Leveraging Circular Economy through a Methodology for Smart Service Systems Engineering

Product Service Systems (PSS) and Smart Services are powerful means for deploying Circular Economy (CE) goals in industrial practices, through dematerialization, extension of product lifetime and efficiency increase by digitization. Within this article, approaches from PSS design, Smart Service design and Model-based Systems Engineering (MBSE) are combined to form a Methodology for Smart Service Architecture Definition (MESSIAH). First, analyses of present system modelling procedures and systems modelling notations in terms of their suitability for Smart Service development are presented. The results indicate that current notations and tools do not entirely fit the requirements of Smart Service development, but that they can be adapted in order to do so. The developed methodology includes a modelling language system, the MESSIAH Blueprinting framework, a systematic procedure and MESSIAH CE, which is specifically designed for addressing CE strategies and practices. The methodology was validated on the example of a Smart Sustainable Street Light System for Cycling Security (SHEILA). MESSIAH proved useful to help Smart Service design teams develop service-driven and robust Smart Services. By applying MESSIAH CE, a sustainable Smart Service, which addresses CE goals, has been developed

Development of a mapping system engineering approaches to classic product development processes of technical products: A work project of project management in product development

Project Work presented as the partial requirement for obtaining a Master's degree in Information Management, specialization in Information Systems and Technologies ManagementThe automotive industry faces the challenge of meeting customer requirements while ensuring technological advancements, fast and cost-effective development, and high-quality production. Information systems play a crucial role in efficiently designing internal processes and meeting customer demands. Personalized solutions are increasingly adopted to cater to individual preferences while maintaining up-to-date technology. Information systems are utilized to record and manage customer requirements, optimize production processes, control inventories, and facilitate effective communication between departments. Product data management (PDM) solutions are widely employed, with 77% of automotive companies implementing them. PDM encompasses the storage and management of data relevant to product development, supporting the entire product lifecycle. As product complexity grows, efficient management of product data becomes essential, along with the optimization of business processes to shorten development time and parallelize tasks. CAx coordination, involving computer-aided design (CAD), manufacturing (CAM), and engineering (CAE), ensures smooth communication and coordination across the product development process. PDM systems act as intermediaries between CAx coordination and enterprise resource planning systems, facilitating seamless integration of design and manufacturing processes. Leading providers of enterprise resource planning and CAD systems offer software solutions for product lifecycle management and PDM, enabling centralized and accessible product information, streamlining development and management processes

The relevance of chemical dereplication in microbial natural product screening

Natural products (NPs) continue to play an important role for the discovery of new therapeutic candidates. Over the past 30 years, NPs or their derivatives have accounted for 60% of new anticancer agents and almost 75% of all new antibacterial molecules [1-3]. One hundred NP and NP-derived substances were being evaluated in clinical trials or were being registered at the end of 2013 [4]. NPs have been isolated from many terrestrial and marine organisms, including plants, marine invertebrates, and microorganisms, the latter being the source selected more often for pharmaceutical drug discovery programs. Microorganisms (traditionally actinobacteria and fungi, but more recently cyanobacteria and myxobacteria as well) are one of the most prolific sources among living organisms for the production of bioactive molecules. Exploitation of their specialized (commonly termed secondary) metabolism has guaranteed for decades already the discovery of novel antibiotics and other compounds with unprecedented chemical characteristics and biological properties not existing in screening libraries of synthetic compounds [1,5]. Querying the literature, we previously reported [6,7] that among more than 31600 microbial products discovered from 1900 onwards, ca. 20200 possess some biological activity. Among them 35% were produced from filamentous fungi, 48% from actinomycetes, and 17% from other bacteria. According to Berdy [2] ca. 20000 and 22000 bioactive microbial secondary metabolites had been described in the scientific and patent literature by the end of 2000 and 2002, respectively. About 38% of these molecules are produced by filamentous fungi, whereas the largest group (45%) derives from actinomycetes (7600 metabolites from Streptomyces and 2500 from the so-called rare filamentous actinomycetes). The remaining 17% is produced by other bacteria such as Bacillus, Pseudomonas, myxobacteria, and cyanobacteria. During the past 15 years, we have registered the proJOURNAL OF APPLIED BIOANALYSIS, Apr. 2015, p. 55-67. http://dx.doi.org/10.17145/jab.15.010 Vol. 1, No.

Influence of genetic variability on the clinical pharmacology of carbamazepine and lamotrigine

This research programme investigates the influence of genetic variability on the clinical pharmacology of carbamazepine (CBZ) and lamotrigine (LTG). Common polymorphisms in genes that may influence the response to CBZ and LTG include CYP3A4 g.-392A>G, CYP3A5 g.6986A>G, CYP1A2 g.5734C>A, EPHX1 c.337T>C, EPHX1 c.416A>G, UGT2B7 c.802C>T, ABCB1 c.1236C>T, ABCB1 c.2677G>T/A, ABCB1 c.3435C>T and SCN2A c.56G>A. The prevalence of these common polymorphisms was evaluated in a 400-strong study population from a single research unit. Minor allele frequency ranged between 3.5% (CYP3A4 -392G) and 48.0% (ABCB1 1236T). Allele and genotype distributions were comparable to published data for other Caucasian populations. The influence of common polymorphisms in drug metabolising enzyme (DME) and sodium channel genes on the optimal dose of CBZ was assessed in a cohort of 70 patients. This study revealed that age and common polymorphisms in the EPHX1 gene (c.337T>C and c.416A>G) are potential predictors for optimal dose of CBZ. The significant effects of EPHX1 variants may be explained by their significant contribution to the inactivation of CBZ. These potential predictors explain approximately 15% of the inter-individual variation in CBZ dose requirements. Preliminary findings suggest that common polymorphisms in DME genes do not form a unique profile which increases the risk of developing intolerable CBZ adverse effects. It is unlikely that common polymorphisms in ABCB1 and SCN2A genes influence the expression and/or activity of their respective proteins to the level at which they can dictate response to LTG therapy. The influence of common polymorphisms in ABCB1 and SCN2A genes on the optimal dose of LTG was assessed in a cohort of 94 patients. Optimal dose in this study was defined as the final dose given to the patients that successfully maintained seizure freedom for at least 1 year with LTG monotherapy. Several basic clinical factors such as age and gender were also examined as potential predictors. The effect of predictors on the optimal dose of LTG was investigated using linear regression analysis. This study revealed that gender and common polymorphisms in the ABCB1 gene (c.1236C>T and c.3435C>T) are potential predictors for optimal dose of LTG. These predictors explain approximately 17% of the inter-individual variation in LTG dose requirement. These findings further highlight the potential role of P-gp in the management of epilepsy. The final study investigated the influence of ABCB1 c.1236C>T and ABCB1 c.3435C>T polymorphisms on the pharmacokinetics of LTG. A total of 156 blood samples from 50 patients receiving LTG monotherapy were available for analysis. The influence of ABCB1 variants was evaluated by population pharmacokinetics. This approach successfully estimated the oral clearance of LTG monotherapy at steady-state. However, the absorption rate constant (Ka) and volume of distribution (Vd) of LTG were poorly estimated. The inclusion of common polymorphisms in the ABCB1 gene in the pharmacokinetic model did not improve the estimation of oral clearance. This may indicate that common variants of ABCB1 do not influence clearance of LTG

Fermented probiotic beverage based on quinoa : Functionality, hygiene, and health effects

White quinoa grains were used as a source of novel beneficial microorganisms and as a matrix for development of a fermented plant-based drink. Studies on the quinoa grain microbiota were performed by applying spontaneous fermentation to allow isolation of autochthonous Lactiplantibacillus strains with potential to be used as starter cultures. The quinoa-based drink was fermented with the commercial probiotic strain Lactiplantibacillus plantarum DSM9843 (=299v), or with autochthonous Lactiplantibacillus strains. The efficiency of the strains as starter cultures were determined by monitoring changes in the bacteriological community during fermentation. Additionally, interactions between polyphenols and the strains during fermentation were analysed in the beverage and finally, in an attempt to categorize one of the strains as future probiotics, the modified microbiota composition in healthy volunteers was determined after consumption.The experimental procedure was designed to characterize the grain microbiota on the surface as well as inside the grains through preparation of a liquid quinoa dough fermented spontaneously at 30 °C for 8 days. Samples were cultured and viable cells were isolated and genetically analysed applying Sanger sequencing. A consortium of potential pathogenic and beneficial bacteria co-existed and changed positively during quinoa dough fermentation, with the Lactobacillaceae family overtaking the niche. Isolates of autochthonous Lactiplantibacillus strains were further investigated and a phenotypical characterization of the enzymatic capacity of the strains on different carbohydrates and on degradation of tannins were performed. The results showed that the L. plantarum strains were able to ferment a large array of carbohydrates, including xylose and glycerol. Furthermore, tannase degradation was also observed for most of the tested strains.When using starter cultures to ferment the quinoa-based beverage, the commercial strain L. plantarum DSM9843 proved to be a strong inhibitor of undesirable microorganisms for up to 28 days of storage time. However, viable cells of Enterococcus spp., remained present, questioning the efficiency of the commercial strain as starter culture and the limitations of using pH values of 4 or below as parameter of safeness. As a second approach, the quinoa grains were toasted, mixed with sterile water, and inoculated with four of the previously isolated strains: L. plantarum 3, L. plantarum 5, L. plantarum 9, and L. plantarum 10, respectively. Mapping the bacterial community by next generation sequencing (NGS) showed that Firmicutes dominated after fermentation. Changes in the content of polyphenolic compounds were analysed using reversed phase high-performance liquid chromatography (RP-HPLC). No significant variation was observed in the total content of polyphenols or flavonoids between beverages fermented with the different strains, but significant variations were observed for different compounds such as gallic acid, vanillic acid, syringic acid, quercetin 3O-glucoside and rutin.Furthermore, one of the isolated strains, L. plantarum 3, was tested as a first step to categorize the bacterium as a future probiotic strain. Healthy volunteers consumed the fermented quinoa-based beverage for 14 days. Saliva and stool samples were collected and analysed qualitatively and quantitatively by quantitative-polymerase chain reaction (q-PCR), terminal restriction fragment length polymorphism (T-RLFP) and NGS. A modified microbiota composition was found and the increase of the amount of Lactobacillaceae species may indicate that the bacterium did survive the transit through the gastrointestinal trac

Efficient Algorithms for Solving Facility Problems with Disruptions

This study investigates facility location problems in the presence of facility disruptions. Two types of problems are investigated. Firstly, we study a facility location problem considering random disruptions. Secondly, we study a facility fortification problem considering disruptions caused by random failures and intelligent attacks.We first study a reliable facility location problem in which facilities are faced with the risk of random disruptions. In the literature, reliable facility location models and solution methods have been proposed under different assumptions of the disruption distribution. In most of these models, the disruption distribution is assumed to be completely known, that is, the disruptions are known to be uncorrelated or to follow a certain distribution. In practice, we may have only limited information about the distribution. In this work, we propose a robust reliable facility location model that considers the worst-case distribution with incomplete information. Because the model imposes fewer distributional assumptions, it includes several important reliable facility location problems as special cases. We propose an effective cutting plane algorithm based on the supermodularity of the problem. For the case in which the distribution is completely known, we develop a heuristic algorithm called multi-start tabu search to solve very large instances.In the second part of the work, we study an r-interdiction median problem with fortification that simultaneously considers two types of disruption risks: random disruptions that happen probabilistically and disruptions caused by intentional attacks. The problem is to determine the allocation of limited facility fortification resources to an existing network. The problem is modeled as a bi-level programming model that generalizes the r-interdiction median problem with probabilistic fortification. The lower level problem, that is, the interdiction problem, is a challenging high-degree non-linear model. In the literature, only the enumeration method is applied to solve a special case of the problem. By exploring the special structure property of the problem, we propose an exact cutting plane method for the problem. For the fortification problem, an effective logic based Benders decomposition algorithm is proposed

An Orchestration Method for Integrated Multi-Disciplinary Simulation in Digital Twin Applications

In recent years, the methodology of Model-Based System Engineering (MBSE) has become relevant to the design of complex products, especially when safety critical systems need to be addressed. It allows, in fact, the deployment of product development directly through some digital models, allowing an effective traceability of requirements, being allocated upon the system functions, components, and parts. This approach enhances the designer capabilities in controlling the product development, manufacturing and after-market services. However, the application of such a methodology requires overcoming several technological barriers, especially in terms of models integration. The interoperability and management of several models—developed within different software to cover multiple levels of detail across several technical disciplines—is still very difficult, despite the level of maturation achieved by Systems Engineering. This paper describes a possible approach to provide such a connection between tools to allow a complete multi-disciplinary and heterogeneous simulation to analyse complex systems, such as safety-critical ones, which are typical of aerospace applications. Such an application is within a defined industrial context, placing particular attention on the compatibility of the approach with the legacy processes and tool