Practical computational toolkits for dendrimers and dendrons structure design

Dendrimers and dendrons offer an excellent platform for developing novel drug delivery systems and medicines. The rational design and further development of these repetitively branched systems are restricted by difficulties in scalable synthesis and structural determination, which can be overcome by judicious use of molecular modelling and molecular simulations. A major difficulty to utilise in silico studies to design dendrimers lies in the laborious generation of their structures. Current modelling tools utilise automated assembly of simpler dendrimers or the inefficient manual assembly of monomer precursors to generate more complicated dendrimer structures. Herein we describe two novel graphical user interface (GUI) toolkits written in Python that provide an improved degree of automation for rapid assembly of dendrimers and generation of their 2D and 3D structures. Our first toolkit uses the RDkit library, SMILES nomenclature of monomers and SMARTS reaction nomenclature to generate SMILES and mol files of dendrimers without 3D coordinates. These files are used for simple graphical representations and storing their structures in databases. The second toolkit assembles complex topology dendrimers from monomers to construct 3D dendrimer structures to be used as starting points for simulation using existing and widely available software and force fields. Both tools were validated for ease-of-use to prototype dendrimer structure and the second toolkit was especially relevant for dendrimers of high complexity and size.Peer reviewe

CO2-based heavy oil recovery processes for post-CHOPS reservoirs

Authors would like to thank the financial support of the Petroleum Technology Research Centre Saskatchewan (PTRC) for this project, and Computer Modeling Group Ltd. for the use of their thermal reservoir simulation software CMG STARSTM. We would also like to thank Jacky Wang for his help and comments on the modeling part of this study.Peer reviewedPostprin

Continuum Modeling and Simulation in Bone Tissue Engineering

Bone tissue engineering is currently a mature methodology from a research perspective. Moreover, modeling and simulation of involved processes and phenomena in BTE have been proved in a number of papers to be an excellent assessment tool in the stages of design and proof of concept through in-vivo or in-vitro experimentation. In this paper, a review of the most relevant contributions in modeling and simulation, in silico, in BTE applications is conducted. The most popular in silico simulations in BTE are classified into: (i) Mechanics modeling and sca old design, (ii) transport and flow modeling, and (iii) modeling of physical phenomena. The paper is restricted to the review of the numerical implementation and simulation of continuum theories applied to di erent processes in BTE, such that molecular dynamics or discrete approaches are out of the scope of the paper. Two main conclusions are drawn at the end of the paper: First, the great potential and advantages that in silico simulation o ers in BTE, and second, the need for interdisciplinary collaboration to further validate numerical models developed in BTE.Ministerio de Economía y Competitividad del Gobierno España DPI2017-82501-

Analysis of planar compliant mechanisms based on non-linear analytical modeling including shear and lateral contraction

Compliant mechanisms are commonly used in precision engineering while analyzing their deflection is particularly challenging. Often, FEM simulations are chosen in an iterative process. Analytical approaches that consider pure bending, shear or other effects are usually limited to the mechanism as a system. However, certain configurations comprise compliant elements with different aspect ratios. The aim of this paper is to integrate the theories of shear and lateral contraction into a unified form with the existing theory of bending for large deflections and make them applicable individually for specific sections of continuous compliant mechanisms. Recommendations are made as to when which theory should be used. Building on that, a comprehensive tool for analyzing compliant mechanisms developed in Python is introduced. The tool offers the possibility to create arbitrary compliant mechanisms including branched links and various boundary conditions. A tool for parametric studies allows to optimize the given geometry for realizing a specific motion task. Further, FEM and measurement results correlate well with the application results. The presented user interface can be beneficial for the accelerated analysis and synthesis of compliant mechanisms

Speech Communication

Contains research objectives and summary of research on three research projects and reports on three research projects.National Institutes of Health (Grant 5 RO1 NS04332-12)U. S. Navy Office of Naval Research (Contract ONR N00014-67-A-0204-0069)Joint Services Electronics Program (Contract DAAB07-74-C-0630)National Institutes of Health (Grant 2 RO1 NS04332-11

Design and synthesis of novel ligands for Serotonin (5-HT6) receptor and inhibitors of ABCB1 Efflux pump

Selenium and Biology have a unique relationship. Selenium is an element which exists in several amino acids, including selenocysteine and selenomethionine. It plays several vital roles in the human body and is essential for several physiological processes. The last few years have witnessed the development of a new generation of biologically active and pharmaceutically relevant organo-selenium compounds, ranging from effective anticancer agents to novel ligands for serotonin 5-HT6 receptors and ABCB1 efflux pump modulators. This study describes the role of phenylselenoether-hydantoin hybrids as ABCB1 efflux pump modulating agents. Moreover, this work aims to synthesize novel and highly (re)active agents employing triazine-methyl piperazine hybrids for therapeutic applications in the treatment of current civilization central nervous system disorder. In summary, a library of 50 active novel compounds has been prepared to serve as efflux pump modulators or 5-HT6 ligands. Melting point, mass spectroscopy (MS), and nuclear magnetic resonance spectroscopy (NMR) evaluation have been employed to establish and confirm the structure of the compounds. The biological assays have been performed to evaluate their affinity towards 5HT6 receptor or efflux pump modulating ability. Finally, structure-activity relationship analysis has been performed to review and suggest modifications for the pharmacophore features.Selen ist ein Element, das in mehreren Aminosäuren, einschließlich Selenocystein und Selenomethionin, vorkommt. Es spielt verschiedene lebenswichtige Rollen im menschlichen Körper und ist für zahlreiche physiologische Prozesse unerlässlich. In den letzten Jahren wurde eine neue Generation biologisch aktiver und pharmazeutisch relevanter Organo-Selen-Verbindungen entwickelt, die von wirksamen Krebsbekämpfungsmitteln bis hin zu neuartigen Liganden für Serotonin-5-HT6-Rezeptoren und ABCB1-Effluxpumpenmodulatoren reichen. Diese Studie beschreibt die Rolle von Phenylselenoether-Hydantoin-Hybriden als ABCB1- Effluxpumpenmodulatoren sowie die Synthese von neuartigen und hoch (re)aktiven Wirkstoffen unter Verwendung von Triazin-Methylpiperazin-Hybriden für therapeutische Anwendungen bei der Behandlung von Störungen des Zentralnervensystems der modernen Gesellschaft Zivilisation. Zusammenfassend lässt sich sagen, dass eine Bibliothek von 50 aktiven neuartigen Verbindungen vorbereitet wurde, die als Effluxpumpenmodulatoren oder 5-HT6-Liganden dienen sollen. Die Verbindungen wurden durch Schmelzpunkt-, Massenspektroskopie- (MS) und Kernresonanzspektroskopie- (NMR) charakterisiert. Biologische Assays wurden durchgeführt, um die Fähigkeit der synthetisierten Verbindungen zur Modulierung des 5HT6-Rezeptors oder der Effluxpumpe zu bestimmen. Schließlich wurde eine Struktur-Aktivitäts Beziehungsanalyse durchgeführt, um die pharmakophoren Eigenschaften zu überprüfen und Änderungen vorzuschlagen

Interactive DNA Sequence and Structure Design for DNA Nanotechnology and DNA Computation

DNA sequence and structure design are very important for DNA nanotechnology and DNA computation. A computer aided design tool is needed for exploring DNA sequence and structure of interests before experimental synthesis, which is a very time and labor consuming process. In this paper, an interactive DNA sequence and structure design software tool called DNA shop is proposed and implemented

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 336)

This bibliography lists 111 reports, articles and other documents introduced into the NASA Scientific and Technical Information System during April 1990. Subject coverage includes: aerospace medicine and psychology, life support systems and controlled environments, safety equipment, exobiology and extraterrestrial life, and flight crew behavior and performance

The Emergence of Canalization and Evolvability in an Open-Ended, Interactive Evolutionary System

Natural evolution has produced a tremendous diversity of functional organisms. Many believe an essential component of this process was the evolution of evolvability, whereby evolution speeds up its ability to innovate by generating a more adaptive pool of offspring. One hypothesized mechanism for evolvability is developmental canalization, wherein certain dimensions of variation become more likely to be traversed and others are prevented from being explored (e.g. offspring tend to have similarly sized legs, and mutations affect the length of both legs, not each leg individually). While ubiquitous in nature, canalization almost never evolves in computational simulations of evolution. Not only does that deprive us of in silico models in which to study the evolution of evolvability, but it also raises the question of which conditions give rise to this form of evolvability. Answering this question would shed light on why such evolvability emerged naturally and could accelerate engineering efforts to harness evolution to solve important engineering challenges. In this paper we reveal a unique system in which canalization did emerge in computational evolution. We document that genomes entrench certain dimensions of variation that were frequently explored during their evolutionary history. The genetic representation of these organisms also evolved to be highly modular and hierarchical, and we show that these organizational properties correlate with increased fitness. Interestingly, the type of computational evolutionary experiment that produced this evolvability was very different from traditional digital evolution in that there was no objective, suggesting that open-ended, divergent evolutionary processes may be necessary for the evolution of evolvability.Comment: SI can be found at: http://www.evolvingai.org/files/SI_0.zi