Browsing by Author "Carvalho, Mariana"
Now showing 1 - 4 of 4
Results Per Page
Sort Options
- Development of a conceptual model integrating management systems and the Shingo Model towards operational excellencePublication . Carvalho, Mariana; Sá, José Carlos; Marques, Pedro Alexandre; Santos, Gilberto; Pereira, António MárioTo remain competitive in the marketplace, organizations are seeking the adoption of management models and tools that will allow them to find better and more effective practices to reinvent themselves, and continuously improve their business processes and product’s quality in a sustainable way, hence pursuing the ultimate goal of reaching enterprise excellence. The purpose of this paper is to present a conceptual model that relates the requirements of the ISO Management System Standards with the dimensions and guiding principles of the Shingo Model for Operational Excellence. The proposed approach allows an organization with and existing management system based on one or more ISO Management System Standards to adopt and perform an assessment tool to evaluate its level of maturity regarding the adoption of the best practices and behaviours prescribed by the Shingo Model, which is a novelty contribution of this research. The validation of the proposed assessment tool took place in a Portuguese organization from the automotive sector, having comprised two moments: in the first one, an external assessor performed a set of behavioural observations that acted as a base to assign a score, while in the second moment such score was internally obtained through a survey that was filled by the organization’s employees. The results reveal that these two methods converge to similar conclusions, hence confirming that the proposed model has the potential to enable an organization to assess the maturity level of its management system regarding the adoption of the guiding principles of the Shingo Model for Operational Excellence. A limitation of this research is that the model was only validated in a single company.
- Development of a conceptual model integrating management systems and the Shingo Model towards operational excellencePublication . Carvalho, Mariana; Sá, José Carlos; Marques, Pedro Alexandre; Santos, Gilberto; Pereira, António MárioTo remain competitive in the marketplace, organizations are seeking the adoption of management models and tools that will allow them to find better and more effective practices to reinvent themselves, and continuously improve their business processes and product’s quality in a sustainable way, hence pursuing the ultimate goal of reaching enterprise excellence. The purpose of this paper is to present a conceptual model that relates the requirements of the ISO Management System Standards with the dimensions and guiding principles of the Shingo Model for Operational Excellence. The proposed approach allows an organization with and existing management system based on one or more ISO Management System Standards to adopt and perform an assessment tool to evaluate its level of maturity regarding the adoption of the best practices and behaviours prescribed by the Shingo Model, which is a novelty contribution of this research. The validation of the proposed assessment tool took place in a Portuguese organization from the automotive sector, having comprised two moments: in the first one, an external assessor performed a set of behavioural observations that acted as a base to assign a score, while in the second moment such score was internally obtained through a survey that was filled by the organization’s employees. The results reveal that these two methods converge to similar conclusions, hence confirming that the proposed model has the potential to enable an organization to assess the maturity level of its management system regarding the adoption of the guiding principles of the Shingo Model for Operational Excellence. A limitation of this research is that the model was only validated in a single company.
- In vitro and in silico evaluation of 5-MeO-DMT, LSD, and mescaline’s interaction with CYP450 enzymesPublication . Brito-da-Costa, Andreia Machado; Carvalho, Mariana; Dinis-Oliveira, Ricardo Jorge; Madureira-Carvalho, Áurea; Sousa, Sérgio F.; Silva, Diana Dias da; Dias da Silva, Diana Cristina5-Methoxy-N,N-dimethyltryptamine(5-MeO-DMT), lysergic acid diethylamide (LSD), and mescaline are classic hallucinogens known for their recreational use, which increased in the last dec-ades. Despite some available data on the metabolism of these drugs [1-3], a scientific gap exists regarding their possible interactions with CYP450 enzymes. Nevertheless, this information is of crucial relevance to predict drug-drug interactions and understand toxicological phenomena, in particular interindividual variability. This study aimed to evaluate in vitroand in silicothe interaction of 5-MeO-DMT, LSD, and mescaline with the enzymes CYP2A6/2B6/2D6/2E1/3A4. The in vitroassessment of CYP450 inhibition was performed using the Vivid®CYP450 screening kits. IC50 was calculated using GraphPad Prism 9.3.0. For in silicoassessment, molecular dynamics were performed using the PMEMD.cuda module in AMBER16. Calculations were made on the last 100 ns of the trajectory (stable zone) to assess the interaction mode/strength between enzyme and ligand, namely MMGBSA, per-residue decomposition energy, and hydrogen bonds. Based on the IC50(μM), LSD (0.35) and 5-MeO-DMT (3.47) present the capacity to be inhibitors of CYP2D6. Based on the MMGBSA (kcal/mol), LSD showed the highest binding affinities for all enzymes, while mescaline showed the lowest. The strong interaction of LSD with CYP2A6 is mediated by a hydrogen bond established with the protein residue Asn297. For interaction with CYP2B6, the residues Thr302 and Lys479 were important in mediating the interaction with 5-MeO-DMT and LSD. Key residues mediating the interaction of 5-MeO-DMT and LSD with CYP2D6 included Phe120, Leu213, and Phe483. For interaction with CYP2E1, residues Phe207, Phe298, and Thr303 are important; and for CYP3A4, an important hydrogen bond between LSD and Ala370 was identified.Conclusions: Both LSD and 5-MeO-DMT are predicted to have strong potential to be CYP2D6 inhibitors. A strong interaction was also identified in silicobetween LSD and CYP2A6.
- In vitro and in silico evaluation of psilocybin and psilocin’s interaction with CYP450 enzymesPublication . Brito-da-Costa, Andreia Machado; Carvalho, Mariana; Dinis-Oliveira, Ricardo Jorge; Madureira-Carvalho, Áurea; Sousa, Sérgio F.; Silva, Diana Dias da; Dias da Silva, Diana CristinaPsilocybin is a hallucinogen produced by “magic mushrooms”, being rapidly metabolized in the organism into psilocin [1, 2]. A scientific gap exists regarding the possible interactions between psilocybin/psilocin and CYP450 enzymes. Given their biological importance, and since the binding of drugs to CYP450 enzymes can interfere with the metabolism of other substrates leading to drug-drug interactions, this research topic is of utmost importance. This study aimed to evaluate in silicoand in vitrothe interaction of psilocybin and psilocin with the enzymes CYP2A6/2B6/2D6/2E1/3A4. The in vitroassessment of inhibition was performed using the Vivid®CYP450 screening kits. IC50 was calculated using GraphPad Prism 9.3.0. For in silico assessment, molecular dynamics were per-formed using the PMEMD.cuda module in AMBER16. Calculations were made on the last 100 ns of the trajectory (stable zone) to assess the interaction between enzyme and ligand, namely MMGBSA, per-residue decomposition energy, and hydrogen bonds. Psilocin showed the capacity to be an in-hibitor of CYP2A6/2B6/2D6/2E1/3A4, based on the respective IC50 values (μM) of 2.06, 6.17, 11.89, 6.37, and 2.36. Considering the MMGBSA, higher values were obtained for psilocin, corroborating the stronger binding affinity of this compound. The interaction of psilocybin/psilocin with CYP2A6 is medi-ated by a hydrogen bond established with the protein residue Asn297. Other important residues include Phe107 and Ile366. For CYP2B6, the strong binding of psilocin is mediated by interactions with Ile114, Thr302 (hydrogen bond), and Leu363. For interaction with CYP2D6, the most important residue seems to be Ser304, with which it forms a hydrogen bond; for CYP2E1, key residues include Phe207, Thr303, and Phe478. A strong hydrogen bond is formed between psilocin and CYP3A4 residue Phe304, contrib-uting to the high binding affinity. The results suggest a potential for psilocin to inhibit all enzymes, especially CYP2A6 and CYP3A4.