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It is by now widely recognized that atherosclerosis – with its burden of consequences in cerebro- and cardiovascular diseases – is just a chronic inflammatory process of the arterial wall. A very peculiar, complex and as yet still poorly understood process, upon which hundreds of scientists from several different fields are continuously concentrating their investigative efforts in search of possible leads to therapeutic approaches. Initiation of the disease is given by deposition of lipid in the intimal layers, resulting in endothelial activation and infiltration of blood-derived mononuclear cells. These mature into macrophages, become activated, express scavenger receptors such as SR-A and CD36 and ingest the oxidized lipoprotein accumulating in the lesion. Macrophages thus represent an obvious target for intervention, as they play a crucial role in the progression of the atherosclerotic inflammation. Studies have shown that hypercholesterolaemia can increase monocyte mobilisation from bone marrow into the circulation, and several chemokines and their receptors are involved in the recruitment of blood borne monocytes into the arterial wall. Monocyte-derived macrophages are capable of sustaining their local proliferation, but resident macrophages possibly also participate in progression of the disease. Remarkably, smooth muscle cells can acquire macrophage-like features during atherogenesis, including the ability to uptake lipid, thus becoming a significant proportion of the CD68+ so called ‘foam cells’. Lipid-laden macrophages induce extracellular matrix degradation, while lipid uptake eventually causes their death with formation of a necrotic core. The efficiency in clearance of dead cells by phagocytes (efferocytosis), can also be considered as a determinant of plaque vulnerability. An important feature of macrophages is their great plasticity and functional diversity in response to signals from the plaque microenvironment. Several such ‘signals’ (cholesterol, oxidative stress, hypoxia, cytokines…) can in fact modulate cell differentiation at transcriptional and epigenetic levels, thus altering the balance between the effector vs. reparative functions of macrophages. A whole gamut of specific subsets are thus originated, which appear to be simultaneously present in lesions with proportions that vary according to their location, the disease stage, and the presence of additional cell types such as e.g. dendritic cells. The result is a multiplicity of potential pharmacological targets, representing a major obstacle for the devisement of therapeutic strategies. Experimental approaches have been attempted in diverse directions: e.g. modulating the macrophage phenotype to an anti-inflammatory and resolving state, or blocking pro-inflammatory cytokines that macrophages produce, or alternatively enhancing efferocytosis in order to favour the resolution of inflammation and stabilization of plaques. Blocking monocyte recruitment was proposed in order to hinder the initial steps of atherogenesis. Other treatments were aimed to inhibiting local proliferation of pro-inflammatory macrophages. Specific targeting of macrophages has however to date not yet provided significant, translational results. The present Research Topic collects articles to help unravel the complexity of macrophage behaviour in atherosclerosis and identify innovative pharmacological approaches.

Science: general issues --- Pharmacology --- monocytes/macrophages --- inflammation --- foam cell formation --- smooth muscle cells --- atherosclerosis progression --- monocytes/macrophages --- inflammation --- foam cell formation --- smooth muscle cells --- atherosclerosis progression

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It is by now widely recognized that atherosclerosis – with its burden of consequences in cerebro- and cardiovascular diseases – is just a chronic inflammatory process of the arterial wall. A very peculiar, complex and as yet still poorly understood process, upon which hundreds of scientists from several different fields are continuously concentrating their investigative efforts in search of possible leads to therapeutic approaches. Initiation of the disease is given by deposition of lipid in the intimal layers, resulting in endothelial activation and infiltration of blood-derived mononuclear cells. These mature into macrophages, become activated, express scavenger receptors such as SR-A and CD36 and ingest the oxidized lipoprotein accumulating in the lesion. Macrophages thus represent an obvious target for intervention, as they play a crucial role in the progression of the atherosclerotic inflammation. Studies have shown that hypercholesterolaemia can increase monocyte mobilisation from bone marrow into the circulation, and several chemokines and their receptors are involved in the recruitment of blood borne monocytes into the arterial wall. Monocyte-derived macrophages are capable of sustaining their local proliferation, but resident macrophages possibly also participate in progression of the disease. Remarkably, smooth muscle cells can acquire macrophage-like features during atherogenesis, including the ability to uptake lipid, thus becoming a significant proportion of the CD68+ so called ‘foam cells’. Lipid-laden macrophages induce extracellular matrix degradation, while lipid uptake eventually causes their death with formation of a necrotic core. The efficiency in clearance of dead cells by phagocytes (efferocytosis), can also be considered as a determinant of plaque vulnerability. An important feature of macrophages is their great plasticity and functional diversity in response to signals from the plaque microenvironment. Several such ‘signals’ (cholesterol, oxidative stress, hypoxia, cytokines…) can in fact modulate cell differentiation at transcriptional and epigenetic levels, thus altering the balance between the effector vs. reparative functions of macrophages. A whole gamut of specific subsets are thus originated, which appear to be simultaneously present in lesions with proportions that vary according to their location, the disease stage, and the presence of additional cell types such as e.g. dendritic cells. The result is a multiplicity of potential pharmacological targets, representing a major obstacle for the devisement of therapeutic strategies. Experimental approaches have been attempted in diverse directions: e.g. modulating the macrophage phenotype to an anti-inflammatory and resolving state, or blocking pro-inflammatory cytokines that macrophages produce, or alternatively enhancing efferocytosis in order to favour the resolution of inflammation and stabilization of plaques. Blocking monocyte recruitment was proposed in order to hinder the initial steps of atherogenesis. Other treatments were aimed to inhibiting local proliferation of pro-inflammatory macrophages. Specific targeting of macrophages has however to date not yet provided significant, translational results. The present Research Topic collects articles to help unravel the complexity of macrophage behaviour in atherosclerosis and identify innovative pharmacological approaches.

monocytes/macrophages --- inflammation --- foam cell formation --- smooth muscle cells --- atherosclerosis progression

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This book, as a Special Issue, is a collection of some of the latest advancements in designing and scheduling smart manufacturing systems. The smart manufacturing concept is undoubtedly considered a paradigm shift in manufacturing technology. This conception is part of the Industry 4.0 strategy, or equivalent national policies, and brings new challenges and opportunities for the companies that are facing tough global competition. Industry 4.0 should not only be perceived as one of many possible strategies for manufacturing companies, but also as an important practice within organizations. The main focus of Industry 4.0 implementation is to combine production, information technology, and the internet. The presented Special Issue consists of ten research papers presenting the latest works in the field. The papers include various topics, which can be divided into three categories—(i) designing and scheduling manufacturing systems (seven articles), (ii) machining process optimization (two articles), (iii) digital insurance platforms (one article). Most of the mentioned research problems are solved in these articles by using genetic algorithms, the harmony search algorithm, the hybrid bat algorithm, the combined whale optimization algorithm, and other optimization and decision-making methods. The above-mentioned groups of articles are briefly described in this order in this book.

flexible job-shop scheduling problem --- combinatorial optimization --- genetic algorithm --- candidate order-based genetic algorithm --- multichromosome --- facility layout --- optimization --- metaheuristic algorithm --- cell formation --- design of experiments --- digital platforms --- decision-making --- insurance --- Baltic --- customization --- personalization --- assembly line balancing --- group technology --- cluster algorithm --- bottleneck station --- output rate --- tolerance allocation --- machine and process selection --- heuristic approach --- univariate search method --- whale optimization algorithm --- selective assembly --- overrunning clutch assembly --- harmony search algorithm --- Hastelloy X --- turning --- cutting force --- surface roughness --- liquid nitrogen --- grass-hooper optimization algorithm --- moth-flame optimization algorithm --- hybrid bat algorithm --- optimization problem --- the distributed assembly permutation flowshop scheduling problem --- variable neighborhood descent --- multi-criteria assessment --- cell manufacturing design --- operational complexity --- makespan --- production line balancing rate --- electrochemical machining (ECM) --- material removal rate (MRR) --- nickel presence (NP) --- grey wolf optimizer (GWO) --- moth-flame optimization algorithm (MFO) --- Monel 400 alloys --- n/a

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Although the design and management of manufacturing systems have been explored in the literature for many years now, they still remain topical problems in the current scientific research. The changing market trends, globalization, the constant pressure to reduce production costs, and technical and technological progress make it necessary to search for new manufacturing methods and ways of organizing them, and to modify manufacturing system design paradigms. This book presents current research in different areas connected with the design and management of manufacturing systems and covers such subject areas as: methods supporting the design of manufacturing systems, methods of improving maintenance processes in companies, the design and improvement of manufacturing processes, the control of production processes in modern manufacturing systems production methods and techniques used in modern manufacturing systems and environmental aspects of production and their impact on the design and management of manufacturing systems. The wide range of research findings reported in this book confirms that the design of manufacturing systems is a complex problem and that the achievement of goals set for modern manufacturing systems requires interdisciplinary knowledge and the simultaneous design of the product, process and system, as well as the knowledge of modern manufacturing and organizational methods and techniques.

Technology: general issues --- efficiency --- production processes --- machinery --- production maintenance --- logistic regression --- production process capability --- product quality --- monitoring of production processes --- process variables --- production planning optimization --- closed-loop green supply chain --- government subsidy --- stackelberg game --- re-manufacturing --- polish manufacturing company --- additive manufacturing technology --- questionnaire survey --- empirical research --- semi-Markov model --- Markov model --- empirical data distribution --- readiness --- production machines --- 8 disciplines method --- custom cable assemblies --- defects --- functional test --- customer satisfaction --- hard computing approach --- p-median problem --- generalized cell formation --- assembly-line balancing --- multi-objective optimization --- simulated annealing --- multilayer network --- production process design --- unit and small-lot production design for manufacturability --- fuzzy logic --- eco-design --- end-of-life treatment --- recycling --- solar power plant --- wind power plant --- life cycle analysis --- advanced industrial engineering --- modelling and simulation --- factory of the future --- smart factory --- manufacturing systems --- production planning optimisation --- decision support --- additive manufacturing --- fused filament fabrication --- CFR-PEEK --- optimal process parameters --- manufacturing performance --- multiple response optimization --- reconfigurable manufacturing system --- Petri net --- deadlock --- siphon --- supervisory controller --- reengineering --- simulation --- productivity --- batch processors --- real-time control --- dispatching --- wafer fabrication --- semiconductor manufacturing --- system-wide performance --- robust scheduling --- predictive scheduling --- machine failure --- failure prediction --- constraint programming --- constraint satisfaction problem --- cost estimation --- decision support systems --- multicriteria optimization --- production planning --- project management --- layout --- 3D printing devices --- methods of optimizing the arrangement of workstations --- car tire production process --- rubber industry --- environmental impact --- Life Cycle Assessment --- entire product lifecycle --- decision-making process --- lean maintenance --- effectiveness --- decision trees --- rough set theory --- n/a

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Although the design and management of manufacturing systems have been explored in the literature for many years now, they still remain topical problems in the current scientific research. The changing market trends, globalization, the constant pressure to reduce production costs, and technical and technological progress make it necessary to search for new manufacturing methods and ways of organizing them, and to modify manufacturing system design paradigms. This book presents current research in different areas connected with the design and management of manufacturing systems and covers such subject areas as: methods supporting the design of manufacturing systems, methods of improving maintenance processes in companies, the design and improvement of manufacturing processes, the control of production processes in modern manufacturing systems production methods and techniques used in modern manufacturing systems and environmental aspects of production and their impact on the design and management of manufacturing systems. The wide range of research findings reported in this book confirms that the design of manufacturing systems is a complex problem and that the achievement of goals set for modern manufacturing systems requires interdisciplinary knowledge and the simultaneous design of the product, process and system, as well as the knowledge of modern manufacturing and organizational methods and techniques.

Technology: general issues --- efficiency --- production processes --- machinery --- production maintenance --- logistic regression --- production process capability --- product quality --- monitoring of production processes --- process variables --- production planning optimization --- closed-loop green supply chain --- government subsidy --- stackelberg game --- re-manufacturing --- polish manufacturing company --- additive manufacturing technology --- questionnaire survey --- empirical research --- semi-Markov model --- Markov model --- empirical data distribution --- readiness --- production machines --- 8 disciplines method --- custom cable assemblies --- defects --- functional test --- customer satisfaction --- hard computing approach --- p-median problem --- generalized cell formation --- assembly-line balancing --- multi-objective optimization --- simulated annealing --- multilayer network --- production process design --- unit and small-lot production design for manufacturability --- fuzzy logic --- eco-design --- end-of-life treatment --- recycling --- solar power plant --- wind power plant --- life cycle analysis --- advanced industrial engineering --- modelling and simulation --- factory of the future --- smart factory --- manufacturing systems --- production planning optimisation --- decision support --- additive manufacturing --- fused filament fabrication --- CFR-PEEK --- optimal process parameters --- manufacturing performance --- multiple response optimization --- reconfigurable manufacturing system --- Petri net --- deadlock --- siphon --- supervisory controller --- reengineering --- simulation --- productivity --- batch processors --- real-time control --- dispatching --- wafer fabrication --- semiconductor manufacturing --- system-wide performance --- robust scheduling --- predictive scheduling --- machine failure --- failure prediction --- constraint programming --- constraint satisfaction problem --- cost estimation --- decision support systems --- multicriteria optimization --- production planning --- project management --- layout --- 3D printing devices --- methods of optimizing the arrangement of workstations --- car tire production process --- rubber industry --- environmental impact --- Life Cycle Assessment --- entire product lifecycle --- decision-making process --- lean maintenance --- effectiveness --- decision trees --- rough set theory --- efficiency --- production processes --- machinery --- production maintenance --- logistic regression --- production process capability --- product quality --- monitoring of production processes --- process variables --- production planning optimization --- closed-loop green supply chain --- government subsidy --- stackelberg game --- re-manufacturing --- polish manufacturing company --- additive manufacturing technology --- questionnaire survey --- empirical research --- semi-Markov model --- Markov model --- empirical data distribution --- readiness --- production machines --- 8 disciplines method --- custom cable assemblies --- defects --- functional test --- customer satisfaction --- hard computing approach --- p-median problem --- generalized cell formation --- assembly-line balancing --- multi-objective optimization --- simulated annealing --- multilayer network --- production process design --- unit and small-lot production design for manufacturability --- fuzzy logic --- eco-design --- end-of-life treatment --- recycling --- solar power plant --- wind power plant --- life cycle analysis --- advanced industrial engineering --- modelling and simulation --- factory of the future --- smart factory --- manufacturing systems --- production planning optimisation --- decision support --- additive manufacturing --- fused filament fabrication --- CFR-PEEK --- optimal process parameters --- manufacturing performance --- multiple response optimization --- reconfigurable manufacturing system --- Petri net --- deadlock --- siphon --- supervisory controller --- reengineering --- simulation --- productivity --- batch processors --- real-time control --- dispatching --- wafer fabrication --- semiconductor manufacturing --- system-wide performance --- robust scheduling --- predictive scheduling --- machine failure --- failure prediction --- constraint programming --- constraint satisfaction problem --- cost estimation --- decision support systems --- multicriteria optimization --- production planning --- project management --- layout --- 3D printing devices --- methods of optimizing the arrangement of workstations --- car tire production process --- rubber industry --- environmental impact --- Life Cycle Assessment --- entire product lifecycle --- decision-making process --- lean maintenance --- effectiveness --- decision trees --- rough set theory