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1.
Adv Exp Med Biol ; 1232: 299-306, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31893424

RESUMO

Hypoxic ischemic encephalopathy (HIE) is a significant cause of death and neurological disability in newborns. Therapeutic hypothermia at 33.5 °C is one of the most common treatments in HIE and generally improves outcome; however 45-55% of injuries still result in death or severe neurodevelopmental disability. We have developed a systems biology model of cerebral oxygen transport and metabolism to model the impact of hypothermia on the piglet brain (the neonatal preclinical animal model) tissue physiology. This computational model is an extension of the BrainSignals model of the adult brain. The model predicts that during hypothermia there is a 5.1% decrease in cerebral metabolism, 1.1% decrease in blood flow and 2.3% increase in cerebral tissue oxygenation saturation. The model can be used to simulate effects of hypothermia on the brain and to help interpret bedside recordings.


Assuntos
Circulação Cerebrovascular , Cérebro , Hipotermia , Modelos Biológicos , Animais , Animais Recém-Nascidos , Circulação Cerebrovascular/fisiologia , Cérebro/metabolismo , Simulação por Computador , Humanos , Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Suínos
2.
Adv Exp Med Biol ; 1232: 307-313, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31893425

RESUMO

Near infrared optical tomography (NIROT) is a non-invasive imaging technique to provide physiological information e.g. the oxygenation of tissue. For image reconstruction in clinical and preclinical scenarios, models to accurately describe light propagation are needed. This work aims to assess the accuracy and efficiency of different models, which paves the way for an optimal design of model-based image reconstruction algorithms in NIROT for realistic tissue geometries and heterogeneities. Two popular simulators were evaluated: the Monte Carlo (MC) method based MCX and the finite element method (FEM) based Toast++. We compared simulated results with experimental data measured on a homogeneous silicone phantom with well-calibrated parameters. The laser light was focused on the center of the phantom surface and images were captured by a CCD camera in both reflection and transmission modes. For transmittance measurements, the two models showed good agreement. Both achieve a cosine similarity of ~99%. In contrast, for reflectance measurements, FEM results deviated more from the measured values than MC, yielding similarity values of 86% and 94%, respectively. This study recommends the use of MC for NIROT in reflection mode and both MC and FEM yield excellent results for transmission mode.


Assuntos
Análise de Elementos Finitos , Modelos Teóricos , Método de Monte Carlo , Tomografia Óptica , Algoritmos , Simulação por Computador , Análise de Elementos Finitos/normas , Luz , Imagens de Fantasmas
3.
Phys Chem Chem Phys ; 22(3): 1611-1623, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31894790

RESUMO

Electronic circular dichroism is one of the most used spectroscopic techniques for peptide and protein structural characterization. However, while valuable experimental spectra exist for α-helix, ß-sheet and random coil secondary structures, previous studies showed important discrepancies for ß-turns, limiting their use as a reference for structural studies. In this paper, we simulated circular dichroism spectra for the best-characterized ß-turns in peptides, namely types I, II, I' and II'. In particular, by combining classical molecular dynamics simulations and state-of-the-art quantum time-dependent density functional theory (with the polarizable embedding multiscale model) computations, two common electronic circular dichroism patterns were found for couples of ß-turn types (namely, type I/type II' and type II/type I'), at first for a minimal di-peptide model (Ace-Ala-Ala-NHMe), but also for all sequences tested with non-aromatic residues in the central positions. On the other hand, as expected, aromatic substitution causes important perturbations to the previously found ECD patterns. Finally, by applying suitable approximations, these patterns were subsequently rationalized based on the exciton chirality rule. All these results provide useful predictions and pave the way for a possible experimental characterization of ß-turns based on circular dichroism spectroscopy.


Assuntos
Dicroísmo Circular , Simulação de Dinâmica Molecular , Simulação por Computador , Conformação Proteica em Folha beta , Estrutura Terciária de Proteína
4.
J Agric Food Chem ; 68(2): 523-529, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31908169

RESUMO

The present work sought to contribute to the development of new nematicides. Benzaldehydes were initially converted to nitrile oxides that underwent 1,3-dipolar cycloaddition reactions with methyl acrylate to generate 4,5-dihydroisoxazoles. In in vitro tests, methyl 3-phenyl-4,5-dihydroisoxazole-5-carboxylate (1) and methyl 3-(4-chlorophenyl)-4,5-dihydroisoxazole-5-carboxylate (4) increased the mortality of Meloidogyne exigua and Meloidogyne incognita second-stage juveniles (J2). Compounds 1 and 4 presented necessary concentrations of 398 and 501 µg mL-1, respectively, to kill 50% of M. incognita J2 (LC50 values), while the value for carbofuran (positive control) was 168 µg mL-1. In in vivo tests, compounds 1 and 4 reduced the number of M. incognita galls in tomato roots by 70 and 40%, respectively, and the number of eggs by 89 and 44%. Using an in silico approach, we showed that compounds 1 and 4 were toxic to the nematodes by binding to the allosteric binding sites of the agonist-binding domains of the nematode nicotinic acetylcholine receptors. These results opened up possibilities for further investigations aimed at developing novel commercial nematicides.


Assuntos
Antinematódeos/toxicidade , Isoxazóis/toxicidade , Doenças das Plantas/parasitologia , Tylenchoidea/efeitos dos fármacos , Animais , Antinematódeos/química , Simulação por Computador , Proteínas de Helminto/química , Proteínas de Helminto/metabolismo , Isoxazóis/química , Lycopersicon esculentum/parasitologia , Raízes de Plantas/parasitologia , Receptores Nicotínicos/química , Receptores Nicotínicos/metabolismo , Tylenchoidea/crescimento & desenvolvimento , Tylenchoidea/metabolismo
5.
Food Microbiol ; 85: 103285, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31500704

RESUMO

The objective of this study was to determine the kinetic parameters and apply Markov Chain Monte Carlo (MCMC) simulation to predict the growth of Clostridium perfringens from spores in cooked ground chicken meat during dynamic cooling. Inoculated samples were exposed to various cooling conditions to observe dynamic growth. A combination of 4 cooling profiles was used in one-step inverse analysis with the Baranyi model as the primary model and the cardinal parameters model as the secondary model. Six kinetic parameters of the Baranyi model and the cardinal parameters model, including Q0, Ymax, µopt, Tmin, Topt, and Tmax, were estimated. The estimated Tmin, Topt, and Tmax were 14.8, 42.9, and 50.5 °C, respectively, with a µopt of 5.25 h-1 and maximum cell density of 8.4 log CFU/g. Correlation analysis showed that both Q0 and Ymax are weakly correlated to other parameters, while the remaining parameters are mostly mildly to strongly correlated with each other. Although it may be difficult to estimate highly correlated parameters using a single temperature profile, one-step analysis with multiple different temperature profiles helped estimate them successfully. The estimated parameters were used as the prior information to construct the posterior distribution for Bayesian analysis. MCMC simulation was used to predict the bacterial growth using different dynamic temperature profiles for validation of the accuracy of the predictive models. The MCMC simulation results showed that the Bayesian analysis produced more accurate predictions of bacterial growth during cooling than the deterministic method. With Bayesian analysis, the root-mean-square-error (RMSE) of prediction was only 0.1 log CFU/g with all residual errors within ±0.25 log CFU/g. Therefore, Bayesian analysis is recommended for predicting the growth of C. perfringens in cooked meat during cooling.


Assuntos
Clostridium perfringens/crescimento & desenvolvimento , Culinária , Manipulação de Alimentos , Produtos da Carne/microbiologia , Temperatura Ambiente , Animais , Teorema de Bayes , Galinhas , Contagem de Colônia Microbiana , Simulação por Computador , Cinética , Cadeias de Markov , Modelos Biológicos , Método de Monte Carlo , Esporos Bacterianos/crescimento & desenvolvimento
6.
Syst Biol ; 69(1): 194-207, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31086978

RESUMO

Despite the ubiquitous use of statistical models for phylogenomic and population genomic inferences, this model-based rigor is rarely applied to post hoc comparison of trees. In a recent study, Garba et al. derived new methods for measuring the distance between two gene trees computed as the difference in their site pattern probability distributions. Unlike traditional metrics that compare trees solely in terms of geometry, these measures consider gene trees and associated parameters as probabilistic models that can be compared using standard information theoretic approaches. Consequently, probabilistic measures of phylogenetic tree distance can be far more informative than simply comparisons of topology and/or branch lengths alone. However, in their current form, these distance measures are not suitable for the comparison of species tree models in the presence of gene tree heterogeneity. Here, we demonstrate an approach for how the theory of Garba et al. (2018), which is based on gene tree distances, can be extended naturally to the comparison of species tree models. Multispecies coalescent (MSC) models parameterize the discrete probability distribution of gene trees conditioned upon a species tree with a particular topology and set of divergence times (in coalescent units), and thus provide a framework for measuring distances between species tree models in terms of their corresponding gene tree topology probabilities. We describe the computation of probabilistic species tree distances in the context of standard MSC models, which assume complete genetic isolation postspeciation, as well as recent theoretical extensions to the MSC in the form of network-based MSC models that relax this assumption and permit hybridization among taxa. We demonstrate these metrics using simulations and empirical species tree estimates and discuss both the benefits and limitations of these approaches. We make our species tree distance approach available as an R package called pSTDistanceR, for open use by the community.


Assuntos
Classificação/métodos , Modelos Biológicos , Filogenia , Simulação por Computador , Software
7.
Syst Biol ; 69(1): 76-90, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31125064

RESUMO

A statistical framework to infer areas of endemism from geographic distributions is proposed. This novel method is based on hidden Markov random fields (HMRFs), a type of undirected graph model commonly used in computer vision. This framework assumes areas of endemism are the states of the hidden layer of the model, whereas taxon distributions are emitted values in the observed layer. Taxon distributions are associated to the observed layer through a clustering procedure based on the extent of overlap. Observations are emitted by the hidden layer according to a Gaussian distribution, whereas the joint distribution of the hidden layer follows a Potts model. State and parameter inference of the maximum a posteriori configuration is performed through a modified version of the expectation-maximization algorithm. The optimal number of areas of endemism in the data set is estimated through the pseudolikelihood information criterion, a model selection procedure that uses an approximation to likelihood. The performance of the new algorithm was assessed on simulated data, and compared with the most popular methods for delimitation of areas of endemism: biotic element analysis, parsimony analysis of endemism, and endemicity analysis. HMRFs efficiently recovered the true pattern across a wide range of uncertainty values. The performance was also examined on empirical data: South African weevils (Sciobius) and Central American ground beetles and funnel-web tarantulas (Carabidae and Dipluridae, respectively). HMRFs uncovered six areas of endemism from the weevil data set, whereas eight were estimated for the Central American arthropods (compared with 3-5 and 3-14 from the other methods, respectively).


Assuntos
Distribuição Animal , Modelos Estatísticos , Algoritmos , Animais , Simulação por Computador , Cadeias de Markov
8.
Chemosphere ; 240: 124789, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31561157

RESUMO

Poly- and perfluorinated compounds (PFCs) may induce potential endocrine-disrupting hormonal effects. However, the molecular mechanism of the toxicology of PFCs remains unclear, and the insufficient information is available on the biological activities of PFCs at present. In this study, the cell-based reporter gene assays were used to determine the agonistic activity of PFCs on the human pregnane X receptor (hPXR). The heuristic method combined with best subset modeling (HM-BSM) based on Dragon descriptors and comparative similarity indices analysis (CoMSIA) were employed to build classical quantitative structure-activity relationship (QSAR) and three-dimensional QSAR models, respectively. The applicability domain (AD) of the classical QSAR model was assessed. Both the HM-BSM and CoMSIA approaches demonstrated good robustness, predictive ability, and mechanistic interpretability. The r2 and leave-one-out cross-validation squared correlated coefficient (q2LOO) values were 0.872 and 0.759 for the HM-BSM, and 0.976 and 0.751 for the CoMSIA model, respectively. The hPXR agonistic activity of the PFCs predicted by the built HM-BSM and CoMSIA agreed well with experimental activity, with root mean square error (RMSE) values of 0.0803 and 0.117, respectively, and external validation squared correlated coefficients (q2EXT) of 0.972 and 0.932, respectively. The hPXR agonistic activity of PFCs was related to their molecular polarizability, charge and atomic mass. Hydrogen bonding and hydrophobic interactions constituted the primary intermolecular forces between PFCs and the hPXR. The developed models were used to screen the PFCs with high hPXR agonistic activity.


Assuntos
Fluorcarbonetos/química , Receptor de Pregnano X/química , Simulação por Computador , Heurística , Humanos , Ligações de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Relação Quantitativa Estrutura-Atividade
9.
Phys Chem Chem Phys ; 22(3): 971-975, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31854402

RESUMO

An environment far from equilibrium is thought to be a necessary condition for the origin and persistence of life. In this context we report open-flow simulations of a non-enzymic proto-metabolic system, in which hydrogen peroxide acts both as oxidant and driver of thermochemical cycling. We find that a Gaussian perturbed input produces a non-Boltzmann output fluctuation distribution around the mean oscillation maximum. Our main result is that net biosynthesis can occur under fluctuating cyclical but not steady drive. Consequently we may revise the necessary condition to "dynamically far from equilibrium".


Assuntos
Fenômenos Bioquímicos/fisiologia , Origem da Vida , Termodinâmica , Simulação por Computador , Modelos Químicos
10.
Phys Chem Chem Phys ; 22(3): 1392-1399, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31859314

RESUMO

Detailed knowledge of intramolecular hydrogen bonds, including their nanomechanics, in a peptide secondary structure is crucial for understanding mechanisms of numerous biochemical processes. Single-molecule force spectroscopy has become a powerful tool to study directly the mechanical properties of single biopolymers and monitoring the hydrogen bonds. However, the interpretation of such experiments, due to their poor temporal resolution relative to the rate of intramolecular dynamics, requires the support of molecular simulations. In this work, we provide a methodology for determining the kinetic and energetic characteristics of hydrogen bonds in a template model of the protein secondary structure. Our approach, based on the steered molecular dynamics method, employs dynamic force spectroscopy calculations and uses two advanced theoretical models of force-induced unbinding. A systematic analysis of the simulated data with these models allowed for quantitative characterization of a single hydrogen bond in the α-helix of the AAKA(AEAAKA)5AC peptide model and detailed explanation of the mechanism of the α-helix unfolding. The methodology proposed here may be extended to other molecular structures stabilized by internal hydrogen bonds.


Assuntos
Química/métodos , Ligações de Hidrogênio , Modelos Químicos , Peptídeos/química , Simulação por Computador , Estrutura Secundária de Proteína , Análise Espectral
11.
Phys Chem Chem Phys ; 22(3): 1511-1524, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31872826

RESUMO

The transcriptional regulator TtgR belongs to the TetR family of transcriptional repressors. It depresses the transcription of the TtgABC operon and itself and thus regulates the extrusion of noxious chemicals with efflux pumps in bacterial cells. As the ligand-binding domain of TtgR is rather flexible, it can bind with a number of structurally diverse ligands, such as antibiotics, flavonoids and aromatic solvents. In the current work, we perform equilibrium and nonequilibrium alchemical free energy simulation to predict the binding affinities of a series of ligands targeting the TtgR protein and an agreement between the theoretical prediction and the experimental result is observed. End-point methods MM/PBSA and MM/GBSA are also employed for comparison. We further study the interaction maps and contacts between the protein and the ligand and identify important interactions in the protein-ligand binding cases. The dynamics fluctuation and secondary structures are also investigated. The current work sheds light on atomic and thermodynamic understanding of the TtgR-ligand interactions.


Assuntos
Modelos Teóricos , Proteínas Repressoras/metabolismo , Termodinâmica , Simulação por Computador , Ligantes , Ligação Proteica
12.
J Colloid Interface Sci ; 559: 76-87, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610307

RESUMO

Exploring and controlling chemical reactions in compartments opens new platforms for designing bioinspired catalysts and energy-autonomous systems. Aqueous polymer networks or hydrogels serve as a perfect model for biological tissues, allowing systematic investigations of chemical transformations in compartments. Herein, we report the synthesis of a versatile, colloidal microgel catalyst containing covalently bound l-proline as an organocatalyst. The key finding of our work is that the catalytic activity can be tuned by adjusting the distribution of the organocatalyst in the microgel network as well as the properties of the solvent. We demonstrate that l-proline groups integrated into microgels enable the reaction of 4-nitrobenzaldehyde and cyclohexanone in a heterogeneous reaction mixture in which free l-proline is not active. By controlling the localization of the l-proline groups within the microgel network (core or corona), the rate of the aldol reaction in homogenous and heterogeneous reaction mixtures can be modulated. Furthermore, microgels with covalently attached catalysts can be recycled and reused in sequential catalytic runs without deterioration of the catalyst performance in terms of activity and selectivity. The internal structure of the microgel in heterogeneous reaction mixtures was studied by computer simulations.


Assuntos
Materiais Biomiméticos/química , Coloides/química , Hidrogéis/química , Prolina/química , Aldeídos/química , Benzaldeídos/química , Catálise , Simulação por Computador , Reagentes para Ligações Cruzadas/química , Cicloexanonas/química , Cinética , Polimerização , Solventes/química , Água
13.
Chemosphere ; 238: 124604, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31450113

RESUMO

Accurate in silico predictions of chemical substance ecotoxicity has become an important issue in recent years. Most conventional methods, such as the Ecological Structure-Activity Relationship (ECOSAR) model, cluster chemical substances empirically based on structural information and then predict toxicity by employing a log P linear regression model. Due to empirical classification, the prediction accuracy does not improve even if new ecotoxicity test data are added. In addition, most of the conventional methods are not appropriate for predicting the ecotoxicity on inorganic and/or ionized compounds. Furthermore, a user faces difficulty in handling multiple Quantitative Structure-Activity Relationship (QSAR) formulas with one chemical substance. To overcome the flaws of the conventional methods, in this study a new method was developed that applied unsupervised machine learning and graph theory to predict acute ecotoxicity. The proposed machine learning technique is based on the large AIST-MeRAM ecotoxicity test dataset, a software program developed by the National Institute of Advanced Industry Science and Technology for Multi-purpose Ecological Risk Assessment and Management, and the Molecular ACCess System (MACCS) keys that vectorize a chemical structure to 166-bit binary information. The acute toxicity of fish, daphnids, and algae can be predicted with good accuracy, without requiring log P and linear regression models in existing methods. Results from the new method were cross-validated and compared with ECOSAR predictions and show that the new method provides better accuracy for a wider range of chemical substances, including inorganic and ionized compounds.


Assuntos
Ecotoxicologia/métodos , Aprendizado de Máquina , Poluentes Químicos da Água/toxicidade , Poluição Química da Água/análise , Animais , Simulação por Computador , Daphnia/efeitos dos fármacos , Peixes , Modelos Lineares , Modelos Teóricos , Relação Quantitativa Estrutura-Atividade , Medição de Risco/métodos , Software , Poluentes Químicos da Água/química
14.
Vasc Endovascular Surg ; 54(1): 5-11, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31506033

RESUMO

INTRODUCTION: High flow rates may develop in arteriovenous fistula (AVF), resulting in clinical syndromes of steal, aneurysmal fistula, or high-output cardiac failure. Various techniques with varying success have been advocated to treat this difficult problem. We present a hemodynamically validated novel banding technique. METHODS: We designed a computational fluid dynamic (CFD) model of the native high-flow AVF and tested various juxta-anastomotic venous diameters to determine the effect on AVF blood flow and pressure. We translated this principle in our banding technique, wherein adjustable banding was performed in conjunction with ultrasound-guided brachial artery flow measurement to determine the optimal band diameter. Polyurethane patch was used to fashion the adjustable band. Patient demographics, AVF flow parameters pre- and postintervention, operative intervention, and ultrasound follow-up data were collected prospectively. RESULTS: Our CFD testing demonstrated that the band diameter needed to achieve optimal distal blood pressure and preserve AVF flow depending on blood pressure, end capillary pressure, venous pressure, and vascular diameters. Five patients subsequently underwent dynamic banding of symptomatic high-flow AVF. Mean brachial artery blood flow rates pre- and postbanding were 2964 mL/min (confidence interval [CI]: 1487-4440 mL/min) and 1099 mL/min (CI: 571.7-1627 mL/min), respectively (P = .01). All patients had symptomatic improvement, and at a mean follow-up of 1 year, this benefit was sustained with no AVF thrombosis or loss. CONCLUSION: Adjustable dynamic band using ultrasound-guided brachial artery flow shows promising results in producing accurate AVF blood flow reduction with sustained efficacy in the short term for patients with symptomatic high-flow AVF.


Assuntos
Derivação Arteriovenosa Cirúrgica/efeitos adversos , Artéria Braquial/fisiopatologia , Hemodinâmica , Complicações Pós-Operatórias/cirurgia , Diálise Renal , Adolescente , Idoso , Idoso de 80 Anos ou mais , Velocidade do Fluxo Sanguíneo , Artéria Braquial/diagnóstico por imagem , Simulação por Computador , Humanos , Ligadura , Pessoa de Meia-Idade , Modelos Cardiovasculares , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/fisiopatologia , Estudos Prospectivos , Fluxo Sanguíneo Regional , Reoperação , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia de Intervenção
15.
Wiad Lek ; 72(11 cz 1): 2089-2093, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31860852

RESUMO

OBJECTIVE: Introduction: To date, there are techniques that allow dental surgeons to restore the lost volume of bone mass, but the level of complications during augmentation remains consistently high. One of the main types of postoperative complications is the exposure of bone augmentate and its infection as a result of ischemic or destructive processes in the mucous shreds, which cover the augmentate, resulting from their overgrowth. The aim: The purpose of our research was to increase bone augmentation effectiveness in patients with secondary edentulism and to reduce risk of postoperative complications caused by ischemia of the mucous membranes because of their tension by mathematical simulation of tensile limits and permissible deformation for the mucous membranes of the oral cavity. PATIENTS AND METHODS: Materials and methods: As a research method was selected a two-component Mooney-Rivlin model, taking into account the indicators of elasticity and static strength of flat samples in tension, which allows them to perform hyperprime behavior at small and moderate deformations. For computer simulation of epithelial flap deformation during operation by finite element method we used ANSYS software environment. RESULTS: Results: Since elastic forces are potential, the work of forces does not depend on the way of tension. Only the initial and final states of the sample, i.e. its initial and final forms, play a role. CONCLUSION: Conclusions: The flap of 30 × 25 mm can be stretched and thus it is necessary to eliminate the deficit of fabric up to 5 mm wide in the direction of the Y axis (vertical axis). The relative elongation is λ = 25/20 = 1.25. The flap tension first occurs in the y direction.


Assuntos
Modelos Teóricos , Retalhos Cirúrgicos , Simulação por Computador , Elasticidade , Humanos , Boca
16.
Phys Rev Lett ; 123(22): 228102, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31868410

RESUMO

Biological function requires cell-cell adhesions to tune their cohesiveness; for instance, during the opening of new fluid-filled cavities under hydraulic pressure. To understand the physical mechanisms supporting this adaptability, we develop a stochastic model for the hydraulic fracture of adhesive interfaces bridged by molecular bonds. We find that surface tension strongly enhances the stability of these interfaces by controlling flaw sensitivity, lifetime, and optimal architecture in terms of bond clustering. We also show that bond mobility embrittles adhesions and changes the mechanism of decohesion. Our study provides a mechanistic background to understand the biological regulation of cell-cell cohesion and fracture.


Assuntos
Adesão Celular/fisiologia , Junções Intercelulares/química , Junções Intercelulares/fisiologia , Modelos Biológicos , Membrana Celular/química , Membrana Celular/fisiologia , Simulação por Computador , Processos Estocásticos , Tensão Superficial
17.
Int. arch. otorhinolaryngol. (Impr.) ; 23(4): 451-454, Out.-Dez. 2019. ilus
Artigo em Inglês | LILACS | ID: biblio-1024494

RESUMO

Introduction: The anatomy of the temporal bone is complex due to the large number of structures and functions grouped in this small bone space, which do not exist in any other region in the human body. With the difficulty of obtaining anatomical parts and the increasing number of ear, nose and throat (ENT) doctors, there was a need to create alternatives as real as possible for training otologic surgeons. Objective: Developing a technique to produce temporal bone models that allow them to maintain the external and internal anatomical features faithful to the natural bone. Methods: For this study, we used a computed tomography (CT) scan of the temporal bones of a 30-year-old male patient, with no structural morphological changes or any other pathology detected in the examination, which was later sent to a 3D printer in order to produce a temporal bone biomodel. Results: After dissection, the lead author evaluated the plasticity of the part and its similarity in drilling a natural bone as grade "4" on a scale of 0 to 5, in which 5 is the closest to the natural bone and 0 the farthest from the natural bone. All structures proposed in the method were found with the proposed color. Conclusion: It is concluded that it is feasible to use biomodels in surgical training of specialist doctors. After dissection of the bone biomodel, it was possible to find the anatomical structures proposed, and to reproduce the surgical approaches most used in surgical practice and training implants (AU)


Assuntos
Humanos , Masculino , Adulto , Osso Temporal/cirurgia , Simulação por Computador , Impressão Tridimensional , Modelos Anatômicos , Procedimentos Cirúrgicos Otológicos/métodos , Osso Temporal/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Educação Médica , Treinamento por Simulação
18.
Beijing Da Xue Xue Bao Yi Xue Ban ; 51(6): 1130-1137, 2019 Dec 18.
Artigo em Chinês | MEDLINE | ID: mdl-31848517

RESUMO

OBJECTIVE: To explore the effects from the thread shapes of custom-made root-analogue implant (RAI) on distributions of von Mises stress around the peri-implant bone. METHODS: Five one-stage RAI three-dimensional finite element (FE) models with different thread shapes (V-shaped design, square design, buttress design, reverse buttress design and none thread design) and congruent bone were created through reverse engineering technology. The data of the five models were imported into the FE analysis software to calculate. A force of 100 N was applied parallelly and of 45° to the implant axis respectively. Analysis was performed to evaluate the von Mises stress distributions at the peri-implant regions with the help of the Ansys 16 software. RESULTS: The von Mises stresses distributed mostly at the implant cervical regions and the tip ends of the threads on the cortical bone under oblique loading, while on the cancellous bone, the stresses concentrated mostly on the implant lateral cervical regions, the tip ends of the threads and the apical regions. When under vertical loading, the von Mises stresses distributed mostly at the implant cervical regions on the cortical bone while at the tip ends of the threads and the lateral apical regions on the cancellous bone. The von Mises stresses were better distributed on the thread groups under both kinds of loadings compared with no thread design. But there was no obvious difference among the different thread groups. The concentrations of the von Mises stresses on the cancellous bone in the thread groups were mostly at the tip ends of the threads while less in the apical area. The von Mises stresses were better distributed on the cancellous bone on the other three thread designs than on square design. CONCLUSION: Thread designs are advocated for the reason that adding thread designs to the RAI standard design will have a positive effect on stress distributions at the peri-implant regions and it will reduce the concentrations of von Mises stresses on the cortical bone. From the standpoint of the stress distribution, V-shaped design, buttress design and reverse buttress design are more suitable for RAI than square design. There is no difference of the distributions of the von Mises stresses in the RAI between different thread designs.


Assuntos
Implantes Dentários , Planejamento de Prótese Dentária , Fenômenos Biomecânicos , Simulação por Computador , Análise do Estresse Dentário , Análise de Elementos Finitos , Software , Estresse Mecânico
20.
Biomed Khim ; 65(6): 468-476, 2019 Oct.
Artigo em Russo | MEDLINE | ID: mdl-31876517

RESUMO

We present a novel computational ligand-based virtual screening approach with scaffold hopping capabilities for the identification of novel inhibitors of ß-lactamases which confer bacterial resistance to ß-lactam antibiotics. The structures of known ß-lactamase inhibitors were used as query ligands, and a virtual in silico screening a database of 8 million drug-like compounds was performed in order to select the ligands with similar shape and charge distribution. A set of numerical descriptors was used such as chirality, eigen spectrum of matrices of interatomic distances and connectivity together with higher order moment invariants that showed their efficiency in the field of pattern recognition but have not yet been employed in drug discovery. The developed scaffold-hopping approach was applied for the discovery of analogues of four allosteric inhibitors of serine ß-lactamases. After a virtual in silico screening, the effect of two selected ligands on the activity of TEM type ß-lactamase was studied experimentally. New non-ß-lactam inhibitors were found that showed more effective inhibition of ß-lactamases compared to query ligands.


Assuntos
Antibacterianos/química , Descoberta de Drogas , Inibidores de beta-Lactamases/química , Simulação por Computador , Bases de Dados de Compostos Químicos , Modelos Químicos
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