LQTA-QSAR: A New 4D-QSAR Methodology Martins, João Paulo A; Barbosa, Euzébio G; Pasqualoto, Kerly F. M ...
Journal of Chemical Information and Modeling,
06/2009, Letnik:
49, Številka:
6
Journal Article
Recenzirano
A novel 4D-QSAR approach which makes use of the molecular dynamics (MD) trajectories and topology information retrieved from the GROMACS package is presented in this study. This new methodology, ...named LQTA-QSAR (LQTA, Laboratório de Quimiometria Teórica e Aplicada), has a module (LQTAgrid) that calculates intermolecular interaction energies at each grid point considering probes and all aligned conformations resulting from MD simulations. These interaction energies are the independent variables or descriptors employed in a QSAR analysis. The comparison of the proposed methodology to other 4D-QSAR and CoMFA formalisms was performed using a set of forty-seven glycogen phosphorylase b inhibitors (data set 1) and a set of forty-four MAP p38 kinase inhibitors (data set 2). The QSAR models for both data sets were built using the ordered predictor selection (OPS) algorithm for variable selection. Model validation was carried out applying y-randomization and leave-N-out cross-validation in addition to the external validation. PLS models for data set 1 and 2 provided the following statistics: q 2 = 0.72, r 2 = 0.81 for 12 variables selected and 2 latent variables and q 2 = 0.82, r 2 = 0.90 for 10 variables selected and 5 latent variables, respectively. Visualization of the descriptors in 3D space was successfully interpreted from the chemical point of view, supporting the applicability of this new approach in rational drug design.
Copper (Cu) plays crucial biochemical and physiological functions in plants. However, at high concentrations, Cu can become extremely toxic, inducing several physiological changes and symptoms of ...toxicity. The aim was to analyze the anatomical and physiological changes of the bromeliad, Billbergia zebrina, in response to Cu excess under in vitro conditions. B. zebrina plants, previously established in vitro, were transferred to culture media containing 0, 2, 20, or 200 µM Cu. Growth traits and enzyme activity of superoxide dismutase and ascorbate peroxidase were measured over a period of 80 days. To verify the biological activity of roots grown under different Cu concentrations, a biospeckle laser was used at 20 and 80 days. Biomass accumulation, Cu content and anatomical analyses were performed at 80 days. Plants did not show any visible signs of disturbance and all plants survived the experimental treatments. Plants grown with 200 µM Cu showed anatomical changes, such as increased stomatal index and thicker exodermal cell walls of the roots, which may aid in heavy metal tolerance. High biological activity was observed only at 20 days. This biological activity was linked to increased thickness of the cell wall at the exodermis. The Cu content evidenced that the anatomical changes were effective against the transport of excess Cu into the plants. Although Cu exposure affected leaf and root anatomy as well as growth, exposure only induced minimal changes in the antioxidant system. B. zebrina tolerates high amounts of Cu and could potentially be used as a bioindicator species.
Injection lap riveting Ferreira, Francisco R.; Pragana, João P.M.; Bragança, Ivo M.F. ...
CIRP annals,
2021, 2021-00-00, Letnik:
70, Številka:
1
Journal Article
Recenzirano
This paper presents an injection lap riveting process to connect two sheets placed one on top of the other. The process is carried out at ambient temperature and differs from self-pierce riveting ...because its joining principle is based on plasticity and friction without fracture and formation of new surfaces. The working principle is based on two consecutive operations - first, a dovetail ring hole is machined in the lower sheet and then a semi tubular rivet is injected through the upper sheet into the dovetail ring hole of the lower sheet, by compression with a punch. The presentation is based on a combined experimental and numerical investigation and special emphasis is put on the influence of the dovetail ring hole geometry in material flow, riveting force, and pull-out and shear destructive forces. The last past of the paper includes details of a prototype cutting tool that was developed by the authors for producing the dovetail ring holes in-site and fostering the portability and applicability of the process.
Introduction: Studies prove that the use of medicinal plants is a custom carried out by man since ancient times, the evolution of the pharmaceutical industry makes more people consume more natural ...products. Currently, we can observe that mouthwashes containing natural compounds have shown a growth in demand in the markets and in the professional community. Objective: The present study aims to carry out the chemical characterization and microbiological potential of Piper mikanianum (Kunth) Steud essential oil (EOPm), providing data that allows the development of a low‐cost mouthwash formulation aimed at vulnerable communities. Methods: The evaluation of the antibacterial activity and modulator of bacterial resistance was performed by the microdilution method to determine the minimum inhibitory concentration (MIC). The chemical components were characterized by gas chromatography coupled to mass spectrometry, identified 28 constituents, in which Safrole Phenylpropanoid is the major compound, representing 72.6 % of the total composition, followed by α‐pinene (10.7 %), Limonene (2 %), β‐caryophyllene (2 %), E‐nerolidol (1.9 %), spathulenol (1.3 %) and camphene (1.1 %). Results: The EOPm showed a MIC minimum inhibitory concentration≥1024 μg/mL for all bacterial strains used in the tests. When the EOPm modulating activity combined with chlorhexidine, mouthwash, ampicillin, gentamicin and penicillin G was evaluated against bacterial resistance, the oil showed significant synergistic activity, reducing the MIC of the products tested in combination, in percentage between 20.6 % to 98 .4 %. Conclusions: We recommend the expansion of tests with greater variation of EOPm concentration combinations and the products used in this study, as well as toxicity evaluation and in vivo tests, seeking the development of a possible low‐cost mouthwash formulation accessible to the most vulnerable population.
This study aimed to analyze the knowledge of dental surgeons concerning the pharmacological effects of bisphosphonates (BP) and their impact on the health of patients undergoing oral surgery ...treatment.
A quantitative study was conducted with professionals in the Cariri region of Ceará, Brazil. The data were collected using a semi-structured questionnaire to interview the dental surgeons who met the inclusion criteria. The data were analyzed by Chi-square and Fischer's Exact tests using the SPSS program version 22.0.
The results indicated that most interviewed subjects have no experience with the dental treatment of individuals under treatment with bisphosphonates. When a sample of the medication was presented, a significant number of the participants (65.3%) did not recognize the drug. Among those who recognized it, 66.5% did not know how to treat bisphosphonate-using patients in the clinical routine. However, 95.1% of the professionals who recognized the need to discontinue these drugs admitted contacting the prescriber to establish the best dental conduct. Our results also showed that recently graduated professionals better understood the need to stop BP use before invasive treatment, although they did not know the protocol.
In conclusion, a better knowledge of the pharmacological effects of BP is crucial for conducting adequate anamnesis, requesting additional tests, and performing medical monitoring, which has a significant impact on the clinical practice of dental surgeons.
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•Aromatic sulfones: chemicals used in agrochemical and pharmaceutical industries.•A QSAR study about their environmental toxicity was carried out.•It also assessed the relationship ...between this endpoint and the water solubility.•The models, including by PLS2, indicate some relation between the endpoints.•However, the results indicate that the toxicity is due to enzyme inhibition.
Aromatic sulfones comprise a class of chemicals used in agrochemical and pharmaceutical industries and as floatation and extractant agents in petrochemical and metallurgy industries. In this study, new QSA(P)R studies were carried out to predict the toxicity against Vibrio fischeri of a set of 52 aromatic sulfones. The same approach was used to evaluate the relationship between these endpoint and the water solubility, another important environmental endpoint. The study resulted in models of good statistical quality and mechanistic interpretation with a possible correlation between the two endpoints, but the toxic effect is also likely to depend on other physicochemical properties. The use of the PLS2, a method not commonly used in QSA(P)R studies, also produced models of greater reliability, and the relationship between the two endpoints was reinforced to some degree. These results are useful for better understanding the process by which these compounds exert their environmental toxicity, thus aiding in the development of industrially useful compounds with less potential environmental damage.
Apesar de extensamente abordados na Crónica de 1344, os feitos de Fernando Magno são descritos pontualmente no Livro de Linhagens do Conde D. Pedro, enumerando-se as suas conquistas beirãs de uma ...forma desordenada no segmento final de uma síntese biográfica dedicada a Rodrigo Dias de Vivar e retomando-se esta linha de eventos somente num título dedicado aos Trava-Trastâmara, onde, a exemplo da relação entre o Cid e Sancho II, Rodrigo Froilaz de Trastâmara é apresentado como arauto da fidelidade aristocrática portuguesa a Garcia II, encarnando a oposição vivida entre Portugal e Castela no século XIV.Com efeito, o nobiliário não revela a mesma ligação da Crónica de 1344 à tradição emanada das Mocedades de Rodrigo por via da célebre Crónica de Castela, que, para além de colocar Rodrigo Dias no centro das conquistas beirãs, o transforma no principal agente de poder deste monarca. Por isso, justifica-se uma revisitação da tradição textual contruída em torno destas campanhas, uma refiliação da discursividade de D. Pedro no universo cidiano e uma análise da intervenção dos Pereira nesta matéria específica do nobiliário, visando a construção da personagem de Rodrigo Froilaz.
Abstract Objective To evaluate the efficacy and outcomes of the surgical treatment for pelvic organ prolapse (POP) in stages III and IV by sacrospinous ligament fixation (SSLF) or uterosacral ...ligament suspension (USLS) by comparing anatomical and subjective cure rates and quality-of-life parameters (through the version validated for the Portuguese language of the Prolapse Quality of Life P-QoL questionnaire) under two definitions: genital prolapse Ba, Bp, and C < −1 (stage I) and Ba, Bp, and C ≤ 0 (stage II). Materials and Methods After we obtained approval from the Ethics Committee (under CAAE 0833/06) and registered the study in ClinicalTrials.gov (NCT 01347021), 51 patients were randomized into two groups: the USLS group (N = 26) and the SSLF group (N = 25), with follow-up 6 and 12 months after the procedures. Results There was a significant improvement in the P-QoL score and anatomical measurements of all compartments in both groups after 12 months (p < 0.001). The anatomical cure rates in the USLS and SSLF groups, considering stage 1, were of 34.6% and 40% (anterior) respectively; of 100% both for groups (apical); and of 73.1% and 92% (posterior) respectively. The rates of adverse outcomes were of 42% (N = 11) and 36% (N = 11) for the USLS and SSLF groups respectively (p = 0.654), and those outcomes were excessive bleeding, bladder perforation (intraoperative) or gluteal pain, and urinary infection (postoperative), among others, without differences between the groups. Conclusion High cure rates in all compartments were observed according to the anatomical criterion (stage I), without differences in P-QoL scores and complications either with USLS or SSLF for the surgical treatment of accentuated POP.
Resumo O linfedema é uma doença crônica e progressiva caracterizada pelo acúmulo de fluidos, provocando edema tecidual em decorrência de um sistema linfático comprometido. A ultrassonografia ...diagnóstica (USD) é um método capaz de avaliar as características dos tecidos moles, podendo ser utilizada de maneira confiável para o diagnóstico do linfedema, além de mensurar a complacência tecidual em um cenário clínico. Esta é uma revisão sistemática, objetivando avaliar artigos que fizessem o uso da USD na abordagem do linfedema secundário ao câncer de mama. Foram selecionados 565 artigos, que foram exportados para o programa de revisão Rayyan QCRI e, em seguida, triados por dois pesquisadores. Dessa busca, foram obtidos 25 artigos selecionados após consenso entre os autores e que foram catalogados quanto aos seus resultados principais. A USD foi identificada como um método vantajoso por ser seguro, pouco invasivo, de baixo custo, sem uso de radiação, além de ser útil para avaliar a eficácia de terapias no tratamento do linfedema.
Abstract Lymphedema is a chronic and progressive disease characterized by fluid accumulation, causing tissue edema as a result of a compromised lymphatic system. Diagnostic ultrasound (DUS) is a method capable of assessing soft tissue characteristics that can be used reliably to diagnose lymphedema as well as for measuring tissue compliance in a clinical setting. This is a systematic review, aiming to evaluate articles that made use of DUS in management of lymphedema secondary to breast cancer. A total of 570 articles were selected, exported to the Rayyan QCRI review program, and then screened by two researchers. From this search, 25 articles were selected after the authors reached consensus and were catalogued as to their main results. Diagnostic ultrasound was identified as an advantageous method that is safe, minimally invasive, low cost, and radiation free and is useful for evaluating the efficacy of therapies used in lymphedema treatment.
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