1,720,997 research outputs found
Monoglyceride lipase: Structure and inhibitors
Full text linkMonoglyceride lipase (MGL), the main enzyme responsible for the hydrolytic deactivation of the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG), is an intracellular serine hydrolase that plays critical roles in many physiological and pathological processes, such as pain, inflammation, neuroprotection and cancer. The crystal structures of MGL that are currently available provide valuable information about how this enzyme might function and interact with site-directed small-molecule inhibitors. On the other hand, its conformational equilibria and the contribution of regulatory cysteine residues present within the substrate-binding pocket or on protein surface remain open issues. Several classes of MGL inhibitors have been developed, from early reversible ones, such as URB602 and pristimerin, to carbamoylating agents that react with the catalytic serine, such as JZL184 and more recent O-hexafluoroisopropyl carbamates. Other inhibitors that modulate MGL activity by interacting with conserved regulatory cysteines act through mechanisms that deserve to be more thoroughly investigated
The Servitization revolution for Sustainability
Full text linkDue to increasing concerns about climate change, overexploitation of the earth’s finite resources, raw material extraction, increasing waste, and pollution, there is an urgent need to shift to economic models that guarantee environmental sustainability.
Servitization proposes a paradigm shift of business models that increase value creation for the customers by changing the perspective: from the making of products and the transfer of ownership, to the provision of integrated solutions enabled by those products, through lifecycle services. This paradigm shift also responds to the call for environmentally sustainable business models, as the move to a performance economy (or outcome-based) through servitization, demonstrated a great potential to radically reduce the environmental impacts of business, taking advantage of offering
products “as-a-service”. While moving from services that restore an asset’s conditions towards providing support the customer’s value chain processes that rely on that asset. In fact, providers of servitized business models (or product-service systems) take over an increasing share of risk from the customer. This also opens several opportunities
for reducing the environmental impact, either incrementally or radically, and to set up truly circular business models.
How can these results be achieved? Different factors influence the how (through which mechanisms) and the how much (to what extent) of the environmental sustainability impact of servitization:
- The type of business model or product-service system offered, and the circular strategies enabled (Chapters 1, 2, and 3). Different classes of servitized business models enable different circular economy strategies, namely reduce (increasing resource efficiency), reuse of products at the end of the usage cycle, remanufacture of subsystems and components, and recycle to recover materials.
- Product-oriented is the more traditional business model, where, besides selling products, a company provides supplementary services such as repair, maintenance, training, and advice/optimisation or end-of-life management. It entails only incremental sustainability benefits, mainly related to operational optimisation, lifecycle extension, or enabling the proper collection and recycling of products.
- Use-oriented models, such as the typical “as-a-service” case, do not transfer the product ownership to the customer. Therefore, contractual relationships between providers and customers may incentivise the design of products for circularity, reduce operational costs, facilitate maintenance, intensify the use of materials, increase resource efficiency, and closing the loop. These drivers entail significant sustainability benefits.
- Result-orientated business models link the provider-customer relationship and the monetary flows to the achievement of specified outcomes or performance targets from asset usage. In these models, the provider takes over the responsibility for (most of) lifecycle costs. This will trigger great resource efficiency, lifecycle extension, and/or the product and business model design for multiple lifecycles. These mechanisms promise the most radical environmental gains
Research Community ASAP 2025. Servitization and Sustainability: allineare valore economico e ambientale delle soluzioni prodotto-servizio
Full text linkXXII ASAP FORUM – Day 1: Leading the Servitization Journey
Full text linkThe session “Understanding and guiding servitisation” of the XXII ASAP Forum explored how manufacturing companies can manage the transition towards service-oriented business models in an increasingly complex economic, technological, and regulatory environment. Through the joint contributions of academic researchers and industry practitioners, the session highlighted servitisation as a systemic transformation affecting business models, organisational structures, sustainability strategies, regulatory compliance, and skills.
The discussion on Everything-as-a-Service (XaaS) business models, illustrated through the Stulz case, showed how advanced servitisation enables long-term value creation by shifting the focus from product sales to usage and performance-based offerings. While these models offer economic, relational, and environmental benefits, they require significant organisational change, new capabilities, and a gradual implementation strategy to overcome market resistance and internal barriers.
The ABB case demonstrated the importance of integrating economic and environmental impact assessment when designing and selling Product–Service Systems. By combining Total Cost of Ownership and Life Cycle Assessment, the proposed model supports more informed customer decisions and strengthens service-based value propositions, while highlighting the need for robust data and a broader, multi-stakeholder perspective.
The session also addressed corporate resilience in the face of regulatory change, focusing on the EU Data Act through the Tetra Pak case. The findings showed that proactive regulatory management, supported by cross-functional coordination and data governance, can transform compliance requirements into opportunities for innovation, competitive advantage, and enhanced digital services.
Finally, the Scandicar case highlighted skills as a critical enabler of servitisation, particularly in the automotive sector. The analysis revealed growing skill gaps, the central role of soft and digital skills, and increasing challenges in attracting and retaining qualified personnel. Addressing these challenges requires a holistic approach centred on employee experience, inclusive leadership, and continuous capability development.
Overall, the session underscored that successful servitisation depends on integrating business model innovation, sustainability, regulatory readiness, and human capital development, positioning services as a key driver of resilience and long-term competitiveness
Moving Towards Everything-as-a-Service: A Multiple Case Study in Manufacturing
No full textPart 3: Everything-as-a-Service (XaaS) Business Models in the Manufacturing IndustryInternational audienceIn the current economic environment, there is a growing trend in exploring the adoption of “as-a-service” business models to cope with competition, customer focus on cash conservation and reduced capital expenditures and exploit opportunities offered by new digital technologies. Also in the manufacturing sector, the “Everything-as-a-Service” paradigm is getting more attention. The adoption of such models, in fact, attracts companies’ interest in the possibility of establishing long-term partnerships with customers, providing solutions on an ongoing basis in exchange for recurring payments. This emerging trend, however, finds limited application in practice as it is poorly understood. To fill this gap, this paper proposes an empirical analysis involving 7 manufacturing companies to investigate the opportunities and challenges of this transformation. Evidence from case studies allows researchers also to identify the main elements that manufacturing companies must consider in order to adopt as-a-service models. In particular, the case analysis shows that the presence of strategic partnerships, particularly for financial risk management, and technology are relevant aspects in order to adopt an as-a-service model in manufacturing
Fighting tertiary mutations in EGFR-driven lung-cancers: Current advances and future perspectives in medicinal chemistry
Full text linkThird-generation inhibitors of the epidermal growth factor receptor (EGFR), best exemplified by osimertinib, have been developed to selectively target variants of EGFR bearing activating mutations and the mutation of gatekeeper T790 in patients with EGFR-mutated forms of Non-Small Cell Lung Cancer (NSCLC). While the application of third-generation inhibitors has represented an effective first- and second-line treatment, the efficacy of this class of inhibitors has been hampered by the novel, tertiary mutation C797S, which may occur after the treatment with osimertinib. More recently, other point mutations, including L718Q, G796D, G724S, L792 and G719, have emerged as mutations mediating resistance to third-generation inhibitors. The challenge of overcoming newly developed and recurrent resistances mediated by EGFR-mutations is thus driving the search of alternative strategies in the design of new therapeutic agents able to block EGFR-driven tumor growth. In this manuscript we review the recently emerged EGFR-dependent mechanisms of resistance to third-generation inhibitors, and the achievements lately obtained in the development of next-generation EGFR inhibitors
In silico drug discovery of melatonin receptor ligands with therapeutic potential
No full textThe neurohormone melatonin (N-acetyl-5-methoxytryptamine) regulates circadian rhythms exerting a variety of effects in the central nervous system and in periphery. These activities are mainly mediated by activation of MT1 and MT2 GPCRs. MT1/MT2 agonist compounds are used clinically for insomnia, depression, and circadian rhythm disturbances
N-Acylethanolamine Acid Amidase (NAAA): Structure, Function, and Inhibition
Full text linkN-Acylethanolamine acid amidase (NAAA) is an N-terminal cysteine hydrolase primarily found in the endosomal-lysosomal compartment of innate and adaptive immune cells. NAAA catalyzes the hydrolytic deactivation of palmitoylethanolamide (PEA), a lipid-derived peroxisome proliferator-activated receptor-α (PPAR-α) agonist that exerts profound anti-inflammatory effects in animal models. Emerging evidence points to NAAA-regulated PEA signaling at PPAR-α as a critical control point for the induction and the resolution of inflammation and to NAAA itself as a target for anti-inflammatory medicines. The present Perspective discusses three key aspects of this hypothesis: the role of NAAA in controlling the signaling activity of PEA; the structural bases for NAAA function and inhibition by covalent and noncovalent agents; and finally, the potential value of NAAA-targeting drugs in the treatment of human inflammatory disorders
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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