explain the mechanism of action of M4 and M1 receptor agonists, for example xanomeline combined with trospium or emraclidine, and trace-amine-associated receptor 1 agonists (TAAR1), for example ulataront. Phase 3 clinical trials of new third generation antipsychotic drugs are presented. Novel antipsychotic drugs with a partial agonism at D2 and D3 receptors improve positive and negative schizophrenia symptoms as well as cognitive symptoms better than second generation antipsychotic drugs. Besides, they are well tolerated. M4 and M1 receptor agonists, i.e. xanomeline combined with trospium or emraclidine, and TAAR1 agonists, i.e. ulataront, have promising results in clinical trials; they well improve negative schizophrenia symptoms and cognitive functions. Phase 3 clinical trials offer promising results for anti-dopaminergic and non-anti-dopaminergic novel antipsychotic drugs. These new non-anti-dopaminergic antipsychotic drugs better emend negative schizophrenia symptoms, and they better improve cognitive functions than second-generation antipsychotic drugs. Promising new antipsychotic drugs are cariprazine, brexipiprazole, lumateperone, ulataront, and xanomeline combined with trospium. Although phase 3 clinical studies are not yet completed, they showed a therapeutic effect superior to those achieved by second-generation antipsychotic drugs. They are tolerated very well, and they better treat negative schizophrenia symptoms and improve cognitive functions.

Strong yet ductile alloys have long been desired for industrial applications to enhance structural reliability. This work produced two (CoCrNi)93.5Al3Ti3C0.5 medium-entropy alloys with exceptional strength-ductility combinations, via short/medium (3 min/30 min)-time annealing after hot-rolling. Three types of intergranular precipitates including MC, M23C6 carbides, and L12 phase were detected in both the samples. Noticeably, the high density of intragranular L12 precipitates were only founded in the medium-time annealed sample but not in another one. Upon inspection of deformed substructure, it was revealed that the plane slip is the dominant deformation mechanism of both the alloys. This is related to the lower stacking fault energy, higher lattice friction induced by C solute, and slip plane softening caused by intragranular dense L12 precipitates. Additionally, we noted that the stacking fault and twinning act as the mediated mechanisms in deformation of the short-time annealed alloy, while only the former in the medium-time annealed one. It is attributed to the higher energy stacking faults and the increased critical twinning stress caused by intragranular dense L12 precipitates that inhibited the twinning tendency. Our present findings provide not only a guidance for optimizing the mechanical properties of high/medium-entropy alloys, but also a fundamental understanding of deformation mechanisms.

The early elongation events in transcription or translational control in the N-terminal of genes are assuming critical roles in their heterologous expression. The secretory expression of the alkaline pectin lyase APL in B. subtilis were studied to explore the effects of the N-terminal 5-7 amino acids sequences of different signal peptides on gene transcription and protein secretion in this study. The first 5 amino acid sequences of the N-terminal of the signal peptide LipA were identified to play an important role in promoting the expression of APL for the first time. Meanwhile, it also revealed that the signal peptide LipA could lead to higher secretory expression than other signal peptides not because of its sequence structure associated with secretion is stronger but because the N-terminal sequences showed greater advantages in gene transcription. At this basis, the recombinant strain structed in this work showed a new record for the highest extracellular yields (12 295 U/ml) of APL in B. subtilis which was 1.9 times higher than that expressed in the recombinant Escherichia coli strain we had reported before. The novel theories revealed in this study would assuming significance roles for improving expression of foreign proteins in or out of the cells.

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

Receptor–ligand interactions at cell interfaces initiate signaling cascades essential for cellular communication and effector functions. Specifically, T cell receptor (TCR) interactions with pathogen-derived peptides presented by the major histocompatibility complex (pMHC) molecules on antigen-presenting cells are crucial for T cell activation. The binding duration, or dwell time, of TCR–pMHC interactions correlates with downstream signaling efficacy, with strong agonists exhibiting longer lifetimes compared to weak agonists. Traditional surface plasmon resonance (SPR) methods quantify 3D affinity but lack cellular context and fail to account for factors like membrane fluctuations. In the recent years, single-molecule Förster resonance energy transfer (smFRET) has been applied to measure 2D binding kinetics of TCR–pMHC interactions in a cellular context. Here, we introduce a rigorous mathematical model based on survival analysis to determine exponentially distributed receptor–ligand interaction lifetimes, verified through simulated data. Additionally, we developed a comprehensive analysis pipeline to extract interaction lifetimes from raw microscopy images, demonstrating the model’s accuracy and robustness across multiple TCR–pMHC pairs. Our new software suite automates data processing to enhance throughput and reduce bias. This methodology provides a refined tool for investigating T cell activation mechanisms, offering insights into immune response modulation.

The article explores the concept of 'synthetic man' (SM) in the context of 'synthetic biology' (SB), analysing the potential, challenges, and ethical implications of these achievements. Through dialogue with ChatGPT 4, an in-depth understanding of the evolution, contributions of SM, ChatGPT's contribution, and concerns associated with SM is sought, providing insight into how this technology could affect our society. Our study uses a structured dialogue framework with ChatGPT that addresses essential SM questions regarding SM history, contributions, challenges, and concerns. ChatGPT responses are analysed to extract relevant information and identify trends and insights. The ChatGPT dialogue reveals that MS is still a theoretical and speculative concept with significant advances in gene therapy and genetic engineering. The potential contributions of SM in addressing global challenges such as health, environment and education are identified. Ethical and social concerns such as health risks and psychological impact are also highlighted. Differences in ChatGPT responses were observed between different sessions or even within the same session, which highlighted the limitations in the replicability of the research and sometimes the need for clarification of the questions. The article is distinguished by its unique approach of using an advanced language model to explore a complex and speculative topic. The LLM Dialogue Framework on Technology (LLM-DFonTech) framework proposal for structured dialogue with ChatGPT on various technological topics related to the original contribution provides an adaptable tool for interdisciplinary research in emerging technologies. This methodology opens up new possibilities for analyzing and developing trends in technology and society.

Natural host defensins, also sometimes termed antimicrobial peptides, are evolutionarily conserved. They have been studied as antimicrobials, but some pharmaceutical properties, undesirable for clinical use, led to the development of synthetic molecules with constructed peptide arrangements and/or peptides not found in nature. The leading development currently is synthetic small molecule nonpeptide mimetics, whose physical properties capture the characteristics of the natural molecules, and share their biological attributes. We studied brilacidin, an arylamide of this type, for its activity in vitro against fungi (40 clinical isolates, 20 species) that the World Health Organization has highlighted as problem human pathogens. We find antifungal activity at low concentrations for many pathogens, which indicates further screening for activity, particularly in vivo, is justified to evaluate this compound, and other mimetics, as attractive leads for development of effective antifungal agents.

Machine Learning (ML) methods have become important to enhance the performance of decision-support predictive models. However, class imbalance is one of the main challenges for developing ML models, because it limits the generalization of these models, and biases the learning algorithms. In this paper, we consider oversampling methods for generating synthetic categorical clinical data aiming to improve the predictive performance in ML models, and the identification of risk factors for cardiovascular diseases (CVDs). We performed a comparative study of several categorical synthetic data generation methods, including Generative Adversarial Networks (GANs). Then, we assessed the impact of combining oversampling strategies and linear and nonlinear supervised ML methods. Lastly, we conducted a post-hoc model interpretability based on the importance of the risk factors. Experimental results show the potential of GAN-based models for generating high-quality categorical synthetic data, yielding probability mass functions that are highly close to real data, maintaining relevant insights, and contributing to increase the predictive performance. The GAN-based model and a linear classifier outperforms other oversampling techniques, improving 2\% the area under the curve. These results demonstrate the capability of synthetic data to help both in determining risk factors and building models for CVD prediction.

Microbial fuel cells (MFCs) offer sustainable solutions for various biotechnological applications and are a crucial area of research in biotechnology. MFCs can effectively treat wastewater and biodiesel waste by decomposing organic matter and generating electricity. Certain Pseudomonas species possess extracellular electron transfer (EET) pathways, enabling them to transfer electrons from organic compounds to the MFC's anode. Moreover, Pseudomonas species can grow under low oxygen conditions, which is advantageous considering that the electron transfer process in an MFC typically leads to reduced oxygen levels at the anode. This study focuses on evaluating MFCs inoculated with a new Pseudomonas species, grown with 1 g.L-1 glycerol, a common byproduct of biodiesel production. Pseudomonas sp. BJa5 exhibited a maximum power density of 39 mW.m-2. Also, the observed voltammograms and genome analysis indicate the potential production of novel redox mediators by BJa5. Additionally, we investigated the bacterium's potential as a synthetic biology non model chassis. Through testing various genetic parts, including constitutive promoters, replication origins, and cargos using pSEVA vectors as a scaffold, we assessed the bacterium's suitability. Overall, our findings offer valuable insights into utilizing Pseudomonas spp. BJa5 as a novel chassis for MFCs. Synthetic biology approaches can further enhance the performance of this bacterium in MFCs, providing avenues for improvement.

In this study, we demonstrate the direct preparation of dihalo-γ-lactams featuring two distinct halogens from dichloroamides using a novel Atom Exchange Radical Cyclization (AERC) procedure. This method integrates the established Atom Transfer Radical Cyclization with halogen exchange in solution. The technique operates under mild conditions and requires little amounts of metallic copper, serving as both a supplemental activator and reducing agent.

Thioethers are critical in the fields of pharmaceuticals and organic synthesis, but most of the methods for synthesizing alkyl thioethers employ foul-smelling thiols as starting materials or generate them as by-products. Additionally, most thiols are air-sensitive and are easily oxidized to produce disulfides under atmospheric conditions; thus, a novel method for synthesizing thioethers is necessary. This paper reports a simple, effective, green method for synthesizing dialkyl or alkyl aryl thioether derivatives using odorless, stable, low-cost ROCS2K as a thiol surrogate. This transformation offers a broad substrate scope and good functional group tolerance with excellent selectivity. The reaction likely proceeds via xanthate intermediates, which can be readily generated via the nucleophilic substitution of alkyl halides or aryl halides with ROCS2K under transition-metal-free and base-free conditions.

With the development of the energy sector based on renewable primary sources, structural changes are emerging for the entire national energy system. Initially, it was estimated that energy generation based on fossil fuels would decrease until its disappearance. However, the evolution of CO2 capture capacity leads to a possible coexistence for a certain period with the renewable energy sector. The paper develops this concept of coexistence of the two systems, with the positioning of green hydrogen not only within the renewable energy sector but also as a transformation vector for carbon dioxide captured in the form of synthetic fuels such as CH4 and CH3OH. The paper also analyzes the economic aspects related to price differences for energy produced in the two sectors, as well as their interconnection. The technical aspect, as well as the economic one, for storage through various other solutions besides hydrogen, has been highlighted. The development of the renewable energy sector and its demarcation from the fossil fuel energy sector, even with the transcendent vector represented by green hydrogen, leads to the deepening of dispersion aspects between the electricity sector and the thermal energy sector, a less mentioned aspect in current works but of great importance.

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

The raw material purchasing (RMP) problem is to determine the purchasing quantities of raw materials in given periods or cycles. Raw material purchasing optimization is crucial for large-scale steel plants because it is closely related to the supply of raw materials and cost savings. The raw material purchasing of large-scale steel enterprises is characterized by many varieties, large quantities, and high costs. The RMP objective is to minimize the total purchasing cost consisting of the price of raw materials, purchasing set-up costs, and inventory costs and meet product demand. We present a mixed integer linear programming (MILP) model and a column generation (CG) solution for the resulting optimization problem. The column generation algorithm is the generalization of the branch & bound algorithm with solving the linear programming (LP) relaxation of MILP using column generation (CG), and its advantage is to handle large-sized MILPs. Experimental results show the effectiveness and efficiency of the solution.

: Tunnel instability and lining integrity are intimately tied to the creep properties of the surrounding rock. The acquisition of rock mass creep parameters is critical in ascertaining the appropriate timing for lining construction. Nevertheless, creep tests on rock specimens conducted in a controlled setting cannot be straightforwardly extrapolated to rock mass creep analysis. This study performs laboratory-based creep tests on mudstone samples and establishes the corresponding creep constitutive model. Integration of a Mohr-Coulomb element with the Burgers model in series serves to characterise the yield creep behaviour of the rock mass. Additionally, the research outlines a series of 100 orthogonal experiments utilising randomised creep parameters, and formulates a GA-BP neural network inversion model. Employing long-term deformation measurements from the crown and sidewalls of the project site, this study deduces the creep parameters of the mudstone in the investigated tunnel section and examines the prolonged deformation traits of the surrounding rock. Drawing on the deformation traits of the surrounding rock and the forces impacting the primary support and lining structures, this paper evaluates the earliest and latest viable lining casting periods and pinpoints an optimal timing interval for lining implementation. The methodologies employed herein can serve as a benchmark for analogous endeavors internationally.

Modification of electrode surface with a selective layer gives the possibility to detect target ana-lytes of forensic interest. 3-(4-trifluoromethyl)-phenyl)-thiophene (ThPhCF3) was deposited on a graphite (G) electrode by electrochemical oxidation and characterized as a receptor for the recognition of synthetic stimulants (2-aminoindane, buphedrone, naphyrone). First, the structural characterization of the polymeric layer were obtained from Raman spectroscopy. Second, the electrochemical profiles of selected synthetic stimulants and their affinity to ThPhCF3/G-modified electrodes were studied using square wave voltammetry and electrochemical impedance spec-troscopy. The values of the adsorption constant show the importance of – PhCF3 groups in the interaction with synthetic stimulants, namely recognition by the formation of hydrogen bonds (Kads (buphedrone) < Kads (2-AI)) and interaction with aromatic H atoms (Kads (buphedrone) < Kads (naphyrone)). It was demonstrated that the polymeric layer derived from thiophene with – PhCF3 group is capable to increase the intensity of the electrochemical signal.

Storage, transmission and processing of data become a significant problem when large digital data files or databases are involved, as in the case of decentralized online global databases such as blockchain. Here we propose a novel method that allows the scalability of digital assets, including blockchain databases in the download, validation and confidentiality process, by developing a lightweight blockchain technology called Entropic Blockchain. This is a computer-implemented mathematical method to generate an information-entropic numerical representation of a digital asset, which can be utilized on its own, or as an optically machine-readable entropic barcode, for data secure transmission, processing, labelling, identification, one-way encryption and compression, validation, and digital tamper-proof check.

The purpose of this paper is to explore the implementation of Retrieval-Augmented Gen- 14 eration (RAG) technology with open-source Large Language Models (LLMs). For this purpose, a 15 web-based application named PaSSER that integrates RAG with three models - Mistral:7b, 16 Llama2:7b: Orca2:7b, is developed. In its development various technologies are used, including 17 Blockchain for managing and storing assessment results of built-in testing modules. PaSSER em- 18 ploys a set of evaluation metrics for LLMs’ performance - METEOR, ROUGE, BLEU, Perplexity, 19 Cosine similarity, Pearson correlation, and F1 score. The specialized knowledge base is in the smart 20 agriculture domain. As an illustration, the paper presents results and analysis of two tests. First one 21 is assessing the performance of LLMs across different hardware configurations, the other is deter- 22 mining the model that delivers most accurate and contextually relevant responses within the RAG. 23 The paper also discusses the integration of blockchain technology with LLMs to manage and store 24 assessment results within a blockchain environment. The tests revealed that Mistral:7b demon- 25 strates the best results across most of the evaluated metrics. The discussion section comments on 26 technical and hardware considerations that affect the performance of LLMs. Future development 27 will focus in leveraging new larger pre-trained open-source LLMs, exploring different finetuning 28 approaches, and further integration with Blockchain and IPFS.

Recommender Systems (RecSys) are crucial in managing information overload and enhancing user satisfaction across various digital platforms, including e-commerce and entertainment. Evolving from traditional models to Deep Neural Networks (DNNs) and, more recently, Large Language Models (LLMs), these systems leverage sophisticated algorithms to analyze user behaviors and preferences. LLMs, such as GPT-4, are trained on extensive datasets to comprehend and generate natural language, significantly advancing their ability to deliver personalized recommendations. This tutorial explores the transformative impact of LLMs on RecSys, discussing their development, application in handling complex datasets, and the integration of contextual insights. Real-world examples illustrate how LLMs enhance recommendation accuracy and user experience, highlighting challenges and future directions in the field.

This paper performs a comprehensive analysis of the wind energy potential of onshore regions in Greece with emphasis on quantifying the volume risk and the spatial covariance structure. Optimization techniques are employed to derive efficient wind capacity allocation plans (also known as generation portfolios) incorporating different yield aspirations. The generation profile of minimum variance and other optimal portfolios along the efficient frontier are subject to rigorous evaluation using a fusion of descriptive and statistical methods. In particular, principal component analysis is employed to estimate factor models and investigate the spatiotemporal properties of wind power generation, providing valuable insights into the persistence of volume risk. The overarching goal of the study is to employ a set of statistical and mathematical programming tools guiding investors, aggregators and policy makers in their selection of wind energy generating assets. The findings of this research challenge the effectiveness of current policies and industry practices, offering a new perspective on wind energy harvesting with a focus on the management of volume risk.

The article features the structure and functions of plant synthetic promoters frequently exercised to precisely regulate complex regulatory routes. The composition of plant native promoters together with interacting proteins is presented to provide a better understanding of tasks associated with synthetic promoter development. The production of synthetic promoters is conferred on relatively small libraries produced generally by basic molecular or genetic engineering methods such as cis-element shuffling or domain swapping. Moreover, the preparation of large-scale libraries supported by synthetic DNA fragments, directed evolution, and machine or deep learning methodologies is presented. A particularly interesting group of synthetic promoters are bidirectional forms that enable the putative expression of up to 6–8 genes by one regulatory element. The introduction and controlled expression of several genes after one transgenic event strongly decreases the frequency of such problems as complex segregation patterns and random integration of multiple transgenes. These complications are commonly observed during transgenic crop development through traditional, multistep transformation by genetic constructs containing a single gene. Another path to solving problems associated with the low complexity and homology of already tested DNA fragments is through orthogonal expression systems composed of synthetic promoters and trans-factors that do not occur in nature or arise from different species. Their structure, functions, and applications are rendered in the article.

Abstract: The biological process of photosynthesis was critical in catalyzing the oxygenation of Earth’s atmosphere 2.5 billion years ago, changing the course of development of life on Earth. Recently, the fields of applied and synthetic photosynthesis have utilized the light-driven protein-pigment supercomplexes central to photosynthesis for the photocatalytic production of fuel and other various valuable products. The reaction center Photosystem I is of particular interest in applied photosynthesis due to its high stability post-purification, non-geopolitical limitation, and its ability to generate the greatest reducing power found in Nature. These remarkable properties have been harnessed for the photocatalytic production of a number of valuable products in the applied photosynthesis research field. These primarily include photocurrents and molecular hydrogen as fuels. The use of artificial reaction centers to generate substrates and reducing equivalents to drive non-photoactive enzymes for valuable product generation has been a long-standing area of interest of the synthetic photosynthesis research field. In this review, we cover advances in these areas and further speculate synthetic and applied photosynthesis as photocatalysts for the generation of valuable products.

High resolution information on nucleotide arrangement in the genome of any or-ganism is critical to understand its genetic makeup, function, and evolutionary his-tory. For years, DNA sequencing has provided crucial breakthroughs in the field of genomics and molecular biology. With the advent of technology, Next Generation Sequencing has now transformed the whole genome sequencing prospects, thus unveiling the novel and interesting features of an organism genome that can behold. Next generation sequencing platforms offer realistic approach to identify and anal-yses whole genome with high throughput, accuracy, scalability in a very short time span. Information obtained can be further used in improving our existing healthcare systems, designing novel and personalized therapeutic modules, making the envi-ronment sustainable and proactively preparing ourselves for future pandemics and outbreaks. This article discusses the various NGS technologies and approaches, their advantages, drawbacks, and futuristic usage in different fields. Though still in nascent stages and marred with flaws, with ongoing advancement, NGS will indeed have promising impacts in the future.

Functional dependence of the axial zero-field splitting parameter D with respect to a properly chosen geometrical parameter (Dstr) in metal complexes is termed the Magnetostructural D-Correlation. In mononuclear hexacoordinate Ni(II) complexes with the ground electronic term 3B1g (3A2g in the regular octahedron) it proceeds along two intercepting straight lines allowing to predict the sign and magnitude of the D-parameter by knowing the X-ray structure alone; Dstr is constructed from the metal-ligand bond lengths. In hexacoordinate Co(II) complexes it is applicable only in the segment of the compressed bipyramid where the ground electronic term 4B1g is orbitally non-degenerate so that the spin Hamiltonian formalism holds true. The D vs Dstr correlation is strongly non-linear and it is represented by a set of decreasing exponentials. In tetracoordinate Co(II) complexes, on the contrary, the angular distortion from the regular tetrahedron is crucial so that the appropriate structural parameter Dstr is constructed of bond angles. All of these empirical correlations originate in the electronic structure of metal complexes that can be modelled by the generalized crystal-field theory. As the barrier to spin reversal in the single-molecule magnets is proportional to the D-value, for a rational tuning and/or prediction of the single-molecule magnetic behavior knowledge/prediction of the D-parameter is beneficial. In this review, we present the statistical processing of an extensive set of structural and magnetic data of Co(II) and Ni(II) complexes, which were published over the past 15 years. Magnetostructural D-correlations defined for this data set are reviewed in detail.

Serotonin (5-HT) show important relations to stress, and this relationship is crucial to understanding the psychobiology of common mental disorders. Environmental stressors regulate phasic and tonic serotonin levels, which are related to valence and outcome probabilities. This regulation takes place at smaller timescales, but also at the level of gene expression regulation. Moreover, genes related to the synthesis, metabolism, and transport of 5-HT are also involved in this regulation. Genetic variations in these genes modulate how stressors can lead to mental distress, but stressors also modulate gene expression in a genotype-dependent manner. As a result, the relationship between psychosocial stress and the regulation of the expression of 5-HTergic genes is bidirectional. This suggests a “circular causality” in which gene variations control tonic and phasic 5-HT signals (“upward causality”), while configurations and functions of the entire organism determine which genes are up- or downregulated, or which gene products are actually relevant in each situation (“downward causality”). The highly important role of social factors in human psychopathology is highlighted, and factors such as attachment and socioeconomic status modulate how the circular vertical causality between genes, neurotransmitters, and behavior is organized, representing circular horizontal causality. These complex interrelationships also suggest that more refined epistemologies are needed to fully grasp the relationship between 5-HT and common mental disorders.

The application of non-uniform spiral gratings to control structure, topological parameters and propagation of orbital angular momentum (OAM) beams was studied experimentally with coherent near-infrared light. Adapted digital spiral grating structures were programmed into the phase map of a high-resolution liquid-crystal-on-silicon spatial light modulator (LCoS-SLM). It is shown that characteristic spatio-spectral anomalies related to Gouy phase shift can be used as pointers to quantify rotational beam properties. Depending on sign and gradient of spatially variable periods of chirped spiral gratings (CSG), variations of rotation angle and angular velocity as a function of propagation distance were measured. Propagation-dependent self-torque is introduced in analogy to known local self-torque phenomena of OAM beams as obtained by the superposition of temporally chirped or phase modulated wavepackets.

Due to related uncertainties brought by changes in energy consumption and the integration of rooftop photovoltaic systems, the accuracy and availability of load profiling data are difficult to achieve. However, project managers and planners use a precise load profile as a crucial tool when determining whether the feeder must be updated or de-loaded. The paper aims to create a non-intrusive monitoring system that predicts the synthetic load profiles behavior of energy consumption using a Light Gradient Boosted and Support Vector Machine (SVM) machine learning technique. The most effective ML algorithm is chosen, and it has the potential to be assessed and verified using validation curves, residuals model generation, and prediction error metrics based on the following key statistical indicators: Mean Absolute Error, Mean Square Error, Root Mean Square Error, R-Square, Root Mean Squared Logarithmic Error, and Mean Absolute Percentage Error. The most effective ML has the potential to be assessed and verified using validation curves, residual model generation, and prediction error metrics based on the following key statistical indicators. The result shows that the estimation of the Irms avg -based on LightGBM is more accurate than the SVM because of its quick, economical, and difficult to overfit, particularly with high-dimensional data, speed, and efficiency of the MAE (3.0698), MSE (15.2757), RMSE (3.9020), RMSLE (0.1433), and MAPE (0.0049) respectively. Additionally, the machine learning model shows that, when compared to the SVM, the LightGBM model had the highest accurate prediction, with R-Square values of 89.8%, 90.3%, and 88.5% for Irms_A_avg, Irms_B_avg, and Irms_C_avg, respectively for Brakfontein Substation supply region, and best represents a diverse customer base.

This paper designed a new type of generator, transgenerator, that integrates the wind turbine and flywheel into one system, aiming to make the flywheel distributed energy storage (FDES) more modular and scalable than the conventional FDES. The transgenerator is a three-member dual-mechanical-port (DMP) machine with two rotating members (inner and outer rotors) and one stationary member (stator). The transgenerator-flywheel system is introduced with the system configuration, transgenerator overview, flywheel operation principle and power management strategies, and control system. Simulations are performed in MATLAB/ Simulink to verify the system viability, including control system verification and the flywheel storage performance evaluation. Results show that the inner and outer rotors can be controlled independently with accurate and fast control response, and the grid-side control works properly. The flywheel performs well with considerable charging power and storage capacity.

Historically the use of artificial intelligence (AI) in paediatrics dates back to 1984 with the intro-duction of a computer-assisted medical decision-making system called SHELP. Since then, research on the use of AI in pediatrics has become much more popular, and the number of reviewed publications largely increased. Consequently, a need for a holistic research landscape enabling researchers and other interested parties to gain insights into, deepen their knowledge about or inform them about the use of AI in pediatrics arised. To fill this gap a novel methodology named synthetic knowledge synthesis was applied. Using SKS we identified most prolific countries, in-stitutions, source titles, funding agencies, research themes, research gaps and hot spots.

The transformation of the state of polarization of a light beam by its linear interaction with a material medium can be modeled through the Stokes-Mueller formalism. The Mueller matrix associated with a given interaction depends on many aspects of the measurement configuration. In particular, different Mueller matrices can be measured for a fixed material sample depending on the spectral profile of the light probe. For a given light probe and a given sample with inhomogeneous spatial behavior, the polarimetric descriptors of the point-to-point Mueller matrices can be mapped leading to respective polarimetric images. The procedure can be repeated sequentially by using light probes with different central frequencies. In addition, the point-to-point Mueller matrices consecutively measured can be combined synthetically through convex sums leading to respective new Mueller matrices, in general with increased polarimetric randomness, thus exhibiting specific values for the associated polarimetric descriptors, including the indices of polarimetric purity, and generating new polarimetric images which are different from those obtained from the original Mueller matrices. In this work, the fundamentals for such synthetic generation of additional polarimetric images are described, providing a new tool that enhances the exploitation of Mueller polarimetry.

Large Language Models (LLMs) have demonstrated promising capabilities to solve complex tasks in critical sectors such as healthcare. However, LLMs are limited by their training data which is often outdated, the tendency to generate inaccurate ("hallucinated") content and a lack of transparency in the content they generate. To address these limitations, retrieval augmented generation (RAG) grounds the responses of LLMs by exposing them to external knowledge sources. However, in the healthcare domain there is currently a lack of systematic understanding of which datasets, RAG methodologies and evaluation frameworks are available. This review aims to bridge this gap by assessing RAG-based approaches employed by LLMs in healthcare, focusing on the different steps of retrieval, augmentation and generation. Additionally, we identify the limitations, strengths and gaps in the existing literature. Our synthesis shows that proprietary models such as GPT-3.5/4 are the most used for RAG applications in healthcare. Also, there is a lack of standardized evaluation frameworks for RAG-based applications. In addition, the majority of the studies do not assess or address ethical considerations related to RAG in healthcare. It is important to account for ethical challenges that are inherent when AI systems are implemented in the clinical setting. Lastly, we highlight the need for further research and development to ensure responsible and effective adoption of RAG in the medical domain.

The introduction of biologic therapies has led to dramatic improvements in the management of moderate-to-severe psoriasis. Even though the efficacy and safety of the newer biologic agents are difficult to match, oral administration is considered an important advantage by many patients. Current research is focused on development of oral therapies with improved efficacy and safety compared to available alternatives, as exemplified by deucravacitinib, the first oral allosteric Tyk2 inhibitor approved for the treatment of moderate-to-severe psoriasis in adults. Recent advances in our knowledge of psoriasis pathogenesis have also led to the development of targeted topical molecules, mostly focused on intracellular signaling pathways, such as AhR, PDE-4 and Jak-STAT. Topical tapinarof, an AhR modulator, and roflumilast, a PDE-4 inhibitor, have exhibited favorable efficacy and safety outcomes have been approved by the FDA for the topical treatment of plaque psoriasis. This revision focuses on the most recent oral and topical therapies available for psoriasis and specially on those that are currently under evaluation and development for the treatment of psoriasis.

The World Health Organization (WHO) recently added snakebite envenoming to the priority list of Neglected Tropical Diseases (NTD). It is thought that ~75% of mortality following snakebite occurs outside the hospital setting, making the temporal gap between a bite and antivenom administration a major therapeutic challenge. Small molecule therapeutics (SMTs) have been proposed as potential pre-referral treatments for snakebite to help address this gap. Herein, we discuss the characteristics, potential uses and development of SMTs as potential treatments for snakebite envenomation. We focus on SMTs that are secretory phospholipase A2 (sPLA2) inhibitors and metalloprotease (MP) inhibitors.

While Retrieval-Augmented Generation (RAG) enhances Large Language Models (LLMs), it also presents challenges that can affect model accuracy and performance. Practical applications show that RAG can mask the intrinsic capabilities of LLMs. Firstly, LLMs may become overly dependent on external retrieval, underutilizing their own knowledge and inference abilities, which can reduce responsiveness. Secondly, RAG techniques might introduce irrelevant or low-quality information, adding noise to the LLM. This can disrupt the normal generation process, leading to inefficient and low-quality content, especially when dealing with complex problems. This paper proposes a RAG framework that uses reflective tags to control retrieval. This framework evaluates retrieved documents in parallel and incorporates the Chain of Thought (CoT) technique for step-by-step content generation. The model selects the highest quality and most accurate content for final generation. The main contributions include: 1) Reducing the hallucination problem by selectively utilizing high-scoring document, 2) Enhancing real-time performance through timely external database retrieval, and 3) Minimizing negative impacts by filtering out irrelevant or unreliable information through parallel content generation and reflective tagging. These advancements aim to optimize the integration of retrieval mechanisms with LLMs, ensuring high-quality and reliable outputs.

The reviews usefulness has been the aim of several research studies. However, results regarding the significance of usefulness determinants are often contradicting, thus decreasing the accuracy of reviews’ helpfulness estimation. Also, bias in user reviews attributed to differences e.g. in gender, nationality, etc., may result into misleading judgments thus diminishing reviews’ usefulness. Research is needed for sentiment analysis algorithms that incorporate bias embedded in reviews, thus improving their usefulness, readability, credibility, etc. This study utilizes fuzzy relations and fuzzy synthetic evaluation (FSE) in order to calculate reviews’ usefulness by incorporating users’ biases as expressed in terms of reviews’ articulacy and sentiment polarity. It selected and analysed 95.678 hotel user reviews from Tripadvisor, for five nationalities. The findings indicate that there are differences among nationalities. The British are most consistent in their judgments expressed in titles and review documents. The British and the Greek review titles suffice to convey any negative sentiments. The Dutch use fewer words in their reviews than the other nationalities. This study suggests that fuzzy logic captures subjectivity which is often found in reviews, and it can be used to quantify users’ behavioral differences, calculate reviews usefulness, and provide the means for developing more accurate voting systems.

Reviewed are recent efforts leading to chemo-enzymatic syntheses of strongly fluorescent ribosides of nucleobase analogs, potentially applicable in analytical biochemistry and cell biology. Described are syntheses and properties of fluorescent purine, 8-azapurine and etheno-purine ribosides, obtained using various types of the purine nucleoside phosphorylase (PNP) as catalysts of ribosylation, and -ribose-1-phosphate (r1P) as a second substrate. In several instances, the ribosylation sites were different than the canonical purine N9. Some of the obtained ribosides show fluorescence yields close to 100%. Their main applications are assays of PNP, nucleoside hydrolases, and other enzyme activities both in vitro and, possibly, within the living cells, using fluorescence microscopy.

This study considers an application of the first-order Grey Markov Model to foresee the values of Italian power generation in relation to the available energy sources. The model is used to fit data from the Italian energy system from 2000 to 2022. The integration of Markovian error introduces a random element to the model, which is able now to capture inherent uncertainties and misalignments between the Grey model predictions and the real data. This application provides valuable insights for strategic planning in the energy sector and future developments. The results show good accuracy of the predictions, which provides powerful information for the effective implementation of energy policies concerning the evolution of energy demand in the country. Despite advancements, Italy’s 2032 energy mix will still significantly rely on fossil fuels, emphasizing the need for sustained efforts beyond 2032 to enhance sustainability.

Despite significant advancements in Artificial Intelligence (AI) and Large Language Models (LLMs), detecting and mitigating bias remains a critical challenge, particularly within social media platforms like X (formerly Twitter) and in addressing cyberbullying present on them. This research investigates the effectiveness of leading LLMs in generating synthetic biased and cyberbullying data and evaluates the proficiency of Transformer AI models in detecting bias and cyberbullying within both authentic and synthetic contexts. The study involves semantic analysis and feature engineering on a dataset of over 48,000 sentences related to cyberbullying collected from Twitter (before it became X). Leveraging state-of-the-art LLMs such as ChatGPT-4o, Pi AI, Claude 3 Opus, and Gemini-1.5, synthetic biased, cyberbullying, and neutral data were generated to deepen the understanding of bias in human-generated data. AI models including DeBERTa, Longformer, BigBird, HateBERT, MobileBERT, DistilBERT, BERT, RoBERTa, ELECTRA, and XLNet were initially trained to classify Twitter cyberbullying data and subsequently fine-tuned, optimized, and quantized for multilabel classification (detecting both biases and cyberbullying). The study's outcomes include a prototype of a hybrid application that combines a Bias Data Detector and a Bias Data Generator, validated through extensive testing.

This paper introduces an innovative energy circuit that challenges conventional understandings of energy conservation, marking a significant departure from traditional frameworks. Seeking to enhance energy generation within existing paradigms, this innovation holds promise for addressing pressing global issues such as the energy crisis and environmental sustainability, while also stimulating scientific inquiry. In contrast to prevalent misconceptions rooted in philosophical and scientific constraints, this study refutes the notion of generating energy from nothing and questions the viability of perpetual motion machines as conceptual models. Instead, it proposes a novel circuit design derived from an unconventional electrical short circuit, which is shown to disrupt the established principles of energy conservation. This circuit offers a transformative approach with diverse applications, including self-recharging capabilities for electric vehicles, bolstering microgrid infrastructure, and facilitating the integration of renewable energy sources. Transcending conventional scientific boundaries, this paper prompts philosophical reflections on the evolving nature of scientific exploration. Ultimately, the energy circuit represents a pivotal step towards mitigating the global energy crisis by reducing reliance on finite resources and fostering sustainability. The paper concludes by illustrating the circuit's potential to revolutionize energy systems and contribute to a more resilient and sustainable future.

The rapid and accurate detection of viruses and the discovery of single nucleotide polymorphisms (SNPs) are crucial for disease management and understanding viral evolution. In this study, a pipeline for virus detection, validation, and SNP discovery from next-generation sequencing (NGS) data is presented. By integrating state-of-the-art bioinformatics tools with artificial intelligence, the pipeline processes raw sequencing data to identify viral sequences with high accuracy and sensitivity. Before aligning the reads to the reference genomes, quality control measures and adapter trimming are performed to ensure the integrity of the data. Unmapped reads are subjected to de novo assembly to reveal novel viral sequences and genetic elements. The effectiveness of the pipeline is demonstrated by the identification of virus sequences, illustrating its potential for the detection of known and emerging pathogens. SNP discovery is performed using a custom Python script that compares the entire population of sequenced viral reads to a reference genome. This approach provides a comprehensive overview of viral genetic diversity and identifies dominant variants and a spectrum of genetic variations. The robustness of the pipeline is confirmed by the recovery of complete viral sequences, which improves our understanding of viral genomics. This study highlights the synergy between traditional bioinformatics techniques and modern approaches, providing a robust tool for analyzing viral genomes and contributing to the broader field of viral genomics.

This study investigates job satisfaction, burnout, and well-being among first-generation migrant physicians in anesthesia and intensive care medicine in Germany, comparing them to their native German counterparts. Utilizing a cross-sectional survey design, the study collected data from 513 physicians, 110 of whom identified as having a migration background. Job satisfaction was measured using the German version of the Warr-Cook-Wall (WCW) Job Satisfaction Scale, burnout was assessed with the Copenhagen Burnout Inventory (CBI), and well-being was evaluated using the WHO-5 Well-Being Index. The job satisfaction ratings revealed no significant differences between migrant and German physicians in most dimensions, including physical workload, freedom to choose work methods, satisfaction with colleagues, responsibility, income, skill utilization, and variety in work tasks. However, migrant physicians reported significantly higher satisfaction with recognition received for their work and lower dissatisfaction with working hours. Burnout assessments showed that migrant physicians experienced higher psychological strain, perceiving every work hour as more exhausting and having significantly less energy for family and friends. Notably, migrant physicians reported higher difficulty and frustration in working with patients. Well-being ratings indicated that migrant physicians felt less energetic and active but found their daily life more filled with interesting activities. The findings underscore the unique challenges faced by migrant physicians, particularly in terms of recognition and patient-related burnout. These results highlight the need for targeted interventions to support migrant physicians, including cultural competence training and flexible working hours to enhance their job satisfaction and overall well-being. Addressing these issues is crucial for maintaining the quality of patient care and the occupational health of migrant physicians in Germany.

Diarrhea remains one of the leading causes of mortality worldwide, especially among children. Recent epidemiological studies conducted in developing countries identified Shigella species as the most predominant pathogenic bacteria responsible for diarrhea. Antimicrobial therapy is necessary for Shigella infections; however, the rapid emergence of resistance against existing antimicrobials in Shigella spp. poses a serious global health problem. To identify alternative antimicrobial compounds with activity against Shigella species, the pathogens responsible for bacterial diarrhea. In this study, we have applied antibacterial phenotypic screening to identify potent anti-Shigella compounds across a broad chemical diversity, including selected acetaminophen derivatives containing benzothiazoles backbone, and their combination with certain antibiotics. In continuation to our effort in searching potent antimicrobial compounds, we have found this time around that two acetaminophen derivatives containing benzothiazoles backbone (4a and 4b) could inhibit the growth of Shigella flexneri with common MIC value of 12.5 µg/ml. These compounds were established through a time-kill kinetics’ study to be bactericidal. Meanwhile, the 2-aminobenzothiazoles (1a and 1b) used for the synthesis of compounds 4 (a & b) were found to be poorly active (MIC: 100 µg/ml) against this pathogen. Combination studies of 4a and 4b with the least susceptible antibiotics (ceftriaxone and cotrimoxazole) demonstrated synergistic anti-Shigella activity. The present study demonstrates that the azobenzothiazole dyes 4 (a & b) can be repurposed as potential anti-Shigella compounds, which can serve as scaffolds for the development of new agents against infectious diarrhea caused by Shigella and other enteric pathogens, especially in developing countries.

Dynamic optical structural color is always desired in various display applications and usually involves active materials. Full-color generation, especially bi-directional full-color generation in both reflective and transmissive modes, without any active materials included has been rarely investigated. Herein, we demonstrate a scheme of bi-directional full-color generation based on a plasmonic metasurface modulated by rotation of the polarization angle of the incident light without varying the geometry and the optical properties of the materials and the environment where the metasurface resides. The metasurface unit cell consists of plasmonic modules aligning in three directions and is patterned in a square array. The metasurface structural color device generates full colors in both reflection and transmission. Based on the proposed polarization-dependent structural color, information encoding of three multiplexed animal images and quick-responsive (QR) codes is demonstrated to verify the efficient information encoding and decoding of the proposed scheme. The animals can be seen under different polarization incidence and the QR codes can be successfully decoded by the polarization rotation in transmission. The proposed bi-directional full-color generation metasurface has great potential in applications such as kaleidoscope generation, anti-counterfeiting, dynamic color display, and optical information encoding.

The ability to read and quantify nucleic acids such as DNA and RNA using sequencing technologies has revolutionized our understanding of life. With the emergence of synthetic biology, these tools are now being put to work in new ways - enabling de novo biological design. Here, we show how sequencing is supporting the creation of a new wave of biological parts and systems, as well as providing the vast data sets needed for the machine learning of design rules for predictive bioengineering. However, we believe this is only the tip of the iceberg and end by providing an outlook on recent advances that will likely broaden the role of sequencing in synthetic biology and its deployment in real-world environments.

Bone is a dynamic tissue with the capacity of repair and regeneration in specific conditions. Nevertheless, due to the increased incidence of bone disorders, the need of bone grafts has been growing over the past decades and the development of an ideal bone graft with optimal properties remains a clinical challenge. This review addresses the bone properties (morphology, composition and their repair and regeneration capacity) and puts the main focus on the potential strategies for developing bone repair and regeneration materials. It describes the requirements for designing a suitable scaffold material, types of materials (polymers, ceramics and composites) and techniques to obtain the porous structures (additive manufacturing techniques/robocasting or derived from marine skeletons) for bone tissue engineering applications. The main objective of this review is to gather the knowledge on the materials and methods for the production of scaffolds for bone tissue engineering and highlighting the potential of natural porous structures such as marine skeletons as promising alternative bone graft substitute materials without any further mineralogical changes, or after partial or total transformation into calcium phosphate. The suitability of the marine-derived porous bone graft substitutes for the intended applications will be also discussed.

Microalgae have emerged as potential feed stock for third generation biofuel and other bioactive compounds. In the present investigation we have evaluated the two native strains of Oscillatoria (O. subbrevis MTC-20702 and O. sancta MTC-20703) isolated from two different fresh water biotopes of Meerut, U.P., India and were subjected for the characterization of generation time, biomass, bio-molecules including Chlorophyll-a, carotenoids, carbohydrate, lipids, phycobilins and proteins. Both strains of Oscillatoria were grown in batch culture till the initiation of declining phase and were harvested on every 10th day of incubation till the starting of declining phase. Result of the present investigation revealed that O. subbrevis MTC-20702 can be potentially exploited for the production of high algal biomass, feed stock for biofuel, Chl-a, carotenoids, c-Allophycocyanin and maximum yield of these bioactive compounds can be achieved on 20th day. However, O. santa could be very good source for c-Phyocyanin, c-Phycoerythrin, carbohydrate and protein and these also can be achieved highest on 20th day of incubation. In addition, as these two strains were isolated from water reservoirs and they can be cultivated in large scale for the production of desired bio-molecules.

MIMO (multiple-input multiple-output) radar provides much more flexibility than the traditional radar for its ability to realize far more observation channels than the actual number of T/R (transmit and receive) elements. Designing the array of MIMO imaging radar, the commonly used virtual array theory generally assumes that all elements are placed on the same line. However, due to the physical size of the antennas and coupling effect between T/R elements, a certain height difference between T/R arrays is essential, resulting in the defocusing of edge points of the scene. On the other hand, the virtual array theory implies far-field approximation, leading to inevitable high grating lobes in the imaging result of near-field edge points of the scene observed by common MIMO array. To tackle these problems, this paper derives the relationship between target’s PSF (point spread function) and pattern of T/R arrays, by which the design criterion of near-field imaging MIMO array is presented. Firstly, the proper height between T/R arrays is designed to focus the near-field edge points well. Secondly, the far-field array is modified to suppress the grating lobes in the near-field area. Finally, the validity of the proposed methods is verified by simulations and an experiment.

The aim of this study was to evaluate the use of a flexible synthetic polymer bone graft to provide implant stability in the absence of implant stability during implant placement in a dense cortical bone model. Sockets were prepared on polyurethane blocks according to the standard implant socket drilling protocol in the control group, both oversizing and deepening in group 2, and oversizing only in group 3. In groups 2 and 3, flexible synthetic polymer bone grafts were placed in the sockets prior to implant placement. The implants were placed at bone level in all groups. The highest torque value obtained was recorded as the insertion torque. 75 implant sites in 3 groups were included in the study. The torque values of the implants in the control group were significantly higher than those of the implants with the oversized and deepened sockets and the oversized-only sockets (p&lt;0.05; p&lt;0.01).The torque values of the implants with the oversized and deepened sockets were significantly higher than those of the implants with the oversized-only sockets (p&lt;0.01). In this study, flexible synthetic polymer bone graft was shown to be effective in achieving implant stability in the management of implants with loss of primary stability.

Raman spectra of [TeX6](Y2) (X, Y - Cl, Br, I) were recorded in the temperature range 5-300 K. The vibration frequency of molecular halogens as function on temperature and the type of halogen X- in the [TeX6]2- complex was obtained. The vibration frequency of the molecular halogen Y2 depends on the type of halogen X- complex [TeX6]2- The temperature dependence of the Y2 frequency is anomalous compared to what was expected for a conventional anharmonic oscillator. It is shown that the interpretation of the experimental results based on the concept of traditional chemical bonding is quite satisfactory in all cases. The study was motivated by the need to consider the mechanism of interaction in the X-Y2 contacts.

Molecule radiation can be used as a tool to study colder regions in switching arc plasmas like arc fringes in contact to walls and ranges around current zero (CZ). This is demonstrated in the present study for the first time for the case of ablation-dominated high–current arcs as key elements of self–blast circuit breakers. The arc in a model circuit breaker (MCB) in CO2 with and an arc in a long nozzle under ambient conditions with peak currents between 5 and 10 kA were studied by emission and absorption spectroscopy in the visible spectral range. The nozzle material was polytetrafluoroethylene (PTFE) in both cases. Imaging spectroscopy was carried out either with high-speed cameras or with intensified CCD cameras. A pulsed high-intensity Xe lamp was applied as background radiator for the broad-band absorption spectroscopy. Emission of Swan bands from carbon dimers was observed at the edge of nozzles only or across the whole nozzle radius with highest intensity in the arc center, depending on current and nozzle geometry. Furthermore, absorption of C2 Swan bands and CuF bands were found with the arc plasma serving as background radiator. After CZ, only CuF was detected in absorption experiments.

Multicellularity is one of the major evolutionary transitions, and its rise provided the ingredients for the emergence of a biosphere inhabited by complex organisms. Over the last decades, the potential for bioengineering multicellular systems has been instrumental in interrogating nature and exploring novel paths to regeneration and disease, as well as cognition and behaviour. Here, we provide a list of open problems that encapsulate many of the ongoing and future challenges in the field, and we suggest conceptual approaches that may facilitate progress.

Biometric fingerprint identification hinges on the reliability of its sensors, however, calibrating and standardizing these sensors poses significant challenges, particularly in regard to repeatability and data diversity. To tackle these issues, we propose methodologies for fabricating synthetic 3D fingerprint targets, or phantoms, that closely emulate real human fingerprints. These phantoms enable the precise evaluation and validation of fingerprint sensors under controlled and repeatable conditions. Our research employs laser engraving, 3D printing, and CNC machining techniques, utilizing different materials. We assess the phantoms' fidelity to synthetic fingerprint patterns, intra-class variability, and interoperability across different manufacturing methods. The findings demonstrate that a combination of laser engraving or CNC machining with silicone casting produces finger-like shaped phantoms with high accuracy and consistency for rolled fingerprint recordings. For slap recordings, direct laser engraving of flat silicone targets excels and in the contactless fingerprint sensor setting, 3D printing and silicone filling provides the most favorable attributes. Our work enables a comprehensive, method-independent comparison of various fabrication methodologies, offering a unique perspective on the strengths and weaknesses of each approach. This facilitates a broader understanding of fingerprint recognition system validation and performance assessment.

While rapidly becoming a main thread in the development of new therapies, the rise of synthetic biology is also tied to concerns about the potential impact on ecosystems. That is particularly relevant in the of deployment in natural habitats, including the human microbiome. These concerns have boosted the analysis of diverse strategies of containment, from engineered cell death to xenobiology to the creation of Xeno nucleic acids. However, little attention has been paid to the potential containment implicit in nonlinear ecological interactions and the lessons provided by the population dynamics models used in community ecology. If we consider synthetic strains as some class of "species" embedded within an ecological context, it is possible to show that some network interaction patterns and their associated nonlinear responses can offer a reliable source of containment. Here we present and discuss some simple examples of these "ecological firewalls" that could help provide a self-regulating biocontainment. Our firewall designs can help to ensure that engineered organisms have a limited spread while, when required, preventing their extinction. The basic synthetic designs and their dynamical behaviour are presented, each one inspired in a given ecological class of interaction. Their possible applications are discussed and the broader connection with invasion ecology outlined.

Cognitive networks have evolved to cope with uncertain environments in order to make reliable decisions. Such decision making circuits need to respond to the external world in efficient and flexible ways, and one potentially general mechanism of achieving this is grounded in critical states. Mounting evidence has shown that brains operate close to such critical boundaries consistent with self-organized criticality (SOC). Is this also taking place in small-scale living systems, such as cells? Here we explore a recent model of engineered gene networks that have been shown to exploit the feedback between order and control parameters (as defined by expression levels of two coupled genes) to achieve a SOC state. We suggest that such SOC motif could be exploited to generate adaptive behavioral patterns and might help design fast responses in synthetic cellular and multicellular organisms.

A tetraphenylethylene-derived compound, TPEPhDAT, has been prepared by successive Suzuki-Miyaura coupling and ring-closing reactions. This compound exhibits aggregation-induced emission (AIE) properties in the DMSO/MeOH system, with a fluorescence emission intensity in the aggregated state that is 5-fold higher than that of its counterpart in a dilute solution. Moreover, the diaminotriazine structure of the molecule is a good acceptor of protons, and thus the TPEPhDAT molecule exhibits acid-responsive fluorescence. TPEPhDAT was protonated by trifluoroacetic acid (TFA), leading to a fluorescence quenching, which was reversibly restored by treatment with ammonia (On-Off switch). Time-dependent density functional theory (TDDFT) computational studies have shown that protonation enhances the electron-withdrawing capacity of the triazine nucleus and reduces the bandgap, producing a more intense intramolecular charge transfer (ICT), thus leading to fluorescence quenching. MeOH can easily remove the protonated TPEPhDAT, and this acid-induced discolouration and erasable property can be applied in anti-counterfeiting.

Inhibition of amyloid fibril formation could benefit patients with systemic amyloidosis. In this group of diseases, deposition of amyloid fibrils derived from normally soluble proteins leads to progressive tissue damage and organ failure. Although many small molecules have been proposed as inhibitors of amyloid formation, few have been successful in clinical trials. Amyloid formation is complex and several individual steps could be targeted by small molecules. However, the exact mechanism of action for a molecule is often not known, which impedes medicinal chemistry efforts to develop more potent molecules. Furthermore, commonly used assays are prone to artifacts that must be controlled for. Here, potential mechanisms by which small molecules could inhibit aggregation of immunoglobulin light chain dimers, the precursor proteins for AL amyloidosis are studied in assays that recapitulate different aspects of amyloidogenesis in vitro. One molecule reduced unfolding-coupled proteolysis of light chains, but no molecules inhibited aggregation of light chains or disrupted pre-formed amyloid fibrils. This work demonstrates the challenges associated with drug development for amyloidosis, but also highlights the potential to combine therapies that target different aspects of amyloidogenesis.

We tested the hypothesis that concatemers of ancestral tRNAs gave rise to the 16S ribosomal RNA. We built an ancestral sequence of proto-tRNAs that showed a significant identity of 51.69% and a percentage of structural identity of 0.941 with the 16S ribosomal molecule. We also propose a hypothesis for the emergence of translation.

Indole is a versatile pharmacophore widely distributed in bioactive natural products. This privileged scaffold has been found in a variety of molecules isolated from marine organisms such as algae and sponges. Among these, indole alkaloids represent one of the biggest, most promising family of compounds, having shown a wide range of pharmacological properties, including anti-inflammatory, antiviral and anticancer activities. The aim of this review is to show the current scenario of marine indole alkaloid derivatives, covering not only the most common chemical structures, but also new synthetic routes developed during the last years as well as promising therapeutic applications.

This article titled "AI and IoT in Automation and Security: A Vision for Next Generation Applications," explored the implications of marrying IoT with AI in the realms of automation and security; this piece goes further into what that entails. In this paper, we present innovative application descriptions arising from this technology convergence and its future-generation applications. We found that AI brings strong cyber security, predictive maintenance, and decision-making capabilities to the table due to its advanced algorithms and machine learning models. IoT has the potential to allow businesses to extract and generate big data, automate processes, and monitor in real-time thousands and even millions of businesses at once. For now, we believe some of the possible main conclusions will be that the smart city, stand-alone systems, and user experience will be quite consumer-friendly. Importantly, the study also assessed facets such as data protection, system interoperability, and a few others. Our vision underscores the essential of a strong structure to connect the full latent of AI and IoT, finally aiming to create more capable, protected, and approachable environments. Significant results include achieving 95.8% accuracy in anomaly detection and 93.4% accuracy in predictive maintenance. The showcasing results efficacy of AI models to enhance system reliability as well as operational efficiency. Vigorous encryption protocols performance ensures data security hence addressing issues of privacy. These culminations underscore the transformative potential of AI-IoT integration in next-generation automation and security applications.

The wastewater problem is becoming an increasingly significant environmental issue affecting various aspects of human activities. The generation of reactive oxygen species (ROS) in water through certain physicochemical processes, which can oxidize or degrade various organic and chemical compounds, offers an effective purification method. The main advantage of these methods is the elimination of chemical reagents. Aim of this work is to investigate the possibility of regulating the ROS content in water by altering the characteristics of the plasma discharge that occurs under hydrodynamic cavitation in the water flow. ROS concentration was determined using the permanganate oxidation titration technique. It was found that the content of various reactive oxygen species in water after treatment can be controlled by varying the power of the electrical pulses applied. Additionally, the study obtained the dependence of ROS concentration in treated water samples on storage time, indicating a prolonged effect of sonoplasma treatment on the antibacterial properties of water. Analysis of water samples using a biological test culture of Salmonella typhimurium revealed bacteriostatic properties of the water for at least 48 hours after sonoplasma discharge treatment.

Background: IoT and Big Data are newer technologies that can provide substantial support for healthcare systems and help overcome their shortcomings. The aim of this paper was to analyze literature production descriptively, thematically, and chronologically from an interdisciplinary perspective in a holistic way to identify the most prolific research entities and themes. Methods: The synthetic knowledge synthesis qualitatively and quantitatively analyzes the production of literature through a combination of descriptive bibliometrics, bibliometric mapping and content analysis. For this analysis the Scopus bibliometric database was used. Results: In the Scopus database, 2272 publications were found, which were published between 1985 and June 10, 2024. The first article in this field was published in 1985. Until 2012 the production of literature was steady increasing, after that exponential growth began, which reached its peak in 2023. The most productive countries were the USA, India, China, the United Kingdom, South Korea, Germany and Italy. The content analysis resulted in 8 themes (four from the perspective of computer science and four from the perspective of medicine) and 21 thematic concepts (eight from the perspective of computer science and 13 from the perspective of medicine). Conclusions: The results show that IoT and Big Data have become key technologies in preventive health. The study outcomes might represent a starting point for the further development of research that combines multidisciplinary aspects of healthcare.

The dynamics of surface and sub-surface water events can lead to slope instability resulting in anomalies such as slough slides on earthen levees. Early detection of these anomalies by a remote sensing approach could save time versus direct assessment. We have implemented a supervised Mahalanobis distance classification algorithm for the detection of slough slides on levees using complex polarimetric Synthetic Aperture Radar (polSAR) data. The classifier output was followed by a spatial majority filter post-processing step which improved the accuracy. The effectiveness of the algorithm is demonstrated using fully quad-polarimetric L-band Synthetic Aperture Radar (SAR) imagery from the NASA Jet Propulsion Laboratory’s (JPL’s) Uninhabited Aerial Vehicle Synthetic Aperture Radar (UAVSAR). The study area is a section of the lower Mississippi River valley in the southern USA. Slide detection accuracy of up to 98 percent was achieved, although the number of available slides examples was small.

In this work, satellite data from the Clouds and Earth’s Radiant Energy System (CERES) and Moderate Resolution Imaging Spectroradiometer (MODIS) instruments is analyzed to determine how the global absorbed sunlight and global entropy generation rate have changed during the time period from 2002 to 2023. The data is used to test hypotheses derived from the Maximum Power Principle (MPP) and Maximum Entropy Production Principle (MEP) about the evolution of earth’s surface and atmosphere. The results indicate that the amount of absorbed sunlight has increased over the last 20 years but rising surface temperatures have caused the entropy generation rate to remain approximately constant despite that decrease in albedo. The results are simpler to explain using the MPP but do not completely rule out the MEP. Given the acceptance of the MPP or MEP, some extensions and nuances are discussed.

In this research, catalytic steam reforming acetic acid derived from the aqueous portion of bio-oil for hydrogen production was investigated by using different Ni/ATC (Attapulgite Clay) catalysts prepared by precipitation, impregnation and mechanical blending methods. The fresh and reduced catalysts were characterized by XRD, N₂ adsorption-desorption, TEM and H₂-TPR. The comprehensive results demonstrated that the interaction between active metallic Ni and ATC carrier was significantly improved in Ni/ATC catalyst prepared by precipitation method, and in which the mean Ni particle size was the smallest (~13 nm) resulted in the highest metal dispersion (7.5%). The catalytic performance of the three catalysts was evaluated through the process of steam reforming of acetic acid in a fixed-bed reactor under atmospheric pressure at two different temperatures, such as 550 ℃ and 650 ℃. Results showed that the Ni/ATC (PM-N/ATC) prepared by precipitation method, achieved the highest H₂ yield of ~82% and little lower acetic acid conversion efficiency of ~85% than that (~95%) of Ni/ATC (IM-NATC) prepared by impregnation method. In addition, the deactivation catalysts after reaction for 4 h were analyzed by XRD, TGA-DTG and TEM, which demonstrated that the catalyst deactivation was not caused by the amount of carbon deposition, but owed to the significant agglomeration and sintering of Ni particles in the carrier.

The two combined technologies WPT and AI still have huge prospects for several industries such as consumer electronics and industry. This paper looks at the recent developments in WPT, particularly concerning AI-improved efficiency, range, and reliability. AI-driven also works to control power, manage device alignment, and test when maintenance is necessary, this makes powering smarter and more efficient. Accuracy is given by deploying machine learning and computer vision, and on the other hand, the maintenance procedure is done through predictions. Furthermore, the ability of the management system to include the use of AI in power regulation enables the control of consumption based on the load. In this study, the positive future effect of AI is discussed concerning improvements in WPT technologies, which is paramount in subsequent applications. Based on the results, it is essential to continue the investigation of the topic within this interdisciplinary science to advance existing problems and discover novel possibilities for evolution. Data based on experiments shows a significant improvement in the efficiency of information transfer where AI is used with rates up to 25% higher than those using the traditional ways. Additionally, advanced maintenance forecasting algorithms improve system availability by cutting down on 30% of the downtimes when applied in real-life applications of AI technology. The study also looks at the possibilities of the outlook to the future including emergence of the distributed artificial intelligence for autonomous WPT network, and additional potential of quantum computing for the use to improve the algorithm. This indicates that there is a new era for the convergence of WPT and AI to enhance the progress of power transfer system in conditions of elegant, efficient, and robust.

In this paper is described the obtention of fourteen derivatives from four natural labdane diterpenes isolated from Copaifera oleoresin, named ent-copalic acid (1), ¬ent-3beta-acetoxy copalic acid (2), ent-3beta-hydroxy copalic acid (3) and ent-agathic acid (4). All eighteen compounds were assayed against promastigote form of Leishmania amazonensis and trypomastigote forms of Trypanosoma cruzi, revealing two promising compounds related to leishmanicidal activity (IC50 = 5.94 micromolar and 5.31 micromolar) and three promising compounds with trypanocidal activity, two of them (IC50 = 13.31micromolar and IC50 = 15.05micromolar) displaying similar activity as the reference drug (IC50 = 13.12micromolar) and one of them even more potent with IC50 = 0.425micromolar.

Rapid haemostasis during surgery is essential when one wants to reduce the duration of opera-tions, reduce the need for transfusions, and above all when one wants to achieve better patient management. The use of haemostatic agents, sealants and adhesives improves the haemostatic process by offering several advantages, especially in vascular surgery. These agents vary widely in their mechanism of action, composition, ease of application, adhesion to wet or dry tissue, im-munogenicity and cost. The most used are cyanoacrylate-based glues (Glubran 2) or polysaccharide hydrogel-microsphere powder (AristaTMAH). This work is based on a retrospective study carried out on a sample of patients with different vascular diseases (FAV, pseudoaneurysm and PICC application) in which two different haemostatic sealants were used. The aim was to assess the safety, the advantages and the ability of both sealants to activate the haemostatic process at the affected site, also in relation to their chemical-physical characteristics. The obtained results showed that the application of Glubran 2 and AristaTMAH as surgical wound closure systems is effective and safe as the success achieved was ≥94% on anastomoses of FAV; 100% on stabilization of Picc catheters; ≤95% on pseudoaneurysms.

The structure of synthetic mRNAs as used in vaccination against cancer and infectious diseases contain specifically designed caps followed by sequences of the 5’ untranslated repeats of β-globin gene. The strategy for successful design of synthetic mRNAs by chemically modifying their caps aims to increase resistance to the enzymatic deccapping complex, offer a higher affinity for binding to the eukaryotic translation initiation factor 4E (elF4E) protein and enforce increased translation of their encoded proteins. However, the cellular homeostasis is finely balanced and obeys to specific laws of thermodynamics conferring balance between complexity and growth rate in evolution. An overwhelming and forced translation even under alarming conditions of the cell during a concurrent viral infection, or when molecular pathways are trying to circumvent precursor events that lead to autoimmunity and cancer, may cause the recipient cells to ignore their differential sensitivities which are essential for keeping normal conditions. The elF4E which is a powerful RNA regulon and a potent oncogene governing cell cycle progression and proliferation at a post-transcriptional level, may then be a great contributor to disease development. The mechanistic target of rapamycin (mTOR) axis manly inhibits the elF4E to proceed with mRNA translation but disturbance in fine balances between mTOR and elF4E action may provide a premature step towards oncogenesis, ignite pre-causal mechanisms of immune deregulation and cause maturation (aging) defects.

Saponite is a trioctahedral 2:1 smectite with the ideal composition MxMg3AlxSi4-xO10(OH,F)2.nH2O (M = interlayer cation). Both the success of the saponite synthesis and the determination of its applications depends on robust knowledge of the structure and composition of saponite. Among the routine characterization techniques spectroscopic methods are the most common. This review, thus, provides an overview of various spectroscopic methods to characterize natural and synthetic saponite with focus on the extensive work by one of the authors (JTK). The IR and Raman spectra of natural and synthetic saponites are discussed in detail including the assignment of the observed bands. The crystallization of saponite is discussed based on the changes in the IR and Raman spectra and a possible crystallization model is provided. Infrared emission spectroscopy has been used to study the thermal changes of saponite in-situ including the dehydration and (partial) dehydroxylation up to 750˚C. 27Al and 29Si Magic-Angle-Spinning Nuclear Magnetic Resonance Spectroscopy is discussed (as well as 11B and 71Ga for B- and Ga-Si substitution) with respect to, in particular, Al(IV)/Al(VI) and Si/Al(IV) ratios. X-ray Photoelectron Spectroscopy provides besides chemical information also some information related to the local environments of the different elements in the saponite structure as reflected by their binding energies.

Adenylosuccinic acid (ASA) is a small molecule dicarboxylate that could be a strong clinical development candidate for inherited myopathies involving dysregulated purine nucleotide metabo-lism. Currently, there are no published pharmacokinetic/dynamic or toxicology data available, albeit 10-year clinical trial data in Duchenne muscular dystrophy patients suggests a chronically safe drug. In this study, we tested the toxicity of ASA to cultured myoblasts in vitro and acute systemic toxicity in mice. ASA is a non-toxic small molecule with an LD50> 5000mg/kg. Some background necrotic foci in the liver, kidney and gastrointestinal tract were shown that are likely incidental but warrant follow-up sub-/chronic oral exposure studies.

Single-molecule magnets (SMMs) have garnered significant interest in the field of molecular magnetism due to their unique magnetic properties at the nanoscale. These molecular systems exhibit magnetisation behaviour reminiscent of conventional bulk magnets but with distinct advantages such as size-dependent properties and potential applications in quantum computing and high-density data storage. However, challenges remain in harnessing their properties for practical applications, including their susceptibility to degradation and limited control over their assembly and organisation.

Live cell imaging is a powerful technique to study the dynamics and mechanics of various biological molecules like proteins, organelles, DNA, and RNA. With the rapid evolution of optical microscopy, our understanding of how these molecules is implicated in the cells’ most critical physiological roles deepens. Here in this review, we focus on how spatiotemporal nanoscale live cell imaging on a single molecule level allows for profound contributions towards new discoveries in life science. This review will start by summarizing how single molecule tracking has been used to analyze membrane dynamics, receptor ligand interactions, protein-protein interactions, inner- and extracellular transport, gene expression/transcription, and whole organelle tracking. We then move on to how current authors are trying to improve single molecule tracking and overcome current limitations by offering new ways in labeling protein of interests, multi-channel/color detection, improvements in time laps imaging, and new methods and programs to analyze colocalization and movement of targets. We later discuss how single molecule tracking can be a beneficial tool used for medical diagnosis. Finally wrapping up with limitation and future perspective of single molecule tracking and total internal refection microscopy.

Microfluidic devices have been extensively investigated in recent years in fields including ligand-binding analysis, chromatographic separation, molecular dynamics, and DNA sequencing. To prolong the observation of a single molecule in aqueous buffer, the solution in a sub-micron scale channel is driven by the electric field and reversed after a fixed delay following each passage, so that the molecule passes back and forth through the laser focus and the time before irreversible photobleaching is extended. However, this practice requires complex chemical treatment to the inner surface of the channel to prevent unexpected sticking to the surface and the confined space renders features, such as a higher viscosity and lower dielectric constant, which slow the Brownian motion of the molecule compared to the bulk liquid. In this paper, we have fixed a capillary microchannel with an inner diameter of 2 microns on top of a piezo stage to recycle the molecule and collected the fluorescence by a confocal microscope. The passing times of the molecule through the laser focus are calculated by a real-time control system based on an FPGA and the commands of translation are given to the piezo stage through a feedback algorithm. We have achieved a maximum number of recycles of more than 200 and developed a maximum-likelihood estimation of the diffusivity of the molecule, which attains results of the same magnitude as previous reports. This technique simplifies the overall procedure of the single-molecule recycling and could be useful for the ligand-binding studies of biomolecules.

Recently concluded, large-scale cancer genomics studies involving multiregion sequencing of primary tumors and paired metastases appear to indicate that many or most cancer patients have one or more “clonal" mutations in their tumors. Clonal mutations are those that are present in all of a patient’s cancer cells. Clonally mutated proteins can potentially be targeted by inhibitors or E3 ligase small molecule glues, but developing new small molecule drugs for each patient is not feasible currently. Achilles Therapeutics is currently the only company specifically targeting clonal mutations. However, they are doing so with tumor-derived T cells. To address the potential limitations of immunotherapy, I have devised another approach for exploiting clonal mutations, which I call “Oncolytic Vector Efficient Replication Contingent on Omnipresent Mutation Engagement” (OVERCOME). The ideal version of OVERCOME would likely employ a bioengineered facultative intracellular bacterium. The bacterium would initially be attenuated, but (transiently) reverse its attenuation upon clonal mutation detection.

Endocrine disruptors are molecules that can interfere with the proper functioning of the endocrine system and lead to harmful effects in living organisms. This review focuses on the impact of synthetic fragrances, which are commonly found in personal care and household products, on the endocrine system. The article discusses the different types of hormones in the body and how they interact with receptors to produce signals. It also explores how endocrine disruptors can interfere with hormone signaling and transport, leading to adverse effects in the body. This work underscores the crucial need for further research into the impact of synthetic fragrances on the endocrine system and the importance of using safer alternatives in personal care and household products.

A wide variety of bacteria, fungi and plants can produce bioactive secondary metabolites, which are often referred to as natural products. With the rapid development of DNA sequencing technology and bioinformatics, a large number of putative biosynthetic gene clusters have been reported. However, only a few natural products can be detected when isolated species are grown under conventional laboratory conditions, as most biosynthetic gene clusters are not expressed or are expressed at extremely low levels at these conditions. With the rapid development of synthetic biology, advanced genome mining and modification strategies have been reported, and they provide new opportunities for discovery of natural products. This review discusses advances in recent years that can accelerate the design, build, test, and learn (DBTL) cycle of natural product discovery, and prospects trends and key challenges for future research directions.

After screening nearly 1000 synthetic peptides, a synthetic peptide termed JAL-AK22 (KYEGHWYPEKPYKGSGFRCIHI) derived from the BoxA domain in Tob1 protein was found to activate both unfolded and folded proMMP-7. In addition, JAL-AK22 showed auto-proteolytic activity. Interestingly, the smaller derivative of JAL-AK22 termed JAL-TA9 (YKGSGFRMI) also possessed auto-proteolytic activity and cleaved 2 fragment peptides (MMP18-33 and MMP18-40) derived from the prodomain of proMMP-7 under physiological conditions. These proteolytic activities were inhibited by AEBSF, a serine protease inhibitor. Our results demonstrate that a small synthetic peptide consisting of only 9 amino acids has serine protease-like activity and activates proMMP-7 by cleaving the prodomain region. We thus propose calling small peptides possessing with protease-like activity Catalytides (catalytic peptides). We expect that our findings will stimulate the development of novel Catalytides and related applications.

The field of personalized medicine is undergoing a transformative shift through the integration of multi-omics data, which encompasses genomics, transcriptomics, proteomics, and metabolomics. This synergy allows for a comprehensive understanding of individual health by analyzing genetic, molecular, and biochemical profiles. The generation and integration of multi-omics data enable more precise and tailored therapeutic strategies, improving the efficacy of treatments and reducing adverse effects. However, several challenges hinder the full realization of personalized medicine. Key hurdles include the complexity of data integration across different omics layers, the need for advanced computational tools, and the high cost of comprehensive data generation. Additionally, issues related to data privacy, standardization, and the need for robust validation in diverse populations remain significant obstacles. Looking ahead, the future of personalized medicine promises advancements in technology and methodologies that will address these challenges. Emerging innovations in data analytics, machine learning, and high-throughput sequencing are expected to enhance the integration of multi-omics data, making personalized medicine more accessible and effective. Collaborative efforts among researchers, clinicians, and industry stakeholders are crucial to overcoming these hurdles and fully harnessing the potential of multi-omics for individualized healthcare.

Puerto Rico's geographic and climatic conditions render it highly susceptible to natural disasters, particularly hurricanes. The devastation caused by Hurricane Maria in 2017 highlighted the fragility of the island's centralized energy infrastructure, which led to prolonged power outages and severe disruptions in essential services. This review explores the potential of biomass energy to enhance resilience in post-disaster scenarios, focusing on Puerto Rico as a case study. Biomass energy, derived from organic materials like agricultural residues, woody biomass, and municipal solid waste, offers a renewable and locally sourced power solution that can be rapidly deployed. Key biomass conversion technologies, including direct combustion, gasification, anaerobic digestion, and pyrolysis, are examined for their applicability and benefits in emergency energy provision. The implementation of biomass-powered microgrids in Puerto Rico, such as those by Casa Pueblo and Arensis, demonstrates the feasibility and effectiveness of decentralized energy systems in disaster recovery. These microgrids provide reliable power to critical infrastructure, reduce dependence on fossil fuels, and support waste management efforts. The review also discusses ongoing research and development in advanced biomass technologies, such as second-generation biofuels, algae-based biomass, and biomass-to-hydrogen conversion, which can further enhance energy efficiency and sustainability. Additionally, the economic, environmental, and social impacts of biomass energy are evaluated, highlighting its role in job creation, waste reduction, emission control, and community resilience. Policy recommendations include streamlining permitting processes, enhancing financial incentives, developing feedstock supply chains, and incorporating biomass into disaster recovery plans. The findings suggest that integrating biomass energy into Puerto Rico’s energy strategy can significantly improve its capacity to respond to and recover from natural disasters, promoting long-term sustainability and resilience.

This paper proposes two fully-automatic machine-extracted linguistic features from an unlimited text input for Mandarin prosody generation. One is the punctuation confidence (PC) which measures the likelihood of inserting a major punctuation mark (PM) at a word boundary. Another is the quotation confidence (QC) which measures the likelihood of a word string to be quoted as a meaningful or emphasized unit in text. Because a major PM in a text is highly correlated with a prosodic break, and a quoted word string plays an important role in human language understanding, the two features potentially could provide useful information for prosody generation. The idea is first realized by employing conditional random field (CRF)-based models to predict major PMs, quoted word string locations, and their associated confidences, i.e., the PC and the QC, for each word boundary. Then, the predicted punctuations and their confidences are combined with traditional contextual linguistic features to predict prosodic-acoustic features. Both objective and subjective tests showed that the prosody generation with the proposed linguistic features performed better than the one without the proposed features. So, the proposed PC and QC are promising features for Mandarin prosody generation.

The automotive market is very competitive and presents a demand for the consistent improvement of the used technologies and reduction of the product cost and dimensions with each product model iteration. Hence, it is important to have access to well-defined reference designs of high quality products, in order to evaluate the new ideas and technologies. This paper provides the readers with a numerical model of such a high quality product, i.e., the IPMSM type traction motor from the 4th generation of the Toyota Prius hybrid transaxle. In the introductory section, the brief history of the Prius model is given together with the references to the reverse engineering reports. Afterwards, the machine dimensions, material properties and winding configuration are described. Then, the model is validated with the torque measurements at constant speed. In the next chapters the simulation results are presented and the numerical source data are supplied to the reader. Finally, the design philosophy of the Toyota drive is briefly discussed in comparison with the BMWi3 drive and the results are concluded in the last section.