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

Mapping customer needs to engineering characteristics: an aerospace perspective for conceptual design

Designing complex engineering systems, such as an aircraft or an aero-engine, is immensely challenging. Formal Systems Engineering (SE) practices are widely used in the aerospace industry throughout the overall design process to minimise the overall design effort, corrective re-work, and ultimately overall development and manufacturing costs. Incorporating the needs and requirements from customers and other stakeholders into the conceptual and early design process is vital for the success and viability of any development programme. This paper presents a formal methodology, the Value-Driven Design (VDD) methodology that has been developed for collaborative and iterative use in the Extended Enterprise (EE) within the aerospace industry, and that has been applied using the Concept Design Analysis (CODA) method to map captured Customer Needs (CNs) into Engineering Characteristics (ECs) and to model an overall ‘design merit’ metric to be used in design assessments, sensitivity analyses, and engineering design optimisation studies. Two different case studies with increasing complexity are presented to elucidate the application areas of the CODA method in the context of the VDD methodology for the EE within the aerospace secto

Simulation of urban system evolution in a synergetic modelling framework. The case of Attica, Greece

Spatial analysis and evolution simulation of such complex and dynamic systems as modern urban areas could greatly benefit from the synergy of methods and techniques that constitute the core of the fields of Information Technology and Artificial Intelligence. Additionally, if during the decision making process, a consistent methodology is applied and assisted by a user-friendly interface, premium and pragmatic solution strategies can be tested and evaluated. In such a framework, this paper presents both a prototype Decision Support System and a consorting spatio-temporal methodology, for modelling urban growth. Its main focus is on the analysis of current trends, the detection of the factors that mostly affect the evolution process and the examination of user-defined hypotheses regarding future states of the problem environment. According to the approach, a neural network model is formulated for a specific time intervals and each different group of spatial units, mainly based to the degree of their contiguity and spatial interaction. At this stage, fuzzy logic provides a precise image of spatial entities, further exploited in a twofold way. First, for the analysis and interpretation of up-to-date urban evolution and second, for the formulation of a robust spatial simulation model. It should be stressed, however, that the neural network model is not solely used to define future urban images, but also to evaluate the degree of influence that each variable as a significant of problem parameter, contributes to the final result. Thus, the formulation and the analysis of alternative planning scenarios are assisted. Both the proposed methodological framework and the prototype Decision Support System are utilized during the study of Attica, Greece?s principal prefecture and the definition of a twenty-year forecast. The variables considered and projected refer to population data derived from the 1961-1991 censuses and building uses aggregated in ten different categories. The final results are visualised through thematic maps in a GIS environment. Finally, the performance of the methodology is evaluated as well as directions for further improvements and enhancements are outlined. Keywords: Computational geography, Spatial modelling, Neural network models, Fuzzy logic.

Machine Learning and Integrative Analysis of Biomedical Big Data.

Recent developments in high-throughput technologies have accelerated the accumulation of massive amounts of omics data from multiple sources: genome, epigenome, transcriptome, proteome, metabolome, etc. Traditionally, data from each source (e.g., genome) is analyzed in isolation using statistical and machine learning (ML) methods. Integrative analysis of multi-omics and clinical data is key to new biomedical discoveries and advancements in precision medicine. However, data integration poses new computational challenges as well as exacerbates the ones associated with single-omics studies. Specialized computational approaches are required to effectively and efficiently perform integrative analysis of biomedical data acquired from diverse modalities. In this review, we discuss state-of-the-art ML-based approaches for tackling five specific computational challenges associated with integrative analysis: curse of dimensionality, data heterogeneity, missing data, class imbalance and scalability issues

Type-2 fuzzy logic system applications for power systems

PhD ThesisIn the move towards ubiquitous information & communications technology, an opportunity for further optimisation of the power system as a whole has arisen. Nonetheless, the fast growth of intermittent generation concurrently with markets deregulation is driving a need for timely algorithms that can derive value from these new data sources. Type-2 fuzzy logic systems can offer approximate solutions to these computationally hard tasks by expressing non-linear relationships in a more flexible fashion. This thesis explores how type-2 fuzzy logic systems can provide solutions to two of these challenging power system problems; short-term load forecasting and voltage control in distribution networks. On one hand, time-series forecasting is a key input for economic secure power systems as there are many tasks that require a precise determination of the future short-term load (e.g. unit commitment or security assessment among others), but also when dealing with electricity as commodity. As a consequence, short-term load forecasting becomes essential for energy stakeholders and any inaccuracy can be directly translated into their financial performance. All these is reflected in current power systems literature trends where a significant number of papers cover the subject. Extending the existing literature, this work focuses in how these should be implemented from beginning to end to bring to light their predictive performance. Following this research direction, this thesis introduces a novel framework to automatically design type-2 fuzzy logic systems. On the other hand, the low-carbon economy is pushing the grid status even closer to its operational limits. Distribution networks are becoming active systems with power flows and voltages defined not only by load, but also by generation. As consequence, even if it is not yet absolutely clear how power systems will evolve in the long-term, all plausible future scenarios claim for real-time algorithms that can provide near optimal solutions to this challenging mixed-integer non-linear problem. Aligned with research and industry efforts, this thesis introduces a scalable implementation to tackle this task in divide-and-conquer fashio

Neuro-fuzzy knowledge processing in intelligent learning environments for improved student diagnosis

In this paper, a neural network implementation for a fuzzy logic-based model of the diagnostic process is proposed as a means to achieve accurate student diagnosis and updates of the student model in Intelligent Learning Environments. The neuro-fuzzy synergy allows the diagnostic model to some extent "imitate" teachers in diagnosing students' characteristics, and equips the intelligent learning environment with reasoning capabilities that can be further used to drive pedagogical decisions depending on the student learning style. The neuro-fuzzy implementation helps to encode both structured and non-structured teachers' knowledge: when teachers' reasoning is available and well defined, it can be encoded in the form of fuzzy rules; when teachers' reasoning is not well defined but is available through practical examples illustrating their experience, then the networks can be trained to represent this experience. The proposed approach has been tested in diagnosing aspects of student's learning style in a discovery-learning environment that aims to help students to construct the concepts of vectors in physics and mathematics. The diagnosis outcomes of the model have been compared against the recommendations of a group of five experienced teachers, and the results produced by two alternative soft computing methods. The results of our pilot study show that the neuro-fuzzy model successfully manages the inherent uncertainty of the diagnostic process; especially for marginal cases, i.e. where it is very difficult, even for human tutors, to diagnose and accurately evaluate students by directly synthesizing subjective and, some times, conflicting judgments