1,720,983 research outputs found
Everything-as-a-Service in manufacturing: a literature analysis and a definition
No full textCurrently, several companies are progressively transitioning from an offering focused on products to providing services and solutions, a phenomenon known as servitization. Manufacturers address this transformation in order to face competition, meet the growing demand for a more flexible offering, minimize capital expenditure, and exploit the opportunities offered by digitalization. Thus, new business models which a focus on selling the usage or outcome of a product rather than the product itself are increasingly receiving attention, as they can give companies the possibility to establish long-term partnerships with customers by providing solutions on a continuous basis in return for recurring payments. In recent years, this approach has become popular, particularly in the management community, with the term "Everything-as-a-service" (XaaS). The concept of XaaS has its origin in the information technology domain but, given the context described above, its application is becoming today more and more relevant for manufacturing companies. Various declinations of the XaaS concept in manufacturing have emerged, generally linked to the sales object and the application sector (e.g. Equipment-as-a-service, Consumable-as service, Heat-as-a-Service, ...). Moreover, the literature on this topic appears very fragmented and scattered across several similar and well-established research domains, such as servitization, integrated solutions, and product-service systems. Thus, a clear and agreed definition of the term is still lacking today and the boundaries of application are also unclear. In order to fill these gaps, this paper provides a structured analysis of the literature, in order to: i) define the current state of art, ii) identify the key elements and characteristics and iii) provide a new comprehensive definition of the XaaS paradigm in manufacturing
Aligning product-service systems with environmental sustainability: Investigating the key role of revenue and pricing mechanisms
No full textProduct-Service Systems (PSS) have a potential to increase environmental sustainability, e.g. by extending product lifespan through multiple usage cycles or enhancing resource efficiency during the usage phase. However, the actual achievement of environmental benefits through PSS has been questioned, due to contradictions between business and sustainability logics. This paper advocates a stronger alignment between PSS and environmental sustainability, through the role of revenue models and pricing mechanisms, in order to move beyond environmental gains as mere "additional effects" of PSS. Based on a conceptual elaboration of the literature, the paper develops morphological boxes to link revenue and pricing mechanisms with environmental value drivers of different PSS types. It shows how diverse revenue and pricing mechanisms may misalign with environmental value drivers and suggests alignment criteria. It also explores innovative “pay-per-emission” revenue models and "emission-based" pricing mechanisms to achieve such an alignment. The proposed framework, presented as a morphological toolkit, includes a process model for practitioners and policymakers to assess the alignment of current and new PSS offerings with environmental drivers
Mechanistic Modeling of Monoglyceride Lipase Covalent Modification Elucidates the Role of Leaving Group Expulsion and Discriminates Inhibitors with High and Low Potency
No full textInhibition of monoglyceride lipase (MGL), also known as monoacylglycerol lipase (MAGL), has emerged as a promising approach for treating neurological diseases. To gain useful insights in the design of agents with balanced potency and reactivity, we investigated the mechanism of MGL carbamoylation by the reference triazole urea SAR629 (IC50 = 0.2 nM) and two recently described inhibitors featuring a pyrazole (IC50 = 1800 nM) or a 4-cyanopyrazole (IC50 = 8 nM) leaving group (LG), using a hybrid quantum mechanics/molecular mechanics (QM/MM) approach. Opposite to what was found for substrate 2-arachidonoyl-sn-glycerol (2-AG), covalent modification of MGL by azole ureas is controlled by LG expulsion. Simulations indicated that changes in the electronic structure of the LG greatly affect reaction energetics with triazole and 4-cyanopyrazole inhibitors following a more accessible carbamoylation path compared to the unsubstituted pyrazole derivative. The computational protocol provided reaction barriers able to discriminate between MGL inhibitors with different potencies. These results highlight how QM/MM simulations can contribute to elucidating structure-activity relationships and provide insights for the design of covalent inhibitors
Design and SAR Analysis of Covalent Inhibitors Driven by Hybrid QM/MM Simulations
Full text linkQuantum mechanics/molecular mechanics (QM/MM) hybrid technique is emerging as a reliable computational method to investigate and characterize chemical reactions occurring in enzymes. From a drug discovery perspective, a thorough understanding of enzyme catalysis appears pivotal to assist the design of inhibitors able to covalently bind one of the residues belonging to the enzyme catalytic machinery. Thanks to the current advances in computer power, and the availability of more efficient algorithms for QM-based simulations, the use of QM/MM methodology is becoming a viable option in the field of covalent inhibitor design. In the present review, we summarized our experience in the field of QM/MM simulations applied to drug design problems which involved the optimization of agents working on two well-known drug targets, namely fatty acid amide hydrolase (FAAH) and epidermal growth factor receptor (EGFR). In this context, QM/MM simulations gave valuable information in terms of geometry (i.e., of transition states and metastable intermediates) and reaction energetics that allowed to correctly predict inhibitor binding orientation and substituent effect on enzyme inhibition. What is more, enzyme reaction modelling with QM/MM provided insights that were translated into the synthesis of new covalent inhibitor featured by a unique combination of intrinsic reactivity, on-target activity, and selectivity
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
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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