BioCAD: an information fusion platform for bio-network inference and analysis

Background : As systems biology has begun to draw growing attention, bio-network inference and analysis have become more and more important. Though there have been many efforts for bio-network inference, they are still far from practical applications due to too many false inferences and lack of comprehensible interpretation in the biological viewpoints. In order for applying to real problems, they should provide effective inference, reliable validation, rational elucidation, and sufficient extensibility to incorporate various relevant information sources. Results : We have been developing an information fusion software platform called BioCAD. It is utilizing both of local and global optimization for bio-network inference, text mining techniques for network validation and annotation, and Web services-based workflow techniques. In addition, it includes an effective technique to elucidate network edges by integrating various information sources. This paper presents the architecture of BioCAD and essential modules for bio-network inference and analysis. Conclusion : BioCAD provides a convenient infrastructure for network inference and network analysis. It automates series of users' processes by providing data preprocessing tools for various formats of data. It also helps inferring more accurate and reliable bio-networks by providing network inference tools which utilize information from distinct sources. And it can be used to analyze and validate the inferred bio-networks using information fusion tools.ope

DeviceEditor visual biological CAD canvas

<p>Abstract</p> <p>Background</p> <p>Biological Computer Aided Design (bioCAD) assists the <it>de novo </it>design and selection of existing genetic components to achieve a desired biological activity, as part of an integrated design-build-test cycle. To meet the emerging needs of Synthetic Biology, bioCAD tools must address the increasing prevalence of combinatorial library design, design rule specification, and scar-less multi-part DNA assembly.</p> <p>Results</p> <p>We report the development and deployment of web-based bioCAD software, DeviceEditor, which provides a graphical design environment that mimics the intuitive visual whiteboard design process practiced in biological laboratories. The key innovations of DeviceEditor include visual combinatorial library design, direct integration with scar-less multi-part DNA assembly design automation, and a graphical user interface for the creation and modification of design specification rules. We demonstrate how biological designs are rendered on the DeviceEditor canvas, and we present effective visualizations of genetic component ordering and combinatorial variations within complex designs.</p> <p>Conclusions</p> <p>DeviceEditor liberates researchers from DNA base-pair manipulation, and enables users to create successful prototypes using standardized, functional, and visual abstractions. Open and documented software interfaces support further integration of DeviceEditor with other bioCAD tools and software platforms. DeviceEditor saves researcher time and institutional resources through correct-by-construction design, the automation of tedious tasks, design reuse, and the minimization of DNA assembly costs.</p

Comparison between two design methods implants, based on reverse engineering, design and engineering technologies, BIOCAD/CAD/CAE

Resumen El principal propósito del presente artículo de investigación, fue comparar dos métodos usados para el diseño y evaluación biomecánica de implantes dentales. El primer método se desarrolló basado en la integración de una técnica imagenológica usada en diagnóstico de imágenes tomográficas, para la reconstrucción de modelos 3D virtuales óseos con herramientas software de ingeniería inversa, articulada al diseño aplicado en ingeniería e ingeniería mecánica aplicada. En el segundo método, la probeta de mandíbula fue modelada en un software CAD (Computer Aided Design) que fue utilizado para el diseño del implante; posteriormente fue realizado la simulación biomecánica estática en un entorno CAE (Computer Aided Engineering), aplicando cargas incrementales de torque de inserción en la interfase hueso implante. Los análisis por simulación en ambos métodos fueron realizados basados en los mismos criterios de evaluación. Se corroboró por simulación los valores de torque de inserción apropiados para mantener una adecuada relación en la interfase hueso implante. Por otra parte los resultados obtenidos por la aplicación de cada método de diseño fueron analizados y comparados para conocer el efecto de la integración de las técnicas imagenológicas apropiadas desde el software Bio CAD y articulado con las tecnologías software CAD CAE. Abstract The main objective of this research work was to make a comparison between two methods used for design and biomechanical assessment of dental implants.. The first method is based on integration of an imaging technique used in diagnosis of tomographic images applied to 3D bone model reconstruction with reverse engineering software tools implemented on engineering applications. In the second method a specimen of jaw modeled in CAD (Computer Aided Design) software used to implant design was implemented, then a static simulation biomechanics was performed in a CAE (Computer Aided Engineering) environment, applying elementary insertion torque loads at the bone-implant interface. Simulations Analysis were performed for both methods, using the same evaluation criteria. Appropriate insertion torque values were confirmed with simulations as appropriate to maintain a proper relationship at the bone-implant interface. The results obtained using each method were analyzed and compared to determine the effect on appropriate integration of BioCAD imaging techniques and articulation with Technologies CAD and CAE

Standardized 3D bioprinting of soft tissue models with human primary cells

Cells grown in 3D are more physiologically relevant than cells cultured in 2D. To use 3D models in substance testing and regenerative medicine, reproducibility and standardization are important. Bioprinting offers not only automated standardizable processes but also the production of complex tissue-like structures in an additive manner. We developed an all-in-one bioprinting solution to produce soft tissue models. The holistic approach included (1) a bioprinter in a sterile environment, (2) a light-induced bioink polymerization unit, (3) a user-friendly software, (4) the capability to print in standard labware for high-throughput screening, (5) cell-compatible inkjet-based printheads, (6) a cell-compatible ready-to-use BioInk, and (7) standard operating procedures. In a proof-of-concept study, skin as a reference soft tissue model was printed. To produce dermal equivalents, primary human dermal fibroblasts were printed in alternating layers with BioInk and cultured for up to 7 weeks. During long-term cultures, the models were remodeled and fully populated with viable and spreaded fibroblasts. Primary human dermal keratinocytes were seeded on top of dermal equivalents, and epidermis-like structures were formed as verified with hematoxylin and eosin staining and immunostaining. However, a fully stratified epidermis was not achieved. Nevertheless, this is one of the first reports of an integrative bioprinting strategy for industrial routine application

Mathematical Modeling of a Bioluminescent E. Coli Based Biosensor

In this work we present a mathematical model for the bioreporter activity of&nbsp;an E. coli based bioluminescent bioreporter. This bioreporter is based on a genetically&nbsp;modified E. coli which harbors the recA promoter, a member of the bacterial SOS&nbsp;response, fused to the bacterial luminescence (lux) genes. This bioreporter responds&nbsp;to the presence of DNA damaging agents such as heavy metals, H2O2 and Nalidixic&nbsp;Acid (NA) that activate the SOS response. In our mathematical model we implemented&nbsp;basic physiological mechanisms such as: the penetration of the NA into the biosensor;&nbsp;gyrase enzyme inhibition by the NA; gyrase level regulation; creation of chromosomal&nbsp;DNA damage; DNA repair and release of ssDNA into the cytoplasm; SOS induction and&nbsp;chromosomal DNA repair; activation of lux genes by the fused recA promoter carried on&nbsp;a plasmidal DNA; transcription and translation of the luminescence responsible enzymes;&nbsp;luminescence cycle; energy molecules level regulation and the regulation of the O2&nbsp;consumption. The mathematical model was defined using a set of ordinary differential&nbsp;equations (ODE) and solved numerically. We simulated the system for different concentrations of NA in water for specific biosensors concentration, and under limited O2&nbsp;conditions. The simulated results were compared to experimental data and satisfactory&nbsp;matching was obtained. This manuscript presents a proof of concept showing that&nbsp;real biosensors can be modeled and simulated. This sets the ground to the next stage&nbsp;of implementing a comprehensive physiological model using experimentally extracted&nbsp;parameters. Following the completion of the next stage, it will be possible to construct&nbsp;a “Computer Aided Design” tool for the simulation of the genetically engineered&nbsp;biosensors. We define a term “bioCAD” for a Biological System Computer Aided Design.&nbsp;The specific bioCAD that is described here is aimed towards whole cell biosensors which&nbsp;are under investigation today for functional sensing. Usage of the bioCAD will improve&nbsp;the biosensors design process and boost their performance. It will also reduce Non&nbsp;Recurring Engineering (NRE) cost and time. Finally, using a parameterized solution&nbsp;will allow fair and quick evaluation of whole cell biosensors for various applications

Estudo comparativo sobre métodos de geração de modelos geométricos por análise de elementos finitos

The aim of this study was to assess the influence of different methods for generating geometric models on stress values and distributions of endodontically treated teeth using a three-dimensional finite element analysis (3D-FEA). An endodontically treated human maxillary canine restored with glass fiber post and ceramic-fused-to-metal crown was scanned by microcomputed tomography and three-dimensionally reconstructed. Based on the microcomputed tomography images, 2 geometric models were generated and divided into the following groups: Group GCAD - only the root dentine was reconstructed based on a microcomputed tomography image while the remaining structures were generated by GCAD software simulation, and Group GTC - the whole assembly was obtained from scanning and rehabilitated by microcomputed tomography. Loading of 180N at 45° of the tooth long axis was applied on the lingual surface of the incisal third and the models were supported by a periodontal ligament fixed into the 3 axes of the Cartesian system (x=y=z=0). von Mises stress (VMS) were calculated. Differences in stress value and distribution between the generation methods of the geometric models were found. The lowest ratio difference in GTC/GCAD was for resin cement and core. Thus, the method for generation of the geometric model in finite element analysis was found to influence the research results, suggesting difference between the methods proposed.O objetivo deste estudo foi avaliar a influência de diferentes métodos para a geração de modelos geométricos em valores de tensões e distrubuições de dentes tratados endodônticamente, utilizando-se uma análise tridimensional de elementos finitos (3D-FEA). Canino superior humano tratado endodonticamente, restaurado com pino de fibra de vidro e coroa metalocerâmica foi escaneado por meio de microtomografia computadorizada e reconstruído tridimensionalmente. Baseadas nas imagens de microtomografia computadorizada, foram gerados 2 modelos geométricos e divididos nos seguintes grupos: grupo GCAD-apenas a dentina radicular foi reconstruída baseada na imagem obtida por meio de microtomografia computadorizada, enquanto as estruturas remanescentes foram geradas por simulação de software de CAD, e grupo GTC-todo conjunto inteiro foi obtido do escaneamento e reabilitado pela microtomografia computadorizada. O carregamento de 180N em 45° do longo eixo do dente foi aplicado na superfície lingual do terço incisal e os modelos foram suportados por um ligamento periodontal fixado nos 3 eixos do sistema cartesiano (x = y = z = 0). Tensões equivalents de von Mises (VMS) foram calculados. Foram encontradas diferenças no valor de tensões e distribuição entre os métodos de geração dos modelos geométricos. A menor razão entre GTC/GCAD foi para o cimento de resinoso e núcleo. Assim, verificou-se que o método de geração do modelo geométrico na análise de elementos finitos influenciou os resultados da pesquisa, sugerindo melhores resultados para o método GCAD

Engineering News, Spring 2021

https://scholarcommons.scu.edu/eng_news/1046/thumbnail.jp

Mechanical Behavior of Different Restorative Materials and Onlay Preparation Designs in Endodontically Treated Molars

This study evaluated the effect of the combination of three different onlay preparation designs and two restorative materials on the stress distribution, using 3D-finite element analysis. Six models of first lower molars were created according to three preparation designs: non-retentive (nRET), traditional with occlusal isthmus reduction (IST), and traditional without occlusal isthmus reduction (wIST); and according to two restorative materials: lithium-disilicate (LD) and nanoceramic resin (NR). A 600 N axial load was applied at the central fossa. All solids were considered isotropic, homogeneous, and linearly elastic. A static linear analysis was performed, and the Maximum Principal Stress (MPS) criteria were used to evaluate the results and compare the stress in MPa on the restoration, cement layer, and tooth structure (enamel and dentin). A novel statistical approach was used for quantitative analysis of the finite element analysis results. On restoration and cement layer, nRET showed a more homogeneous stress distribution, while the highest stress peaks were calculated for LD onlays (restoration: 69-110; cement layer: 10.2-13.3). On the tooth structure, the material had more influence, with better results for LD (27-38). It can be concluded that nRET design showed the best mechanical behavior compared to IST and wIST, with LD being more advantageous for tooth structure and NR for the restoration and cement layer

Multi-Target Analysis and Design of Mitochondrial Metabolism.

Analyzing and optimizing biological models is often identified as a research priority in biomedical engineering. An important feature of a model should be the ability to find the best condition in which an organism has to be grown in order to reach specific optimal output values chosen by the researcher. In this work, we take into account a mitochondrial model analyzed with flux-balance analysis. The optimal design and assessment of these models is achieved through single- and/or multi-objective optimization techniques driven by epsilon-dominance and identifiability analysis. Our optimization algorithm searches for the values of the flux rates that optimize multiple cellular functions simultaneously. The optimization of the fluxes of the metabolic network includes not only input fluxes, but also internal fluxes. A faster convergence process with robust candidate solutions is permitted by a relaxed Pareto dominance, regulating the granularity of the approximation of the desired Pareto front. We find that the maximum ATP production is linked to a total consumption of NADH, and reaching the maximum amount of NADH leads to an increasing request of NADH from the external environment. Furthermore, the identifiability analysis characterizes the type and the stage of three monogenic diseases. Finally, we propose a new methodology to extend any constraint-based model using protein abundances.PL has received funding from (FP7-Health-F5-2012) under grant agreement no. 305280 (MIMOmics). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This is the final version of the article. It first appeared from PLoS via http://dx.doi.org/10.1371/journal.pone.013382