Predicting Skin Permeability by means of Computational Approaches : Reliability and Caveats in Pharmaceutical Studies

© 2019 American Chemical Society.The skin is the main barrier between the internal body environment and the external one. The characteristics of this barrier and its properties are able to modify and affect drug delivery and chemical toxicity parameters. Therefore, it is not surprising that permeability of many different compounds has been measured through several in vitro and in vivo techniques. Moreover, many different in silico approaches have been used to identify the correlation between the structure of the permeants and their permeability, to reproduce the skin behavior, and to predict the ability of specific chemicals to permeate this barrier. A significant number of issues, like interlaboratory variability, experimental conditions, data set building rationales, and skin site of origin and hydration, still prevent us from obtaining a definitive predictive skin permeability model. This review wants to show the main advances and the principal approaches in computational methods used to predict this property, to enlighten the main issues that have arisen, and to address the challenges to develop in future research.Peer reviewedFinal Accepted Versio

Modelling interactions of acid–base balance and respiratory status in the toxicity of metal mixtures in the American oyster Crassostrea virginica

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Comparative Biochemistry and Physiology - Part A: Molecular & Integrative Physiology 155 (2010): 341-349, doi:10.1016/j.cbpa.2009.11.019.Heavy metals, such as copper, zinc and cadmium, represent some of the most common and serious pollutants in coastal estuaries. In the present study, we used a combination of linear and artificial neural network (ANN) modelling to detect and explore interactions among low-dose mixtures of these heavy metals and their impacts on fundamental physiological processes in tissues of the Eastern oyster, Crassostrea virginica. Animals were exposed to Cd (0.001 – 0.400 μM), Zn (0.001 – 3.059 μM) or Cu (0.002 – 0.787 μM), either alone or in combination for 1 to 27 days. We measured indicators of acid-base balance (hemolymph pH and total CO2), gas exchange (Po2), immunocompetence (total hemocyte counts, numbers of invasive bacteria), antioxidant status (glutathione, GSH), oxidative damage (lipid peroxidation; LPx), and metal accumulation in the gill and the hepatopancreas. Linear analysis showed that oxidative membrane damage from tissue accumulation of environmental metals was correlated with impaired acid-base balance in oysters. ANN analysis revealed interactions of metals with hemolymph acid-base chemistry in predicting oxidative damage that were not evident from linear analyses. These results highlight the usefulness of machine learning approaches, such as ANNs, for improving our ability to recognize and understand the effects of sub-acute exposure to contaminant mixtures.This study was supported by NOAA’s Center of Excellence in Oceans and Human Health at HML and the National Science Foundation

ADAPTS: An Intelligent Sustainable Conceptual Framework for Engineering Projects

This paper presents a conceptual framework for the optimization of environmental sustainability in engineering projects, both for products and industrial facilities or processes. The main objective of this work is to propose a conceptual framework to help researchers to approach optimization under the criteria of sustainability of engineering projects, making use of current Machine Learning techniques. For the development of this conceptual framework, a bibliographic search has been carried out on the Web of Science. From the selected documents and through a hermeneutic procedure the texts have been analyzed and the conceptual framework has been carried out. A graphic representation pyramid shape is shown to clearly define the variables of the proposed conceptual framework and their relationships. The conceptual framework consists of 5 dimensions; its acronym is ADAPTS. In the base are: (1) the Application to which it is intended, (2) the available DAta, (3) the APproach under which it is operated, and (4) the machine learning Tool used. At the top of the pyramid, (5) the necessary Sensing. A study case is proposed to show its applicability. This work is part of a broader line of research, in terms of optimization under sustainability criteria.Telefónica Chair “Intelligence in Networks” of the University of Seville (Spain

MODELLING OF CO2 SOLUBILITY IN DIETHANOLAMINE, NMETHYLDIETHANOLAMINE AND THEIR MIXTURES USING ARTIFICIAL NEURAL NETWORK

Natural gas has a wide range of acid gas concentrations, from parts per million to 50 volume percent and higher, depending on the nature of the rock formation from which it comes. Because of the corrosiveness of H2S and CO2 in the presence of water and because of the toxicity of H2S and the lack of heating value of CO2, sales gas is required to be sweetened to contain no more than a quarter grain H2S per 100 standard cubic feet (4 parts per million) and to have a heating value of no less than 920 to 980 Btu/SCF, depending on the contract. The most widely used processes to sweeten natural gas are those using the alkanolamines, and of the alkanolamines the two most common are n-methyldiethanolamine (MDEA) and diethanolamine (DEA). In this research, data from Khalid Osman et al (2012), A. Benamor et al (2005) and Zhang et al (2002) will be used to simulate the solubility of CO2 in MDEA + DEA aqueous solution using ANN model and the performance will be compared to show which model is better for CO2 absorption. Besides, the study of CO2 solubility in MDEA and DEA aqueous solution respectively will be using data from Jou et al (1982) and Lee et al (1972) works and simulation of ANN model was used to compare the performance between ANN model and the reference research works mentioned earlier. Developed model has an absolute relative deviation (δAAD) of 8.71% while δAAD for data from Khalid Osman et al (2012), A. Benamor et al (2005) and Zhang et al (2002) are 17.06%, 12.09% and 9.82% respectively. In terms of pure amine prediction, ANN model of CO2 solubility predicted in pure MDEA has δAAD of 8.29% while the reference paper which is A. Benamor et al (2005) has absolute relative deviation of 10.76%. For prediction in pure DEA, the model has δAAD of 3.33% compared to reference paper which is also from A. Benamor et al (2005) with 4.72%. ANN has great ability to predict CO2 solubility in pure MDEA, DEA, and their mixtures only by developing models for each situation and condition due to the limitation of ANN itself which cannot simulate the new input data if they do not have same patterns with the one that has been used to develop the model

ARTIFICIAL NEURAL NETWORKS: FUNCTIONINGANDAPPLICATIONS IN PHARMACEUTICAL INDUSTRY

Artificial Neural Network (ANN) technology is a group of computer designed algorithms for simulating neurological processing to process information and produce outcomes like the thinking process of humans in learning, decision making and solving problems. The uniqueness of ANN is its ability to deliver desirable results even with the help of incomplete or historical data results without a need for structured experimental design by modeling and pattern recognition. It imbibes data through repetition with suitable learning models, similarly to humans, without actual programming. It leverages its ability by processing elements connected with the user given inputs which transfers as a function and provides as output. Moreover, the present output by ANN is a combinational effect of data collected from previous inputs and the current responsiveness of the system. Technically, ANN is associated with highly monitored network along with a back propagation learning standard. Due to its exceptional predictability, the current uses of ANN can be applied to many more disciplines in the area of science which requires multivariate data analysis. In the pharmaceutical process, this flexible tool is used to simulate various non-linear relationships. It also finds its application in the enhancement of pre-formulation parameters for predicting physicochemical properties of drug substances. It also finds its applications in pharmaceutical research, medicinal chemistry, QSAR study, pharmaceutical instrumental engineering. Its multi-objective concurrent optimization is adopted in the drug discovery process, protein structure, rational data analysis also

Using Artificial Neural Networks to Predict Disease Associations for Chemicals Present in Burn Pit Emissions

In June of 2015, 27,378 of the 28,000 returning Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) veterans report being exposed to burn pits. According to Barth et al. (2014), 9,660 returning OIF/OEF veterans were diagnosed with respiratory diseases, to include asthma, bronchitis, and sinusitis, thus strengthening the need to develop decision support tools that can be used to understand the relationships between chemical exposure and disease. In this study an Artificial Neural Network (ANN) was used to predict the chemical-disease associations for burn pit constituents. Ten burn pit constituents were tested using varying hidden layers, similar chemical structure relationships, and three Training, Validation, and Testing (TVT) ratios. The ANN predicted misidentification rates of 73% or greater when the hidden layer size varied between 1 and 5. Misidentification rates of 75% or greater were observed for ANN simulations when the TVT ratios ranged from 60/20/20 to 80/10/10. ANN-based screening of chemical groups containing chemicals with benzene rings and chemicals containing hydrocarbon chains produced misidentification rates of 73% or greater, and R2 values of 0.0762 and lower. Hidden Layer size, TVT ratios, and chemical structure had little effect on the model’s performance; additional training data is needed to improve the predictive capability of the ANN. The ANN-based screening of individual burn pit constituents produced several chemicals with R2 values greater than 0.8. These chemicals have been prioritized to further develop predictive ANN models for human health force support, resulting in the first research screening burn pit constituents with an ANN, and the first to prioritize burn pit emissions for future testing

Improving soil stability with alum sludge : an ai-enabled approach for accurate prediction of california bearing ratio

Alum sludge is a byproduct of water treatment plants, and its use as a soil stabilizer has gained increasing attention due to its economic and environmental benefits. Its application has been shown to improve the strength and stability of soil, making it suitable for various engineering applications. However, to go beyond just measuring the effects of alum sludge as a soil stabilizer, this study investigates the potential of artificial intelligence (AI) methods for predicting the California bearing ratio (CBR) of soils stabilized with alum sludge. Three AI methods, including two black box methods (artificial neural network and support vector machines) and one grey box method (genetic programming), were used to predict CBR, based on a database with nine input parameters. The results demonstrate the effectiveness of AI methods in predicting CBR with good accuracy (R2 values ranging from 0.94 to 0.99 and MAE values ranging from 0.30 to 0.51). Moreover, a novel approach, using genetic programming, produced an equation that accurately estimated CBR, incorporating seven inputs. The analysis of parameter sensitivity and importance, revealed that the number of hammer blows for compaction was the most important parameter, while the parameters for maximum dry density of soil and mixture were the least important. This study highlights the potential of AI methods as a useful tool for predicting the performance of alum sludge as a soil stabilizer. © 2023 by the authors

Computationally Linking Chemical Exposure to Molecular Effects with Complex Data: Comparing Methods to Disentangle Chemical Drivers in Environmental Mixtures and Knowledge-based Deep Learning for Predictions in Environmental Toxicology

Chemical exposures affect the environment and may lead to adverse outcomes in its organisms. Omics-based approaches, like standardised microarray experiments, have expanded the toolbox to monitor the distribution of chemicals and assess the risk to organisms in the environment. The resulting complex data have extended the scope of toxicological knowledge bases and published literature. A plethora of computational approaches have been applied in environmental toxicology considering systems biology and data integration. Still, the complexity of environmental and biological systems given in data challenges investigations of exposure-related effects. This thesis aimed at computationally linking chemical exposure to biological effects on the molecular level considering sources of complex environmental data. The first study employed data of an omics-based exposure study considering mixture effects in a freshwater environment. We compared three data-driven analyses in their suitability to disentangle mixture effects of chemical exposures to biological effects and their reliability in attributing potentially adverse outcomes to chemical drivers with toxicological databases on gene and pathway levels. Differential gene expression analysis and a network inference approach resulted in toxicologically meaningful outcomes and uncovered individual chemical effects — stand-alone and in combination. We developed an integrative computational strategy to harvest exposure-related gene associations from environmental samples considering mixtures of lowly concentrated compounds. The applied approaches allowed assessing the hazard of chemicals more systematically with correlation-based compound groups. This dissertation presents another achievement toward a data-driven hypothesis generation for molecular exposure effects. The approach combined text-mining and deep learning. The study was entirely data-driven and involved state-of-the-art computational methods of artificial intelligence. We employed literature-based relational data and curated toxicological knowledge to predict chemical-biomolecule interactions. A word embedding neural network with a subsequent feed-forward network was implemented. Data augmentation and recurrent neural networks were beneficial for training with curated toxicological knowledge. The trained models reached accuracies of up to 94% for unseen test data of the employed knowledge base. However, we could not reliably confirm known chemical-gene interactions across selected data sources. Still, the predictive models might derive unknown information from toxicological knowledge sources, like literature, databases or omics-based exposure studies. Thus, the deep learning models might allow predicting hypotheses of exposure-related molecular effects. Both achievements of this dissertation might support the prioritisation of chemicals for testing and an intelligent selection of chemicals for monitoring in future exposure studies.:Table of Contents ... I Abstract ... V Acknowledgements ... VII Prelude ... IX 1 Introduction 1.1 An overview of environmental toxicology ... 2 1.1.1 Environmental toxicology ... 2 1.1.2 Chemicals in the environment ... 4 1.1.3 Systems biological perspectives in environmental toxicology ... 7 Computational toxicology ... 11 1.2.1 Omics-based approaches ... 12 1.2.2 Linking chemical exposure to transcriptional effects ... 14 1.2.3 Up-scaling from the gene level to higher biological organisation levels ... 19 1.2.4 Biomedical literature-based discovery ... 24 1.2.5 Deep learning with knowledge representation ... 27 1.3 Research question and approaches ... 29 2 Methods and Data ... 33 2.1 Linking environmental relevant mixture exposures to transcriptional effects ... 34 2.1.1 Exposure and microarray data ... 34 2.1.2 Preprocessing ... 35 2.1.3 Differential gene expression ... 37 2.1.4 Association rule mining ... 38 2.1.5 Weighted gene correlation network analysis ... 39 2.1.6 Method comparison ... 41 Predicting exposure-related effects on a molecular level ... 44 2.2.1 Input ... 44 2.2.2 Input preparation ... 47 2.2.3 Deep learning models ... 49 2.2.4 Toxicogenomic application ... 54 3 Method comparison to link complex stream water exposures to effects on the transcriptional level ... 57 3.1 Background and motivation ... 58 3.1.1 Workflow ... 61 3.2 Results ... 62 3.2.1 Data preprocessing ... 62 3.2.2 Differential gene expression analysis ... 67 3.2.3 Association rule mining ... 71 3.2.4 Network inference ... 78 3.2.5 Method comparison ... 84 3.2.6 Application case of method integration ... 87 3.3 Discussion ... 91 3.4 Conclusion ... 99 4 Deep learning prediction of chemical-biomolecule interactions ... 101 4.1 Motivation ... 102 4.1.1Workflow ...105 4.2 Results ... 107 4.2.1 Input preparation ... 107 4.2.2 Model selection ... 110 4.2.3 Model comparison ... 118 4.2.4 Toxicogenomic application ... 121 4.2.5 Horizontal augmentation without tail-padding ...123 4.2.6 Four-class problem formulation ... 124 4.2.7 Training with CTD data ... 125 4.3 Discussion ... 129 4.3.1 Transferring biomedical knowledge towards toxicology ... 129 4.3.2 Deep learning with biomedical knowledge representation ...133 4.3.3 Data integration ...136 4.4 Conclusion ... 141 5 Conclusion and Future perspectives ... 143 5.1 Conclusion ... 143 5.1.1 Investigating complex mixtures in the environment ... 144 5.1.2 Complex knowledge from literature and curated databases predict chemical- biomolecule interactions ... 145 5.1.3 Linking chemical exposure to biological effects by integrating CTD ... 146 5.2 Future perspectives ... 147 S1 Supplement Chapter 1 ... 153 S1.1 Example of an estrogen bioassay ... 154 S1.2 Types of mode of action ... 154 S1.3 The dogma of molecular biology ... 157 S1.4 Transcriptomics ... 159 S2 Supplement Chapter 3 ... 161 S3 Supplement Chapter 4 ... 175 S3.1 Hyperparameter tuning results ... 176 S3.2 Functional enrichment with predicted chemical-gene interactions and CTD reference pathway genesets ... 179 S3.3 Reduction of learning rate in a model with large word embedding vectors ... 183 S3.4 Horizontal augmentation without tail-padding ... 183 S3.5 Four-relationship classification ... 185 S3.6 Interpreting loss observations for SemMedDB trained models ... 187 List of Abbreviations ... i List of Figures ... vi List of Tables ... x Bibliography ... xii Curriculum scientiae ... xxxix Selbständigkeitserklärung ... xlii

Application of AI in Modeling of Real System in Chemistry

In recent years, discharge of synthetic dye waste from different industries leading to aquatic and environmental pollution is a serious global problem of great concern. Hence, the removal of dye prediction plays an important role in wastewater management and conservation of nature. Artificial intelligence methods are popular owing due to its ease of use and high level of accuracy. This chapter proposes a detailed review of artificial intelligence-based removal dye prediction methods particularly multiple linear regression (MLR), artificial neural networks (ANNs), and least squares-support vector machine (LS-SVM). Furthermore, this chapter will focus on ensemble prediction models (EPMs) used for removal dye prediction. EPMs improve the prediction accuracy by integrating several prediction models. The principles, advantages, disadvantages, and applications of these artificial intelligence-based methods are explained in this chapter. Furthermore, future directions of the research on artificial intelligence-based removal dye prediction methods are discussed

SciTech News Volume 71, No. 1 (2017)

Columns and Reports From the Editor 3 Division News Science-Technology Division 5 Chemistry Division 8 Engineering Division Aerospace Section of the Engineering Division 9 Architecture, Building Engineering, Construction and Design Section of the Engineering Division 11 Reviews Sci-Tech Book News Reviews 12 Advertisements IEEE