553 research outputs found

    Computational and experimental studies on the reaction mechanism of bio-oil components with additives for increased stability and fuel quality

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    As one of the world’s largest palm oil producers, Malaysia encountered a major disposal problem as vast amount of oil palm biomass wastes are produced. To overcome this problem, these biomass wastes can be liquefied into biofuel with fast pyrolysis technology. However, further upgradation of fast pyrolysis bio-oil via direct solvent addition was required to overcome it’s undesirable attributes. In addition, the high production cost of biofuels often hinders its commercialisation. Thus, the designed solvent-oil blend needs to achieve both fuel functionality and economic targets to be competitive with the conventional diesel fuel. In this thesis, a multi-stage computer-aided molecular design (CAMD) framework was employed for bio-oil solvent design. In the design problem, molecular signature descriptors were applied to accommodate different classes of property prediction models. However, the complexity of the CAMD problem increases as the height of signature increases due to the combinatorial nature of higher order signature. Thus, a consistency rule was developed reduce the size of the CAMD problem. The CAMD problem was then further extended to address the economic aspects via fuzzy multi-objective optimisation approach. Next, a rough-set based machine learning (RSML) model has been proposed to correlate the feedstock characterisation and pyrolysis condition with the pyrolysis bio-oil properties by generating decision rules. The generated decision rules were analysed from a scientific standpoint to identify the underlying patterns, while ensuring the rules were logical. The decision rules generated can be used to select optimal feedstock composition and pyrolysis condition to produce pyrolysis bio-oil of targeted fuel properties. Next, the results obtained from the computational approaches were verified through experimental study. The generated pyrolysis bio-oils were blended with the identified solvents at various mixing ratio. In addition, emulsification of the solvent-oil blend in diesel was also conducted with the help of surfactants. Lastly, potential extensions and prospective work for this study have been discuss in the later part of this thesis. To conclude, this thesis presented the combination of computational and experimental approaches in upgrading the fuel properties of pyrolysis bio-oil. As a result, high quality biofuel can be generated as a cleaner burning replacement for conventional diesel fuel

    Unveiling the frontiers of deep learning: innovations shaping diverse domains

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    Deep learning (DL) enables the development of computer models that are capable of learning, visualizing, optimizing, refining, and predicting data. In recent years, DL has been applied in a range of fields, including audio-visual data processing, agriculture, transportation prediction, natural language, biomedicine, disaster management, bioinformatics, drug design, genomics, face recognition, and ecology. To explore the current state of deep learning, it is necessary to investigate the latest developments and applications of deep learning in these disciplines. However, the literature is lacking in exploring the applications of deep learning in all potential sectors. This paper thus extensively investigates the potential applications of deep learning across all major fields of study as well as the associated benefits and challenges. As evidenced in the literature, DL exhibits accuracy in prediction and analysis, makes it a powerful computational tool, and has the ability to articulate itself and optimize, making it effective in processing data with no prior training. Given its independence from training data, deep learning necessitates massive amounts of data for effective analysis and processing, much like data volume. To handle the challenge of compiling huge amounts of medical, scientific, healthcare, and environmental data for use in deep learning, gated architectures like LSTMs and GRUs can be utilized. For multimodal learning, shared neurons in the neural network for all activities and specialized neurons for particular tasks are necessary.Comment: 64 pages, 3 figures, 3 table

    Computational Approaches to Drug Profiling and Drug-Protein Interactions

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    Despite substantial increases in R&D spending within the pharmaceutical industry, denovo drug design has become a time-consuming endeavour. High attrition rates led to a long period of stagnation in drug approvals. Due to the extreme costs associated with introducing a drug to the market, locating and understanding the reasons for clinical failure is key to future productivity. As part of this PhD, three main contributions were made in this respect. First, the web platform, LigNFam enables users to interactively explore similarity relationships between ‘drug like’ molecules and the proteins they bind. Secondly, two deep-learning-based binding site comparison tools were developed, competing with the state-of-the-art over benchmark datasets. The models have the ability to predict offtarget interactions and potential candidates for target-based drug repurposing. Finally, the open-source ScaffoldGraph software was presented for the analysis of hierarchical scaffold relationships and has already been used in multiple projects, including integration into a virtual screening pipeline to increase the tractability of ultra-large screening experiments. Together, and with existing tools, the contributions made will aid in the understanding of drug-protein relationships, particularly in the fields of off-target prediction and drug repurposing, helping to design better drugs faster

    A computational view on nanomaterial intrinsic and extrinsic features for nanosafety and sustainability

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    In recent years, an increasing number of diverse Engineered Nano-Materials (ENMs), such as nanoparticles and nanotubes, have been included in many technological applications and consumer products. The desirable and unique properties of ENMs are accompanied by potential hazards whose impacts are difficult to predict either qualitatively or in a quantitative and predictive manner. Alongside established methods for experimental and computational characterisation, physics-based modelling tools like molecular dynamics are increasingly considered in Safe and Sustainability-by-design (SSbD) strategies that put user health and environmental impact at the centre of the design and development of new products. Hence, the further development of such tools can support safe and sustainable innovation and its regulation. This paper stems from a community effort and presents the outcome of a four-year-long discussion on the benefits, capabilities and limitations of adopting physics-based modelling for computing suitable features of nanomaterials that can be used for toxicity assessment of nanomaterials in combination with data-based models and experimental assessment of toxicity endpoints. We review modern multiscale physics-based models that generate advanced system-dependent (intrinsic) or timeand environment-dependent (extrinsic) descriptors/features of ENMs (primarily, but not limited to nanoparticles, NPs), with the former being related to the bare NPs and the latter to their dynamic fingerprinting upon entering biological media. The focus is on (i) effectively representing all nanoparticle attributes for multicomponent nanomaterials, (ii) generation and inclusion of intrinsic nanoform properties, (iii) inclusion of selected extrinsic properties, (iv) the necessity of considering distributions of structural advanced features rather than only averages. This review enables us to identify and highlight a number of key challenges associated with ENMs’ data generation, curation, representation and use within machine learning or other advanced data-driven models to ultimately enhance toxicity assessment. Finally, the set up of dedicated databases as well as the development of grouping and read-across strategies based on the mode of action of ENMs using omics methods are identified as emerging methodologies for safety assessment and reduction of animal testing

    A Tale of Two Approaches: Comparing Top-Down and Bottom-Up Strategies for Analyzing and Visualizing High-Dimensional Data

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    The proliferation of high-throughput and sensory technologies in various fields has led to a considerable increase in data volume, complexity, and diversity. Traditional data storage, analysis, and visualization methods are struggling to keep pace with the growth of modern data sets, necessitating innovative approaches to overcome the challenges of managing, analyzing, and visualizing data across various disciplines. One such approach is utilizing novel storage media, such as deoxyribonucleic acid~(DNA), which presents efficient, stable, compact, and energy-saving storage option. Researchers are exploring the potential use of DNA as a storage medium for long-term storage of significant cultural and scientific materials. In addition to novel storage media, scientists are also focussing on developing new techniques that can integrate multiple data modalities and leverage machine learning algorithms to identify complex relationships and patterns in vast data sets. These newly-developed data management and analysis approaches have the potential to unlock previously unknown insights into various phenomena and to facilitate more effective translation of basic research findings to practical and clinical applications. Addressing these challenges necessitates different problem-solving approaches. Researchers are developing novel tools and techniques that require different viewpoints. Top-down and bottom-up approaches are essential techniques that offer valuable perspectives for managing, analyzing, and visualizing complex high-dimensional multi-modal data sets. This cumulative dissertation explores the challenges associated with handling such data and highlights top-down, bottom-up, and integrated approaches that are being developed to manage, analyze, and visualize this data. The work is conceptualized in two parts, each reflecting the two problem-solving approaches and their uses in published studies. The proposed work showcases the importance of understanding both approaches, the steps of reasoning about the problem within them, and their concretization and application in various domains

    Development and implementation of in silico molecule fragmentation algorithms for the cheminformatics analysis of natural product spaces

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    Computational methodologies extracting specific substructures like functional groups or molecular scaffolds from input molecules can be grouped under the term “in silico molecule fragmentation”. They can be used to investigate what specifically characterises a heterogeneous compound class, like pharmaceuticals or Natural Products (NP) and in which aspects they are similar or dissimilar. The aim is to determine what specifically characterises NP structures to transfer patterns favourable for bioactivity to drug development. As part of this thesis, the first algorithmic approach to in silico deglycosylation, the removal of glycosidic moieties for the study of aglycones, was developed with the Sugar Removal Utility (SRU) (Publication A). The SRU has also proven useful for investigating NP glycoside space. It was applied to one of the largest open NP databases, COCONUT (COlleCtion of Open Natural prodUcTs), for this purpose (Publication B). A contribution was made to the Chemistry Development Kit (CDK) by developing the open Scaffold Generator Java library (Publication C). Scaffold Generator can extract different scaffold types and dissect them into smaller parent scaffolds following the scaffold tree or scaffold network approach. Publication D describes the OngLai algorithm, the first automated method to identify homologous series in input datasets, group the member structures of each group, and extract their common core. To support the development of new fragmentation algorithms, the open Java rich client graphical user interface application MORTAR (MOlecule fRagmenTAtion fRamework) was developed as part of this thesis (Publication E). MORTAR allows users to quickly execute the steps of importing a structural dataset, applying a fragmentation algorithm, and visually inspecting the results in different ways. All software developed as part of this thesis is freely and openly available (see https://github.com/JonasSchaub)

    In silico prediction of acute chemical toxicity of biocides in marine crustaceans using machine learning

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    Biocides are a heterogeneous group of chemical substances intended to control the growth or kill undesired organisms. Due to their extensive use, they enter marine ecosystems via non-point sources and may pose a threat to ecologically important non-target organisms. Consequently, industries and regulatory agencies have recognized the ecotoxicological hazard potential of biocides. However, the prediction of biocide chemical toxicity on marine crustaceans has not been previously evaluated. This study aims to provide in silico models capable of classifying structurally diverse biocidal chemicals into different toxicity categories and predict acute chemical toxicity (LC50) in marine crustaceans using a set of calculated 2D molecular descriptors. The models were built following the guidelines recommended by the OECD (Organization for Economic Cooperation and Development) and validated through stringent processes (internal and external validation). Six machine learning (ML) models were built and compared (linear regression: LR; support vector machine: SVM; random forest: RF; feed-forward backpropagation-based artificial neural network: ANN; decision trees: DT and naĂŻve Bayes: NB) for regression and classification analysis to predict toxicities. All the models displayed encouraging results with high generalisability: the feed-forward-based backpropagation method showed the best results with determination coefficient R2 values of 0.82 and 0.94, respectively, for training set (TS) and validation set (VS). For classification-based modelling, the DT model performed the best with an accuracy (ACC) of 100 % and an area under curve (AUC) value of 1 for both TS and VS. These models showed the potential to replace animal testing for the chemical hazard assessment of untested biocides if they fall within the applicability domain of the proposed models. In general, the models are highly interpretable and robust, with good predictive performance. The models also displayed a trend indicating that toxicity is largely influenced by factors such as lipophilicity, branching, non-polar bonding and saturation of molecules

    Enantioseparations with polysaccharide-based chiral stationary phases in HPLC. Application to the enantioselective evaluation of the biodegradability of chiral drugs in activated sludge from a Valencian waste water treatment plant

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    The chiral nature of living systems has obvious implications for the biologically active compounds that interact with them. At the molecular level, chirality represents an intrinsic property of the essential building blocks of life, such as amino acids and sugars, and therefore, of peptides, proteins, enzymes, carbohydrates, nucleosides and a number of alkaloids and hormones. As a consequence, processes mediated by biological systems are stereochemistry-sensitive, and a pair of enantiomers can have different effects on living organisms. The scientific community has been studying the implications of chirality for life for more than a century. Today, it is still a topic of active research and debate due to the large number of chiral molecules that are part of living organisms and of our everyday life. In this context, analytical methods for the separation of the enantiomers of chiral molecules play a crucial role. Undoubtedly, the use of chiral stationary phases (CSPs) in high performance liquid chromatography (HPLC) is the preferred choice for enantioseparations. This is evidenced by the huge number of CSPs available on the market. This fact, together with the trial-and-error methods commonly used to select the most suitable chromatographic system (CSP/mobile phase combination) for a given enantioseparation, results in enormous cost and experimental effort. This makes it necessary to develop strategies to simplify this important task. This Doctoral Thesis has two clearly differentiated main objectives: (i) To contribute to the knowledge of chiral HPLC with polysaccharide-based CSPs (the most popular commercial ones: three amylose and five cellulose derivatives), and hydro-organic mobile phases (comprising acetonitrile (ACN) and methanol (MeOH) aqueous solutions compatible with aqueous matrices and mass spectrometry (MS) detection). To this end, the following specific objectives were set: (a) to contribute to a rational selection of the chromatographic system to separate the enantiomers of a given compound. To this end, the retention and enantioresolution of a large dataset of structurally unrelated chiral compounds (approximately 60 basic and neutral drugs and pesticides) in the chromatographic systems above-indicated is compared. Moreover, quantitative structure-property relationships (QSPRs) for enantioresolution related data obtained in some of the chromatographic systems studied are developed. (b) To explore the use of deconvolution of overlapping peaks to achieve the mathematical resolution when the baseline resolution cannot be achieved experimentally. To illustrate the potential of this peak model strategy, the enantioseparation of eight chiral drugs in five polysaccharide-based CSPs and ACN or MeOH hydro-organic mobile phases at different separation temperatures is considered. (ii) To contribute to the advancement of knowledge of the risks and hazards of chiral pollutants. To this end, OECD (Organisation for Economic Co-operation and Development) biodegradability tests using activated sludge from a Valencian waste water treatment plant (Quart BenĂ ger) are performed for some common chiral pharmaceutical pollutants: trimeprazine, ibuprofen, ketoprofen, bupivacaine, mepivacaine, prilocaine and propanocaine. Next, the separation and determination of the enantiomers of the intact compound is performed using chiral HPLC methods (with amylose- or cellulose-based CSPs and ACN or MeOH hydro-organic mobile phases compatible with aqueous matrices and MS detection) developed for that purpose
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