A bio-molecular inspired electronic architecture: bio-based device concepts for enhanced sensing (Invited Paper)

NASA Astrophysics Data System (ADS)

Woolard, Dwight L.; Luo, Ying; Gelmont, Boris L.; Globus, Tatiana; Jensen, James O.

2005-05-01

A biological(bio)-molecular inspired electronic architecture is presented that offers the potential for defining nanoscale sensor platforms with enhanced capabilities for sensing terahertz (THz) frequency bio-signatures. This architecture makes strategic use of integrated biological elements to enable communication and high-level function within densely-packed nanoelectronic systems. In particular, this architecture introduces a new paradigm for establishing hybrid Electro-THz-Optical (ETO) communication channels where the THz-frequency spectral characteristics that are uniquely associated with the embedded bio-molecules are utilized directly. Since the functionality of this architecture is built upon the spectral characteristics of bio-molecules, this immediately allows for defining new methods for enhanced sensing of THz bio-signatures. First, this integrated sensor concept greatly facilitates the collection of THz bio-signatures associated with embedded bio-molecules via interactions with the time-dependent signals propagating through the nanoelectronic circuit. Second, it leads to a new Multi-State Spectral Sensing (MS3) approach where bio-signature information can be collected from multiple metastable state conformations. This paper will also introduce a new class of prototype devices that utilize THz-sensitive bio-molecules to achieve molecular-level sensing and functionality. Here, new simulation results are presented for a class of bio-molecular components that exhibit the prescribed type of ETO characteristics required for realizing integrated sensor platforms. Most noteworthy, this research derives THz spectral bio-signatures for organic molecules that are amenable to photo-induced metastable-state conformations and establishes an initial scientific foundation and design blueprint for an enhanced THz bio-signature sensing capability.

Possible Circuit Architectures for Molecular Nanoelectronics

NASA Astrophysics Data System (ADS)

Likharev, Konstantin

2003-03-01

Chemically-directed self-assembly of molecular devices is apparently the only feasible way to continue the fast progress of microelectronics after its Moore-Laws-based development runs into the wall of physical and economic limitations [1]. The architectures of VLSI circuits using such devices should be substantially fault-tolerant and accommodate other their features including low transconductance. The most significant feature of all promising suggested architectures is the hybridization of three technologies: advanced CMOS, simple nanowire arrays, and molecular devices self-assembling on these wires. Molecular memory arrays may have a simple structure, and their simple prototypes have already been implemented experimentally [2]. In contrast, the logic circuit development is just starting. I will describe a family of neuromorphic networks based on so-called CrossNet arrays [3] that look promising for advanced information processing, starting from fast image recognition and beyond. This architecture may combine very high density (above 10^12 functions per cm^2) and relatively high speed (100-ns-scale latency of cell-to-cell communications) at acceptable power consumption. In future, these features may allow to put an artificial analog of the human cerebral cortex, capable of processing information and (hopefully) self-evolution at 4 to 5 orders of magnitude faster than its biological prototype, on a 20x20 cm^2 silicon wafer. [1] K. Likharev, "Electronics Below 20-nm", see http://rsfq1.physics.sunysb.edu/ likharev/nano/ForMorkoc.pdf. [2] See, e.g, http://nanotechweb.org/articles/news/1/9/8/1. [3] O. Turel and K. Likharev, Int. J. of Circuit Theory and Applications 31, No.1 (2003); see http://rsfq1.physics.sunysb.edu/ likharev/nano/Preprint070102.pdf.

The future of computing--new architectures and new technologies.

PubMed

Warren, P

2004-02-01

All modern computers are designed using the 'von Neumann' architecture and built using silicon transistor technology. Both architecture and technology have been remarkably successful. Yet there are a range of problems for which this conventional architecture is not particularly well adapted, and new architectures are being proposed to solve these problems, in particular based on insight from nature. Transistor technology has enjoyed 50 years of continuing progress. However, the laws of physics dictate that within a relatively short time period this progress will come to an end. New technologies, based on molecular and biological sciences as well as quantum physics, are vying to replace silicon, or at least coexist with it and extend its capability. The paper describes these novel architectures and technologies, places them in the context of the kinds of problems they might help to solve, and predicts their possible manner and time of adoption. Finally it describes some key questions and research problems associated with their use.

Novel Molecular Architectures Developed for Improved Solid Polymer Electrolytes for Lithium Polymer Batteries

NASA Technical Reports Server (NTRS)

Meador, Mary Ann B.; Kinder, James D.; Bennett, William R.

2002-01-01

Lithium-based polymer batteries for aerospace applications need the ability to operate in temperatures ranging from -70 to 70 C. Current state-of-the-art solid polymer electrolytes (based on amorphous polyethylene oxide, PEO) have acceptable ionic conductivities (10-4 to 10-3 S/cm) only above 60 C. Higher conductivity can be achieved in the current systems by adding solvent or plasticizers to the solid polymer to improve ion transport. However, this can compromise the dimensional and thermal stability of the electrolyte, as well as compatibility with electrode materials. One of NASA Glenn Research Center's objectives in the PERS program is to develop new electrolytes having unique molecular architectures and/or novel ion transport mechanisms, leading to good ionic conductivity at room temperature and below without solvents or plasticizers.

A DICOM-based 2nd generation Molecular Imaging Data Grid implementing the IHE XDS-i integration profile.

PubMed

Lee, Jasper; Zhang, Jianguo; Park, Ryan; Dagliyan, Grant; Liu, Brent; Huang, H K

2012-07-01

A Molecular Imaging Data Grid (MIDG) was developed to address current informatics challenges in archival, sharing, search, and distribution of preclinical imaging studies between animal imaging facilities and investigator sites. This manuscript presents a 2nd generation MIDG replacing the Globus Toolkit with a new system architecture that implements the IHE XDS-i integration profile. Implementation and evaluation were conducted using a 3-site interdisciplinary test-bed at the University of Southern California. The 2nd generation MIDG design architecture replaces the initial design's Globus Toolkit with dedicated web services and XML-based messaging for dedicated management and delivery of multi-modality DICOM imaging datasets. The Cross-enterprise Document Sharing for Imaging (XDS-i) integration profile from the field of enterprise radiology informatics was adopted into the MIDG design because streamlined image registration, management, and distribution dataflow are likewise needed in preclinical imaging informatics systems as in enterprise PACS application. Implementation of the MIDG is demonstrated at the University of Southern California Molecular Imaging Center (MIC) and two other sites with specified hardware, software, and network bandwidth. Evaluation of the MIDG involves data upload, download, and fault-tolerance testing scenarios using multi-modality animal imaging datasets collected at the USC Molecular Imaging Center. The upload, download, and fault-tolerance tests of the MIDG were performed multiple times using 12 collected animal study datasets. Upload and download times demonstrated reproducibility and improved real-world performance. Fault-tolerance tests showed that automated failover between Grid Node Servers has minimal impact on normal download times. Building upon the 1st generation concepts and experiences, the 2nd generation MIDG system improves accessibility of disparate animal-model molecular imaging datasets to users outside a molecular imaging facility's LAN using a new architecture, dataflow, and dedicated DICOM-based management web services. Productivity and efficiency of preclinical research for translational sciences investigators has been further streamlined for multi-center study data registration, management, and distribution.

Molecular graph convolutions: moving beyond fingerprints

PubMed Central

Kearnes, Steven; McCloskey, Kevin; Berndl, Marc; Pande, Vijay; Riley, Patrick

2016-01-01

Molecular “fingerprints” encoding structural information are the workhorse of cheminformatics and machine learning in drug discovery applications. However, fingerprint representations necessarily emphasize particular aspects of the molecular structure while ignoring others, rather than allowing the model to make data-driven decisions. We describe molecular graph convolutions, a machine learning architecture for learning from undirected graphs, specifically small molecules. Graph convolutions use a simple encoding of the molecular graph—atoms, bonds, distances, etc.—which allows the model to take greater advantage of information in the graph structure. Although graph convolutions do not outperform all fingerprint-based methods, they (along with other graph-based methods) represent a new paradigm in ligand-based virtual screening with exciting opportunities for future improvement. PMID:27558503

The origin of cellular life.

PubMed

Ingber, D E

2000-12-01

This essay presents a scenario of the origin of life that is based on analysis of biological architecture and mechanical design at the microstructural level. My thesis is that the same architectural and energetic constraints that shape cells today also guided the evolution of the first cells and that the molecular scaffolds that support solid-phase biochemistry in modern cells represent living microfossils of past life forms. This concept emerged from the discovery that cells mechanically stabilize themselves using tensegrity architecture and that these same building rules guide hierarchical self-assembly at all size scales (Sci. Amer 278:48-57;1998). When combined with other fundamental design principles (e.g., energy minimization, topological constraints, structural hierarchies, autocatalytic sets, solid-state biochemistry), tensegrity provides a physical basis to explain how atomic and molecular elements progressively self-assembled to create hierarchical structures with increasingly complex functions, including living cells that can self-reproduce.

The origin of cellular life

NASA Technical Reports Server (NTRS)

Ingber, D. E.

2000-01-01

This essay presents a scenario of the origin of life that is based on analysis of biological architecture and mechanical design at the microstructural level. My thesis is that the same architectural and energetic constraints that shape cells today also guided the evolution of the first cells and that the molecular scaffolds that support solid-phase biochemistry in modern cells represent living microfossils of past life forms. This concept emerged from the discovery that cells mechanically stabilize themselves using tensegrity architecture and that these same building rules guide hierarchical self-assembly at all size scales (Sci. Amer 278:48-57;1998). When combined with other fundamental design principles (e.g., energy minimization, topological constraints, structural hierarchies, autocatalytic sets, solid-state biochemistry), tensegrity provides a physical basis to explain how atomic and molecular elements progressively self-assembled to create hierarchical structures with increasingly complex functions, including living cells that can self-reproduce.

Antifouling Properties of Fluoropolymer Brushes toward Organic Polymers: The Influence of Composition, Thickness, Brush Architecture, and Annealing.

PubMed

Wang, Zhanhua; Zuilhof, Han

2016-07-05

Fluoropolymer brushes are widely used to prevent nonspecific adsorption of commercial polymeric or biological materials due to their strongly hydrophobic character. Herein, a series of fluoropolymer brushes with different compositions, thicknesses and molecular architectures was prepared via surface-initiated atom transfer radical polymerization (ATRP). Subsequently, the antifouling properties of these fluoropolymer brushes against organic polymers were studied in detail using X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) measurements and polystyrene as a representative fouling polymer. Among all of the molecular architectures studied, homopolymerized methacrylate-based fluoropolymer brushes (PMAF17) show the best antifouling properties. Annealing the fluoropolymer brushes improves the antifouling property dramatically due to the reregulated surface composition. These fluoropolymer brushes can be combined with, e.g., micro- and nanostructuring and other advanced materials properties to yield even better long-term antifouling behavior under harsh environments.

Modelling of internal architecture of kinesin nanomotor as a machine language.

PubMed

Khataee, H R; Ibrahim, M Y

2012-09-01

Kinesin is a protein-based natural nanomotor that transports molecular cargoes within cells by walking along microtubules. Kinesin nanomotor is considered as a bio-nanoagent which is able to sense the cell through its sensors (i.e. its heads and tail), make the decision internally and perform actions on the cell through its actuator (i.e. its motor domain). The study maps the agent-based architectural model of internal decision-making process of kinesin nanomotor to a machine language using an automata algorithm. The applied automata algorithm receives the internal agent-based architectural model of kinesin nanomotor as a deterministic finite automaton (DFA) model and generates a regular machine language. The generated regular machine language was acceptable by the architectural DFA model of the nanomotor and also in good agreement with its natural behaviour. The internal agent-based architectural model of kinesin nanomotor indicates the degree of autonomy and intelligence of the nanomotor interactions with its cell. Thus, our developed regular machine language can model the degree of autonomy and intelligence of kinesin nanomotor interactions with its cell as a language. Modelling of internal architectures of autonomous and intelligent bio-nanosystems as machine languages can lay the foundation towards the concept of bio-nanoswarms and next phases of the bio-nanorobotic systems development.

Geometry induced sequence of nanoscale Frank–Kasper and quasicrystal mesophases in giant surfactants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yue, Kan; Huang, Mingjun; Marson, Ryan L.

Frank–Kasper (F-K) and quasicrystal phases were originally identified in metal alloys and only sporadically reported in soft materials. These unconventional sphere-packing schemes open up possibilities to design materials with different properties. The challenge in soft materials is how to correlate complex phases built from spheres with the tunable parameters of chemical composition and molecular architecture. Here, we report a complete sequence of various highly ordered mesophases by the self-assembly of specifically designed and synthesized giant surfactants, which are conjugates of hydrophilic polyhedral oligomeric silsesquioxane cages tethered with hydrophobic polystyrene tails. We show that the occurrence of these mesophases results frommore » nanophase separation between the heads and tails and thus is critically dependent on molecular geometry. Variations in molecular geometry achieved by changing the number of tails from one to four not only shift compositional phase boundaries but also stabilize F-K and quasicrystal phases in regions where simple phases of spheroidal micelles are typically observed. These complex self-assembled nanostructures have been identified by combining X-ray scattering techniques and real-space electron microscopy images. Brownian dynamics simulations based on a simplified molecular model confirm the architecture-induced sequence of phases. Our results demonstrate the critical role of molecular architecture in dictating the formation of supramolecular crystals with “soft” spheroidal motifs and provide guidelines to the design of unconventional self-assembled nanostructures.« less

Geometry induced sequence of nanoscale Frank–Kasper and quasicrystal mesophases in giant surfactants

PubMed Central

Yue, Kan; Huang, Mingjun; Marson, Ryan L.; He, Jinlin; Huang, Jiahao; Zhou, Zhe; Wang, Jing; Liu, Chang; Yan, Xuesheng; Wu, Kan; Guo, Zaihong; Liu, Hao; Ni, Peihong; Wesdemiotis, Chrys; Zhang, Wen-Bin; Glotzer, Sharon C.; Cheng, Stephen Z. D.

2016-01-01

Frank–Kasper (F-K) and quasicrystal phases were originally identified in metal alloys and only sporadically reported in soft materials. These unconventional sphere-packing schemes open up possibilities to design materials with different properties. The challenge in soft materials is how to correlate complex phases built from spheres with the tunable parameters of chemical composition and molecular architecture. Here, we report a complete sequence of various highly ordered mesophases by the self-assembly of specifically designed and synthesized giant surfactants, which are conjugates of hydrophilic polyhedral oligomeric silsesquioxane cages tethered with hydrophobic polystyrene tails. We show that the occurrence of these mesophases results from nanophase separation between the heads and tails and thus is critically dependent on molecular geometry. Variations in molecular geometry achieved by changing the number of tails from one to four not only shift compositional phase boundaries but also stabilize F-K and quasicrystal phases in regions where simple phases of spheroidal micelles are typically observed. These complex self-assembled nanostructures have been identified by combining X-ray scattering techniques and real-space electron microscopy images. Brownian dynamics simulations based on a simplified molecular model confirm the architecture-induced sequence of phases. Our results demonstrate the critical role of molecular architecture in dictating the formation of supramolecular crystals with “soft” spheroidal motifs and provide guidelines to the design of unconventional self-assembled nanostructures. PMID:27911786

Antibody-controlled actuation of DNA-based molecular circuits.

PubMed

Engelen, Wouter; Meijer, Lenny H H; Somers, Bram; de Greef, Tom F A; Merkx, Maarten

2017-02-17

DNA-based molecular circuits allow autonomous signal processing, but their actuation has relied mostly on RNA/DNA-based inputs, limiting their application in synthetic biology, biomedicine and molecular diagnostics. Here we introduce a generic method to translate the presence of an antibody into a unique DNA strand, enabling the use of antibodies as specific inputs for DNA-based molecular computing. Our approach, antibody-templated strand exchange (ATSE), uses the characteristic bivalent architecture of antibodies to promote DNA-strand exchange reactions both thermodynamically and kinetically. Detailed characterization of the ATSE reaction allowed the establishment of a comprehensive model that describes the kinetics and thermodynamics of ATSE as a function of toehold length, antibody-epitope affinity and concentration. ATSE enables the introduction of complex signal processing in antibody-based diagnostics, as demonstrated here by constructing molecular circuits for multiplex antibody detection, integration of multiple antibody inputs using logic gates and actuation of enzymes and DNAzymes for signal amplification.

Antibody-controlled actuation of DNA-based molecular circuits

NASA Astrophysics Data System (ADS)

Engelen, Wouter; Meijer, Lenny H. H.; Somers, Bram; de Greef, Tom F. A.; Merkx, Maarten

2017-02-01

DNA-based molecular circuits allow autonomous signal processing, but their actuation has relied mostly on RNA/DNA-based inputs, limiting their application in synthetic biology, biomedicine and molecular diagnostics. Here we introduce a generic method to translate the presence of an antibody into a unique DNA strand, enabling the use of antibodies as specific inputs for DNA-based molecular computing. Our approach, antibody-templated strand exchange (ATSE), uses the characteristic bivalent architecture of antibodies to promote DNA-strand exchange reactions both thermodynamically and kinetically. Detailed characterization of the ATSE reaction allowed the establishment of a comprehensive model that describes the kinetics and thermodynamics of ATSE as a function of toehold length, antibody-epitope affinity and concentration. ATSE enables the introduction of complex signal processing in antibody-based diagnostics, as demonstrated here by constructing molecular circuits for multiplex antibody detection, integration of multiple antibody inputs using logic gates and actuation of enzymes and DNAzymes for signal amplification.

Understanding transparency perception in architecture: presentation of the simplified perforated model.

PubMed

Brzezicki, Marcin

2013-01-01

Issues of transparency perception are addressed from an architectural perspective, pointing out previously neglected factors that greatly influence this phenomenon in the scale of a building. The simplified perforated model of a transparent surface presented in the paper has been based on previously developed theories and involves the balance of light reflected versus light transmitted. Its aim is to facilitate an understanding of non-intuitive phenomena related to transparency (eg dynamically changing reflectance) for readers without advanced knowledge of molecular physics. A verification of the presented model has been based on the comparison of optical performance of the model with the results of Fresnel's equations for light-transmitting materials. The presented methodology is intended to be used both in the design and explanatory stages of architectural practice and vision research. Incorporation of architectural issues could enrich the perspective of scientists representing other disciplines.

An {Fe60} tetrahedral cage: building nanoscopic molecular assemblies through cyanometallate and alkoxo linkers.

PubMed

Jiménez, J-R; Mondal, A; Chamoreau, L-M; Fertey, P; Tuna, F; Julve, M; Bousseksou, A; Lescouëzec, R; Lisnard, L

2016-11-08

A nanoscopic {Fe 60 } coordination cage (approximately 3 nm) was prepared by the self assembly of a partially blocked tricyanidoferrate(iii) complex and tris(alkoxo)-based iron(iii) coordination motifs. This cage is a rare example of a mixed cyanido/alkoxo-bridged high nuclearity complex and it exemplifies the great potential of this new synthetic route to generate uncommon molecular architectures using cyanometallates as metalloligands versus alkoxo-based polynuclear entities.

NanoDesign: Concepts and Software for a Nanotechnology Based on Functionalized Fullerenes

NASA Technical Reports Server (NTRS)

Globus, Al; Jaffe, Richard; Chancellor, Marisa K. (Technical Monitor)

1996-01-01

Eric Drexler has proposed a hypothetical nanotechnology based on diamond and investigated the properties of such molecular systems. While attractive, diamonoid nanotechnology is not physically accessible with straightforward extensions of current laboratory techniques. We propose a nanotechnology based on functionalized fullerenes and investigate carbon nanotube based gears with teeth added via a benzyne reaction known to occur with C60. The gears are single-walled carbon nanotubes with appended coenzyme groups for teeth. Fullerenes are in widespread laboratory use and can be functionalized in many ways. Companion papers computationally demonstrate the properties of these gears (they appear to work) and the accessibility of the benzyne/nanotube reaction. This paper describes the molecular design techniques and rationale as well as the software that implements these design techniques. The software is a set of persistent C++ objects controlled by TCL command scripts. The c++/tcl interface is automatically generated by a software system called tcl_c++ developed by the author and described here. The objects keep track of different portions of the molecular machinery to allow different simulation techniques and boundary conditions to be applied as appropriate. This capability has been required to demonstrate (computationally) our gear's feasibility. A new distributed software architecture featuring a WWW universal client, CORBA distributed objects, and agent software is under consideration. The software architecture is intended to eventually enable a widely disbursed group to develop complex simulated molecular machines.

Wavelength-scale Microlasers based on VCSEL-Photonic Crystal Architecture

DTIC Science & Technology

2015-01-20

molecular beam epitaxy , MBE). We will also assume the triangular lattice of air...Abbreviations, and Acronyms InP: indium phosphide InGaAsP: indium gallium arsenide phosphide MBE: molecular beam epiitaxy VCSEL : vertical cavity...substrates and were grown by MBE. Electron beam lithography and reactive ion etching was used to deep‐etch the holes of the PhC‐ VCSELS ,

SpectraPlot.com: Integrated spectroscopic modeling of atomic and molecular gases

NASA Astrophysics Data System (ADS)

Goldenstein, Christopher S.; Miller, Victor A.; Mitchell Spearrin, R.; Strand, Christopher L.

2017-10-01

SpectraPlot is a web-based application for simulating spectra of atomic and molecular gases. At the time this manuscript was written, SpectraPlot consisted of four primary tools for calculating: (1) atomic and molecular absorption spectra, (2) atomic and molecular emission spectra, (3) transition linestrengths, and (4) blackbody emission spectra. These tools currently employ the NIST ASD, HITRAN2012, and HITEMP2010 databases to perform line-by-line simulations of spectra. SpectraPlot employs a modular, integrated architecture, enabling multiple simulations across multiple databases and/or thermodynamic conditions to be visualized in an interactive plot window. The primary objective of this paper is to describe the architecture and spectroscopic models employed by SpectraPlot in order to provide its users with the knowledge required to understand the capabilities and limitations of simulations performed using SpectraPlot. Further, this manuscript discusses the accuracy of several underlying approximations used to decrease computational time, in particular, the use of far-wing cutoff criteria.

Synthesis of Novel Hydrocarbon Soluble Multifunctional Anionic Initiators: Tools for Synthesis of Novel Dendrimer and Molecular Brush Polymer Architectures

DTIC Science & Technology

2015-02-09

Synthesis of Novel Dendrimer and Molecular Brush Polymer Architectures. Research Area:7.4 The views, opinions and/or findings contained in this report...journals: Final Report: Synthesis of Novel Hydrocarbon Soluble Multifunctional Anionic Initiators: Tools for Synthesis of Novel Dendrimer and Molecular

A Cobalt Supramolecular Triple-Stranded Helicate-based Discrete Molecular Cage

PubMed Central

Mai, Hien Duy; Kang, Philjae; Kim, Jin Kyung; Yoo, Hyojong

2017-01-01

We report a strategy to achieve a discrete cage molecule featuring a high level of structural hierarchy through a multiple-assembly process. A cobalt (Co) supramolecular triple-stranded helicate (Co-TSH)-based discrete molecular cage (1) is successfully synthesized and fully characterized. The solid-state structure of 1 shows that it is composed of six triple-stranded helicates interconnected by four linking cobalt species. This is an unusual example of a highly symmetric cage architecture resulting from the coordination-driven assembly of metallosupramolecular modules. The molecular cage 1 shows much higher CO2 uptake properties and selectivity compared with the separate supramolecular modules (Co-TSH, complex 2) and other molecular platforms. PMID:28262690

Molecular basis of angiosperm tree architecture.

PubMed

Hollender, Courtney A; Dardick, Chris

2015-04-01

The architecture of trees greatly impacts the productivity of orchards and forestry plantations. Amassing greater knowledge on the molecular genetics that underlie tree form can benefit these industries, as well as contribute to basic knowledge of plant developmental biology. This review describes the fundamental components of branch architecture, a prominent aspect of tree structure, as well as genetic and hormonal influences inferred from studies in model plant systems and from trees with non-standard architectures. The bulk of the molecular and genetic data described here is from studies of fruit trees and poplar, as these species have been the primary subjects of investigation in this field of science. No claim to original US Government works. New Phytologist © 2014 New Phytologist Trust.

Probing the emitter site of Renilla luciferase using small organic molecules; an attempt to understand the molecular architecture of the emitter site.

PubMed

Salehi, Farajollah; Emamzadeh, Rahman; Nazari, Mahboobeh; Rasa, Seyed Mohammad Mahdi

2016-12-01

Renilla luciferase is a sensitive enzyme and has wide applications in biotechnology such as drug screening. Previous studies have tried to show the catalytic residues, nevertheless, the accurate architecture and molecular behavior of its emitter site remains uncharacterized. In this study, the activity of Renilla luciferase, in the presence of two small organic molecules including dimethyl sulfoxide (DMSO) and isopropanol was considered and the structure was studied by circular dichroism (CD) and fluorescence spectroscopy. Moreover, the interaction of small organic molecules with the Renilla luciferase was studied using molecular dynamics simulations. Kinetics studies showed that at low concentration of DMSO (16.6-66mM) and isopropanol (19.3-76mM) the K m changed and a competitive inhibition pattern was observed. Moreover, spectroscopy studies reveled that the changes of activity of Renilla luciferase in the presence of low concentrations of small organic molecules was not associated with structural collapse or severe changes in the enzyme conformation. Molecular dynamics simulations indicated that DMSO and isopropanol, as probing molecules, were both able to bind to the emitter site and remained with the residues of the emitter site. Based on the probing data, the architecture of the emitter site in the "non-binding" model was proposed. Copyright © 2016 Elsevier B.V. All rights reserved.

Molecular basis of angiosperm tree architecture

USDA-ARS?s Scientific Manuscript database

The shoot architecture of trees greatly impacts orchard and forest management methods. Amassing greater knowledge of the molecular genetics behind tree form can benefit these industries as well as contribute to basic knowledge of plant developmental biology. This review covers basic components of ...

Combination of molecular, morphological, and interfacial engineering to achieve highly efficient and stable plastic solar cells.

PubMed

Chang, Chih-Yu; Cheng, Yen-Ju; Hung, Shih-Hsiu; Wu, Jhong-Sian; Kao, Wei-Shun; Lee, Chia-Hao; Hsu, Chain-Shu

2012-01-24

A flexible solar device showing exceptional air and mechanical stability is produced by simultaneously optimizing molecular structure, active layer morphology, and interface characteristics. The PFDCTBT-C8-based devices with inverted architecture exhibited excellent power conversion efficiencies of 7.0% and 6.0% on glass and flexible substrates, respectively. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Impact of higher order diagrams on phase equilibrium calculations for small molecules using lattice cluster theory

NASA Astrophysics Data System (ADS)

Zimmermann, Patrick; Walowski, Christoph; Enders, Sabine

2018-03-01

The Lattice Cluster Theory (LCT) provides a powerful tool to predict thermodynamic properties of large molecules (e.g., polymers) of different molecular architectures. When the pure-component parameters of a certain compound have been derived by adjustment to experimental data and the number of atoms is held constant within the molecule so that only the architecture is changed, the LCT is capable of predicting the properties of isomers without further parameter adjustment just based on the incorporation of molecular architecture. Trying to predict the thermodynamic properties of smaller molecules, one might face some challenges, which are addressed in this contribution. After factoring out the mean field term of the partition function, the LCT poses an expression that involves corrections to the mean field depending on molecular architecture, resulting in the free energy formally being expressed as a double series expansion in lattice coordination number z and interaction energy ɛ ˜ . In the process of deriving all contributing sub-structures within a molecule, some parts have been neglected to this point due to the double series expansion being truncated after the order ɛ˜ 2z-2. We consider the neglected parts that are of the order z-3 and reformulate the expression for the free energy within the LCT to achieve a higher predictive capability of the theory when it comes to small isomers and compressible systems. The modified version was successfully applied for phase equilibrium calculations of binary mixtures composed of linear and branched alkanes.

Towards advanced biological detection using surface enhanced raman scattering (SERS)-based sensors

NASA Astrophysics Data System (ADS)

Hankus, Mikella E.; Stratis-Cullum, Dimitra N.; Pellegrino, Paul M.

2010-08-01

The Army has a need for an accurate, fast, reliable and robust means to identify and quantify defense related materials. Raman spectroscopy is a form of vibrational spectroscopy that is rapidly becoming a valuable tool for homeland defense applications, as it is well suited for the molecular identification of a variety of compounds, including explosives and chemical and biological hazards. To measure trace levels of these types of materials, surface enhanced Raman scattering (SERS), a specialized form of Raman scattering, can be employed. The SERS enhancements are produced on, or in close proximity to, a nanoscale roughened metal surface and are typically associated with increased local electromagnetic field strengths. However, before application of SERS in the field and in particular to biological and other hazard sensing applications, significant improvements in substrate performance are needed. In this work, we will report the use of several SERS substrate architectures (colloids, film-over-nanospheres (FONs) and commercially available substrates) for detecting and differentiating numerous endospore samples. The variance in spectra as obtained using different sensing architectures will also be discussed. Additionally, the feasibility of using a modified substrate architecture that is tailored with molecular recognition probe system for detecting biological samples will be explored. We will discuss the progress towards an advanced, hybrid molecular recognition with a SERS/Fluorescence nanoprobe system including the optimization, fabrication, and spectroscopic analysis of samples on a commercially available substrate. Additionally, the feasibility of using this single-step switching architecture for hazard material detection will also be explored.

Fundamental Studies of Hydroporphyrin Architectures for Solar-Energy Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lindsey, Jonathan S.; Bocian, David F.; Holten, Dewey

2013-10-30

The long-term objective of the Bocian/Holten&Kirmaier/Lindsey research program is to design, synthesize, and characterize tetrapyrrole-based molecular architectures that absorb sunlight, funnel energy, and separate charge with high efficiency and in a manner compatible with current and future solar-energy conversion schemes. The synthetic tetrapyrroles include porphyrins and hydroporphyrins; the latter classes of molecules encompass analogues of the naturally occurring chlorophylls and bacteriochlorophylls (e.g., chlorins, bacteriochlorins, and their derivatives). The attainment of the goals of the research program requires the close interplay of molecular design and synthesis (Lindsey group), static and time-resolved optical spectroscopic measurements (Holten&Kirmaier group), and electrochemical, electron paramagnetic resonance,more » resonance Raman, and infrared studies, as well as density functional theory calculations (Bocian Group). The proposed research encompasses four interrelated themes: (i) Gain a deeper understanding of the spectral and electronic properties of bacteriochlorins, with a subsidiary aim of learning how to shift the long-wavelength absorption band deeper into the NIR region. Bacteriochlorins bearing diverse substituents, including annulated rings, will be prepared and examined. A set of bacteriochlorins with site-specific isotopic (13C, 2H) substitution patterns about the macrocycle perimeter will be prepared for studies of vibrational and electronic properties. (ii) Examine the underlying electronic origin of panchromatic absorption and excited-state behavior of strongly coupled rylene–tetrapyrrole arrays. The rylene constituents include a perylene-monoimide and a terrylene-monoimide. The tetrapyrroles include porphyrins (meso- or β-linked) and bacteriochlorins (β-linked). The objective is to achieve panchromatic absorption while preserving a viable, long-lived excited singlet state. (iii) Determine the rates of ground-state hole/electron transfer between (hydro)porphyrins as a function of array size, distance between components, linker type, site of linker connection, and frontier molecular orbital composition. (iv) Build upon the results of the aforementioned studies to design, synthesize, and characterize integrated architectures that incorporate a panchromatic absorber and other molecular components that that afford efficient hole/electron migration and long-lived charge separation. Such architectures will be examined on solid substrates to explore the viability of the component parts and processes under application-oriented conditions. Such architectures or successors may prove directly useful for solar-energy conversion systems. An equally important attribute is to serve as a test-bed for successful integration of the requisite properties and processes, some of which require rather weak coupling between constituents, some of which require very strong electronic interactions to elicit the desired behavior, and all of which should be tunable under molecular design control to the extent possible. Collectively, the proposed studies will provide fundamental insights into molecular properties, interactions, and processes relevant to the design of molecular architectures for solar-energy conversion. The accomplishment of these goals is only possible through a highly synergistic program that encompasses molecular design, synthesis, and in-depth characterization.« less

Design of two-photon molecular tandem architectures for solar cells by ab initio theory

DOE PAGES

Ornso, Kristian B.; Garcia-Lastra, Juan M.; De La Torre, Gema; ...

2015-03-04

An extensive database of spectroscopic properties of molecules from ab initio calculations is used to design molecular complexes for use in tandem solar cells that convert two photons into a single electron–hole pair, thereby increasing the output voltage while covering a wider spectral range. Three different architectures are considered: the first two involve a complex consisting of two dye molecules with appropriately matched frontier orbitals, connected by a molecular diode. Optimized combinations of dye molecules are determined by taking advantage of our computational database of the structural and energetic properties of several thousand porphyrin dyes. The third design is amore » molecular analogy of the intermediate band solar cell, and involves a single dye molecule with strong intersystem crossing to ensure a long lifetime of the intermediate state. Based on the calculated energy levels and molecular orbitals, energy diagrams are presented for the individual steps in the operation of such tandem solar cells. We find that theoretical open circuit voltages of up to 1.8 V can be achieved using these tandem designs. Questions about the practical implementation of prototypical devices, such as the synthesis of the tandem molecules and potential loss mechanisms, are addressed.« less

Clathrate colloidal crystals

NASA Astrophysics Data System (ADS)

Lin, Haixin; Lee, Sangmin; Sun, Lin; Spellings, Matthew; Engel, Michael; Glotzer, Sharon C.; Mirkin, Chad A.

2017-03-01

DNA-programmable assembly has been used to deliberately synthesize hundreds of different colloidal crystals spanning dozens of symmetries, but the complexity of the achieved structures has so far been limited to small unit cells. We assembled DNA-modified triangular bipyramids (~250-nanometer long edge, 177-nanometer short edge) into clathrate architectures. Electron microscopy images revealed that at least three different structures form as large single-domain architectures or as multidomain materials. Ordered assemblies, isostructural to clathrates, were identified with the help of molecular simulations and geometric analysis. These structures are the most sophisticated architectures made via programmable assembly, and their formation can be understood based on the shape of the nanoparticle building blocks and mode of DNA functionalization.

Computational Nanotechnology of Materials, Devices, and Machines: Carbon Nanotubes

NASA Technical Reports Server (NTRS)

Srivastava, Deepak; Kwak, Dolhan (Technical Monitor)

2000-01-01

The mechanics and chemistry of carbon nanotubes have relevance for their numerous electronic applications. Mechanical deformations such as bending and twisting affect the nanotube's conductive properties, and at the same time they possess high strength and elasticity. Two principal techniques were utilized including the analysis of large scale classical molecular dynamics on a shared memory architecture machine and a quantum molecular dynamics methodology. In carbon based electronics, nanotubes are used as molecular wires with topological defects which are mediated through various means. Nanotubes can be connected to form junctions.

De novo design of molecular architectures by evolutionary assembly of drug-derived building blocks.

PubMed

Schneider, G; Lee, M L; Stahl, M; Schneider, P

2000-07-01

An evolutionary algorithm was developed for fragment-based de novo design of molecules (TOPAS, TOPology-Assigning System). This stochastic method aims at generating a novel molecular structure mimicking a template structure. A set of approximately 25,000 fragment structures serves as the building block supply, which were obtained by a straightforward fragmentation procedure applied to 36,000 known drugs. Eleven reaction schemes were implemented for both fragmentation and building block assembly. This combination of drug-derived building blocks and a restricted set of reaction schemes proved to be a key for the automatic development of novel, synthetically tractable structures. In a cyclic optimization process, molecular architectures were generated from a parent structure by virtual synthesis, and the best structure of a generation was selected as the parent for the subsequent TOPAS cycle. Similarity measures were used to define 'fitness', based on 2D-structural similarity or topological pharmacophore distance between the template molecule and the variants. The concept of varying library 'diversity' during a design process was consequently implemented by using adaptive variant distributions. The efficiency of the design algorithm was demonstrated for the de novo construction of potential thrombin inhibitors mimicking peptide and non-peptide template structures.

Functional Nanostructured Materials Based on Polymerized Surfactant Liquid Crystal Assemblies Liquid Crystal Assemblies

NASA Astrophysics Data System (ADS)

Gin, Douglas

2003-03-01

The development of materials with controlled nanostructures is one of the most important new areas of scientific research in chemistry and engineering. Our research group has developed a novel approach for making nanostructured polymer materials with unique functional properties using liquid crystals as starting materials. In this approach, we design polymerizable organic building blocks based on lyotropic liquid crystals (LLCs) (i.e., amphiphiles or surfactants) that carry, or can accommodate, a functional property of general interest. Through appropriate molecular design, these monomers self-assemble in the presence of water into fluid, yet ordered phase-separated, water-hydrocarbon assemblies with predictable nanoscale geometries. The architectures of these LLC phases can range from stacked two-dimensional lamellae to hexagonally ordered cylindrical channels with uniform feature sizes in the 1-10 nm range. These LLC phases are then photopolymerized into robust polymer networks with preservation of their small-scale structures. This approach allows us to investigate the effect of nanometer-scale architecture on important bulk properties, as well as to engineer chemical environments on the nanometer-scale for several areas of application. In this talk, new functional materials based on the polymerization of the lyotropic inverted hexagonal phase will be presented as one example of our general approach. Issues in the design and photopolymerization of functional amphiphilic monomers that adopt this LC architecture will be discussed. More importantly, the use of the resulting nanostructured polymer networks in three areas of application will be presented: (1) as templates for the synthesis of functional nanocomposites; (2) as tunable heterogeneous catalysts, and (3) as nanoporous membrane and separation media. In particular, issues pertaining to the contribution of nanoscale architecture to the performance of these systems will be highlighted. Opportunities for tailoring the nanoscale chemical environment and architecture of these materials through molecular design will be presented. Finally, the development of methods for controlling macroscopic orientation through processing will also be discussed.

Molecular rheology of branched polymers: decoding and exploring the role of architectural dispersity through a synergy of anionic synthesis, interaction chromatography, rheometry and modeling.

PubMed

van Ruymbeke, E; Lee, H; Chang, T; Nikopoulou, A; Hadjichristidis, N; Snijkers, F; Vlassopoulos, D

2014-07-21

An emerging challenge in polymer physics is the quantitative understanding of the influence of a macromolecular architecture (i.e., branching) on the rheological response of entangled complex polymers. Recent investigations of the rheology of well-defined architecturally complex polymers have determined the composition in the molecular structure and identified the role of side-products in the measured samples. The combination of different characterization techniques, experimental and/or theoretical, represents the current state-of-the-art. Here we review this interdisciplinary approach to molecular rheology of complex polymers, and show the importance of confronting these different tools for ensuring an accurate characterization of a given polymeric sample. We use statistical tools in order to relate the information available from the synthesis protocols of a sample and its experimental molar mass distribution (typically obtained from size exclusion chromatography), and hence obtain precise information about its structural composition, i.e. enhance the existing sensitivity limit. We critically discuss the use of linear rheology as a reliable quantitative characterization tool, along with the recently developed temperature gradient interaction chromatography. The latter, which has emerged as an indispensable characterization tool for branched architectures, offers unprecedented sensitivity in detecting the presence of different molecular structures in a sample. Combining these techniques is imperative in order to quantify the molecular composition of a polymer and its consequences on the macroscopic properties. We validate this approach by means of a new model asymmetric comb polymer which was synthesized anionically. It was thoroughly characterized and its rheology was carefully analyzed. The main result is that the rheological signal reveals fine molecular details, which must be taken into account to fully elucidate the viscoelastic response of entangled branched polymers. It is important to appreciate that, even optimal model systems, i.e., those synthesized with high-vacuum anionic methods, need thorough characterization via a combination of techniques. Besides helping to improve synthetic techniques, this methodology will be significant in fine-tuning mesoscopic tube-based models and addressing outstanding issues such as the quantitative description of the constraint release mechanism.

Controlled molecular self-assembly of complex three-dimensional structures in soft materials

PubMed Central

Huang, Changjin; Quinn, David; Suresh, Subra

2018-01-01

Many applications in tissue engineering, flexible electronics, and soft robotics call for approaches that are capable of producing complex 3D architectures in soft materials. Here we present a method using molecular self-assembly to generate hydrogel-based 3D architectures that resembles the appealing features of the bottom-up process in morphogenesis of living tissues. Our strategy effectively utilizes the three essential components dictating living tissue morphogenesis to produce complex 3D architectures: modulation of local chemistry, material transport, and mechanics, which can be engineered by controlling the local distribution of polymerization inhibitor (i.e., oxygen), diffusion of monomers/cross-linkers through the porous structures of cross-linked polymer network, and mechanical constraints, respectively. We show that oxygen plays a role in hydrogel polymerization which is mechanistically similar to the role of growth factors in tissue growth, and the continued growth of hydrogel enabled by diffusion of monomers/cross-linkers into the porous hydrogel similar to the mechanisms of tissue growth enabled by material transport. The capability and versatility of our strategy are demonstrated through biomimetics of tissue morphogenesis for both plants and animals, and its application to generate other complex 3D architectures. Our technique opens avenues to studying many growth phenomena found in nature and generating complex 3D structures to benefit diverse applications. PMID:29255037

Course 6: Physics of Composite Cell Membrane and Actin Based Cytoskeleton

NASA Astrophysics Data System (ADS)

Sackmann, E.; Bausch, A. R.; Vonna, L.

1 Architecture of composite cell membranes 1.1 The lipid/protein bilayer is a multicomponent smectic phase with mosaic like architecture 1.2 The spectrin/actin cytoskeleton as hyperelastic cell stabilizer 1.3 The actin cortex: Architecture and function 2 Physics of the actin based cytoskeleton 2.1 Actin is a living semiflexible polymer 2.2 Actin network as viscoelastic body 2.3 Correlation between macroscopic viscoelasticity and molecular 3 Heterogeneous actin gels in cells and biological function 3.1 Manipulation of actin gels 3.2 Control of organization and function of actin cortex by cell signalling 4 Micromechanics and microrheometry of cells 5 Activation of endothelial cells: On the possibility of formation of stress fibers as phase transition of actin-network triggered by cell signalling pathways 6 On cells as adaptive viscoplastic bodies 7 Controll of cellular protrusions controlled by actin/myosin cortex

Beyond Standard Molecular Dynamics: Investigating the Molecular Mechanisms of G Protein-Coupled Receptors with Enhanced Molecular Dynamics Methods

PubMed Central

Johnston, Jennifer M.

2014-01-01

The majority of biological processes mediated by G Protein-Coupled Receptors (GPCRs) take place on timescales that are not conveniently accessible to standard molecular dynamics (MD) approaches, notwithstanding the current availability of specialized parallel computer architectures, and efficient simulation algorithms. Enhanced MD-based methods have started to assume an important role in the study of the rugged energy landscape of GPCRs by providing mechanistic details of complex receptor processes such as ligand recognition, activation, and oligomerization. We provide here an overview of these methods in their most recent application to the field. PMID:24158803

Evaluation of a deep learning architecture for MR imaging prediction of ATRX in glioma patients

NASA Astrophysics Data System (ADS)

Korfiatis, Panagiotis; Kline, Timothy L.; Erickson, Bradley J.

2018-02-01

Predicting mutation/loss of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) gene utilizing MR imaging is of high importance since it is a predictor of response and prognosis in brain tumors. In this study, we compare a deep neural network approach based on a residual deep neural network (ResNet) architecture and one based on a classical machine learning approach and evaluate their ability in predicting ATRX mutation status without the need for a distinct tumor segmentation step. We found that the ResNet50 (50 layers) architecture, pre trained on ImageNet data was the best performing model, achieving an accuracy of 0.91 for the test set (classification of a slice as no tumor, ATRX mutated, or mutated) in terms of f1 score in a test set of 35 cases. The SVM classifier achieved 0.63 for differentiating the Flair signal abnormality regions from the test patients based on their mutation status. We report a method that alleviates the need for extensive preprocessing and acts as a proof of concept that deep neural network architectures can be used to predict molecular biomarkers from routine medical images.

To Your Health: NLM update transcript - Genetic architecture of mental disorders

MedlinePlus

... html To Your Health: NLM update Transcript Genetic architecture of mental disorders : 04/30/2018 To use ... disorders may have a distinctive molecular or genetic architecture that may provide a way to better diagnose ...

Effect of fiber architecture on flexural characteristics and fracture of fiber-reinforced dental composites.

PubMed

Karbhari, Vistasp M; Strassler, Howard

2007-08-01

The aim of this study was to compare and elucidate the differences in damage mechanisms and response of fiber-reinforced dental resin composites based on three different brands under flexural loading. The types of reinforcement consisted of a unidirectional E-glass prepreg (Splint-It from Jeneric/Petron Inc.), an ultrahigh molecular weight polyethylene fiber based biaxial braid (Connect, Kerr) and an ultrahigh molecular weight polyethylene fiber based leno-weave (Ribbond). Three different commercially available fiber reinforcing systems were used to fabricate rectangular bars, with the fiber reinforcement close to the tensile face, which were tested in flexure with an emphasis on studying damage mechanisms and response. Eight specimens (n=8) of each type were tested. Overall energy capacity as well as flexural strength and modulus were determined and results compared in light of the different abilities of the architectures used. Under flexural loading unreinforced and unidirectional prepreg reinforced dental composites failed in a brittle fashion, whereas the braid and leno-weave reinforced materials underwent significant deformation without rupture. The braid reinforced specimens showed the highest peak load. The addition of the unidirectional to the matrix resulted in an average strain of 0.06mm/mm which is 50% greater than the capacity of the unreinforced matrix, whereas the addition of the braid and leno-weave resulted in increases of 119 and 126%, respectively, emphasizing the higher capacity of both the UHM polyethylene fibers and the architectures to hold together without rupture under flexural loading. The addition of the fiber reinforcement substantially increases the level of strain energy in the specimens with the maximum being attained in the braid reinforced specimens with a 433% increase in energy absorption capability above the unreinforced case. The minimum scatter and highest consistency in response is seen in the leno-weave reinforced specimens due to the details of the architecture which restrict fabric shearing and movement during placement. It is crucial that the appropriate selection of fiber architectures be made not just from a perspective of highest strength, but overall damage tolerance and energy absorption. Differences in weaves and architectures can result in substantially different performance and appropriate selection can mitigate premature and catastrophic failure. The study provides details of materials level response characteristics which are useful in selection of the fiber reinforcement based on specifics of application.

Engineering the architectural diversity of heterogeneous metallic nanocrystals.

PubMed

Yu, Yue; Zhang, Qingbo; Xie, Jianping; Lee, Jim Yang

2013-01-01

Similar to molecular engineering where structural diversity is used to create more property variations for application explorations, the architectural engineering of heterogeneous metallic nanocrystals (HMNCs) can likewise increase the versatility of metallic nanocrystals (NCs). Here we present a synthesis strategy capable of engineering the architectural diversity of HMNCs through rational and independent programming of every architecture-determining element, that is, the shape and size of the component NCs and their spatial arrangement. The strategy is based on the galvanic replacement reaction of a self-sustaining layer formed by underpotential deposition on a polyhedral NC. The selective deposition of satellite NCs on specific site of the central NC is realized by creating a geometry-dependent heterogeneous electron distribution. This site-selective deposition approach is applicable to central NCs in various polyhedral shapes and sizes. The satellite NCs can further develop their own shape and size through crystal growth kinetics control.

Application of Renyi entropy for ultrasonic molecular imaging.

PubMed

Hughes, M S; Marsh, J N; Arbeit, J M; Neumann, R G; Fuhrhop, R W; Wallace, K D; Thomas, L; Smith, J; Agyem, K; Lanza, G M; Wickline, S A; McCarthy, J E

2009-05-01

Previous work has demonstrated that a signal receiver based on a limiting form of the Shannon entropy is, in certain settings, more sensitive to subtle changes in scattering architecture than conventional energy-based signal receivers [M. S. Hughes et al., J. Acoust. Soc. Am. 121, 3542-3557 (2007)]. In this paper new results are presented demonstrating further improvements in sensitivity using a signal receiver based on the Renyi entropy.

Nanopatterning of Surfaces with Monometallic and Heterobimetallic 1D Coordination Polymers: A Molecular Tectonics Approach at the Solid/Liquid Interface.

PubMed

El Garah, Mohamed; Marets, Nicolas; Mauro, Matteo; Aliprandi, Alessandro; Bonacchi, Sara; De Cola, Luisa; Ciesielski, Artur; Bulach, Véronique; Hosseini, Mir Wais; Samorì, Paolo

2015-07-08

The self-assembly of multiple molecular components into complex supramolecular architectures is ubiquitous in nature and constitutes one of the most powerful strategies to fabricate multifunctional nanomaterials making use of the bottom-up approach. When spatial confinement in two dimensions on a solid substrate is employed, this approach can be exploited to generate periodically ordered structures from suitably designed molecular tectons. In this study we demonstrate that physisorbed directional periodic arrays of monometallic or heterobimetallic coordination polymers can be generated on a highly oriented pyrolitic graphite surface by combinations of a suitably designed directional organic tecton or metallatecton based on a porphyrin or nickel(II) metalloporphyrin backbone bearing both a pyridyl unit and a terpyridyl unit acting as coordinating sites for CoCl2. The periodic architectures were visualized at the solid/liquid interface with a submolecular resolution by scanning tunneling microscopy and corroborated by combined density functional and time-dependent density functional theory calculations. The capacity to nanopattern the surface for the first time with two distinct metallic centers exhibiting different electronic and optical properties is a key step toward the bottom-up construction of robust multicomponent and, thus, multifunctional molecular nanostructures and nanodevices.

Dual-Spectroscopy Platform for the Surveillance of Mars Mineralogy Using a Decisions Fusion Architecture on Simultaneous LIBS-Raman Data.

PubMed

Moros, Javier; ElFaham, Mohamed Mostafa; Laserna, J Javier

2018-02-06

A single platform, integrated by a laser-induced breakdown spectroscopy detector and a Raman spectroscopy sensor, has been designed to remotely (5 m) and simultaneously register the elemental and molecular signatures of rocks under Martian surface conditions. From this information, new data fusion architecture at decisions level is proposed for the correct categorization of the rocks. The approach is based on a decision-making process from the sequential checking of the spectral features representing the cationic and anionic counterparts of the specimen. The scrutiny of the LIBS response by using a moving-window algorithm informs on the diversity of the elemental constituents. The output rate of emission lines allows projecting in a loop the elements as the cationic counterpart of the rock. In parallel, the Raman response of the unknown is compared with all the molecular counterparts of the hypothesized cation that are stored in a spectral library. The largest similarity rate unveils the final identity of the unknown. The identification capabilities of the architecture have been underscored through blind tests of 10 natural rocks with different origins. The great majority of forecasts have matched with the real identities of the inspected targets. The strength of this platform to simultaneously acquire the multielemental and the molecular information from a specimen by using the same laser events greatly enhances the "on-surface" missions for the surveillance of mineralogy.

Design of two-photon molecular tandem architectures for solar cells by ab initio theory† †Electronic supplementary information (ESI) available: Visualizations of molecular orbitals, one-particle mechanisms and a table with Kohn–Sham eigenvalues. See DOI: 10.1039/c4sc03835e

PubMed Central

Garcia-Lastra, Juan M.; De La Torre, Gema; Himpsel, F. J.; Rubio, Angel

2015-01-01

An extensive database of spectroscopic properties of molecules from ab initio calculations is used to design molecular complexes for use in tandem solar cells that convert two photons into a single electron–hole pair, thereby increasing the output voltage while covering a wider spectral range. Three different architectures are considered: the first two involve a complex consisting of two dye molecules with appropriately matched frontier orbitals, connected by a molecular diode. Optimized combinations of dye molecules are determined by taking advantage of our computational database of the structural and energetic properties of several thousand porphyrin dyes. The third design is a molecular analogy of the intermediate band solar cell, and involves a single dye molecule with strong intersystem crossing to ensure a long lifetime of the intermediate state. Based on the calculated energy levels and molecular orbitals, energy diagrams are presented for the individual steps in the operation of such tandem solar cells. We find that theoretical open circuit voltages of up to 1.8 V can be achieved using these tandem designs. Questions about the practical implementation of prototypical devices, such as the synthesis of the tandem molecules and potential loss mechanisms, are addressed. PMID:29142685

Photo-control of nanointeractions.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomes, William Joseph, Jr.; Potter, Barrett George, Jr.; Jiang, Liu

2005-02-01

The manipulation of physical interactions between structural moieties on the molecular scale is a fundamental hurdle in the realization and operation of nanostructured materials and high surface area microsystem architectures. These include such nano-interaction-based phenomena as self-assembly, fluid flow, and interfacial tribology. The proposed research utilizes photosensitive molecular structures to tune such interactions reversibly. This new material strategy provides optical actuation of nano-interactions impacting behavior on both the nano- and macroscales and with potential to impact directed nanostructure formation, microfluidic rheology, and tribological control.

Self-Consistent Field Theories for the Role of Large Length-Scale Architecture in Polymers

NASA Astrophysics Data System (ADS)

Wu, David

At large length-scales, the architecture of polymers can be described by a coarse-grained specification of the distribution of branch points and monomer types within a molecule. This includes molecular topology (e.g., cyclic or branched) as well as distances between branch points or chain ends. Design of large length-scale molecular architecture is appealing because it offers a universal strategy, independent of monomer chemistry, to tune properties. Non-linear analogs of linear chains differ in molecular-scale properties, such as mobility, entanglements, and surface segregation in blends that are well-known to impact rheological, dynamical, thermodynamic and surface properties including adhesion and wetting. We have used Self-Consistent Field (SCF) theories to describe a number of phenomena associated with large length-scale polymer architecture. We have predicted the surface composition profiles of non-linear chains in blends with linear chains. These predictions are in good agreement with experimental results, including from neutron scattering, on a range of well-controlled branched (star, pom-pom and end-branched) and cyclic polymer architectures. Moreover, the theory allows explanation of the segregation and conformations of branched polymers in terms of effective surface potentials acting on the end and branch groups. However, for cyclic chains, which have no end or junction points, a qualitatively different topological mechanism based on conformational entropy drives cyclic chains to a surface, consistent with recent neutron reflectivity experiments. We have also used SCF theory to calculate intramolecular and intermolecular correlations for polymer chains in the bulk, dilute solution, and trapped at a liquid-liquid interface. Predictions of chain swelling in dilute star polymer solutions compare favorably with existing PRISM theory and swelling at an interface helps explain recent measurements of chain mobility at an oil-water interface. In collaboration with: Renfeng Hu, Colorado School of Mines, and Mark Foster, University of Akron. This work was supported by NSF Grants No. CBET- 0730692 and No. CBET-0731319.

Classification of coordination polygons and polyhedra according to their mode of self-assembly.

PubMed

Swiegers, G F; Malefetse, T J

2001-09-03

This work extends techniques for the controlled formation of synthetic molecular containers by metal-mediated self-assembly. A new classification system based on the self-assembly of such species is proposed. The system: 1) allows a systematic identification of suitable acceptor-donor combinations, 2) widens the variety of design possibilities available, 3) allows a ready comparison of the self-assembly of different compounds, 4) reveals useful commonalities between different compounds, 5) aids in the development of novel architectures, and 6) permits identification of systems capable of being switched back-and-forth between architectures.

Application of Renyi entropy for ultrasonic molecular imaging

PubMed Central

Hughes, M. S.; Marsh, J. N.; Arbeit, J. M.; Neumann, R. G.; Fuhrhop, R. W.; Wallace, K. D.; Thomas, L.; Smith, J.; Agyem, K.; Lanza, G. M.; Wickline, S. A.; McCarthy, J. E.

2009-01-01

Previous work has demonstrated that a signal receiver based on a limiting form of the Shannon entropy is, in certain settings, more sensitive to subtle changes in scattering architecture than conventional energy-based signal receivers [M. S. Hughes et al., J. Acoust. Soc. Am. 121, 3542–3557 (2007)]. In this paper new results are presented demonstrating further improvements in sensitivity using a signal receiver based on the Renyi entropy. PMID:19425656

Talin determines the nanoscale architecture of focal adhesions.

PubMed

Liu, Jaron; Wang, Yilin; Goh, Wah Ing; Goh, Honzhen; Baird, Michelle A; Ruehland, Svenja; Teo, Shijia; Bate, Neil; Critchley, David R; Davidson, Michael W; Kanchanawong, Pakorn

2015-09-01

Insight into how molecular machines perform their biological functions depends on knowledge of the spatial organization of the components, their connectivity, geometry, and organizational hierarchy. However, these parameters are difficult to determine in multicomponent assemblies such as integrin-based focal adhesions (FAs). We have previously applied 3D superresolution fluorescence microscopy to probe the spatial organization of major FA components, observing a nanoscale stratification of proteins between integrins and the actin cytoskeleton. Here we combine superresolution imaging techniques with a protein engineering approach to investigate how such nanoscale architecture arises. We demonstrate that talin plays a key structural role in regulating the nanoscale architecture of FAs, akin to a molecular ruler. Talin diagonally spans the FA core, with its N terminus at the membrane and C terminus demarcating the FA/stress fiber interface. In contrast, vinculin is found to be dispensable for specification of FA nanoscale architecture. Recombinant analogs of talin with modified lengths recapitulated its polarized orientation but altered the FA/stress fiber interface in a linear manner, consistent with its modular structure, and implicating the integrin-talin-actin complex as the primary mechanical linkage in FAs. Talin was found to be ∼97 nm in length and oriented at ∼15° relative to the plasma membrane. Our results identify talin as the primary determinant of FA nanoscale organization and suggest how multiple cellular forces may be integrated at adhesion sites.

Controlled molecular self-assembly of complex three-dimensional structures in soft materials.

PubMed

Huang, Changjin; Quinn, David; Suresh, Subra; Hsia, K Jimmy

2018-01-02

Many applications in tissue engineering, flexible electronics, and soft robotics call for approaches that are capable of producing complex 3D architectures in soft materials. Here we present a method using molecular self-assembly to generate hydrogel-based 3D architectures that resembles the appealing features of the bottom-up process in morphogenesis of living tissues. Our strategy effectively utilizes the three essential components dictating living tissue morphogenesis to produce complex 3D architectures: modulation of local chemistry, material transport, and mechanics, which can be engineered by controlling the local distribution of polymerization inhibitor (i.e., oxygen), diffusion of monomers/cross-linkers through the porous structures of cross-linked polymer network, and mechanical constraints, respectively. We show that oxygen plays a role in hydrogel polymerization which is mechanistically similar to the role of growth factors in tissue growth, and the continued growth of hydrogel enabled by diffusion of monomers/cross-linkers into the porous hydrogel similar to the mechanisms of tissue growth enabled by material transport. The capability and versatility of our strategy are demonstrated through biomimetics of tissue morphogenesis for both plants and animals, and its application to generate other complex 3D architectures. Our technique opens avenues to studying many growth phenomena found in nature and generating complex 3D structures to benefit diverse applications. Copyright © 2017 the Author(s). Published by PNAS.

The Molecular Genetic Architecture of Self-Employment

PubMed Central

van der Loos, Matthijs J. H. M.; Rietveld, Cornelius A.; Eklund, Niina; Koellinger, Philipp D.; Rivadeneira, Fernando; Abecasis, Gonçalo R.; Ankra-Badu, Georgina A.; Baumeister, Sebastian E.; Benjamin, Daniel J.; Biffar, Reiner; Blankenberg, Stefan; Boomsma, Dorret I.; Cesarini, David; Cucca, Francesco; de Geus, Eco J. C.; Dedoussis, George; Deloukas, Panos; Dimitriou, Maria; Eiriksdottir, Guðny; Eriksson, Johan; Gieger, Christian; Gudnason, Vilmundur; Höhne, Birgit; Holle, Rolf; Hottenga, Jouke-Jan; Isaacs, Aaron; Järvelin, Marjo-Riitta; Johannesson, Magnus; Kaakinen, Marika; Kähönen, Mika; Kanoni, Stavroula; Laaksonen, Maarit A.; Lahti, Jari; Launer, Lenore J.; Lehtimäki, Terho; Loitfelder, Marisa; Magnusson, Patrik K. E.; Naitza, Silvia; Oostra, Ben A.; Perola, Markus; Petrovic, Katja; Quaye, Lydia; Raitakari, Olli; Ripatti, Samuli; Scheet, Paul; Schlessinger, David; Schmidt, Carsten O.; Schmidt, Helena; Schmidt, Reinhold; Senft, Andrea; Smith, Albert V.; Spector, Timothy D.; Surakka, Ida; Svento, Rauli; Terracciano, Antonio; Tikkanen, Emmi; van Duijn, Cornelia M.; Viikari, Jorma; Völzke, Henry; Wichmann, H. -Erich; Wild, Philipp S.; Willems, Sara M.; Willemsen, Gonneke; van Rooij, Frank J. A.; Groenen, Patrick J. F.; Uitterlinden, André G.; Hofman, Albert; Thurik, A. Roy

2013-01-01

Economic variables such as income, education, and occupation are known to affect mortality and morbidity, such as cardiovascular disease, and have also been shown to be partly heritable. However, very little is known about which genes influence economic variables, although these genes may have both a direct and an indirect effect on health. We report results from the first large-scale collaboration that studies the molecular genetic architecture of an economic variable–entrepreneurship–that was operationalized using self-employment, a widely-available proxy. Our results suggest that common SNPs when considered jointly explain about half of the narrow-sense heritability of self-employment estimated in twin data (σg 2/σP 2 = 25%, h 2 = 55%). However, a meta-analysis of genome-wide association studies across sixteen studies comprising 50,627 participants did not identify genome-wide significant SNPs. 58 SNPs with p<10−5 were tested in a replication sample (n = 3,271), but none replicated. Furthermore, a gene-based test shows that none of the genes that were previously suggested in the literature to influence entrepreneurship reveal significant associations. Finally, SNP-based genetic scores that use results from the meta-analysis capture less than 0.2% of the variance in self-employment in an independent sample (p≥0.039). Our results are consistent with a highly polygenic molecular genetic architecture of self-employment, with many genetic variants of small effect. Although self-employment is a multi-faceted, heavily environmentally influenced, and biologically distal trait, our results are similar to those for other genetically complex and biologically more proximate outcomes, such as height, intelligence, personality, and several diseases. PMID:23593239

Light-operated machines based on threaded molecular structures.

PubMed

Credi, Alberto; Silvi, Serena; Venturi, Margherita

2014-01-01

Rotaxanes and related species represent the most common implementation of the concept of artificial molecular machines, because the supramolecular nature of the interactions between the components and their interlocked architecture allow a precise control on the position and movement of the molecular units. The use of light to power artificial molecular machines is particularly valuable because it can play the dual role of "writing" and "reading" the system. Moreover, light-driven machines can operate without accumulation of waste products, and photons are the ideal inputs to enable autonomous operation mechanisms. In appropriately designed molecular machines, light can be used to control not only the stability of the system, which affects the relative position of the molecular components but also the kinetics of the mechanical processes, thereby enabling control on the direction of the movements. This step forward is necessary in order to make a leap from molecular machines to molecular motors.

Replica Exchange Molecular Dynamics in the Age of Heterogeneous Architectures

NASA Astrophysics Data System (ADS)

Roitberg, Adrian

2014-03-01

The rise of GPU-based codes has allowed MD to reach timescales only dreamed of only 5 years ago. Even within this new paradigm there is still need for advanced sampling techniques. Modern supercomputers (e.g. Blue Waters, Titan, Keeneland) have made available to users a significant number of GPUS and CPUS, which in turn translate into amazing opportunities for dream calculations. Replica-exchange based methods can optimally use tis combination of codes and architectures to explore conformational variabilities in large systems. I will show our recent work in porting the program Amber to GPUS, and the support for replica exchange methods, where the replicated dimension could be Temperature, pH, Hamiltonian, Umbrella windows and combinations of those schemes.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rizzi, Silvio; Hereld, Mark; Insley, Joseph

In this work we perform in-situ visualization of molecular dynamics simulations, which can help scientists to visualize simulation output on-the-fly, without incurring storage overheads. We present a case study to couple LAMMPS, the large-scale molecular dynamics simulation code with vl3, our parallel framework for large-scale visualization and analysis. Our motivation is to identify effective approaches for covisualization and exploration of large-scale atomistic simulations at interactive frame rates.We propose a system of coupled libraries and describe its architecture, with an implementation that runs on GPU-based clusters. We present the results of strong and weak scalability experiments, as well as future researchmore » avenues based on our results.« less

Quantitative image analysis of cellular heterogeneity in breast tumors complements genomic profiling.

PubMed

Yuan, Yinyin; Failmezger, Henrik; Rueda, Oscar M; Ali, H Raza; Gräf, Stefan; Chin, Suet-Feung; Schwarz, Roland F; Curtis, Christina; Dunning, Mark J; Bardwell, Helen; Johnson, Nicola; Doyle, Sarah; Turashvili, Gulisa; Provenzano, Elena; Aparicio, Sam; Caldas, Carlos; Markowetz, Florian

2012-10-24

Solid tumors are heterogeneous tissues composed of a mixture of cancer and normal cells, which complicates the interpretation of their molecular profiles. Furthermore, tissue architecture is generally not reflected in molecular assays, rendering this rich information underused. To address these challenges, we developed a computational approach based on standard hematoxylin and eosin-stained tissue sections and demonstrated its power in a discovery and validation cohort of 323 and 241 breast tumors, respectively. To deconvolute cellular heterogeneity and detect subtle genomic aberrations, we introduced an algorithm based on tumor cellularity to increase the comparability of copy number profiles between samples. We next devised a predictor for survival in estrogen receptor-negative breast cancer that integrated both image-based and gene expression analyses and significantly outperformed classifiers that use single data types, such as microarray expression signatures. Image processing also allowed us to describe and validate an independent prognostic factor based on quantitative analysis of spatial patterns between stromal cells, which are not detectable by molecular assays. Our quantitative, image-based method could benefit any large-scale cancer study by refining and complementing molecular assays of tumor samples.

Reductive evolution of architectural repertoires in proteomes and the birth of the tripartite world

PubMed Central

Wang, Minglei; Yafremava, Liudmila S.; Caetano-Anollés, Derek; Mittenthal, Jay E.; Caetano-Anollés, Gustavo

2007-01-01

The repertoire of protein architectures in proteomes is evolutionarily conserved and capable of preserving an accurate record of genomic history. Here we use a census of protein architecture in 185 genomes that have been fully sequenced to generate genome-based phylogenies that describe the evolution of the protein world at fold (F) and fold superfamily (FSF) levels. The patterns of representation of F and FSF architectures over evolutionary history suggest three epochs in the evolution of the protein world: (1) architectural diversification, where members of an architecturally rich ancestral community diversified their protein repertoire; (2) superkingdom specification, where superkingdoms Archaea, Bacteria, and Eukarya were specified; and (3) organismal diversification, where F and FSF specific to relatively small sets of organisms appeared as the result of diversification of organismal lineages. Functional annotation of FSF along these architectural chronologies revealed patterns of discovery of biological function. Most importantly, the analysis identified an early and extensive differential loss of architectures occurring primarily in Archaea that segregates the archaeal lineage from the ancient community of organisms and establishes the first organismal divide. Reconstruction of phylogenomic trees of proteomes reflects the timeline of architectural diversification in the emerging lineages. Thus, Archaea undertook a minimalist strategy using only a small subset of the full architectural repertoire and then crystallized into a diversified superkingdom late in evolution. Our analysis also suggests a communal ancestor to all life that was molecularly complex and adopted genomic strategies currently present in Eukarya. PMID:17908824

Advanced nanoelectronic architectures for THz-based biological agent detection

NASA Astrophysics Data System (ADS)

Woolard, Dwight L.; Jensen, James O.

2009-02-01

The U.S. Army Research Office (ARO) and the U.S. Army Edgewood Chemical Biological Center (ECBC) jointly lead and support novel research programs that are advancing the state-of-the-art in nanoelectronic engineering in application areas that have relevance to national defense and security. One fundamental research area that is presently being emphasized by ARO and ECBC is the exploratory investigation of new bio-molecular architectural concepts that can be used to achieve rapid, reagent-less detection and discrimination of biological warfare (BW) agents, through the control of multi-photon and multi-wavelength processes at the nanoscale. This paper will overview an ARO/ECBC led multidisciplinary research program presently under the support of the U.S. Defense Threat Reduction Agency (DTRA) that seeks to develop new devices and nanoelectronic architectures that are effective for extracting THz signatures from target bio-molecules. Here, emphasis will be placed on the new nanosensor concepts and THz/Optical measurement methodologies for spectral-based sequencing/identification of genetic molecules.

Design Principles of Regulatory Networks: Searching for the Molecular Algorithms of the Cell

PubMed Central

Lim, Wendell A.; Lee, Connie M.; Tang, Chao

2013-01-01

A challenge in biology is to understand how complex molecular networks in the cell execute sophisticated regulatory functions. Here we explore the idea that there are common and general principles that link network structures to biological functions, principles that constrain the design solutions that evolution can converge upon for accomplishing a given cellular task. We describe approaches for classifying networks based on abstract architectures and functions, rather than on the specific molecular components of the networks. For any common regulatory task, can we define the space of all possible molecular solutions? Such inverse approaches might ultimately allow the assembly of a design table of core molecular algorithms that could serve as a guide for building synthetic networks and modulating disease networks. PMID:23352241

Molecular Architecture of Full-length TRF1 Favors Its Interaction with DNA.

PubMed

Boskovic, Jasminka; Martinez-Gago, Jaime; Mendez-Pertuz, Marinela; Buscato, Alberto; Martinez-Torrecuadrada, Jorge Luis; Blasco, Maria A

2016-10-07

Telomeres are specific DNA-protein structures found at both ends of eukaryotic chromosomes that protect the genome from degradation and from being recognized as double-stranded breaks. In vertebrates, telomeres are composed of tandem repeats of the TTAGGG sequence that are bound by a six-subunit complex called shelterin. Molecular mechanisms of telomere functions remain unknown in large part due to lack of structural data on shelterins, shelterin complex, and its interaction with the telomeric DNA repeats. TRF1 is one of the best studied shelterin components; however, the molecular architecture of the full-length protein remains unknown. We have used single-particle electron microscopy to elucidate the structure of TRF1 and its interaction with telomeric DNA sequence. Our results demonstrate that full-length TRF1 presents a molecular architecture that assists its interaction with telometic DNA and at the same time makes TRFH domains accessible to other TRF1 binding partners. Furthermore, our studies suggest hypothetical models on how other proteins as TIN2 and tankyrase contribute to regulate TRF1 function. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Mechanotransduction through Cytoskeleton

NASA Technical Reports Server (NTRS)

Ingber, Donald

2002-01-01

The goal of this project was to characterize the molecular mechanism by which cells recognize and respond to physical forces in their local environment. The project was based on the working hypothesis that cells sense mechanical stresses, such as those due to gravity, through their cell surface adhesion receptors (e.g., integrins) and that they respond as a result of structural arrangements with their internal cytoskeleton (CSK) which are orchestrated through use of tensegrity architecture. In this project, we carried out studies to define the architectural and molecular basis of cellular mechanotransduction. Our major goal was to define the molecular pathway that mediates mechanical force transfer between integrins and the CSK and to determine how mechanical deformation of integrin-CSK linkages is transduced into a biochemical response. Elucidation of the mechanism by which cells sense mechanical stresses through integrins and translate them into a biochemical response should help us to understand the molecular basis of the cellular response to gravity as well as many other forms of mechanosensation and tissue regulation. The specific aims of this proposal were: 1. To define the molecular basis of mechanical coupling between integrins, vinculin, and the actin CSK; 2. To develop a computer simulation of how mechanical stresses alter CSK structure and test this model in living cells; 3. To determine how mechanical deformation of integrin-CSK linkages is transduced into a biochemical response.

Controlling Styrene Maleic Acid Lipid Particles through RAFT.

PubMed

Smith, Anton A A; Autzen, Henriette E; Laursen, Tomas; Wu, Vincent; Yen, Max; Hall, Aaron; Hansen, Scott D; Cheng, Yifan; Xu, Ting

2017-11-13

The ability of styrene maleic acid copolymers to dissolve lipid membranes into nanosized lipid particles is a facile method of obtaining membrane proteins in solubilized lipid discs while conserving part of their native lipid environment. While the currently used copolymers can readily extract membrane proteins in native nanodiscs, their highly disperse composition is likely to influence the dispersity of the discs as well as the extraction efficiency. In this study, reversible addition-fragmentation chain transfer was used to control the polymer architecture and dispersity of molecular weights with a high-precision. Based on Monte Carlo simulations of the polymerizations, the monomer composition was predicted and allowed a structure-function analysis of the polymer architecture, in relation to their ability to assemble into lipid nanoparticles. We show that a higher degree of control of the polymer architecture generates more homogeneous samples. We hypothesize that low dispersity copolymers, with control of polymer architecture are an ideal framework for the rational design of polymers for customized isolation and characterization of integral membrane proteins in native lipid bilayer systems.

Tuning complement activation and pathway through controlled molecular architecture of dextran chains in nanoparticle corona.

PubMed

Coty, Jean-Baptiste; Eleamen Oliveira, Elquio; Vauthier, Christine

2017-11-05

The understanding of complement activation by nanomaterials is a key to a rational design of safe and efficient nanomedicines. This work proposed a systematic study investigating how molecular design of nanoparticle coronas made of dextran impacts on mechanisms that trigger complement activation. The nanoparticles used for this work consisted of dextran-coated poly(isobutylcyanoacrylate) (PIBCA) nanoparticles have already been thoroughly characterized. Their different capacity to trigger complement activation established on the cleavage of the protein C3 was also already described making these nanoparticles good models to investigate the relation between the molecular feature of their corona and the mechanism by which they triggered complement activation. Results of this new study show that complement activation pathways can be selected by distinct architectures formed by dextran chains composing the nanoparticle corona. Assumptions that explain the relation between complement activation mechanisms triggered by the nanoparticles and the nanoparticle corona molecular feature were proposed. These results are of interest to better understand how the design of dextran-coated nanomaterials will impact interactions with the complement system. It can open perspectives with regard to the selection of a preferential complement activation pathway or prevent the nanoparticles to activate the complement system, based on a rational choice of the corona configuration. Copyright © 2017 Elsevier B.V. All rights reserved.

Fundamental studies of energy-and hole/electron- transfer in hydroporphyrin architectures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bocian, David F.

2014-08-20

The long-term objective of the Bocian/Holten/Lindsey research program is to design, synthesize, and characterize tetrapyrrole-based molecular architectures that absorb sunlight, funnel energy, and separate charge with high efficiency and in a manner compatible with current and future solar-energy conversion schemes. The synthetic tetrapyrroles include porphyrins and hydroporphyrins; the latter classes of molecules encompass analogues of the naturally occurring chlorophylls and bacteriochlorophylls (e.g., chlorins, bacteriochlorins, and their derivatives). The attainment of the goals of the research program requires the close interplay of molecular design and synthesis (Lindsey group), static and time-resolved optical spectroscopic measurements (Holten group), and electrochemical, electron paramagnetic resonance,more » and resonance Raman studies, as well as density functional theory calculations (Bocian Group). The proposed research encompasses four interrelated themes: (1) Determination of the rates of ground-state hole/electron transfer between (hydro)porphyrins in multipigment arrays as a function of array size, distance between components, linker type, site of linker connection, and frontier molecular orbital composition. (2) Examination of excited-state energy transfer among hydroporphyrins in multipigment arrrays, including both pairwise and non-adjacent transfer, with a chief aim to identify the relative contributions of through-space (Förster) and through-bond (Dexter) mechanisms of energy transfer, including the roles of site of linker connection and frontier molecular orbital composition. (3) Elucidation of the role of substituents in tuning the spectral and electronic properties of bacteriochlorins, with a primary aim of learning how to shift the long-wavelength absorption band deeper into the near-infrared region. (4) Continued development of the software package PhotochemCAD for spectral manipulations and calculations through the compilation of a database of spectra for naturally occurring and synthetic hydroporphyrins. The availability of such data should augment efforts in the design of light-harvesting systems where spectral coverage in the red and near-infrared regions is desired. Collectively, the proposed studies will provide fundamental insights into molecular properties, interactions, and processes relevant to the design of molecular architectures for solar-energy conversion. The accomplishment of these goals is only possible through a highly synergistic program that encompasses molecular design, synthesis, and characterization.« less

Computational Nanotechnology of Materials, Electronics and Machines: Carbon Nanotubes

NASA Technical Reports Server (NTRS)

Srivastava, Deepak

2001-01-01

This report presents the goals and research of the Integrated Product Team (IPT) on Devices and Nanotechnology. NASA's needs for this technology are discussed and then related to the research focus of the team. The two areas of focus for technique development are: 1) large scale classical molecular dynamics on a shared memory architecture machine; and 2) quantum molecular dynamics methodology. The areas of focus for research are: 1) nanomechanics/materials; 2) carbon based electronics; 3) BxCyNz composite nanotubes and junctions; 4) nano mechano-electronics; and 5) nano mechano-chemistry.

Spectral imaging perspective on cytomics.

PubMed

Levenson, Richard M

2006-07-01

Cytomics involves the analysis of cellular morphology and molecular phenotypes, with reference to tissue architecture and to additional metadata. To this end, a variety of imaging and nonimaging technologies need to be integrated. Spectral imaging is proposed as a tool that can simplify and enrich the extraction of morphological and molecular information. Simple-to-use instrumentation is available that mounts on standard microscopes and can generate spectral image datasets with excellent spatial and spectral resolution; these can be exploited by sophisticated analysis tools. This report focuses on brightfield microscopy-based approaches. Cytological and histological samples were stained using nonspecific standard stains (Giemsa; hematoxylin and eosin (H&E)) or immunohistochemical (IHC) techniques employing three chromogens plus a hematoxylin counterstain. The samples were imaged using the Nuance system, a commercially available, liquid-crystal tunable-filter-based multispectral imaging platform. The resulting data sets were analyzed using spectral unmixing algorithms and/or learn-by-example classification tools. Spectral unmixing of Giemsa-stained guinea-pig blood films readily classified the major blood elements. Machine-learning classifiers were also successful at the same task, as well in distinguishing normal from malignant regions in a colon-cancer example, and in delineating regions of inflammation in an H&E-stained kidney sample. In an example of a multiplexed ICH sample, brown, red, and blue chromogens were isolated into separate images without crosstalk or interference from the (also blue) hematoxylin counterstain. Cytomics requires both accurate architectural segmentation as well as multiplexed molecular imaging to associate molecular phenotypes with relevant cellular and tissue compartments. Multispectral imaging can assist in both these tasks, and conveys new utility to brightfield-based microscopy approaches. Copyright 2006 International Society for Analytical Cytology.

"ICT-not-quenching" near infrared ratiometric fluorescent detection of picric acid in aqueous media.

PubMed

Xu, Yongqian; Li, Benhao; Li, Weiwei; Zhao, Jie; Sun, Shiguo; Pang, Yi

2013-05-25

The first "off-on" and ratiometric fluorescent method based on ICT mechanism for picric acid (PA) recognition in the near infrared region was constructed. Key advantages of the unique molecular architecture can fulfil the ratiometric response to electron-deficient featured PA which inclines to quench fluorescence of all reported sensors for PA.

Influence of macromolecular architecture on necking in polymer extrusion film casting process

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pol, Harshawardhan; Banik, Sourya; Azad, Lal Busher

2015-05-22

Extrusion film casting (EFC) is an important polymer processing technique that is used to produce several thousand tons of polymer films/coatings on an industrial scale. In this research, we are interested in understanding quantitatively how macromolecular chain architecture (for example long chain branching (LCB) or molecular weight distribution (MWD or PDI)) influences the necking and thickness distribution of extrusion cast films. We have used different polymer resins of linear and branched molecular architecture to produce extrusion cast films under controlled experimental conditions. The necking profiles of the films were imaged and the velocity profiles during EFC were monitored using particlemore » tracking velocimetry (PTV) technique. Additionally, the temperature profiles were captured using an IR thermography and thickness profiles were calculated. The experimental results are compared with predictions of one-dimensional flow model of Silagy et al{sup 1} wherein the polymer resin rheology is modeled using molecular constitutive equations such as the Rolie-Poly (RP) and extended Pom Pom (XPP). We demonstrate that the 1-D flow model containing the molecular constitutive equations provides new insights into the role of macromolecular chain architecture on film necking.{sup 1}D. Silagy, Y. Demay, and J-F. Agassant, Polym. Eng. Sci., 36, 2614 (1996)« less

Design and evaluation of basic standard encryption algorithm modules using nanosized complementary metal oxide semiconductor molecular circuits

NASA Astrophysics Data System (ADS)

Masoumi, Massoud; Raissi, Farshid; Ahmadian, Mahmoud; Keshavarzi, Parviz

2006-01-01

We are proposing that the recently proposed semiconductor-nanowire-molecular architecture (CMOL) is an optimum platform to realize encryption algorithms. The basic modules for the advanced encryption standard algorithm (Rijndael) have been designed using CMOL architecture. The performance of this design has been evaluated with respect to chip area and speed. It is observed that CMOL provides considerable improvement over implementation with regular CMOS architecture even with a 20% defect rate. Pseudo-optimum gate placement and routing are provided for Rijndael building blocks and the possibility of designing high speed, attack tolerant and long key encryptions are discussed.

Triazine-based sequence-defined polymers with side-chain diversity and backbone-backbone interaction motifs

DOE PAGES

Grate, Jay W.; Mo, Kai -For; Daily, Michael D.

2016-02-10

Sequence control in polymers, well-known in nature, encodes structure and functionality. Here we introduce a new architecture, based on the nucleophilic aromatic substitution chemistry of cyanuric chloride, that creates a new class of sequence-defined polymers dubbed TZPs. Proof of concept is demonstrated with two synthesized hexamers, having neutral and ionizable side chains. Molecular dynamics simulations show backbone–backbone interactions, including H-bonding motifs and pi–pi interactions. This architecture is arguably biomimetic while differing from sequence-defined polymers having peptide bonds. In conclusion, the synthetic methodology supports the structural diversity of side chains known in peptides, as well as backbone–backbone hydrogen-bonding motifs, and willmore » thus enable new macromolecules and materials with useful functions.« less

Triazine-Based Sequence-Defined Polymers with Side-Chain Diversity and Backbone-Backbone Interaction Motifs.

PubMed

Grate, Jay W; Mo, Kai-For; Daily, Michael D

2016-03-14

Sequence control in polymers, well-known in nature, encodes structure and functionality. Here we introduce a new architecture, based on the nucleophilic aromatic substitution chemistry of cyanuric chloride, that creates a new class of sequence-defined polymers dubbed TZPs. Proof of concept is demonstrated with two synthesized hexamers, having neutral and ionizable side chains. Molecular dynamics simulations show backbone-backbone interactions, including H-bonding motifs and pi-pi interactions. This architecture is arguably biomimetic while differing from sequence-defined polymers having peptide bonds. The synthetic methodology supports the structural diversity of side chains known in peptides, as well as backbone-backbone hydrogen-bonding motifs, and will thus enable new macromolecules and materials with useful functions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Triazine-based sequence-defined polymers with side-chain diversity and backbone-backbone interaction motifs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grate, Jay W.; Mo, Kai -For; Daily, Michael D.

Sequence control in polymers, well-known in nature, encodes structure and functionality. Here we introduce a new architecture, based on the nucleophilic aromatic substitution chemistry of cyanuric chloride, that creates a new class of sequence-defined polymers dubbed TZPs. Proof of concept is demonstrated with two synthesized hexamers, having neutral and ionizable side chains. Molecular dynamics simulations show backbone–backbone interactions, including H-bonding motifs and pi–pi interactions. This architecture is arguably biomimetic while differing from sequence-defined polymers having peptide bonds. In conclusion, the synthetic methodology supports the structural diversity of side chains known in peptides, as well as backbone–backbone hydrogen-bonding motifs, and willmore » thus enable new macromolecules and materials with useful functions.« less

Scaffold architecture and pharmacophoric properties of natural products and trade drugs: application in the design of natural product-based combinatorial libraries.

PubMed

Lee, M L; Schneider, G

2001-01-01

Natural products were analyzed to determine whether they contain appealing novel scaffold architectures for potential use in combinatorial chemistry. Ring systems were extracted and clustered on the basis of structural similarity. Several such potential scaffolds for combinatorial chemistry were identified that are not present in current trade drugs. For one of these scaffolds a virtual combinatorial library was generated. Pharmacophoric properties of natural products, trade drugs, and the virtual combinatorial library were assessed using a self-organizing map. Obviously, current trade drugs and natural products have several topological pharmacophore patterns in common. These features can be systematically explored with selected combinatorial libraries based on a combination of natural product-derived and synthetic molecular building blocks.

Probing the molecular design of hyper-branched aryl polyesters towards lubricant applications

DOE PAGES

Robinson, Joshua W.; Zhou, Yan; Bhattacharya, Priyanka; ...

2016-01-05

We report novel polymeric materials that may be used as viscosity index improvers (VII) for lubricant applications. Our efforts included probing the comb-burst hyper-branched aryl polyester architecture for beneficial viscosity and friction behavior when utilized as an additive in a group I oil. The monomer was designed as to undergo polymerization via polycondensation within the architectural construct (AB2), typical of hyperbranched polymers. The monomer design was comprised of aliphatic arms (12 or 16 methylenes) to provide the necessary lipophilicity to achieve solubility in a non-polar medium. Once polymerized, via catalyst and heat, the surface alcohols were functionalized with fatty acidsmore » (lauric and palmitic). Controlling the aliphatic nature of the internal arms and peripheral end-groups provided four unique flexible polymer designs. Changing the reaction time and concentration provided opportunities to investigate the influence of molecular weight and branching density on oil-solubility, viscosity, and friction. Oil-solubility was found to decrease with fewer internal carbons, but the number of internal carbons appears to have little influence on the bulk solution viscosity. Increased branching and degree of polymerization, and thus molecular weight, were found to reduce the solubility of these systems in the base oil. At concentrations of 2 wt % in a group I base oil, these polymer additives demonstrated improved viscosity index and reduced friction coefficient, validating the basic approach.« less

Probing the molecular design of hyper-branched aryl polyesters towards lubricant applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robinson, Joshua W.; Zhou, Yan; Bhattacharya, Priyanka

We report novel polymeric materials that may be used as viscosity index improvers (VII) for lubricant applications. Our efforts included probing the comb-burst hyper-branched aryl polyester architecture for beneficial viscosity and friction behavior when utilized as an additive in a group I oil. The monomer was designed as to undergo polymerization via polycondensation within the architectural construct (AB2), typical of hyperbranched polymers. The monomer design was comprised of aliphatic arms (12 or 16 methylenes) to provide the necessary lipophilicity to achieve solubility in a non-polar medium. Once polymerized, via catalyst and heat, the surface alcohols were functionalized with fatty acidsmore » (lauric and palmitic). Controlling the aliphatic nature of the internal arms and peripheral end-groups provided four unique flexible polymer designs. Changing the reaction time and concentration provided opportunities to investigate the influence of molecular weight and branching density on oil-solubility, viscosity, and friction. Oil-solubility was found to decrease with fewer internal carbons, but the number of internal carbons appears to have little influence on the bulk solution viscosity. Increased branching and degree of polymerization, and thus molecular weight, were found to reduce the solubility of these systems in the base oil. At concentrations of 2 wt % in a group I base oil, these polymer additives demonstrated improved viscosity index and reduced friction coefficient, validating the basic approach.« less

Solution processed molecular floating gate for flexible flash memories

NASA Astrophysics Data System (ADS)

Zhou, Ye; Han, Su-Ting; Yan, Yan; Huang, Long-Biao; Zhou, Li; Huang, Jing; Roy, V. A. L.

2013-10-01

Solution processed fullerene (C60) molecular floating gate layer has been employed in low voltage nonvolatile memory device on flexible substrates. We systematically studied the charge trapping mechanism of the fullerene floating gate for both p-type pentacene and n-type copper hexadecafluorophthalocyanine (F16CuPc) semiconductor in a transistor based flash memory architecture. The devices based on pentacene as semiconductor exhibited both hole and electron trapping ability, whereas devices with F16CuPc trapped electrons alone due to abundant electron density. All the devices exhibited large memory window, long charge retention time, good endurance property and excellent flexibility. The obtained results have great potential for application in large area flexible electronic devices.

Solution processed molecular floating gate for flexible flash memories

PubMed Central

Zhou, Ye; Han, Su-Ting; Yan, Yan; Huang, Long-Biao; Zhou, Li; Huang, Jing; Roy, V. A. L.

2013-01-01

Solution processed fullerene (C60) molecular floating gate layer has been employed in low voltage nonvolatile memory device on flexible substrates. We systematically studied the charge trapping mechanism of the fullerene floating gate for both p-type pentacene and n-type copper hexadecafluorophthalocyanine (F16CuPc) semiconductor in a transistor based flash memory architecture. The devices based on pentacene as semiconductor exhibited both hole and electron trapping ability, whereas devices with F16CuPc trapped electrons alone due to abundant electron density. All the devices exhibited large memory window, long charge retention time, good endurance property and excellent flexibility. The obtained results have great potential for application in large area flexible electronic devices. PMID:24172758

Supramolecular chemistry: from molecular information towards self-organization and complex matter

NASA Astrophysics Data System (ADS)

Lehn, Jean-Marie

2004-03-01

Molecular chemistry has developed a wide range of very powerful procedures for constructing ever more sophisticated molecules from atoms linked by covalent bonds. Beyond molecular chemistry lies supramolecular chemistry, which aims at developing highly complex chemical systems from components interacting via non-covalent intermolecular forces. By the appropriate manipulation of these interactions, supramolecular chemistry became progressively the chemistry of molecular information, involving the storage of information at the molecular level, in the structural features, and its retrieval, transfer, and processing at the supramolecular level, through molecular recognition processes operating via specific interactional algorithms. This has paved the way towards apprehending chemistry also as an information science. Numerous receptors capable of recognizing, i.e. selectively binding, specific substrates have been developed, based on the molecular information stored in the interacting species. Suitably functionalized receptors may perform supramolecular catalysis and selective transport processes. In combination with polymolecular organization, recognition opens ways towards the design of molecular and supramolecular devices based on functional (photoactive, electroactive, ionoactive, etc) components. A step beyond preorganization consists in the design of systems undergoing self-organization, i.e. systems capable of spontaneously generating well-defined supramolecular architectures by self-assembly from their components. Self-organization processes, directed by the molecular information stored in the components and read out at the supramolecular level through specific interactions, represent the operation of programmed chemical systems. They have been implemented for the generation of a variety of discrete functional architectures of either organic or inorganic nature. Self-organization processes also give access to advanced supramolecular materials, such as supramolecular polymers and liquid crystals, and provide an original approach to nanoscience and nanotechnology. In particular, the spontaneous but controlled generation of well-defined, functional supramolecular architectures of nanometric size through self-organization represents a means of performing programmed engineering and processing of nanomaterials. Supramolecular chemistry is intrinsically a dynamic chemistry, in view of the lability of the interactions connecting the molecular components of a supramolecular entity and the resulting ability of supramolecular species to exchange their constituents. The same holds for molecular chemistry when a molecular entity contains covalent bonds that may form and break reversibly, so as to make possible a continuous change in constitution and structure by reorganization and exchange of building blocks. This behaviour defines a constitutional dynamic chemistry that allows self-organization by selection as well as by design at both the molecular and supramolecular levels. Whereas self-organization by design strives to achieve full control over the output molecular or supramolecular entity by explicit programming, self-organization by selection operates on dynamic constitutional diversity in response to either internal or external factors to achieve adaptation in a Darwinistic fashion. The merging of the features, information and programmability, dynamics and reversibility, constitution and structural diversity, points towards the emergence of adaptative and evolutionary chemistry. Together with the corresponding fields of physics and biology, it constitutes a science of informed matter, of organized, adaptative complex matter. This article was originally published in 2003 by the Israel Academy of Sciences and Humanities in the framework of its Albert Einstein Memorial Lectures series. Reprinted by permission of the Israel Academy of Sciences and Humanities.

Architectonics: Design of Molecular Architecture for Functional Applications.

PubMed

Avinash, M B; Govindaraju, Thimmaiah

2018-02-20

The term architectonics has its roots in the architectural and philosophical (as early as 1600s) literature that refers to "the theory of structure" and "the structure of theory", respectively. The concept of architectonics has been adapted to advance the field of molecular self-assembly and termed as molecular architectonics. In essence, the methodology of organizing molecular units in the required and controlled configurations to develop advanced functional systems for materials and biological applications comprises the field of molecular architectonics. This concept of designing noncovalent systems enables to focus on different functional aspects of designer molecules for biological and nonbiological applications and also strengthens our efforts toward the mastery over the art of controlled molecular self-assemblies. Programming complex molecular interactions and assemblies for specific functions has been one of the most challenging tasks in the modern era. Meticulously ordered molecular assemblies can impart remarkable developments in several areas spanning energy, health, and environment. For example, the well-defined nano-, micro-, and macroarchitectures of functional molecules with specific molecular ordering possess potential applications in flexible electronics, photovoltaics, photonic crystals, microreactors, sensors, drug delivery, biomedicine, and superhydrophobic coatings, among others. The functional molecular architectures having unparalleled properties are widely evident in various designs of Nature. By drawing inspirations from Nature, intended molecular architectures can be designed and developed to harvest various functions, as there is an inexhaustible resource and scope. In this Account, we present exquisite designer molecules developed by our group and others with an objective to master the art of molecular recognition and self-assembly for functional applications. We demonstrate the tailor-ability of molecular self-assemblies by employing biomolecules like amino acids and nucleobases as auxiliaries. Naphthalenediimide (NDI), perylenediimide (PDI), and few other molecular systems serve as functional modules. The effects of stereochemistry and minute structural modifications in the molecular designs on the supramolecular interactions, and construction of self-assembled zero-dimensional (OD), one-dimensional (1D), and two-dimensional (2D) nano- and microarchitectures like particles, spheres, cups, bowls, fibers, belts, helical belts, supercoiled helices, sheets, fractals, and honeycomb-like arrays are discussed in extensive detail. Additionally, we present molecular systems that showcase the elegant designs of coassembly, templated assembly, hierarchical assembly, transient self-assembly, chiral denaturation, retentive helical memory, self-replication, supramolecular regulation, supramolecular speciation, supernon linearity, dynamic pathway complexity, supramolecular heterojunction, living supramolecular polymerization, and molecular machines. Finally, we describe the molecular engineering principles learnt over the years that have led to several applications, namely, organic electronics, self-cleaning, high-mechanical strength, and tissue engineering.

Three Dimensional Architecture of Membrane-Embedded MscS in the Closed Conformation

PubMed Central

Vásquez, Valeria; Sotomayor, Marcos; Cortes, D. Marien; Roux, Benoît; Schulten, Klaus; Perozo, Eduardo

2009-01-01

The mechanosensitive channel of small conductance (MscS) is part of a coordinated response to osmotic challenges in E. coli. MscS opens as a result of membrane tension changes, thereby releasing small solutes and effectively acting as an osmotic safety valve. Both, the functional state depicted by its crystal structure and its gating mechanism remain unclear. Here, we combine site-directed spin labeling, electron paramagnetic resonance (EPR) spectroscopy, and molecular dynamics simulations with novel energy restraints based on experimental EPR data to investigate the native transmembrane and periplasmic molecular architecture of closed MscS in a lipid bilayer. In the closed conformation, MscS shows a more compact transmembrane domain than in the crystal structure, characterized by a realignment of the transmembrane segments towards the normal of the membrane. The previously unresolved NH2-terminus forms a short helical hairpin capping the extracellular ends of TM1 and TM2 and in close interaction with the bilayer interface. The present three-dimensional model of membrane-embedded MscS in the closed state represents a key step in determining the molecular mechanism of MscS gating. PMID:18343404

Mechanical response of two polyimides through coarse-grained molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Sudarkodi, V.; Sooraj, K.; Nair, Nisanth N.; Basu, Sumit; Parandekar, Priya V.; Sinha, Nishant K.; Prakash, Om; Tsotsis, Tom

2018-03-01

Coarse-grained molecular dynamics (MD) simulations allow us to predict the mechanical responses of polymers, starting merely with a description of their molecular architectures. It is interesting to ask whether, given two competing molecular architectures, coarse-grained MD simulations can predict the differences that can be expected in their mechanical responses. We have studied two crosslinked polyimides PMR15 and HFPE52—both used in high- temperature applications—to assess whether the subtle differences in their uniaxial stress-strain responses, revealed by experiments, can be reproduced by carefully coarse-grained MD models. The coarse graining procedure for PMR15 is outlined in this work, while the coarse grain forcefields for HFPE52 are borrowed from an earlier one (Pandiyan et al 2015 Macromol. Theory Simul. 24 513-20). We show that the stress-strain responses of both these polyimides are qualitatively reproduced, and important insights into their deformation and failure mechanisms are obtained. More importantly, the differences in the molecular architecture between the polyimides carry over to the differences in the stress-strain responses in a manner that parallels the experimental results. A critical assessment of the successes and shortcomings of predicting mechanical responses through coarse-grained MD simulations has been made.

Architecture of a Diels-Alderase ribozyme with a preformed catalytic pocket.

PubMed

Keiper, Sonja; Bebenroth, Dirk; Seelig, Burckhard; Westhof, Eric; Jäschke, Andres

2004-09-01

Artificial ribozymes catalyze a variety of chemical reactions. Their structures and reaction mechanisms are largely unknown. We have analyzed a ribozyme catalyzing Diels-Alder cycloaddition reactions by comprehensive mutation analysis and a variety of probing techniques. New tertiary interactions involving base pairs between nucleotides of the 5' terminus and a large internal loop forming a pseudoknot fold were identified. The probing data indicate a preformed tertiary structure that shows no major changes on substrate or product binding. Based on these observations, a molecular architecture featuring a Y-shaped arrangement is proposed. The tertiary structure is formed in a rather unusual way; that is, the opposite sides of the asymmetric internal loop are clamped by the four 5'-terminal nucleotides, forming two adjacent two base-pair helices. It is proposed that the catalytic pocket is formed by a wedge within one of these helices.

Bisphenol A (BPA) binding on full-length architectures of estrogen receptor.

PubMed

Liu, Yaquan; Qu, Kaili; Hai, Ying; Zhao, Chunyan

2018-08-01

Previous research has shown that the major toxicity mechanism for many environment chemicals is binding with estrogen receptor (ER) and blocking endogenous estrogen access, including bisphenol A (BPA). However, the molecular level understanding the global consequence of BPA binding on the full-length architectures of ER is largely unknown, which is a necessary stage to evaluate estrogen-like toxicity of BPA. In the present work, the consequence of BPA on full-length architectures of ER was firstly modeled based on molecular dynamics, focusing on the cross communication between multi-domains including ligand binding domain (LBD) and DNA binding domain (DBD). The study proved consequence of BPA upon full-length ER structure was dependent on long-range communications between multiple protein domains. The allosteric effects occurring in LBD units could alter dimerization formation through a crucial change in residue-residue connections, which resulted in relaxation of DBD. It indicated BPA could present consequence on the full-size receptor, not only on the separate domains, but also on the cross communication among LBD, DBD, and DNA molecules. It might provide detailed insight into the knowledge about the structural characteristics of ER and its role in gene regulation, which eventually helped us evaluate the estrogen-like toxicity upon BPA binding with full-length ER. © 2018 Wiley Periodicals, Inc.

Predicting chromatin architecture from models of polymer physics.

PubMed

Bianco, Simona; Chiariello, Andrea M; Annunziatella, Carlo; Esposito, Andrea; Nicodemi, Mario

2017-03-01

We review the picture of chromatin large-scale 3D organization emerging from the analysis of Hi-C data and polymer modeling. In higher mammals, Hi-C contact maps reveal a complex higher-order organization, extending from the sub-Mb to chromosomal scales, hierarchically folded in a structure of domains-within-domains (metaTADs). The domain folding hierarchy is partially conserved throughout differentiation, and deeply correlated to epigenomic features. Rearrangements in the metaTAD topology relate to gene expression modifications: in particular, in neuronal differentiation models, topologically associated domains (TADs) tend to have coherent expression changes within architecturally conserved metaTAD niches. To identify the nature of architectural domains and their molecular determinants within a principled approach, we discuss models based on polymer physics. We show that basic concepts of interacting polymer physics explain chromatin spatial organization across chromosomal scales and cell types. The 3D structure of genomic loci can be derived with high accuracy and its molecular determinants identified by crossing information with epigenomic databases. In particular, we illustrate the case of the Sox9 locus, linked to human congenital disorders. The model in-silico predictions on the effects of genomic rearrangements are confirmed by available 5C data. That can help establishing new diagnostic tools for diseases linked to chromatin mis-folding, such as congenital disorders and cancer.

Membrane-Based Gas Separation Accelerated by Hollow Nanosphere Architectures

DOE PAGES

Zhang, Jinshui; Schott, Jennifer Ann; Univ. of Tennessee, Knoxville, TN; ...

2016-11-15

We report that the coupling of hollow carbon nanospheres with triblock copolymers is a promising strategy to fabricate mixed-matrix membranes, because the symmetric microporous shells combine with the hollow space to promote gas transport and the unique soft-rigid molecular structure of triblock copolymers can accommodate a high loading of fillers without a significant loss of mechanical strength.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ozolins, Vidvuds

Molecularly Engineered Energy Materials (MEEM) was established as an interdisciplinary cutting-edge UCLA-based research center uniquely equipped to attack the challenge of rationally designing, synthesizing and testing revolutionary new energy materials. Our mission was to achieve transformational improvements in the performance of materials via controlling the nano-and mesoscale structure using selectively designed, earth-abundant, inexpensive molecular building blocks. MEEM has focused on materials that are inherently abundant, can be easily assembled from intelligently designed building blocks (molecules, nanoparticles), and have the potential to deliver transformative economic benefits in comparison with the current crystalline-and polycrystalline-based energy technologies. MEEM addressed basic science issues relatedmore » to the fundamental mechanisms of carrier generation, energy conversion, as well as transport and storage of charge and mass in tunable, architectonically complex materials. Fundamental understanding of these processes will enable rational design, efficient synthesis and effective deployment of novel three-dimensional material architectures for energy applications. Three interrelated research directions were initially identified where these novel architectures hold great promise for high-reward research: solar energy generation, electrochemical energy storage, and materials for CO 2 capture. Of these, the first two remained throughout the project performance period, while carbon capture was been phased out in consultation and with approval from BES program manager.« less

Molecular Architecture of Full-length TRF1 Favors Its Interaction with DNA*

PubMed Central

Boskovic, Jasminka; Martinez-Gago, Jaime; Mendez-Pertuz, Marinela; Buscato, Alberto; Martinez-Torrecuadrada, Jorge Luis; Blasco, Maria A.

2016-01-01

Telomeres are specific DNA-protein structures found at both ends of eukaryotic chromosomes that protect the genome from degradation and from being recognized as double-stranded breaks. In vertebrates, telomeres are composed of tandem repeats of the TTAGGG sequence that are bound by a six-subunit complex called shelterin. Molecular mechanisms of telomere functions remain unknown in large part due to lack of structural data on shelterins, shelterin complex, and its interaction with the telomeric DNA repeats. TRF1 is one of the best studied shelterin components; however, the molecular architecture of the full-length protein remains unknown. We have used single-particle electron microscopy to elucidate the structure of TRF1 and its interaction with telomeric DNA sequence. Our results demonstrate that full-length TRF1 presents a molecular architecture that assists its interaction with telometic DNA and at the same time makes TRFH domains accessible to other TRF1 binding partners. Furthermore, our studies suggest hypothetical models on how other proteins as TIN2 and tankyrase contribute to regulate TRF1 function. PMID:27563064

Correlation dynamics and enhanced signals for the identification of serial biomolecules and DNA bases.

PubMed

Ahmed, Towfiq; Haraldsen, Jason T; Rehr, John J; Di Ventra, Massimiliano; Schuller, Ivan; Balatsky, Alexander V

2014-03-28

Nanopore-based sequencing has demonstrated a significant potential for the development of fast, accurate, and cost-efficient fingerprinting techniques for next generation molecular detection and sequencing. We propose a specific multilayered graphene-based nanopore device architecture for the recognition of single biomolecules. Molecular detection and analysis can be accomplished through the detection of transverse currents as the molecule or DNA base translocates through the nanopore. To increase the overall signal-to-noise ratio and the accuracy, we implement a new 'multi-point cross-correlation' technique for identification of DNA bases or other molecules on the single molecular level. We demonstrate that the cross-correlations between each nanopore will greatly enhance the transverse current signal for each molecule. We implement first-principles transport calculations for DNA bases surveyed across a multilayered graphene nanopore system to illustrate the advantages of the proposed geometry. A time-series analysis of the cross-correlation functions illustrates the potential of this method for enhancing the signal-to-noise ratio. This work constitutes a significant step forward in facilitating fingerprinting of single biomolecules using solid state technology.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, Huajuan; Zhao, Yanbao, E-mail: zhaoyb902@henu.edu.cn; Sun, Lei

Graphical abstract: A simple method for the synthesis of novel micrometer flower-like Cu/PVP architectures was introduced. Highlights: {yields} Micrometer flower-like copper/polyvinylpyrrolidone architectures were obtained by a simple chemical route. {yields} The amount of N{sub 2}H{sub 4}{center_dot}H{sub 2}O, the reaction temperature, the molar ratio of CuCl{sub 2} to PVP and different molecular weights of PVP play an important role in the controlling the morphology of the Cu/PVP architectures. {yields} A possible mechanism of the formation of Cu/PVP architectures was discussed. -- Abstract: Micrometer-sized flower-like Cu/polyvinylpyrrolidone (PVP) architectures are synthesized by the reduction of copper (II) salt with hydrazine hydrate in aqueousmore » solution in the presence of PVP capping agent. The resulting Cu/PVP architectures are investigated by UV-vis spectroscopy, transmission electron microscopy (TEM), X-ray powder diffraction (XRD), and scanning electron microscopy (SEM). The Cu/PVP flowers have uniform morphologies with an average diameter of 10 {mu}m, made of several intercrossing plates. The formation of Cu/PVP flowers is a new kinetic control process, and the factors such as the amount of N{sub 2}H{sub 4}{center_dot}H{sub 2}O, reaction temperature, molar ratio of CuCl{sub 2} to PVP and molecular weight of PVP have significant effect on the morphology of Cu/PVP architectures. A possible mechanism of the formation of micrometer Cu/PVP architectures was discussed.« less

Molecular engineering of colloidal liquid crystals using DNA origami

NASA Astrophysics Data System (ADS)

Siavashpouri, Mahsa; Wachauf, Christian; Zakhary, Mark; Praetorius, Florian; Dietz, Hendrik; Dogic, Zvonimir

Understanding the microscopic origin of cholesteric phase remains a foundational, yet unresolved problem in the field of liquid crystals. Lack of experimental model system that allows for the systematic control of the microscopic chiral structure makes it difficult to investigate this problem for several years. Here, using DNA origami technology, we systematically vary the chirality of the colloidal particles with molecular precision and establish a quantitative relationship between the microscopic structure of particles and the macroscopic cholesteric pitch. Our study presents a new methodology for predicting bulk behavior of diverse phases based on the microscopic architectures of the constituent molecules.

Architecture of Eph receptor clusters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Himanen, Juha P.; Yermekbayeva, Laila; Janes, Peter W.

2010-10-04

Eph receptor tyrosine kinases and their ephrin ligands regulate cell navigation during normal and oncogenic development. Signaling of Ephs is initiated in a multistep process leading to the assembly of higher-order signaling clusters that set off bidirectional signaling in interacting cells. However, the structural and mechanistic details of this assembly remained undefined. Here we present high-resolution structures of the complete EphA2 ectodomain and complexes with ephrin-A1 and A5 as the base unit of an Eph cluster. The structures reveal an elongated architecture with novel Eph/Eph interactions, both within and outside of the Eph ligand-binding domain, that suggest the molecular mechanismmore » underlying Eph/ephrin clustering. Structure-function analysis, by using site-directed mutagenesis and cell-based signaling assays, confirms the importance of the identified oligomerization interfaces for Eph clustering.« less

Enumeration of virtual libraries of combinatorial modular macrocyclic (bracelet, necklace) architectures and their linear counterparts.

PubMed

Taniguchi, Masahiko; Du, Hai; Lindsey, Jonathan S

2013-09-23

A wide variety of cyclic molecular architectures are built of modular subunits and can be formed combinatorially. The mathematics for enumeration of such objects is well-developed yet lacks key features of importance in chemistry, such as specifying (i) the structures of individual members among a set of isomers, (ii) the distribution (i.e., relative amounts) of products, and (iii) the effect of nonequal ratios of reacting monomers on the product distribution. Here, a software program (Cyclaplex) has been developed to determine the number, identity (including isomers), and relative amounts of linear and cyclic architectures from a given number and ratio of reacting monomers. The program includes both mathematical formulas and generative algorithms for enumeration; the latter go beyond the former to provide desired molecular-relevant information and data-mining features. The program is equipped to enumerate four types of architectures: (i) linear architectures with directionality (macroscopic equivalent = electrical extension cords), (ii) linear architectures without directionality (batons), (iii) cyclic architectures with directionality (necklaces), and (iv) cyclic architectures without directionality (bracelets). The program can be applied to cyclic peptides, cycloveratrylenes, cyclens, calixarenes, cyclodextrins, crown ethers, cucurbiturils, annulenes, expanded meso-substituted porphyrin(ogen)s, and diverse supramolecular (e.g., protein) assemblies. The size of accessible architectures encompasses up to 12 modular subunits derived from 12 reacting monomers or larger architectures (e.g. 13-17 subunits) from fewer types of monomers (e.g. 2-4). A particular application concerns understanding the possible heterogeneity of (natural or biohybrid) photosynthetic light-harvesting oligomers (cyclic, linear) formed from distinct peptide subunits.

ls1 mardyn: The Massively Parallel Molecular Dynamics Code for Large Systems.

PubMed

Niethammer, Christoph; Becker, Stefan; Bernreuther, Martin; Buchholz, Martin; Eckhardt, Wolfgang; Heinecke, Alexander; Werth, Stephan; Bungartz, Hans-Joachim; Glass, Colin W; Hasse, Hans; Vrabec, Jadran; Horsch, Martin

2014-10-14

The molecular dynamics simulation code ls1 mardyn is presented. It is a highly scalable code, optimized for massively parallel execution on supercomputing architectures and currently holds the world record for the largest molecular simulation with over four trillion particles. It enables the application of pair potentials to length and time scales that were previously out of scope for molecular dynamics simulation. With an efficient dynamic load balancing scheme, it delivers high scalability even for challenging heterogeneous configurations. Presently, multicenter rigid potential models based on Lennard-Jones sites, point charges, and higher-order polarities are supported. Due to its modular design, ls1 mardyn can be extended to new physical models, methods, and algorithms, allowing future users to tailor it to suit their respective needs. Possible applications include scenarios with complex geometries, such as fluids at interfaces, as well as nonequilibrium molecular dynamics simulation of heat and mass transfer.

Molecularly Engineered Polymer-Based Systems in Drug Delivery and Regenerative Medicine.

PubMed

Piluso, Susanna; Soultan, Al Halifa; Patterson, Jennifer

2017-01-01

Polymer-based systems are attractive in drug delivery and regenerative medicine due to the possibility of tailoring their properties and functions to a specific application. The present review provides several examples of molecularly engineered polymer systems, including stimuli responsive polymers and supramolecular polymers. The advent of controlled polymerization techniques has enabled the preparation of polymers with controlled molecular weight and well-defined architecture. By using these techniques coupled to orthogonal chemical modification reactions, polymers can be molecularly engineered to incorporate functional groups able to respond to small changes in the local environment or to a specific biological signal. This review highlights the properties and applications of stimuli-responsive systems and polymer therapeutics, such as polymer-drug conjugates, polymer-protein conjugates, polymersomes, and hyperbranched systems. The applications of polymeric membranes in regenerative medicine are also discussed. The examples presented in this review suggest that the combination of membranes with polymers that are molecularly engineered to respond to specific biological functions could be relevant in the field of regenerative medicine. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

MOF-Based Membrane Encapsulated ZnO Nanowires for Enhanced Gas Sensor Selectivity.

PubMed

Drobek, Martin; Kim, Jae-Hun; Bechelany, Mikhael; Vallicari, Cyril; Julbe, Anne; Kim, Sang Sub

2016-04-06

Gas sensors are of a great interest for applications including toxic or explosive gases detection in both in-house and industrial environments, air quality monitoring, medical diagnostics, or control of food/cosmetic properties. In the area of semiconductor metal oxides (SMOs)-based sensors, a lot of effort has been devoted to improve the sensing characteristics. In this work, we report on a general methodology for improving the selectivity of SMOx nanowires sensors, based on the coverage of ZnO nanowires with a thin ZIF-8 molecular sieve membrane. The optimized ZnO@ZIF-8-based nanocomposite sensor shows markedly selective response to H2 in comparison with the pristine ZnO nanowires sensor, while showing the negligible sensing response to C7H8 and C6H6. This original MOF-membrane encapsulation strategy applied to nanowires sensor architecture pave the way for other complex 3D architectures and various types of applications requiring either gas or ion selectivity, such as biosensors, photo(catalysts), and electrodes.

Integrated Genomic and Network-Based Analyses of Complex Diseases and Human Disease Network.

PubMed

Al-Harazi, Olfat; Al Insaif, Sadiq; Al-Ajlan, Monirah A; Kaya, Namik; Dzimiri, Nduna; Colak, Dilek

2016-06-20

A disease phenotype generally reflects various pathobiological processes that interact in a complex network. The highly interconnected nature of the human protein interaction network (interactome) indicates that, at the molecular level, it is difficult to consider diseases as being independent of one another. Recently, genome-wide molecular measurements, data mining and bioinformatics approaches have provided the means to explore human diseases from a molecular basis. The exploration of diseases and a system of disease relationships based on the integration of genome-wide molecular data with the human interactome could offer a powerful perspective for understanding the molecular architecture of diseases. Recently, subnetwork markers have proven to be more robust and reliable than individual biomarker genes selected based on gene expression profiles alone, and achieve higher accuracy in disease classification. We have applied one of these methodologies to idiopathic dilated cardiomyopathy (IDCM) data that we have generated using a microarray and identified significant subnetworks associated with the disease. In this paper, we review the recent endeavours in this direction, and summarize the existing methodologies and computational tools for network-based analysis of complex diseases and molecular relationships among apparently different disorders and human disease network. We also discuss the future research trends and topics of this promising field. Copyright © 2015 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

Nanotubule and Tour Molecule Based Molecular Electronics: Suggestion for a Hybrid Approach

NASA Technical Reports Server (NTRS)

Srivastava, Deepak; Saini, Subhash (Technical Monitor)

1998-01-01

Recent experimental and theoretical attempts and results indicate two distinct broad pathways towards future molecular electronic devices and architectures. The first is the approach via Tour type ladder molecules and their junctions which can be fabricated with solution phase chemical approaches. Second are fullerenes or nanotubules and their junctions which may have better conductance, switching and amplifying characteristics but can not be made through well controlled and defined chemical means. A hybrid approach combining the two pathways to take advantage of the characteristics of both is suggested. Dimension and scale of such devices would be somewhere in between isolated molecule and nanotubule based devices but it maybe possible to use self-assembly towards larger functional and logicalunits.

Structural DNA Nanotechnology: State of the Art and Future Perspective

PubMed Central

2015-01-01

Over the past three decades DNA has emerged as an exceptional molecular building block for nanoconstruction due to its predictable conformation and programmable intra- and intermolecular Watson–Crick base-pairing interactions. A variety of convenient design rules and reliable assembly methods have been developed to engineer DNA nanostructures of increasing complexity. The ability to create designer DNA architectures with accurate spatial control has allowed researchers to explore novel applications in many directions, such as directed material assembly, structural biology, biocatalysis, DNA computing, nanorobotics, disease diagnosis, and drug delivery. This Perspective discusses the state of the art in the field of structural DNA nanotechnology and presents some of the challenges and opportunities that exist in DNA-based molecular design and programming. PMID:25029570

Pathogenesis of Acute and Delayed Corneal Lesions After Ocular Exposure to Sulfur Mustard Vapor

DTIC Science & Technology

2012-03-01

using a vapor cup delivery system. The transition from acute to delayed injury was characterized by clinical, histological, and ultrastructural metrics...These data demonstrate a system-based approach combining ultrastructural analysis , histochemistry, and molecular evaluation that links architectural...predictive of the 11% of corneas that underwent asymptomatic recovery. Ultrastructural comparison of asymptomatic and MGK corneas at 8 weeks indicates that MGK

Statistical Analysis of the Processes Controlling Choline and Ethanolamine Glycerophospholipid Molecular Species Composition

PubMed Central

Kiebish, Michael A.; Yang, Kui; Han, Xianlin; Gross, Richard W.; Chuang, Jeffrey

2012-01-01

The regulation and maintenance of the cellular lipidome through biosynthetic, remodeling, and catabolic mechanisms are critical for biological homeostasis during development, health and disease. These complex mechanisms control the architectures of lipid molecular species, which have diverse yet highly regulated fatty acid chains at both the sn1 and sn2 positions. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) serve as the predominant biophysical scaffolds in membranes, acting as reservoirs for potent lipid signals and regulating numerous enzymatic processes. Here we report the first rigorous computational dissection of the mechanisms influencing PC and PE molecular architectures from high-throughput shotgun lipidomic data. Using novel statistical approaches, we have analyzed multidimensional mass spectrometry-based shotgun lipidomic data from developmental mouse heart and mature mouse heart, lung, brain, and liver tissues. We show that in PC and PE, sn1 and sn2 positions are largely independent, though for low abundance species regulatory processes may interact with both the sn1 and sn2 chain simultaneously, leading to cooperative effects. Chains with similar biochemical properties appear to be remodeled similarly. We also see that sn2 positions are more regulated than sn1, and that PC exhibits stronger cooperative effects than PE. A key aspect of our work is a novel statistically rigorous approach to determine cooperativity based on a modified Fisher's exact test using Markov Chain Monte Carlo sampling. This computational approach provides a novel tool for developing mechanistic insight into lipidomic regulation. PMID:22662143

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Jinshui; Qiao, Zhenan -An; Mahurin, Shannon Mark

A soft chemistry synthetic strategy based on a Friedel Crafts alkylation reaction is developed for the textural engineering of phenolic resin (PR) with a robust mesoporous framework to avoid serious framework shrinkage and maximize retention of organic functional moieties. By taking advantage of the structural benefits of molecular bridges, the resultant sample maintains a bimodal micro-mesoporous architecture with well-preserved organic functional groups, which is effective for carbon capture. Furthermore, this soft chemistry synthetic protocol can be further extended to nanotexture other aromatic-based polymers with robust frameworks.

Density functional study of molecular interactions in secondary structures of proteins.

PubMed

Takano, Yu; Kusaka, Ayumi; Nakamura, Haruki

2016-01-01

Proteins play diverse and vital roles in biology, which are dominated by their three-dimensional structures. The three-dimensional structure of a protein determines its functions and chemical properties. Protein secondary structures, including α-helices and β-sheets, are key components of the protein architecture. Molecular interactions, in particular hydrogen bonds, play significant roles in the formation of protein secondary structures. Precise and quantitative estimations of these interactions are required to understand the principles underlying the formation of three-dimensional protein structures. In the present study, we have investigated the molecular interactions in α-helices and β-sheets, using ab initio wave function-based methods, the Hartree-Fock method (HF) and the second-order Møller-Plesset perturbation theory (MP2), density functional theory, and molecular mechanics. The characteristic interactions essential for forming the secondary structures are discussed quantitatively.

A refined model of claudin-15 tight junction paracellular architecture by molecular dynamics simulations

PubMed Central

Alberini, Giulio; Benfenati, Fabio

2017-01-01

Tight-junctions between epithelial cells of biological barriers are specialized molecular structures that regulate the flux of solutes across the barrier, parallel to cell walls. The tight-junction backbone is made of strands of transmembrane proteins from the claudin family, but the molecular mechanism of its function is still not completely understood. Recently, the crystal structure of a mammalian claudin-15 was reported, displaying for the first time the detailed features of transmembrane and extracellular domains. Successively, a structural model of claudin-15-based paracellular channels has been proposed, suggesting a putative assembly that illustrates how claudins associate in the same cell (via cis interactions) and across adjacent cells (via trans interactions). Although very promising, the model offers only a static conformation, with residues missing in the most important extracellular regions and potential steric clashes. Here we present detailed atomic models of paracellular single and double pore architectures, obtained from the putative assembly and refined via structural modeling and all-atom molecular dynamics simulations in double membrane bilayer and water environment. Our results show an overall stable configuration of the complex with a fluctuating pore size. Extracellular residue loops in trans interaction are able to form stable contacts and regulate the size of the pore, which displays a stationary radius of 2.5–3.0 Å at the narrowest region. The side-by-side interactions of the cis configuration are preserved via stable hydrogen bonds, already predicted by cysteine crosslinking experiments. Overall, this work introduces an improved version of the claudin-15-based paracellular channel model that strengthens its validity and that can be used in further computational studies to understand the structural features of tight-junctions regulation. PMID:28863193

Genome-Wide Binding Analysis of the Transcription Activator IDEAL PLANT ARCHITECTURE1 Reveals a Complex Network Regulating Rice Plant Architecture[W

PubMed Central

Lu, Zefu; Yu, Hong; Xiong, Guosheng; Wang, Jing; Jiao, Yongqing; Liu, Guifu; Jing, Yanhui; Meng, Xiangbing; Hu, Xingming; Qian, Qian; Fu, Xiangdong; Wang, Yonghong; Li, Jiayang

2013-01-01

IDEAL PLANT ARCHITECTURE1 (IPA1) is critical in regulating rice (Oryza sativa) plant architecture and substantially enhances grain yield. To elucidate its molecular basis, we first confirmed IPA1 as a functional transcription activator and then identified 1067 and 2185 genes associated with IPA1 binding sites in shoot apices and young panicles, respectively, through chromatin immunoprecipitation sequencing assays. The SQUAMOSA PROMOTER BINDING PROTEIN-box direct binding core motif GTAC was highly enriched in IPA1 binding peaks; interestingly, a previously uncharacterized indirect binding motif TGGGCC/T was found to be significantly enriched through the interaction of IPA1 with proliferating cell nuclear antigen PROMOTER BINDING FACTOR1 or PROMOTER BINDING FACTOR2. Genome-wide expression profiling by RNA sequencing revealed IPA1 roles in diverse pathways. Moreover, our results demonstrated that IPA1 could directly bind to the promoter of rice TEOSINTE BRANCHED1, a negative regulator of tiller bud outgrowth, to suppress rice tillering, and directly and positively regulate DENSE AND ERECT PANICLE1, an important gene regulating panicle architecture, to influence plant height and panicle length. The elucidation of target genes of IPA1 genome-wide will contribute to understanding the molecular mechanisms underlying plant architecture and to facilitating the breeding of elite varieties with ideal plant architecture. PMID:24170127

The molecular mechanism of plant gravitropism.

PubMed

Wu, Di; Huang, Lin-zhou; Gao, Jin; Wang, Yong-hong

2016-07-20

Gravity is an important environmental factor that regulates plant growth and morphogenesis. In response to gravity stimulus, plants can set the optimum angle between the organs and the gravity vector. Plant gravitropism is divided into four sequential steps, including gravity perception, signal transduction, asymmetrical distribution of auxin, and organ curvature. In recent years, large numbers of mutants with defective gravitropism have been identified and genes involved in the regulation of gravitropism have been functionally characterized. In particular, progress has been achieved on elucidating the molecular mechanisms of gravity perception and asymmetrical distribution of auxin. As one of the most important strategies for plant to adapt environmental changes, gravitropism is also involved in the regulation of rice plant architecture and grain yield through modulating rice tiller angle. Therefore, the investigation of plant gravitropism not only contributes to decipher the regulatory mechanisms of plant growth and development, but also helps to guide the genetic improvement of crop architecture. However, the molecular mechanisms and regulatory network of gravitropism remain to be elusive. In this review, we focus on recent progress on elucidating molecular mechanisms underlying gravitropism and its involvement in regulating rice tiller angle, which is an important agronomic trait that determines rice plant architecture and thus grain yields.

Performance Evaluation of NWChem Ab-Initio Molecular Dynamics (AIMD) Simulations on the Intel® Xeon Phi™ Processor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bylaska, Eric J.; Jacquelin, Mathias; De Jong, Wibe A.

2017-10-20

Ab-initio Molecular Dynamics (AIMD) methods are an important class of algorithms, as they enable scientists to understand the chemistry and dynamics of molecular and condensed phase systems while retaining a first-principles-based description of their interactions. Many-core architectures such as the Intel® Xeon Phi™ processor are an interesting and promising target for these algorithms, as they can provide the computational power that is needed to solve interesting problems in chemistry. In this paper, we describe the efforts of refactoring the existing AIMD plane-wave method of NWChem from an MPI-only implementation to a scalable, hybrid code that employs MPI and OpenMP tomore » exploit the capabilities of current and future many-core architectures. We describe the optimizations required to get close to optimal performance for the multiplication of the tall-and-skinny matrices that form the core of the computational algorithm. We present strong scaling results on the complete AIMD simulation for a test case that simulates 256 water molecules and that strong-scales well on a cluster of 1024 nodes of Intel Xeon Phi processors. We compare the performance obtained with a cluster of dual-socket Intel® Xeon® E5–2698v3 processors.« less

Branched terthiophenes in organic electronics: from small molecules to polymers.

PubMed

Scheuble, Martin; Goll, Miriam; Ludwigs, Sabine

2015-01-01

A zoo of chemical structures is accessible when the branched unit 2,2':3',2″-terthiophene (3T) is included both in structurally well-defined small molecules and polymer-like architectures. The first part of this review article highlights literature on all-thiophene based branched oligomers including dendrimers as well as combinations of 3T-units with functional moieties for light-harvesting systems. Motivated by the perfectly branched macromolecular dendrimers both electropolymerization as well as chemical approaches are presented as methods for the preparation of branched polythiophenes with different branching densities. Structure-function relationships between the molecular architecture and optical and electronic properties are discussed throughout the article. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The effect of polymer architecture on the interdiffusion in thin polymer films

NASA Astrophysics Data System (ADS)

Caglayan, Ayse; Yuan, Guangcui; Satija, Sushil K.; Uhrig, David; Hong, Kunlun; Akgun, Bulent

Branched polymer chains have been traditionally used in industrial applications as additives. Recently they have found applications in electrochromic displays, lithography, biomedical coatings and targeting multidrug resistant bacteria. In some of these applications where they are confined in thin layers, it is important to understand the relation between the mobility and polymer chain architecture to optimize the processing conditions. Earlier interdiffusion measurements on linear and cyclic polymer chains demonstrated the key role of chain architecture on mobility. We have determined the vertical diffusion coefficients of the star polystyrene chains in thin films as a function of number of polymer arms, molecular weight per arm, and film thickness using neutron reflectivity (NR) and compare our results with linear chains of identical total molecular weight. Bilayer samples of 4-arm and 8-arm protonated polystyrenes (hPS) and deuterated polystyrenes (dPS) were used to elucidate the effect of polymer chain architecture on polymer diffusion. NR measurements indicate that the mobility of polymer chains in thin films get faster as the number of polymer arms increases and the arm molecular weight decreases. Both star polymers showed faster interdiffusion compared to their linear analog. Diffusion coefficient of branched PS chains has a weak dependence on the film thickness.

Metascalable molecular dynamics simulation of nano-mechano-chemistry

NASA Astrophysics Data System (ADS)

Shimojo, F.; Kalia, R. K.; Nakano, A.; Nomura, K.; Vashishta, P.

2008-07-01

We have developed a metascalable (or 'design once, scale on new architectures') parallel application-development framework for first-principles based simulations of nano-mechano-chemical processes on emerging petaflops architectures based on spatiotemporal data locality principles. The framework consists of (1) an embedded divide-and-conquer (EDC) algorithmic framework based on spatial locality to design linear-scaling algorithms, (2) a space-time-ensemble parallel (STEP) approach based on temporal locality to predict long-time dynamics, and (3) a tunable hierarchical cellular decomposition (HCD) parallelization framework to map these scalable algorithms onto hardware. The EDC-STEP-HCD framework exposes and expresses maximal concurrency and data locality, thereby achieving parallel efficiency as high as 0.99 for 1.59-billion-atom reactive force field molecular dynamics (MD) and 17.7-million-atom (1.56 trillion electronic degrees of freedom) quantum mechanical (QM) MD in the framework of the density functional theory (DFT) on adaptive multigrids, in addition to 201-billion-atom nonreactive MD, on 196 608 IBM BlueGene/L processors. We have also used the framework for automated execution of adaptive hybrid DFT/MD simulation on a grid of six supercomputers in the US and Japan, in which the number of processors changed dynamically on demand and tasks were migrated according to unexpected faults. The paper presents the application of the framework to the study of nanoenergetic materials: (1) combustion of an Al/Fe2O3 thermite and (2) shock initiation and reactive nanojets at a void in an energetic crystal.

Solid-state NMR Reveals the Carbon-based Molecular Architecture of Cryptococcus neoformans Fungal Eumelanins in the Cell Wall.

PubMed

Chatterjee, Subhasish; Prados-Rosales, Rafael; Itin, Boris; Casadevall, Arturo; Stark, Ruth E

2015-05-29

Melanin pigments protect against both ionizing radiation and free radicals and have potential soil remediation capabilities. Eumelanins produced by pathogenic Cryptococcus neoformans fungi are virulence factors that render the fungal cells resistant to host defenses and certain antifungal drugs. Because of their insoluble and amorphous characteristics, neither the pigment bonding framework nor the cellular interactions underlying melanization of C. neoformans have yielded to comprehensive molecular-scale investigation. This study used the C. neoformans requirement of exogenous obligatory catecholamine precursors for melanization to produce isotopically enriched pigment "ghosts" and applied 2D (13)C-(13)C correlation solid-state NMR to reveal the carbon-based architecture of intact natural eumelanin assemblies in fungal cells. We demonstrated that the aliphatic moieties of solid C. neoformans melanin ghosts include cell-wall components derived from polysaccharides and/or chitin that are associated proximally with lipid membrane constituents. Prior to development of the mature aromatic fungal pigment, these aliphatic moieties form a chemically resistant framework that could serve as the scaffold for melanin synthesis. The indole-based core aromatic moieties show interconnections that are consistent with proposed melanin structures consisting of stacked planar assemblies, which are associated spatially with the aliphatic scaffold. The pyrrole aromatic carbons of the pigments bind covalently to the aliphatic framework via glycoside or glyceride functional groups. These findings establish that the structure of the pigment assembly changes with time and provide the first biophysical information on the mechanism by which melanin is assembled in the fungal cell wall, offering vital insights that can advance the design of bioinspired conductive nanomaterials and novel therapeutics. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Molecular Innovation in Ciliates with Complex Genome Rearrangements

NASA Astrophysics Data System (ADS)

Neme, R.; Landweber, L. F.

2017-07-01

We study molecular innovation in several ciliate species with unique massive genome rearrangements to understand how a radically distinct genome architecture can shape the process of acquiring new functions, genes and structures.

XaNSoNS: GPU-accelerated simulator of diffraction patterns of nanoparticles

NASA Astrophysics Data System (ADS)

Neverov, V. S.

XaNSoNS is an open source software with GPU support, which simulates X-ray and neutron 1D (or 2D) diffraction patterns and pair-distribution functions (PDF) for amorphous or crystalline nanoparticles (up to ∼107 atoms) of heterogeneous structural content. Among the multiple parameters of the structure the user may specify atomic displacements, site occupancies, molecular displacements and molecular rotations. The software uses general equations nonspecific to crystalline structures to calculate the scattering intensity. It supports four major standards of parallel computing: MPI, OpenMP, Nvidia CUDA and OpenCL, enabling it to run on various architectures, from CPU-based HPCs to consumer-level GPUs.

Scale-space measures for graph topology link protein network architecture to function.

PubMed

Hulsman, Marc; Dimitrakopoulos, Christos; de Ridder, Jeroen

2014-06-15

The network architecture of physical protein interactions is an important determinant for the molecular functions that are carried out within each cell. To study this relation, the network architecture can be characterized by graph topological characteristics such as shortest paths and network hubs. These characteristics have an important shortcoming: they do not take into account that interactions occur across different scales. This is important because some cellular functions may involve a single direct protein interaction (small scale), whereas others require more and/or indirect interactions, such as protein complexes (medium scale) and interactions between large modules of proteins (large scale). In this work, we derive generalized scale-aware versions of known graph topological measures based on diffusion kernels. We apply these to characterize the topology of networks across all scales simultaneously, generating a so-called graph topological scale-space. The comprehensive physical interaction network in yeast is used to show that scale-space based measures consistently give superior performance when distinguishing protein functional categories and three major types of functional interactions-genetic interaction, co-expression and perturbation interactions. Moreover, we demonstrate that graph topological scale spaces capture biologically meaningful features that provide new insights into the link between function and protein network architecture. Matlab(TM) code to calculate the scale-aware topological measures (STMs) is available at http://bioinformatics.tudelft.nl/TSSA © The Author 2014. Published by Oxford University Press.

The semantic architecture of the World-Wide Molecular Matrix (WWMM)

PubMed Central

2011-01-01

The World-Wide Molecular Matrix (WWMM) is a ten year project to create a peer-to-peer (P2P) system for the publication and collection of chemical objects, including over 250, 000 molecules. It has now been instantiated in a number of repositories which include data encoded in Chemical Markup Language (CML) and linked by URIs and RDF. The technical specification and implementation is now complete. We discuss the types of architecture required to implement nodes in the WWMM and consider the social issues involved in adoption. PMID:21999475

The semantic architecture of the World-Wide Molecular Matrix (WWMM).

PubMed

Murray-Rust, Peter; Adams, Sam E; Downing, Jim; Townsend, Joe A; Zhang, Yong

2011-10-14

The World-Wide Molecular Matrix (WWMM) is a ten year project to create a peer-to-peer (P2P) system for the publication and collection of chemical objects, including over 250, 000 molecules. It has now been instantiated in a number of repositories which include data encoded in Chemical Markup Language (CML) and linked by URIs and RDF. The technical specification and implementation is now complete. We discuss the types of architecture required to implement nodes in the WWMM and consider the social issues involved in adoption.

φ-evo: A program to evolve phenotypic models of biological networks.

PubMed

Henry, Adrien; Hemery, Mathieu; François, Paul

2018-06-01

Molecular networks are at the core of most cellular decisions, but are often difficult to comprehend. Reverse engineering of network architecture from their functions has proved fruitful to classify and predict the structure and function of molecular networks, suggesting new experimental tests and biological predictions. We present φ-evo, an open-source program to evolve in silico phenotypic networks performing a given biological function. We include implementations for evolution of biochemical adaptation, adaptive sorting for immune recognition, metazoan development (somitogenesis, hox patterning), as well as Pareto evolution. We detail the program architecture based on C, Python 3, and a Jupyter interface for project configuration and network analysis. We illustrate the predictive power of φ-evo by first recovering the asymmetrical structure of the lac operon regulation from an objective function with symmetrical constraints. Second, we use the problem of hox-like embryonic patterning to show how a single effective fitness can emerge from multi-objective (Pareto) evolution. φ-evo provides an efficient approach and user-friendly interface for the phenotypic prediction of networks and the numerical study of evolution itself.

Polyphosphazene Based Star-Branched and Dendritic Molecular Brushes.

PubMed

Henke, Helena; Posch, Sandra; Brüggemann, Oliver; Teasdale, Ian

2016-05-01

A new synthetic procedure is described for the preparation of poly(organo)phosphazenes with star-branched and star dendritic molecular brush type structures, thus describing the first time it has been possible to prepare controlled, highly branched architectures for this type of polymer. Furthermore, as a result of the extremely high-arm density generated by the phosphazene repeat unit, the second-generation structures represent quite unique architectures for any type of polymer. Using two relativity straight forward iterative syntheses it is possible to prepare globular highly branched polymers with up to 30 000 functional end groups, while keeping relatively narrow polydispersities (1.2-1.6). Phosphine mediated polymerization of chlorophosphoranimine is first used to prepare three-arm star polymers. Subsequent substitution with diphenylphosphine moieties gives poly(organo)phosphazenes to function as multifunctional macroinitiators for the growth of a second generation of polyphosphazene arms. Macrosubstitution with Jeffamine oligomers gives a series of large, water soluble branched macromolecules with high-arm density and hydrodynamic diameters between 10 and 70 nm. © 2016 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Supramolecular architectures of iron phthalocyanine Langmuir-Blodgett films: The role played by the solution solvents

NASA Astrophysics Data System (ADS)

Rubira, Rafael Jesus Gonçalves; Aoki, Pedro Henrique Benites; Constantino, Carlos José Leopoldo; Alessio, Priscila

2017-09-01

The developing of organic-based devices has been widely explored using ultrathin films as the transducer element, whose supramolecular architecture plays a central role in the device performance. Here, Langmuir and Langmuir-Blodgett (LB) ultrathin films were fabricated from iron phthalocyanine (FePc) solutions in chloroform (CHCl3), dichloromethane (CH2Cl2), dimethylformamide (DMF), and tetrahydrofuran (THF) to determine the influence of different solvents on the supramolecular architecture of the ultrathin films. The UV-vis absorption spectroscopy shows a strong dependence of the FePc aggregation on these solvents. As a consequence, the surface pressure vs. mean molecular area (π-A) isotherms and Brewster angle microscopy (BAM) reveal a more homogeneous (surface morphology) Langmuir film at the air/water interface for FePc in DMF. The same morphological pattern observed for the Langmuir films is preserved upon LB deposition onto solid substrates. The Raman and FTIR analyses indicate the DMF-FePc interaction relies on coordination bonds between N atom (from DMF) and Fe atom (from FePc). Besides, the FePc molecular organization was also found to be affected by the DMF-FePc chemical interaction. It is interesting to note that, if the DMF-FePc leads to less aggregated FePc either in solution or ultrathin films (Langmuir and LB), with time (one week) the opposite trend is found. Taking into account the N-Fe interaction, the performance of the FePc ultrathin films with distinct supramolecular architectures composing sensing units was explored as proof-of-principle in the detection of trace amounts of atrazine herbicide in water using impedance spectroscopy. Further statistical and computational analysis reveal not only the role played by FePc supramolecular architecture but also the sensitivity of the system to detect atrazine solutions down to 10-10 mol/L, which is sufficient to monitor the quality of drinking water even according to the most stringent international regulations.

Structure and dynamics of the peptide strand KRFK from the thrombospondin TSP-1 in water.

PubMed

Taleb Bendiab, W; Benomrane, B; Bounaceur, B; Dauchez, M; Krallafa, A M

2018-02-14

Theoretical investigations of a solute in liquid water at normal temperature and pressure can be performed at different levels of theory. Static quantum calculations as well as classical and ab initio molecular dynamics are used to completely explore the conformational space for large solvated molecular systems. In the classical approach, it is essential to describe all of the interactions of the solute and the solvent in detail. Water molecules are very often described as rigid bodies when the most commonly used interaction potentials, such as the SPCE and the TIP4P models, are employed. Recently, a physical model based upon a cluster of rigid water molecules with a tetrahedral architecture (AB 4 ) was proposed that describes liquid water as a mixture of both TIP4P and SPCE molecular species that occur in the proportions implied by the tetrahedral architecture (one central molecule versus four outer molecules; i.e., 20% TIP4P versus 80% SPCE molecules). In this work, theoretical spectroscopic data for a peptide strand were correlated with the structural properties of the peptide strand solvated in water, based on data calculated using different theoretical approaches and physical models. We focused on a particular peptide strand, KRFK (lysine-arginine-phenylalanine-lysine), found in the thrombospondin TSP-1, due to its interesting properties. As the activity and electronic structure of this system is strongly linked to its structure, we correlated its structure with charge-density maps obtained using different semi-empirical charge Q eq equations. The structural and thermodynamic properties obtained from classical simulations were correlated with ab initio molecular dynamics (AIMD) data. Structural changes in the peptide strand were rationalized in terms of the motions of atoms and groups of atoms. To achieve this, conformational changes were investigated using calculated infrared spectra for the peptide in the gas phase and in water solvent. The calculated AIMD infrared spectrum for the peptide was correlated with static quantum calculations of the molecular system based on a harmonic approach as well as the VDOS (vibrational density of states) spectra obtained using various classical solvent models (SPCE, TIP4P, and AB 4 ) and charge maps.

Molecular Imaging Probe Development using Microfluidics

PubMed Central

Liu, Kan; Wang, Ming-Wei; Lin, Wei-Yu; Phung, Duy Linh; Girgis, Mark D.; Wu, Anna M.; Tomlinson, James S.; Shen, Clifton K.-F.

2012-01-01

In this manuscript, we review the latest advancement of microfluidics in molecular imaging probe development. Due to increasing needs for medical imaging, high demand for many types of molecular imaging probes will have to be met by exploiting novel chemistry/radiochemistry and engineering technologies to improve the production and development of suitable probes. The microfluidic-based probe synthesis is currently attracting a great deal of interest because of their potential to deliver many advantages over conventional systems. Numerous chemical reactions have been successfully performed in micro-reactors and the results convincingly demonstrate with great benefits to aid synthetic procedures, such as purer products, higher yields, shorter reaction times compared to the corresponding batch/macroscale reactions, and more benign reaction conditions. Several ‘proof-of-principle’ examples of molecular imaging probe syntheses using microfluidics, along with basics of device architecture and operation, and their potential limitations are discussed here. PMID:22977436

Ab Initio Reactive Computer Aided Molecular Design

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martínez, Todd J.

Few would dispute that theoretical chemistry tools can now provide keen insights into chemical phenomena. Yet the holy grail of efficient and reliable prediction of complex reactivity has remained elusive. Fortunately, recent advances in electronic structure theory based on the concepts of both element- and rank-sparsity, coupled with the emergence of new highly parallel computer architectures, have led to a significant increase in the time and length scales which can be simulated using first principles molecular dynamics. This then opens the possibility of new discovery-based approaches to chemical reactivity, such as the recently proposed ab initio nanoreactor. Here, we arguemore » that due to these and other recent advances, the holy grail of computational discovery for complex chemical reactivity is rapidly coming within our reach.« less

Ab Initio Reactive Computer Aided Molecular Design

DOE PAGES

Martínez, Todd J.

2017-03-21

Few would dispute that theoretical chemistry tools can now provide keen insights into chemical phenomena. Yet the holy grail of efficient and reliable prediction of complex reactivity has remained elusive. Fortunately, recent advances in electronic structure theory based on the concepts of both element- and rank-sparsity, coupled with the emergence of new highly parallel computer architectures, have led to a significant increase in the time and length scales which can be simulated using first principles molecular dynamics. This then opens the possibility of new discovery-based approaches to chemical reactivity, such as the recently proposed ab initio nanoreactor. Here, we arguemore » that due to these and other recent advances, the holy grail of computational discovery for complex chemical reactivity is rapidly coming within our reach.« less

Synthetic biology, inspired by synthetic chemistry.

PubMed

Malinova, V; Nallani, M; Meier, W P; Sinner, E K

2012-07-16

The topic synthetic biology appears still as an 'empty basket to be filled'. However, there is already plenty of claims and visions, as well as convincing research strategies about the theme of synthetic biology. First of all, synthetic biology seems to be about the engineering of biology - about bottom-up and top-down approaches, compromising complexity versus stability of artificial architectures, relevant in biology. Synthetic biology accounts for heterogeneous approaches towards minimal and even artificial life, the engineering of biochemical pathways on the organismic level, the modelling of molecular processes and finally, the combination of synthetic with nature-derived materials and architectural concepts, such as a cellular membrane. Still, synthetic biology is a discipline, which embraces interdisciplinary attempts in order to have a profound, scientific base to enable the re-design of nature and to compose architectures and processes with man-made matter. We like to give an overview about the developments in the field of synthetic biology, regarding polymer-based analogs of cellular membranes and what questions can be answered by applying synthetic polymer science towards the smallest unit in life, namely a cell. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Defining scaffold geometries for interacting with proteins: geometrical classification of secondary structure linking regions.

PubMed

Tran, Tran T; Kulis, Christina; Long, Steven M; Bryant, Darryn; Adams, Peter; Smythe, Mark L

2010-11-01

Medicinal chemists synthesize arrays of molecules by attaching functional groups to scaffolds. There is evidence suggesting that some scaffolds yield biologically active molecules more than others, these are termed privileged substructures. One role of the scaffold is to present its side-chains for molecular recognition, and biologically relevant scaffolds may present side-chains in biologically relevant geometries or shapes. Since drug discovery is primarily focused on the discovery of compounds that bind to proteinaceous targets, we have been deciphering the scaffold shapes that are used for binding proteins as they reflect biologically relevant shapes. To decipher the scaffold architecture that is important for binding protein surfaces, we have analyzed the scaffold architecture of protein loops, which are defined in this context as continuous four residue segments of a protein chain that are not part of an α-helix or β-strand secondary structure. Loops are an important molecular recognition motif of proteins. We have found that 39 clusters reflect the scaffold architecture of 89% of the 23,331 loops in the dataset, with average intra-cluster and inter-cluster RMSD of 0.47 and 1.91, respectively. These protein loop scaffolds all have distinct shapes. We have used these 39 clusters that reflect the scaffold architecture of protein loops as biological descriptors. This involved generation of a small dataset of scaffold-based peptidomimetics. We found that peptidomimetic scaffolds with reported biological activities matched loop scaffold geometries and those peptidomimetic scaffolds with no reported biologically activities did not. This preliminary evidence suggests that organic scaffolds with tight matches to the preferred loop scaffolds of proteins, implies the likelihood of the scaffold to be biologically relevant.

Defining scaffold geometries for interacting with proteins: geometrical classification of secondary structure linking regions

NASA Astrophysics Data System (ADS)

Tran, Tran T.; Kulis, Christina; Long, Steven M.; Bryant, Darryn; Adams, Peter; Smythe, Mark L.

2010-11-01

Medicinal chemists synthesize arrays of molecules by attaching functional groups to scaffolds. There is evidence suggesting that some scaffolds yield biologically active molecules more than others, these are termed privileged substructures. One role of the scaffold is to present its side-chains for molecular recognition, and biologically relevant scaffolds may present side-chains in biologically relevant geometries or shapes. Since drug discovery is primarily focused on the discovery of compounds that bind to proteinaceous targets, we have been deciphering the scaffold shapes that are used for binding proteins as they reflect biologically relevant shapes. To decipher the scaffold architecture that is important for binding protein surfaces, we have analyzed the scaffold architecture of protein loops, which are defined in this context as continuous four residue segments of a protein chain that are not part of an α-helix or β-strand secondary structure. Loops are an important molecular recognition motif of proteins. We have found that 39 clusters reflect the scaffold architecture of 89% of the 23,331 loops in the dataset, with average intra-cluster and inter-cluster RMSD of 0.47 and 1.91, respectively. These protein loop scaffolds all have distinct shapes. We have used these 39 clusters that reflect the scaffold architecture of protein loops as biological descriptors. This involved generation of a small dataset of scaffold-based peptidomimetics. We found that peptidomimetic scaffolds with reported biological activities matched loop scaffold geometries and those peptidomimetic scaffolds with no reported biologically activities did not. This preliminary evidence suggests that organic scaffolds with tight matches to the preferred loop scaffolds of proteins, implies the likelihood of the scaffold to be biologically relevant.

High-performance functional ecopolymers based on flora and fauna.

PubMed

Kaneko, Tatsuo

2007-01-01

Liquid crystalline (LC) polymers of rigid monomers based on flora and fauna were prepared by in-bulk polymerization. Para-coumaric (p-coumaric) acid [4-hydroxycinnamic acid (4HCA)] and its derivatives were selected as phytomonomers and bile acids were selected as biomonomers. The 4HCA homopolymer showed a thermotropic LC phase only in a state of low molecular weight. The copolymers of 4HCA with bile acids such as lithocholic acid (LCA) and cholic acid (CA) showed excellent cell compatibilities but low molecular weights. However, P(4HCA-co-CA)s allowed LC spinning to create molecularly oriented biofibers, presumably due to the chain entanglement that occurs during in-bulk chain propagation into hyperbranching architecture. P[4HCA-co-3,4-dihydroxycinnamic acid (DHCA)]s showed high molecular weight, high mechanical strength, high Young's modulus, and high softening temperature, which may be achieved through the entanglement by in-bulk formation of hyperbranching, rigid structures. P(4HCA-co-DHCA)s showed a smooth hydrolysis, in-soil degradation, and photo-tunable hydrolysis. Thus, P(4HCA-co-DHCA)s might be applied as an environmentally degradable plastic with extremely high performance.

Molecular structure of bottlebrush polymers in melts

PubMed Central

Paturej, Jarosław; Sheiko, Sergei S.; Panyukov, Sergey; Rubinstein, Michael

2016-01-01

Bottlebrushes are fascinating macromolecules that display an intriguing combination of molecular and particulate features having vital implications in both living and synthetic systems, such as cartilage and ultrasoft elastomers. However, the progress in practical applications is impeded by the lack of knowledge about the hierarchic organization of both individual bottlebrushes and their assemblies. We delineate fundamental correlations between molecular architecture, mesoscopic conformation, and macroscopic properties of polymer melts. Numerical simulations corroborate theoretical predictions for the effect of grafting density and side-chain length on the dimensions and rigidity of bottlebrushes, which effectively behave as a melt of flexible filaments. These findings provide quantitative guidelines for the design of novel materials that allow architectural tuning of their properties in a broad range without changing chemical composition. PMID:28861466

Crystal structure of an EfPDF complex with Met-Ala-Ser based on crystallographic packing.

PubMed

Nam, Ki Hyun; Kim, Kook-Han; Kim, Eunice Eun Kyeong; Hwang, Kwang Yeon

2009-04-17

PDF (peptide deformylase) plays a critical role in the production of mature proteins by removing the N-formyl polypeptide of nascent proteins in the prokaryote cell system. This protein is essential for bacterial growth, making it an attractive target for the design of new antibiotics. Accordingly, PDF has been evaluated as a drug target; however, architectural mechanism studies of PDF have not yet fully elucidated its molecular function. We recently reported the crystal structure of PDF produced by Enterococcus faecium [K.H. Nam, J.I. Ham, A. Priyadarshi, E.E. Kim, N. Chung, K.Y. Hwang, "Insight into the antibacterial drug design and architectural mechanism of peptide recognition from the E. faecium peptide deformylase structure", Proteins 74 (2009) 261-265]. Here, we present the crystal structure of the EfPDF complex with MAS (Met-Ser-Ala), thereby not only delineating the architectural mechanism for the recognition of mimic-peptides by N-terminal cleaved expression peptide, but also suggesting possible targets for rational design of antibacterial drugs. In addition to their implications for drug design, these structural studies will facilitate elucidation of the architectural mechanism responsible for the peptide recognition of PDF.

Modular architecture of protein binding units for designing properties of cellulose nanomaterials.

PubMed

Malho, Jani-Markus; Arola, Suvi; Laaksonen, Päivi; Szilvay, Géza R; Ikkala, Olli; Linder, Markus B

2015-10-05

Molecular biomimetic models suggest that proteins in the soft matrix of nanocomposites have a multimodular architecture. Engineered proteins were used together with nanofibrillated cellulose (NFC) to show how this type of architecture leads to function. The proteins consist of two cellulose-binding modules (CBM) separated by 12-, 24-, or 48-mer linkers. Engineering the linkers has a considerable effects on the interaction between protein and NFC in both wet colloidal state and a dry film. The protein optionally incorporates a multimerizing hydrophobin (HFB) domain connected by another linker. The modular structure explains effects in the hydrated gel state, as well as the deformation of composite materials through stress distribution and crosslinking. Based on this work, strategies can be suggested for tuning the mechanical properties of materials through the coupling of protein modules and their interlinking architectures. © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Network analyses based on comprehensive molecular interaction maps reveal robust control structures in yeast stress response pathways

PubMed Central

Kawakami, Eiryo; Singh, Vivek K; Matsubara, Kazuko; Ishii, Takashi; Matsuoka, Yukiko; Hase, Takeshi; Kulkarni, Priya; Siddiqui, Kenaz; Kodilkar, Janhavi; Danve, Nitisha; Subramanian, Indhupriya; Katoh, Manami; Shimizu-Yoshida, Yuki; Ghosh, Samik; Jere, Abhay; Kitano, Hiroaki

2016-01-01

Cellular stress responses require exquisite coordination between intracellular signaling molecules to integrate multiple stimuli and actuate specific cellular behaviors. Deciphering the web of complex interactions underlying stress responses is a key challenge in understanding robust biological systems and has the potential to lead to the discovery of targeted therapeutics for diseases triggered by dysregulation of stress response pathways. We constructed large-scale molecular interaction maps of six major stress response pathways in Saccharomyces cerevisiae (baker’s or budding yeast). Biological findings from over 900 publications were converted into standardized graphical formats and integrated into a common framework. The maps are posted at http://www.yeast-maps.org/yeast-stress-response/ for browse and curation by the research community. On the basis of these maps, we undertook systematic analyses to unravel the underlying architecture of the networks. A series of network analyses revealed that yeast stress response pathways are organized in bow–tie structures, which have been proposed as universal sub-systems for robust biological regulation. Furthermore, we demonstrated a potential role for complexes in stabilizing the conserved core molecules of bow–tie structures. Specifically, complex-mediated reversible reactions, identified by network motif analyses, appeared to have an important role in buffering the concentration and activity of these core molecules. We propose complex-mediated reactions as a key mechanism mediating robust regulation of the yeast stress response. Thus, our comprehensive molecular interaction maps provide not only an integrated knowledge base, but also a platform for systematic network analyses to elucidate the underlying architecture in complex biological systems. PMID:28725465

Density functional theory based study of molecular interactions, recognition, engineering, and quantum transport in π molecular systems.

PubMed

Cho, Yeonchoo; Cho, Woo Jong; Youn, Il Seung; Lee, Geunsik; Singh, N Jiten; Kim, Kwang S

2014-11-18

CONSPECTUS: In chemical and biological systems, various interactions that govern the chemical and physical properties of molecules, assembling phenomena, and electronic transport properties compete and control the microscopic structure of materials. The well-controlled manipulation of each component can allow researchers to design receptors or sensors, new molecular architectures, structures with novel morphology, and functional molecules or devices. In this Account, we describe the structures and electronic and spintronic properties of π-molecular systems that are important for controlling the architecture of a variety of carbon-based systems. Although DFT is an important tool for describing molecular interactions, the inability of DFT to accurately represent dispersion interactions has made it difficult to properly describe π-interactions. However, the recently developed dispersion corrections for DFT have allowed us to include these dispersion interactions cost-effectively. We have investigated noncovalent interactions of various π-systems including aromatic-π, aliphatic-π, and non-π systems based on dispersion-corrected DFT (DFT-D). In addition, we have addressed the validity of DFT-D compared with the complete basis set (CBS) limit values of coupled cluster theory with single, double, and perturbative triple excitations [CCSD(T)] and Møller-Plesset second order perturbation theory (MP2). The DFT-D methods are still unable to predict the correct ordering in binding energies within the benzene dimer and the cyclohexane dimer. Nevertheless, the overall DFT-D predicted binding energies are in reasonable agreement with the CCSD(T) results. In most cases, results using the B97-D3 method closely reproduce the CCSD(T) results with the optimized energy-fitting parameters. On the other hand, vdW-DF2 and PBE0-TS methods estimate the dispersion energies from the calculated electron density. In these approximations, the interaction energies around the equilibrium point are reasonably close to the CCSD(T) results but sometimes slightly deviate from them because interaction energies were not particularly optimized with parameters. Nevertheless, because the electron cloud deforms when neighboring atoms/ions induce an electric field, both vdW-DF2 and PBE0-TS seem to properly reproduce the resulting change of dispersion interaction. Thus, improvements are needed in both vdW-DF2 and PBE0-TS to better describe the interaction energies, while the B97-D3 method could benefit from the incorporation of polarization-driven energy changes that show highly anisotropic behavior. Although the current DFT-D methods need further improvement, DFT-D is very useful for computer-aided molecular design. We have used these newly developed DFT-D methods to calculate the interactions between graphene and DNA nucleobases. Using DFT-D, we describe the design of molecular receptors of π-systems, graphene based electronic devices, metalloporphyrin half-metal based spintronic devices as graphene nanoribbon (GNR) analogs, and graphene based molecular electronic devices for DNA sequencing. DFT-D has also helped us understand quantum phenomena in materials and devices of π-systems including graphene.

Hypercrosslinked phenolic polymers with well developed mesoporous frameworks

DOE PAGES

Zhang, Jinshui; Qiao, Zhenan -An; Mahurin, Shannon Mark; ...

2015-02-12

A soft chemistry synthetic strategy based on a Friedel Crafts alkylation reaction is developed for the textural engineering of phenolic resin (PR) with a robust mesoporous framework to avoid serious framework shrinkage and maximize retention of organic functional moieties. By taking advantage of the structural benefits of molecular bridges, the resultant sample maintains a bimodal micro-mesoporous architecture with well-preserved organic functional groups, which is effective for carbon capture. Furthermore, this soft chemistry synthetic protocol can be further extended to nanotexture other aromatic-based polymers with robust frameworks.

Functional Interfaces Constructed by Controlled/Living Radical Polymerization for Analytical Chemistry.

PubMed

Wang, Huai-Song; Song, Min; Hang, Tai-Jun

2016-02-10

The high-value applications of functional polymers in analytical science generally require well-defined interfaces, including precisely synthesized molecular architectures and compositions. Controlled/living radical polymerization (CRP) has been developed as a versatile and powerful tool for the preparation of polymers with narrow molecular weight distributions and predetermined molecular weights. Among the CRP system, atom transfer radical polymerization (ATRP) and reversible addition-fragmentation chain transfer (RAFT) are well-used to develop new materials for analytical science, such as surface-modified core-shell particles, monoliths, MIP micro- or nanospheres, fluorescent nanoparticles, and multifunctional materials. In this review, we summarize the emerging functional interfaces constructed by RAFT and ATRP for applications in analytical science. Various polymers with precisely controlled architectures including homopolymers, block copolymers, molecular imprinted copolymers, and grafted copolymers were synthesized by CRP methods for molecular separation, retention, or sensing. We expect that the CRP methods will become the most popular technique for preparing functional polymers that can be broadly applied in analytical chemistry.

Non-equilibrium responses of PFPE lubricants with various atomistic/molecular architecture at elevated temperature

NASA Astrophysics Data System (ADS)

Chung, Pil Seung; Song, Wonyup; Biegler, Lorenz T.; Jhon, Myung S.

2017-05-01

During the operation of hard disk drive (HDD), the perfluoropolyether (PFPE) lubricant experiences elastic or viscous shear/elongation deformations, which affect the performance and reliability of the HDD. Therefore, the viscoelastic responses of PFPE could provide a finger print analysis in designing optimal molecular architecture of lubricants to control the tribological phenomena. In this paper, we examine the rheological responses of PFPEs including storage (elastic) and loss (viscous) moduli (G' and G″) by monitoring the time-dependent-stress-strain relationship via non-equilibrium molecular dynamics simulations. We analyzed the rheological responses by using Cox-Merz rule, and investigated the molecular structural and thermal effects on the solid-like and liquid-like behaviors of PFPEs. The temperature dependence of the endgroup agglomeration phenomena was examined, where the functional endgroups are decoupled as the temperature increases. By analyzing the relaxation processes, the molecular rheological studies will provide the optimal lubricant selection criteria to enhance the HDD performance and reliability for the heat-assisted magnetic recording applications.

Nuclear Architecture Organized by Rif1 Underpins the Replication-Timing Program

PubMed Central

Foti, Rossana; Gnan, Stefano; Cornacchia, Daniela; Dileep, Vishnu; Bulut-Karslioglu, Aydan; Diehl, Sarah; Buness, Andreas; Klein, Felix A.; Huber, Wolfgang; Johnstone, Ewan; Loos, Remco; Bertone, Paul; Gilbert, David M.; Manke, Thomas; Jenuwein, Thomas; Buonomo, Sara C.B.

2016-01-01

Summary DNA replication is temporally and spatially organized in all eukaryotes, yet the molecular control and biological function of the replication-timing program are unclear. Rif1 is required for normal genome-wide regulation of replication timing, but its molecular function is poorly understood. Here we show that in mouse embryonic stem cells, Rif1 coats late-replicating domains and, with Lamin B1, identifies most of the late-replicating genome. Rif1 is an essential determinant of replication timing of non-Lamin B1-bound late domains. We further demonstrate that Rif1 defines and restricts the interactions between replication-timing domains during the G1 phase, thereby revealing a function of Rif1 as organizer of nuclear architecture. Rif1 loss affects both number and replication-timing specificity of the interactions between replication-timing domains. In addition, during the S phase, Rif1 ensures that replication of interacting domains is temporally coordinated. In summary, our study identifies Rif1 as the molecular link between nuclear architecture and replication-timing establishment in mammals. PMID:26725008

Super-resolution Imaging of Chemical Synapses in the Brain

PubMed Central

Dani, Adish; Huang, Bo; Bergan, Joseph; Dulac, Catherine; Zhuang, Xiaowei

2010-01-01

Determination of the molecular architecture of synapses requires nanoscopic image resolution and specific molecular recognition, a task that has so far defied many conventional imaging approaches. Here we present a super-resolution fluorescence imaging method to visualize the molecular architecture of synapses in the brain. Using multicolor, three-dimensional stochastic optical reconstruction microscopy, the distributions of synaptic proteins can be measured with nanometer precision. Furthermore, the wide-field, volumetric imaging method enables high-throughput, quantitative analysis of a large number of synapses from different brain regions. To demonstrate the capabilities of this approach, we have determined the organization of ten protein components of the presynaptic active zone and the postsynaptic density. Variations in synapse morphology, neurotransmitter receptor composition, and receptor distribution were observed both among synapses and across different brain regions. Combination with optogenetics further allowed molecular events associated with synaptic plasticity to be resolved at the single-synapse level. PMID:21144999

Rosetta3: An Object-Oriented Software Suite for the Simulation and Design of Macromolecules

PubMed Central

Leaver-Fay, Andrew; Tyka, Michael; Lewis, Steven M.; Lange, Oliver F.; Thompson, James; Jacak, Ron; Kaufman, Kristian; Renfrew, P. Douglas; Smith, Colin A.; Sheffler, Will; Davis, Ian W.; Cooper, Seth; Treuille, Adrien; Mandell, Daniel J.; Richter, Florian; Ban, Yih-En Andrew; Fleishman, Sarel J.; Corn, Jacob E.; Kim, David E.; Lyskov, Sergey; Berrondo, Monica; Mentzer, Stuart; Popović, Zoran; Havranek, James J.; Karanicolas, John; Das, Rhiju; Meiler, Jens; Kortemme, Tanja; Gray, Jeffrey J.; Kuhlman, Brian; Baker, David; Bradley, Philip

2013-01-01

We have recently completed a full re-architecturing of the Rosetta molecular modeling program, generalizing and expanding its existing functionality. The new architecture enables the rapid prototyping of novel protocols by providing easy to use interfaces to powerful tools for molecular modeling. The source code of this rearchitecturing has been released as Rosetta3 and is freely available for academic use. At the time of its release, it contained 470,000 lines of code. Counting currently unpublished protocols at the time of this writing, the source includes 1,285,000 lines. Its rapid growth is a testament to its ease of use. This document describes the requirements for our new architecture, justifies the design decisions, sketches out central classes, and highlights a few of the common tasks that the new software can perform. PMID:21187238

Design and synthesis of molecular donors for solution-processed high-efficiency organic solar cells.

PubMed

Coughlin, Jessica E; Henson, Zachary B; Welch, Gregory C; Bazan, Guillermo C

2014-01-21

Organic semiconductors incorporated into solar cells using a bulk heterojunction (BHJ) construction show promise as a cleaner answer to increasing energy needs throughout the world. Organic solar cells based on the BHJ architecture have steadily increased in their device performance over the past two decades, with power conversion efficiencies reaching 10%. Much of this success has come with conjugated polymer/fullerene combinations, where optimized polymer design strategies, synthetic protocols, device fabrication procedures, and characterization methods have provided significant advancements in the technology. More recently, chemists have been paying particular attention to well-defined molecular donor systems due to their ease of functionalization, amenability to standard organic purification and characterization methods, and reduced batch-to-batch variability compared to polymer counterparts. There are several critical properties for efficient small molecule donors. First, broad optical absorption needs to extend towards the near-IR region to achieve spectral overlap with the solar spectrum. Second, the low lying highest occupied molecular orbital (HOMO) energy levels need to be between -5.2 and -5.5 eV to ensure acceptable device open circuit voltages. Third, the structures need to be relatively planar to ensure close intermolecular contacts and high charge carrier mobilities. And last, the small molecule donors need to be sufficiently soluble in organic solvents (≥10 mg/mL) to facilitate solution deposition of thin films of appropriate uniformity and thickness. Ideally, these molecules should be constructed from cost-effective, sustainable building blocks using established, high yielding reactions in as few steps as possible. The structures should also be easy to functionalize to maximize tunability for desired properties. In this Account, we present a chronological description of our thought process and design strategies used in the development of highly efficient molecular donors that achieve power conversion efficiencies greater than 7%. The molecules are based on a modular D(1)-A-D(2)-A-D(1) architecture, where A is an asymmetric electron deficient heterocycle, which allowed us to quickly access a library of compounds and develop structure-property-performance relationships. Modifications to the D1 and D2 units enable spectral coverage throughout the entire visible region and control of HOMO energy levels, while adjustments to the pendant alkyl substituents dictate molecular solubility, thermal transition temperatures, and solid-state organizational tendencies. Additionally, we discuss regiochemical considerations that highlight how individual atom placements can significantly influence molecular and subsequently device characteristics. Our results demonstrate the utility of this architecture for generating promising materials to be integrated into organic photovoltaic devices, call attention to areas for improvement, and provide guiding principles to sustain the steady increases necessary to move this technology forward.

Programmable chemical controllers made from DNA.

PubMed

Chen, Yuan-Jyue; Dalchau, Neil; Srinivas, Niranjan; Phillips, Andrew; Cardelli, Luca; Soloveichik, David; Seelig, Georg

2013-10-01

Biological organisms use complex molecular networks to navigate their environment and regulate their internal state. The development of synthetic systems with similar capabilities could lead to applications such as smart therapeutics or fabrication methods based on self-organization. To achieve this, molecular control circuits need to be engineered to perform integrated sensing, computation and actuation. Here we report a DNA-based technology for implementing the computational core of such controllers. We use the formalism of chemical reaction networks as a 'programming language' and our DNA architecture can, in principle, implement any behaviour that can be mathematically expressed as such. Unlike logic circuits, our formulation naturally allows complex signal processing of intrinsically analogue biological and chemical inputs. Controller components can be derived from biologically synthesized (plasmid) DNA, which reduces errors associated with chemically synthesized DNA. We implement several building-block reaction types and then combine them into a network that realizes, at the molecular level, an algorithm used in distributed control systems for achieving consensus between multiple agents.

Programmable chemical controllers made from DNA

NASA Astrophysics Data System (ADS)

Chen, Yuan-Jyue; Dalchau, Neil; Srinivas, Niranjan; Phillips, Andrew; Cardelli, Luca; Soloveichik, David; Seelig, Georg

2013-10-01

Biological organisms use complex molecular networks to navigate their environment and regulate their internal state. The development of synthetic systems with similar capabilities could lead to applications such as smart therapeutics or fabrication methods based on self-organization. To achieve this, molecular control circuits need to be engineered to perform integrated sensing, computation and actuation. Here we report a DNA-based technology for implementing the computational core of such controllers. We use the formalism of chemical reaction networks as a 'programming language' and our DNA architecture can, in principle, implement any behaviour that can be mathematically expressed as such. Unlike logic circuits, our formulation naturally allows complex signal processing of intrinsically analogue biological and chemical inputs. Controller components can be derived from biologically synthesized (plasmid) DNA, which reduces errors associated with chemically synthesized DNA. We implement several building-block reaction types and then combine them into a network that realizes, at the molecular level, an algorithm used in distributed control systems for achieving consensus between multiple agents.

Dielectrophoresis-Based Sample Handling in General-Purpose Programmable Diagnostic Instruments

PubMed Central

Gascoyne, Peter R. C.; Vykoukal, Jody V.

2009-01-01

As the molecular origins of disease are better understood, the need for affordable, rapid, and automated technologies that enable microscale molecular diagnostics has become apparent. Widespread use of microsystems that perform sample preparation and molecular analysis could ensure that the benefits of new biomedical discoveries are realized by a maximum number of people, even those in environments lacking any infrastructure. While progress has been made in developing miniaturized diagnostic systems, samples are generally processed off-device using labor-intensive and time-consuming traditional sample preparation methods. We present the concept of an integrated programmable general-purpose sample analysis processor (GSAP) architecture where raw samples are routed to separation and analysis functional blocks contained within a single device. Several dielectrophoresis-based methods that could serve as the foundation for building GSAP functional blocks are reviewed including methods for cell and particle sorting, cell focusing, cell ac impedance analysis, cell lysis, and the manipulation of molecules and reagent droplets. PMID:19684877

Programmable chemical controllers made from DNA

PubMed Central

Chen, Yuan-Jyue; Dalchau, Neil; Srinivas, Niranjan; Phillips, Andrew; Cardelli, Luca; Soloveichik, David; Seelig, Georg

2014-01-01

Biological organisms use complex molecular networks to navigate their environment and regulate their internal state. The development of synthetic systems with similar capabilities could lead to applications such as smart therapeutics or fabrication methods based on self-organization. To achieve this, molecular control circuits need to be engineered to perform integrated sensing, computation and actuation. Here we report a DNA-based technology for implementing the computational core of such controllers. We use the formalism of chemical reaction networks as a 'programming language', and our DNA architecture can, in principle, implement any behaviour that can be mathematically expressed as such. Unlike logic circuits, our formulation naturally allows complex signal processing of intrinsically analogue biological and chemical inputs. Controller components can be derived from biologically synthesized (plasmid) DNA, which reduces errors associated with chemically synthesized DNA. We implement several building-block reaction types and then combine them into a network that realizes, at the molecular level, an algorithm used in distributed control systems for achieving consensus between multiple agents. PMID:24077029

Federated ontology-based queries over cancer data

PubMed Central

2012-01-01

Background Personalised medicine provides patients with treatments that are specific to their genetic profiles. It requires efficient data sharing of disparate data types across a variety of scientific disciplines, such as molecular biology, pathology, radiology and clinical practice. Personalised medicine aims to offer the safest and most effective therapeutic strategy based on the gene variations of each subject. In particular, this is valid in oncology, where knowledge about genetic mutations has already led to new therapies. Current molecular biology techniques (microarrays, proteomics, epigenetic technology and improved DNA sequencing technology) enable better characterisation of cancer tumours. The vast amounts of data, however, coupled with the use of different terms - or semantic heterogeneity - in each discipline makes the retrieval and integration of information difficult. Results Existing software infrastructures for data-sharing in the cancer domain, such as caGrid, support access to distributed information. caGrid follows a service-oriented model-driven architecture. Each data source in caGrid is associated with metadata at increasing levels of abstraction, including syntactic, structural, reference and domain metadata. The domain metadata consists of ontology-based annotations associated with the structural information of each data source. However, caGrid's current querying functionality is given at the structural metadata level, without capitalising on the ontology-based annotations. This paper presents the design of and theoretical foundations for distributed ontology-based queries over cancer research data. Concept-based queries are reformulated to the target query language, where join conditions between multiple data sources are found by exploiting the semantic annotations. The system has been implemented, as a proof of concept, over the caGrid infrastructure. The approach is applicable to other model-driven architectures. A graphical user interface has been developed, supporting ontology-based queries over caGrid data sources. An extensive evaluation of the query reformulation technique is included. Conclusions To support personalised medicine in oncology, it is crucial to retrieve and integrate molecular, pathology, radiology and clinical data in an efficient manner. The semantic heterogeneity of the data makes this a challenging task. Ontologies provide a formal framework to support querying and integration. This paper provides an ontology-based solution for querying distributed databases over service-oriented, model-driven infrastructures. PMID:22373043

Molecular basis for photoreceptor outer segment architecture

PubMed Central

Goldberg, Andrew F. X.; Moritz, Orson L.; Williams, David S.

2016-01-01

To serve vision, vertebrate rod and cone photoreceptors must detect photons, convert the light stimuli into cellular signals, and then convey the encoded information to downstream neurons. Rods and cones are sensory neurons that each rely on specialized ciliary organelles to detect light. These organelles, called outer segments, possess elaborate architectures that include many hundreds of light-sensitive membranous disks arrayed one atop another in precise register. These stacked disks capture light and initiate the chain of molecular and cellular events that underlie normal vision. Outer segment organization is challenged by an inherently dynamic nature; these organelles are subject to a renewal process that replaces a significant fraction of their disks (up to ~10%) on a daily basis. In addition, a broad range of environmental and genetic insults can disrupt outer segment morphology to impair photoreceptor function and viability. In this chapter, we survey the major progress that has been made for understanding the molecular basis of outer segment architecture. We also discuss key aspects of organelle lipid and protein composition, and highlight distributions, interactions, and potential structural functions of key OS-resident molecules, including: kinesin-2, actin, RP1, prominin-1, protocadherin 21, peripherin-2/rds, rom-1, glutamic acid-rich proteins, and rhodopsin. Finally, we identify key knowledge gaps and challenges that remain for understanding how normal outer segment architecture is established and maintained. PMID:27260426

Optimal use of novel agents in chronic lymphocytic leukemia.

PubMed

Smith, Mitchell R; Weiss, Robert F

2018-05-07

Novel agents are changing therapy for patients with CLL, but their optimal use remains unclear. We model the clinical situation in which CLL responds to therapy, but resistant clones, generally carrying del17p, progress and lead to relapse. Sub-clones of varying growth rates and treatment sensitivity affect predicted therapy outcomes. We explore effects of different approaches to starting novel agent in relation to bendamustine-rituximab induction therapy: at initiation of therapy, at the end of chemo-immunotherapy, at molecular relapse, or at clinical detection of relapse. The outcomes differ depending on the underlying clonal architecture, raising the concept that personalized approaches based on clinical evaluation of each patient's clonal architecture might optimize outcomes while minimizing toxicity and cost. Copyright © 2018 Elsevier Ltd. All rights reserved.

MIDG-Emerging grid technologies for multi-site preclinical molecular imaging research communities.

PubMed

Lee, Jasper; Documet, Jorge; Liu, Brent; Park, Ryan; Tank, Archana; Huang, H K

2011-03-01

Molecular imaging is the visualization and identification of specific molecules in anatomy for insight into metabolic pathways, tissue consistency, and tracing of solute transport mechanisms. This paper presents the Molecular Imaging Data Grid (MIDG) which utilizes emerging grid technologies in preclinical molecular imaging to facilitate data sharing and discovery between preclinical molecular imaging facilities and their collaborating investigator institutions to expedite translational sciences research. Grid-enabled archiving, management, and distribution of animal-model imaging datasets help preclinical investigators to monitor, access and share their imaging data remotely, and promote preclinical imaging facilities to share published imaging datasets as resources for new investigators. The system architecture of the Molecular Imaging Data Grid is described in a four layer diagram. A data model for preclinical molecular imaging datasets is also presented based on imaging modalities currently used in a molecular imaging center. The MIDG system components and connectivity are presented. And finally, the workflow steps for grid-based archiving, management, and retrieval of preclincial molecular imaging data are described. Initial performance tests of the Molecular Imaging Data Grid system have been conducted at the USC IPILab using dedicated VMware servers. System connectivity, evaluated datasets, and preliminary results are presented. The results show the system's feasibility, limitations, direction of future research. Translational and interdisciplinary research in medicine is increasingly interested in cellular and molecular biology activity at the preclinical levels, utilizing molecular imaging methods on animal models. The task of integrated archiving, management, and distribution of these preclinical molecular imaging datasets at preclinical molecular imaging facilities is challenging due to disparate imaging systems and multiple off-site investigators. A Molecular Imaging Data Grid design, implementation, and initial evaluation is presented to demonstrate the secure and novel data grid solution for sharing preclinical molecular imaging data across the wide-area-network (WAN).

Molecular architecture requirements for polymer-grafted lignin superplasticizers.

PubMed

Gupta, Chetali; Sverdlove, Madeline J; Washburn, Newell R

2015-04-07

Superplasticizers are a class of anionic polymer dispersants used to inhibit aggregation in hydraulic cement, lowering the yield stress of cement pastes to improve workability and reduce water requirements. The plant-derived biopolymer lignin is commonly used as a low-cost/low-performance plasticizer, but attempts to improve its effects on cement rheology through copolymerization with synthetic monomers have not led to significant improvements. Here we demonstrate that kraft lignin can form the basis for high-performance superplasticizers in hydraulic cement, but the molecular architecture must be based on a lignin core with a synthetic-polymer corona that can be produced via controlled radical polymerization. Using slump tests of ordinary Portland cement pastes, we show that polyacrylamide-grafted lignin prepared via reversible addition-fragmentation chain transfer polymerization can reduce the yield stress of cement paste to similar levels as a leading commercial polycarboxylate ether superplasticizer at concentrations ten-fold lower, although the lignin material produced via controlled radical polymerization does not appear to reduce the dynamic viscosity of cement paste as effectively as the polycarboxylate superplasticizer, despite having a similar affinity for the individual mineral components of ordinary Portland cement. In contrast, polyacrylamide copolymerized with a methacrylated kraft lignin via conventional free radical polymerization having a similar overall composition did not reduce the yield stress or the viscosity of cement pastes. While further work is required to elucidate the mechanism of this effect, these results indicate that controlling the architecture of polymer-grafted lignin can significantly enhance its performance as a superplasticizer for cement.

Unveiling the hybrid interface in polymer nanocomposites enclosing silsesquioxanes with tunable molecular structure: Spectroscopic, thermal and mechanical properties.

PubMed

D'Arienzo, Massimiliano; Diré, Sandra; Redaelli, Matteo; Borovin, Evgeny; Callone, Emanuela; Di Credico, Barbara; Morazzoni, Franca; Pegoretti, Alessandro; Scotti, Roberto

2018-02-15

Organic-inorganic nanobuilding blocks (NBBs) based on silsesquioxanes (SSQs) have potential applications as nanofillers, thermal stabilizers, and rheological modifiers, which can improve thermomechanical properties of polymer hosts. The possibility to tune both siloxane structure and pendant groups can promote compatibilization and peculiar interactions with a plethora of polymers. However, the control on SSQs molecular architecture and functionalities is usually delicate and requires careful synthetic details. Moreover, investigating the influence of NBBs loading and structure on the hybrid interface and, in turn, on the polymer chains mobility and mechanical properties, may be challenging, especially for low-loaded materials. Herein, we describe the preparation and characterization of polybutadiene (PB) nanocomposites using as innovative fillers thiol-functionalized SSQs nanobuilding blocks (SH-NBBs), with both tailorable functionality and structure. Swelling experiments and, more clearly, solid-state NMR, enlightened a remarkable effect of SH-NBBs on the molecular structure and mobility of the polymeric chains, envisaging the occurrence of chemical interactions at the hybrid interface. Finally, thermal and DMTA analyses revealed that nanocomposites, even containing very low filler loadings (i.e. 1, 3 wt%), exhibited enhanced thermomechanical properties, which seem to be connected not only to the loading, but also to the peculiar cage or ladder-like architecture of SH-NBBs. Copyright © 2017 Elsevier Inc. All rights reserved.

The influence of polymer architecture on the assembly of poly(ethylene oxide) grafted C60 fullerene clusters in aqueous solution: a molecular dynamics simulation study.

PubMed

Hooper, Justin B; Bedrov, Dmitry; Smith, Grant D

2009-03-28

The effect of polymer architecture on the aggregation behavior of C60 fullerenes tethered with a single chain of poly(ethylene oxide) (PEO) in aqueous solution has been investigated using coarse-grained, implicit solvent molecular dynamics simulations. The PEO-grafted fullerenes were comprised of a single tether of 60 repeat units represented as a linear polymer, a three-arm star (20 repeat units/arm) or a six-arm star (10 repeat units/arm). Additionally, the influence of arm length on self-assembly of the PEO-fullerene conjugates was investigated for the three-arm stars. Self-assembly is driven by favorable fullerene-fullerene and fullerene-PEO interactions. Our simulations reveal that it should be possible to control the size and geometry of the self-assembled fullerene aggregates in water through variation of PEO architecture and PEO molecular weight. We found that aggregate size and shape could be understood qualitatively in terms of the packing parameter concept that has been employed for diblock polymer and surfactant self-assembly. Higher molecular weight PEO (longer arms) and more compact PEO (more arms for the same molecular weight) resulted in greater steric repulsion between fullerenes, engendering greater aggregate surface curvature and hence the formation of smaller, more spherically shaped aggregates. Finally, weak attractive interactions between PEO and the fullerenes were found to play an important role in determining aggregate shape, size and the dynamics of self-assembly.

Biomedical analysis of formalin-fixed, paraffin-embedded tissue samples: The Holy Grail for molecular diagnostics.

PubMed

Donczo, Boglarka; Guttman, Andras

2018-06-05

More than a century ago in 1893, a revolutionary idea about fixing biological tissue specimens was introduced by Ferdinand Blum, a German physician. Since then, a plethora of fixation methods have been investigated and used. Formalin fixation with paraffin embedment became the most widely used types of fixation and preservation method, due to its proper architectural conservation of tissue structures and cellular shape. The huge collection of formalin-fixed, paraffin-embedded (FFPE) sample archives worldwide holds a large amount of unearthed information about diseases that could be the Holy Grail in contemporary biomarker research utilizing analytical omics based molecular diagnostics. The aim of this review is to critically evaluate the omics options for FFPE tissue sample analysis in the molecular diagnostics field. Copyright © 2018. Published by Elsevier B.V.

Biosensor Architectures for High-Fidelity Reporting of Cellular Signaling

PubMed Central

Dushek, Omer; Lellouch, Annemarie C.; Vaux, David J.; Shahrezaei, Vahid

2014-01-01

Understanding mechanisms of information processing in cellular signaling networks requires quantitative measurements of protein activities in living cells. Biosensors are molecular probes that have been developed to directly track the activity of specific signaling proteins and their use is revolutionizing our understanding of signal transduction. The use of biosensors relies on the assumption that their activity is linearly proportional to the activity of the signaling protein they have been engineered to track. We use mechanistic mathematical models of common biosensor architectures (single-chain FRET-based biosensors), which include both intramolecular and intermolecular reactions, to study the validity of the linearity assumption. As a result of the classic mechanism of zero-order ultrasensitivity, we find that biosensor activity can be highly nonlinear so that small changes in signaling protein activity can give rise to large changes in biosensor activity and vice versa. This nonlinearity is abolished in architectures that favor the formation of biosensor oligomers, but oligomeric biosensors produce complicated FRET states. Based on this finding, we show that high-fidelity reporting is possible when a single-chain intermolecular biosensor is used that cannot undergo intramolecular reactions and is restricted to forming dimers. We provide phase diagrams that compare various trade-offs, including observer effects, which further highlight the utility of biosensor architectures that favor intermolecular over intramolecular binding. We discuss challenges in calibrating and constructing biosensors and highlight the utility of mathematical models in designing novel probes for cellular signaling. PMID:25099816

Heterogeneous Integration of Epitaxial Ge on Si using AlAs/GaAs Buffer Architecture: Suitability for Low-power Fin Field-Effect Transistors

PubMed Central

Hudait, Mantu K.; Clavel, Michael; Goley, Patrick; Jain, Nikhil; Zhu, Yan

2014-01-01

Germanium-based materials and device architectures have recently appeared as exciting material systems for future low-power nanoscale transistors and photonic devices. Heterogeneous integration of germanium (Ge)-based materials on silicon (Si) using large bandgap buffer architectures could enable the monolithic integration of electronics and photonics. In this paper, we report on the heterogeneous integration of device-quality epitaxial Ge on Si using composite AlAs/GaAs large bandgap buffer, grown by molecular beam epitaxy that is suitable for fabricating low-power fin field-effect transistors required for continuing transistor miniaturization. The superior structural quality of the integrated Ge on Si using AlAs/GaAs was demonstrated using high-resolution x-ray diffraction analysis. High-resolution transmission electron microscopy confirmed relaxed Ge with high crystalline quality and a sharp Ge/AlAs heterointerface. X-ray photoelectron spectroscopy demonstrated a large valence band offset at the Ge/AlAs interface, as compared to Ge/GaAs heterostructure, which is a prerequisite for superior carrier confinement. The temperature-dependent electrical transport properties of the n-type Ge layer demonstrated a Hall mobility of 370 cm2/Vs at 290 K and 457 cm2/Vs at 90 K, which suggests epitaxial Ge grown on Si using an AlAs/GaAs buffer architecture would be a promising candidate for next-generation high-performance and energy-efficient fin field-effect transistor applications. PMID:25376723

Understanding the development of roots exposed to contaminants and the potential of plant-associated bacteria for optimization of growth

PubMed Central

Remans, Tony; Thijs, Sofie; Truyens, Sascha; Weyens, Nele; Schellingen, Kerim; Keunen, Els; Gielen, Heidi; Cuypers, Ann; Vangronsveld, Jaco

2012-01-01

Background and Scope Plant responses to the toxic effects of soil contaminants, such as excess metals or organic substances, have been studied mainly at physiological, biochemical and molecular levels, but the influence on root system architecture has received little attention. Nevertheless, the precise position, morphology and extent of roots can influence contaminant uptake. Here, data are discussed that aim to increase the molecular and ecological understanding of the influence of contaminants on root system architecture. Furthermore, the potential of plant-associated bacteria to influence root growth by their growth-promoting and stress-relieving capacities is explored. Methods Root growth parameters of Arabidopsis thaliana seedlings grown in vertical agar plates are quantified. Mutants are used in a reverse genetics approach to identify molecular components underlying quantitative changes in root architecture after exposure to excess cadmium, copper or zinc. Plant-associated bacteria are isolated from contaminated environments, genotypically and phenotypically characterized, and used to test plant root growth improvement in the presence of contaminants. Key Results The molecular determinants of primary root growth inhibition and effects on lateral root density by cadmium were identified. A vertical split-root system revealed local effects of cadmium and copper on root development. However, systemic effects of zinc exposure on root growth reduced both the avoidance of contaminated areas and colonization of non-contaminated areas. The potential for growth promotion and contaminant degradation of plant-associated bacteria was demonstrated by improved root growth of inoculated plants exposed to 2,4-di-nitro-toluene (DNT) or cadmium. Conclusions Knowledge concerning the specific influence of different contaminants on root system architecture and the molecular mechanisms by which this is achieved can be combined with the exploitation of plant-associated bacteria to influence root development and increase plant stress tolerance, which should lead to more optimal root systems for application in phytoremediation or safer biomass production. PMID:22634257

Understanding the development of roots exposed to contaminants and the potential of plant-associated bacteria for optimization of growth.

PubMed

Remans, Tony; Thijs, Sofie; Truyens, Sascha; Weyens, Nele; Schellingen, Kerim; Keunen, Els; Gielen, Heidi; Cuypers, Ann; Vangronsveld, Jaco

2012-07-01

Plant responses to the toxic effects of soil contaminants, such as excess metals or organic substances, have been studied mainly at physiological, biochemical and molecular levels, but the influence on root system architecture has received little attention. Nevertheless, the precise position, morphology and extent of roots can influence contaminant uptake. Here, data are discussed that aim to increase the molecular and ecological understanding of the influence of contaminants on root system architecture. Furthermore, the potential of plant-associated bacteria to influence root growth by their growth-promoting and stress-relieving capacities is explored. Root growth parameters of Arabidopsis thaliana seedlings grown in vertical agar plates are quantified. Mutants are used in a reverse genetics approach to identify molecular components underlying quantitative changes in root architecture after exposure to excess cadmium, copper or zinc. Plant-associated bacteria are isolated from contaminated environments, genotypically and phenotypically characterized, and used to test plant root growth improvement in the presence of contaminants. The molecular determinants of primary root growth inhibition and effects on lateral root density by cadmium were identified. A vertical split-root system revealed local effects of cadmium and copper on root development. However, systemic effects of zinc exposure on root growth reduced both the avoidance of contaminated areas and colonization of non-contaminated areas. The potential for growth promotion and contaminant degradation of plant-associated bacteria was demonstrated by improved root growth of inoculated plants exposed to 2,4-di-nitro-toluene (DNT) or cadmium. Knowledge concerning the specific influence of different contaminants on root system architecture and the molecular mechanisms by which this is achieved can be combined with the exploitation of plant-associated bacteria to influence root development and increase plant stress tolerance, which should lead to more optimal root systems for application in phytoremediation or safer biomass production.

The internal architecture of dendritic spines revealed by super-resolution imaging: What did we learn so far?

DOE Office of Scientific and Technical Information (OSTI.GOV)

MacGillavry, Harold D., E-mail: h.d.macgillavry@uu.nl; Hoogenraad, Casper C., E-mail: c.hoogenraad@uu.nl

2015-07-15

The molecular architecture of dendritic spines defines the efficiency of signal transmission across excitatory synapses. It is therefore critical to understand the mechanisms that control the dynamic localization of the molecular constituents within spines. However, because of the small scale at which most processes within spines take place, conventional light microscopy techniques are not adequate to provide the necessary level of resolution. Recently, super-resolution imaging techniques have overcome the classical barrier imposed by the diffraction of light, and can now resolve the localization and dynamic behavior of proteins within small compartments with nanometer precision, revolutionizing the study of dendritic spinemore » architecture. Here, we highlight exciting new findings from recent super-resolution studies on neuronal spines, and discuss how these studies revealed important new insights into how protein complexes are assembled and how their dynamic behavior shapes the efficiency of synaptic transmission.« less

Tissue specific specialization of the nanoscale architecture of Arabidopsis.

PubMed

Liu, Jiliang; Inouye, Hideyo; Venugopalan, Nagarajan; Fischetti, Robert F; Gleber, S Charlotte; Vogt, Stefan; Cusumano, Joanne C; Kim, Jeong Im; Chapple, Clint; Makowski, Lee

2013-11-01

The Arabidopsis stem is composed of five tissues - the pith, xylem, phloem, cortex and epidermis - each of which fulfills specific roles in support of the growth and survival of the organism. The lignocellulosic scaffolding of cell walls is specialized to provide optimal support for the diverse functional roles of these layers, but little is known about this specialization. X-ray scattering can be used to study this tissue-specific diversity because the cellulosic components of the cell walls give rise to recognizable scattering features interpretable in terms of the underlying molecular architecture and distinct from the largely unoriented scatter from other constituents. Here we use scanning X-ray microdiffraction from thin sections to characterize the diversity of molecular architecture in the Arabidopsis stem and correlate that diversity to the functional roles the distinct tissues of the stem play in the growth and survival of the organism. Copyright © 2013. Published by Elsevier Inc.

Simulation studies of DNA at the nanoscale: Interactions with proteins, polycations, and surfaces

NASA Astrophysics Data System (ADS)

Elder, Robert M.

Understanding the nanoscale interactions of DNA, a multifunctional biopolymer with sequence-dependent properties, with other biological and synthetic substrates and molecules is essential to advancing these technologies. This doctoral thesis research is aimed at understanding the thermodynamics and molecular-level structure when DNA interacts with proteins, polycations, and functionalized surfaces. First, we investigate the ability of a DNA damage recognition protein (HMGB1a) to bind to anti-cancer drug-induced DNA damage, seeking to explain how HMGB1a differentiates between the drugs in vivo. Using atomistic molecular dynamics simulations, we show that the structure of the drug-DNA molecule exhibits drug- and base sequence-dependence that explains some of the experimentally observed differential recognition of the drugs in various sequence contexts. Then, we show how steric hindrance from the drug decreases the deformability of the drug-DNA molecule, which decreases recognition by the protein, a concept that can be applied to rational drug design. Second, we study how polycation architecture and chemistry affect polycation-DNA binding so as to design optimal polycations for high efficiency gene (DNA) delivery. Using a multiscale computational approach involving atomistic and coarse-grained simulations, we examine how rearranging polylysine from a linear to a grafted architecture, and several aspects of the grafted architecture, affect polycation-DNA binding and the structure of polycation-DNA complexes. Next, going beyond lysine we examine how oligopeptide chemistry and sequence in the grafted architecture affects polycation-DNA binding and find that strategic placement of hydrophobic peptides might be used to tailor binding strength. Third, we study the adsorption and conformations of single-stranded DNA (an amphiphilic biopolymer) on model hydrophilic and hydrophobic surfaces. Short ssDNA oligomers adsorb to both surfaces with similar strength, with the strength of adsorption to the hydrophobic surface depending on the composition of the DNA strands, i.e. purine or pyrimidine bases. Additionally, DNA-surface and DNA-water interactions near the surfaces govern the adsorption. For longer ssDNA oligomers, the effects of surface chemistry and temperature on ssDNA conformations are rather small, but either the hydrophilic surface or increased temperature favor slightly more compact conformations due to energetic and entropic effects, respectively.

Macromolecular 'size' and 'hardness' drives structure in solvent-swollen blends of linear, cyclic, and star polymers.

PubMed

Gartner, Thomas E; Jayaraman, Arthi

2018-01-17

In this paper, we apply molecular simulation and liquid state theory to uncover the structure and thermodynamics of homopolymer blends of the same chemistry and varying chain architecture in the presence of explicit solvent species. We use hybrid Monte Carlo (MC)/molecular dynamics (MD) simulations in the Gibbs ensemble to study the swelling of ∼12 000 g mol -1 linear, cyclic, and 4-arm star polystyrene chains in toluene. Our simulations show that the macroscopic swelling response is indistinguishable between the various architectures and matches published experimental data for the solvent annealing of linear polystyrene by toluene vapor. We then use standard MD simulations in the NPT ensemble along with polymer reference interaction site model (PRISM) theory to calculate effective polymer-solvent and polymer-polymer Flory-Huggins interaction parameters (χ eff ) in these systems. As seen in the macroscopic swelling results, there are no significant differences in the polymer-solvent and polymer-polymer χ eff between the various architectures. Despite similar macroscopic swelling and effective interaction parameters between various architectures, the pair correlation function between chain centers-of-mass indicates stronger correlations between cyclic or star chains in the linear-cyclic blends and linear-star blends, compared to linear chain-linear chain correlations. Furthermore, we note striking similarities in the chain-level correlations and the radius of gyration of cyclic and 4-arm star architectures of identical molecular weight. Our results indicate that the cyclic and star chains are 'smaller' and 'harder' than their linear counterparts, and through comparison with MD simulations of blends of soft spheres with varying hardness and size we suggest that these macromolecular characteristics are the source of the stronger cyclic-cyclic and star-star correlations.

A confocal microscopy-based atlas of tissue architecture in the tapeworm Hymenolepis diminuta.

PubMed

Rozario, Tania; Newmark, Phillip A

2015-11-01

Tapeworms are pervasive and globally distributed parasites that infect millions of humans and livestock every year, and are the causative agents of two of the 17 neglected tropical diseases prioritized by the World Health Organization. Studies of tapeworm biology and pathology are often encumbered by the complex life cycles of disease-relevant tapeworm species that infect hosts such as foxes, dogs, cattle, pigs, and humans. Thus, studies of laboratory models can help overcome the practical, ethical, and cost-related difficulties faced by tapeworm parasitologists. The rat intestinal tapeworm Hymenolepis diminuta is easily reared in the laboratory and has the potential to enable modern molecular-based experiments that will greatly contribute to our understanding of multiple aspects of tapeworm biology, such as growth and reproduction. As part of our efforts to develop molecular tools for experiments on H. diminuta, we have characterized a battery of lectins, antibodies, and common stains that label different tapeworm tissues and organ structures. Using confocal microscopy, we have assembled an "atlas" of H. diminuta organ architecture that will be a useful resource for helminthologists. The methodologies we describe will facilitate characterization of loss-of-function perturbations using H. diminuta. This toolkit will enable a greater understanding of fundamental tapeworm biology that may elucidate new therapeutic targets toward the eradication of these parasites. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Modelling the degradation and elastic properties of poly(lactic-co-glycolic acid) films and regular open-cell tissue engineering scaffolds.

PubMed

Shirazi, Reyhaneh Neghabat; Ronan, William; Rochev, Yury; McHugh, Peter

2016-02-01

Scaffolding plays a critical rule in tissue engineering and an appropriate degradation rate and sufficient mechanical integrity are required during degradation and healing of tissue. This paper presents a computational investigation of the molecular weight degradation and the mechanical performance of poly(lactic-co-glycolic acid) (PLGA) films and tissue engineering scaffolds. A reaction-diffusion model which predicts the degradation behaviour is coupled with an entropy-based mechanical model which relates Young׳s modulus and the molecular weight. The model parameters are determined based on experimental data for in-vitro degradation of a PLGA film. Microstructural models of three different scaffold architectures are used to investigate the degradation and mechanical behaviour of each scaffold. Although the architecture of the scaffold does not have a significant influence on the degradation rate, it determines the initial stiffness of the scaffold. It is revealed that the size of the scaffold strut controls the degradation rate and the mechanical collapse. A critical length scale due to competition between diffusion of degradation products and autocatalytic degradation is determined to be in the range 2-100μm. Below this range, slower homogenous degradation occurs; however, for larger samples monomers are trapped inside the sample and faster autocatalytic degradation occurs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Light Extraction From Solution-Based Processable Electrophosphorescent Organic Light-Emitting Diodes

NASA Astrophysics Data System (ADS)

Krummacher, Benjamin C.; Mathai, Mathew; So, Franky; Choulis, Stelios; Choong, And-En, Vi

2007-06-01

Molecular dye dispersed solution processable blue emitting organic light-emitting devices have been fabricated and the resulting devices exhibit efficiency as high as 25 cd/A. With down-conversion phosphors, white emitting devices have been demonstrated with peak efficiency of 38 cd/A and luminous efficiency of 25 lm/W. The high efficiencies have been a product of proper tuning of carrier transport, optimization of the location of the carrier recombination zone and, hence, microcavity effect, efficient down-conversion from blue to white light, and scattering/isotropic remission due to phosphor particles. An optical model has been developed to investigate all these effects. In contrast to the common misunderstanding that light out-coupling efficiency is about 22% and independent of device architecture, our device data and optical modeling results clearly demonstrated that the light out-coupling efficiency is strongly dependent on the exact location of the recombination zone. Estimating the device internal quantum efficiencies based on external quantum efficiencies without considering the device architecture could lead to erroneous conclusions.

Single Benzene Green Fluorophore: Solid-State Emissive, Water-Soluble, and Solvent- and pH-Independent Fluorescence with Large Stokes Shifts.

PubMed

Beppu, Teruo; Tomiguchi, Kosuke; Masuhara, Akito; Pu, Yong-Jin; Katagiri, Hiroshi

2015-06-15

Benzene is the simplest aromatic hydrocarbon with a six-membered ring. It is one of the most basic structural units for the construction of π conjugated systems, which are widely used as fluorescent dyes and other luminescent materials for imaging applications and displays because of their enhanced spectroscopic signal. Presented herein is 2,5-bis(methylsulfonyl)-1,4-diaminobenzene as a novel architecture for green fluorophores, established based on an effective push-pull system supported by intramolecular hydrogen bonding. This compound demonstrates high fluorescence emission and photostability and is solid-state emissive, water-soluble, and solvent- and pH-independent with quantum yields of Φ=0.67 and Stokes shift of 140 nm (in water). This architecture is a significant departure from conventional extended π-conjugated systems based on a flat and rigid molecular design and provides a minimum requirement for green fluorophores comprising a single benzene ring. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Component-based integration of chemistry and optimization software.

PubMed

Kenny, Joseph P; Benson, Steven J; Alexeev, Yuri; Sarich, Jason; Janssen, Curtis L; McInnes, Lois Curfman; Krishnan, Manojkumar; Nieplocha, Jarek; Jurrus, Elizabeth; Fahlstrom, Carl; Windus, Theresa L

2004-11-15

Typical scientific software designs make rigid assumptions regarding programming language and data structures, frustrating software interoperability and scientific collaboration. Component-based software engineering is an emerging approach to managing the increasing complexity of scientific software. Component technology facilitates code interoperability and reuse. Through the adoption of methodology and tools developed by the Common Component Architecture Forum, we have developed a component architecture for molecular structure optimization. Using the NWChem and Massively Parallel Quantum Chemistry packages, we have produced chemistry components that provide capacity for energy and energy derivative evaluation. We have constructed geometry optimization applications by integrating the Toolkit for Advanced Optimization, Portable Extensible Toolkit for Scientific Computation, and Global Arrays packages, which provide optimization and linear algebra capabilities. We present a brief overview of the component development process and a description of abstract interfaces for chemical optimizations. The components conforming to these abstract interfaces allow the construction of applications using different chemistry and mathematics packages interchangeably. Initial numerical results for the component software demonstrate good performance, and highlight potential research enabled by this platform.

Multifunctional Graphene-based Hybrid Nanomaterials for Electrochemical Energy Storage.

NASA Astrophysics Data System (ADS)

Gupta, Sanju

Intense research in renewable energy is stimulated by global demand of electric energy. Electrochemical energy storage and conversion systems namely, supercapacitors and batteries, represent the most efficient and environmentally benign technologies. Moreover, controlled nanoscaled architectures and surface chemistry of electrochemical electrodes is enabling emergent next-generation efficient devices approaching theoretical limit of energy and power densities. This talk will present our recent activities to advance design, development and deployment of composition, morphology and microstructure controlled two- and three-dimensional graphene-based hybrids architectures. They are chemically and molecularly bridged with carbon nanotubes, conducting polymers, transition metal oxides and mesoproprous silicon wrapped with graphene nanosheets as engineered electrodes for supercapacitor cathodes and battery anodes. They showed significant enhancement in terms of gravimetric specific capacitance, interfacial capacitance, charging-discharging rate and cyclability. We will also present fundamental physical-chemical interfacial processes (ion transfer kinetics and diffusion), imaging electroactive sites, and topography at electrode/electrolyte interface governing underlying electrochemical mechanisms via scanning electrochemical microscopy. KY NSF EPSCoR.

Molecular Sticker Model Stimulation on Silicon for a Maximum Clique Problem

PubMed Central

Ning, Jianguo; Li, Yanmei; Yu, Wen

2015-01-01

Molecular computers (also called DNA computers), as an alternative to traditional electronic computers, are smaller in size but more energy efficient, and have massive parallel processing capacity. However, DNA computers may not outperform electronic computers owing to their higher error rates and some limitations of the biological laboratory. The stickers model, as a typical DNA-based computer, is computationally complete and universal, and can be viewed as a bit-vertically operating machine. This makes it attractive for silicon implementation. Inspired by the information processing method on the stickers computer, we propose a novel parallel computing model called DEM (DNA Electronic Computing Model) on System-on-a-Programmable-Chip (SOPC) architecture. Except for the significant difference in the computing medium—transistor chips rather than bio-molecules—the DEM works similarly to DNA computers in immense parallel information processing. Additionally, a plasma display panel (PDP) is used to show the change of solutions, and helps us directly see the distribution of assignments. The feasibility of the DEM is tested by applying it to compute a maximum clique problem (MCP) with eight vertices. Owing to the limited computing sources on SOPC architecture, the DEM could solve moderate-size problems in polynomial time. PMID:26075867

Probing the molecular design of hyper-branched aryl polyesters towards lubricant applications

NASA Astrophysics Data System (ADS)

Robinson, Joshua W.; Zhou, Yan; Bhattacharya, Priyanka; Erck, Robert; Qu, Jun; Bays, J. Timothy; Cosimbescu, Lelia

2016-01-01

We report novel polymeric materials that may be used as viscosity index improvers (VII) for lubricant applications. Our efforts included probing the comb-burst hyper-branched aryl polyester architecture for beneficial viscosity and friction behavior when utilized as an additive in a group I oil. The monomer was designed as to undergo polymerization via polycondensation within the architectural construct (AB2), typical of hyperbranched polymers. The monomer design was comprised of aliphatic arms (12 or 16 methylenes) to provide the necessary lipophilicity to achieve solubility in a non-polar medium. Once polymerized, via catalyst and heat, the surface alcohols were functionalized with fatty acids (lauric and palmitic). Controlling the aliphatic nature of the internal arms and peripheral end-groups provided four unique flexible polymer designs. Changing the reaction time and concentration provided opportunities to investigate the influence of molecular weight and branching density on oil-solubility, viscosity, and friction. Oil-solubility was found to decrease with fewer internal carbons, but the number of internal carbons appears to have little influence on the bulk solution viscosity. At concentrations of 2 wt % in a group I base oil, these polymer additives demonstrated an improved viscosity index and reduced friction coefficient, validating the basic approach.

Light-emitting self-assembled peptide nucleic acids exhibit both stacking interactions and Watson-Crick base pairing.

PubMed

Berger, Or; Adler-Abramovich, Lihi; Levy-Sakin, Michal; Grunwald, Assaf; Liebes-Peer, Yael; Bachar, Mor; Buzhansky, Ludmila; Mossou, Estelle; Forsyth, V Trevor; Schwartz, Tal; Ebenstein, Yuval; Frolow, Felix; Shimon, Linda J W; Patolsky, Fernando; Gazit, Ehud

2015-04-01

The two main branches of bionanotechnology involve the self-assembly of either peptides or DNA. Peptide scaffolds offer chemical versatility, architectural flexibility and structural complexity, but they lack the precise base pairing and molecular recognition available with nucleic acid assemblies. Here, inspired by the ability of aromatic dipeptides to form ordered nanostructures with unique physical properties, we explore the assembly of peptide nucleic acids (PNAs), which are short DNA mimics that have an amide backbone. All 16 combinations of the very short di-PNA building blocks were synthesized and assayed for their ability to self-associate. Only three guanine-containing di-PNAs-CG, GC and GG-could form ordered assemblies, as observed by electron microscopy, and these di-PNAs efficiently assembled into discrete architectures within a few minutes. The X-ray crystal structure of the GC di-PNA showed the occurrence of both stacking interactions and Watson-Crick base pairing. The assemblies were also found to exhibit optical properties including voltage-dependent electroluminescence and wide-range excitation-dependent fluorescence in the visible region.

Molecular architecture and biomedical leads of terpenes from red sea marine invertebrates.

PubMed

Hegazy, Mohamed Elamir F; Mohamed, Tarik A; Alhammady, Montaser A; Shaheen, Alaa M; Reda, Eman H; Elshamy, Abdelsamed I; Aziz, Mina; Paré, Paul W

2015-05-20

Marine invertebrates including sponges, soft coral, tunicates, mollusks and bryozoan have proved to be a prolific source of bioactive natural products. Among marine-derived metabolites, terpenoids have provided a vast array of molecular architectures. These isoprenoid-derived metabolites also exhibit highly specialized biological activities ranging from nerve regeneration to blood-sugar regulation. As a result, intense research activity has been devoted to characterizing invertebrate terpenes from both a chemical and biological standpoint. This review focuses on the chemistry and biology of terpene metabolites isolated from the Red Sea ecosystem, a unique marine biome with one of the highest levels of biodiversity and specifically rich in invertebrate species.

Multistate and phase change selection in constitutional multivalent systems.

PubMed

Barboiu, Mihail

2012-01-01

Molecular architectures and materials can be constitutionally self-sorted in the presence of different biomolecular targets or external physical stimuli or chemical effectors, thus responding to an external selection pressure. The high selectivity and specificity of different bioreceptors or self-correlated internal interactions may be used to describe the complex constitutional behaviors through multistate component selection from a dynamic library. The self-selection may result in the dynamic amplification of self-optimized architectures during the phase change process. The sol-gel resolution of dynamic molecular/supramolecular libraries leads to higher self-organized constitutional hybrid materials, in which organic (supramolecular)/inorganic domains are reversibily connected.

Quantitative imaging methods in osteoporosis.

PubMed

Oei, Ling; Koromani, Fjorda; Rivadeneira, Fernando; Zillikens, M Carola; Oei, Edwin H G

2016-12-01

Osteoporosis is characterized by a decreased bone mass and quality resulting in an increased fracture risk. Quantitative imaging methods are critical in the diagnosis and follow-up of treatment effects in osteoporosis. Prior radiographic vertebral fractures and bone mineral density (BMD) as a quantitative parameter derived from dual-energy X-ray absorptiometry (DXA) are among the strongest known predictors of future osteoporotic fractures. Therefore, current clinical decision making relies heavily on accurate assessment of these imaging features. Further, novel quantitative techniques are being developed to appraise additional characteristics of osteoporosis including three-dimensional bone architecture with quantitative computed tomography (QCT). Dedicated high-resolution (HR) CT equipment is available to enhance image quality. At the other end of the spectrum, by utilizing post-processing techniques such as the trabecular bone score (TBS) information on three-dimensional architecture can be derived from DXA images. Further developments in magnetic resonance imaging (MRI) seem promising to not only capture bone micro-architecture but also characterize processes at the molecular level. This review provides an overview of various quantitative imaging techniques based on different radiological modalities utilized in clinical osteoporosis care and research.

ADP1 Affects Plant Architecture by Regulating Local Auxin Biosynthesis

PubMed Central

Li, Shibai; Qin, Genji; Novák, Ondřej; Pěnčík, Aleš; Ljung, Karin; Aoyama, Takashi; Liu, Jingjing; Murphy, Angus; Gu, Hongya; Tsuge, Tomohiko; Qu, Li-Jia

2014-01-01

Plant architecture is one of the key factors that affect plant survival and productivity. Plant body structure is established through the iterative initiation and outgrowth of lateral organs, which are derived from the shoot apical meristem and root apical meristem, after embryogenesis. Here we report that ADP1, a putative MATE (multidrug and toxic compound extrusion) transporter, plays an essential role in regulating lateral organ outgrowth, and thus in maintaining normal architecture of Arabidopsis. Elevated expression levels of ADP1 resulted in accelerated plant growth rate, and increased the numbers of axillary branches and flowers. Our molecular and genetic evidence demonstrated that the phenotypes of plants over-expressing ADP1 were caused by reduction of local auxin levels in the meristematic regions. We further discovered that this reduction was probably due to decreased levels of auxin biosynthesis in the local meristematic regions based on the measured reduction in IAA levels and the gene expression data. Simultaneous inactivation of ADP1 and its three closest homologs led to growth retardation, relative reduction of lateral organ number and slightly elevated auxin level. Our results indicated that ADP1-mediated regulation of the local auxin level in meristematic regions is an essential determinant for plant architecture maintenance by restraining the outgrowth of lateral organs. PMID:24391508

Deletion in a quantitative trait gene qPE9-1 associated with panicle erectness improves plant architecture during rice domestication.

PubMed

Zhou, Yong; Zhu, Jinyan; Li, Zhengyi; Yi, Chuandeng; Liu, Jun; Zhang, Honggen; Tang, Shuzhu; Gu, Minghong; Liang, Guohua

2009-09-01

Rice plant architecture is an important agronomic trait and a major determinant in high productivity. Panicle erectness is the preferred plant architecture in japonica rice, but the molecular mechanism underlying domestication of the erect panicle remains elusive. Here we report the map-based cloning of a major quantitative trait locus, qPE9-1, which plays an integral role in regulation of rice plant architecture including panicle erectness. The R6547 qPE9-1 gene encodes a 426-amino-acid protein, homologous to the keratin-associated protein 5-4 family. The gene is composed of three Von Willebrand factor type C domains, one transmembrane domain, and one 4-disulfide-core domain. Phenotypic comparisons of a set of near-isogenic lines and transgenic lines reveal that the functional allele (qPE9-1) results in drooping panicles, and the loss-of-function mutation (qpe9-1) leads to more erect panicles. In addition, the qPE9-1 locus regulates panicle and grain length, grain weight, and consequently grain yield. We propose that the panicle erectness trait resulted from a natural random loss-of-function mutation for the qPE9-1 gene and has subsequently been the target of artificial selection during japonica rice breeding.

A multi-objective optimization approach accurately resolves protein domain architectures

PubMed Central

Bernardes, J.S.; Vieira, F.R.J.; Zaverucha, G.; Carbone, A.

2016-01-01

Motivation: Given a protein sequence and a number of potential domains matching it, what are the domain content and the most likely domain architecture for the sequence? This problem is of fundamental importance in protein annotation, constituting one of the main steps of all predictive annotation strategies. On the other hand, when potential domains are several and in conflict because of overlapping domain boundaries, finding a solution for the problem might become difficult. An accurate prediction of the domain architecture of a multi-domain protein provides important information for function prediction, comparative genomics and molecular evolution. Results: We developed DAMA (Domain Annotation by a Multi-objective Approach), a novel approach that identifies architectures through a multi-objective optimization algorithm combining scores of domain matches, previously observed multi-domain co-occurrence and domain overlapping. DAMA has been validated on a known benchmark dataset based on CATH structural domain assignments and on the set of Plasmodium falciparum proteins. When compared with existing tools on both datasets, it outperforms all of them. Availability and implementation: DAMA software is implemented in C++ and the source code can be found at http://www.lcqb.upmc.fr/DAMA. Contact: juliana.silva_bernardes@upmc.fr or alessandra.carbone@lip6.fr Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26458889

ADP1 affects plant architecture by regulating local auxin biosynthesis.

PubMed

Li, Ruixi; Li, Jieru; Li, Shibai; Qin, Genji; Novák, Ondřej; Pěnčík, Aleš; Ljung, Karin; Aoyama, Takashi; Liu, Jingjing; Murphy, Angus; Gu, Hongya; Tsuge, Tomohiko; Qu, Li-Jia

2014-01-01

Plant architecture is one of the key factors that affect plant survival and productivity. Plant body structure is established through the iterative initiation and outgrowth of lateral organs, which are derived from the shoot apical meristem and root apical meristem, after embryogenesis. Here we report that ADP1, a putative MATE (multidrug and toxic compound extrusion) transporter, plays an essential role in regulating lateral organ outgrowth, and thus in maintaining normal architecture of Arabidopsis. Elevated expression levels of ADP1 resulted in accelerated plant growth rate, and increased the numbers of axillary branches and flowers. Our molecular and genetic evidence demonstrated that the phenotypes of plants over-expressing ADP1 were caused by reduction of local auxin levels in the meristematic regions. We further discovered that this reduction was probably due to decreased levels of auxin biosynthesis in the local meristematic regions based on the measured reduction in IAA levels and the gene expression data. Simultaneous inactivation of ADP1 and its three closest homologs led to growth retardation, relative reduction of lateral organ number and slightly elevated auxin level. Our results indicated that ADP1-mediated regulation of the local auxin level in meristematic regions is an essential determinant for plant architecture maintenance by restraining the outgrowth of lateral organs.

Integrated analysis of microRNAs, transcription factors and target genes expression discloses a specific molecular architecture of hyperdiploid multiple myeloma

PubMed Central

Caracciolo, Daniele; Agnelli, Luca; Neri, Antonino; Walker, Brian A.; Morgan, Gareth J.; Cannataro, Mario

2015-01-01

Multiple Myeloma (MM) is a malignancy characterized by the hyperdiploid (HD-MM) and the non-hyperdiploid (nHD-MM) subtypes. To shed light within the molecular architecture of these subtypes, we used a novel integromics approach. By annotated MM patient mRNA/microRNA (miRNA) datasets, we investigated mRNAs and miRNAs profiles with relation to changes in transcriptional regulators expression. We found that HD-MM displays specific gene and miRNA expression profiles, involving the Signal Transducer and Activator of Transcription (STAT)3 pathway as well as the Transforming Growth Factor–beta (TGFβ) and the transcription regulator Nuclear Protein-1 (NUPR1). Our data define specific molecular features of HD-MM that may translate in the identification of novel relevant druggable targets. PMID:26056083

Testing the limits of sensitivity in a solid-state structural investigation by combined X-ray powder diffraction, solid-state NMR, and molecular modelling.

PubMed

Filip, Xenia; Borodi, Gheorghe; Filip, Claudiu

2011-10-28

A solid state structural investigation of ethoxzolamide is performed on microcrystalline powder by using a multi-technique approach that combines X-ray powder diffraction (XRPD) data analysis based on direct space methods with information from (13)C((15)N) solid-state Nuclear Magnetic Resonance (SS-NMR) and molecular modeling. Quantum chemical computations of the crystal were employed for geometry optimization and chemical shift calculations based on the Gauge Including Projector Augmented-Wave (GIPAW) method, whereas a systematic search in the conformational space was performed on the isolated molecule using a molecular mechanics (MM) approach. The applied methodology proved useful for: (i) removing ambiguities in the XRPD crystal structure determination process and further refining the derived structure solutions, and (ii) getting important insights into the relationship between the complex network of non-covalent interactions and the induced supra-molecular architectures/crystal packing patterns. It was found that ethoxzolamide provides an ideal case study for testing the accuracy with which this methodology allows to distinguish between various structural features emerging from the analysis of the powder diffraction data. This journal is © the Owner Societies 2011

Zeolites: Can they be synthesized by design

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davis, M.E.

1994-09-01

Zeolites and zeolite-like molecular sieves are crystalline oxides that have high surface-to-volume ratios and are able to recognize, discriminate, and organize molecules with differences of < 1 [angstrom]. The close connection between the atomic structure and macroscopic properties of these materials has led to uses in molecular recognition. For example, zeolites and zeolite-like molecular sieves can reveal marvelous molecular recognition specificity and sensitivity that can be applied to catalysis, separations technology, and chemical sensing. Additionally, they can serve as hosts to organize guest atoms and molecules that endow composite materials with optoelectric and electrochemical properties. Because of the high levelmore » of structural control necessary to create high-performance materials with zeolites or zeolite-like molecular sieves, the design and synthesis of these solids with specific architectures and properties are highly desired. Although this lofty goal is still elusive, advances have been made to allow the serious consideration of designing molecular sieves. Here, the author covers two aspects of this ongoing effort. First, he discusses the feasibility of designing pore architectures through the use of organic structure-directing agents. Second, he explores the possibility of creating zeolites through ''Lego chemistry.''« less

Microfluidic multiplexing of solid-state nanopores

NASA Astrophysics Data System (ADS)

Jain, Tarun; Rasera, Benjamin C.; Guerrero, Ricardo Jose S.; Lim, Jong-Min; Karnik, Rohit

2017-12-01

Although solid-state nanopores enable electronic analysis of many clinically and biologically relevant molecular structures, there are few existing device architectures that enable high-throughput measurement of solid-state nanopores. Herein, we report a method for microfluidic integration of multiple solid-state nanopores at a high density of one nanopore per (35 µm2). By configuring microfluidic devices with microfluidic valves, the nanopores can be rinsed from a single fluid input while retaining compatibility for multichannel electrical measurements. The microfluidic valves serve the dual purpose of fluidic switching and electric switching, enabling serial multiplexing of the eight nanopores with a single pair of electrodes. Furthermore, the device architecture exhibits low noise and is compatible with electroporation-based in situ nanopore fabrication, providing a scalable platform for automated electronic measurement of a large number of integrated solid-state nanopores.

Molecular diodes in optical rectennas

NASA Astrophysics Data System (ADS)

Duché, David; Palanchoke, Ujwol; Terracciano, Luigi; Dang, Florian-Xuan; Patrone, Lionel; Le Rouzo, Judikael; Balaban, Téodore Silviu; Alfonso, Claude; Charai, Ahmed; Margeat, Olivier; Ackermann, Jorg; Gourgon, Cécile; Simon, Jean-Jacques; Escoubas, Ludovic

2016-09-01

The photo conversion efficiencies of the 1st and 2nd generat ion photovoltaic solar cells are limited by the physical phenomena involved during the photo-conversion processes. An upper limit around 30% has been predicted for a monojunction silicon solar cell. In this work, we study 3rd generation solar cells named rectenna which could direct ly convert visible and infrared light into DC current. The rectenna technology is at odds with the actual photovoltaic technologies, since it is not based on the use of semi-conducting materials. We study a rectenna architecture consist ing of plasmonic nano-antennas associated with rectifying self assembled molecular diodes. We first opt imized the geometry of plasmonic nano-antennas using an FDTD method. The optimal antennas are then realized using a nano-imprint process and associated with self assembled molecular diodes in 11- ferrocenyl-undecanethiol. Finally, The I(V) characterist ics in darkness of the rectennas has been carried out using an STM. The molecular diodes exhibit averaged rect ification ratios of 5.

eSBMTools 1.0: enhanced native structure-based modeling tools.

PubMed

Lutz, Benjamin; Sinner, Claude; Heuermann, Geertje; Verma, Abhinav; Schug, Alexander

2013-11-01

Molecular dynamics simulations provide detailed insights into the structure and function of biomolecular systems. Thus, they complement experimental measurements by giving access to experimentally inaccessible regimes. Among the different molecular dynamics techniques, native structure-based models (SBMs) are based on energy landscape theory and the principle of minimal frustration. Typically used in protein and RNA folding simulations, they coarse-grain the biomolecular system and/or simplify the Hamiltonian resulting in modest computational requirements while achieving high agreement with experimental data. eSBMTools streamlines running and evaluating SBM in a comprehensive package and offers high flexibility in adding experimental- or bioinformatics-derived restraints. We present a software package that allows setting up, modifying and evaluating SBM for both RNA and proteins. The implemented workflows include predicting protein complexes based on bioinformatics-derived inter-protein contact information, a standardized setup of protein folding simulations based on the common PDB format, calculating reaction coordinates and evaluating the simulation by free-energy calculations with weighted histogram analysis method or by phi-values. The modules interface with the molecular dynamics simulation program GROMACS. The package is open source and written in architecture-independent Python2. http://sourceforge.net/projects/esbmtools/. alexander.schug@kit.edu. Supplementary data are available at Bioinformatics online.

Outline of a novel architecture for cortical computation.

PubMed

Majumdar, Kaushik

2008-03-01

In this paper a novel architecture for cortical computation has been proposed. This architecture is composed of computing paths consisting of neurons and synapses. These paths have been decomposed into lateral, longitudinal and vertical components. Cortical computation has then been decomposed into lateral computation (LaC), longitudinal computation (LoC) and vertical computation (VeC). It has been shown that various loop structures in the cortical circuit play important roles in cortical computation as well as in memory storage and retrieval, keeping in conformity with the molecular basis of short and long term memory. A new learning scheme for the brain has also been proposed and how it is implemented within the proposed architecture has been explained. A few mathematical results about the architecture have been proposed, some of which are without proof.

Genomics-Based Security Protocols: From Plaintext to Cipherprotein

NASA Technical Reports Server (NTRS)

Shaw, Harry; Hussein, Sayed; Helgert, Hermann

2011-01-01

The evolving nature of the internet will require continual advances in authentication and confidentiality protocols. Nature provides some clues as to how this can be accomplished in a distributed manner through molecular biology. Cryptography and molecular biology share certain aspects and operations that allow for a set of unified principles to be applied to problems in either venue. A concept for developing security protocols that can be instantiated at the genomics level is presented. A DNA (Deoxyribonucleic acid) inspired hash code system is presented that utilizes concepts from molecular biology. It is a keyed-Hash Message Authentication Code (HMAC) capable of being used in secure mobile Ad hoc networks. It is targeted for applications without an available public key infrastructure. Mechanics of creating the HMAC are presented as well as a prototype HMAC protocol architecture. Security concepts related to the implementation differences between electronic domain security and genomics domain security are discussed.

Intravital assessment of myelin molecular order with polarimetric multiphoton microscopy

NASA Astrophysics Data System (ADS)

Turcotte, Raphaël; Rutledge, Danette J.; Bélanger, Erik; Dill, Dorothy; Macklin, Wendy B.; Côté, Daniel C.

2016-08-01

Myelin plays an essential role in the nervous system and its disruption in diseases such as multiple sclerosis may lead to neuronal death, thus causing irreversible functional impairments. Understanding myelin biology is therefore of fundamental and clinical importance, but no tools currently exist to describe the fine spatial organization of myelin sheaths in vivo. Here we demonstrate intravital quantification of the myelin molecular structure using a microscopy method based on polarization-resolved coherent Raman scattering. Developmental myelination was imaged noninvasively in live zebrafish. Longitudinal imaging of individual axons revealed changes in myelin organization beyond the diffraction limit. Applied to promyelination drug screening, the method uniquely enabled the identification of focal myelin regions with differential architectures. These observations indicate that the study of myelin biology and the identification of therapeutic compounds will largely benefit from a method to quantify the myelin molecular organization in vivo.

Designed synthesis and supramolecular architectures of furan-substituted perylene diimide.

PubMed

Yu, Yanwen; Li, Yongjun; Qin, Zhihong; Jiang, Runsheng; Liu, Huibiao; Li, Yuliang

2013-06-01

Novel furan-substituted perylene diimides are successfully synthesized and an efficient supramolecular architecture approach to construct zero/one-dimensional nano- and micro-structures by controlling solvents has been demonstrated. The aggregate structure conversion in different molecular structures can be controlled in the form of sphere-like, rod-like, and vesicle-like structures. As expected, these solid supramolecular rod-like architectures displayed interesting optical waveguide behavior, which indicates the aggregate structure materials of furan-substituted perylene diimides have the potential application as micro-scale photonic elements. Copyright © 2013 Elsevier Inc. All rights reserved.

Discovery of a diazo-forming enzyme in cremeomycin biosynthesis.

PubMed

Waldman, Abraham J; Balskus, Emily P

2018-05-17

The molecular architectures and potent bioactivities of diazo-containing natural products have attracted the interest of synthetic and biological chemists. Despite this attention, the biosynthetic enzymes involved in diazo group construction have not been identified. Here, we show the ATP-dependent enzyme CreM installs the diazo group in cremeomycin via late-stage N-N bond formation using nitrite. This finding should inspire efforts to use diazo-forming enzymes in biocatalysis and synthetic biology and enable genome-based discovery of new diazo-containing metabolites.

Carbon Nanotube Based Groundwater Remediation: The Case of Trichloroethylene.

PubMed

Jha, Kshitij C; Liu, Zhuonan; Vijwani, Hema; Nadagouda, Mallikarjuna; Mukhopadhyay, Sharmila M; Tsige, Mesfin

2016-07-21

Adsorption of chlorinated organic contaminants (COCs) on carbon nanotubes (CNTs) has been gaining ground as a remedial platform for groundwater treatment. Applications depend on our mechanistic understanding of COC adsorption on CNTs. This paper lays out the nature of competing interactions at play in hybrid, membrane, and pure CNT based systems and presents results with the perspective of existing gaps in design strategies. First, current remediation approaches to trichloroethylene (TCE), the most ubiquitous of the COCs, is presented along with examination of forces contributing to adsorption of analogous contaminants at the molecular level. Second, we present results on TCE adsorption and remediation on pure and hybrid CNT systems with a stress on the specific nature of substrate and molecular architecture that would contribute to competitive adsorption. The delineation of intermolecular interactions that contribute to efficient remediation is needed for custom, scalable field design of purification systems for a wide range of contaminants.

Translating genomic information into clinical medicine: lung cancer as a paradigm.

PubMed

Levy, Mia A; Lovly, Christine M; Pao, William

2012-11-01

We are currently in an era of rapidly expanding knowledge about the genetic landscape and architectural blueprints of various cancers. These discoveries have led to a new taxonomy of malignant diseases based upon clinically relevant molecular alterations in addition to histology or tissue of origin. The new molecularly based classification holds the promise of rational rather than empiric approaches for the treatment of cancer patients. However, the accelerated pace of discovery and the expanding number of targeted anti-cancer therapies present a significant challenge for healthcare practitioners to remain informed and up-to-date on how to apply cutting-edge discoveries into daily clinical practice. In this Perspective, we use lung cancer as a paradigm to discuss challenges related to translating genomic information into the clinic, and we present one approach we took at Vanderbilt-Ingram Cancer Center to address these challenges.

Chromosome structure inside the nucleus.

PubMed

Swedlow, J R; Agard, D A; Sedat, J W

1993-06-01

Recent in situ three-dimensional structural studies have provided a new model for the 30 nm chromatin fiber. In addition, research during the past year has revealed some of the molecular complexity of non-histone chromosomal proteins. Still to come is the unification of molecular insights with chromosomal architecture.

The Molecular Basis of Development.

ERIC Educational Resources Information Center

Gehring, Walter J.

1985-01-01

Basic architecture of embryo development appears to be under homeobox control (a short stretch of DNA). Outlines research on this genetic segment in fruit flies which led to identification of this control on the embryo's spatial organization. Indicates that molecular mechanisms underlying development may be much more universal than previously…

Preparation and antifouling properties of 2-(meth-acryloyloxy)ethyl cholinephosphate based polymers modified surface with different molecular architectures by ATRP.

PubMed

Jiang, Yuchen; Su, Yuling; Zhao, Lili; Meng, Fancui; Wang, Quanxin; Ding, Chunmei; Luo, Jianbin; Li, Jianshu

2017-08-01

Choline phosphate (CP) containing polymers modified surfaces have been shown good resist to the adhesion of proteins while prompt the attaching of mammalian cells due to the dipole pairing between the CP groups of the polymer and the phosphorylcholine (PC) groups on the cell membrane. However, the antifouling activities of CP modified surface against microbes have not been investigated at present. In addition, CP containing polymers modified surface with different molecular architectures has not been prepared and studied. To this end, glass slides surface modified with two different 2-(meth-acryloyloxy)ethyl cholinephosphate (MCP) containing polymer (PMCP) structures, i.e. brush-like (Glass-PMCP) and bottle brush-like (Glass-PHEMA-g-PMCP) architectures, were prepared in this work by surface-initiated atom transfer radical polymerization (SI-ATRP). The surface physichemical and antifouling properties of the prepared surfaces were characterized and studied. The Glass-PMCP shows improved antifouling properties against proteins and bacteria as compared to pristine glass slides (Glass-OH) and glass slides grafted with poly(2-hydroxyethyl methacrylate) (Glass-PHEMA). Notably, a synergetic fouling resistant properties of PHEMA and PMCP is presented for Glass-PHEMA-g-PMCP, which shows superior antifouling activities over Glass-PHEMA and Glass-PMCP. Furthermore, glass slides containing PMCP, i.e. Glass-PMCP and Glas-PHEMA-g-PMCP, decrease platelet adhesion and prevent their activation significantly. Therefore, the combination of antifouling PHEMA and PMCP into one system holds potential for prevention of bacterial fouling and biomaterial-centered infections. Copyright © 2017 Elsevier B.V. All rights reserved.

Aggrecan-Like Biomimetic Proteoglycans (BPGs) Composed of Natural Chondroitin Sulfate Bristles Grafted onto Poly(acrylic acid) Core for Molecular Engineering of the Extracellular Matrix.

PubMed

Prudnikova, K; Lightfoot Vidal, S E; Sarkar, S; Yu, T; Yucha, R W; Ganesh, N; Penn, L S; Han, L; Schauer, C L; Vresilovic, E J; Marcolongo, M S

2018-05-10

Biomimetic proteoglycans (BPGs) were designed to mimic the three-dimensional (3D) bottlebrush architecture of natural extracellular matrix (ECM) proteoglycans, such as aggrecan. BPGs were synthesized by grafting native chondroitin sulfate bristles onto a synthetic poly(acrylic acid) core to form BPGs at a molecular weight of approximately ∼1.6 MDa. The aggrecan mimics were characterized chemically, physically, and structurally, confirming the 3D bottlebrush architecture as well as a level of water uptake, which is greater than that of the natural proteoglycan, aggrecan. Aggrecan mimics were cytocompatible at physiological concentrations. Fluorescently labeled BPGs were injected into the nucleus pulposus of the intervertebral disc ex vivo and were retained in tissue before and after static loading and equilibrium conditioning. BPGs infiltrated the tissue, distributed and integrated with the ECM on a molecular scale, in the absence of a bolus, thus demonstrating a new molecular approach to tissue repair: molecular matrix engineering. Molecular matrix engineering may compliment or offer an acellular alternative to current regenerative medicine strategies. Aggrecan is a natural biomolecule that is essential for connective tissue hydration and mechanics. Aggrecan is composed of negatively charged chondroitin sulfate bristles attached to a protein core in a bottlebrush configuration. With age and degeneration, enzymatic degradation of aggrecan outpaces cellular synthesis resulting in a loss of this important molecule. We demonstrate a novel biomimetic molecule composed of natural chondroitin sulfate bristles grafted onto an enzymatically-resistant synthetic core. Our molecule mimics a 3D architecture and charge density of the natural aggrecan, can be delivered via a simple injection and is retained in tissue after equilibrium conditioning and loading. This novel material can serve as a platform for molecular repair, drug delivery and tissue engineering in regenerative medicine approaches. Copyright © 2018. Published by Elsevier Ltd.

Spatially Controlled Noncovalent Functionalization of 2D Materials Based on Molecular Architecture.

PubMed

Bang, Jae Jin; Porter, Ashlin G; Davis, Tyson C; Hayes, Tyler R; Claridge, Shelley A

2018-05-15

Polymerizable amphiphiles can be assembled into lying-down phases on 2D materials such as graphite and graphene to create chemically orthogonal surface patterns at 5-10 nm scales, locally modulating functionality of the 2D basal plane. Functionalization can be carried out through Langmuir-Schaefer conversion, in which a subset of molecules is transferred out of a standing phase film on water onto the 2D substrate. Here, we leverage differences in molecular structure to spatially control transfer at both nanoscopic and microscopic scales. We compare transfer properties of five different single- and dual-chain amphiphiles, demonstrating that those with strong lateral interactions (e.g., hydrogen-bonding networks) exhibit the lowest transfer efficiencies. Since molecular structures also influence microscopic domain morphologies in Langmuir films, we show that it is possible to transfer such microscale patterns, taking advantage of variations in the local transfer rates based on the structural heterogeneity in Langmuir films. Nanoscale domain morphologies also vary in ways that are consistent with predicted relative transfer and diffusion rates. These results suggest strategies to tailor noncovalent functionalization of 2D substrates through controlled LS transfer.

Generation of Well-Relaxed All-Atom Models of Large Molecular Weight Polymer Melts: A Hybrid Particle-Continuum Approach Based on Particle-Field Molecular Dynamics Simulations.

PubMed

De Nicola, Antonio; Kawakatsu, Toshihiro; Milano, Giuseppe

2014-12-09

A procedure based on Molecular Dynamics (MD) simulations employing soft potentials derived from self-consistent field (SCF) theory (named MD-SCF) able to generate well-relaxed all-atom structures of polymer melts is proposed. All-atom structures having structural correlations indistinguishable from ones obtained by long MD relaxations have been obtained for poly(methyl methacrylate) (PMMA) and poly(ethylene oxide) (PEO) melts. The proposed procedure leads to computational costs mainly related on system size rather than to the chain length. Several advantages of the proposed procedure over current coarse-graining/reverse mapping strategies are apparent. No parametrization is needed to generate relaxed structures of different polymers at different scales or resolutions. There is no need for special algorithms or back-mapping schemes to change the resolution of the models. This characteristic makes the procedure general and its extension to other polymer architectures straightforward. A similar procedure can be easily extended to the generation of all-atom structures of block copolymer melts and polymer nanocomposites.

Synthesis and Characterization of Elastin-Mimetic Hybrid Polymers with Multiblock, Alternating Molecular Architecture and Elastomeric Properties

PubMed Central

Grieshaber, Sarah E.; Farran, Alexandra J. E.; Lin-Gibson, Sheng; Kiick, Kristi L.; Jia, Xinqiao

2009-01-01

We are interested in developing elastin–mimetic hybrid polymers (EMHPs) that capture the multiblock molecular architecture of tropoelastin as well as the remarkable elasticity of mature elastin. In this study, multiblock EMHPs containing flexible synthetic segments based on poly(ethylene glycol) (PEG) alternating with alanine-rich, lysine-containing peptides were synthesized by step-growth polymerization using α,ω-azido-PEG and alkyne-terminated AKA3KA (K = lysine, A = alanine) peptide, employing orthogonal click chemistry. The resulting EMHPs contain an estimated three to five repeats of PEG and AKA3KA and have an average molecular weight of 34 kDa. While the peptide alone exhibited α-helical structures at high pH, the fractional helicity for EMHPs was reduced. Covalent cross-linking of EMHPs with hexamethylene diisocyanate (HMDI) through the lysine residue in the peptide domain afforded an elastomeric hydrogel (xEMHP) with a compressive modulus of 0.12 MPa when hydrated. The mechanical properties of xEMHP are comparable to a commercial polyurethane elastomer (Tecoflex SG80A) under the same conditions. In vitro toxicity studies showed that while the soluble EMHPs inhibited the growth of primary porcine vocal fold fibroblasts (PVFFs) at concentrations ≥0.2 mg/mL, the cross-linked hybrid elastomers did not leach out any toxic reagents and allowed PVFFs to grow and proliferate normally. The hybrid and modular approach provides a new strategy for developing elastomeric scaffolds for tissue engineering. PMID:19763157

A simple theory of molecular organization in fullerene-containing liquid crystals

NASA Astrophysics Data System (ADS)

Peroukidis, S. D.; Vanakaras, A. G.; Photinos, D. J.

2005-10-01

Systematic efforts to synthesize fullerene-containing liquid crystals have produced a variety of successful model compounds. We present a simple molecular theory, based on the interconverting shape approach [Vanakaras and Photinos, J. Mater. Chem. 15, 2002 (2005)], that relates the self-organization observed in these systems to their molecular structure. The interactions are modeled by dividing each molecule into a number of submolecular blocks to which specific interactions are assigned. Three types of blocks are introduced, corresponding to fullerene units, mesogenic units, and nonmesogenic linkage units. The blocks are constrained to move on a cubic three-dimensional lattice and molecular flexibility is allowed by retaining a number of representative conformations within the block representation of the molecule. Calculations are presented for a variety of molecular architectures including twin mesogenic branch monoadducts of C60, twin dendromesogenic branch monoadducts, and conical (badminton shuttlecock) multiadducts of C60. The dependence of the phase diagrams on the interaction parameters is explored. In spite of its many simplifications and the minimal molecular modeling used (three types of chemically distinct submolecular blocks with only repulsive interactions), the theory accounts remarkably well for the phase behavior of these systems.

EFFECT OF MOLECULAR ARCHITECTURE ON DBS-INDUCED BLOCK COPOLYMER GELS: A RHEOLOGICAL STUDY

EPA Science Inventory

Dibenzylidene sorbitol (DBS) is capable of gelling a variety of organic solvents and polymeric materials by forming a rigid, 3-D hydrogen-bonded network. In this work, two poly(siloxane)/poly(propylene oxide) segmented copolymers of equal composition and molecular weight, but di...

Polymer Architecture Effects in Confined Geometry: Molecular Dynamics Simulation Study

NASA Astrophysics Data System (ADS)

Wijesinghe, Sidath; Perahia, Dvora; Grest, Gary

Luminescent rigid polymers confined into nanoparticles, or polydots, are emerging as a promising tool for nano medicine. The constrained architecture of a rigid backbone trapped in nano-dimensions results in photophysics that differs from that of spontaneously assembled rigid polymers. Incorporating ionizable functionalities in the polymers, often required for therapeutics, impacts the polymer conformation in solution. Here we report fully atomistic molecular dynamics simulations on the structure of dialkyl p-phenylene ethynylene confined into polydots. We find that the structure and thermal stability of polydots are sensitive to both the molecular weight n and the carboxylation fraction f. At room temperature , polydots remain confined regardless of n and f . However, as temperature is increased, polydots with lower n or f rearrange whereas polydots with higher n or fremain confined, though no direct clustering of the ionic groups was observed. NSF CHE 1308298 is acknowledged.

Scalable synthesis of sequence-defined, unimolecular macromolecules by Flow-IEG

PubMed Central

Leibfarth, Frank A.; Johnson, Jeremiah A.; Jamison, Timothy F.

2015-01-01

We report a semiautomated synthesis of sequence and architecturally defined, unimolecular macromolecules through a marriage of multistep flow synthesis and iterative exponential growth (Flow-IEG). The Flow-IEG system performs three reactions and an in-line purification in a total residence time of under 10 min, effectively doubling the molecular weight of an oligomeric species in an uninterrupted reaction sequence. Further iterations using the Flow-IEG system enable an exponential increase in molecular weight. Incorporating a variety of monomer structures and branching units provides control over polymer sequence and architecture. The synthesis of a uniform macromolecule with a molecular weight of 4,023 g/mol is demonstrated. The user-friendly nature, scalability, and modularity of Flow-IEG provide a general strategy for the automated synthesis of sequence-defined, unimolecular macromolecules. Flow-IEG is thus an enabling tool for theory validation, structure–property studies, and advanced applications in biotechnology and materials science. PMID:26269573

A combined computational and structural model of the full-length human prolactin receptor

PubMed Central

Bugge, Katrine; Papaleo, Elena; Haxholm, Gitte W.; Hopper, Jonathan T. S.; Robinson, Carol V.; Olsen, Johan G.; Lindorff-Larsen, Kresten; Kragelund, Birthe B.

2016-01-01

The prolactin receptor is an archetype member of the class I cytokine receptor family, comprising receptors with fundamental functions in biology as well as key drug targets. Structurally, each of these receptors represent an intriguing diversity, providing an exceptionally challenging target for structural biology. Here, we access the molecular architecture of the monomeric human prolactin receptor by combining experimental and computational efforts. We solve the NMR structure of its transmembrane domain in micelles and collect structural data on overlapping fragments of the receptor with small-angle X-ray scattering, native mass spectrometry and NMR spectroscopy. Along with previously published data, these are integrated by molecular modelling to generate a full receptor structure. The result provides the first full view of a class I cytokine receptor, exemplifying the architecture of more than 40 different receptor chains, and reveals that the extracellular domain is merely the tip of a molecular iceberg. PMID:27174498

Embracing the comparative approach: how robust phylogenies and broader developmental sampling impacts the understanding of nervous system evolution.

PubMed

Hejnol, Andreas; Lowe, Christopher J

2015-12-19

Molecular biology has provided a rich dataset to develop hypotheses of nervous system evolution. The startling patterning similarities between distantly related animals during the development of their central nervous system (CNS) have resulted in the hypothesis that a CNS with a single centralized medullary cord and a partitioned brain is homologous across bilaterians. However, the ability to precisely reconstruct ancestral neural architectures from molecular genetic information requires that these gene networks specifically map with particular neural anatomies. A growing body of literature representing the development of a wider range of metazoan neural architectures demonstrates that patterning gene network complexity is maintained in animals with more modest levels of neural complexity. Furthermore, a robust phylogenetic framework that provides the basis for testing the congruence of these homology hypotheses has been lacking since the advent of the field of 'evo-devo'. Recent progress in molecular phylogenetics is refining the necessary framework to test previous homology statements that span large evolutionary distances. In this review, we describe recent advances in animal phylogeny and exemplify for two neural characters-the partitioned brain of arthropods and the ventral centralized nerve cords of annelids-a test for congruence using this framework. The sequential sister taxa at the base of Ecdysozoa and Spiralia comprise small, interstitial groups. This topology is not consistent with the hypothesis of homology of tripartitioned brain of arthropods and vertebrates as well as the ventral arthropod and rope-like ladder nervous system of annelids. There can be exquisite conservation of gene regulatory networks between distantly related groups with contrasting levels of nervous system centralization and complexity. Consequently, the utility of molecular characters to reconstruct ancestral neural organization in deep time is limited. © 2015 The Authors.

Embracing the comparative approach: how robust phylogenies and broader developmental sampling impacts the understanding of nervous system evolution

PubMed Central

Hejnol, Andreas; Lowe, Christopher J.

2015-01-01

Molecular biology has provided a rich dataset to develop hypotheses of nervous system evolution. The startling patterning similarities between distantly related animals during the development of their central nervous system (CNS) have resulted in the hypothesis that a CNS with a single centralized medullary cord and a partitioned brain is homologous across bilaterians. However, the ability to precisely reconstruct ancestral neural architectures from molecular genetic information requires that these gene networks specifically map with particular neural anatomies. A growing body of literature representing the development of a wider range of metazoan neural architectures demonstrates that patterning gene network complexity is maintained in animals with more modest levels of neural complexity. Furthermore, a robust phylogenetic framework that provides the basis for testing the congruence of these homology hypotheses has been lacking since the advent of the field of ‘evo-devo’. Recent progress in molecular phylogenetics is refining the necessary framework to test previous homology statements that span large evolutionary distances. In this review, we describe recent advances in animal phylogeny and exemplify for two neural characters—the partitioned brain of arthropods and the ventral centralized nerve cords of annelids—a test for congruence using this framework. The sequential sister taxa at the base of Ecdysozoa and Spiralia comprise small, interstitial groups. This topology is not consistent with the hypothesis of homology of tripartitioned brain of arthropods and vertebrates as well as the ventral arthropod and rope-like ladder nervous system of annelids. There can be exquisite conservation of gene regulatory networks between distantly related groups with contrasting levels of nervous system centralization and complexity. Consequently, the utility of molecular characters to reconstruct ancestral neural organization in deep time is limited. PMID:26554039

Effects of p-(Trifluoromethoxy)benzyl and p-(Trifluoromethoxy)phenyl Molecular Architecture on the Performance of Naphthalene Tetracarboxylic Diimide-Based Air-Stable n-Type Semiconductors.

PubMed

Zhang, Dongwei; Zhao, Liang; Zhu, Yanan; Li, Aiyuan; He, Chao; Yu, Hongtao; He, Yaowu; Yan, Chaoyi; Goto, Osamu; Meng, Hong

2016-07-20

N,N'-Bis(4-trifluoromethoxyphenyl) naphthalene-1,4,5,8-tetracarboxylic acid diimide (NDI-POCF3) and N,N'-bis(4-trifluoromethoxybenzyl) naphthalene-1,4,5,8-tetracarboxylic acid diimide (NDI-BOCF3) have similar optical and electrochemical properties with a deep LUMO level of approximately 4.2 eV, but exhibit significant differences in electron mobility and molecular packing. NDI-POCF3 exhibits nondetectable charge mobility. Interestingly, NDI-BOCF3 shows air-stable electron transfer performance with enhanced mobility by increasing the deposition temperature onto the octadecyltrichlorosilane (OTS)-modified SiO2/Si substrates and achieves electron mobility as high as 0.7 cm(2) V(-1) s(-1) in air. The different mobilities of those two materials can be explained by several factors including thin-film morphology and crystallinity. In contrast to the poor thin-film morphology and crystallinity of NDI-POCF3, NDI-BOCF3 exhibits larger grain sizes and improved crystallinities due to the higher deposition temperature. In addition, the theoretical calculated transfer integrals of the intermolecular lowest unoccupied molecular orbital (LUMO) of the two materials further show that a large intermolecular orbital overlap of NDI-BOCF3 can transfer electron more efficiently than NDI-POCF3 in thin-film transistors. On the basis of fact that the theoretical calculations are consistent with the experimental results, it can be concluded that the p-(trifluoromethoxy) benzyl (BOCF3) molecular architecture on the former position of the naphthalene tetracarboxylic diimides (NDI) core provides a more effective way to enhance the intermolecular electron transfer property than the p-(trifluoromethoxy) phenyl (POCF3) group for the future design of NDI-related air-stable n-channel semiconductor.

Molecular Architecture and Biomedical Leads of Terpenes from Red Sea Marine Invertebrates

PubMed Central

Hegazy, Mohamed Elamir F.; Mohamed, Tarik A.; Alhammady, Montaser A.; Shaheen, Alaa M.; Reda, Eman H.; Elshamy, Abdelsamed I.; Aziz, Mina; Paré, Paul W.

2015-01-01

Marine invertebrates including sponges, soft coral, tunicates, mollusks and bryozoan have proved to be a prolific source of bioactive natural products. Among marine-derived metabolites, terpenoids have provided a vast array of molecular architectures. These isoprenoid-derived metabolites also exhibit highly specialized biological activities ranging from nerve regeneration to blood-sugar regulation. As a result, intense research activity has been devoted to characterizing invertebrate terpenes from both a chemical and biological standpoint. This review focuses on the chemistry and biology of terpene metabolites isolated from the Red Sea ecosystem, a unique marine biome with one of the highest levels of biodiversity and specifically rich in invertebrate species. PMID:26006713

Transcriptional Architecture of Synaptic Communication Delineates GABAergic Neuron Identity.

PubMed

Paul, Anirban; Crow, Megan; Raudales, Ricardo; He, Miao; Gillis, Jesse; Huang, Z Josh

2017-10-19

Understanding the organizational logic of neural circuits requires deciphering the biological basis of neuronal diversity and identity, but there is no consensus on how neuron types should be defined. We analyzed single-cell transcriptomes of a set of anatomically and physiologically characterized cortical GABAergic neurons and conducted a computational genomic screen for transcriptional profiles that distinguish them from one another. We discovered that cardinal GABAergic neuron types are delineated by a transcriptional architecture that encodes their synaptic communication patterns. This architecture comprises 6 categories of ∼40 gene families, including cell-adhesion molecules, transmitter-modulator receptors, ion channels, signaling proteins, neuropeptides and vesicular release components, and transcription factors. Combinatorial expression of select members across families shapes a multi-layered molecular scaffold along the cell membrane that may customize synaptic connectivity patterns and input-output signaling properties. This molecular genetic framework of neuronal identity integrates cell phenotypes along multiple axes and provides a foundation for discovering and classifying neuron types. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular architecture of botulinum neurotoxin E revealed by single particle electron microscopy.

PubMed

Fischer, Audrey; Garcia-Rodriguez, Consuelo; Geren, Isin; Lou, Jianlong; Marks, James D; Nakagawa, Terunaga; Montal, Mauricio

2008-02-15

Clostridial botulinum neurotoxin (BoNT) causes a neuroparalytic condition recognized as botulism by arresting synaptic vesicle exocytosis. Although the crystal structures of full-length BoNT/A and BoNT/B holotoxins are known, the molecular architecture of the five other serotypes remains elusive. Here, we present the structures of BoNT/A and BoNT/E using single particle electron microscopy. Labeling of the particles with three different monoclonal antibodies raised against BoNT/E revealed the positions of their epitopes in the electron microscopy structure, thereby identifying the three hallmark domains of BoNT (protease, translocation, and receptor binding). Correspondingly, these antibodies selectively inhibit BoNT translocation activity as detected using a single molecule assay. The global structure of BoNT/E is strikingly different from that of BoNT/A despite strong sequence similarity. We postulate that the unique architecture of functionally conserved modules underlies the distinguishing attributes of BoNT/E and contributes to differences with BoNT/A.

Molecular Architecture of Contactin-associated Protein-like 2 (CNTNAP2) and Its Interaction with Contactin 2 (CNTN2).

PubMed

Lu, Zhuoyang; Reddy, M V V V Sekhar; Liu, Jianfang; Kalichava, Ana; Liu, Jiankang; Zhang, Lei; Chen, Fang; Wang, Yun; Holthauzen, Luis Marcelo F; White, Mark A; Seshadrinathan, Suchithra; Zhong, Xiaoying; Ren, Gang; Rudenko, Gabby

2016-11-11

Contactin-associated protein-like 2 (CNTNAP2) is a large multidomain neuronal adhesion molecule implicated in a number of neurological disorders, including epilepsy, schizophrenia, autism spectrum disorder, intellectual disability, and language delay. We reveal here by electron microscopy that the architecture of CNTNAP2 is composed of a large, medium, and small lobe that flex with respect to each other. Using epitope labeling and fragments, we assign the F58C, L1, and L2 domains to the large lobe, the FBG and L3 domains to the middle lobe, and the L4 domain to the small lobe of the CNTNAP2 molecular envelope. Our data reveal that CNTNAP2 has a very different architecture compared with neurexin 1α, a fellow member of the neurexin superfamily and a prototype, suggesting that CNTNAP2 uses a different strategy to integrate into the synaptic protein network. We show that the ectodomains of CNTNAP2 and contactin 2 (CNTN2) bind directly and specifically, with low nanomolar affinity. We show further that mutations in CNTNAP2 implicated in autism spectrum disorder are not segregated but are distributed over the whole ectodomain. The molecular shape and dimensions of CNTNAP2 place constraints on how CNTNAP2 integrates in the cleft of axo-glial and neuronal contact sites and how it functions as an organizing and adhesive molecule. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Magnetic field controlled graphene oxide-based origami with enhanced surface area and mechanical properties.

PubMed

Park, Ok-Kyung; Tiwary, Chandra Sekhar; Yang, Yang; Bhowmick, Sanjit; Vinod, Soumya; Zhang, Qingbo; Colvin, Vicki L; Asif, S A Syed; Vajtai, Robert; Penev, Evgeni S; Yakobson, Boris I; Ajayan, Pulickel M

2017-06-01

One can utilize the folding of paper to build fascinating 3D origami architectures with extraordinary mechanical properties and surface area. Inspired by the same, the morphology of 2D graphene can be tuned by addition of magnetite (Fe 3 O 4 ) nanoparticles in the presence of a magnetic field. The innovative 3D architecture with enhanced mechanical properties also shows a high surface area (∼2500 m 2 g -1 ) which is utilized for oil absorption. Detailed microscopy and spectroscopy reveal rolling of graphene oxide (GO) sheets due to the magnetic field driven action of magnetite particles, which is further supported by molecular dynamics (MD) simulations. The macroscopic and local deformation resulting from in situ mechanical loading inside a scanning electron microscope reveals a change in the mechanical response due to a change internal morphology, which is further supported by MD simulation.

Defining the landscape of adaptive genetic diversity.

PubMed

Eckert, Andrew J; Dyer, Rodney J

2012-06-01

Whether they are used to describe fitness, genome architecture or the spatial distribution of environmental variables, the concept of a landscape has figured prominently in our collective reasoning. The tradition of landscapes in evolutionary biology is one of fitness mapped onto axes defined by phenotypes or molecular sequence states. The characteristics of these landscapes depend on natural selection, which is structured across both genomic and environmental landscapes, and thus, the bridge among differing uses of the landscape concept (i.e. metaphorically or literally) is that of an adaptive phenotype and its distribution across geographical landscapes in relation to selective pressures. One of the ultimate goals of evolutionary biology should thus be to construct fitness landscapes in geographical space. Natural plant populations are ideal systems with which to explore the feasibility of attaining this goal, because much is known about the quantitative genetic architecture of complex traits for many different plant species. What is less known are the molecular components of this architecture. In this issue of Molecular Ecology, Parchman et al. (2012) pioneer one of the first truly genome-wide association studies in a tree that moves us closer to this form of mechanistic understanding for an adaptive phenotype in natural populations of lodgepole pine (Pinus contorta Dougl. ex Loud.). © 2012 Blackwell Publishing Ltd.

Using dSTORM to probe the molecular architecture of filopodia

NASA Astrophysics Data System (ADS)

Ahmed, Sohail; Chou, Amy; Sem, K. P.; Thankiah, Sudaharan; Wright, Graham; Lim, John; Hariharan, Srivats

2014-03-01

IRSp53 is a Cdc42 effector and a member of the Inverse-Bin-Amphiphysins-Rvs (I-BAR) domain family which can induce negative membrane curvature. IRSp53 generates filopodia by coupling membrane protrusion (I-BAR domain) with actin dynamics through its SH3 domain binding partners. Dynamin 1 (Dyn1), a large GTPase associated with endocytosis, is a novel interacting partner of IRSp53 that localises to filopodia. Using rapid time-lapse TIRF microscopy we have shown that Dyn1 localized to a subcellular region just behind Mena at the leading edge, or in filopodial tip complexes when co-expressed with IRSp53. Dyn1-GFP was strongly localized in the filopodial shaft during the early phase of elongation, after which it moved rearward, suggestive of a role in early filopodia assembly. Mena and Eps8, accumulate at the tip complex in sequence and are involved in filopodial extension and retraction, respectively (Chou at al, 2014 submitted). Here we describe the use of dSTORM to investigate the molecular architecture of filopodia and in particular the size of the F-actin bundle in these structures. The data suggest that direct Stochastic Optical Reconstruction Microscopy (dSTORM) in combination with other techniques will allow the molecular architecture of

When 2D Materials Meet Molecules: Opportunities and Challenges of Hybrid Organic/Inorganic van der Waals Heterostructures.

PubMed

Gobbi, Marco; Orgiu, Emanuele; Samorì, Paolo

2018-05-01

van der Waals heterostructures, composed of vertically stacked inorganic 2D materials, represent an ideal platform to demonstrate novel device architectures and to fabricate on-demand materials. The incorporation of organic molecules within these systems holds an immense potential, since, while nature offers a finite number of 2D materials, an almost unlimited variety of molecules can be designed and synthesized with predictable functionalities. The possibilities offered by systems in which continuous molecular layers are interfaced with inorganic 2D materials to form hybrid organic/inorganic van der Waals heterostructures are emphasized. Similar to their inorganic counterpart, the hybrid structures have been exploited to put forward novel device architectures, such as antiambipolar transistors and barristors. Moreover, specific molecular groups can be employed to modify intrinsic properties and confer new capabilities to 2D materials. In particular, it is highlighted how molecular self-assembly at the surface of 2D materials can be mastered to achieve precise control over position and density of (molecular) functional groups, paving the way for a new class of hybrid functional materials whose final properties can be selected by careful molecular design. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Supramolecular Architectures and Mimics of Complex Natural Folds Derived from Rationally Designed alpha-Helical Protein Structures

NASA Astrophysics Data System (ADS)

Tavenor, Nathan Albert

Protein-based supramolecular polymers (SMPs) are a class of biomaterials which draw inspiration from and expand upon the many examples of complex protein quaternary structures observed in nature: collagen, microtubules, viral capsids, etc. Designing synthetic supramolecular protein scaffolds both increases our understanding of natural superstructures and allows for the creation of novel materials. Similar to small-molecule SMPs, protein-based SMPs form due to self-assembly driven by intermolecular interactions between monomers, and monomer structure determines the properties of the overall material. Using protein-based monomers takes advantage of the self-assembly and highly specific molecular recognition properties encodable in polypeptide sequences to rationally design SMP architectures. The central hypothesis underlying our work is that alpha-helical coiled coils, a well-studied protein quaternary folding motif, are well-suited to SMP design through the addition of synthetic linkers at solvent-exposed sites. Through small changes in the structures of the cross-links and/or peptide sequence, we have been able to control both the nanoscale organization and the macroscopic properties of the SMPs. Changes to the linker and hydrophobic core of the peptide can be used to control polymer rigidity, stability, and dimensionality. The gaps in knowledge that this thesis sought to fill on this project were 1) the relationship between the molecular structure of the cross-linked polypeptides and the macroscopic properties of the SMPs and 2) a means of creating materials exhibiting multi-dimensional net or framework topologies. Separate from the above efforts on supramolecular architectures was work on improving backbone modification strategies for an alpha-helix in the context of a complex protein tertiary fold. Earlier work in our lab had successfully incorporated unnatural building blocks into every major secondary structure (beta-sheet, alpha-helix, loops and beta-turns) of a small protein with a tertiary fold. Although the tertiary fold of the native sequence was mimicked by the resulting artificial protein, the thermodynamic stability was greatly compromised. Most of this energetic penalty derived from the modifications present in the alpha-helix. The contribution within this thesis was direct comparison of several alpha-helical design strategies and establishment of the thermodynamic consequences of each.

Structural Studies of Geosmin Synthase, a Bifunctional Sesquiterpene Synthase with Alpha-Alpha Domain Architecture that Catalyzes a Unique Cyclization-Fragmentation Reaction Sequence

PubMed Central

Harris, Golda G.; Lombardi, Patrick M.; Pemberton, Travis A.; Matsui, Tsutomu; Weiss, Thomas M.; Cole, Kathryn E.; Köksal, Mustafa; Murphy, Frank V.; Vedula, L. Sangeetha; Chou, Wayne K.W.; Cane, David E.; Christianson, David W.

2015-01-01

Geosmin synthase from Streptomyces coelicolor (ScGS) catalyzes an unusual, metal-dependent terpenoid cyclization and fragmentation reaction sequence. Two distinct active sites are required for catalysis: the N-terminal domain catalyzes the ionization and cyclization of farnesyl diphosphate to form germacradienol and inorganic pyrophosphate (PPi), and the C-terminal domain catalyzes the protonation, cyclization, and fragmentation of germacradienol to form geosmin and acetone through a retro-Prins reaction. A unique αα domain architecture is predicted for ScGS based on amino acid sequence: each domain contains the metal-binding motifs typical of a class I terpenoid cyclase, and each domain requires Mg2+ for catalysis. Here, we report the X-ray crystal structure of the unliganded N-terminal domain of ScGS and the structure of its complex with 3 Mg2+ ions and alendronate. These structures highlight conformational changes required for active site closure and catalysis. Although neither full-length ScGS nor constructs of the C-terminal domain could be crystallized, homology models of the C-terminal domain were constructed based on ~36% sequence identity with the N-terminal domain. Small-angle X-ray scattering experiments yield low resolution molecular envelopes into which the N-terminal domain crystal structure and the C-terminal domain homology model were fit, suggesting possible αα domain architectures as frameworks for bifunctional catalysis. PMID:26598179

Embedded CMOS basecalling for nanopore DNA sequencing.

PubMed

Chengjie Wang; Junli Zheng; Magierowski, Sebastian; Ghafar-Zadeh, Ebrahim

2016-08-01

DNA sequencing based on nanopore sensors is now entering the marketplace. The ability to interface this technology to established CMOS microelectronics promises significant improvements in functionality and miniaturization. Among the key functions to benefit from this interface will be basecalling, the conversion of raw electronic molecular signatures to nucleotide sequence predictions. This paper presents the design and performance potential of custom CMOS base-callers embedded alongside nanopore sensors. A basecalliing architecture implemented in 32-nm technology is discussed with the ability to process the equivalent of 20 human genomes per day in real-time at a power density of 5 W/cm2 assuming a 3-mer nanopore sensor.

Bottlebrush elastomers: a promising molecular engineering route to tunable, prestrain-free dielectric elastomers (Conference Presentation)

NASA Astrophysics Data System (ADS)

Vatankhah-Varnosfaderani, Mohammad; Daniel, William F. M.; Zhushma, Alexandr P.; Li, Qiaoxi; Morgan, Benjamin J.; Matyjaszewski, Krzysztof; Armstrong, Daniel P.; Dobrynin, Andrey V.; Sheyko, Sergei S.; Spontak, Richard J.

2017-04-01

Electroactive polymers (EAPs) refer to a broad range of relatively soft materials that change size and/or shape upon application of an electrical stimulus. Of these, dielectric elastomers (DEs) generated from either chemically- or physically-crosslinked polymer networks afford the highest levels of electroactuation strain, thereby making this class of EAPs the leading technology for artificial-muscle applications. While mechanically prestraining elastic networks remarkably enhances DEs electroactuation, external prestrain protocols severely limit both actuator performance and device implementation due to gradual DE stress relaxation and the presence of a cumbersome load frame. These drawbacks have persisted with surprisingly minimal advances in the actuation of single-component elastomers since the dawn of the "pre-strain era" introduced by Pelrine et al. (Science, 2000). In this work, we present a bottom-up, molecular-based strategy for the design of prestrain-free (freestanding) DEs derived from covalently-crosslinked bottlebrush polymers. This architecture, wherein design factors such as crosslink density, graft density and graft length can all be independently controlled, yields inherently strained polymer networks that can be readily adapted to a variety of chemistries. To validate the use of these molecularly-tunable materials as DEs, we have synthesized a series of bottlebrush silicone elastomers in as-cast shapes. Examination of these materials reveals that they undergo giant electroactuation strains (>300%) at relatively low fields (<10 V/m), thereby outperforming all commercial DEs to date and opening new opportunities in responsive soft-material technologies (e.g., robotics). The molecular design approach to controlling (electro)mechanical developed here is independent of chemistry and permits access to an unprecedented range of actuation properties from elastomeric materials with traditionally modest electroactuation performance (e.g., polydimethylsiloxane, PDMS). Experimental results obtained here compare favorably with theoretical predictions and demonstrate that the unique behavior of these materials is a direct consequence of the molecular architecture.

Probing the molecular design of hyper-branched aryl polyesters towards lubricant applications

PubMed Central

Robinson, Joshua W.; Zhou, Yan; Bhattacharya, Priyanka; Erck, Robert; Qu, Jun; Bays, J. Timothy; Cosimbescu, Lelia

2016-01-01

We report novel polymeric materials that may be used as viscosity index improvers (VII) for lubricant applications. Our efforts included probing the comb-burst hyper-branched aryl polyester architecture for beneficial viscosity and friction behavior when utilized as an additive in a group I oil. The monomer was designed as to undergo polymerization via polycondensation within the architectural construct (AB2), typical of hyperbranched polymers. The monomer design was comprised of aliphatic arms (12 or 16 methylenes) to provide the necessary lipophilicity to achieve solubility in a non-polar medium. Once polymerized, via catalyst and heat, the surface alcohols were functionalized with fatty acids (lauric and palmitic). Controlling the aliphatic nature of the internal arms and peripheral end-groups provided four unique flexible polymer designs. Changing the reaction time and concentration provided opportunities to investigate the influence of molecular weight and branching density on oil-solubility, viscosity, and friction. Oil-solubility was found to decrease with fewer internal carbons, but the number of internal carbons appears to have little influence on the bulk solution viscosity. At concentrations of 2 wt % in a group I base oil, these polymer additives demonstrated an improved viscosity index and reduced friction coefficient, validating the basic approach. PMID:26727881

The Molecular Architecture for the Intermediate Filaments of Hard α -Keratin Based on the Superlattice Data Obtained from a Study of Mammals Using Synchrotron Fibre Diffraction

DOE PAGES

James, Veronica

2011-01-01

High- and low-angle X-ray diffraction studies of hard α -keratin have been studied, and various models have been proposed over the last 70 years. Most of these studies have been confined to one or two forms of alpha keratin. This high- and low-angle synchrotron fibre diffraction study extends the study to cover all available data for all known forms of hard α -keratin including hairs, fingernails, hooves, horn, and quills from mammals, marsupials, and a monotreme, and it confirms that the model proposed is universally acceptable for all mammals. A complete Bragg analysis of the meridional diffraction patterns, including multiple-timemore » exposures to verify any weak reflections, verified the existence of a superlattice consisting of two infinite lattices and three finite lattices. An analysis of the equatorial patterns establishes the radii of the oligomeric levels of dimers, tetramers, and intermediate filaments (IFs) together with the centre to centre distance for the IFs, thus confirming the proposed helices within helices molecular architecture for hard α -keratin. The results verify that the structure proposed by Feughelman and James meets the criteria for a valid α -keratin structure.« less

Probing the molecular design of hyper-branched aryl polyesters towards lubricant applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robinson, Joshua W.; Zhou, Yan; Bhattacharya, Priyanka

We report novel polymeric materials that may be used as viscosity index improvers (VII) for lubricant applications. Our efforts included probing the comb-burst hyper-branched aryl polyester architecture for beneficial viscosity and friction behavior when utilized as an additive in a group I oil. The monomer was designed as to undergo polymerization via polycondensation within the architectural construct (AB2), typical of hyperbranched polymers. The monomer design was comprised of aliphatic arms (12 or 16 methylenes) to provide the necessary lipophilicity to achieve solubility in a non-polar medium. Once polymerized, via catalyst and heat, the surface alcohols were functionalized with fatty acidsmore » (lauric and palmitic). Controlling the aliphatic nature of the internal arms and peripheral end-groups provided four unique flexible polymer designs. Changing the reaction time and concentration provided opportunities to investigate the influence of molecular weight and branching density on oil-solubility, viscosity, and friction. Oil-solubility was found to decrease with fewer internal carbons, but the number of internal carbons appears to have little influence on the bulk solution viscosity. At concentrations of 2 wt % in a group I base oil, these polymer additives demonstrated an improved viscosity index and reduced friction coefficient, validating the basic approach.« less

The Molecular Architecture for the Intermediate Filaments of Hard [alpha]-Keratin Based on the Superlattice Data Obtained from a Study ofMammals Using Synchrotron Fibre Diffraction

DOE Office of Scientific and Technical Information (OSTI.GOV)

James, Veronica

2014-09-24

High- and low-angle X-ray diffraction studies of hard {alpha}-keratin have been studied, and various models have been proposed over the last 70 years. Most of these studies have been confined to one or two forms of alpha keratin. This high- and low-angle synchrotron fibre diffraction study extends the study to cover all available data for all known forms of hard {alpha}-keratin including hairs, fingernails, hooves, horn, and quills from mammals, marsupials, and a monotreme, and it confirms that the model proposed is universally acceptable for all mammals. A complete Bragg analysis of the meridional diffraction patterns, including multiple-time exposures tomore » verify any weak reflections, verified the existence of a superlattice consisting of two infinite lattices and three finite lattices. An analysis of the equatorial patterns establishes the radii of the oligomeric levels of dimers, tetramers, and intermediate filaments (IFs) together with the centre to centre distance for the IFs, thus confirming the proposed helices within helices molecular architecture for hard {alpha}-keratin. The results verify that the structure proposed by Feughelman and James meets the criteria for a valid {alpha}-keratin structure.« less

The genetic architecture of economic and political preferences

PubMed Central

Benjamin, Daniel J.; Cesarini, David; van der Loos, Matthijs J. H. M.; Dawes, Christopher T.; Koellinger, Philipp D.; Magnusson, Patrik K. E.; Chabris, Christopher F.; Conley, Dalton; Laibson, David; Johannesson, Magnus; Visscher, Peter M.

2012-01-01

Preferences are fundamental building blocks in all models of economic and political behavior. We study a new sample of comprehensively genotyped subjects with data on economic and political preferences and educational attainment. We use dense single nucleotide polymorphism (SNP) data to estimate the proportion of variation in these traits explained by common SNPs and to conduct genome-wide association study (GWAS) and prediction analyses. The pattern of results is consistent with findings for other complex traits. First, the estimated fraction of phenotypic variation that could, in principle, be explained by dense SNP arrays is around one-half of the narrow heritability estimated using twin and family samples. The molecular-genetic–based heritability estimates, therefore, partially corroborate evidence of significant heritability from behavior genetic studies. Second, our analyses suggest that these traits have a polygenic architecture, with the heritable variation explained by many genes with small effects. Our results suggest that most published genetic association studies with economic and political traits are dramatically underpowered, which implies a high false discovery rate. These results convey a cautionary message for whether, how, and how soon molecular genetic data can contribute to, and potentially transform, research in social science. We propose some constructive responses to the inferential challenges posed by the small explanatory power of individual SNPs. PMID:22566634

The Molecular Architecture for the Intermediate Filaments of Hard α -Keratin Based on the Superlattice Data Obtained from a Study of Mammals Using Synchrotron Fibre Diffraction

DOE Office of Scientific and Technical Information (OSTI.GOV)

James, Veronica

High- and low-angle X-ray diffraction studies of hard α -keratin have been studied, and various models have been proposed over the last 70 years. Most of these studies have been confined to one or two forms of alpha keratin. This high- and low-angle synchrotron fibre diffraction study extends the study to cover all available data for all known forms of hard α -keratin including hairs, fingernails, hooves, horn, and quills from mammals, marsupials, and a monotreme, and it confirms that the model proposed is universally acceptable for all mammals. A complete Bragg analysis of the meridional diffraction patterns, including multiple-timemore » exposures to verify any weak reflections, verified the existence of a superlattice consisting of two infinite lattices and three finite lattices. An analysis of the equatorial patterns establishes the radii of the oligomeric levels of dimers, tetramers, and intermediate filaments (IFs) together with the centre to centre distance for the IFs, thus confirming the proposed helices within helices molecular architecture for hard α -keratin. The results verify that the structure proposed by Feughelman and James meets the criteria for a valid α -keratin structure.« less

The genetic architecture of economic and political preferences.

PubMed

Benjamin, Daniel J; Cesarini, David; van der Loos, Matthijs J H M; Dawes, Christopher T; Koellinger, Philipp D; Magnusson, Patrik K E; Chabris, Christopher F; Conley, Dalton; Laibson, David; Johannesson, Magnus; Visscher, Peter M

2012-05-22

Preferences are fundamental building blocks in all models of economic and political behavior. We study a new sample of comprehensively genotyped subjects with data on economic and political preferences and educational attainment. We use dense single nucleotide polymorphism (SNP) data to estimate the proportion of variation in these traits explained by common SNPs and to conduct genome-wide association study (GWAS) and prediction analyses. The pattern of results is consistent with findings for other complex traits. First, the estimated fraction of phenotypic variation that could, in principle, be explained by dense SNP arrays is around one-half of the narrow heritability estimated using twin and family samples. The molecular-genetic-based heritability estimates, therefore, partially corroborate evidence of significant heritability from behavior genetic studies. Second, our analyses suggest that these traits have a polygenic architecture, with the heritable variation explained by many genes with small effects. Our results suggest that most published genetic association studies with economic and political traits are dramatically underpowered, which implies a high false discovery rate. These results convey a cautionary message for whether, how, and how soon molecular genetic data can contribute to, and potentially transform, research in social science. We propose some constructive responses to the inferential challenges posed by the small explanatory power of individual SNPs.

Tropomodulins: pointed-end capping proteins that regulate actin filament architecture in diverse cell types

PubMed Central

Yamashiro, Sawako; Gokhin, David S.; Kimura, Sumiko; Nowak, Roberta B.; Fowler, Velia M.

2012-01-01

Tropomodulins are a family of four proteins (Tmods 1–4) that cap the pointed ends of actin filaments in actin cytoskeletal structures in a developmentally regulated and tissue-specific manner. Unique among capping proteins, Tmods also bind tropomyosins (TMs), which greatly enhance the actin filament pointed-end capping activity of Tmods. Tmods are defined by a tropomyosin (TM)-regulated/Pointed-End Actin Capping (TM-Cap) domain in their unstructured N-terminal portion, followed by a compact, folded Leucine-Rich Repeat/Pointed-End Actin Capping (LRR-Cap) domain. By inhibiting actin monomer association and dissociation from pointed ends, Tmods regulate regulate actin dynamics and turnover, stabilizing actin filament lengths and cytoskeletal architecture. In this review, we summarize the genes, structural features, molecular and biochemical properties, actin regulatory mechanisms, expression patterns, and cell and tissue functions of Tmods. By understanding Tmods’ functions in the context of their molecular structure, actin regulation, binding partners, and related variants (leiomodins 1–3), we can draw broad conclusions that can explain the diverse morphological and functional phenotypes that arise from Tmod perturbation experiments in vitro and in vivo. Tmod-based stabilization and organization of intracellular actin filament networks provide key insights into how the emergent properties of the actin cytoskeleton drive tissue morphogenesis and physiology. PMID:22488942

Distributed chemical computing using ChemStar: an open source java remote method invocation architecture applied to large scale molecular data from PubChem.

PubMed

Karthikeyan, M; Krishnan, S; Pandey, Anil Kumar; Bender, Andreas; Tropsha, Alexander

2008-04-01

We present the application of a Java remote method invocation (RMI) based open source architecture to distributed chemical computing. This architecture was previously employed for distributed data harvesting of chemical information from the Internet via the Google application programming interface (API; ChemXtreme). Due to its open source character and its flexibility, the underlying server/client framework can be quickly adopted to virtually every computational task that can be parallelized. Here, we present the server/client communication framework as well as an application to distributed computing of chemical properties on a large scale (currently the size of PubChem; about 18 million compounds), using both the Marvin toolkit as well as the open source JOELib package. As an application, for this set of compounds, the agreement of log P and TPSA between the packages was compared. Outliers were found to be mostly non-druglike compounds and differences could usually be explained by differences in the underlying algorithms. ChemStar is the first open source distributed chemical computing environment built on Java RMI, which is also easily adaptable to user demands due to its "plug-in architecture". The complete source codes as well as calculated properties along with links to PubChem resources are available on the Internet via a graphical user interface at http://moltable.ncl.res.in/chemstar/.

A Comparison of Two Methods of Teaching Molecular Architecture to High School Chemistry Students.

ERIC Educational Resources Information Center

Halsted, Douglas Alan

This investigation explored the question of how high school chemistry students best learn three-dimensional molecular, ionic, and metallic structures in CHEM Study (Freeman, 1963). The experimenter compared the achievement, attitude, and instructional preferences of 110 randomly selected students taught by two different methods: (1) student…

Computer-Aided Molecular Design of Bis-phosphine Oxide Lanthanide Extractants

DOE PAGES

McCann, Billy W.; Silva, Nuwan De; Windus, Theresa L.; ...

2016-02-17

Computer-aided molecular design and high-throughput screening of viable host architectures can significantly reduce the efforts in the design of novel ligands for efficient extraction of rare earth elements. This paper presents a computational approach to the deliberate design of bis-phosphine oxide host architectures that are structurally organized for complexation of trivalent lanthanides. Molecule building software, HostDesigner, was interfaced with molecular mechanics software, PCModel, providing a tool for generating and screening millions of potential R 2(O)P-link-P(O)R 2 ligand geometries. The molecular mechanics ranking of ligand structures is consistent with both the solution-phase free energies of complexation obtained with density functional theorymore » and the performance of known bis-phosphine oxide extractants. For the case where link is -CH 2-, evaluation of the ligand geometry provides the first characterization of a steric origin for the ‘anomalous aryl strengthening’ effect. The design approach has identified a number of novel bis-phosphine oxide ligands that are better organized for lanthanide complexation than previously studied examples.« less

Molecular Physiology of Root System Architecture in Model Grasses

NASA Astrophysics Data System (ADS)

Hixson, K.; Ahkami, A. H.; Anderton, C.; Veličković, D.; Myers, G. L.; Chrisler, W.; Lindenmaier, R.; Fang, Y.; Yabusaki, S.; Rosnow, J. J.; Farris, Y.; Khan, N. E.; Bernstein, H. C.; Jansson, C.

2017-12-01

Unraveling the molecular and physiological mechanisms involved in responses of Root System Architecture (RSA) to abiotic stresses and shifts in microbiome structure is critical to understand and engineer plant-microbe-soil interactions in the rhizosphere. In this study, accessions of Brachypodium distachyon Bd21 (C3 model grass) and Setaria viridis A10.1 (C4 model grass) were grown in phytotron chambers under current and elevated CO2 levels. Detailed growth stage-based phenotypic analysis revealed different above- and below-ground morphological and physiological responses in C3 and C4 grasses to enhanced CO2 levels. Based on our preliminary results and by screening values of total biomass, water use efficiency, root to shoot ratio, RSA parameters and net assimilation rates, we postulated a three-phase physiological mechanism, i.e. RootPlus, BiomassPlus and YieldPlus phases, for grass growth under elevated CO2 conditions. Moreover, this comprehensive set of morphological and process-based observations are currently in use to develop, test, and calibrate biophysical whole-plant models and in particular to simulate leaf-level photosynthesis at various developmental stages of C3 and C4 using the model BioCro. To further link the observed phenotypic traits at the organismal level to tissue and molecular levels, and to spatially resolve the origin and fate of key metabolites involved in primary carbohydrate metabolism in different root sections, we complement root phenotypic observations with spatial metabolomics data using mass spectrometry imaging (MSI) methods. Focusing on plant-microbe interactions in the rhizosphere, six bacterial strains with plant growth promoting features are currently in use in both gel-based and soil systems to screen root growth and development in Brachypodium. Using confocal microscopy, GFP-tagged bacterial systems are utilized to study the initiation of different root types of RSA, including primary root (PR), coleoptile node axile root (CNR) and leaf node axile root (LNR) during developmental stages of root formation. The root exudates also will be quantified and preliminary data will be used to engineer our microbial consortium to improve plant growth.

Peptide-based biosensors: From self-assembled interfaces to molecular probes in electrochemical assays.

PubMed

Puiu, Mihaela; Bala, Camelia

2018-04-01

Redox-tagged peptides have emerged as functional materials with multiple applications in the area of sensing and biosensing applications due to their high stability, excellent redox properties and versatility of biomolecular interactions. They allow direct observation of molecular interactions in a wide range of affinity and enzymatic assays and act as electron mediators. Short helical peptides possess the ability to self-assemble in specific configurations with the possibility to develop in highly-ordered, stable 1D, 2D and 3D architectures in a hierarchical controlled manner. We provide here a brief overview of the electrochemical techniques available to study the electron transfer in peptide films with particular interest in developing biosensors with immobilized peptide motifs, for biological and clinical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Architecture of the ring formed by the tubulin homologue FtsZ in bacterial cell division

PubMed Central

Szwedziak, Piotr; Wang, Qing; Bharat, Tanmay A M; Tsim, Matthew; Löwe, Jan

2014-01-01

Membrane constriction is a prerequisite for cell division. The most common membrane constriction system in prokaryotes is based on the tubulin homologue FtsZ, whose filaments in E. coli are anchored to the membrane by FtsA and enable the formation of the Z-ring and divisome. The precise architecture of the FtsZ ring has remained enigmatic. In this study, we report three-dimensional arrangements of FtsZ and FtsA filaments in C. crescentus and E. coli cells and inside constricting liposomes by means of electron cryomicroscopy and cryotomography. In vivo and in vitro, the Z-ring is composed of a small, single-layered band of filaments parallel to the membrane, creating a continuous ring through lateral filament contacts. Visualisation of the in vitro reconstituted constrictions as well as a complete tracing of the helical paths of the filaments with a molecular model favour a mechanism of FtsZ-based membrane constriction that is likely to be accompanied by filament sliding. DOI: http://dx.doi.org/10.7554/eLife.04601.001 PMID:25490152

An ultra-high density bin-map for rapid QTL mapping for tassel and ear architecture in a large F₂ maize population.

PubMed

Chen, Zongliang; Wang, Baobao; Dong, Xiaomei; Liu, Han; Ren, Longhui; Chen, Jian; Hauck, Andrew; Song, Weibin; Lai, Jinsheng

2014-06-04

Understanding genetic control of tassel and ear architecture in maize (Zea mays L. ssp. mays) is important due to their relationship with grain yield. High resolution QTL mapping is critical for understanding the underlying molecular basis of phenotypic variation. Advanced populations, such as recombinant inbred lines, have been broadly adopted for QTL mapping; however, construction of large advanced generation crop populations is time-consuming and costly. The rapidly declining cost of genotyping due to recent advances in next-generation sequencing technologies has generated new possibilities for QTL mapping using large early generation populations. A set of 708 F2 progeny derived from inbreds Chang7-2 and 787 were generated and genotyped by whole genome low-coverage genotyping-by-sequencing method (average 0.04×). A genetic map containing 6,533 bin-markers was constructed based on the parental SNPs and a sliding-window method, spanning a total genetic distance of 1,396 cM. The high quality and accuracy of this map was validated by the identification of two well-studied genes, r1, a qualitative trait locus for color of silk (chromosome 10) and ba1 for tassel branch number (chromosome 3). Three traits of tassel and ear architecture were evaluated in this population, a total of 10 QTL were detected using a permutation-based-significance threshold, seven of which overlapped with reported QTL. Three genes (GRMZM2G316366, GRMZM2G492156 and GRMZM5G805008) encoding MADS-box domain proteins and a BTB/POZ domain protein were located in the small intervals of qTBN5 and qTBN7 (~800 Kb and 1.6 Mb in length, respectively) and may be involved in patterning of tassel architecture. The small physical intervals of most QTL indicate high-resolution mapping is obtainable with this method. We constructed an ultra-high-dentisy linkage map for the large early generation population in maize. Our study provides an efficient approach for fast detection of quantitative loci responsible for complex trait variation with high accuracy, thus helping to dissect the underlying molecular basis of phenotypic variation and accelerate improvement of crop breeding in a cost-effective fashion.

Macromolecular scaffolding: the relationship between nanoscale architecture and function in multichromophoric arrays for organic electronics.

PubMed

Palermo, Vincenzo; Schwartz, Erik; Finlayson, Chris E; Liscio, Andrea; Otten, Matthijs B J; Trapani, Sara; Müllen, Klaus; Beljonne, David; Friend, Richard H; Nolte, Roeland J M; Rowan, Alan E; Samorì, Paolo

2010-02-23

The optimization of the electronic properties of molecular materials based on optically or electrically active organic building blocks requires a fine-tuning of their self-assembly properties at surfaces. Such a fine-tuning can be obtained on a scale up to 10 nm by mastering principles of supramolecular chemistry, i.e., by using suitably designed molecules interacting via pre-programmed noncovalent forces. The control and fine-tuning on a greater length scale is more difficult and challenging. This Research News highlights recent results we obtained on a new class of macromolecules that possess a very rigid backbone and side chains that point away from this backbone. Each side chain contains an organic semiconducting moiety, whose position and electronic interaction with neighboring moieties are dictated by the central macromolecular scaffold. A combined experimental and theoretical approach has made it possible to unravel the physical and chemical properties of this system across multiple length scales. The (opto)electronic properties of the new functional architectures have been explored by constructing prototypes of field-effect transistors and solar cells, thereby providing direct insight into the relationship between architecture and function.

Implementation of the force decomposition machine for molecular dynamics simulations.

PubMed

Borštnik, Urban; Miller, Benjamin T; Brooks, Bernard R; Janežič, Dušanka

2012-09-01

We present the design and implementation of the force decomposition machine (FDM), a cluster of personal computers (PCs) that is tailored to running molecular dynamics (MD) simulations using the distributed diagonal force decomposition (DDFD) parallelization method. The cluster interconnect architecture is optimized for the communication pattern of the DDFD method. Our implementation of the FDM relies on standard commodity components even for networking. Although the cluster is meant for DDFD MD simulations, it remains general enough for other parallel computations. An analysis of several MD simulation runs on both the FDM and a standard PC cluster demonstrates that the FDM's interconnect architecture provides a greater performance compared to a more general cluster interconnect. Copyright © 2012 Elsevier Inc. All rights reserved.

Photoresponse of supramolecular self-assembled networks on graphene-diamond interfaces.

PubMed

Wieghold, Sarah; Li, Juan; Simon, Patrick; Krause, Maximilian; Avlasevich, Yuri; Li, Chen; Garrido, Jose A; Heiz, Ueli; Samorì, Paolo; Müllen, Klaus; Esch, Friedrich; Barth, Johannes V; Palma, Carlos-Andres

2016-02-25

Nature employs self-assembly to fabricate the most complex molecularly precise machinery known to man. Heteromolecular, two-dimensional self-assembled networks provide a route to spatially organize different building blocks relative to each other, enabling synthetic molecularly precise fabrication. Here we demonstrate optoelectronic function in a near-to-monolayer molecular architecture approaching atomically defined spatial disposition of all components. The active layer consists of a self-assembled terrylene-based dye, forming a bicomponent supramolecular network with melamine. The assembly at the graphene-diamond interface shows an absorption maximum at 740 nm whereby the photoresponse can be measured with a gallium counter electrode. We find photocurrents of 0.5 nA and open-circuit voltages of 270 mV employing 19 mW cm(-2) irradiation intensities at 710 nm. With an ex situ calculated contact area of 9.9 × 10(2) μm(2), an incident photon to current efficiency of 0.6% at 710 nm is estimated, opening up intriguing possibilities in bottom-up optoelectronic device fabrication with molecular resolution.

Photoresponse of supramolecular self-assembled networks on graphene–diamond interfaces

PubMed Central

Wieghold, Sarah; Li, Juan; Simon, Patrick; Krause, Maximilian; Avlasevich, Yuri; Li, Chen; Garrido, Jose A.; Heiz, Ueli; Samorì, Paolo; Müllen, Klaus; Esch, Friedrich; Barth, Johannes V.; Palma, Carlos-Andres

2016-01-01

Nature employs self-assembly to fabricate the most complex molecularly precise machinery known to man. Heteromolecular, two-dimensional self-assembled networks provide a route to spatially organize different building blocks relative to each other, enabling synthetic molecularly precise fabrication. Here we demonstrate optoelectronic function in a near-to-monolayer molecular architecture approaching atomically defined spatial disposition of all components. The active layer consists of a self-assembled terrylene-based dye, forming a bicomponent supramolecular network with melamine. The assembly at the graphene-diamond interface shows an absorption maximum at 740 nm whereby the photoresponse can be measured with a gallium counter electrode. We find photocurrents of 0.5 nA and open-circuit voltages of 270 mV employing 19 mW cm−2 irradiation intensities at 710 nm. With an ex situ calculated contact area of 9.9 × 102 μm2, an incident photon to current efficiency of 0.6% at 710 nm is estimated, opening up intriguing possibilities in bottom-up optoelectronic device fabrication with molecular resolution. PMID:26911248

Human Prostate Cancer Hallmarks Map

PubMed Central

Datta, Dipamoy; Aftabuddin, Md.; Gupta, Dinesh Kumar; Raha, Sanghamitra; Sen, Prosenjit

2016-01-01

Human prostate cancer is a complex heterogeneous disease that mainly affects elder male population of the western world with a high rate of mortality. Acquisitions of diverse sets of hallmark capabilities along with an aberrant functioning of androgen receptor signaling are the central driving forces behind prostatic tumorigenesis and its transition into metastatic castration resistant disease. These hallmark capabilities arise due to an intense orchestration of several crucial factors, including deregulation of vital cell physiological processes, inactivation of tumor suppressive activity and disruption of prostate gland specific cellular homeostasis. The molecular complexity and redundancy of oncoproteins signaling in prostate cancer demands for concurrent inhibition of multiple hallmark associated pathways. By an extensive manual curation of the published biomedical literature, we have developed Human Prostate Cancer Hallmarks Map (HPCHM), an onco-functional atlas of human prostate cancer associated signaling and events. It explores molecular architecture of prostate cancer signaling at various levels, namely key protein components, molecular connectivity map, oncogenic signaling pathway map, pathway based functional connectivity map etc. Here, we briefly represent the systems level understanding of the molecular mechanisms associated with prostate tumorigenesis by considering each and individual molecular and cell biological events of this disease process. PMID:27476486

Solid-state NMR Reveals the Carbon-based Molecular Architecture of Cryptococcus neoformans Fungal Eumelanins in the Cell Wall*

PubMed Central

Chatterjee, Subhasish; Prados-Rosales, Rafael; Itin, Boris; Casadevall, Arturo; Stark, Ruth E.

2015-01-01

Melanin pigments protect against both ionizing radiation and free radicals and have potential soil remediation capabilities. Eumelanins produced by pathogenic Cryptococcus neoformans fungi are virulence factors that render the fungal cells resistant to host defenses and certain antifungal drugs. Because of their insoluble and amorphous characteristics, neither the pigment bonding framework nor the cellular interactions underlying melanization of C. neoformans have yielded to comprehensive molecular-scale investigation. This study used the C. neoformans requirement of exogenous obligatory catecholamine precursors for melanization to produce isotopically enriched pigment “ghosts” and applied 2D 13C-13C correlation solid-state NMR to reveal the carbon-based architecture of intact natural eumelanin assemblies in fungal cells. We demonstrated that the aliphatic moieties of solid C. neoformans melanin ghosts include cell-wall components derived from polysaccharides and/or chitin that are associated proximally with lipid membrane constituents. Prior to development of the mature aromatic fungal pigment, these aliphatic moieties form a chemically resistant framework that could serve as the scaffold for melanin synthesis. The indole-based core aromatic moieties show interconnections that are consistent with proposed melanin structures consisting of stacked planar assemblies, which are associated spatially with the aliphatic scaffold. The pyrrole aromatic carbons of the pigments bind covalently to the aliphatic framework via glycoside or glyceride functional groups. These findings establish that the structure of the pigment assembly changes with time and provide the first biophysical information on the mechanism by which melanin is assembled in the fungal cell wall, offering vital insights that can advance the design of bioinspired conductive nanomaterials and novel therapeutics. PMID:25825492

Controlling Internal Organization of Multilayer Poly(methacrylic acid) Hydrogels with Polymer Molecular Weight

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kozlovskaya, Veronika; Zavgorodnya, Oleksandra; Ankner, John F.

Here, we report on tailoring the internal architecture of multilayer-derived poly(methacrylic acid) (PMAA) hydrogels by controlling the molecular weight of poly(N-vinylpyrrolidone) (PVPON) in hydrogen-bonded (PMAA/PVPON) layer-by-layer precursor films. The hydrogels are produced by cross-linking PMAA in the spin-assisted multilayers followed by PVPON release. We found that the thickness, morphology, and architecture of hydrogen-bonded films and the corresponding hydrogels are significantly affected by PVPON chain length. For all systems, an increase in PVPON molecular weight from M w = 2.5 to 1300 kDa resulted in increased total film thickness. We also show that increasing polymer M w smooths the hydrogen-bonded filmmore » surfaces but roughens those of the hydrogels. Using deuterated dPMAA marker layers in neutron reflectometry measurements, we found that hydrogen-bonded films reveal a high degree of stratification which is preserved in the cross-linked films. We observed dPMAA to be distributed more widely in the hydrogen-bonded films prepared with small M w PVPON due to the greater mobility of short-chain PVPON. Furthermore, these variations in the distribution of PMAA are erased after cross-linking, resulting in a distribution of dPMAA over about two bilayers for all M w but being somewhat more widely distributed in the films templated with higher M w PVPON. Finally, our results yield new insights into controlling the organization of nanostructured polymer networks using polymer molecular weight and open opportunities for fabrication of thin films with well-organized architecture and controllable function.« less

Controlling Internal Organization of Multilayer Poly(methacrylic acid) Hydrogels with Polymer Molecular Weight

DOE PAGES

Kozlovskaya, Veronika; Zavgorodnya, Oleksandra; Ankner, John F.; ...

2015-11-16

Here, we report on tailoring the internal architecture of multilayer-derived poly(methacrylic acid) (PMAA) hydrogels by controlling the molecular weight of poly(N-vinylpyrrolidone) (PVPON) in hydrogen-bonded (PMAA/PVPON) layer-by-layer precursor films. The hydrogels are produced by cross-linking PMAA in the spin-assisted multilayers followed by PVPON release. We found that the thickness, morphology, and architecture of hydrogen-bonded films and the corresponding hydrogels are significantly affected by PVPON chain length. For all systems, an increase in PVPON molecular weight from M w = 2.5 to 1300 kDa resulted in increased total film thickness. We also show that increasing polymer M w smooths the hydrogen-bonded filmmore » surfaces but roughens those of the hydrogels. Using deuterated dPMAA marker layers in neutron reflectometry measurements, we found that hydrogen-bonded films reveal a high degree of stratification which is preserved in the cross-linked films. We observed dPMAA to be distributed more widely in the hydrogen-bonded films prepared with small M w PVPON due to the greater mobility of short-chain PVPON. Furthermore, these variations in the distribution of PMAA are erased after cross-linking, resulting in a distribution of dPMAA over about two bilayers for all M w but being somewhat more widely distributed in the films templated with higher M w PVPON. Finally, our results yield new insights into controlling the organization of nanostructured polymer networks using polymer molecular weight and open opportunities for fabrication of thin films with well-organized architecture and controllable function.« less

Optoelectronic functional materials based on alkylated-π molecules: self-assembled architectures and nonassembled liquids.

PubMed

Li, Hongguang; Choi, Jiyoung; Nakanishi, Takashi

2013-05-07

The engineering of single molecules into higher-order hierarchical assemblies is a current research focus in molecular materials chemistry. Molecules containing π-conjugated units are an important class of building blocks because their self-assembly is not only of fundamental interest, but also the key to fabricating functional systems for organic electronic and photovoltaic applications. Functionalizing the π-cores with "alkyl chains" is a common strategy in the molecular design that can give the system desirable properties, such as good solubility in organic solvents for solution processing. Moreover, the alkylated-π system can regulate the self-assembly behavior by fine-tuning the intermolecular forces. The optimally assembled structures can then exhibit advanced functions. However, while some general rules have been revealed, a comprehensive understanding of the function played by the attached alkyl chains is still lacking, and current methodology is system-specific in many cases. Better clarification of this issue requires contributions from carefully designed libraries of alkylated-π molecular systems in both self-assembly and nonassembly materialization strategies. Here, based on recent efforts toward this goal, we show the power of the alkyl chains in controlling the self-assembly of soft molecular materials and their resulting optoelectronic properties. The design of alkylated-C60 is selected from our recent research achievements, as the most attractive example of such alkylated-π systems. Some other closely related systems composed of alkyl chains and π-units are also reviewed to indicate the universality of the methodology. Finally, as a contrast to the self-assembled molecular materials, nonassembled, solvent-free, novel functional liquid materials are discussed. In doing so, a new journey toward the ultimate organic "soft" materials is introduced, based on alkylated-π molecular design.

Construction of Polynuclear Lanthanide (Ln = Dy(III), Tb(III), and Nd(III)) Cage Complexes Using Pyridine-Pyrazole-Based Ligands: Versatile Molecular Topologies and SMM Behavior.

PubMed

Bala, Sukhen; Sen Bishwas, Mousumi; Pramanik, Bhaskar; Khanra, Sumit; Fromm, Katharina M; Poddar, Pankaj; Mondal, Raju

2015-09-08

Employment of two different pyridyl-pyrazolyl-based ligands afforded three octanuclear lanthanide(III) (Ln = Dy, Tb) cage compounds and one hexanuclear neodymium(III) coordination cage, exhibiting versatile molecular architectures including a butterfly core. Relatively less common semirigid pyridyl-pyrazolyl-based asymmetric ligand systems show an interesting trend of forming polynuclear lanthanide cage complexes with different coordination environments around the metal centers. It is noteworthy here that construction of lanthanide complex itself is a challenging task in a ligand system as soft N-donor rich as pyridyl-pyrazol. We report herein some lanthanide complexes using ligand containing only one or two O-donors compare to five N-coordinating sites. The resultant multinuclear lanthanide complexes show interesting magnetic and spectroscopic features originating from different spatial arrangements of the metal ions. Alternating current (ac) susceptibility measurements of the two dysprosium complexes display frequency- and temperature-dependent out-of-phase signals in zero and 0.5 T direct current field, a typical characteristic feature of single-molecule magnet (SMM) behavior, indicating different energy reversal barriers due to different molecular topologies. Another aspect of this work is the occurrence of the not-so-common SMM behavior of the terbium complex, further confirmed by ac susceptibility measurement.

Molecular dynamics simulations of theoretical cellulose nanotube models.

PubMed

Uto, Takuya; Kodama, Yuta; Miyata, Tatsuhiko; Yui, Toshifumi

2018-06-15

Nanotubes are remarkable nanoscale architectures for a wide range of potential applications. In the present paper, we report a molecular dynamics (MD) study of the theoretical cellulose nanotube (CelNT) models to evaluate their dynamic behavior in solution (either chloroform or benzene). Based on the one-quarter chain staggering relationship, we constructed six CelNT models by combining the two chain polarities (parallel (P) and antiparallel (AP)) and three symmetry operations (helical right (H R ), helical left (H L ), and rotation (R)) to generate a circular arrangement of molecular chains. Among the four models that retained the tubular form (P-H R , P-H L , P-R, and AP-R), the P-R and AP-R models have the lowest steric energies in benzene and chloroform, respectively. The structural features of the CelNT models were characterized in terms of the hydroxymethyl group conformation and intermolecular hydrogen bonds. Solvent structuring more clearly occurred with benzene than chloroform, suggesting that the CelNT models may disperse in benzene. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Origin of Hierarchical Structure Formation in Highly Grafted Symmetric Supramolecular Double-Comb Diblock Copolymers.

PubMed

Hofman, Anton H; Reza, Mehedi; Ruokolainen, Janne; Ten Brinke, Gerrit; Loos, Katja

2017-09-01

Involving supramolecular chemistry in self-assembling block copolymer systems enables design of complex macromolecular architectures that, in turn, could lead to complex phase behavior. It is an elegant route, as complicated and sensitive synthesis techniques can be avoided. Highly grafted double-comb diblock copolymers based on symmetric double hydrogen bond accepting poly(4-vinylpyridine)-block-poly(N-acryloylpiperidine) diblock copolymers and donating 3-nonadecylphenol amphiphiles are realized and studied systematically by changing the molecular weight of the copolymer. Double perpendicular lamellae-in-lamellae are formed in all complexes, independent of the copolymer molecular weight. Temperature-resolved measurements demonstrate that the supramolecular nature and ability to crystallize are responsible for the formation of such multiblock-like structures. Because of these driving forces and severe plasticization of the complexes in the liquid crystalline state, this supramolecular approach can be useful for steering self-assembly of both low- and high-molecular-weight block copolymer systems. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of Terminal Modification on the Molecular Assembly and Mechanical Properties of Protein-Based Block Copolymers.

PubMed

Jacobsen, Matthew M; Tokareva, Olena S; Ebrahimi, Davoud; Huang, Wenwen; Ling, Shengjie; Dinjaski, Nina; Li, David; Simon, Marc; Staii, Cristian; Buehler, Markus J; Kaplan, David L; Wong, Joyce Y

2017-09-01

Accurate prediction and validation of the assembly of bioinspired peptide sequences into fibers with defined mechanical characteristics would aid significantly in designing and creating materials with desired properties. This process may also be utilized to provide insight into how the molecular architecture of many natural protein fibers is assembled. In this work, computational modeling and experimentation are used in tandem to determine how peptide terminal modification affects a fiber-forming core domain. Modeling shows that increased terminal molecular weight and hydrophilicity improve peptide chain alignment under shearing conditions and promote consolidation of semicrystalline domains. Mechanical analysis shows acute improvements to strength and elasticity, but significantly reduced extensibility and overall toughness. These results highlight an important entropic function that terminal domains of fiber-forming peptides exhibit as chain alignment promoters, which ultimately has notable consequences on the mechanical behavior of the final fiber products. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dearomatization Strategies in the Synthesis of Complex Natural Products

PubMed Central

Roche, Stéphane P.; Porco, John A.

2014-01-01

Evolution in the field of the total synthesis of natural products has led to exciting developments over the last decade. Numerous chemo-selective and enantioselective methodologies have emerged from total syntheses, resulting in efficient access to many important natural product targets. This Review highlights recent developments concerning dearomatization, a powerful strategy for the total synthesis of architecturally complex natural products wherein planar, aromatic scaffolds are converted to three-dimensional molecular architectures. PMID:21506209

Lynx: a database and knowledge extraction engine for integrative medicine.

PubMed

Sulakhe, Dinanath; Balasubramanian, Sandhya; Xie, Bingqing; Feng, Bo; Taylor, Andrew; Wang, Sheng; Berrocal, Eduardo; Dave, Utpal; Xu, Jinbo; Börnigen, Daniela; Gilliam, T Conrad; Maltsev, Natalia

2014-01-01

We have developed Lynx (http://lynx.ci.uchicago.edu)--a web-based database and a knowledge extraction engine, supporting annotation and analysis of experimental data and generation of weighted hypotheses on molecular mechanisms contributing to human phenotypes and disorders of interest. Its underlying knowledge base (LynxKB) integrates various classes of information from >35 public databases and private collections, as well as manually curated data from our group and collaborators. Lynx provides advanced search capabilities and a variety of algorithms for enrichment analysis and network-based gene prioritization to assist the user in extracting meaningful knowledge from LynxKB and experimental data, whereas its service-oriented architecture provides public access to LynxKB and its analytical tools via user-friendly web services and interfaces.

Whole-genome sequencing provides new insights into the clonal architecture of Barrett’s esophagus and esophageal adenocarcinoma

PubMed Central

Warren, Andrew; Cheetham, R. Keira; Northen, Helen; O’Donovan, Maria; Malhotra, Shalini; di Pietro, Massimiliano; Ivakhno, Sergii; He, Miao; Weaver, Jamie M.J.; Lynch, Andy G.; Kingsbury, Zoya; Ross, Mark; Humphray, Sean; Bentley, David; Fitzgerald, Rebecca C.

2015-01-01

The molecular genetic relationship between esophageal adenocarcinoma (EAC) and its precursor lesion, Barrett’s esophagus, is poorly understood. Using whole-genome sequencing on 23 paired Barrett’s esophagus and EAC samples, together with one in-depth Barrett’s esophagus case-study sampled over time and space, we have provided new insights on the following aspects: i) Barrett’s esophagus is polyclonal and highly mutated even in the absence of dysplasia; ii) when cancer develops, copy number increases and heterogeneity persists such that the spectrum of mutations often shows surprisingly little overlap between EAC and adjacent Barrett’s esophagus; and iii) despite differences in specific coding mutations the mutational context suggests a common causative insult underlying these two conditions. From a clinical perspective, the histopathological assessment of dysplasia appears to be a poor reflection of the molecular disarray within the Barrett’s epithelium and a molecular Cytosponge™ technique overcomes sampling bias and has capacity to reflect the entire clonal architecture. PMID:26192915

Molecular architecture and function of the SEA complex, a modulator of the TORC1 pathway.

PubMed

Algret, Romain; Fernandez-Martinez, Javier; Shi, Yi; Kim, Seung Joong; Pellarin, Riccardo; Cimermancic, Peter; Cochet, Emilie; Sali, Andrej; Chait, Brian T; Rout, Michael P; Dokudovskaya, Svetlana

2014-11-01

The TORC1 signaling pathway plays a major role in the control of cell growth and response to stress. Here we demonstrate that the SEA complex physically interacts with TORC1 and is an important regulator of its activity. During nitrogen starvation, deletions of SEA complex components lead to Tor1 kinase delocalization, defects in autophagy, and vacuolar fragmentation. TORC1 inactivation, via nitrogen deprivation or rapamycin treatment, changes cellular levels of SEA complex members. We used affinity purification and chemical cross-linking to generate the data for an integrative structure modeling approach, which produced a well-defined molecular architecture of the SEA complex and showed that the SEA complex comprises two regions that are structurally and functionally distinct. The SEA complex emerges as a platform that can coordinate both structural and enzymatic activities necessary for the effective functioning of the TORC1 pathway. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Linear motif-mediated interactions have contributed to the evolution of modularity in complex protein interaction networks.

PubMed

Kim, Inhae; Lee, Heetak; Han, Seong Kyu; Kim, Sanguk

2014-10-01

The modular architecture of protein-protein interaction (PPI) networks is evident in diverse species with a wide range of complexity. However, the molecular components that lead to the evolution of modularity in PPI networks have not been clearly identified. Here, we show that weak domain-linear motif interactions (DLIs) are more likely to connect different biological modules than strong domain-domain interactions (DDIs). This molecular division of labor is essential for the evolution of modularity in the complex PPI networks of diverse eukaryotic species. In particular, DLIs may compensate for the reduction in module boundaries that originate from increased connections between different modules in complex PPI networks. In addition, we show that the identification of biological modules can be greatly improved by including molecular characteristics of protein interactions. Our findings suggest that transient interactions have played a unique role in shaping the architecture and modularity of biological networks over the course of evolution.

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCann, Billy W.; Silva, Nuwan De; Windus, Theresa L.

Computer-aided molecular design and high-throughput screening of viable host architectures can significantly reduce the efforts in the design of novel ligands for efficient extraction of rare earth elements. This paper presents a computational approach to the deliberate design of bis-phosphine oxide host architectures that are structurally organized for complexation of trivalent lanthanides. Molecule building software, HostDesigner, was interfaced with molecular mechanics software, PCModel, providing a tool for generating and screening millions of potential R 2(O)P-link-P(O)R 2 ligand geometries. The molecular mechanics ranking of ligand structures is consistent with both the solution-phase free energies of complexation obtained with density functional theorymore » and the performance of known bis-phosphine oxide extractants. For the case where link is -CH 2-, evaluation of the ligand geometry provides the first characterization of a steric origin for the ‘anomalous aryl strengthening’ effect. The design approach has identified a number of novel bis-phosphine oxide ligands that are better organized for lanthanide complexation than previously studied examples.« less

Effect of Chemical and Physical Properties on the In Vitro Degradation of 3D Printed High Resolution Poly(propylene fumarate) Scaffolds.

PubMed

Walker, Jason M; Bodamer, Emily; Krebs, Olivia; Luo, Yuanyuan; Kleinfehn, Alex; Becker, Matthew L; Dean, David

2017-04-10

Two distinct molecular masses of poly(propylene fumarate) (PPF) are combined with an additive manufacturing process to fabricate highly complex scaffolds possessing controlled chemical properties and porous architecture. Scaffolds were manufactured with two polymer molecular masses and two architecture styles. Degradation was assessed in an accelerated in vitro environment. The purpose of the degradation study is not to model or mimic in vivo degradation, but to efficiently compare the effect of modulating scaffold properties. This is the first study addressing degradation of chain-growth synthesized PPF, a process that allows for considerably more control over molecular mass distribution. It demonstrates that, with greater process control, not only is scaffold fabrication reproducible, but the mechanical properties and degradation kinetics can be tailored by altering the physical properties of the scaffold. This is a clear step forward in using PPF to address unmet medical needs while meeting regulatory demands and ultimately obtaining clinical relevancy.

Molecular Architecture of Contactin-associated Protein-like 2 (CNTNAP2) and Its Interaction with Contactin 2 (CNTN2)*

PubMed Central

Lu, Zhuoyang; Reddy, M. V. V. V. Sekhar; Liu, Jianfang; Kalichava, Ana; Liu, Jiankang; Zhang, Lei; Chen, Fang; Wang, Yun; Holthauzen, Luis Marcelo F.; White, Mark A.; Seshadrinathan, Suchithra; Zhong, Xiaoying; Ren, Gang; Rudenko, Gabby

2016-01-01

Contactin-associated protein-like 2 (CNTNAP2) is a large multidomain neuronal adhesion molecule implicated in a number of neurological disorders, including epilepsy, schizophrenia, autism spectrum disorder, intellectual disability, and language delay. We reveal here by electron microscopy that the architecture of CNTNAP2 is composed of a large, medium, and small lobe that flex with respect to each other. Using epitope labeling and fragments, we assign the F58C, L1, and L2 domains to the large lobe, the FBG and L3 domains to the middle lobe, and the L4 domain to the small lobe of the CNTNAP2 molecular envelope. Our data reveal that CNTNAP2 has a very different architecture compared with neurexin 1α, a fellow member of the neurexin superfamily and a prototype, suggesting that CNTNAP2 uses a different strategy to integrate into the synaptic protein network. We show that the ectodomains of CNTNAP2 and contactin 2 (CNTN2) bind directly and specifically, with low nanomolar affinity. We show further that mutations in CNTNAP2 implicated in autism spectrum disorder are not segregated but are distributed over the whole ectodomain. The molecular shape and dimensions of CNTNAP2 place constraints on how CNTNAP2 integrates in the cleft of axo-glial and neuronal contact sites and how it functions as an organizing and adhesive molecule. PMID:27621318

CMOL: A New Concept for Nanoelectronics

NASA Astrophysics Data System (ADS)

Likharev, Konstantin

2005-03-01

I will review the recent work on devices and architectures for future hybrid semiconductor/molecular integrated circuits, in particular those of ``CMOL'' variety [1]. Such circuits would combine an advanced CMOS subsystem fabricated by the usual lithographic patterning, two layers of parallel metallic nanowires formed, e.g., by nanoimprint, and two-terminal molecular devices self-assembled on the nanowire crosspoints. Estimates show that this powerful combination may allow CMOL circuits to reach an unparalleled density (up to 10^12 functions per cm^2) and ultrahigh rate of information processing (up to 10^20 operations per second on a single chip), at acceptable power dissipation. The main challenges on the way toward practical CMOL technology are: (i) reliable chemically-directed self-assembly of mid-size organic molecules, and (ii) the development of efficient defect-tolerant architectures for CMOL circuits. Our recent work has shown that such architectures may be developed not only for terabit-scale memories and naturally defect-tolerant mixed-signal neuromorphic networks, but (rather unexpectedly) also for FPGA-style digital Boolean circuits. [1] For details, see http://rsfq1.physics.sunysb.edu/˜likharev/nano/Springer04.pdf

Architecture-Dependent Robustness and Bistability in a Class of Genetic Circuits

PubMed Central

Zhang, Jiajun; Yuan, Zhanjiang; Li, Han-Xiong; Zhou, Tianshou

2010-01-01

Understanding the relationship between genotype and phenotype is a challenge in systems biology. An interesting yet related issue is why a particular circuit topology is present in a cell when the same function can supposedly be obtained from an alternative architecture. Here we analyzed two topologically equivalent genetic circuits of coupled positive and negative feedback loops, named NAT and ALT circuits, respectively. The computational search for the oscillation volume of the entire biologically reasonable parameter region through large-scale random samplings shows that the NAT circuit exhibits a distinctly larger fraction of the oscillatory region than the ALT circuit. Such a global robustness difference between two circuits is supplemented by analyzing local robustness, including robustness to parameter perturbations and to molecular noise. In addition, detailed dynamical analysis shows that the molecular noise of both circuits can induce transient switching of the different mechanism between a stable steady state and a stable limit cycle. Our investigation on robustness and dynamics through examples provides insights into the relationship between network architecture and its function. PMID:20712986

Molecular Origin of the Self-Assembly of Lanreotide into Nanotubes: A Mutational Approach☆

PubMed Central

Valéry, Céline; Pouget, Emilie; Pandit, Anjali; Verbavatz, Jean-Marc; Bordes, Luc; Boisdé, Isabelle; Cherif-Cheikh, Roland; Artzner, Franck; Paternostre, Maité

2008-01-01

Lanreotide, a synthetic, therapeutic octapeptide analog of somatostatin, self-assembles in water into perfectly hollow and monodisperse (24-nm wide) nanotubes. Lanreotide is a cyclic octapeptide that contains three aromatic residues. The molecular packing of the peptide in the walls of a nanotube has recently been characterized, indicating four hierarchical levels of organization. This is a fascinating example of spontaneous self-organization, very similar to the formation of the gas vesicle walls of Halobacterium halobium. However, this unique peptide self-assembly raises important questions about its molecular origin. We adopted a directed mutation approach to determine the molecular parameters driving the formation of such a remarkable peptide architecture. We have modified the conformation by opening the cycle and by changing the conformation of a Lys residue, and we have also mutated the aromatic side chains of the peptide. We show that three parameters are essential for the formation of lanreotide nanotubes: i), the specificity of two of the three aromatic side chains, ii), the spatial arrangement of the hydrophilic and hydrophobic residues, and iii), the aromatic side chain in the β-turn of the molecule. When these molecular characteristics are modified, either the peptides lose their self-assembling capability or they form less-ordered architectures, such as amyloid fibers and curved lamellae. Thus we have determined key elements of the molecular origins of lanreotide nanotube formation. PMID:17993497

Mechanism for starch granule ghost formation deduced from structural and enzyme digestion properties.

PubMed

Zhang, Bin; Dhital, Sushil; Flanagan, Bernadine M; Gidley, Michael J

2014-01-22

After heating in excess water under little or no shear, starch granules do not dissolve completely but persist as highly swollen fragile forms, commonly termed granule "ghosts". The macromolecular architecture of these ghosts has not been defined, despite their importance in determining characteristic properties of starches. In this study, amylase digestion of isolated granule ghosts from maize and potato starches is used as a probe to study the mechanism of ghost formation, through microstructural, mesoscopic, and molecular scale analyses of structure before and after digestion. Digestion profiles showed that neither integral nor surface proteins/lipids were crucial for control of either ghost digestion or integrity. On the basis of the molecular composition and conformation of enzyme-resistant fractions, it was concluded that the condensed polymeric surface structure of ghost particles is mainly composed of nonordered but entangled amylopectin (and some amylose) molecules, with limited reinforcement through partially ordered enzyme-resistant structures based on amylose (for maize starch; V-type order) or amylopectin (for potato starch; B-type order). The high level of branching and large molecular size of amylopectin is proposed to be the origin for the unusual stability of a solid structure based primarily on temporary entanglements.

Molecular sensing using monolayer floating gate, fully depleted SOI MOSFET acting as an exponential transducer.

PubMed

Takulapalli, Bharath R

2010-02-23

Field-effect transistor-based chemical sensors fall into two broad categories based on the principle of signal transduction-chemiresistor or Schottky-type devices and MOSFET or inversion-type devices. In this paper, we report a new inversion-type device concept-fully depleted exponentially coupled (FDEC) sensor, using molecular monolayer floating gate fully depleted silicon on insulator (SOI) MOSFET. Molecular binding at the chemical-sensitive surface lowers the threshold voltage of the device inversion channel due to a unique capacitive charge-coupling mechanism involving interface defect states, causing an exponential increase in the inversion channel current. This response of the device is in opposite direction when compared to typical MOSFET-type sensors, wherein inversion current decreases in a conventional n-channel sensor device upon addition of negative charge to the chemical-sensitive device surface. The new sensor architecture enables ultrahigh sensitivity along with extraordinary selectivity. We propose the new sensor concept with the aid of analytical equations and present results from our experiments in liquid phase and gas phase to demonstrate the new principle of signal transduction. We present data from numerical simulations to further support our theory.

Memristor-Based Computing Architecture: Design Methodologies and Circuit Techniques

DTIC Science & Technology

2013-03-01

MEMRISTOR-BASED COMPUTING ARCHITECTURE : DESIGN METHODOLOGIES AND CIRCUIT TECHNIQUES POLYTECHNIC INSTITUTE OF NEW YORK UNIVERSITY...TECHNICAL REPORT 3. DATES COVERED (From - To) OCT 2010 – OCT 2012 4. TITLE AND SUBTITLE MEMRISTOR-BASED COMPUTING ARCHITECTURE : DESIGN METHODOLOGIES...schemes for a memristor-based reconfigurable architecture design have not been fully explored yet. Therefore, in this project, we investigated

Structural diversity in binary superlattices self-assembled from polymer-grafted nanocrystals

DOE PAGES

Ye, Xingchen; Zhu, Chenhui; Ercius, Peter; ...

2015-12-02

Multicomponent nanocrystal superlattices represent an interesting class of material that derives emergent properties from mesoscale structure, yet their programmability can be limited by the alkyl-chain-based ligands decorating the surfaces of the constituent nanocrystals. Polymeric ligands offer distinct advantages, as they allow for more precise tuning of the effective size and ‘interaction softness’ through changes to the polymer’s molecular weight, chemical nature, architecture, persistence length and surrounding solvent. Here we show the formation of 10 different binary nanocrystal superlattices (BNSLs) with both two- and three-dimensional order through independent adjustment of the core size of spherical nanocrystals and the molecular weight ofmore » densely grafted polystyrene ligands. These polymer-brush-based ligands introduce new energetic contributions to the interparticle potential that stabilizes various BNSL phases across a range of length scales and interparticle spacings. In conclusion, our study opens the door for nanocrystals to become modular elements in the design of functional particle brush solids with controlled nanoscale interfaces and mesostructures.« less

MyLabStocks: a web-application to manage molecular biology materials

PubMed Central

Chuffart, Florent; Yvert, Gaël

2014-01-01

Laboratory stocks are the hardware of research. They must be stored and managed with mimimum loss of material and information. Plasmids, oligonucleotides and strains are regularly exchanged between collaborators within and between laboratories. Managing and sharing information about every item is crucial for retrieval of reagents, for planning experiments and for reproducing past experimental results. We have developed a web-based application to manage stocks commonly used in a molecular biology laboratory. Its functionalities include user-defined privileges, visualization of plasmid maps directly from their sequence and the capacity to search items from fields of annotation or directly from a query sequence using BLAST. It is designed to handle records of plasmids, oligonucleotides, yeast strains, antibodies, pipettes and notebooks. Based on PHP/MySQL, it can easily be extended to handle other types of stocks and it can be installed on any server architecture. MyLabStocks is freely available from: https://forge.cbp.ens-lyon.fr/redmine/projects/mylabstocks under an open source licence. PMID:24643870

Global RNA Fold and Molecular Recognition for a pfl Riboswitch Bound to ZMP, a Master Regulator of One-Carbon Metabolism

DOE PAGES

Ren, Aiming; Rajashankar, Kanagalaghatta R.; Patel, Dinshaw J.

2015-06-25

ZTP, the pyrophosphorylated analog of ZMP (5- amino-4-imidazole carboxamide ribose-5'-monophosphate), was identified as an alarmone that senses 10-formyl-tetrahydroflate deficiency in bacteria. Recently, a pfl riboswitch was identified that selectively binds ZMP and regulates genes associated with purine biosynthesis and one-carbon metabolism. Here we report on the structure of the ZMP-bound Thermosinus carboxydivorans pfl riboswitch sensing domain, thereby defining the pseudoknot-based tertiary RNA fold, the binding-pocket architecture, and principles underlying ligand recognition specificity. Molecular recognition involves shape complementarity, with the ZMP 5-amino and carboxamide groups paired with the Watson-Crick edge of an invariant uracil, and the imidazole ring sandwiched between guanines,more » while the sugar hydroxyls form intermolecular hydrogen bond contacts. The burial of the ZMP base and ribose moieties, together with unanticipated coordination of the carboxamide by Mg 2+, contrasts with exposure of the 5'-phosphate to solvent. Lastly, our studies highlight the principles underlying RNA-based recognition of ZMP, a master regulator of one-carbon metabolism.« less

Global RNA Fold and Molecular Recognition for a pfl Riboswitch Bound to ZMP, a Master Regulator of One-Carbon Metabolism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ren, Aiming; Rajashankar, Kanagalaghatta R.; Patel, Dinshaw J.

ZTP, the pyrophosphorylated analog of ZMP (5- amino-4-imidazole carboxamide ribose-5'-monophosphate), was identified as an alarmone that senses 10-formyl-tetrahydroflate deficiency in bacteria. Recently, a pfl riboswitch was identified that selectively binds ZMP and regulates genes associated with purine biosynthesis and one-carbon metabolism. Here we report on the structure of the ZMP-bound Thermosinus carboxydivorans pfl riboswitch sensing domain, thereby defining the pseudoknot-based tertiary RNA fold, the binding-pocket architecture, and principles underlying ligand recognition specificity. Molecular recognition involves shape complementarity, with the ZMP 5-amino and carboxamide groups paired with the Watson-Crick edge of an invariant uracil, and the imidazole ring sandwiched between guanines,more » while the sugar hydroxyls form intermolecular hydrogen bond contacts. The burial of the ZMP base and ribose moieties, together with unanticipated coordination of the carboxamide by Mg 2+, contrasts with exposure of the 5'-phosphate to solvent. Lastly, our studies highlight the principles underlying RNA-based recognition of ZMP, a master regulator of one-carbon metabolism.« less

A Suite of Tetraphenylethylene-Based Discrete Organoplatinum(II) Metallacycles: Controllable Structure and Stoichiometry, Aggregation-Induced Emission, and Nitroaromatics Sensing.

PubMed

Yan, Xuzhou; Wang, Haoze; Hauke, Cory E; Cook, Timothy R; Wang, Ming; Saha, Manik Lal; Zhou, Zhixuan; Zhang, Mingming; Li, Xiaopeng; Huang, Feihe; Stang, Peter J

2015-12-09

Materials that organize multiple functionally active sites, especially those with aggregation-induced emission (AIE) properties, are of growing interest due to their widespread applications. Despite promising early architectures, the fabrication and preparation of multiple AIEgens, such as multiple tetraphenylethylene (multi-TPE) units, in a single entity remain a big challenge due to the tedious covalent synthetic procedures often accompanying such preparations. Coordination-driven self-assembly is an alternative synthetic methodology with the potential to deliver multi-TPE architectures with light-emitting characteristics. Herein, we report the preparation of a new family of discrete multi-TPE metallacycles in which two pendant phenyl rings of the TPE units remain unused as a structural element, representing novel AIE-active metal-organic materials based on supramolecular coordination complex platforms. These metallacycles possess relatively high molar absorption coefficients but weak fluorescent emission under dilute conditions because of the ability of the untethered phenyl rings to undergo torsional motion as a non-radiative decay pathway. Upon molecular aggregation, the multi-TPE metallacycles show AIE-activity with markedly enhanced quantum yields. Moreover, on account of their AIE characteristics in the condensed state and ability to interact with electron-deficient substrates, the photophysics of these metallacycles is sensitive to the presence of nitroaromatics, motivating their use as sensors. This work represents a unification of themes including molecular self-assembly, AIE, and fluorescence sensing and establishes structure-property-application relationships of multi-TPE scaffolds. The fundamental knowledge obtained from the current research facilitates progress in the field of metal-organic materials, metal-coordination-induced emission, and fluorescent sensing.

Memristor-Based Synapse Design and Training Scheme for Neuromorphic Computing Architecture

DTIC Science & Technology

2012-06-01

system level built upon the conventional Von Neumann computer architecture [2][3]. Developing the neuromorphic architecture at chip level by...SCHEME FOR NEUROMORPHIC COMPUTING ARCHITECTURE 5a. CONTRACT NUMBER FA8750-11-2-0046 5b. GRANT NUMBER N/A 5c. PROGRAM ELEMENT NUMBER 62788F 6...creation of memristor-based neuromorphic computing architecture. Rather than the existing crossbar-based neuron network designs, we focus on memristor

Monte Carlo simulation of star/linear and star/star blends with chemically identical monomers

NASA Astrophysics Data System (ADS)

Theodorakis, P. E.; Avgeropoulos, A.; Freire, J. J.; Kosmas, M.; Vlahos, C.

2007-11-01

The effects of chain size and architectural asymmetry on the miscibility of blends with chemically identical monomers, differing only in their molecular weight and architecture, are studied via Monte Carlo simulation by using the bond fluctuation model. Namely, we consider blends composed of linear/linear, star/linear and star/star chains. We found that linear/linear blends are more miscible than the corresponding star/star mixtures. In star/linear blends, the increase in the volume fraction of the star chains increases the miscibility. For both star/linear and star/star blends, the miscibility decreases with the increase in star functionality. When we increase the molecular weight of linear chains of star/linear mixtures the miscibility decreases. Our findings are compared with recent analytical and experimental results.

Self-assembly of Janus dendrimers into uniform dendrimersomes and other complex architectures.

PubMed

Percec, Virgil; Wilson, Daniela A; Leowanawat, Pawaret; Wilson, Christopher J; Hughes, Andrew D; Kaucher, Mark S; Hammer, Daniel A; Levine, Dalia H; Kim, Anthony J; Bates, Frank S; Davis, Kevin P; Lodge, Timothy P; Klein, Michael L; DeVane, Russell H; Aqad, Emad; Rosen, Brad M; Argintaru, Andreea O; Sienkowska, Monika J; Rissanen, Kari; Nummelin, Sami; Ropponen, Jarmo

2010-05-21

Self-assembled nanostructures obtained from natural and synthetic amphiphiles serve as mimics of biological membranes and enable the delivery of drugs, proteins, genes, and imaging agents. Yet the precise molecular arrangements demanded by these functions are difficult to achieve. Libraries of amphiphilic Janus dendrimers, prepared by facile coupling of tailored hydrophilic and hydrophobic branched segments, have been screened by cryogenic transmission electron microscopy, revealing a rich palette of morphologies in water, including vesicles, denoted dendrimersomes, cubosomes, disks, tubular vesicles, and helical ribbons. Dendrimersomes marry the stability and mechanical strength obtainable from polymersomes with the biological function of stabilized phospholipid liposomes, plus superior uniformity of size, ease of formation, and chemical functionalization. This modular synthesis strategy provides access to systematic tuning of molecular structure and of self-assembled architecture.

Transforming Benzophenoxazine Laser Dyes into Chromophores for Dye-Sensitized Solar Cells: A Molecular Engineering Approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schröder, Florian A. Y. N.; Cole, Jacqueline M.; Waddell, Paul G.

2015-02-03

The re-functionalization of a series of four well-known industrial laser dyes, based on benzophenoxazine, is explored with the prospect of molecularly engineering new chromophores for dye-sensitized solar cell (DSC) applications. Such engineering is important since a lack of suitable dyes is stifling the progress of DSC technology. The conceptual idea involves making laser dyes DSC-active by chemical modification, while maintaining their key property attributes that are attractive to DSC applications. This molecular engineering follows a step-wise approach. Firstly, molecular structures and optical absorption properties are determined for the parent laser dyes: Cresyl Violet (1); Oxazine 170 (2); Nile Blue Amore » (3), Oxazine 750 (4). These reveal structure-property relationships which define the prerequisites for computational molecular design of DSC dyes; the nature of their molecular architecture (D-π-A) and intramolecular charge transfer. Secondly, new DSC dyes are computationally designed by the in silico addition of a carboxylic acid anchor at various chemical substitution points in the parent laser dyes. A comparison of the resulting frontier molecular orbital energy levels with the conduction band edge of a TiO2 DSC photoanode and the redox potential of two electrolyte options I-/I3- and Co(II/III)tris(bipyridyl) suggests promise for these computationally designed dyes as co-sensitizers for DSC applications.« less

Biomolecular Architectures Molecular Biology

DTIC Science & Technology

2013-08-31

when the Salmonella beacon (13 nM) was tested in the presence of 800 ng bacterial genomic DNA in chicken broth (33%) (data not shown). Since it was...bacterium, Bacillus thuringiensis, transgenic tobacco containing the transgene, Bt cry1Ac, the Gram-negative bacterium, Salmonella Typhimurium, and the Gram... Salmonella Typhimurium, and the Gram-positive bacterium, Listeria monocytogenes, were monitored for detection by coupling molecular beacon (MB

Generation of a Multicomponent Library of Disulfide Donor-Acceptor Architectures Using Dynamic Combinatorial Chemistry

PubMed Central

Drożdż, Wojciech; Kołodziejski, Michał; Markiewicz, Grzegorz; Jenczak, Anna; Stefankiewicz, Artur R.

2015-01-01

We describe here the generation of new donor-acceptor disulfide architectures obtained in aqueous solution at physiological pH. The application of a dynamic combinatorial chemistry approach allowed us to generate a large number of new disulfide macrocyclic architectures together with a new type of [2]catenanes consisting of four distinct components. Up to fifteen types of structurally-distinct dynamic architectures have been generated through one-pot disulfide exchange reactions between four thiol-functionalized aqueous components. The distribution of disulfide products formed was found to be strongly dependent on the structural features of the thiol components employed. This work not only constitutes a success in the synthesis of topologically- and morphologically-complex targets, but it may also open new horizons for the use of this methodology in the construction of molecular machines. PMID:26193265

Generation of a Multicomponent Library of Disulfide Donor-Acceptor Architectures Using Dynamic Combinatorial Chemistry.

PubMed

Drożdż, Wojciech; Kołodziejski, Michał; Markiewicz, Grzegorz; Jenczak, Anna; Stefankiewicz, Artur R

2015-07-17

We describe here the generation of new donor-acceptor disulfide architectures obtained in aqueous solution at physiological pH. The application of a dynamic combinatorial chemistry approach allowed us to generate a large number of new disulfide macrocyclic architectures together with a new type of [2]catenanes consisting of four distinct components. Up to fifteen types of structurally-distinct dynamic architectures have been generated through one-pot disulfide exchange reactions between four thiol-functionalized aqueous components. The distribution of disulfide products formed was found to be strongly dependent on the structural features of the thiol components employed. This work not only constitutes a success in the synthesis of topologically- and morphologically-complex targets, but it may also open new horizons for the use of this methodology in the construction of molecular machines.

Unique thylakoid membrane architecture of a unicellular N2-fixing cyanobacterium revealed by electron tomography.

PubMed

Liberton, Michelle; Austin, Jotham R; Berg, R Howard; Pakrasi, Himadri B

2011-04-01

Cyanobacteria, descendants of the endosymbiont that gave rise to modern-day chloroplasts, are vital contributors to global biological energy conversion processes. A thorough understanding of the physiology of cyanobacteria requires detailed knowledge of these organisms at the level of cellular architecture and organization. In these prokaryotes, the large membrane protein complexes of the photosynthetic and respiratory electron transport chains function in the intracellular thylakoid membranes. Like plants, the architecture of the thylakoid membranes in cyanobacteria has direct impact on cellular bioenergetics, protein transport, and molecular trafficking. However, whole-cell thylakoid organization in cyanobacteria is not well understood. Here we present, by using electron tomography, an in-depth analysis of the architecture of the thylakoid membranes in a unicellular cyanobacterium, Cyanothece sp. ATCC 51142. Based on the results of three-dimensional tomographic reconstructions of near-entire cells, we determined that the thylakoids in Cyanothece 51142 form a dense and complex network that extends throughout the entire cell. This thylakoid membrane network is formed from the branching and splitting of membranes and encloses a single lumenal space. The entire thylakoid network spirals as a peripheral ring of membranes around the cell, an organization that has not previously been described in a cyanobacterium. Within the thylakoid membrane network are areas of quasi-helical arrangement with similarities to the thylakoid membrane system in chloroplasts. This cyanobacterial thylakoid arrangement is an efficient means of packing a large volume of membranes in the cell while optimizing intracellular transport and trafficking.

A new application of the phase-field method for understanding the mechanisms of nuclear architecture reorganization.

PubMed

Lee, S Seirin; Tashiro, S; Awazu, A; Kobayashi, R

2017-01-01

Specific features of nuclear architecture are important for the functional organization of the nucleus, and chromatin consists of two forms, heterochromatin and euchromatin. Conventional nuclear architecture is observed when heterochromatin is enriched at nuclear periphery, and it represents the primary structure in the majority of eukaryotic cells, including the rod cells of diurnal mammals. In contrast to this, inverted nuclear architecture is observed when the heterochromatin is distributed at the center of the nucleus, which occurs in the rod cells of nocturnal mammals. The inverted architecture found in the rod cells of the adult mouse is formed through the reorganization of conventional architecture during terminal differentiation. Although a previous experimental approach has demonstrated the relationship between these two nuclear architecture types at the molecular level, the mechanisms underlying long-range reorganization processes remain unknown. The details of nuclear structures and their spatial and temporal dynamics remain to be elucidated. Therefore, a comprehensive approach, using mathematical modeling, is required, in order to address these questions. Here, we propose a new mathematical approach to the understanding of nuclear architecture dynamics using the phase-field method. We successfully recreated the process of nuclear architecture reorganization, and showed that it is robustly induced by physical features, independent of a specific genotype. Our study demonstrates the potential of phase-field method application in the life science fields.

Influence of architecture on the kinetic stability of molecular assemblies.

PubMed

Patel, Amesh B; Allen, Stephanie; Davies, Martyn C; Roberts, Clive J; Tendler, Saul J B; Williams, Philip M

2004-02-11

The strength of a multimolecular system depends on the number of interactions that hold it together. Using dynamic force spectroscopy, we show how the kinetic stability of a system decreases as the number of molecular bonds is increased, as predicted by theory. The data raise important considerations for experimental tests of bond strength and, as a paradigm, suggest both routes to and pitfalls in methods for computational simulation of molecular transitions, such as ligand binding and protein folding.

Matriarch: A Python Library for Materials Architecture.

PubMed

Giesa, Tristan; Jagadeesan, Ravi; Spivak, David I; Buehler, Markus J

2015-10-12

Biological materials, such as proteins, often have a hierarchical structure ranging from basic building blocks at the nanoscale (e.g., amino acids) to assembled structures at the macroscale (e.g., fibers). Current software for materials engineering allows the user to specify polypeptide chains and simple secondary structures prior to molecular dynamics simulation, but is not flexible in terms of the geometric arrangement of unequilibrated structures. Given some knowledge of a larger-scale structure, instructing the software to create it can be very difficult and time-intensive. To this end, the present paper reports a mathematical language, using category theory, to describe the architecture of a material, i.e., its set of building blocks and instructions for combining them. While this framework applies to any hierarchical material, here we concentrate on proteins. We implement this mathematical language as an open-source Python library called Matriarch. It is a domain-specific language that gives the user the ability to create almost arbitrary structures with arbitrary amino acid sequences and, from them, generate Protein Data Bank (PDB) files. In this way, Matriarch is more powerful than commercial software now available. Matriarch can be used in tandem with molecular dynamics simulations and helps engineers design and modify biologically inspired materials based on their desired functionality. As a case study, we use our software to alter both building blocks and building instructions for tropocollagen, and determine their effect on its structure and mechanical properties.

Strategies for electrooptic film fabrication. Influence of pyrrole-pyridine-based dibranched chromophore architecture on covalent self-assembly, thin-film microstructure, and nonlinear optical response.

PubMed

Facchetti, Antonio; Beverina, Luca; van der Boom, Milko E; Dutta, Pulak; Evmenenko, Guennadi; Shukla, Atindra D; Stern, Charlotte E; Pagani, Giorgio A; Marks, Tobin J

2006-02-15

The new dibranched, heterocyclic "push-pull" chromophores bis{1-(pyridin-4-yl)-2-[2-(N-methylpyrrol-5-yl)]ethane}methane (1), 1-(pyrid-4-yl)-2-(N-methyl-5-formylpyrrol-2-yl)ethylene (2), {1-(N-methylpyridinium-4-yl)-2-[2-(N-methylpyrrol-5-yl)]ethane}{(1-(pyridin-4-yl)-2-[2-(N-methylpyrrol-5-yl)]ethane}methane (3), N-methyl-2-[1-(N-methylpyrid-4-yl)ethen-2-yl]-5-[pyrid-4-yl]ethen-2-yl]pyrrole iodide (4), bis{1-(N-methyl-4-pyridinio)-2-[2-(N-methylpyrrol-5-yl)]ethane}methane iodide (5), and N-methyl-2,5-[1-(N-methylpyrid-4-yl)ethen-2-yl]pyrrole iodide (6) have been synthesized and characterized. The neutral (1 and 2) and monomethyl salts (3 and 4) undergo chemisorptive reaction with iodobenzyl-functionalized surfaces to afford chromophore monolayers SA-1/SA-2 and SA-3/SA-4, respectively. Molecular structures and other physicochemical properties have been defined by (1)H NMR, optical spectroscopy, and XRD. Thin-film characterization by a variety of techniques (optical spectroscopy, specular X-ray reflectivity, atomic force microscopy, X-ray photoelectron spectroscopy, and angle-dependent polarized second harmonic generation) underscore the importance of the chromophore molecular architecture as well as film growth method on film microstructure and optical/electrooptic response.

The Structural Architecture of an Infectious Mammalian Prion Using Electron Cryomicroscopy.

PubMed

Vázquez-Fernández, Ester; Vos, Matthijn R; Afanasyev, Pavel; Cebey, Lino; Sevillano, Alejandro M; Vidal, Enric; Rosa, Isaac; Renault, Ludovic; Ramos, Adriana; Peters, Peter J; Fernández, José Jesús; van Heel, Marin; Young, Howard S; Requena, Jesús R; Wille, Holger

2016-09-01

The structure of the infectious prion protein (PrPSc), which is responsible for Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy, has escaped all attempts at elucidation due to its insolubility and propensity to aggregate. PrPSc replicates by converting the non-infectious, cellular prion protein (PrPC) into the misfolded, infectious conformer through an unknown mechanism. PrPSc and its N-terminally truncated variant, PrP 27-30, aggregate into amorphous aggregates, 2D crystals, and amyloid fibrils. The structure of these infectious conformers is essential to understanding prion replication and the development of structure-based therapeutic interventions. Here we used the repetitive organization inherent to GPI-anchorless PrP 27-30 amyloid fibrils to analyze their structure via electron cryomicroscopy. Fourier-transform analyses of averaged fibril segments indicate a repeating unit of 19.1 Å. 3D reconstructions of these fibrils revealed two distinct protofilaments, and, together with a molecular volume of 18,990 Å3, predicted the height of each PrP 27-30 molecule as ~17.7 Å. Together, the data indicate a four-rung β-solenoid structure as a key feature for the architecture of infectious mammalian prions. Furthermore, they allow to formulate a molecular mechanism for the replication of prions. Knowledge of the prion structure will provide important insights into the self-propagation mechanisms of protein misfolding.

Molecular architecture of the 26S proteasome holocomplex determined by an integrative approach

PubMed Central

Lasker, Keren; Förster, Friedrich; Bohn, Stefan; Walzthoeni, Thomas; Villa, Elizabeth; Unverdorben, Pia; Beck, Florian; Aebersold, Ruedi; Sali, Andrej; Baumeister, Wolfgang

2012-01-01

The 26S proteasome is at the executive end of the ubiquitin-proteasome pathway for the controlled degradation of intracellular proteins. While the structure of its 20S core particle (CP) has been determined by X-ray crystallography, the structure of the 19S regulatory particle (RP), which recruits substrates, unfolds them, and translocates them to the CP for degradation, has remained elusive. Here, we describe the molecular architecture of the 26S holocomplex determined by an integrative approach based on data from cryoelectron microscopy, X-ray crystallography, residue-specific chemical cross-linking, and several proteomics techniques. The “lid” of the RP (consisting of Rpn3/5/6/7/8/9/11/12) is organized in a modular fashion. Rpn3/5/6/7/9/12 form a horseshoe-shaped heterohexamer, which connects to the CP and roofs the AAA-ATPase module, positioning the Rpn8/Rpn11 heterodimer close to its mouth. Rpn2 is rigid, supporting the lid, while Rpn1 is conformationally variable, positioned at the periphery of the ATPase ring. The ubiquitin receptors Rpn10 and Rpn13 are located in the distal part of the RP, indicating that they were recruited to the complex late in its evolution. The modular structure of the 26S proteasome provides insights into the sequence of events prior to the degradation of ubiquitylated substrates. PMID:22307589

Multi-scale Visualization of Molecular Architecture Using Real-Time Ambient Occlusion in Sculptor.

PubMed

Wahle, Manuel; Wriggers, Willy

2015-10-01

The modeling of large biomolecular assemblies relies on an efficient rendering of their hierarchical architecture across a wide range of spatial level of detail. We describe a paradigm shift currently under way in computer graphics towards the use of more realistic global illumination models, and we apply the so-called ambient occlusion approach to our open-source multi-scale modeling program, Sculptor. While there are many other higher quality global illumination approaches going all the way up to full GPU-accelerated ray tracing, they do not provide size-specificity of the features they shade. Ambient occlusion is an aspect of global lighting that offers great visual benefits and powerful user customization. By estimating how other molecular shape features affect the reception of light at some surface point, it effectively simulates indirect shadowing. This effect occurs between molecular surfaces that are close to each other, or in pockets such as protein or ligand binding sites. By adding ambient occlusion, large macromolecular systems look much more natural, and the perception of characteristic surface features is strongly enhanced. In this work, we present a real-time implementation of screen space ambient occlusion that delivers realistic cues about tunable spatial scale characteristics of macromolecular architecture. Heretofore, the visualization of large biomolecular systems, comprising e.g. hundreds of thousands of atoms or Mega-Dalton size electron microscopy maps, did not take into account the length scales of interest or the spatial resolution of the data. Our approach has been uniquely customized with shading that is tuned for pockets and cavities of a user-defined size, making it useful for visualizing molecular features at multiple scales of interest. This is a feature that none of the conventional ambient occlusion approaches provide. Actual Sculptor screen shots illustrate how our implementation supports the size-dependent rendering of molecular surface features.

Interview: An architectural journey: from trees, dendrons/dendrimers to nanomedicine. Interview by Hannah Stanwix.

PubMed

Tomalia, Donald A

2012-07-01

Donald Tomalia received his Bachelor of Arts degree in Chemistry from the University of Michigan (MI, USA). He received his PhD in physical-organic Chemistry from Michigan State University (MI, USA) in 1968 while working at The Dow Chemical Company (MI, USA). In 1990 he moved to Michigan Molecular Institute (MI, USA) as Professor and Director of Nanoscale Chemistry and Architecture. He has subsequently founded three dendrimer based-nanotechnology companies, Dendritech, Inc. (MI, USA), Dendritic Nanotechnologies, Inc. (MI, USA) and NanoSynthons LLC (MI, USA). Donald Tomalia is currently Director of the National Dendrimer & Nanotechnology Center (MI, USA), CEO/founder of NanoSynthons LLC (MI, USA), distinguished visiting Professor, Columbia University (NY, USA) and affiliate Professor, Department of Physics, Virginia Commonwealth University (VA, USA). He is best known for his discovery of dendrimers and has received several awards for his accomplishments and contributions to science, including the 2012 Wallace H Carothers Award. He has authored over 250 publications, as well as over 128 patents.

Pectin impacts cellulose fibre architecture and hydrogel mechanics in the absence of calcium.

PubMed

Lopez-Sanchez, Patricia; Martinez-Sanz, Marta; Bonilla, Mauricio R; Wang, Dongjie; Walsh, Cherie T; Gilbert, Elliot P; Stokes, Jason R; Gidley, Michael J

2016-11-20

Pectin is a major polysaccharide in many plant cell walls and recent advances indicate that its role in wall mechanics is more important than previously thought. In this work cellulose hydrogels were synthesised in pectin solutions, as a biomimetic tool to investigate the influence of pectin on cellulose assembly and hydrogel mechanical properties. Most of the pectin (60-80%) did not interact at the molecular level with cellulose, as judged by small angle scattering techniques (SAXS and SANS). Despite the lack of strong interactions with cellulose, this pectin fraction impacted the mechanical properties of the hydrogels through poroelastic effects. The other 20-40% of pectin (containing neutral sugar sidechains) was able to interact intimately with cellulose microfibrils at the point of assembly. These results support the need to revise the role of pectin in cell wall architecture and mechanics, and; furthermore they assist the design of cellulose-based products through controlling the viscoelasticity of the fluid phase. Copyright © 2016 Elsevier Ltd. All rights reserved.

Model-based design of RNA hybridization networks implemented in living cells

PubMed Central

Rodrigo, Guillermo; Prakash, Satya; Shen, Shensi; Majer, Eszter

2017-01-01

Abstract Synthetic gene circuits allow the behavior of living cells to be reprogrammed, and non-coding small RNAs (sRNAs) are increasingly being used as programmable regulators of gene expression. However, sRNAs (natural or synthetic) are generally used to regulate single target genes, while complex dynamic behaviors would require networks of sRNAs regulating each other. Here, we report a strategy for implementing such networks that exploits hybridization reactions carried out exclusively by multifaceted sRNAs that are both targets of and triggers for other sRNAs. These networks are ultimately coupled to the control of gene expression. We relied on a thermodynamic model of the different stable conformational states underlying this system at the nucleotide level. To test our model, we designed five different RNA hybridization networks with a linear architecture, and we implemented them in Escherichia coli. We validated the network architecture at the molecular level by native polyacrylamide gel electrophoresis, as well as the network function at the bacterial population and single-cell levels with a fluorescent reporter. Our results suggest that it is possible to engineer complex cellular programs based on RNA from first principles. Because these networks are mainly based on physical interactions, our designs could be expanded to other organisms as portable regulatory resources or to implement biological computations. PMID:28934501

Self-assembly: Misfits unite

NASA Astrophysics Data System (ADS)

Grason, Gregory M.

2017-12-01

The spontaneous assembly of particulate or molecular 'building blocks' into larger architectures underlies structure formation in many biological and synthetic materials. Shape frustration of ill-fitting blocks holds a surprising key to more regular assemblies.

Synthesis and Characterization of the First Liquid Single Source Precursors for the Deposition of Ternary Chalcopyrite (CuInS2) Thin Film Materials

NASA Technical Reports Server (NTRS)

Banger, Kulbinder K.; Cowen, Jonathan; Hepp, Aloysius

2002-01-01

Molecular engineering of ternary single source precursors based on the [{PBu3}2Cu(SR')2In(SR')2] architecture have afforded the first liquid CIS ternary single source precursors (when R = Et, n-Pr), which are suitable for low temperature deposition (< 350 C). Thermogravimetric analyses (TGA) and modulated-differential scanning calorimetry (DSC) confirm their liquid phase and reduced stability. X-ray diffraction studies, energy dispersive analyzer (EDS), and scanning electron microscopy (SEM) support the formation of the single-phase chalcopyrite CuInS2 at low temperatures.

Structure, recognition and adaptive binding in RNA aptamer complexes.

PubMed

Patel, D J; Suri, A K; Jiang, F; Jiang, L; Fan, P; Kumar, R A; Nonin, S

1997-10-10

Novel features of RNA structure, recognition and discrimination have been recently elucidated through the solution structural characterization of RNA aptamers that bind cofactors, aminoglycoside antibiotics, amino acids and peptides with high affinity and specificity. This review presents the solution structures of RNA aptamer complexes with adenosine monophosphate, flavin mononucleotide, arginine/citrulline and tobramycin together with an example of hydrogen exchange measurements of the base-pair kinetics for the AMP-RNA aptamer complex. A comparative analysis of the structures of these RNA aptamer complexes yields the principles, patterns and diversity associated with RNA architecture, molecular recognition and adaptive binding associated with complex formation.

Selective MBE growth of hexagonal networks of trapezoidal and triangular GaAs nanowires on patterned (1 1 1)B substrates

NASA Astrophysics Data System (ADS)

Tamai, Isao; Hasegawa, Hideki

2007-04-01

As a combination of novel hardware architecture and novel system architecture for future ultrahigh-density III-V nanodevice LSIs, the authors' group has recently proposed a hexagonal binary decision diagram (BDD) quantum circuit approach where gate-controlled path switching BDD node devices for a single or few electrons are laid out on a hexagonal nanowire network to realize a logic function. In this paper, attempts are made to establish a method to grow highly dense hexagonal nanowire networks for future BDD circuits by selective molecular beam epitaxy (MBE) on (1 1 1)B substrates. The (1 1 1)B orientation is suitable for BDD architecture because of the basic three-fold symmetry of the BDD node device. The growth experiments showed complex evolution of the cross-sectional structures, and it was explained in terms of kinetics determining facet boundaries. Straight arrays of triangular nanowires with 60 nm base width as well as hexagonal arrays of trapezoidal nanowires with a node density of 7.5×10 6 cm -2 were successfully grown with the aid of computer simulation. The result shows feasibility of growing high-density hexagonal networks of GaAs nanowires with precise control of the shape and size.

Cas5d Protein Processes Pre-crRNA and Assembles into a Cascade-like Interference Complex in Subtype I-C/Dvulg CRISPR-Cas System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nam, Ki Hyun; Haitjema, Charles; Liu, Xueqi

Clustered regularly interspaced short palindromic repeats (CRISPRs), together with an operon of CRISPR-associated (Cas) proteins, form an RNA-based prokaryotic immune system against exogenous genetic elements. Cas5 family proteins are found in several type I CRISPR-Cas systems. Here, we report the molecular function of subtype I-C/Dvulg Cas5d from Bacillus halodurans. We show that Cas5d cleaves pre-crRNA into unit length by recognizing both the hairpin structure and the 3 single stranded sequence in the CRISPR repeat region. Cas5d structure reveals a ferredoxin domain-based architecture and a catalytic triad formed by Y46, K116, and H117 residues. We further show that after pre-crRNA processing,more » Cas5d assembles with crRNA, Csd1, and Csd2 proteins to form a multi-sub-unit interference complex similar to Escherichia coli Cascade (CRISPR-associated complex for antiviral defense) in architecture. Our results suggest that formation of a crRNA-presenting Cascade-like complex is likely a common theme among type I CRISPR subtypes.« less

Lynx: a database and knowledge extraction engine for integrative medicine

PubMed Central

Sulakhe, Dinanath; Balasubramanian, Sandhya; Xie, Bingqing; Feng, Bo; Taylor, Andrew; Wang, Sheng; Berrocal, Eduardo; Dave, Utpal; Xu, Jinbo; Börnigen, Daniela; Gilliam, T. Conrad; Maltsev, Natalia

2014-01-01

We have developed Lynx (http://lynx.ci.uchicago.edu)—a web-based database and a knowledge extraction engine, supporting annotation and analysis of experimental data and generation of weighted hypotheses on molecular mechanisms contributing to human phenotypes and disorders of interest. Its underlying knowledge base (LynxKB) integrates various classes of information from >35 public databases and private collections, as well as manually curated data from our group and collaborators. Lynx provides advanced search capabilities and a variety of algorithms for enrichment analysis and network-based gene prioritization to assist the user in extracting meaningful knowledge from LynxKB and experimental data, whereas its service-oriented architecture provides public access to LynxKB and its analytical tools via user-friendly web services and interfaces. PMID:24270788

Recent Design Development in Molecular Imaging for Breast Cancer Detection Using Nanometer CMOS Based Sensors.

PubMed

Nguyen, Dung C; Ma, Dongsheng Brian; Roveda, Janet M W

2012-01-01

As one of the key clinical imaging methods, the computed X-ray tomography can be further improved using new nanometer CMOS sensors. This will enhance the current technique's ability in terms of cancer detection size, position, and detection accuracy on the anatomical structures. The current paper reviewed designs of SOI-based CMOS sensors and their architectural design in mammography systems. Based on the existing experimental results, using the SOI technology can provide a low-noise (SNR around 87.8 db) and high-gain (30 v/v) CMOS imager. It is also expected that, together with the fast data acquisition designs, the new type of imagers may play important roles in the near-future high-dimensional images in additional to today's 2D imagers.

Nanopore Electrochemistry: A Nexus for Molecular Control of Electron Transfer Reactions

PubMed Central

2018-01-01

Pore-based structures occur widely in living organisms. Ion channels embedded in cell membranes, for example, provide pathways, where electron and proton transfer are coupled to the exchange of vital molecules. Learning from mother nature, a recent surge in activity has focused on artificial nanopore architectures to effect electrochemical transformations not accessible in larger structures. Here, we highlight these exciting advances. Starting with a brief overview of nanopore electrodes, including the early history and development of nanopore sensing based on nanopore-confined electrochemistry, we address the core concepts and special characteristics of nanopores in electron transfer. We describe nanopore-based electrochemical sensing and processing, discuss performance limits and challenges, and conclude with an outlook for next-generation nanopore electrode sensing platforms and the opportunities they present. PMID:29392173

Recent advances in magnetic resonance microscopy to the physical structure characterization of carbonaceous and inorganic materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gregory, D.M.; Gerald, R.E.; Cody, G.D.

1997-04-01

Magnetic resonance microscopy (MRM) techniques have been employed to study the molecular architectures and properties of structural polymers, fossil fuels, microporous carbons and inorganic catalysts.

Four Bed Molecular Sieve - Exploration (4BMS-X) Virtual Heater Design and Optimization

NASA Technical Reports Server (NTRS)

Schunk, R. Gregory; Peters, Warren T.; Thomas, John T., Jr.

2017-01-01

A 4BMS-X (Four Bed Molecular Sieve - Exploration) design and heater optimization study for CO2 sorbent beds in proposed exploration system architectures is presented. The primary objectives of the study are to reduce heater power and thermal gradients within the CO2 sorbent beds while minimizing channeling effects. Some of the notable changes from the ISS (International Space Station) CDRA (Carbon Dioxide Removal Assembly) to the proposed exploration system architecture include cylindrical beds, alternate sorbents and an improved heater core. Results from both 2D and 3D sorbent bed thermal models with integrated heaters are presented. The 2D sorbent bed models are used to optimize heater power and fin geometry while the 3D models address end effects in the beds for more realistic thermal gradient and heater power predictions.

Promoter architecture dictates cell-to-cell variability in gene expression.

PubMed

Jones, Daniel L; Brewster, Robert C; Phillips, Rob

2014-12-19

Variability in gene expression among genetically identical cells has emerged as a central preoccupation in the study of gene regulation; however, a divide exists between the predictions of molecular models of prokaryotic transcriptional regulation and genome-wide experimental studies suggesting that this variability is indifferent to the underlying regulatory architecture. We constructed a set of promoters in Escherichia coli in which promoter strength, transcription factor binding strength, and transcription factor copy numbers are systematically varied, and used messenger RNA (mRNA) fluorescence in situ hybridization to observe how these changes affected variability in gene expression. Our parameter-free models predicted the observed variability; hence, the molecular details of transcription dictate variability in mRNA expression, and transcriptional noise is specifically tunable and thus represents an evolutionarily accessible phenotypic parameter. Copyright © 2014, American Association for the Advancement of Science.

Collagen fibril architecture, domain organization, and triple-helical conformation govern its proteolysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perumal, Shiamalee; Antipova, Olga; Orgel, Joseph P.R.O.

We describe the molecular structure of the collagen fibril and how it affects collagen proteolysis or 'collagenolysis.' The fibril-forming collagens are major components of all mammalian connective tissues, providing the structural and organizational framework for skin, blood vessels, bone, tendon, and other tissues. The triple helix of the collagen molecule is resistant to most proteinases, and the matrix metalloproteinases that do proteolyze collagen are affected by the architecture of collagen fibrils, which are notably more resistant to collagenolysis than lone collagen monomers. Until now, there has been no molecular explanation for this. Full or limited proteolysis of the collagen fibrilmore » is known to be a key process in normal growth, development, repair, and cell differentiation, and in cancerous tumor progression and heart disease. Peptide fragments generated by collagenolysis, and the conformation of exposed sites on the fibril as a result of limited proteolysis, regulate these processes and that of cellular attachment, but it is not known how or why. Using computational and molecular visualization methods, we found that the arrangement of collagen monomers in the fibril (its architecture) protects areas vulnerable to collagenolysis and strictly governs the process. This in turn affects the accessibility of a cell interaction site located near the cleavage region. Our observations suggest that the C-terminal telopeptide must be proteolyzed before collagenase can gain access to the cleavage site. Collagenase then binds to the substrate's 'interaction domain,' which facilitates the triple-helix unwinding/dissociation function of the enzyme before collagenolysis.« less

Molecular Architecture of Contactin-associated Protein-like 2 (CNTNAP2) and Its Interaction with Contactin 2 (CNTN2)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, Zhuoyang; Reddy, M. V. V. V. Sekhar; Liu, Jianfang

Contactin-associated protein-like 2 (CNTNAP2) is a large multidomain neuronal adhesion molecule implicated in a number of neurological disorders, including epilepsy, schizophrenia, autism spectrum disorder, intellectual disability, and language delay. We reveal in this paper by electron microscopy that the architecture of CNTNAP2 is composed of a large, medium, and small lobe that flex with respect to each other. Using epitope labeling and fragments, we assign the F58C, L1, and L2 domains to the large lobe, the FBG and L3 domains to the middle lobe, and the L4 domain to the small lobe of the CNTNAP2 molecular envelope. Our data revealmore » that CNTNAP2 has a very different architecture compared with neurexin 1α, a fellow member of the neurexin superfamily and a prototype, suggesting that CNTNAP2 uses a different strategy to integrate into the synaptic protein network. We show that the ectodomains of CNTNAP2 and contactin 2 (CNTN2) bind directly and specifically, with low nanomolar affinity. We show further that mutations in CNTNAP2 implicated in autism spectrum disorder are not segregated but are distributed over the whole ectodomain. Finally, the molecular shape and dimensions of CNTNAP2 place constraints on how CNTNAP2 integrates in the cleft of axo-glial and neuronal contact sites and how it functions as an organizing and adhesive molecule.« less

Molecular Architecture of Contactin-associated Protein-like 2 (CNTNAP2) and Its Interaction with Contactin 2 (CNTN2)

DOE PAGES

Lu, Zhuoyang; Reddy, M. V. V. V. Sekhar; Liu, Jianfang; ...

2016-09-12

Contactin-associated protein-like 2 (CNTNAP2) is a large multidomain neuronal adhesion molecule implicated in a number of neurological disorders, including epilepsy, schizophrenia, autism spectrum disorder, intellectual disability, and language delay. We reveal in this paper by electron microscopy that the architecture of CNTNAP2 is composed of a large, medium, and small lobe that flex with respect to each other. Using epitope labeling and fragments, we assign the F58C, L1, and L2 domains to the large lobe, the FBG and L3 domains to the middle lobe, and the L4 domain to the small lobe of the CNTNAP2 molecular envelope. Our data revealmore » that CNTNAP2 has a very different architecture compared with neurexin 1α, a fellow member of the neurexin superfamily and a prototype, suggesting that CNTNAP2 uses a different strategy to integrate into the synaptic protein network. We show that the ectodomains of CNTNAP2 and contactin 2 (CNTN2) bind directly and specifically, with low nanomolar affinity. We show further that mutations in CNTNAP2 implicated in autism spectrum disorder are not segregated but are distributed over the whole ectodomain. Finally, the molecular shape and dimensions of CNTNAP2 place constraints on how CNTNAP2 integrates in the cleft of axo-glial and neuronal contact sites and how it functions as an organizing and adhesive molecule.« less

Collagen fibril architecture, domain organization, and triple-helical conformation govern its proteolysis.

PubMed

Perumal, Shiamalee; Antipova, Olga; Orgel, Joseph P R O

2008-02-26

We describe the molecular structure of the collagen fibril and how it affects collagen proteolysis or "collagenolysis." The fibril-forming collagens are major components of all mammalian connective tissues, providing the structural and organizational framework for skin, blood vessels, bone, tendon, and other tissues. The triple helix of the collagen molecule is resistant to most proteinases, and the matrix metalloproteinases that do proteolyze collagen are affected by the architecture of collagen fibrils, which are notably more resistant to collagenolysis than lone collagen monomers. Until now, there has been no molecular explanation for this. Full or limited proteolysis of the collagen fibril is known to be a key process in normal growth, development, repair, and cell differentiation, and in cancerous tumor progression and heart disease. Peptide fragments generated by collagenolysis, and the conformation of exposed sites on the fibril as a result of limited proteolysis, regulate these processes and that of cellular attachment, but it is not known how or why. Using computational and molecular visualization methods, we found that the arrangement of collagen monomers in the fibril (its architecture) protects areas vulnerable to collagenolysis and strictly governs the process. This in turn affects the accessibility of a cell interaction site located near the cleavage region. Our observations suggest that the C-terminal telopeptide must be proteolyzed before collagenase can gain access to the cleavage site. Collagenase then binds to the substrate's "interaction domain," which facilitates the triple-helix unwinding/dissociation function of the enzyme before collagenolysis.

Mesoporous Silica Chips for Selective Enrichment and Stabilization of Low Molecular Weight Proteome

PubMed Central

Bouamrani, Ali; Hu, Ye; Tasciotti, Ennio; Li, Li; Chiappini, Ciro; Liu, Xuewu; Ferrari, Mauro

2010-01-01

The advanced properties of mesoporous silica have been demonstrated in applications which include chemical sensing, filtration, catalysis, drug-delivery and selective biomolecular uptake. These properties depend on the architectural, physical and chemical properties of the material, which in turn are determined by the processing parameters in evaporation-induced self-assembly. In this study, we introduce a combinatorial approach for the removal of the high molecular weight proteins and for the specific isolation and enrichment of low molecular weight species. This approach is based on Mesoporous Silica Chips able to fractionate, selectively harvest and protect from enzymatic degradation, peptides and proteins present in complex human biological fluids. We present the characterization of the harvesting properties of a wide range of mesoporous chips using a library of peptides and proteins standard and their selectivity on the recovery of serum peptidome. Using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, we established the correlation between the harvesting specificity and the physico-chemical properties of mesoporous silica surfaces. The introduction of this mesoporous material with fine controlled properties will provide a powerful platform for proteomics application offering a rapid and efficient methodology for low molecular weight biomarker discovery. PMID:20013801

Mesoporous silica chips for selective enrichment and stabilization of low molecular weight proteome.

PubMed

Bouamrani, Ali; Hu, Ye; Tasciotti, Ennio; Li, Li; Chiappini, Ciro; Liu, Xuewu; Ferrari, Mauro

2010-02-01

The advanced properties of mesoporous silica have been demonstrated in applications, which include chemical sensing, filtration, catalysis, drug delivery and selective biomolecular uptake. These properties depend on the architectural, physical and chemical properties of the material, which in turn are determined by the processing parameters in evaporation-induced self-assembly. In this study, we introduce a combinatorial approach for the removal of the high molecular weight proteins and for the specific isolation and enrichment of low molecular weight species. This approach is based on mesoporous silica chips able to fractionate, selectively harvest and protect from enzymatic degradation, peptides and proteins present in complex human biological fluids. We present the characterization of the harvesting properties of a wide range of mesoporous chips using a library of peptides and proteins standard and their selectivity on the recovery of serum peptidome. Using MALDI-TOF-MS, we established the correlation between the harvesting specificity and the physicochemical properties of mesoporous silica surfaces. The introduction of this mesoporous material with fine controlled properties will provide a powerful platform for proteomics application offering a rapid and efficient methodology for low molecular weight biomarker discovery.

The domain architecture of the PtkA, the first tyrosine kinase from Mycobacterium tuberculosis differs from the conventional kinase architecture.

PubMed

Niesteruk, Anna; Jonker, Hendrik R A; Richter, Christian; Linhard, Verena; Sreeramulu, Sridhar; Schwalbe, Harald

2018-06-08

The discovery that MptpA (low-molecular-weight protein tyrosine phosphatase A) from Mycobacterium tuberculosis ( Mtb ) has an essential role for Mtb virulence has motivated research of tyrosine-specific phosphorylation in Mtb and other pathogenic bacteria. The phosphatase activity of MptpA is regulated via phosphorylation on Tyr-128 and Tyr-129. Thus far, only a single tyrosine-specific kinase, protein tyrosine kinase A (PtkA), encoded by the Rv2232 gene has been identified within the Mtb genome. MptpA undergoes phosphorylation by PtkA. PtkA is an atypical bacterial tyrosine kinase, as its sequence differs from the sequence consensus within this family. The lack of structural information on PtkA hampers the detailed characterization of the MptpA-PtkA interaction. Here, using NMR spectroscopy, we provide a detailed structural characterization of the PtkA architecture and describe its intra- and intermolecular interactions with MptpA. We found that PtkA's domain architecture differs from the conventional kinase architecture and is composed of two domains, the N-terminal highly flexible IDD PtkA and the C-terminal rigid KCD PtkA The interaction studies between the two domains together with the structural model of the IDD-KCD complex proposed in this study reveals that the IDD is unstructured and highly dynamic, allowing for a "fly-casting" like mechanism of transient interactions with the rigid KCD. This interaction modulates the accessibility of the KCD active site. In general, the structural and functional knowledge of PtkA gained in this study, is crucial for understanding the MptpA-PtkA interactions, catalytic mechanism and the role of kinase-phosphatase regulatory system in Mtb virulence. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

A Metascalable Computing Framework for Large Spatiotemporal-Scale Atomistic Simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nomura, K; Seymour, R; Wang, W

2009-02-17

A metascalable (or 'design once, scale on new architectures') parallel computing framework has been developed for large spatiotemporal-scale atomistic simulations of materials based on spatiotemporal data locality principles, which is expected to scale on emerging multipetaflops architectures. The framework consists of: (1) an embedded divide-and-conquer (EDC) algorithmic framework based on spatial locality to design linear-scaling algorithms for high complexity problems; (2) a space-time-ensemble parallel (STEP) approach based on temporal locality to predict long-time dynamics, while introducing multiple parallelization axes; and (3) a tunable hierarchical cellular decomposition (HCD) parallelization framework to map these O(N) algorithms onto a multicore cluster based onmore » hybrid implementation combining message passing and critical section-free multithreading. The EDC-STEP-HCD framework exposes maximal concurrency and data locality, thereby achieving: (1) inter-node parallel efficiency well over 0.95 for 218 billion-atom molecular-dynamics and 1.68 trillion electronic-degrees-of-freedom quantum-mechanical simulations on 212,992 IBM BlueGene/L processors (superscalability); (2) high intra-node, multithreading parallel efficiency (nanoscalability); and (3) nearly perfect time/ensemble parallel efficiency (eon-scalability). The spatiotemporal scale covered by MD simulation on a sustained petaflops computer per day (i.e. petaflops {center_dot} day of computing) is estimated as NT = 2.14 (e.g. N = 2.14 million atoms for T = 1 microseconds).« less

Viscoelastic properties of dendrimers in the melt from nonequlibrium molecular dynamics

NASA Astrophysics Data System (ADS)

Bosko, Jaroslaw T.; Todd, B. D.; Sadus, Richard J.

2004-12-01

The viscoelastic properties of dendrimers of generation 1-4 are studied using nonequilibrium molecular dynamics. Flow properties of dendrimer melts under shear are compared to systems composed of linear chain polymers of the same molecular weight, and the influence of molecular architecture is discussed. Rheological material properties, such as the shear viscosity and normal stress coefficients, are calculated and compared for both systems. We also calculate and compare the microscopic properties of both linear chain and dendrimer molecules, such as their molecular alignment, order parameters and rotational velocities. We find that the highly symmetric shape of dendrimers and their highly constrained geometry allows for substantial differences in their material properties compared to traditional linear polymers of equivalent molecular weight.

Strategies of molecular imprinting-based fluorescence sensors for chemical and biological analysis.

PubMed

Yang, Qian; Li, Jinhua; Wang, Xiaoyan; Peng, Hailong; Xiong, Hua; Chen, Lingxin

2018-07-30

One pressing concern today is to construct sensors that can withstand various disturbances for highly selective and sensitive detecting trace analytes in complicated samples. Molecularly imprinted polymers (MIPs) with tailor-made binding sites are preferred to be recognition elements in sensors for effective targets detection, and fluorescence measurement assists in highly sensitive detection and user-friendly control. Accordingly, molecular imprinting-based fluorescence sensors (MI-FL sensors) have attracted great research interest in many fields such as chemical and biological analysis. Herein, we comprehensively review the recent advances in MI-FL sensors construction and applications, giving insights on sensing principles and signal transduction mechanisms, focusing on general construction strategies for intrinsically fluorescent or nonfluorescent analytes and improvement strategies in sensing performance, particularly in sensitivity. Construction strategies are well overviewed, mainly including the traditional indirect methods of competitive binding against pre-bound fluorescent indicators, employment of fluorescent functional monomers and embedding of fluorescence substances, and novel rational designs of hierarchical architecture (core-shell/hollow and mesoporous structures), post-imprinting modification, and ratiometric fluorescence detection. Furthermore, MI-FL sensor based microdevices are discussed, involving micromotors, test strips and microfluidics, which are more portable for rapid point-of-care detection and in-field diagnosing. Finally, the current challenges and future perspectives of MI-FL sensors are proposed. Copyright © 2018 Elsevier B.V. All rights reserved.

The Importance of Three-Body Interactions in Molecular Dynamics Simulations of Water with the Fragment Molecular Orbital Method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pruitt, Spencer R.; Nakata, Hiroya; Nagata, Takeshi

2016-04-12

The analytic first derivative with respect to nuclear coordinates is formulated and implemented in the framework of the three-body fragment molecular orbital (FMO) method. The gradient has been derived and implemented for restricted Hartree-Fock, second-order Møller-Plesset perturbation, and density functional theories. The importance of the three-body fully analytic gradient is illustrated through the failure of the two-body FMO method during molecular dynamics simulations of a small water cluster. The parallel implementation of the fragment molecular orbital method, its parallel efficiency, and its scalability on the Blue Gene/Q architecture up to 262,144 CPU cores, are also discussed.

Generation of Synthetic Copolymer Libraries by Combinatorial Assembly on Nucleic Acid Templates.

PubMed

Kong, Dehui; Yeung, Wayland; Hili, Ryan

2016-07-11

Recent advances in nucleic acid-templated copolymerization have expanded the scope of sequence-controlled synthetic copolymers beyond the molecular architectures witnessed in nature. This has enabled the power of molecular evolution to be applied to synthetic copolymer libraries to evolve molecular function ranging from molecular recognition to catalysis. This Review seeks to summarize different approaches available to generate sequence-defined monodispersed synthetic copolymer libraries using nucleic acid-templated polymerization. Key concepts and principles governing nucleic acid-templated polymerization, as well as the fidelity of various copolymerization technologies, will be described. The Review will focus on methods that enable the combinatorial generation of copolymer libraries and their molecular evolution for desired function.

Entropic effects, shape, and size of mixed micelles formed by copolymers with complex architectures

NASA Astrophysics Data System (ADS)

Kalogirou, Andreas; Gergidis, Leonidas N.; Moultos, Othonas; Vlahos, Costas

2015-11-01

The entropic effects in the comicellization behavior of amphiphilic A B copolymers differing in the chain size of solvophilic A parts were studied by means of molecular dynamics simulations. In particular, mixtures of miktoarm star copolymers differing in the molecular weight of solvophilic arms were investigated. We found that the critical micelle concentration values show a positive deviation from the analytical predictions of the molecular theory of comicellization for chemically identical copolymers. This can be attributed to the effective interactions between copolymers originated from the arm size asymmetry. The effective interactions induce a very small decrease in the aggregation number of preferential micelles triggering the nonrandom mixing between the solvophilic moieties in the corona. Additionally, in order to specify how the chain architecture affects the size distribution and the shape of mixed micelles we studied star-shaped, H-shaped, and homo-linked-rings-linear mixtures. In the first case the individual constituents form micelles with preferential and wide aggregation numbers and in the latter case the individual constituents form wormlike and spherical micelles.

Entropic effects, shape, and size of mixed micelles formed by copolymers with complex architectures.

PubMed

Kalogirou, Andreas; Gergidis, Leonidas N; Moultos, Othonas; Vlahos, Costas

2015-11-01

The entropic effects in the comicellization behavior of amphiphilic AB copolymers differing in the chain size of solvophilic A parts were studied by means of molecular dynamics simulations. In particular, mixtures of miktoarm star copolymers differing in the molecular weight of solvophilic arms were investigated. We found that the critical micelle concentration values show a positive deviation from the analytical predictions of the molecular theory of comicellization for chemically identical copolymers. This can be attributed to the effective interactions between copolymers originated from the arm size asymmetry. The effective interactions induce a very small decrease in the aggregation number of preferential micelles triggering the nonrandom mixing between the solvophilic moieties in the corona. Additionally, in order to specify how the chain architecture affects the size distribution and the shape of mixed micelles we studied star-shaped, H-shaped, and homo-linked-rings-linear mixtures. In the first case the individual constituents form micelles with preferential and wide aggregation numbers and in the latter case the individual constituents form wormlike and spherical micelles.

Molecular architectures and functions of radical enzymes and their (re)activating proteins.

PubMed

Shibata, Naoki; Toraya, Tetsuo

2015-10-01

Certain proteins utilize the high reactivity of radicals for catalysing chemically challenging reactions. These proteins contain or form a radical and therefore named 'radical enzymes'. Radicals are introduced by enzymes themselves or by (re)activating proteins called (re)activases. The X-ray structures of radical enzymes and their (re)activases revealed some structural features of these molecular apparatuses which solved common enigmas of radical enzymes—i.e. how the enzymes form or introduce radicals at the active sites, how they use the high reactivity of radicals for catalysis, how they suppress undesired side reactions of highly reactive radicals and how they are (re)activated when inactivated by extinction of radicals. This review highlights molecular architectures of radical B12 enzymes, radical SAM enzymes, tyrosyl radical enzymes, glycyl radical enzymes and their (re)activating proteins that support their functions. For generalization, comparisons of the recently reported structures of radical enzymes with those of canonical radical enzymes are summarized here. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Tensegrity: the architectural basis of cellular mechanotransduction

NASA Technical Reports Server (NTRS)

Ingber, D. E.

1997-01-01

Physical forces of gravity, hemodynamic stresses, and movement play a critical role in tissue development. Yet, little is known about how cells convert these mechanical signals into a chemical response. This review attempts to place the potential molecular mediators of mechanotransduction (e.g. stretch-sensitive ion channels, signaling molecules, cytoskeleton, integrins) within the context of the structural complexity of living cells. The model presented relies on recent experimental findings, which suggests that cells use tensegrity architecture for their organization. Tensegrity predicts that cells are hard-wired to respond immediately to mechanical stresses transmitted over cell surface receptors that physically couple the cytoskeleton to extracellular matrix (e.g. integrins) or to other cells (cadherins, selectins, CAMs). Many signal transducing molecules that are activated by cell binding to growth factors and extracellular matrix associate with cytoskeletal scaffolds within focal adhesion complexes. Mechanical signals, therefore, may be integrated with other environmental signals and transduced into a biochemical response through force-dependent changes in scaffold geometry or molecular mechanics. Tensegrity also provides a mechanism to focus mechanical energy on molecular transducers and to orchestrate and tune the cellular response.

Achieving Better Buying Power through Acquisition of Open Architecture Software Systems for Web-Based and Mobile Devices

DTIC Science & Technology

2015-05-01

Achieving Better Buying Power through Acquisition of Open Architecture Software Systems for Web-Based and Mobile Devices Walt Scacchi and Thomas...2015 to 00-00-2015 4. TITLE AND SUBTITLE Achieving Better Buying Power through Acquisition of Open Architecture Software Systems for Web-Based and...architecture (OA) software systems  Emerging challenges in achieving Better Buying Power (BBP) via OA software systems for Web- based and Mobile devices

Design, synthesis, and characterization of lightly sulfonated multigraft acrylate-based copolymer superelastomers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Misichronis, Konstantinos; Wang, Weiyu; Cheng, Shiwang

2018-01-29

Multigraft copolymer superelastomers consisting of a poly(n-butyl acrylate) backbone and polystyrene side chains were synthesized and the viscoelastic properties of the non-sulfonated and sulfonated final materials were investigated using extensional rheology (SER3). The non-linear viscoelastic experiments revealed significantly increased true stresses (up to 10 times higher) after sulfonating only 2–3% of the copolymer while the materials maintained high elongation (<700%). The linear viscoelastic experiments showed that the storage and loss modulus are increased by sulfonation and that the copolymers can be readily tuned and further improved by increasing the number of branching points and the molecular weight of the backbone.more » Here, in this way, we show that by tuning not only the molecular characteristics of the multigraft copolymers but also their architecture and chemical interaction, we can acquire thermoplastic superelastomer materials with desired viscoelastic properties.« less

Photoactuators for Direct Optical-to-Mechanical Energy Conversion: From Nanocomponent Assembly to Macroscopic Deformation.

PubMed

Hu, Ying; Li, Zhe; Lan, Tian; Chen, Wei

2016-12-01

Photoactuators with integrated optical-to-mechanical energy conversion capacity have attracted growing research interest in the last few decades due to their unique features of remote control and their wide applications ranging from bionic robots, biomedical devices, and switches to motors. For the photoactuator design, the energy conversion route and structure assembly are two important parts, which directly affect the performance of the photoactuators. In particular, the architectural designs at the molecular, nano-, micro-, and macro- level, are found to play a significant role in accumulating molecular-scale strain/stress to macroscale strain/stress. Here, recent progress on photoactuators based on photochemical and photothermal effects is summarized, followed by a discussion of the important assembly strategies for the amplification of the photoresponsive components at nanoscale to macroscopic scale motions. The application advancement of current photoactuators is also presented. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Materials for n-type organic electronics: synthesis and properties of fluoroarene-thiophene semiconductors

NASA Astrophysics Data System (ADS)

Facchetti, Antonio; Yoon, Myung-Han; Katz, Howard E.; Marks, Tobin J.

2003-11-01

Recent progress in the field of organic electronics is due to a fruitful combination of both innovative molecular design and promising low-cost material/device assembly. Targeting the first strategy, we present here the general synthesis of fluoroarene-containing thiophene-based semiconductors and the study of their properties with respect to the corresponding fluorine-free hole-transporting analogues. The new compounds have been characterized by elemental analysis, mass spectrometry, and 1H- and 19F NMR. The dramatic influence of fluorine substitution and molecular architecture has been investigated by solution/film optical absorption, fluorescence emission, and cyclic voltammetry. Single crystal data for all of the oligomers have been obtained and will be presented. Film microstructure and morphology of this new class of materials have been studied by XRD and SEM. Particular emphasis will be posed on the solution-processable oligomers and polymers.

Artificial transmembrane ion channels from self-assembling peptide nanotubes

NASA Astrophysics Data System (ADS)

Ghadiri, M. Reza; Granja, Juan R.; Buehler, Lukas K.

1994-05-01

NATURALLY occurring membrane channels and pores are formed from a large family of diverse proteins, peptides and organic secon-dary metabolites whose vital biological functions include control of ion flow, signal transduction, molecular transport and produc-tion of cellular toxins. But despite the availability of a large amount of biochemical information about these molecules1, the design and synthesis of artificial systems that can mimic the bio-logical function of natural compounds remains a formidable task2-12. Here we present a simple strategy for the design of artifi-cial membrane ion channels based on a self-assembled cylindrical β-sheet peptide architecture13. Our systems-essentially stacks of peptide rings-display good channel-mediated ion-transport activ-ity with rates exceeding 107 ions s-1, rivalling the performance of many naturally occurring counterparts. Such molecular assemblies should find use in the design of novel cytotoxic agents, membrane transport vehicles and drug-delivery systems.

A spatially localized architecture for fast and modular DNA computing

NASA Astrophysics Data System (ADS)

Chatterjee, Gourab; Dalchau, Neil; Muscat, Richard A.; Phillips, Andrew; Seelig, Georg

2017-09-01

Cells use spatial constraints to control and accelerate the flow of information in enzyme cascades and signalling networks. Synthetic silicon-based circuitry similarly relies on spatial constraints to process information. Here, we show that spatial organization can be a similarly powerful design principle for overcoming limitations of speed and modularity in engineered molecular circuits. We create logic gates and signal transmission lines by spatially arranging reactive DNA hairpins on a DNA origami. Signal propagation is demonstrated across transmission lines of different lengths and orientations and logic gates are modularly combined into circuits that establish the universality of our approach. Because reactions preferentially occur between neighbours, identical DNA hairpins can be reused across circuits. Co-localization of circuit elements decreases computation time from hours to minutes compared to circuits with diffusible components. Detailed computational models enable predictive circuit design. We anticipate our approach will motivate using spatial constraints for future molecular control circuit designs.

Ndarts

NASA Technical Reports Server (NTRS)

Jain, Abhinandan

2011-01-01

Ndarts software provides algorithms for computing quantities associated with the dynamics of articulated, rigid-link, multibody systems. It is designed as a general-purpose dynamics library that can be used for the modeling of robotic platforms, space vehicles, molecular dynamics, and other such applications. The architecture and algorithms in Ndarts are based on the Spatial Operator Algebra (SOA) theory for computational multibody and robot dynamics developed at JPL. It uses minimal, internal coordinate models. The algorithms are low-order, recursive scatter/ gather algorithms. In comparison with the earlier Darts++ software, this version has a more general and cleaner design needed to support a larger class of computational dynamics needs. It includes a frames infrastructure, allows algorithms to operate on subgraphs of the system, and implements lazy and deferred computation for better efficiency. Dynamics modeling modules such as Ndarts are core building blocks of control and simulation software for space, robotic, mechanism, bio-molecular, and material systems modeling.

Exosomal microRNA Biomarkers: Emerging Frontiers in Colorectal and Other Human Cancers

PubMed Central

Goel, Ajay; Tovar-Camargo, Oscar A; Toden, Shusuke

2016-01-01

Diagnostic strategies, particularly non-invasive blood-based screening approaches, are gaining increased attention for the early detection and attenuation of mortality associated with colorectal cancer (CRC). However, the majority of current screening approaches are inadequate at replacing the conventional CRC diagnostic procedures. Yet, due to technological advances and a better understanding of molecular events underlying human cancer, a new category of biomarkers are on the horizon. Recent evidence indicates that cells release a distinct class of small vesicles called ‘exosomes’, which contain nucleic acids and proteins that reflect and typify host-cell molecular architecture. Intriguingly, exosomes released from cancer cells have a distinct genetic and epigenetic makeup, which allows them to undertake their tumorigenic function. From a clinical standpoint, these unique cancer-specific fingerprints present in exosomes appear to be detectable in a small amount of blood, making them very attractive substrates for developing cancer biomarkers, particularly noninvasive diagnostic approaches. PMID:26892862

A task-based support architecture for developing point-of-care clinical decision support systems for the emergency department.

PubMed

Wilk, S; Michalowski, W; O'Sullivan, D; Farion, K; Sayyad-Shirabad, J; Kuziemsky, C; Kukawka, B

2013-01-01

The purpose of this study was to create a task-based support architecture for developing clinical decision support systems (CDSSs) that assist physicians in making decisions at the point-of-care in the emergency department (ED). The backbone of the proposed architecture was established by a task-based emergency workflow model for a patient-physician encounter. The architecture was designed according to an agent-oriented paradigm. Specifically, we used the O-MaSE (Organization-based Multi-agent System Engineering) method that allows for iterative translation of functional requirements into architectural components (e.g., agents). The agent-oriented paradigm was extended with ontology-driven design to implement ontological models representing knowledge required by specific agents to operate. The task-based architecture allows for the creation of a CDSS that is aligned with the task-based emergency workflow model. It facilitates decoupling of executable components (agents) from embedded domain knowledge (ontological models), thus supporting their interoperability, sharing, and reuse. The generic architecture was implemented as a pilot system, MET3-AE--a CDSS to help with the management of pediatric asthma exacerbation in the ED. The system was evaluated in a hospital ED. The architecture allows for the creation of a CDSS that integrates support for all tasks from the task-based emergency workflow model, and interacts with hospital information systems. Proposed architecture also allows for reusing and sharing system components and knowledge across disease-specific CDSSs.

Natural genetic variation of root system architecture from Arabidopsis to Brachypodium: towards adaptive value.

PubMed

Pacheco-Villalobos, David; Hardtke, Christian S

2012-06-05

Root system architecture is a trait that displays considerable plasticity because of its sensitivity to environmental stimuli. Nevertheless, to a significant degree it is genetically constrained as suggested by surveys of its natural genetic variation. A few regulators of root system architecture have been isolated as quantitative trait loci through the natural variation approach in the dicotyledon model, Arabidopsis. This provides proof of principle that allelic variation for root system architecture traits exists, is genetically tractable, and might be exploited for crop breeding. Beyond Arabidopsis, Brachypodium could serve as both a credible and experimentally accessible model for root system architecture variation in monocotyledons, as suggested by first glimpses of the different root morphologies of Brachypodium accessions. Whether a direct knowledge transfer gained from molecular model system studies will work in practice remains unclear however, because of a lack of comprehensive understanding of root system physiology in the native context. For instance, apart from a few notable exceptions, the adaptive value of genetic variation in root system modulators is unknown. Future studies should thus aim at comprehensive characterization of the role of genetic players in root system architecture variation by taking into account the native environmental conditions, in particular soil characteristics.

Recent advances in "bioartificial polymeric materials" based nanovectors

NASA Astrophysics Data System (ADS)

Conte, Raffaele; De Luca, Ilenia; Valentino, Anna; Di Salle, Anna; Calarco, Anna; Riccitiello, Francesco; Peluso, Gianfranco

2017-04-01

This chapter analyzes the advantages of the use of bioartificial polymers as carriers and the main strategies used for their design. Despite the enormous progresses in this field, more studies are required for the fully evaluation of these nanovectors in complex organisms and for the characterization of the pharmacodynamic and pharmacokinetic of the loaded drugs. Moreover, progresses in polymer chemistry are introducing a wide range of functionalities in the bioartificial polymeric material (BPM) nanostructures leading to a second generation of bioartificial polymer therapeutics based on novel and heterogeneous architectures with higher molecular weight and predictable structures, in order to achieve greater multivalency and increased loading capacity. Therefore, research on bioartificial polymeric nanovectors is an "on-going" field capable of attracting medical interest.

Parallelization of MRCI based on hole-particle symmetry.

PubMed

Suo, Bing; Zhai, Gaohong; Wang, Yubin; Wen, Zhenyi; Hu, Xiangqian; Li, Lemin

2005-01-15

The parallel implementation of multireference configuration interaction program based on the hole-particle symmetry is described. The platform to implement the parallelization is an Intel-Architectural cluster consisting of 12 nodes, each of which is equipped with two 2.4-G XEON processors, 3-GB memory, and 36-GB disk, and are connected by a Gigabit Ethernet Switch. The dependence of speedup on molecular symmetries and task granularities is discussed. Test calculations show that the scaling with the number of nodes is about 1.9 (for C1 and Cs), 1.65 (for C2v), and 1.55 (for D2h) when the number of nodes is doubled. The largest calculation performed on this cluster involves 5.6 x 10(8) CSFs.

Hybrid permeable metal-base transistor with large common-emitter current gain and low operational voltage.

PubMed

Feng, Chengang; Yi, Mingdong; Yu, Shunyang; Hümmelgen, Ivo A; Zhang, Tong; Ma, Dongge

2008-04-01

We demonstrate the suitability of N,N'-diphenyl-N,N'-bis(1-naphthylphenyl)-1,1'-biphenyl-4,4'-diamine (NPB), an organic semiconductor widely used in organic light-emitting diodes (OLEDs), for high-gain, low operational voltage nanostructured vertical-architecture transistors, which operate as permeable-base transistors. By introducing vanadium oxide (V2O5) between the injecting metal and NPB layer at the transistor emitter, we reduced the emitter operational voltage. The addition of two Ca layers, leading to a Ca/Ag/Ca base, allowed to obtain a large value of common-emitter current gain, but still retaining the permeable-base transistor character. This kind of vertical devices produced by simple technologies offer attractive new possibilities due to the large variety of available molecular semiconductors, opening the possibility of incorporating new functionalities in silicon-based devices.

The nuclear envelope as an integrator of nuclear and cytoplasmic architecture.

PubMed

Crisp, Melissa; Burke, Brian

2008-06-18

Initially perceived as little more than a container for the genome, our view of the nuclear envelope (NE) and its role in defining global nuclear architecture has evolved significantly in recent years. The recognition that certain human diseases arise from defects in NE components has provided new insight into its structural and regulatory functions. In particular, NE defects associated with striated muscle disease have been shown to cause structural perturbations not just of the nucleus itself but also of the cytoplasm. It is now becoming increasingly apparent that these two compartments display co-dependent mechanical properties. The identification of cytoskeletal binding complexes that localize to the NE now reveals a molecular framework that can seamlessly integrate nuclear and cytoplasmic architecture.

Cell-wall recovery after irreversible deformation of wood

NASA Astrophysics Data System (ADS)

Keckes, Jozef; Burgert, Ingo; Frühmann, Klaus; Müller, Martin; Kölln, Klaas; Hamilton, Myles; Burghammer, Manfred; Roth, Stephan V.; Stanzl-Tschegg, Stefanie; Fratzl, Peter

2003-12-01

The remarkable mechanical properties of biological materials reside in their complex hierarchical architecture and in specific molecular mechanistic phenomena. The fundamental importance of molecular interactions and bond recovery has been suggested by studies on deformation and fracture of bone and nacre. Like these mineral-based materials, wood also represents a complex nanocomposite with excellent mechanical performance, despite the fact that it is mainly based on polymers. In wood, however, the mechanistic contribution of processes in the cell wall is not fully understood. Here we have combined tensile tests on individual wood cells and on wood foils with simultaneous synchrotron X-ray diffraction analysis in order to separate deformation mechanisms inside the cell wall from those mediated by cell-cell interactions. We show that tensile deformation beyond the yield point does not deteriorate the stiffness of either individual cells or foils. This indicates that there is a dominant recovery mechanism that re-forms the amorphous matrix between the cellulose microfibrils within the cell wall, maintaining its mechanical properties. This stick-slip mechanism, rather like Velcro operating at the nanometre level, provides a 'plastic response' similar to that effected by moving dislocations in metals. We suggest that the molecular recovery mechanism in the cell matrix is a universal phenomenon dominating the tensile deformation of different wood tissue types.

Cell Line Data Base: structure and recent improvements towards molecular authentication of human cell lines

PubMed Central

Romano, Paolo; Manniello, Assunta; Aresu, Ottavia; Armento, Massimiliano; Cesaro, Michela; Parodi, Barbara

2009-01-01

The Cell Line Data Base (CLDB) is a well-known reference information source on human and animal cell lines including information on more than 6000 cell lines. Main biological features are coded according to controlled vocabularies derived from international lists and taxonomies. HyperCLDB (http://bioinformatics.istge.it/hypercldb/) is a hypertext version of CLDB that improves data accessibility by also allowing information retrieval through web spiders. Access to HyperCLDB is provided through indexes of biological characteristics and navigation in the hypertext is granted by many internal links. HyperCLDB also includes links to external resources. Recently, an interest was raised for a reference nomenclature for cell lines and CLDB was seen as an authoritative system. Furthermore, to overcome the cell line misidentification problem, molecular authentication methods, such as fingerprinting, single-locus short tandem repeat (STR) profile and single nucleotide polymorphisms validation, were proposed. Since this data is distributed, a reference portal on authentication of human cell lines is needed. We present here the architecture and contents of CLDB, its recent enhancements and perspectives. We also present a new related database, the Cell Line Integrated Molecular Authentication (CLIMA) database (http://bioinformatics.istge.it/clima/), that allows to link authentication data to actual cell lines. PMID:18927105

Cell Line Data Base: structure and recent improvements towards molecular authentication of human cell lines.

PubMed

Romano, Paolo; Manniello, Assunta; Aresu, Ottavia; Armento, Massimiliano; Cesaro, Michela; Parodi, Barbara

2009-01-01

The Cell Line Data Base (CLDB) is a well-known reference information source on human and animal cell lines including information on more than 6000 cell lines. Main biological features are coded according to controlled vocabularies derived from international lists and taxonomies. HyperCLDB (http://bioinformatics.istge.it/hypercldb/) is a hypertext version of CLDB that improves data accessibility by also allowing information retrieval through web spiders. Access to HyperCLDB is provided through indexes of biological characteristics and navigation in the hypertext is granted by many internal links. HyperCLDB also includes links to external resources. Recently, an interest was raised for a reference nomenclature for cell lines and CLDB was seen as an authoritative system. Furthermore, to overcome the cell line misidentification problem, molecular authentication methods, such as fingerprinting, single-locus short tandem repeat (STR) profile and single nucleotide polymorphisms validation, were proposed. Since this data is distributed, a reference portal on authentication of human cell lines is needed. We present here the architecture and contents of CLDB, its recent enhancements and perspectives. We also present a new related database, the Cell Line Integrated Molecular Authentication (CLIMA) database (http://bioinformatics.istge.it/clima/), that allows to link authentication data to actual cell lines.

39 CFR 501.7 - Postage Evidencing System requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Performance Criteria for Information-Based Indicia and Security Architecture for Open IBI Postage Evidencing Systems or Performance Criteria for Information-Based Indicia and Security Architecture for Closed IBI... Information-Based Indicia and Security Architecture for Open IBI Postage Evidencing Systems or Performance...

39 CFR 501.7 - Postage Evidencing System requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Performance Criteria for Information-Based Indicia and Security Architecture for Open IBI Postage Evidencing Systems or Performance Criteria for Information-Based Indicia and Security Architecture for Closed IBI... Information-Based Indicia and Security Architecture for Open IBI Postage Evidencing Systems or Performance...

Surface Modification Engineered Assembly of Novel Quantum Dot Architectures for Advanced Applications

DTIC Science & Technology

2008-02-09

Campbell, S. Ogata, and F. Shimojo, “ Multimillion atom simulations of nanosystems on parallel computers,” in Proceedings of the International...nanomesas: multimillion -atom molecular dynamics simulations on parallel computers,” J. Appl. Phys. 94, 6762 (2003). 21. P. Vashishta, R. K. Kalia...and A. Nakano, “ Multimillion atom molecular dynamics simulations of nanoparticles on parallel computers,” Journal of Nanoparticle Research 5, 119-135

Functional polymers as therapeutic agents: concept to market place.

PubMed

Dhal, Pradeep K; Polomoscanik, Steven C; Avila, Louis Z; Holmes-Farley, S Randall; Miller, Robert J

2009-11-12

Biologically active synthetic polymers have received considerable scientific interest and attention in recent years for their potential as promising novel therapeutic agents to treat human diseases. Although a significant amount of research has been carried out involving polymer-linked drugs as targeted and sustained release drug delivery systems and prodrugs, examples on bioactive polymers that exhibit intrinsic therapeutic properties are relatively less. Several appealing characteristics of synthetic polymers including high molecular weight, molecular architecture, and controlled polydispersity can all be utilized to discover a new generation of therapies. For example, high molecular weight bioactive polymers can be restricted to gastrointestinal tract, where they can selectively recognize, bind, and remove target disease causing substances from the body. The appealing features of GI tract restriction and stability in biological environment render these polymeric drugs to be devoid of systemic toxicity that are generally associated with small molecule systemic drugs. The present article highlights recent developments in the rational design and synthesis of appropriate functional polymers that have resulted in a number of promising polymer based therapies and biomaterials, including some marketed products.

Molecular Basis of Ligand Dissociation from G Protein-Coupled Receptors and Predicting Residence Time.

PubMed

Guo, Dong; IJzerman, Adriaan P

2018-01-01

G protein-coupled receptors (GPCRs) are integral membrane proteins and represent the largest class of drug targets. During the past decades progress in structural biology has enabled the crystallographic elucidation of the architecture of these important macromolecules. It also provided atomic-level visualization of ligand-receptor interactions, dramatically boosting the impact of structure-based approaches in drug discovery. However, knowledge obtained through crystallography is limited to static structural information. Less information is available showing how a ligand associates with or dissociates from a given receptor, whose importance is in fact increasingly recognized by the drug research community. Owing to recent advances in computer power and algorithms, molecular dynamics stimulations have become feasible that help in analyzing the kinetics of the ligand binding process. Here, we review what is currently known about the dynamics of GPCRs in the context of ligand association and dissociation, as determined through both crystallography and computer simulations. We particularly focus on the molecular basis of ligand dissociation from GPCRs and provide case studies that predict ligand dissociation pathways and residence time.

A Self-Assembled Trigonal Prismatic Molecular Vessel for Catalytic Dehydration Reactions in Water.

PubMed

Das, Paramita; Kumar, Atul; Howlader, Prodip; Mukherjee, Partha Sarathi

2017-09-12

A water-soluble Pd 6 trigonal prism (A) was synthesized by two-component coordination-driven self-assembly of a Pd II 90° acceptor with a tetraimidazole donor. The walls of the prism are constructed by three conjugated aromatic building blocks, which means that the confined pocket of the prism is hydrophobic. In addition to the hydrophobic cavity, large product egress windows make A an ideal molecular vessel to catalyze otherwise challenging pseudo-multicomponent dehydration reactions in its confined nanospace in aqueous medium. This study is an attempt at selective generation of the intermediate tetraketones and xanthenes by fine-tuning the reaction conditions employing a supramolecular molecular vessel. Moreover, either poor or no yield of the dehydrated products in the absence of A under similar reaction conditions supports the ability of the confined space of the barrel to promote such reactions in water. Furthermore, we focused on the rigidification of the tetraphenylethylene-based tetraimidazole unit anchored within the Pd II coordination architecture; enabling counter-anion dependent aggregation induced emission in the presence of water. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Design, Synthesis, and Study of Solid-State Molecular Rotors: Structure/Function Relationships for Condensed-Phase Anisotropic Dynamics

NASA Astrophysics Data System (ADS)

Vogelsberg, Cortnie Sue

Amphidynamic crystals are an extremely promising platform for the development of artificial molecular machines and stimuli-responsive materials. In analogy to skeletal muscle, their function will rely upon the collective operation of many densely packed molecular machines (i.e. actin-bound myosin) that are self-assembled in a highly organized anisotropic medium. By choosing lattice-forming elements and moving "parts" with specific functionalities, individual molecular machines may be synthesized and self-assembled in order to carry out desirable functions. In recent years, efforts in the design of amphidynamic materials based on molecular gyroscopes and compasses have shown that a certain amount of free volume is essential to facilitate internal rotation and reorientation within a crystal. In order to further establish structure/function relationships to advance the development of increasingly complex molecular machinery, molecular rotors and a molecular "spinning" top were synthesized and incorporated into a variety of solid-state architectures with different degrees of periodicity, dimensionality, and free volume. Specifically, lamellar molecular crystals, hierarchically ordered periodic mesoporous organosilicas, and metal-organic frameworks were targeted for the development of solid-state molecular machines. Using an array of solid-state nuclear magnetic resonance spectroscopy techniques, the dynamic properties of these novel molecular machine assemblies were determined and correlated with their corresponding structural features. It was found that architecture type has a profound influence on functional dynamics. The study of layered molecular crystals, composed of either molecular rotors or "spinning" tops, probed functional dynamics within dense, highly organized environments. From their study, it was discovered that: 1) crystallographically distinct sites may be utilized to differentiate machine function, 2) halogen bonding interactions are sufficiently strong to direct an assembly of molecular machines, 3) the relative flexibility of the crystal environment proximate to a dynamic component may have a significant effect on its function, and, 4) molecular machines, which possess both solid-state photochemical reactivity and dynamics may show complex reaction kinetics if the correlation time of the dynamic process and the lifetime of the excited state occur on the same time scale and the dynamic moiety inherently participates as a reaction intermediate. The study of periodic mesoporous organosilica with hierarchical order probed molecular dynamics within 2D layers of molecular rotors, organized in only one dimension and with ca. 50% exposed to the mesopore free volume. From their study, it was discovered that: 1) molecular rotors, which comprise the layers of the mesopore walls, form a 2D rotational glass, 2) rotator dynamics within the 2D rotational glass undergo a transition to a 2D rotational fluid, and, 3) a 2D rotational glass transition may be exploited to develop hyper-sensitive thermally activated molecular machines. The study of a metal-organic framework assembled from molecular rotors probed dynamics in a periodic three-dimensional free-volume environment, without the presence of close contacts. From the study of this solid-state material, it was determined that: 1) the intrinsic electronic barrier is one of the few factors, which may affect functional dynamics in a true free-volume environment, and, 2) molecular machines with dynamic barriers <

Jupiter Europa Orbiter Architecture Definition Process

NASA Technical Reports Server (NTRS)

Rasmussen, Robert; Shishko, Robert

2011-01-01

The proposed Jupiter Europa Orbiter mission, planned for launch in 2020, is using a new architectural process and framework tool to drive its model-based systems engineering effort. The process focuses on getting the architecture right before writing requirements and developing a point design. A new architecture framework tool provides for the structured entry and retrieval of architecture artifacts based on an emerging architecture meta-model. This paper describes the relationships among these artifacts and how they are used in the systems engineering effort. Some early lessons learned are discussed.

From data towards knowledge: revealing the architecture of signaling systems by unifying knowledge mining and data mining of systematic perturbation data.

PubMed

Lu, Songjian; Jin, Bo; Cowart, L Ashley; Lu, Xinghua

2013-01-01

Genetic and pharmacological perturbation experiments, such as deleting a gene and monitoring gene expression responses, are powerful tools for studying cellular signal transduction pathways. However, it remains a challenge to automatically derive knowledge of a cellular signaling system at a conceptual level from systematic perturbation-response data. In this study, we explored a framework that unifies knowledge mining and data mining towards the goal. The framework consists of the following automated processes: 1) applying an ontology-driven knowledge mining approach to identify functional modules among the genes responding to a perturbation in order to reveal potential signals affected by the perturbation; 2) applying a graph-based data mining approach to search for perturbations that affect a common signal; and 3) revealing the architecture of a signaling system by organizing signaling units into a hierarchy based on their relationships. Applying this framework to a compendium of yeast perturbation-response data, we have successfully recovered many well-known signal transduction pathways; in addition, our analysis has led to many new hypotheses regarding the yeast signal transduction system; finally, our analysis automatically organized perturbed genes as a graph reflecting the architecture of the yeast signaling system. Importantly, this framework transformed molecular findings from a gene level to a conceptual level, which can be readily translated into computable knowledge in the form of rules regarding the yeast signaling system, such as "if genes involved in the MAPK signaling are perturbed, genes involved in pheromone responses will be differentially expressed."

Practical Application of Model-based Programming and State-based Architecture to Space Missions

NASA Technical Reports Server (NTRS)

Horvath, Gregory; Ingham, Michel; Chung, Seung; Martin, Oliver; Williams, Brian

2006-01-01

A viewgraph presentation to develop models from systems engineers that accomplish mission objectives and manage the health of the system is shown. The topics include: 1) Overview; 2) Motivation; 3) Objective/Vision; 4) Approach; 5) Background: The Mission Data System; 6) Background: State-based Control Architecture System; 7) Background: State Analysis; 8) Overview of State Analysis; 9) Background: MDS Software Frameworks; 10) Background: Model-based Programming; 10) Background: Titan Model-based Executive; 11) Model-based Execution Architecture; 12) Compatibility Analysis of MDS and Titan Architectures; 13) Integrating Model-based Programming and Execution into the Architecture; 14) State Analysis and Modeling; 15) IMU Subsystem State Effects Diagram; 16) Titan Subsystem Model: IMU Health; 17) Integrating Model-based Programming and Execution into the Software IMU; 18) Testing Program; 19) Computationally Tractable State Estimation & Fault Diagnosis; 20) Diagnostic Algorithm Performance; 21) Integration and Test Issues; 22) Demonstrated Benefits; and 23) Next Steps

Fundamentals and applications of SERS-based bioanalytical sensing

NASA Astrophysics Data System (ADS)

Kahraman, Mehmet; Mullen, Emma R.; Korkmaz, Aysun; Wachsmann-Hogiu, Sebastian

2017-03-01

Plasmonics is an emerging field that examines the interaction between light and metallic nanostructures at the metal-dielectric interface. Surface-enhanced Raman scattering (SERS) is a powerful analytical technique that uses plasmonics to obtain detailed chemical information of molecules or molecular assemblies adsorbed or attached to nanostructured metallic surfaces. For bioanalytical applications, these surfaces are engineered to optimize for high enhancement factors and molecular specificity. In this review we focus on the fabrication of SERS substrates and their use for bioanalytical applications. We review the fundamental mechanisms of SERS and parameters governing SERS enhancement. We also discuss developments in the field of novel SERS substrates. This includes the use of different materials, sizes, shapes, and architectures to achieve high sensitivity and specificity as well as tunability or flexibility. Different fundamental approaches are discussed, such as label-free and functional assays. In addition, we highlight recent relevant advances for bioanalytical SERS applied to small molecules, proteins, DNA, and biologically relevant nanoparticles. Subsequently, we discuss the importance of data analysis and signal detection schemes to achieve smaller instruments with low cost for SERS-based point-of-care technology developments. Finally, we review the main advantages and challenges of SERS-based biosensing and provide a brief outlook.

3D polylactide-based scaffolds for studying human hepatocarcinoma processes in vitro

NASA Astrophysics Data System (ADS)

Scaffaro, Roberto; Lo Re, Giada; Rigogliuso, Salvatrice; Ghersi, Giulio

2012-08-01

We evaluated the combination of leaching techniques and melt blending of polymers and particles for the preparation of highly interconnected three-dimensional polymeric porous scaffolds for in vitro studies of human hepatocarcinoma processes. More specifically, sodium chloride and poly(ethylene glycol) (PEG) were used as water-soluble porogens to form porous and solvent-free poly(L,D-lactide) (PLA)-based scaffolds. Several characterization techniques, including porosimetry, image analysis and thermogravimetry, were combined to improve the reliability of measurements and mapping of the size, distribution and microarchitecture of pores. We also investigated the effect of processing, in PLA-based blends, on the simultaneous bulk/surface modifications and pore architectures in the scaffolds, and assessed the effects on human hepatocarcinoma viability and cell adhesion. The influence of PEG molecular weight on the scaffold morphology and cell viability and adhesion were also investigated. Morphological studies indicated that it was possible to obtain scaffolds with well-interconnected pores of assorted sizes. The analysis confirmed that SK-Hep1 cells adhered well to the polymeric support and emitted surface protrusions necessary to grow and differentiate three-dimensional systems. PEGs with higher molecular weight showed the best results in terms of cell adhesion and viability.

Structural basis for the antifolding activity of a molecular chaperone

NASA Astrophysics Data System (ADS)

Huang, Chengdong; Rossi, Paolo; Saio, Tomohide; Kalodimos, Charalampos G.

2016-09-01

Molecular chaperones act on non-native proteins in the cell to prevent their aggregation, premature folding or misfolding. Different chaperones often exert distinct effects, such as acceleration or delay of folding, on client proteins via mechanisms that are poorly understood. Here we report the solution structure of SecB, a chaperone that exhibits strong antifolding activity, in complex with alkaline phosphatase and maltose-binding protein captured in their unfolded states. SecB uses long hydrophobic grooves that run around its disk-like shape to recognize and bind to multiple hydrophobic segments across the length of non-native proteins. The multivalent binding mode results in proteins wrapping around SecB. This unique complex architecture alters the kinetics of protein binding to SecB and confers strong antifolding activity on the chaperone. The data show how the different architectures of chaperones result in distinct binding modes with non-native proteins that ultimately define the activity of the chaperone.

Actin dynamics, architecture, and mechanics in cell motility.

PubMed

Blanchoin, Laurent; Boujemaa-Paterski, Rajaa; Sykes, Cécile; Plastino, Julie

2014-01-01

Tight coupling between biochemical and mechanical properties of the actin cytoskeleton drives a large range of cellular processes including polarity establishment, morphogenesis, and motility. This is possible because actin filaments are semi-flexible polymers that, in conjunction with the molecular motor myosin, can act as biological active springs or "dashpots" (in laymen's terms, shock absorbers or fluidizers) able to exert or resist against force in a cellular environment. To modulate their mechanical properties, actin filaments can organize into a variety of architectures generating a diversity of cellular organizations including branched or crosslinked networks in the lamellipodium, parallel bundles in filopodia, and antiparallel structures in contractile fibers. In this review we describe the feedback loop between biochemical and mechanical properties of actin organization at the molecular level in vitro, then we integrate this knowledge into our current understanding of cellular actin organization and its physiological roles.

Electron cryo-microscopy structure of the canonical TRPC4 ion channel

PubMed Central

Vinayagam, Deivanayagabarathy; Mager, Thomas; Apelbaum, Amir; Bothe, Arne; Merino, Felipe; Hofnagel, Oliver; Gatsogiannis, Christos

2018-01-01

Canonical transient receptor channels (TRPC) are non-selective cation channels. They are involved in receptor-operated Ca2+ signaling and have been proposed to act as store-operated channels (SOC). Their malfunction is related to cardiomyopathies and their modulation by small molecules has been shown to be effective against renal cancer cells. The molecular mechanism underlying the complex activation and regulation is poorly understood. Here, we report the electron cryo-microscopy structure of zebrafish TRPC4 in its unliganded (apo), closed state at an overall resolution of 3.6 Å. The structure reveals the molecular architecture of the cation conducting pore, including the selectivity filter and lower gate. The cytoplasmic domain contains two key hubs that have been shown to interact with modulating proteins. Structural comparisons with other TRP channels give novel insights into the general architecture and domain organization of this superfamily of channels and help to understand their function and pharmacology. PMID:29717981

Graphene-Based Platform for Infrared Near-Field Nanospectroscopy of Water and Biological Materials in an Aqueous Environment.

PubMed

Khatib, Omar; Wood, Joshua D; McLeod, Alexander S; Goldflam, Michael D; Wagner, Martin; Damhorst, Gregory L; Koepke, Justin C; Doidge, Gregory P; Rangarajan, Aniruddh; Bashir, Rashid; Pop, Eric; Lyding, Joseph W; Thiemens, Mark H; Keilmann, Fritz; Basov, D N

2015-08-25

Scattering scanning near-field optical microscopy (s-SNOM) has emerged as a powerful nanoscale spectroscopic tool capable of characterizing individual biomacromolecules and molecular materials. However, applications of scattering-based near-field techniques in the infrared (IR) to native biosystems still await a solution of how to implement the required aqueous environment. In this work, we demonstrate an IR-compatible liquid cell architecture that enables near-field imaging and nanospectroscopy by taking advantage of the unique properties of graphene. Large-area graphene acts as an impermeable monolayer barrier that allows for nano-IR inspection of underlying molecular materials in liquid. Here, we use s-SNOM to investigate the tobacco mosaic virus (TMV) in water underneath graphene. We resolve individual virus particles and register the amide I and II bands of TMV at ca. 1520 and 1660 cm(-1), respectively, using nanoscale Fourier transform infrared spectroscopy (nano-FTIR). We verify the presence of water in the graphene liquid cell by identifying a spectral feature associated with water absorption at 1610 cm(-1).

Efficient Construction of Mesostate Networks from Molecular Dynamics Trajectories.

PubMed

Vitalis, Andreas; Caflisch, Amedeo

2012-03-13

The coarse-graining of data from molecular simulations yields conformational space networks that may be used for predicting the system's long time scale behavior, to discover structural pathways connecting free energy basins in the system, or simply to represent accessible phase space regions of interest and their connectivities in a two-dimensional plot. In this contribution, we present a tree-based algorithm to partition conformations of biomolecules into sets of similar microstates, i.e., to coarse-grain trajectory data into mesostates. On account of utilizing an architecture similar to that of established tree-based algorithms, the proposed scheme operates in near-linear time with data set size. We derive expressions needed for the fast evaluation of mesostate properties and distances when employing typical choices for measures of similarity between microstates. Using both a pedagogically useful and a real-word application, the algorithm is shown to be robust with respect to tree height, which in addition to mesostate threshold size is the main adjustable parameter. It is demonstrated that the derived mesostate networks can preserve information regarding the free energy basins and barriers by which the system is characterized.

MyLabStocks: a web-application to manage molecular biology materials.

PubMed

Chuffart, Florent; Yvert, Gaël

2014-05-01

Laboratory stocks are the hardware of research. They must be stored and managed with mimimum loss of material and information. Plasmids, oligonucleotides and strains are regularly exchanged between collaborators within and between laboratories. Managing and sharing information about every item is crucial for retrieval of reagents, for planning experiments and for reproducing past experimental results. We have developed a web-based application to manage stocks commonly used in a molecular biology laboratory. Its functionalities include user-defined privileges, visualization of plasmid maps directly from their sequence and the capacity to search items from fields of annotation or directly from a query sequence using BLAST. It is designed to handle records of plasmids, oligonucleotides, yeast strains, antibodies, pipettes and notebooks. Based on PHP/MySQL, it can easily be extended to handle other types of stocks and it can be installed on any server architecture. MyLabStocks is freely available from: https://forge.cbp.ens-lyon.fr/redmine/projects/mylabstocks under an open source licence. © 2014 Laboratoire de Biologie Moleculaire de la Cellule CNRS. Yeast published by John Wiley & Sons, Ltd.

A Sparse Self-Consistent Field Algorithm and Its Parallel Implementation: Application to Density-Functional-Based Tight Binding.

PubMed

Scemama, Anthony; Renon, Nicolas; Rapacioli, Mathias

2014-06-10

We present an algorithm and its parallel implementation for solving a self-consistent problem as encountered in Hartree-Fock or density functional theory. The algorithm takes advantage of the sparsity of matrices through the use of local molecular orbitals. The implementation allows one to exploit efficiently modern symmetric multiprocessing (SMP) computer architectures. As a first application, the algorithm is used within the density-functional-based tight binding method, for which most of the computational time is spent in the linear algebra routines (diagonalization of the Fock/Kohn-Sham matrix). We show that with this algorithm (i) single point calculations on very large systems (millions of atoms) can be performed on large SMP machines, (ii) calculations involving intermediate size systems (1000-100 000 atoms) are also strongly accelerated and can run efficiently on standard servers, and (iii) the error on the total energy due to the use of a cutoff in the molecular orbital coefficients can be controlled such that it remains smaller than the SCF convergence criterion.

Polymerization and Structure of Bio-Based Plastics: A Computer Simulation

NASA Astrophysics Data System (ADS)

Khot, Shrikant N.; Wool, Richard P.

2001-03-01

We recently examined several hundred chemical pathways to convert chemically functionalized plant oil triglycerides, monoglycerides and reactive diluents into high performance plastics with a broad range of properties (US Patent No. 6,121,398). The resulting polymers had linear, branched, light- and highly-crosslinked chain architectures and could be used as pressure sensitive adhesives, elastomers and high performance rigid thermoset composite resins. To optimize the molecular design and minimize the number of chemical trials in this system with excess degrees of freedom, we developed a computer simulation of the free radical polymerization process. The triglyceride structure, degree of chemical substitution, mole fractions, fatty acid distribution function, and reaction kinetic parameters were used as initial inputs on a 3d lattice simulation. The evolution of the network fractal structure was computed and used to measure crosslink density, dangling ends, degree of reaction and defects in the lattice. The molecular connectivity was used to determine strength via a vector percolation model of fracture. The simulation permitted the optimal design of new bio-based materials with respect to monomer selection, cure reaction conditions and desired properties. Supported by the National Science Foundation

Study on the contract characteristics of Internet architecture

NASA Astrophysics Data System (ADS)

Fu, Chuan; Zhang, Guoqing; Yang, Jing; Liu, Xiaona

2011-11-01

The importance of Internet architecture goes beyond the technical aspects. The architecture of Internet has a profound influence on the Internet-based economy in term of how the profits are shared by different market participants (Internet Server Provider, Internet Content Provider), since it is the physical foundation upon which the profit-sharing contracts are derived. In order to facilitate the continuing growth of the Internet, it is necessary to systematically study factors that curtail the Internet-based economy including the existing Internet architecture. In this paper, we used transaction cost economics and contract economics as new tools to analyse the contracts derived from the current Internet architecture. This study sheds light on how the macro characteristics of Internet architecture effect the microeconomical decisions of market participants. Based on the existing Internet architecture, we discuss the possibility of promoting Internet-based economy by encouraging user to connect their private stub network to the Internet and giving the user more right of self-governing.

SiC: An Agent Based Architecture for Preventing and Detecting Attacks to Ubiquitous Databases

NASA Astrophysics Data System (ADS)

Pinzón, Cristian; de Paz, Yanira; Bajo, Javier; Abraham, Ajith; Corchado, Juan M.

One of the main attacks to ubiquitous databases is the structure query language (SQL) injection attack, which causes severe damages both in the commercial aspect and in the user’s confidence. This chapter proposes the SiC architecture as a solution to the SQL injection attack problem. This is a hierarchical distributed multiagent architecture, which involves an entirely new approach with respect to existing architectures for the prevention and detection of SQL injections. SiC incorporates a kind of intelligent agent, which integrates a case-based reasoning system. This agent, which is the core of the architecture, allows the application of detection techniques based on anomalies as well as those based on patterns, providing a great degree of autonomy, flexibility, robustness and dynamic scalability. The characteristics of the multiagent system allow an architecture to detect attacks from different types of devices, regardless of the physical location. The architecture has been tested on a medical database, guaranteeing safe access from various devices such as PDAs and notebook computers.

Probing Molecular Mechanisms of the Hsp90 Chaperone: Biophysical Modeling Identifies Key Regulators of Functional Dynamics

PubMed Central

Dixit, Anshuman; Verkhivker, Gennady M.

2012-01-01

Deciphering functional mechanisms of the Hsp90 chaperone machinery is an important objective in cancer biology aiming to facilitate discovery of targeted anti-cancer therapies. Despite significant advances in understanding structure and function of molecular chaperones, organizing molecular principles that control the relationship between conformational diversity and functional mechanisms of the Hsp90 activity lack a sufficient quantitative characterization. We combined molecular dynamics simulations, principal component analysis, the energy landscape model and structure-functional analysis of Hsp90 regulatory interactions to systematically investigate functional dynamics of the molecular chaperone. This approach has identified a network of conserved regions common to the Hsp90 chaperones that could play a universal role in coordinating functional dynamics, principal collective motions and allosteric signaling of Hsp90. We have found that these functional motifs may be utilized by the molecular chaperone machinery to act collectively as central regulators of Hsp90 dynamics and activity, including the inter-domain communications, control of ATP hydrolysis, and protein client binding. These findings have provided support to a long-standing assertion that allosteric regulation and catalysis may have emerged via common evolutionary routes. The interaction networks regulating functional motions of Hsp90 may be determined by the inherent structural architecture of the molecular chaperone. At the same time, the thermodynamics-based “conformational selection” of functional states is likely to be activated based on the nature of the binding partner. This mechanistic model of Hsp90 dynamics and function is consistent with the notion that allosteric networks orchestrating cooperative protein motions can be formed by evolutionary conserved and sparsely connected residue clusters. Hence, allosteric signaling through a small network of distantly connected residue clusters may be a rather general functional requirement encoded across molecular chaperones. The obtained insights may be useful in guiding discovery of allosteric Hsp90 inhibitors targeting protein interfaces with co-chaperones and protein binding clients. PMID:22624053

Protected Amine Labels: A Versatile Molecular Scaffold for Multiplexed Nominal Mass and Sub-Da Isotopologue Quantitative Proteomic Reagents

PubMed Central

Ficarro, Scott B.; Biagi, Jessica M.; Wang, Jinhua; Scotcher, Jenna; Koleva, Rositsa I.; Card, Joseph D.; Adelmant, Guillaume; He, Huan; Askenazi, Manor; Marshall, Alan G.; Young, Nicolas L.; Gray, Nathanael S.; Marto, Jarrod A.

2014-01-01

We assemble a versatile molecular scaffold from simple building blocks to create binary and multiplexed stable isotope reagents for quantitative mass spectrometry. Termed Protected Amine Labels (PAL), these reagents offer multiple analytical figures of merit including, (i) robust targeting of peptide N-termini and lysyl side chains, (ii) optimal mass spectrometry ionization efficiency through regeneration of primary amines on labeled peptides, (iii) an amino acid-based mass tag that incorporates heavy isotopes of carbon, nitrogen, and oxygen to ensure matched physicochemical and MS/MS fragmentation behavior among labeled peptides, and (iv) a molecularly efficient architecture, in which the majority of hetero-atom centers can be used to synthesize a variety of nominal mass and sub-Da isotopologue stable isotope reagents. We demonstrate the performance of these reagents in well-established strategies whereby up to four channels of peptide isotopomers, each separated by 4 Da are quantified in MS-level scans with accuracies comparable to current commercial reagents. In addition we utilize the PAL scaffold to create isotopologue reagents in which labeled peptide analogs differ in mass based on the binding energy in carbon and nitrogen nuclei, thereby allowing quantification based on MS or MS/MS spectra. We demonstrate accurate quantification for reagents that support 6-plex labeling and propose extension of this scheme to 9-channels based on a similar PAL scaffold. Finally we provide exemplar data that extends the application of isotopologe-based quantification reagents to medium resolution, quadrupole time-of-flight mass spectrometers. PMID:24496597

Marshall Application Realignment System (MARS) Architecture

NASA Technical Reports Server (NTRS)

Belshe, Andrea; Sutton, Mandy

2010-01-01

The Marshall Application Realignment System (MARS) Architecture project was established to meet the certification requirements of the Department of Defense Architecture Framework (DoDAF) V2.0 Federal Enterprise Architecture Certification (FEAC) Institute program and to provide added value to the Marshall Space Flight Center (MSFC) Application Portfolio Management process. The MARS Architecture aims to: (1) address the NASA MSFC Chief Information Officer (CIO) strategic initiative to improve Application Portfolio Management (APM) by optimizing investments and improving portfolio performance, and (2) develop a decision-aiding capability by which applications registered within the MSFC application portfolio can be analyzed and considered for retirement or decommission. The MARS Architecture describes a to-be target capability that supports application portfolio analysis against scoring measures (based on value) and overall portfolio performance objectives (based on enterprise needs and policies). This scoring and decision-aiding capability supports the process by which MSFC application investments are realigned or retired from the application portfolio. The MARS Architecture is a multi-phase effort to: (1) conduct strategic architecture planning and knowledge development based on the DoDAF V2.0 six-step methodology, (2) describe one architecture through multiple viewpoints, (3) conduct portfolio analyses based on a defined operational concept, and (4) enable a new capability to support the MSFC enterprise IT management mission, vision, and goals. This report documents Phase 1 (Strategy and Design), which includes discovery, planning, and development of initial architecture viewpoints. Phase 2 will move forward the process of building the architecture, widening the scope to include application realignment (in addition to application retirement), and validating the underlying architecture logic before moving into Phase 3. The MARS Architecture key stakeholders are most interested in Phase 3 because this is where the data analysis, scoring, and recommendation capability is realized. Stakeholders want to see the benefits derived from reducing the steady-state application base and identify opportunities for portfolio performance improvement and application realignment.

Secondary Analysis and Integration of Existing Data to Elucidate the Genetic Architecture of Cancer Risk and Related Outcomes, R21 | Informatics Technology for Cancer Research (ITCR)

Cancer.gov

This funding opportunity announcement (FOA) encourages applications that propose to conduct secondary data analysis and integration of existing datasets and database resources, with the ultimate aim to elucidate the genetic architecture of cancer risk and related outcomes. The goal of this initiative is to address key scientific questions relevant to cancer epidemiology by supporting the analysis of existing genetic or genomic datasets, possibly in combination with environmental, outcomes, behavioral, lifestyle, and molecular profiles data.

Secondary Analysis and Integration of Existing Data to Elucidate the Genetic Architecture of Cancer Risk and Related Outcomes, R01 | Informatics Technology for Cancer Research (ITCR)

Cancer.gov

This funding opportunity announcement (FOA) encourages applications that propose to conduct secondary data analysis and integration of existing datasets and database resources, with the ultimate aim to elucidate the genetic architecture of cancer risk and related outcomes. The goal of this initiative is to address key scientific questions relevant to cancer epidemiology by supporting the analysis of existing genetic or genomic datasets, possibly in combination with environmental, outcomes, behavioral, lifestyle, and molecular profiles data.

Imparting the unique properties of DNA into complex material architectures and functions.

PubMed

Xu, Phyllis F; Noh, Hyunwoo; Lee, Ju Hun; Domaille, Dylan W; Nakatsuka, Matthew A; Goodwin, Andrew P; Cha, Jennifer N

2013-07-01

While the remarkable chemical and biological properties of DNA have been known for decades, these properties have only been imparted into materials with unprecedented function much more recently. The inimitable ability of DNA to form programmable, complex assemblies through stable, specific, and reversible molecular recognition has allowed the creation of new materials through DNA's ability to control a material's architecture and properties. In this review we discuss recent progress in how DNA has brought unmatched function to materials, focusing specifically on new advances in delivery agents, devices, and sensors.

Rotaxanes and Photovoltaic Materials Based on Pi-Conjugated Donors and Acceptors: Toward Energy Transduction on the Nanoscale

NASA Astrophysics Data System (ADS)

Bruns, Carson J.

The flow of energy between its various forms is central to our understanding of virtually all natural phenomena, from the origins and fate of the universe to the mechanisms that underpin Life. Therefore, a deeper fundamental understanding of how to manage energy processes at the molecular scale will open new doors in science and technology. This dissertation describes organic molecules and materials that are capable of transducing various forms of energy on the nanoscale, namely, a class of mechanically interlocked molecules known as rotaxanes for electrochemical-to-mechanical energy transduction (Part I), and a class of thin films known as organic photovoltaics (OPVs) for solar-to-electric energy transduction (Part II). These materials are all based on conjugated molecules with a capacity to donate or accept pi-electrons. A contemporary challenge in molecular nanotechnology is the development of artificial molecular machines (AMMs) that mimic the ability of motor proteins (e.g. myosin, kinesin) to perform mechanical work by leveraging a combination of energy sources and rich structural chemistry. Part I describes the synthesis, characterization, molecular dynamics, and switching properties of a series of `daisy chain' and oligorotaxane AMM prototypes. All compounds are templated by charge transfer and hydrogen bonding interactions between pi-associated 1,5-dioxynaphthlene donors appended with polyether groups and pi-acceptors of either neutral (naphthalenediimide) or charged (4,4´-bipyridinium) varieties, and are synthesized using efficient one-pot copper(I)-catalyzed azide-alkyne cycloaddition `click chemistry' protocols. The interlocked architectures of these rotaxanes enable them to express sophisticated secondary structures (i.e. foldamers) and mechanical motions in solution, which have been elucidated using dynamic 1H NMR spectroscopy. Furthermore, molecular dynamics simulations, cyclic voltammetry, and spectroelectrochemistry experiments have demonstrated that the muscle-like contractile-extensile motions of the daisy chains can be controlled by redox or thermal stimuli. It is concluded that donor-acceptor daisy chains and oligorotaxanes of unprecendented complexity can be readily prepared using click chemistry and actuated in solution. Motivated by the global demand for low-cost renewable energy, novel pi-donor molecules based on thiophene and diketopyrrolopyrrole (DPP) moieties are investigated in the context of thin-film materials for OPV technologies in Part II. Homologous families of small-molecule donors have been synthesized to investigate the effects of various molecular design principles on the morphological, optical, electronic, and photovoltaic properties of the corresponding thin-film materials. This strategy has been executed in the context of inorganic-organic hybrid OPVs and also more conventional bulk heterojunction (BHJ) OPVs. In the former case, a series of terthiophene surfactants with systematic variations in valency, geometry, and flexibility are electrodeposited on transparent electrodes from aqueous solutions to yield lamellar Zn(OH)2 materials with nanoscale periodicity, which are characterized by scanning electron miscroscopy and two-dimensional grazing incidence X-ray scattering. It is concluded that monovalent, flexible, linear surfactants yield the most dense and anisotropic nanostructures that are ideal for OPVs. For BHJ OPVs, the family of compounds under investigation are small molecule (SM) donors based on electron-rich heterocyclic acenes (benzodithiophene, benzodifuran, naphtho-dithiophene) and electron-poor thiophene-flanked DPP units. Single crystal X-ray structures of the SM donors are compared with morphological, hole mobility, photovoltaic efficiency data on their blends with a common fullerene acceptor to elucidate the optimal molecular design principles for this class of OPVs. It is concluded that the best-performing molecules have a symmetric architecture in which the central acene core comprises an extended pi-system.

Molecular architecture of the human protein deacetylase Sirt1 and its regulation by AROS and resveratrol

PubMed Central

Lakshminarasimhan, Mahadevan; Curth, Ute; Moniot, Sebastien; Mosalaganti, Shyamal; Raunser, Stefan; Steegborn, Clemens

2013-01-01

Sirtuins are NAD+-dependent protein deacetylases regulating metabolism, stress responses and ageing processes. Among the seven mammalian Sirtuins, Sirt1 is the physiologically best-studied isoform. It regulates nuclear functions such as chromatin remodelling and gene transcription, and it appears to mediate beneficial effects of a low calorie diet which can partly be mimicked by the Sirt1 activating polyphenol resveratrol. The molecular details of Sirt1 domain architecture and regulation, however, are little understood. It has a unique N-terminal domain and CTD (C-terminal domain) flanking a conserved Sirtuin catalytic core and these extensions are assumed to mediate Sirt1-specific features such as homo-oligomerization and activation by resveratrol. To analyse the architecture of human Sirt1 and functions of its N- and C-terminal extensions, we recombinantly produced Sirt1 and Sirt1 deletion constructs as well as the AROS (active regulator of Sirt1) protein. We then studied Sirt1 features such as molecular size, secondary structure and stimulation by small molecules and AROS. We find that Sirt1 is monomeric and has extended conformations in its flanking domains, likely disordered especially in the N-terminus, resulting in an increased hydrodynamic radius. Nevertheless, both termini increase Sirt1 deacetylase activity, indicating a regulatory function. We also find an unusual but defined conformation for AROS protein, which fails, however, to stimulate Sirt1. Resveratrol, in contrast, activates the Sirt1 catalytic core independent of the terminal domains, indicating a binding site within the catalytic core and suggesting that small molecule activators for other isoforms might also exist. PMID:23548308

Molecular characterization of PRM associated endometrial changes, PAEC, following mifepristone treatment.

PubMed

Berger, C; Boggavarapu, N; Norlin, E; Queckbörner, S; Hörnaeus, K; Falk, A; Engman, M; Ramström, M; Lalitkumar, P G L; Gemzell-Danielsson, K

2018-06-08

The progesterone receptor modulator (PRM) Mifepristone hold the potential to be developed for regular contraception. However, long-term treatment can cause thickening of the endometrium and PRM associated endometrial changes (PAEC). The objective of this study was to explore the molecular expression of endometrium displaying PAEC after mifepristone treatment, in order to understand the future implications of PAEC and safety of long-term use. Endometrial biopsies were obtained from pre-menopausal women following three months of continuous mifepristone treatment. The biopsies were evaluated regarding occurrence of PAEC and followed up by a comparative analysis of gene expression in PAEC endometrium (n=7) with endometrium not displaying PAEC (n=4). Methods used included microarray analysis, Ingenuity Pathway Analysis and real time PCR. Three genes relevant within endometrial function were upregulated with PAEC; THY1 (p=0.02), ADAM12 (p=0.04) and TN-C (p=0.04). The proliferation marker MKi67 was not altered (p=0.31). None of the differentially regulated genes were involved in the endometrial cancer-signaling pathway (based on IPA knowledge database). The genes altered in endometrium displaying PAEC after three months of mifepristone exposure are mainly involved in the structural architecture of tissue. PAEC features may be explained by the altered genes and their networks affecting tissue architecture although not involved in endometrial cancer signaling pathways and thus treatment with mifepristone at this dosage does not show any adverse effect at endometrial level. Copyright © 2018. Published by Elsevier Inc.

Homology modeling, docking studies and molecular dynamic simulations using graphical processing unit architecture to probe the type-11 phosphodiesterase catalytic site: a computational approach for the rational design of selective inhibitors.

PubMed

Cichero, Elena; D'Ursi, Pasqualina; Moscatelli, Marco; Bruno, Olga; Orro, Alessandro; Rotolo, Chiara; Milanesi, Luciano; Fossa, Paola

2013-12-01

Phosphodiesterase 11 (PDE11) is the latest isoform of the PDEs family to be identified, acting on both cyclic adenosine monophosphate and cyclic guanosine monophosphate. The initial reports of PDE11 found evidence for PDE11 expression in skeletal muscle, prostate, testis, and salivary glands; however, the tissue distribution of PDE11 still remains a topic of active study and some controversy. Given the sequence similarity between PDE11 and PDE5, several PDE5 inhibitors have been shown to cross-react with PDE11. Accordingly, many non-selective inhibitors, such as IBMX, zaprinast, sildenafil, and dipyridamole, have been documented to inhibit PDE11. Only recently, a series of dihydrothieno[3,2-d]pyrimidin-4(3H)-one derivatives proved to be selective toward the PDE11 isoform. In the absence of experimental data about PDE11 X-ray structures, we found interesting to gain a better understanding of the enzyme-inhibitor interactions using in silico simulations. In this work, we describe a computational approach based on homology modeling, docking, and molecular dynamics simulation to derive a predictive 3D model of PDE11. Using a Graphical Processing Unit architecture, it is possible to perform long simulations, find stable interactions involved in the complex, and finally to suggest guideline for the identification and synthesis of potent and selective inhibitors. © 2013 John Wiley & Sons A/S.

Shared Genetic Architecture in the Relationship between Adult Stature and Subclinical Coronary Artery Atherosclerosis

PubMed Central

Cassidy-Bushrow, Andrea E.; Bielak, Lawrence F.; Sheedy, Patrick F.; Turner, Stephen T.; Chu, Julia S.; Peyser, Patricia A.

2011-01-01

Background Short stature is associated with increased risk of coronary heart disease (CHD); although the mechanisms for this relationship are unknown, shared genetic factors have been proposed. Subclinical atherosclerosis, measured by coronary artery calcification (CAC), is associated with CHD events and represents part of the biological continuum to overt CHD. Many molecular mechanisms of CAC development are shared with bone growth. Thus, we examined whether there was evidence of shared genes (pleiotropy) between adult stature and CAC. Methods 877 asymptomatic white adults (46% men) from 625 families in a community-based sample had computed tomography measures of CAC. Pleiotropy between height and CAC was determined using maximum-likelihood estimation implemented in SOLAR. Results Adult height was significantly and inversely associated with CAC score (P=0.01). After adjusting for age, sex, and CHD risk factors, the estimated genetic correlation between height and CAC score was -0.37 and was significantly different than 0 (P=0.001) and -1 (P<0.001). The environmental correlation between height and CAC score was 0.60 and was significantly different than 0 (P=0.024). Conclusions Further studies of shared genetic factors between height and CAC may provide important insight into the complex genetic architecture of CHD, in part through increased understanding of the molecular pathways underlying the process of both normal growth and disease development. Bivariate genetic linkage analysis may provide a powerful mechanism for identifying specific genomic regions associated with both height and CAC. PMID:21937044

Shared genetic architecture in the relationship between adult stature and subclinical coronary artery atherosclerosis.

PubMed

Cassidy-Bushrow, Andrea E; Bielak, Lawrence F; Sheedy, Patrick F; Turner, Stephen T; Chu, Julia S; Peyser, Patricia A

2011-12-01

Short stature is associated with increased risk of coronary heart disease (CHD); although the mechanisms for this relationship are unknown, shared genetic factors have been proposed. Subclinical atherosclerosis, measured by coronary artery calcification (CAC), is associated with CHD events and represents part of the biological continuum to overt CHD. Many molecular mechanisms of CAC development are shared with bone growth. Thus, we examined whether there was evidence of shared genes (pleiotropy) between adult stature and CAC. 877 Asymptomatic white adults (46% men) from 625 families in a community-based sample had computed tomography measures of CAC. Pleiotropy between height and CAC was determined using maximum-likelihood estimation implemented in SOLAR. Adult height was significantly and inversely associated with CAC score (P = 0.01). After adjusting for age, sex and CHD risk factors, the estimated genetic correlation between height and CAC score was -0.37 and was significantly different than 0 (P = 0.001) and -1 (P < 0.001). The environmental correlation between height and CAC score was 0.60 and was significantly different than 0 (P = 0.024). Further studies of shared genetic factors between height and CAC may provide important insight into the complex genetic architecture of CHD, in part through increased understanding of the molecular pathways underlying the process of both normal growth and disease development. Bivariate genetic linkage analysis may provide a powerful mechanism for identifying specific genomic regions associated with both height and CAC. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Hypercubane: DFT-based prediction of an Oh-symmetric double-shell hydrocarbon

NASA Astrophysics Data System (ADS)

Pichierri, Fabio

2014-09-01

Using density functional theory we design a molecular analog of the four-dimensional hypercube or tesseract which we called hypercubane. The title hydrocarbon (C40H24) is Oh-symmetric like cubane and is characterized by a double-shell architecture. The perfluorinated analog of hypercubane also is stable with a positive value of the electron affinity. Removal of the C8 core from hypercubane yields a hollowed Oh-symmetric hydrocarbon with enough room to host a single atom/ion guest. The resonances of the NMR-active 13C and 1H nuclei have been computed so as to assist the spectroscopic identification of the predicted molecules.

Potential Energy Surfaces and Dynamics for Energetic Ionic Liquids

DTIC Science & Technology

2012-04-09

advantage of such architectures12. Very recently, we have implemented the FMO method on the BG/ P system at Argonne National Laboratory, demonstrating that...Molecular Orbital Method”, J. Comp. Theoret. Chem., 6, 1 (2010). 4. T. Nagata, D . Fedorov, K. Kitaura, and M.S. Gordon, “A Combined Effective Fragment...Chem., 3, 177 (2007). 6. T. Nagata, D . Fedorov, K. Kitaura, and M.S. Gordon, “A Combined Effective Fragment Potential - Fragment Molecular Orbital

Architecture and Surface Chemistry of Compound Nanoclusters

DTIC Science & Technology

2012-07-31

Inorganic and organic chemistry in the gas phase," Molecular Dynamics Seminar, Fritz Haber Institute, Berlin, Germany, June 2010. 12. "Infrared...Patent Disclosures none Pi Honors/Awards Alexander von Humboldt Fellowship ( Fritz Haber Institute, Berlin), 2007-present American Chemical

Architecture and Surface Chemistry of Compound Nanoclusters

DTIC Science & Technology

2012-08-01

spectroscopy of metal carbonyls and carbocations: Inorganic and organic chemistry in the gas phase," Molecular Dynamics Seminar, Fritz Haber Institute...Disclosures none Pi Honors/Awards Alexander von Humboldt Fellowship ( Fritz Haber Institute, Berlin), 2007-present American Chemical Society

Formal Foundations for the Specification of Software Architecture.

DTIC Science & Technology

1995-03-01

Architectures For- mally: A Case-Study Using KWIC." Kestrel Institute, Palo Alto, CA 94304, April 1994. 58. Kang, Kyo C. Feature-Oriented Domain Analysis ( FODA ...6.3.5 Constraint-Based Architectures ................. 6-60 6.4 Summary ......... ............................. 6-63 VII. Analysis of Process-Based...between these architec- ture theories were investigated. A feasibility analysis on an image processing application demonstrated that architecture theories

Autonomous, Decentralized Grid Architecture: Prosumer-Based Distributed Autonomous Cyber-Physical Architecture for Ultra-Reliable Green Electricity Networks

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

2012-01-11

GENI Project: Georgia Tech is developing a decentralized, autonomous, internet-like control architecture and control software system for the electric power grid. Georgia Tech’s new architecture is based on the emerging concept of electricity prosumers—economically motivated actors that can produce, consume, or store electricity. Under Georgia Tech’s architecture, all of the actors in an energy system are empowered to offer associated energy services based on their capabilities. The actors achieve their sustainability, efficiency, reliability, and economic objectives, while contributing to system-wide reliability and efficiency goals. This is in marked contrast to the current one-way, centralized control paradigm.

Antibody-based analysis reveals “filamentous vs. non-filamentous” and “cytoplasmic vs. nuclear” crosstalk of cytoskeletal proteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumeta, Masahiro, E-mail: kumeta@lif.kyoto-u.ac.jp; Hirai, Yuya; Yoshimura, Shige H.

2013-12-10

To uncover the molecular composition and dynamics of the functional scaffold for the nucleus, three fractions of biochemically-stable nuclear protein complexes were extracted and used as immunogens to produce a variety of monoclonal antibodies. Many helix-based cytoskeletal proteins were identified as antigens, suggesting their dynamic contribution to nuclear architecture and function. Interestingly, sets of antibodies distinguished distinct subcellular localization of a single isoform of certain cytoskeletal proteins; distinct molecular forms of keratin and actinin were found in the nucleus. Their nuclear shuttling properties were verified by the apparent nuclear accumulations under inhibition of CRM1-dependent nuclear export. Nuclear keratins do notmore » take an obvious filamentous structure, as was revealed by non-filamentous cytoplasmic keratin-specific monoclonal antibody. These results suggest the distinct roles of the helix-based cytoskeletal proteins in the nucleus. - Highlights: • A set of monoclonal antibodies were raised against nuclear scaffold proteins. • Helix-based cytoskeletal proteins were involved in nuclear scaffold. • Many cytoskeletal components shuttle into the nucleus in a CRM1-dependent manner. • Sets of antibodies distinguished distinct subcellular localization of a single isoform. • Nuclear keratin is soluble and does not form an obvious filamentous structure.« less

A DNA-Inspired Encryption Methodology for Secure, Mobile Ad Hoc Networks

NASA Technical Reports Server (NTRS)

Shaw, Harry

2012-01-01

Users are pushing for greater physical mobility with their network and Internet access. Mobile ad hoc networks (MANET) can provide an efficient mobile network architecture, but security is a key concern. A figure summarizes differences in the state of network security for MANET and fixed networks. MANETs require the ability to distinguish trusted peers, and tolerate the ingress/egress of nodes on an unscheduled basis. Because the networks by their very nature are mobile and self-organizing, use of a Public Key Infra structure (PKI), X.509 certificates, RSA, and nonce ex changes becomes problematic if the ideal of MANET is to be achieved. Molecular biology models such as DNA evolution can provide a basis for a proprietary security architecture that achieves high degrees of diffusion and confusion, and resistance to cryptanalysis. A proprietary encryption mechanism was developed that uses the principles of DNA replication and steganography (hidden word cryptography) for confidentiality and authentication. The foundation of the approach includes organization of coded words and messages using base pairs organized into genes, an expandable genome consisting of DNA-based chromosome keys, and a DNA-based message encoding, replication, and evolution and fitness. In evolutionary computing, a fitness algorithm determines whether candidate solutions, in this case encrypted messages, are sufficiently encrypted to be transmitted. The technology provides a mechanism for confidential electronic traffic over a MANET without a PKI for authenticating users.

Model-based design of RNA hybridization networks implemented in living cells.

PubMed

Rodrigo, Guillermo; Prakash, Satya; Shen, Shensi; Majer, Eszter; Daròs, José-Antonio; Jaramillo, Alfonso

2017-09-19

Synthetic gene circuits allow the behavior of living cells to be reprogrammed, and non-coding small RNAs (sRNAs) are increasingly being used as programmable regulators of gene expression. However, sRNAs (natural or synthetic) are generally used to regulate single target genes, while complex dynamic behaviors would require networks of sRNAs regulating each other. Here, we report a strategy for implementing such networks that exploits hybridization reactions carried out exclusively by multifaceted sRNAs that are both targets of and triggers for other sRNAs. These networks are ultimately coupled to the control of gene expression. We relied on a thermodynamic model of the different stable conformational states underlying this system at the nucleotide level. To test our model, we designed five different RNA hybridization networks with a linear architecture, and we implemented them in Escherichia coli. We validated the network architecture at the molecular level by native polyacrylamide gel electrophoresis, as well as the network function at the bacterial population and single-cell levels with a fluorescent reporter. Our results suggest that it is possible to engineer complex cellular programs based on RNA from first principles. Because these networks are mainly based on physical interactions, our designs could be expanded to other organisms as portable regulatory resources or to implement biological computations. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

A wet-tolerant adhesive patch inspired by protuberances in suction cups of octopi

NASA Astrophysics Data System (ADS)

Baik, Sangyul; Kim, Da Wan; Park, Youngjin; Lee, Tae-Jin; Ho Bhang, Suk; Pang, Changhyun

2017-06-01

Adhesion strategies that rely on mechanical interlocking or molecular attractions between surfaces can suffer when coming into contact with liquids. Thus far, artificial wet and dry adhesives have included hierarchical mushroom-shaped or porous structures that allow suction or capillarity, supramolecular structures comprising nanoparticles, and chemistry-based attractants that use various protein polyelectrolytes. However, it is challenging to develop adhesives that are simple to make and also perform well—and repeatedly—under both wet and dry conditions, while avoiding non-chemical contamination on the adhered surfaces. Here we present an artificial, biologically inspired, reversible wet/dry adhesion system that is based on the dome-like protuberances found in the suction cups of octopi. To mimic the architecture of these protuberances, we use a simple, solution-based, air-trap technique that involves fabricating a patterned structure as a polymeric master, and using it to produce a reversed architecture, without any sophisticated chemical syntheses or surface modifications. The micrometre-scale domes in our artificial adhesive enhance the suction stress. This octopus-inspired system exhibits strong, reversible, highly repeatable adhesion to silicon wafers, glass, and rough skin surfaces under various conditions (dry, moist, under water and under oil). To demonstrate a potential application, we also used our adhesive to transport a large silicon wafer in air and under water without any resulting surface contamination.

Novel polyelectrolyte complex based carbon nanotube composite architectures

NASA Astrophysics Data System (ADS)

Razdan, Sandeep

This study focuses on creating novel architectures of carbon nanotubes using polyelectrolytes. Polyelectrolytes are unique polymers possessing resident charges on the macromolecular chains. This property, along with their biocompatibility (true for most polymers used in this study) makes them ideal candidates for a variety of applications such as membranes, drug delivery systems, scaffold materials etc. Carbon nanotubes are also unique one-dimensional nanoscale materials that possess excellent electrical, mechanical and thermal properties owing to their small size, high aspect ratio, graphitic structure and strength arising from purely covalent bonds in the molecular structure. The present study tries to investigate the synthesis processes and material properties of carbon nanotube composites comprising of polyelectrolyte complexes. Carbon nanotubes are dispersed in a polyelectrolyte and are induced into taking part in a complexation process with two oppositely charged polyelectrolytes. The resulting stoichiometric precipitate is then drawn into fiber form and dried as such. The material properties of the carbon nanotube fibers were characterized and related to synthesis parameters and material interactions. Also, an effort was made to understand and predict fiber morphology resulting from the complexation and drawing process. The study helps to delineate the synthesis and properties of the said polyelectrolyte complex-carbon nanotube architectures and highlights useful properties, such as electrical conductivity and mechanical strength, which could make these structures promising candidates for a variety of applications.

A flexible algorithm for calculating pair interactions on SIMD architectures

NASA Astrophysics Data System (ADS)

Páll, Szilárd; Hess, Berk

2013-12-01

Calculating interactions or correlations between pairs of particles is typically the most time-consuming task in particle simulation or correlation analysis. Straightforward implementations using a double loop over particle pairs have traditionally worked well, especially since compilers usually do a good job of unrolling the inner loop. In order to reach high performance on modern CPU and accelerator architectures, single-instruction multiple-data (SIMD) parallelization has become essential. Avoiding memory bottlenecks is also increasingly important and requires reducing the ratio of memory to arithmetic operations. Moreover, when pairs only interact within a certain cut-off distance, good SIMD utilization can only be achieved by reordering input and output data, which quickly becomes a limiting factor. Here we present an algorithm for SIMD parallelization based on grouping a fixed number of particles, e.g. 2, 4, or 8, into spatial clusters. Calculating all interactions between particles in a pair of such clusters improves data reuse compared to the traditional scheme and results in a more efficient SIMD parallelization. Adjusting the cluster size allows the algorithm to map to SIMD units of various widths. This flexibility not only enables fast and efficient implementation on current CPUs and accelerator architectures like GPUs or Intel MIC, but it also makes the algorithm future-proof. We present the algorithm with an application to molecular dynamics simulations, where we can also make use of the effective buffering the method introduces.

Hardware Architecture Study for NASA's Space Software Defined Radios

NASA Technical Reports Server (NTRS)

Reinhart, Richard C.; Scardelletti, Maximilian C.; Mortensen, Dale J.; Kacpura, Thomas J.; Andro, Monty; Smith, Carl; Liebetreu, John

2008-01-01

This study defines a hardware architecture approach for software defined radios to enable commonality among NASA space missions. The architecture accommodates a range of reconfigurable processing technologies including general purpose processors, digital signal processors, field programmable gate arrays (FPGAs), and application-specific integrated circuits (ASICs) in addition to flexible and tunable radio frequency (RF) front-ends to satisfy varying mission requirements. The hardware architecture consists of modules, radio functions, and and interfaces. The modules are a logical division of common radio functions that comprise a typical communication radio. This paper describes the architecture details, module definitions, and the typical functions on each module as well as the module interfaces. Trade-offs between component-based, custom architecture and a functional-based, open architecture are described. The architecture does not specify the internal physical implementation within each module, nor does the architecture mandate the standards or ratings of the hardware used to construct the radios.

Space Telecommunications Radio Systems (STRS) Hardware Architecture Standard: Release 1.0 Hardware Section

NASA Technical Reports Server (NTRS)

Reinhart, Richard C.; Kacpura, Thomas J.; Smith, Carl R.; Liebetreu, John; Hill, Gary; Mortensen, Dale J.; Andro, Monty; Scardelletti, Maximilian C.; Farrington, Allen

2008-01-01

This report defines a hardware architecture approach for software-defined radios to enable commonality among NASA space missions. The architecture accommodates a range of reconfigurable processing technologies including general-purpose processors, digital signal processors, field programmable gate arrays, and application-specific integrated circuits (ASICs) in addition to flexible and tunable radiofrequency front ends to satisfy varying mission requirements. The hardware architecture consists of modules, radio functions, and interfaces. The modules are a logical division of common radio functions that compose a typical communication radio. This report describes the architecture details, the module definitions, the typical functions on each module, and the module interfaces. Tradeoffs between component-based, custom architecture and a functional-based, open architecture are described. The architecture does not specify a physical implementation internally on each module, nor does the architecture mandate the standards or ratings of the hardware used to construct the radios.

A reference architecture for integrated EHR in Colombia.

PubMed

de la Cruz, Edgar; Lopez, Diego M; Uribe, Gustavo; Gonzalez, Carolina; Blobel, Bernd

2011-01-01

The implementation of national EHR infrastructures has to start by a detailed definition of the overall structure and behavior of the EHR system (system architecture). Architectures have to be open, scalable, flexible, user accepted and user friendly, trustworthy, based on standards including terminologies and ontologies. The GCM provides an architectural framework created with the purpose of analyzing any kind of system, including EHR system´s architectures. The objective of this paper is to propose a reference architecture for the implementation of an integrated EHR in Colombia, based on the current state of system´s architectural models, and EHR standards. The proposed EHR architecture defines a set of services (elements) and their interfaces, to support the exchange of clinical documents, offering an open, scalable, flexible and semantically interoperable infrastructure. The architecture was tested in a pilot tele-consultation project in Colombia, where dental EHR are exchanged.

In search of cellular control: signal transduction in context

NASA Technical Reports Server (NTRS)

Ingber, D.

1998-01-01

The field of molecular cell biology has experienced enormous advances over the last century by reducing the complexity of living cells into simpler molecular components and binding interactions that are amenable to rigorous biochemical analysis. However, as our tools become more powerful, there is a tendency to define mechanisms by what we can measure. The field is currently dominated by efforts to identify the key molecules and sequences that mediate the function of critical receptors, signal transducers, and molecular switches. Unfortunately, these conventional experimental approaches ignore the importance of supramolecular control mechanisms that play a critical role in cellular regulation. Thus, the significance of individual molecular constituents cannot be fully understood when studied in isolation because their function may vary depending on their context within the structural complexity of the living cell. These higher-order regulatory mechanisms are based on the cell's use of a form of solid-state biochemistry in which molecular components that mediate biochemical processing and signal transduction are immobilized on insoluble cytoskeletal scaffolds in the cytoplasm and nucleus. Key to the understanding of this form of cellular regulation is the realization that chemistry is structure and hence, recognition of the the importance of architecture and mechanics for signal integration and biochemical control. Recent work that has unified chemical and mechanical signaling pathways provides a glimpse of how this form of higher-order cellular control may function and where paths may lie in the future.

Facile fabrication of superhydrophobic flower-like polyaniline architectures by using valine as a dopant in polymerization

NASA Astrophysics Data System (ADS)

Sun, Jun; Bi, Hong

2012-03-01

A facile method was developed to fabricate superhydrophobic, flower-like polyanline (PANI) architectures with hierarchical nanostructures by adding valine in polymerization as a dopant. The water contact angle of the prepared PANI film was measured to be 155.3°, and the hydrophobic surface of the PANI architectures can be tuned easily by varying the polymerization time as well as valine doping quantity. It is believed that valine plays an important role in not only growth of the hierarchical PANI structures but also formation of the superhydrophobic surface, for it provides functional groups such as sbnd COOH, sbnd NH2 and a hydrophobic terminal group which may further increase intra-/inter-molecular interactions including hydrogen bonding, π-π stacking and hydrophobic properties. Similar flower-like PANI architectures have been prepared successfully by employing other amino acids such as threonine, proline and arginine. This method makes it possible for widespread applications of superhydrophobic PANI film due to its simplicity and practicability.

Immbolization of uricase enzyme in Langmuir and Langmuir-Blodgett films of fatty acids: possible use as a uric acid sensor.

PubMed

Zanon, Nathaly C M; Oliveira, Osvaldo N; Caseli, Luciano

2012-05-01

Preserving the enzyme structure in solid films is key for producing various bioelectronic devices, including biosensors, which has normally been performed with nanostructured films that allow for control of molecular architectures. In this paper, we investigate the adsorption of uricase onto Langmuir monolayers of stearic acid (SA), and their transfer to solid supports as Langmuir-Blodgett (LB) films. Structuring of the enzyme in β-sheets was preserved in the form of 1-layer LB film, which was corroborated with a higher catalytic activity than for other uricase-containing LB film architectures where the β-sheets structuring was not preserved. The optimized architecture was also used to detect uric acid within a range covering typical concentrations in the human blood. The approach presented here not only allows for an optimized catalytic activity toward uric acid but also permits one to explain why some film architectures exhibit a superior performance. Copyright © 2011 Elsevier Inc. All rights reserved.

Solubilization of poorly water-soluble compounds using amphiphilic phospholipid polymers with different molecular architectures.

PubMed

Mu, Mingwei; Konno, Tomohiro; Inoue, Yuuki; Ishihara, Kazuhiko

2017-10-01

To achieve stable and effective solubilization of poorly water-soluble bioactive compounds, water-soluble and amphiphilic polymers composed of hydrophilic 2-methacryloyloxyethyl phosphorylcholine (MPC) units and hydrophobic n-butyl methacrylate (BMA) units were prepared. MPC polymers having different molecular architectures, such as random-type monomer unit sequences and block-type sequences, formed polymer aggregates when they were dissolved in aqueous media. The structure of the random-type polymer aggregate was loose and flexible. On the other hand, the block-type polymer formed polymeric micelles, which were composed of very stable hydrophobic poly(BMA) cores and hydrophilic poly(MPC) shells. The solubilization of a poorly water-soluble bioactive compound, paclitaxel (PTX), in the polymer aggregates was observed, however, solubilizing efficiency and stability were strongly depended on the polymer architecture; in other words, PTX stayed in the poly(BMA) core of the polymer micelle formed by the block-type polymer even when plasma protein was present in the aqueous medium. On the other hand, when the random-type polymer was used, PTX was transferred from the polymer aggregate to the protein. We conclude that water-soluble and amphiphilic MPC polymers are good candidates as solubilizers for poorly water-soluble bioactive compounds. Copyright © 2017 Elsevier B.V. All rights reserved.

Root Architecture Diversity and Meristem Dynamics in Different Populations of Arabidopsis thaliana

PubMed Central

Aceves-García, Pamela; Álvarez-Buylla, Elena R.; Garay-Arroyo, Adriana; García-Ponce, Berenice; Muñoz, Rodrigo; Sánchez, María de la Paz

2016-01-01

Arabidopsis thaliana has been an excellent model system for molecular genetic approaches to development and physiology. More recently, the potential of studying various accessions collected from diverse habitats has been started to exploit. Col-0 has been the best-studied accession but we now know that several traits show significant divergences among them. In this work, we focused in the root that has become a key system for development. We studied root architecture and growth dynamics of 12 Arabidopsis accessions. Our data reveal a wide variability in root architecture and root length among accessions. We also found variability in the root apical meristem (RAM), explained mainly by cell size at the RAM transition domain and possibly by peculiar forms of organization at the stem cell niche in some accessions. Contrary to Col-0 reports, in some accessions the RAM size not always explains the variations in the root length; indicating that elongated cell size could be more relevant in the determination of root length than the RAM size itself. This study contributes to investigations dealing with understanding the molecular and cellular basis of phenotypic variation, the role of plasticity on adaptation, and the developmental mechanisms that may restrict phenotypic variation in response to contrasting environmental conditions. PMID:27379140

Root Architecture Diversity and Meristem Dynamics in Different Populations of Arabidopsis thaliana.

PubMed

Aceves-García, Pamela; Álvarez-Buylla, Elena R; Garay-Arroyo, Adriana; García-Ponce, Berenice; Muñoz, Rodrigo; Sánchez, María de la Paz

2016-01-01

Arabidopsis thaliana has been an excellent model system for molecular genetic approaches to development and physiology. More recently, the potential of studying various accessions collected from diverse habitats has been started to exploit. Col-0 has been the best-studied accession but we now know that several traits show significant divergences among them. In this work, we focused in the root that has become a key system for development. We studied root architecture and growth dynamics of 12 Arabidopsis accessions. Our data reveal a wide variability in root architecture and root length among accessions. We also found variability in the root apical meristem (RAM), explained mainly by cell size at the RAM transition domain and possibly by peculiar forms of organization at the stem cell niche in some accessions. Contrary to Col-0 reports, in some accessions the RAM size not always explains the variations in the root length; indicating that elongated cell size could be more relevant in the determination of root length than the RAM size itself. This study contributes to investigations dealing with understanding the molecular and cellular basis of phenotypic variation, the role of plasticity on adaptation, and the developmental mechanisms that may restrict phenotypic variation in response to contrasting environmental conditions.

Architectural plasticity of AMPK revealed by electron microscopy and X-ray crystallography

PubMed Central

Ouyang, Yan; Zhu, Li; Li, Yifang; Guo, Miaomiao; Liu, Yang; Cheng, Jin; Zhao, Jing; Wu, Yi

2016-01-01

Mammalian AMP-activated protein kinase (AMPK) acts as an important sensor of cellular energy homeostasis related with AMP/ADP to ATP ratio. The overall architecture of AMPK has been determined in either homotrimer or monomer form by electron microscopy (EM) and X-ray crystallography successively. Accordingly proposed models have consistently revealed a key role of the α subunit linker in sensing adenosine nucleoside binding on the γ subunit and mediating allosteric regulation of kinase domain (KD) activity, whereas there are vital differences in orienting N-terminus of α subunit and locating carbohydrate-binding module (CBM) of β subunit. Given that Mg2+, an indispensable cofactor of AMPK was present in the EM sample preparation buffer however absent when forming crystals, here we carried out further reconstructions without Mg2+ to expectably inspect if this ion may contribute to this difference. However, no essential alteration has been found in this study compared to our early work. Further analyses indicate that the intra-molecular movement of the KD and CBM are most likely due to the flexible linkage of the disordered linkers with the rest portion as well as a contribution from the plasticity in the inter-molecular assembly mode, which might ulteriorly reveal an architectural complication of AMPK. PMID:27063142

Influence of the molecular architecture on the adsorption onto solid surfaces: comb-like polymers.

PubMed

Guzmán, Eduardo; Ortega, Francisco; Prolongo, Margarita G; Starov, Victor M; Rubio, Ramón G

2011-09-28

The processes of adsorption of grafted copolymers onto negatively charged surfaces were studied using a dissipative quartz crystal microbalance (D-QCM) and ellipsometry. The control parameters in the study of the adsorption are the existence or absence on the molecular architecture of grafted polyethyleneglycol (PEG) chains with different lengths and the chemical nature of the main chain, poly(allylamine) (PAH) or poly(L-lysine) (PLL). It was found out that the adsorption kinetics of the polymers showed a complex behavior. The total adsorbed amount depends on the architecture of the polymer chains (length of the PEG chains), on the polymer concentration and on the chemical nature of the main chain. The comparison of the thicknesses of the adsorbed layers obtained from D-QCM and from ellipsometry allowed calculation of the water content of the layers that is intimately related to the grafting length. The analysis of D-QCM results also provides information about the shear modulus of the layers, whose values have been found to be typical of a rubber-like polymer system. It is shown that the adsorption of polymers with a charged backbone is not driven exclusively by the electrostatic interactions, but the entropic contributions as a result of the trapping of water in the layer structure are of fundamental importance.

Synthesis of a pH-Sensitive Hetero[4]Rotaxane Molecular Machine that Combines [c2]Daisy and [2]Rotaxane Arrangements.

PubMed

Waelès, Philip; Riss-Yaw, Benjamin; Coutrot, Frédéric

2016-05-10

The synthesis of a novel pH-sensitive hetero[4]rotaxane molecular machine through a self-sorting strategy is reported. The original tetra-interlocked molecular architecture combines a [c2]daisy chain scaffold linked to two [2]rotaxane units. Actuation of the system through pH variation is possible thanks to the specific interactions of the dibenzo-24-crown-8 (DB24C8) macrocycles for ammonium, anilinium, and triazolium molecular stations. Selective deprotonation of the anilinium moieties triggers shuttling of the unsubstituted DB24C8 along the [2]rotaxane units. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Self-Assembly of Optical Molecules with Supramolecular Concepts

PubMed Central

Okamoto, Ken; Chithra, Parayalil; Richards, Gary J.; Hill, Jonathan P.; Ariga, Katsuhiko

2009-01-01

Fabrication of nano-sized objects is one of the most important issues in nanoscience and nanotechnology. Soft nanomaterials with flexible properties have been given much attention and can be obtained through bottom-up processing from functional molecules, where self-assembly based on supramolecular chemistry and designed assembly have become crucial processes and techniques. Among the various functional molecules, dyes have become important materials in certain areas of nanotechnology and their self-assembling behaviors have been actively researched. In this short review, we briefly introduce recent progress in self-assembly of optical molecules and dyes, based mainly on supramolecular concepts. The introduced examples are classified into four categories: self-assembly of (i) low-molecular-weight dyes and (ii) polymeric dyes and dye self-assembly (iii) in nanoscale architectures and (iv) at surfaces. PMID:19564931

The buffering capacity of stems: genetic architecture of nonstructural carbohydrates in cultivated Asian rice, Oryza sativa.

PubMed

Wang, Diane R; Han, Rongkui; Wolfrum, Edward J; McCouch, Susan R

2017-07-01

Harnessing stem carbohydrate dynamics in grasses offers an opportunity to help meet future demands for plant-based food, fiber and fuel production, but requires a greater understanding of the genetic controls that govern the synthesis, interconversion and transport of such energy reserves. We map out a blueprint of the genetic architecture of rice (Oryza sativa) stem nonstructural carbohydrates (NSC) at two critical developmental time-points using a subpopulation-specific genome-wide association approach on two diverse germplasm panels followed by quantitative trait loci (QTL) mapping in a biparental population. Overall, 26 QTL are identified; three are detected in multiple panels and are associated with starch-at-maturity, sucrose-at-maturity and NSC-at-heading. They tag OsHXK6 (rice hexokinase), ISA2 (rice isoamylase) and a tandem array of sugar transporters. This study provides the foundation for more in-depth molecular investigation to validate candidate genes underlying rice stem NSC and informs future comparative studies in other agronomically vital grass species. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

The buffering capacity of stems: genetic architecture of nonstructural carbohydrates in cultivated Asian rice, Oryza sativa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Diane R.; Han, Rongkui; Wolfrum, Edward J.

Harnessing stem carbohydrate dynamics in grasses offers an opportunity to help meet future demands for plant-based food, fiber and fuel production, but requires a greater understanding of the genetic controls that govern the synthesis, interconversion and transport of such energy reserves. We map out a blueprint of the genetic architecture of rice ( Oryza sativa) stem nonstructural carbohydrates (NSC) at two critical developmental time-points using a subpopulation-specific genome-wide association approach on two diverse germplasm panels followed by quantitative trait loci (QTL) mapping in a biparental population. Overall, 26 QTL are identified; three are detected in multiple panels and are associatedmore » with starch-at-maturity, sucrose-at-maturity and NSC-at-heading. They tag OsHXK6 (rice hexokinase), ISA2 (rice isoamylase) and a tandem array of sugar transporters. Furthermore, this study provides the foundation for more in-depth molecular investigation to validate candidate genes underlying rice stem NSC and informs future comparative studies in other agronomically vital grass species.« less

The buffering capacity of stems: genetic architecture of nonstructural carbohydrates in cultivated Asian rice, Oryza sativa

DOE PAGES

Wang, Diane R.; Han, Rongkui; Wolfrum, Edward J.; ...

2017-05-30

Harnessing stem carbohydrate dynamics in grasses offers an opportunity to help meet future demands for plant-based food, fiber and fuel production, but requires a greater understanding of the genetic controls that govern the synthesis, interconversion and transport of such energy reserves. We map out a blueprint of the genetic architecture of rice ( Oryza sativa) stem nonstructural carbohydrates (NSC) at two critical developmental time-points using a subpopulation-specific genome-wide association approach on two diverse germplasm panels followed by quantitative trait loci (QTL) mapping in a biparental population. Overall, 26 QTL are identified; three are detected in multiple panels and are associatedmore » with starch-at-maturity, sucrose-at-maturity and NSC-at-heading. They tag OsHXK6 (rice hexokinase), ISA2 (rice isoamylase) and a tandem array of sugar transporters. Furthermore, this study provides the foundation for more in-depth molecular investigation to validate candidate genes underlying rice stem NSC and informs future comparative studies in other agronomically vital grass species.« less

Nanorobot Hardware Architecture for Medical Defense.

PubMed

Cavalcanti, Adriano; Shirinzadeh, Bijan; Zhang, Mingjun; Kretly, Luiz C

2008-05-06

This work presents a new approach with details on the integrated platform and hardware architecture for nanorobots application in epidemic control, which should enable real time in vivo prognosis of biohazard infection. The recent developments in the field of nanoelectronics, with transducers progressively shrinking down to smaller sizes through nanotechnology and carbon nanotubes, are expected to result in innovative biomedical instrumentation possibilities, with new therapies and efficient diagnosis methodologies. The use of integrated systems, smart biosensors, and programmable nanodevices are advancing nanoelectronics, enabling the progressive research and development of molecular machines. It should provide high precision pervasive biomedical monitoring with real time data transmission. The use of nanobioelectronics as embedded systems is the natural pathway towards manufacturing methodology to achieve nanorobot applications out of laboratories sooner as possible. To demonstrate the practical application of medical nanorobotics, a 3D simulation based on clinical data addresses how to integrate communication with nanorobots using RFID, mobile phones, and satellites, applied to long distance ubiquitous surveillance and health monitoring for troops in conflict zones. Therefore, the current model can also be used to prevent and save a population against the case of some targeted epidemic disease.

Glycan shield and epitope masking of a coronavirus spike protein observed by cryo-electron microscopy

PubMed Central

Walls, Alexandra C.; Tortorici, M. Alejandra; Frenz, Brandon; Snijder, Joost; Li, Wentao; Rey, Félix A.; DiMaio, Frank; Bosch, Berend-Jan; Veesler, David

2017-01-01

The threat of a major coronavirus pandemic urges the development of suitable strategies to combat these pathogens. HCoV-NL63 is an α-coronavirus that can cause severe lower respiratory tract infections requiring hospitalization. We report here the 3.4 Å resolution cryo-electron microscopy reconstruction of the HCoV-NL63 coronavirus spike glycoprotein trimer, which is the conformational machine responsible for entry into host cells and the sole target of neutralizing antibodies during infection. The map resolves the extensive glycan shield obstructing the protein surface and, in combination with mass-spectrometry, provides a structural framework to understand accessibility to antibodies. The structure also reveals a remarkable modular architecture of the receptor-binding subunit and the complete architecture of the fusion machinery including the triggering loop and the C-terminal domains, which contribute to anchoring the trimer to the viral membrane. Our data further suggest that HCoV-NL63 and other coronaviruses use molecular trickery, based on masking of epitopes with glycans and activating conformational changes, to evade the immune system of infected hosts. PMID:27617430

Asynchronous Replica Exchange Software for Grid and Heterogeneous Computing.

PubMed

Gallicchio, Emilio; Xia, Junchao; Flynn, William F; Zhang, Baofeng; Samlalsingh, Sade; Mentes, Ahmet; Levy, Ronald M

2015-11-01

Parallel replica exchange sampling is an extended ensemble technique often used to accelerate the exploration of the conformational ensemble of atomistic molecular simulations of chemical systems. Inter-process communication and coordination requirements have historically discouraged the deployment of replica exchange on distributed and heterogeneous resources. Here we describe the architecture of a software (named ASyncRE) for performing asynchronous replica exchange molecular simulations on volunteered computing grids and heterogeneous high performance clusters. The asynchronous replica exchange algorithm on which the software is based avoids centralized synchronization steps and the need for direct communication between remote processes. It allows molecular dynamics threads to progress at different rates and enables parameter exchanges among arbitrary sets of replicas independently from other replicas. ASyncRE is written in Python following a modular design conducive to extensions to various replica exchange schemes and molecular dynamics engines. Applications of the software for the modeling of association equilibria of supramolecular and macromolecular complexes on BOINC campus computational grids and on the CPU/MIC heterogeneous hardware of the XSEDE Stampede supercomputer are illustrated. They show the ability of ASyncRE to utilize large grids of desktop computers running the Windows, MacOS, and/or Linux operating systems as well as collections of high performance heterogeneous hardware devices.

Using Solid-state NMR to Monitor the Molecular Consequences of Cryptococcus neoformans Melanization with Different Catecholamine Precursors

PubMed Central

Chatterjee, Subhasish; Prados-Rosales, Rafael; Frases, Susana; Itin, Boris; Casadevall, Arturo; Stark, Ruth E.

2012-01-01

Melanins are a class of natural pigments associated with a wide range of biological functions, including microbial virulence, energy transduction, and protection against solar radiation. Because of their insolubility and structural heterogeneity, solid-state nuclear magnetic resonance (NMR) spectroscopy provides an unprecedented means to define the molecular architecture of these enigmatic pigments. The requirement of obligatory catecholamines for melanization of the pathogenic fungus Cryptococcus neoformans also offers unique opportunities for investigating melanin development. In the current study, pigments produced with L-dopa, methyl-L-dopa, epinephrine, and norepinephrine precursors are compared structurally using 13C and 1H magic-angle spinning (MAS) NMR. Striking structural differences were observed for both aromatic and aliphatic molecular constituents of the mature fungal pigment assemblies, thus making it possible to redefine the molecular prerequisites for formation of the aromatic domains of insoluble indole-based biopolymers, to rationalize their distinctive physical characteristics, and to delineate the role of cellular constituents in assembly of the melanized macromolecules with polysaccharides and fatty acyl chain-containing moieties. By achieving an augmented understanding of the mechanisms of C. neoformans melanin biosynthesis and cellular assembly, such studies can guide future drug discovery efforts related to melanin-associated virulence, resistance to tumor therapy, and production of melanin mimetics under cell-free conditions. PMID:22765382

An organic white light-emitting dye: very small molecular architecture displays panchromatic emission.

PubMed

Nandhikonda, Premchendar; Heagy, Michael D

2010-11-14

The synthesis and photophysical characterization of a new white-light fluorophore is described. The optimization of excitation wavelengths allows the naphthalimide (NI) dyes to display blue, green or white light emission depending on the excitation wavelength.

Molecular Architecture of Muscles in an Acoel and Its Evolutionary Implications

PubMed Central

CHIODIN, MARTA; ACHATZ, JOHANNES G.; WANNINGER, ANDREAS; MARTINEZ, PEDRO

2011-01-01

We have characterized the homologs of an actin, a troponin I, and a tropomyosin gene in the acoel Symsagittifera roscoffensis. These genes are expressed in muscles and most likely coexpressed in at least a subset of them. In addition, and for the first time for Acoela, we have produced a species-specific muscular marker, an antibody against the tropomyosin protein. We have followed tropomyosin gene and protein expression during postembryonic development and during the posterior regeneration of amputated adults, showing that preexisting muscle fibers contribute to the wound closure. The three genes characterized in this study interact in the striated muscles of vertebrates and invertebrates, where troponin I and tropomyosin are key regulators of the contraction of the sarcomere. S. roscoffensis and all other acoels so far described have only smooth muscles, but the molecular architecture of these is the same as that of striated fibers of other bilaterians. Given the proposed basal position of acoels within the Bilateria, we suggest that sarcomeric muscles arose from a smooth muscle type, which had the molecular repertoire of striated musculature already in place. We discuss this model in a broad comparative perspective. PMID:21538843

Measurement of Small Molecular Dopant F4TCNQ and C 60F 36 Diffusion in Organic Bilayer Architectures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Jun; Rochester, Chris W.; Jacobs, Ian E.

2015-12-03

The diffusion of molecules through and between organic layers is a serious stability concern in organic electronic devices. In this paper, the temperature-dependent diffusion of molecular dopants through small molecule hole transport layers is observed. Specifically we investigate bilayer stacks of small molecules used for hole transport (MeO-TPD) and p-type dopants (F4TCNQ and C 60F 36) used in hole injection layers for organic light emitting diodes and hole collection electrodes for organic photovoltaics. With the use of absorbance spectroscopy, photoluminescence spectroscopy, neutron reflectometry, and near-edge X-ray absorption fine structure spectroscopy, we are able to obtain a comprehensive picture of themore » diffusion of fluorinated small molecules through MeO-TPD layers. F4TCNQ spontaneously diffuses into the MeO-TPD material even at room temperature, while C 60F 36, a much bulkier molecule, is shown to have a substantially higher morphological stability. Finally, this study highlights that the differences in size/geometry and thermal properties of small molecular dopants can have a significant impact on their diffusion in organic device architectures.« less

Structures of EccB 1 and EccD 1 from the core complex of the mycobacterial ESX-1 type VII secretion system

DOE PAGES

Wagner, Jonathan M.; Chan, Sum; Evans, Timothy J.; ...

2016-02-27

The ESX-1 type VII secretion system is an important determinant of virulence in pathogenic mycobacteria, including Mycobacterium tuberculosis. This complicated molecular machine secretes folded proteins through the mycobacterial cell envelope to subvert the host immune response. Despite its important role in disease very little is known about the molecular architecture of the ESX-1 secretion system. This study characterizes the structures of the soluble domains of two conserved core ESX-1 components – EccB 1 and EccD 1. The periplasmic domain of EccB 1 consists of 4 repeat domains and a central domain, which together form a quasi 2-fold symmetrical structure. Themore » repeat domains of EccB 1 are structurally similar to a known peptidoglycan binding protein suggesting a role in anchoring the ESX-1 system within the periplasmic space. The cytoplasmic domain of EccD 1 has a ubiquitin-like fold and forms a dimer with a negatively charged groove. In conclusion, these structures represent a major step towards resolving the molecular architecture of the entire ESX-1 assembly and may contribute to ESX-1 targeted tuberculosis intervention strategies.« less

Structures of EccB 1 and EccD 1 from the core complex of the mycobacterial ESX-1 type VII secretion system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wagner, Jonathan M.; Chan, Sum; Evans, Timothy J.

The ESX-1 type VII secretion system is an important determinant of virulence in pathogenic mycobacteria, including Mycobacterium tuberculosis. This complicated molecular machine secretes folded proteins through the mycobacterial cell envelope to subvert the host immune response. Despite its important role in disease very little is known about the molecular architecture of the ESX-1 secretion system. This study characterizes the structures of the soluble domains of two conserved core ESX-1 components – EccB 1 and EccD 1. The periplasmic domain of EccB 1 consists of 4 repeat domains and a central domain, which together form a quasi 2-fold symmetrical structure. Themore » repeat domains of EccB 1 are structurally similar to a known peptidoglycan binding protein suggesting a role in anchoring the ESX-1 system within the periplasmic space. The cytoplasmic domain of EccD 1 has a ubiquitin-like fold and forms a dimer with a negatively charged groove. In conclusion, these structures represent a major step towards resolving the molecular architecture of the entire ESX-1 assembly and may contribute to ESX-1 targeted tuberculosis intervention strategies.« less

NASA Enterprise Architecture and Its Use in Transition of Research Results to Operations

NASA Astrophysics Data System (ADS)

Frisbie, T. E.; Hall, C. M.

2006-12-01

Enterprise architecture describes the design of the components of an enterprise, their relationships and how they support the objectives of that enterprise. NASA Stennis Space Center leads several projects involving enterprise architecture tools used to gather information on research assets within NASA's Earth Science Division. In the near future, enterprise architecture tools will link and display the relevant requirements, parameters, observatories, models, decision systems, and benefit/impact information relationships and map to the Federal Enterprise Architecture Reference Models. Components configured within the enterprise architecture serving the NASA Applied Sciences Program include the Earth Science Components Knowledge Base, the Systems Components database, and the Earth Science Architecture Tool. The Earth Science Components Knowledge Base systematically catalogues NASA missions, sensors, models, data products, model products, and network partners appropriate for consideration in NASA Earth Science applications projects. The Systems Components database is a centralized information warehouse of NASA's Earth Science research assets and a critical first link in the implementation of enterprise architecture. The Earth Science Architecture Tool is used to analyze potential NASA candidate systems that may be beneficial to decision-making capabilities of other Federal agencies. Use of the current configuration of NASA enterprise architecture (the Earth Science Components Knowledge Base, the Systems Components database, and the Earth Science Architecture Tool) has far exceeded its original intent and has tremendous potential for the transition of research results to operational entities.

CALISTO - A Novel Architecture for the Single Aperture Far Infrared Observatory

NASA Astrophysics Data System (ADS)

Lester, Daniel F.; Goldsmith, P.; Benford, D.

2007-12-01

Following the success of Spitzer, and in expectation of success with JWST and Herschel, the astronomical community is looking ahead to a large aperture far infrared mission that can build on the scientific results of these missions. This expectation was formalized by the 2000 Decadal recommendation for design studies on a SAFIR - a single aperture far infrared observatory. A JWST-inspired architecture for SAFIR was considered in a Vision Mission study several years ago. We present here a exciting new architecture for this important mission that offers several advantages. This CALISTO (Cryogenic Far-Infrared/Submillimeter Observatory) architecture, originally developed by JPL, builds on the thermally optimized passive cooling design of the Vision Mission version of SAFIR, and focal plane instrument strategies as well, but is based on a 4x6m ellipsoidal primary that greatly simplifies deployment out of an ELV launch shroud. Used off-axis, this design is much less affected by scattered (e.g. galactic plane and ZODI) emission than previous architectures, providing astronomical background-limited facility over much of the sky. Technologies for such a large mirror, diffraction-limited at 20µm, are now becoming credible. Using the large focal plane to host envisioned large format sensor arrays operating with high spatial resolution, CALISTO will resolve the far infrared extragalactic background, and trace the chemical evolution of galaxies. Simple models suggest that detection of the first structure in the universe, marked by cooling primordial clouds of molecular hydrogen at high z, may be achievable with such a telescope. Further building on the work of Spitzer, CALISTO will trace the development of planetary systems, probing the inner structure of star forming disks, and reveal the structure of nearby solar systems using the structure of debris disks that surround them. We review in this paper the science goals and engineering challenges for this mission.

Image Understanding Architecture

DTIC Science & Technology

1991-09-01

architecture to support real-time, knowledge -based image understanding , and develop the software support environment that will be needed to utilize...NUMBER OF PAGES Image Understanding Architecture, Knowledge -Based Vision, AI Real-Time Computer Vision, Software Simulator, Parallel Processor IL PRICE... information . In addition to sensory and knowledge -based processing it is useful to introduce a level of symbolic processing. Thus, vision researchers

Enterprise application architecture development based on DoDAF and TOGAF

NASA Astrophysics Data System (ADS)

Tao, Zhi-Gang; Luo, Yun-Feng; Chen, Chang-Xin; Wang, Ming-Zhe; Ni, Feng

2017-05-01

For the purpose of supporting the design and analysis of enterprise application architecture, here, we report a tailored enterprise application architecture description framework and its corresponding design method. The presented framework can effectively support service-oriented architecting and cloud computing by creating the metadata model based on architecture content framework (ACF), DoDAF metamodel (DM2) and Cloud Computing Modelling Notation (CCMN). The framework also makes an effort to extend and improve the mapping between The Open Group Architecture Framework (TOGAF) application architectural inputs/outputs, deliverables and Department of Defence Architecture Framework (DoDAF)-described models. The roadmap of 52 DoDAF-described models is constructed by creating the metamodels of these described models and analysing the constraint relationship among metamodels. By combining the tailored framework and the roadmap, this article proposes a service-oriented enterprise application architecture development process. Finally, a case study is presented to illustrate the results of implementing the tailored framework in the Southern Base Management Support and Information Platform construction project using the development process proposed by the paper.

Inflammation Modulates Murine Venous Thrombosis Resolution In Vivo: Assessment by Multimodal Fluorescence Molecular Imaging

PubMed Central

Ripplinger, Crystal M.; Kessinger, Chase W.; Li, Chunqiang; Kim, Jin Won; McCarthy, Jason R.; Weissleder, Ralph; Henke, Peter K.; Lin, Charles P.; Jaffer, Farouc A.

2012-01-01

Objective Assessment of thrombus inflammation in vivo could provide new insights into deep vein thrombosis (DVT) resolution. Here we develop and evaluate two integrated fluorescence molecular-structural imaging strategies to quantify DVT-related inflammation and architecture, and to assess the effect of thrombus inflammation on subsequent DVT resolution in vivo. Methods and Results Murine DVT were created with topical 5% FeCl3 application to thigh or jugular veins (n=35). On day 3, mice received macrophage and matrix metalloproteinase (MMP) activity fluorescence imaging agents. On day 4, integrated assessment of DVT inflammation and architecture was performed using confocal fluorescence intravital microscopy (IVM). Day 4 analyses showed robust relationships among in vivo thrombus macrophages, MMP activity, and FITC-dextran deposition (r>0.70, p<0.01). In a serial two-timepoint study, mice with DVT underwent IVM at day 4 and at day 6. Analyses revealed that the intensity of thrombus inflammation at day 4 predicted the magnitude of DVT resolution at day 6 (p<0.05). In a second approach, noninvasive fluorescence molecular tomography-computed tomography (FMT-CT) was employed, and detected macrophages within jugular DVT (p<0.05 vs. sham-controls). Conclusions Integrated fluorescence molecular-structural imaging demonstrates that the DVT-induced inflammatory response can be readily assessed in vivo, and can inform the magnitude of thrombus resolution. PMID:22995524

Two-dimensional optical architectures for the receive mode of phased-array antennas.

PubMed

Pastur, L; Tonda-Goldstein, S; Dolfi, D; Huignard, J P; Merlet, T; Maas, O; Chazelas, J

1999-05-10

We propose and experimentally demonstrate two optical architectures that process the receive mode of a p x p element phased-array antenna. The architectures are based on free-space propagation and switching of the channelized optical carriers of microwave signals. With the first architecture a direct transposition of the received signals in the optical domain is assumed. The second architecture is based on the optical generation and distribution of a microwave local oscillator matched in frequency and direction. Preliminary experimental results at microwave frequencies of approximately 3 GHz are presented.

Relating the structure of geminal amido esters to their molecular hyperpolarizability

DOE PAGES

Cole, Jacqueline M.; Lin, Tze -Chia; Ashcroft, Christopher M.; ...

2016-12-05

Advanced organic non-linear optical (NLO) materials have attracted increasing attention due to their multitude of applications in modern telecommunication devices. Arguably the most important advantage of organic NLO materials, relative to traditionally used inorganic NLO materials, is their short optical response time. Geminal amido esters with their donor-x-acceptor (D-π-A) architecture exhibit high levels of electron delocalization and substantial intramolecular charge transfer, which should endow these materials with short optical response times and large molecular (hyper)polarizabilities. In order to test this hypothesis, the linear and second-order non-linear optical properties of five geminal amido esters, ( E)-ethyl 3-(X-phenylamino)-2-(Y-phenylcarbamoyl)acrylate (1: X = 4-H,Ymore » = 4-H; 2: X= 4-CH 3, Y = 4-CH 3; 3: X = 4-NO 2, Y = 2,5-OCH 3; 4: X = 2-Cl, Y = 2-Cl; 5: X = 4-Cl, Y = 4-Cl) were synthesized and characterized, whereby NLO structure-function relationships were established including intramolecular charge transfer characteristics, crystal field effects, and molecular first hyperpolarizabilities β. Given the typically large errors (10-30%) associated with the determination of (β) coefficients, three independent methods were used: i) density functional theory, ii) hyper-Rayleigh scattering, and iii) high-resolution X-ray diffraction data analysis based on multipolar modeling of electron densities at each atom. These three methods delivered consistent values of β, and based on these results, 3 should hold the most promise for NLO applications. In conclusion, the correlation between the molecular structure of these geminal amido esters and their linear and non-linear optical properties thus provide molecular design guidelines for organic NLO materials; this leads to the ultimate goal of generating bespoke organic molecules to suit a given NLO device application.« less

Hidden Realities inside PBL Design Processes: Is Consensus Design an Impossible Clash of Interest between the Individual and the Collective, and Is Architecture Its First Victim?

ERIC Educational Resources Information Center

Pihl, Ole

2015-01-01

How do architecture students experience the contradictions between the individual and the group at the Department of Architecture and Design of Aalborg University? The Problem-Based Learning model has been extensively applied to the department's degree programs in coherence with the Integrated Design Process, but is a group-based architecture and…

Actin assembly factors regulate the gelation kinetics and architecture of F-actin networks.

PubMed

Falzone, Tobias T; Oakes, Patrick W; Sees, Jennifer; Kovar, David R; Gardel, Margaret L

2013-04-16

Dynamic regulation of the actin cytoskeleton is required for diverse cellular processes. Proteins regulating the assembly kinetics of the cytoskeletal biopolymer F-actin are known to impact the architecture of actin cytoskeletal networks in vivo, but the underlying mechanisms are not well understood. Here, we demonstrate that changes to actin assembly kinetics with physiologically relevant proteins profilin and formin (mDia1 and Cdc12) have dramatic consequences on the architecture and gelation kinetics of otherwise biochemically identical cross-linked F-actin networks. Reduced F-actin nucleation rates promote the formation of a sparse network of thick bundles, whereas increased nucleation rates result in a denser network of thinner bundles. Changes to F-actin elongation rates also have marked consequences. At low elongation rates, gelation ceases and a solution of rigid bundles is formed. By contrast, rapid filament elongation accelerates dynamic arrest and promotes gelation with minimal F-actin density. These results are consistent with a recently developed model of how kinetic constraints regulate network architecture and underscore how molecular control of polymer assembly is exploited to modulate cytoskeletal architecture and material properties. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Actin Assembly Factors Regulate the Gelation Kinetics and Architecture of F-actin Networks

PubMed Central

Falzone, Tobias T.; Oakes, Patrick W.; Sees, Jennifer; Kovar, David R.; Gardel, Margaret L.

2013-01-01

Dynamic regulation of the actin cytoskeleton is required for diverse cellular processes. Proteins regulating the assembly kinetics of the cytoskeletal biopolymer F-actin are known to impact the architecture of actin cytoskeletal networks in vivo, but the underlying mechanisms are not well understood. Here, we demonstrate that changes to actin assembly kinetics with physiologically relevant proteins profilin and formin (mDia1 and Cdc12) have dramatic consequences on the architecture and gelation kinetics of otherwise biochemically identical cross-linked F-actin networks. Reduced F-actin nucleation rates promote the formation of a sparse network of thick bundles, whereas increased nucleation rates result in a denser network of thinner bundles. Changes to F-actin elongation rates also have marked consequences. At low elongation rates, gelation ceases and a solution of rigid bundles is formed. By contrast, rapid filament elongation accelerates dynamic arrest and promotes gelation with minimal F-actin density. These results are consistent with a recently developed model of how kinetic constraints regulate network architecture and underscore how molecular control of polymer assembly is exploited to modulate cytoskeletal architecture and material properties. PMID:23601318

Regulatory modules controlling maize inflorescence architecture

USDA-ARS?s Scientific Manuscript database

Genetic control of branching is a primary determinant of yield, regulating seed number and harvesting ability, yet little is known about the molecular networks that shape grain-bearing inflorescences of cereal crops. Here, we used the maize (Zea mays) inflorescence to investigate gene networks that...

Fundamentals of Atom Transfer Radical Polymerization

ERIC Educational Resources Information Center

Coessens, Veerle M. C.; Matyjaszewski, Krzysztof

2010-01-01

Today's market increasingly demands sophisticated materials for advanced technologies and high-value applications, such as nanocomposites, optoelectronic, or biomedical materials. Therefore, the demand for well-defined polymers with very specific molecular architecture and properties increases. Until recently, these kinds of polymers could only be…

The genomic architecture of mastitis resistance in dairy sheep.

PubMed

Banos, G; Bramis, G; Bush, S J; Clark, E L; McCulloch, M E B; Smith, J; Schulze, G; Arsenos, G; Hume, D A; Psifidi, A

2017-08-16

Mastitis is the most prevalent disease in dairy sheep with major economic, hygienic and welfare implications. The disease persists in all dairy sheep production systems despite the implementation of improved management practises. Selective breeding for enhanced mastitis resistance may provide the means to further control the disease. In the present study, we investigated the genetic architecture of four mastitis traits in dairy sheep. Individual animal records for clinical mastitis occurrence and three mastitis indicator traits (milk somatic cell count, total viable bacterial count in milk and the California mastitis test) were collected monthly throughout lactation for 609 ewes of the Greek Chios breed. All animals were genotyped with a custom-made 960-single nucleotide polymorphism (SNP) DNA array based on markers located in quantitative trait loci (QTL) regions for mastitis resistance previously detected in three other distinct dairy sheep populations. Heritable variation and strong positive genetic correlations were estimated for clinical mastitis occurrence and the three mastitis indicator traits. SNP markers significantly associated with these mastitis traits were confirmed on chromosomes 2, 3, 5, 16 and 19. We identified pathways, molecular interaction networks and functional gene clusters for mastitis resistance. Candidate genes within the detected regions were identified based upon analysis of an ovine transcriptional atlas and transcriptome data derived from milk somatic cells. Relevant candidate genes implicated in innate immunity included SOCS2, CTLA4, C6, C7, C9, PTGER4, DAB2, CARD6, OSMR, PLXNC1, IDH1, ICOS, FYB, and LYFR. The results confirmed the presence of animal genetic variability in mastitis resistance and identified genomic regions associated with specific mastitis traits in the Chios sheep. The conserved genetic architecture of mastitis resistance between distinct dairy sheep breeds suggests that across-breed selection programmes would be feasible.

High surface area silicon materials: fundamentals and new technology.

PubMed

Buriak, Jillian M

2006-01-15

Crystalline silicon forms the basis of just about all computing technologies on the planet, in the form of microelectronics. An enormous amount of research infrastructure and knowledge has been developed over the past half-century to construct complex functional microelectronic structures in silicon. As a result, it is highly probable that silicon will remain central to computing and related technologies as a platform for integration of, for instance, molecular electronics, sensing elements and micro- and nanoelectromechanical systems. Porous nanocrystalline silicon is a fascinating variant of the same single crystal silicon wafers used to make computer chips. Its synthesis, a straightforward electrochemical, chemical or photochemical etch, is compatible with existing silicon-based fabrication techniques. Porous silicon literally adds an entirely new dimension to the realm of silicon-based technologies as it has a complex, three-dimensional architecture made up of silicon nanoparticles, nanowires, and channel structures. The intrinsic material is photoluminescent at room temperature in the visible region due to quantum confinement effects, and thus provides an optical element to electronic applications. Our group has been developing new organic surface reactions on porous and nanocrystalline silicon to tailor it for a myriad of applications, including molecular electronics and sensing. Integration of organic and biological molecules with porous silicon is critical to harness the properties of this material. The construction and use of complex, hierarchical molecular synthetic strategies on porous silicon will be described.

Molecular-level architectural design using benzothiadiazole-based polymers for photovoltaic applications

PubMed Central

Viswanathan, Vinila N; Rao, Arun D; Pandey, Upendra K; Kesavan, Arul Varman

2017-01-01

A series of low band gap, planar conjugated polymers, P1 (PFDTBT), P2 (PFDTDFBT) and P3 (PFDTTBT), based on fluorene and benzothiadiazole, was synthesized. The effect of fluorine substitution and fused aromatic spacers on the optoelectronic and photovoltaic performance was studied. The polymer, derived from dithienylated benzothiodiazole and fluorene, P1, exhibited a highest occupied molecular orbital (HOMO) energy level at −5.48 eV. Density functional theory (DFT) studies as well as experimental measurements suggested that upon substitution of the acceptor with fluorine, both the HOMO and lowest unoccupied molecular orbital (LUMO) energy levels of the resulting polymer, P2, were lowered, leading to a higher open circuit voltage and short circuit current with an overall improvement of more than 110% for the photovoltaic devices. Moreover, a decrease in the torsion angle between the units was also observed for the fluorinated polymer P2 due to the enhanced electrostatic interaction between the fluorine substituents and sulfur atoms, leading to a high hole mobility. The use of a fused π-bridge in polymer P3 for the enhancement of the planarity as compared to the P1 backbone was also studied. This enhanced planarity led to the highest observed mobility among the reported three polymers as well as to an improvement in the device efficiency by more than 40% for P3. PMID:28546844

Field-Theoretic Simulations

NASA Astrophysics Data System (ADS)

Ganesan, Venkat; Fredrickson, Glenn H.

The science and engineering of materials is entering a new era of so-called "designer materials", wherein, based upon the properties required for a particular application, a material is designed by exploiting the self-assembly of appropriately chosen molecular constituents [1]. The desirable and marketable properties of such materials, which include plastic alloys, block and graft copolymers, and polyelectrolyte solutions, complexes, and gels, depend critically on the ability to control and manipulate morphology by adjusting a combination of molecular and macroscopic variables. For example, styrenebutadiene block copolymers can be devised that serve either as rigid, tough, transparent thermoplastics or as soft, flexible, thermoplastic elastomers, by appropriate control of copolymer architecture and styrene/butadiene ratio. In this case, the property profiles are intimately connected to the extent and type of nanoscale self-assembly that is established within the material. One of the main challenges confronting the successful design of nano-structured polymers is the development of a basic understanding of the relationship between the molecular details of the polymer formulation and the morphology that is achieved. Unfortunately, such relationships are still mainly determined by trial and error experimentation. A purely experimental-based program in pursuit of this objective proves cumbersome — primarily, due to the broad parameter space accessible at the time of synthesis and formulation. Consequently, there is a significant motivation for the development of computational tools that can enable a rational exploration of the parameter space.

Preparation Details for Making Silicones: Influence of Molecular Network Architecture on Mechanical and Surface Properties of PDMS Elastomers

NASA Astrophysics Data System (ADS)

Melillo, Matthew; Walker, Edwin; Klein, Zoe; Efimenko, Kirill; Genzer, Jan

Poly(dimethylsiloxane) (PDMS) is one of the most common elastomers, with applications ranging from medical devices to absorbents for water treatment. Fundamental understanding of how liquids spread on the surface of and absorb into PDMS networks is of critical importance for the design and use of another application - microfluidic devices. We have systematically studied the effects of polymer molecular weight, loading of tetra-functional crosslinker, end-group chemical functionality, the extent of dilution of the curing mixture, and gelation kinetics on the mechanical and surface properties of end-linked PDMS networks. The gel and sol fractions, storage and loss moduli, liquid swelling ratios, and water contact angles have all been shown to vary greatly based on the aforementioned variables. Similar trends were observed for the commercial PDMS material, Sylgard-184. Our results have confirmed theories predicting the relationships between modulus and swelling and we've also applied the theory of Macosko-Miller to estimate extent of reaction of crosslinker and polymer groups. Methods for determining the molecular weight between crosslinks from swelling, mechanical, and gelation theories were applied to ascertain their similarities and differences in an effort to identify the most accurate method. These findings will aid in the design and implementation of efficient microfluidics and other PDMS-based materials that involve the transport of liquids.

Autism spectrum disorders: an updated guide for genetic counseling.

PubMed

Griesi-Oliveira, Karina; Sertié, Andréa Laurato

2017-01-01

Autism spectrum disorder is a complex and genetically heterogeneous disorder, which has hampered the identification of the etiological factors in each patient and, consequently, the genetic counseling for families at risk. However, in the last decades, the remarkable advances in the knowledge of genetic aspects of autism based on genetic and molecular research, as well as the development of new molecular diagnostic tools, have substantially changed this scenario. Nowadays, it is estimated that using the currently available molecular tests, a potential underlying genetic cause can be identified in nearly 25% of cases. Combined with clinical assessment, prenatal history evaluation and investigation of other physiological aspects, an etiological explanation for the disease can be found for approximately 30 to 40% of patients. Therefore, in view of the current knowledge about the genetic architecture of autism spectrum disorder, which has contributed for a more precise genetic counseling, and of the potential benefits that an etiological investigation can bring to patients and families, molecular genetic investigation has become increasingly important. Here, we discuss the current view of the genetic architecture of autism spectrum disorder, and list the main associated genetic alterations, the available molecular tests and the key aspects for the genetic counseling of these families. RESUMO O transtorno do espectro autista é um distúrbio complexo e geneticamente heterogêneo, o que sempre dificultou a identificação de sua etiologia em cada paciente em particular e, por consequência, o aconselhamento genético das famílias. Porém, nas últimas décadas, o acúmulo crescente de conhecimento oriundo das pesquisas sobre os aspectos genéticos e moleculares desta doença, assim como o desenvolvimento de novas ferramentas de diagnóstico molecular, tem mudado este cenário de forma substancial. Atualmente, estima-se que, por meio de testes moleculares, é possível detectar uma alteração genética potencialmente causal em cerca de 25% dos casos. Considerando-se também a avaliação clínica, a história pré-natal e a investigação de outros aspectos fisiológicos, pode-se atribuir uma etiologia para aproximadamente 30 a 40% dos pacientes. Assim, em vista do conhecimento atual sobre a arquitetura genética do transtorno do espectro autista, que tem tornado o aconselhamento genético cada vez mais preciso, e dos potenciais benefícios que a investigação etiológica pode trazer aos pacientes e familiares, tornam-se cada vez mais importantes os testes genéticos moleculares. Apresentamos aqui uma breve discussão sobre a visão atual da arquitetura genética dos transtornos do espectro autista, listando as principais alterações genéticas associadas, os testes moleculares disponíveis e os principais aspectos a se considerar para o aconselhamento genético destas famílias.

Real-time FPGA architectures for computer vision

NASA Astrophysics Data System (ADS)

Arias-Estrada, Miguel; Torres-Huitzil, Cesar

2000-03-01

This paper presents an architecture for real-time generic convolution of a mask and an image. The architecture is intended for fast low level image processing. The FPGA-based architecture takes advantage of the availability of registers in FPGAs to implement an efficient and compact module to process the convolutions. The architecture is designed to minimize the number of accesses to the image memory and is based on parallel modules with internal pipeline operation in order to improve its performance. The architecture is prototyped in a FPGA, but it can be implemented on a dedicated VLSI to reach higher clock frequencies. Complexity issues, FPGA resources utilization, FPGA limitations, and real time performance are discussed. Some results are presented and discussed.

Exploring Carbon Nanotubes for Nanoscale Devices

NASA Technical Reports Server (NTRS)

Han, Jie; Dai; Anantram; Jaffe; Saini, Subhash (Technical Monitor)

1998-01-01

Carbon nanotubes (CNTs) are shown to promise great opportunities in nanoelectronic devices and nanoelectromechanical systems (NEMS) because of their inherent nanoscale sizes, intrinsic electric conductivities, and seamless hexagonal network architectures. I present our collaborative work with Stanford on exploring CNTs for nanodevices in this talk. The electrical property measurements suggest that metallic tubes are quantum wires. Furthermore, two and three terminal CNT junctions have been observed experimentally. We have proposed and studied CNT-based molecular switches and logic devices for future digital electronics. We also have studied CNTs based NEMS inclusing gears, cantilevers, and scanning probe microscopy tips. We investigate both chemistry and physics based aspects of the CNT NEMS. Our results suggest that CNT have ideal stiffness, vibrational frequencies, Q-factors, geometry-dependent electric conductivities, and the highest chemical and mechanical stabilities for the NEMS. The use of CNT SPM tips for nanolithography is presented for demonstration of the advantages of the CNT NEMS.

Nanoelectronics from the bottom up.

PubMed

Lu, Wei; Lieber, Charles M

2007-11-01

Electronics obtained through the bottom-up approach of molecular-level control of material composition and structure may lead to devices and fabrication strategies not possible with top-down methods. This review presents a brief summary of bottom-up and hybrid bottom-up/top-down strategies for nanoelectronics with an emphasis on memories based on the crossbar motif. First, we will discuss representative electromechanical and resistance-change memory devices based on carbon nanotube and core-shell nanowire structures, respectively. These device structures show robust switching, promising performance metrics and the potential for terabit-scale density. Second, we will review architectures being developed for circuit-level integration, hybrid crossbar/CMOS circuits and array-based systems, including experimental demonstrations of key concepts such lithography-independent, chemically coded stochastic demultipluxers. Finally, bottom-up fabrication approaches, including the opportunity for assembly of three-dimensional, vertically integrated multifunctional circuits, will be critically discussed.

Confocal Microscopy and Molecular-Specific Optical Contrast Agents for the Detection of Oral Neoplasia

PubMed Central

Carlson, Alicia L.; Gillenwater, Ann M.; Williams, Michelle D.; El-Naggar, Adel K.; Richards-Kortum, R. R.

2009-01-01

Using current clinical diagnostic techniques, it is difficult to visualize tumor morphology and architecture at the cellular level, which is necessary for diagnostic localization of pathologic lesions. Optical imaging techniques have the potential to address this clinical need by providing real-time, sub-cellular resolution images. This paper describes the use of dual mode confocal microscopy and optical molecular-specific contrast agents to image tissue architecture, cellular morphology, and sub-cellular molecular features of normal and neoplastic oral tissues. Fresh tissue slices were prepared from 33 biopsies of clinically normal and abnormal oral mucosa obtained from 14 patients. Reflectance confocal images were acquired after the application of 6% acetic acid, and fluorescence confocal images were acquired after the application of a fluorescence contrast agent targeting the epidermal growth factor receptor (EGFR). The dual imaging modes provided images similar to light microscopy of hematoxylin and eosin and immunohistochemistry staining, but from thick fresh tissue slices. Reflectance images provided information on the architecture of the tissue and the cellular morphology. The nuclear-to-cytoplasmic (N/C) ratio from the reflectance images was at least 7.5 times greater for the carcinoma than the corresponding normal samples, except for one case of highly keratinized carcinoma. Separation of carcinoma from normal and mild dysplasia was achieved using this ratio (p<0.01). Fluorescence images of EGFR expression yielded a mean fluorescence labeling intensity (FLI) that was at least 2.7 times higher for severe dysplasia and carcinoma samples than for the corresponding normal sample, and could be used to distinguish carcinoma from normal and mild dysplasia (p<0.01). Analyzed together, the N/C ratio and the mean FLI may improve the ability to distinguish carcinoma from normal squamous epithelium. PMID:17877424

Bistable mixed-valence molecular architectures for bit storage

NASA Astrophysics Data System (ADS)

Guihery, Nathalie; Durand, Gérard; Lepetit, Marie-Bernadette

1994-05-01

The work examines the possible realization of bit storage at the molecular scale using mixed valence compounds i.e. the existence of two stable and degenerate forms associated with the 0 and 1 positions of the bit. The proposed systems are constituted of two donors (D) and acceptor (A), or one donor and two acceptors, juxtaposed in DAD or ADA architectures. Our proposals take advantage of the possibility of donor—acceptor complexes to exhibit either complete or partial charge transfer. The first system we propose has an essentially neutral ground state. However, the potential energy surface (PES) presents two degenerated minima associated with a partial charge transfer between the donor and one of the two acceptor molecules (A δ-D δ+1 A and AD δ+ A δ-). Systems presenting a complete charge transfer give rise to two stable, weakly coupled, and degenerate ionic electronic states, A - A + A and AD + A - for an ADA architecture and D + A -D and DA -D + for a DAD In these cases, the two forms differ by both their intramolecular geometries and the relative positions of their constituents. It seems rather difficult to conceive such bistable molecular systems using closed-shell molecules, while a donor radical and a closed-shell acceptor or an acceptor radical and closed-shell donor can generate very stable ionic states. It is assumed that the relative positions of the donor and acceptor molecules can be fixed using chemical bridges constituted of rigid or flexible ligands. The writing and reading processes are discussed for each system as well as the information stability when a large number of bits are juxtaposed on a surface.

Topological structure and mechanics of glassy polymer networks.

PubMed

Elder, Robert M; Sirk, Timothy W

2017-11-22

The influence of chain-level network architecture (i.e., topology) on mechanics was explored for unentangled polymer networks using a blend of coarse-grained molecular simulations and graph-theoretic concepts. A simple extension of the Watts-Strogatz model is proposed to control the graph properties of the network such that the corresponding physical properties can be studied with simulations. The architecture of polymer networks assembled with a dynamic curing approach were compared with the extended Watts-Strogatz model, and found to agree surprisingly well. The final cured structures of the dynamically-assembled networks were nearly an intermediate between lattice and random connections due to restrictions imposed by the finite length of the chains. Further, the uni-axial stress response, character of the bond breaking, and non-affine displacements of fully-cured glassy networks were analyzed as a function of the degree of disorder in the network architecture. It is shown that the architecture strongly affects the network stability, flow stress, onset of bond breaking, and ultimate stress while leaving the modulus and yield point nearly unchanged. The results show that internal restrictions imposed by the network architecture alter the chain-level response through changes to the crosslink dynamics in the flow regime and through the degree of coordinated chain failure at the ultimate stress. The properties considered here are shown to be sensitive to even incremental changes to the architecture and, therefore, the overall network architecture, beyond simple defects, is predicted to be a meaningful physical parameter in the mechanics of glassy polymer networks.

Length-Dependent Nanotransport and Charge Hopping Bottlenecks in Long Thiophene-Containing π-Conjugated Molecular Wires.

PubMed

Smith, Christopher E; Odoh, Samuel O; Ghosh, Soumen; Gagliardi, Laura; Cramer, Christopher J; Frisbie, C Daniel

2015-12-23

Self-assembled conjugated molecular wires containing thiophene up to 6 nm in length were grown layer-by-layer using click chemistry. Reflection-absorption infrared spectroscopy, ellipsometry and X-ray photoelectron spectroscopy were used to follow the stepwise growth. The electronic structure of the conjugated wires was studied with cyclic voltammetry and UV-vis spectroscopy as well as computationally with density functional theory (DFT). The current-voltage curves (±1 V) of the conjugated molecular wires were measured with conducting probe atomic force microscopy (CP-AFM) in which the molecular wire film bound to a gold substrate was contacted with a conductive AFM probe. By systematically measuring the low bias junction resistance as a function of length for molecules 1-4 nm long, we extracted the structure dependent tunneling attenuation factor (β) of 3.4 nm(-1) and a contact resistance of 220 kΩ. The crossover from tunneling to hopping transport was observed at a molecular length of 4-5 nm with an activation energy of 0.35 eV extracted from Arrhenius plots of resistance versus temperature. DFT calculations revealed localizations of spin densities (polarons) on molecular wire radical cations. The calculations were employed to gauge transition state energies for hopping of polarons along wire segments. Individual estimated transition state energies were 0.2-0.4 eV, in good agreement with the experimental activation energy. The transition states correspond to flattening of dihedral angles about specific imine bonds. These results open up possibilities to further explore the influence of molecular architecture on hopping transport in molecular junctions, and highlight the utility of DFT to understand charge localization and associated hopping-based transport.

Updates to the NASA Space Telecommunications Radio System (STRS) Architecture

NASA Technical Reports Server (NTRS)

Kacpura, Thomas J.; Handler, Louis M.; Briones, Janette; Hall, Charles S.

2008-01-01

This paper describes an update of the Space Telecommunications Radio System (STRS) open architecture for NASA space based radios. The STRS architecture has been defined as a framework for the design, development, operation and upgrade of space based software defined radios, where processing resources are constrained. The architecture has been updated based upon reviews by NASA missions, radio providers, and component vendors. The STRS Standard prescribes the architectural relationship between the software elements used in software execution and defines the Application Programmer Interface (API) between the operating environment and the waveform application. Modeling tools have been adopted to present the architecture. The paper will present a description of the updated API, configuration files, and constraints. Minimum compliance is discussed for early implementations. The paper then closes with a summary of the changes made and discussion of the relevant alignment with the Object Management Group (OMG) SWRadio specification, and enhancements to the specialized signal processing abstraction.

A Distributed Intelligent E-Learning System

ERIC Educational Resources Information Center

Kristensen, Terje

2016-01-01

An E-learning system based on a multi-agent (MAS) architecture combined with the Dynamic Content Manager (DCM) model of E-learning, is presented. We discuss the benefits of using such a multi-agent architecture. Finally, the MAS architecture is compared with a pure service-oriented architecture (SOA). This MAS architecture may also be used within…

Extensive Evaluation of Using a Game Project in a Software Architecture Course

ERIC Educational Resources Information Center

Wang, Alf Inge

2011-01-01

This article describes an extensive evaluation of introducing a game project to a software architecture course. In this project, university students have to construct and design a type of software architecture, evaluate the architecture, implement an application based on the architecture, and test this implementation. In previous years, the domain…

Molecular Design of Branched and Binary Molecules at Ordered Interfaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Genson, Kirsten Larson

2005-01-01

This study examined five different branched molecular architectures to discern the effect of design on the ability of molecules to form ordered structures at interfaces. Photochromic monodendrons formed kinked packing structures at the air-water interface due to the cross-sectional area mismatch created by varying number of alkyl tails and the hydrophilic polar head group. The lower generations formed orthorhombic unit cell with long range ordering despite the alkyl tails tilted to a large degree. Favorable interactions between liquid crystalline terminal groups and the underlying substrate were observed to compel a flexible carbosilane dendrimer core to form a compressed elliptical conformationmore » which packed stagger within lamellae domains with limited short range ordering. A twelve arm binary star polymer was observed to form two dimensional micelles at the air-water interface attributed to the higher polystyrene block composition. Linear rod-coil molecules formed a multitude of packing structures at the air-water interface due to the varying composition. Tree-like rod-coil molecules demonstrated the ability to form one-dimensional structures at the air-water interface and at the air-solvent interface caused by the preferential ordering of the rigid rod cores. The role of molecular architecture and composition was examined and the influence chemically competing fragments was shown to exert on the packing structure. The amphiphilic balance of the different molecular series exhibited control on the ordering behavior at the air-water interface and within bulk structures. The shell nature and tail type was determined to dictate the preferential ordering structure and molecular reorganization at interfaces with the core nature effect secondary.« less

Convergence of Domain Architecture, Structure, and Ligand Affinity in Animal and Plant RNA-Binding Proteins.

PubMed

Dias, Raquel; Manny, Austin; Kolaczkowski, Oralia; Kolaczkowski, Bryan

2017-06-01

Reconstruction of ancestral protein sequences using phylogenetic methods is a powerful technique for directly examining the evolution of molecular function. Although ancestral sequence reconstruction (ASR) is itself very efficient, downstream functional, and structural studies necessary to characterize when and how changes in molecular function occurred are often costly and time-consuming, currently limiting ASR studies to examining a relatively small number of discrete functional shifts. As a result, we have very little direct information about how molecular function evolves across large protein families. Here we develop an approach combining ASR with structure and function prediction to efficiently examine the evolution of ligand affinity across a large family of double-stranded RNA binding proteins (DRBs) spanning animals and plants. We find that the characteristic domain architecture of DRBs-consisting of 2-3 tandem double-stranded RNA binding motifs (dsrms)-arose independently in early animal and plant lineages. The affinity with which individual dsrms bind double-stranded RNA appears to have increased and decreased often across both animal and plant phylogenies, primarily through convergent structural mechanisms involving RNA-contact residues within the β1-β2 loop and a small region of α2. These studies provide some of the first direct information about how protein function evolves across large gene families and suggest that changes in molecular function may occur often and unassociated with major phylogenetic events, such as gene or domain duplications. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Web-Based Course Management and Web Services

ERIC Educational Resources Information Center

Mandal, Chittaranjan; Sinha, Vijay Luxmi; Reade, Christopher M. P.

2004-01-01

The architecture of a web-based course management tool that has been developed at IIT [Indian Institute of Technology], Kharagpur and which manages the submission of assignments is discussed. Both the distributed architecture used for data storage and the client-server architecture supporting the web interface are described. Further developments…

Floating-point performance of ARM cores and their efficiency in classical molecular dynamics

NASA Astrophysics Data System (ADS)

Nikolskiy, V.; Stegailov, V.

2016-02-01

Supercomputing of the exascale era is going to be inevitably limited by power efficiency. Nowadays different possible variants of CPU architectures are considered. Recently the development of ARM processors has come to the point when their floating point performance can be seriously considered for a range of scientific applications. In this work we present the analysis of the floating point performance of the latest ARM cores and their efficiency for the algorithms of classical molecular dynamics.

Demystifying Mechanosensitive Piezo Ion Channels.

PubMed

Xu, X Z Shawn

2016-06-01

Mechanosensitive channels mediate touch, hearing, proprioception, and blood pressure regulation. Piezo proteins, including Piezo1 and Piezo2, represent a new class of mechanosensitive channels that have been reported to play key roles in most, if not all, of these modalities. The structural architecture and molecular mechanisms by which Piezos act as mechanosensitive channels, however, remain mysterious. Two new studies have now provided critical insights into the atomic structure and molecular basis of the ion permeation and mechano-gating properties of the Piezo1 channel.

Extension of the AMBER molecular dynamics software to Intel's Many Integrated Core (MIC) architecture

NASA Astrophysics Data System (ADS)

Needham, Perri J.; Bhuiyan, Ashraf; Walker, Ross C.

2016-04-01

We present an implementation of explicit solvent particle mesh Ewald (PME) classical molecular dynamics (MD) within the PMEMD molecular dynamics engine, that forms part of the AMBER v14 MD software package, that makes use of Intel Xeon Phi coprocessors by offloading portions of the PME direct summation and neighbor list build to the coprocessor. We refer to this implementation as pmemd MIC offload and in this paper present the technical details of the algorithm, including basic models for MPI and OpenMP configuration, and analyze the resultant performance. The algorithm provides the best performance improvement for large systems (>400,000 atoms), achieving a ∼35% performance improvement for satellite tobacco mosaic virus (1,067,095 atoms) when 2 Intel E5-2697 v2 processors (2 ×12 cores, 30M cache, 2.7 GHz) are coupled to an Intel Xeon Phi coprocessor (Model 7120P-1.238/1.333 GHz, 61 cores). The implementation utilizes a two-fold decomposition strategy: spatial decomposition using an MPI library and thread-based decomposition using OpenMP. We also present compiler optimization settings that improve the performance on Intel Xeon processors, while retaining simulation accuracy.

Field Effect Sensors for Nucleic Acid Detection: Recent Advances and Future Perspectives

PubMed Central

Veigas, Bruno; Fortunato, Elvira; Baptista, Pedro V.

2015-01-01

In the last decade the use of field-effect-based devices has become a basic structural element in a new generation of biosensors that allow label-free DNA analysis. In particular, ion sensitive field effect transistors (FET) are the basis for the development of radical new approaches for the specific detection and characterization of DNA due to FETs’ greater signal-to-noise ratio, fast measurement capabilities, and possibility to be included in portable instrumentation. Reliable molecular characterization of DNA and/or RNA is vital for disease diagnostics and to follow up alterations in gene expression profiles. FET biosensors may become a relevant tool for molecular diagnostics and at point-of-care. The development of these devices and strategies should be carefully designed, as biomolecular recognition and detection events must occur within the Debye length. This limitation is sometimes considered to be fundamental for FET devices and considerable efforts have been made to develop better architectures. Herein we review the use of field effect sensors for nucleic acid detection strategies—from production and functionalization to integration in molecular diagnostics platforms, with special focus on those that have made their way into the diagnostics lab. PMID:25946631

Rheological and Thermal Properties of Bio-based Hyperbranched Polyesters

NASA Astrophysics Data System (ADS)

Bubeck, Robert; Dumitrascu, Adina; Zhang, Tracy; Smith, Patrick

Hyperbranched poly(ester)s (HBPEs) of designed molecular structures and targeted molecular weight can be prepared from a variety of multi-functional acids and alcohols. These polymers find application in the areas of coatings and rheology modifiers for coatings. These functional polymers can be synthesized in variety of architectures, possessing either hydroxyl or carboxyl reactive end-groups suitable for the attachment of active entities. The rheological characteristics as related to variation in molecular structure were determined using cone and plate or couette geometries. Viscosities of the HBPEs were found to be near Newtonian. HB polymers permit the control of Tg that is not as readily attained with linear polymers. Accordingly, Tg and viscosity are affected little as a function of Mw but vary dramatically with the nature of the end-groups, are highly dependent on hydrogen bonding of the hydroxyl end groups, and decrease dramatically with the incorporation of aliphatic end-caps. The thermal properties and the degradation characteristics of the HBPEs were determined. Thermal degradation of the hydroxyl-terminal HBPEs is initiated by dehydrative ether formation (crosslinking) while decarboxylation is the initial decomposition event for the carboxyl-terminal polymers. Midland, MI Campus.

Non-Classical Order in Sphere Forming ABAC Tetrablock Copolymers

NASA Astrophysics Data System (ADS)

Zhang, Jingwen; Sides, Scott; Bates, Frank

2013-03-01

AB diblock and ABC triblock copolymers have been studied thoroughly. ABAC tetrablock copolymers, representing the simplest variation from ABC triblock by breaking the molecular symmetry via inserting some of the A block in between B and C blocks, have been studied systematically in this research. The model system is poly(styrene-b-isoprene-b-styrene-b-ethylene oxide) (SISO) tetrablock terpolymers and the resulting morphologies were characterized by nuclear magnetic resonance, gel permeation chromatography, small-angle X-ray scattering, transmission electron microscopy, differential scanning calorimetry and dynamic mechanical spectroscopy. Two novel phases are first discovered in a single component block copolymers: hexagonally ordered spherical phase and tentatively identified dodecagonal quasicrystalline (QC) phase. In particular, the discovery of QC phase bridges the world of soft matters to that of metals. These unusual sets of morphologies will be discussed in the context of segregation under the constraints associated with the tetrablock molecular architecture. Theoretical calculations based on the assumption of Gaussian chain statistics provide valuable insights into the molecular configurations associated with these morphologies. the U.S. Department of Energy, Basic Energy Sciences, Division of Materials Science and Engineering, under contract number DEAC05-00OR22725 with UT-Battelle LLC at Oak Ridge National Lab.

DASMI: exchanging, annotating and assessing molecular interaction data.

PubMed

Blankenburg, Hagen; Finn, Robert D; Prlić, Andreas; Jenkinson, Andrew M; Ramírez, Fidel; Emig, Dorothea; Schelhorn, Sven-Eric; Büch, Joachim; Lengauer, Thomas; Albrecht, Mario

2009-05-15

Ever increasing amounts of biological interaction data are being accumulated worldwide, but they are currently not readily accessible to the biologist at a single site. New techniques are required for retrieving, sharing and presenting data spread over the Internet. We introduce the DASMI system for the dynamic exchange, annotation and assessment of molecular interaction data. DASMI is based on the widely used Distributed Annotation System (DAS) and consists of a data exchange specification, web servers for providing the interaction data and clients for data integration and visualization. The decentralized architecture of DASMI affords the online retrieval of the most recent data from distributed sources and databases. DASMI can also be extended easily by adding new data sources and clients. We describe all DASMI components and demonstrate their use for protein and domain interactions. The DASMI tools are available at http://www.dasmi.de/ and http://ipfam.sanger.ac.uk/graph. The DAS registry and the DAS 1.53E specification is found at http://www.dasregistry.org/.

Templated bilayer self-assembly of fully conjugated π-expanded macrocyclic oligothiophenes complexed with fullerenes

PubMed Central

Cojal González, José D.; Iyoda, Masahiko; Rabe, Jürgen P.

2017-01-01

Fully conjugated macrocyclic oligothiophenes exhibit a combination of highly attractive structural, optical and electronic properties, and multifunctional molecular thin film architectures thereof are envisioned. However, control over the self-assembly of such systems becomes increasingly challenging, the more complex the target structures are. Here we show a robust self-assembly based on hierarchical non-covalent interactions. A self-assembled monolayer of hydrogen-bonded trimesic acid at the interface between an organic solution and graphite provides host-sites for the epitaxial ordering of Saturn-like complexes of fullerenes with oligothiophene macrocycles in mono- and bilayers. STM tomography verifies the formation of the templated layers. Molecular dynamics simulations corroborate the conformational stability and assign the adsorption sites of the adlayers. Scanning tunnelling spectroscopy determines their rectification characteristics. Current–voltage characteristics reveal the modification of the rectifying properties of the macrocycles by the formation of donor–acceptor complexes in a densely packed all-self-assembled supramolecular nanostructure. PMID:28281557

Optically responsive supramolecular polymer glasses

NASA Astrophysics Data System (ADS)

Balkenende, Diederik W. R.; Monnier, Christophe A.; Fiore, Gina L.; Weder, Christoph

2016-03-01

The reversible and dynamic nature of non-covalent interactions between the constituting building blocks renders many supramolecular polymers stimuli-responsive. This was previously exploited to create thermally and optically healable polymers, but it proved challenging to achieve high stiffness and good healability. Here we present a glass-forming supramolecular material that is based on a trifunctional low-molecular-weight monomer ((UPyU)3TMP). Carrying three ureido-4-pyrimidinone (UPy) groups, (UPyU)3TMP forms a dynamic supramolecular polymer network, whose properties are governed by its cross-linked architecture and the large content of the binding motif. This design promotes the formation of a disordered glass, which, in spite of the low molecular weight of the building block, displays typical polymeric behaviour. The material exhibits a high stiffness and offers excellent coating and adhesive properties. On account of reversible dissociation and the formation of a low-viscosity liquid upon irradiation with ultraviolet light, rapid optical healing as well as (de)bonding on demand is possible.

A molecular nematic liquid crystalline material for high-performance organic photovoltaics

PubMed Central

Sun, Kuan; Xiao, Zeyun; Lu, Shirong; Zajaczkowski, Wojciech; Pisula, Wojciech; Hanssen, Eric; White, Jonathan M.; Williamson, Rachel M.; Subbiah, Jegadesan; Ouyang, Jianyong; Holmes, Andrew B.; Wong, Wallace W.H.; Jones, David J.

2015-01-01

Solution-processed organic photovoltaic cells (OPVs) hold great promise to enable roll-to-roll printing of environmentally friendly, mechanically flexible and cost-effective photovoltaic devices. Nevertheless, many high-performing systems show best power conversion efficiencies (PCEs) with a thin active layer (thickness is ~100 nm) that is difficult to translate to roll-to-roll processing with high reproducibility. Here we report a new molecular donor, benzodithiophene terthiophene rhodanine (BTR), which exhibits good processability, nematic liquid crystalline behaviour and excellent optoelectronic properties. A maximum PCE of 9.3% is achieved under AM 1.5G solar irradiation, with fill factor reaching 77%, rarely achieved in solution-processed OPVs. Particularly promising is the fact that BTR-based devices with active layer thicknesses up to 400 nm can still afford high fill factor of ~70% and high PCE of ~8%. Together, the results suggest, with better device architectures for longer device lifetime, BTR is an ideal candidate for mass production of OPVs. PMID:25586307

Themes in fibrosis and gastrointestinal inflammation

PubMed Central

Lund, P. Kay

2011-01-01

Wound healing is an appropriate response to inflammation and tissue injury in the gastrointestinal tract. If wound healing responses are excessive, perpetuated, or prolonged, they lead to fibrosis, distortion of tissue architecture, and loss of function. This introductory editorial and the minireviews or reviews in this themes series highlight the diversity in severity and location of fibrosis in response to gastrointestinal inflammation. The multiplicity of cellular and molecular mediators and new players, including stem cells or extracellular matrix-producing cells derived from nonmesenchymal cell types, is reviewed. Comparisons of inflammation-induced fibrosis across organ systems and the need for integrated and systems-based molecular approaches, new imaging modalities, well-characterized animal models, cell culture models, and improved diagnostic or predictive markers are reviewed. To date, intestinal fibrosis has received much less attention than inflammation in terms of defining mechanisms and underlying causes. This themes series aims to illustrate the importance of research in this area in gastrointestinal health and disease. PMID:21415411

Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy.

PubMed

Evans, Conor L; Potma, Eric O; Puoris'haag, Mehron; Côté, Daniel; Lin, Charles P; Xie, X Sunney

2005-11-15

Imaging living organisms with molecular selectivity typically requires the introduction of specific labels. Many applications in biology and medicine, however, would significantly benefit from a noninvasive imaging technique that circumvents such exogenous probes. In vivo microscopy based on vibrational spectroscopic contrast offers a unique approach for visualizing tissue architecture with molecular specificity. We have developed a sensitive technique for vibrational imaging of tissues by combining coherent anti-Stokes Raman scattering (CARS) with video-rate microscopy. Backscattering of the intense forward-propagating CARS radiation in tissue gives rise to a strong epi-CARS signal that makes in vivo imaging possible. This substantially large signal allows for real-time monitoring of dynamic processes, such as the diffusion of chemical compounds, in tissues. By tuning into the CH(2) stretching vibrational band, we demonstrate CARS imaging and spectroscopy of lipid-rich tissue structures in the skin of a live mouse, including sebaceous glands, corneocytes, and adipocytes, with unprecedented contrast at subcellular resolution.

Templated bilayer self-assembly of fully conjugated π-expanded macrocyclic oligothiophenes complexed with fullerenes

NASA Astrophysics Data System (ADS)

Cojal González, José D.; Iyoda, Masahiko; Rabe, Jürgen P.

2017-03-01

Fully conjugated macrocyclic oligothiophenes exhibit a combination of highly attractive structural, optical and electronic properties, and multifunctional molecular thin film architectures thereof are envisioned. However, control over the self-assembly of such systems becomes increasingly challenging, the more complex the target structures are. Here we show a robust self-assembly based on hierarchical non-covalent interactions. A self-assembled monolayer of hydrogen-bonded trimesic acid at the interface between an organic solution and graphite provides host-sites for the epitaxial ordering of Saturn-like complexes of fullerenes with oligothiophene macrocycles in mono- and bilayers. STM tomography verifies the formation of the templated layers. Molecular dynamics simulations corroborate the conformational stability and assign the adsorption sites of the adlayers. Scanning tunnelling spectroscopy determines their rectification characteristics. Current-voltage characteristics reveal the modification of the rectifying properties of the macrocycles by the formation of donor-acceptor complexes in a densely packed all-self-assembled supramolecular nanostructure.

Parallel Discrete Molecular Dynamics Simulation With Speculation and In-Order Commitment*†

PubMed Central

Khan, Md. Ashfaquzzaman; Herbordt, Martin C.

2011-01-01

Discrete molecular dynamics simulation (DMD) uses simplified and discretized models enabling simulations to advance by event rather than by timestep. DMD is an instance of discrete event simulation and so is difficult to scale: even in this multi-core era, all reported DMD codes are serial. In this paper we discuss the inherent difficulties of scaling DMD and present our method of parallelizing DMD through event-based decomposition. Our method is microarchitecture inspired: speculative processing of events exposes parallelism, while in-order commitment ensures correctness. We analyze the potential of this parallelization method for shared-memory multiprocessors. Achieving scalability required extensive experimentation with scheduling and synchronization methods to mitigate serialization. The speed-up achieved for a variety of system sizes and complexities is nearly 6× on an 8-core and over 9× on a 12-core processor. We present and verify analytical models that account for the achieved performance as a function of available concurrency and architectural limitations. PMID:21822327

Parallel Discrete Molecular Dynamics Simulation With Speculation and In-Order Commitment.

PubMed

Khan, Md Ashfaquzzaman; Herbordt, Martin C

2011-07-20

Discrete molecular dynamics simulation (DMD) uses simplified and discretized models enabling simulations to advance by event rather than by timestep. DMD is an instance of discrete event simulation and so is difficult to scale: even in this multi-core era, all reported DMD codes are serial. In this paper we discuss the inherent difficulties of scaling DMD and present our method of parallelizing DMD through event-based decomposition. Our method is microarchitecture inspired: speculative processing of events exposes parallelism, while in-order commitment ensures correctness. We analyze the potential of this parallelization method for shared-memory multiprocessors. Achieving scalability required extensive experimentation with scheduling and synchronization methods to mitigate serialization. The speed-up achieved for a variety of system sizes and complexities is nearly 6× on an 8-core and over 9× on a 12-core processor. We present and verify analytical models that account for the achieved performance as a function of available concurrency and architectural limitations.

High performance in silico virtual drug screening on many-core processors.

PubMed

McIntosh-Smith, Simon; Price, James; Sessions, Richard B; Ibarra, Amaurys A

2015-05-01

Drug screening is an important part of the drug development pipeline for the pharmaceutical industry. Traditional, lab-based methods are increasingly being augmented with computational methods, ranging from simple molecular similarity searches through more complex pharmacophore matching to more computationally intensive approaches, such as molecular docking. The latter simulates the binding of drug molecules to their targets, typically protein molecules. In this work, we describe BUDE, the Bristol University Docking Engine, which has been ported to the OpenCL industry standard parallel programming language in order to exploit the performance of modern many-core processors. Our highly optimized OpenCL implementation of BUDE sustains 1.43 TFLOP/s on a single Nvidia GTX 680 GPU, or 46% of peak performance. BUDE also exploits OpenCL to deliver effective performance portability across a broad spectrum of different computer architectures from different vendors, including GPUs from Nvidia and AMD, Intel's Xeon Phi and multi-core CPUs with SIMD instruction sets.

High performance in silico virtual drug screening on many-core processors

PubMed Central

Price, James; Sessions, Richard B; Ibarra, Amaurys A

2015-01-01

Drug screening is an important part of the drug development pipeline for the pharmaceutical industry. Traditional, lab-based methods are increasingly being augmented with computational methods, ranging from simple molecular similarity searches through more complex pharmacophore matching to more computationally intensive approaches, such as molecular docking. The latter simulates the binding of drug molecules to their targets, typically protein molecules. In this work, we describe BUDE, the Bristol University Docking Engine, which has been ported to the OpenCL industry standard parallel programming language in order to exploit the performance of modern many-core processors. Our highly optimized OpenCL implementation of BUDE sustains 1.43 TFLOP/s on a single Nvidia GTX 680 GPU, or 46% of peak performance. BUDE also exploits OpenCL to deliver effective performance portability across a broad spectrum of different computer architectures from different vendors, including GPUs from Nvidia and AMD, Intel’s Xeon Phi and multi-core CPUs with SIMD instruction sets. PMID:25972727

Molecular phylogeny and comparative morphology indicate that odontostomatids (Alveolata, Ciliophora) form a distinct class-level taxon related to Armophorea.

PubMed

Fernandes, Noemi M; Vizzoni, Vinicius F; Borges, Bárbara do N; A G Soares, Carlos; Silva-Neto, Inácio D da; S Paiva, Thiago da

2018-04-18

The odontostomatids are among the least studied ciliates, possibly due to their small sizes, restriction to anaerobic environments and difficulty in culturing. Consequently, their phylogenetic affinities to other ciliate taxa are still poorly understood. In the present study, we analyzed newly obtained ribosomal gene sequences of the odontostomatids Discomorphella pedroeneasi and Saprodinium dentatum, together with sequences from the literature, including Epalxella antiquorum and a large assemblage of ciliate sequences representing the major recognized classes. The results show that D. pedroeneasi and S. dentatum form a deep-diverging branch related to metopid and clevelandellid armophoreans, corroborating the old literature. However E. antiquorum clustered with the morphologically discrepant plagiopylids, indicating that either the complex odontostomatid body architecture evolved convergently, or the positioning of E. antiquorum as a plagiopylid is artifactual. A new ciliate class, Odontostomatea n. cl., is proposed based on molecular analyses and comparative morphology of odontostomatids with related taxa. Copyright © 2018. Published by Elsevier Inc.

Transcriptional architecture of the primate neocortex.

PubMed

Bernard, Amy; Lubbers, Laura S; Tanis, Keith Q; Luo, Rui; Podtelezhnikov, Alexei A; Finney, Eva M; McWhorter, Mollie M E; Serikawa, Kyle; Lemon, Tracy; Morgan, Rebecca; Copeland, Catherine; Smith, Kimberly; Cullen, Vivian; Davis-Turak, Jeremy; Lee, Chang-Kyu; Sunkin, Susan M; Loboda, Andrey P; Levine, David M; Stone, David J; Hawrylycz, Michael J; Roberts, Christopher J; Jones, Allan R; Geschwind, Daniel H; Lein, Ed S

2012-03-22

Genome-wide transcriptional profiling was used to characterize the molecular underpinnings of neocortical organization in rhesus macaque, including cortical areal specialization and laminar cell-type diversity. Microarray analysis of individual cortical layers across sensorimotor and association cortices identified robust and specific molecular signatures for individual cortical layers and areas, prominently involving genes associated with specialized neuronal function. Overall, transcriptome-based relationships were related to spatial proximity, being strongest between neighboring cortical areas and between proximal layers. Primary visual cortex (V1) displayed the most distinctive gene expression compared to other cortical regions in rhesus and human, both in the specialized layer 4 as well as other layers. Laminar patterns were more similar between macaque and human compared to mouse, as was the unique V1 profile that was not observed in mouse. These data provide a unique resource detailing neocortical transcription patterns in a nonhuman primate with great similarity in gene expression to human. Copyright © 2012 Elsevier Inc. All rights reserved.

Genetic architecture of downy mildew resistance in cucumber

USDA-ARS?s Scientific Manuscript database

Downy mildew (DM) caused by the obligate oomycete Pseudoperonospora cubensis is the most devastating fungal disease to cucumber production. The molecular mechanism of DM resistance in cucumber is not well understood. We conducted QTL mapping for DM resistances in four cucumber lines including WI7120...

Filtrates and Residues: Ice Cream: Delicious Chemistry.

ERIC Educational Resources Information Center

Martino, James

1983-01-01

An experiment involving preparation of ice cream is conducted after students complete units on solutions, atomic structure, molecular architecture, and bonding. The laboratory gives practical illustration of relation of physical properties to bond type and solution theory developed. Materials needed, procedures used, and questions asked are…

Molecular Architecture for Reagentless Immunosensors

DTIC Science & Technology

1990-11-01

emphasis on electrochemical signal detection, will be developed. Phase II will be mainly devoted to manufacture development and to clinical trials ...Arbor, MI 48104 Ju - Py- Dis-tri~ l AvV ’. : Cedes :Diet . Schramm & Lawton 24665-LS The overall objective of this project was to investigate new

The Molecules of the Cell Membrane.

ERIC Educational Resources Information Center

Bretscher, Mark S.

1985-01-01

Cell membrane molecules form a simple, two-dimensional liquid controlling what enters and leaves the cell. Discusses cell membrane molecular architecture, plasma membranes, epithelial cells, cycles of endocytosis and exocytosis, and other topics. Indicates that some cells internalize, then recycle, membrane area equivalent to their entire surface…

The Cbf5-Nop10 Complex is a Molecular Bracket that Organizes Box H/ACA RNPs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamma, Tomoko; Reichow, Steve L.; Varani, Gabriele

2005-12-01

Box H/ACA ribonucleoprotein particles (RNPs) catalyze RNA pseudouridylation and direct processing of ribosomal RNA, and are essential architectural components of vertebrate telomerases. H/ACA RNPs comprise four proteins and a multihelical RNA. Two proteins, Cbf5 and Nop10, suffice for basal enzymatic activity in an archaeal in vitro system. We now report their cocrystal structure at 1.95-A resolution. We find that archaeal Cbf5 can assemble with yeast Nop10 and with human telomerase RNA, consistent with the high sequence identity of the RNP componenets between archaea and eukarya. Thus, the Cbf5-Nop10 architecture is phylogenetically conserved. The structure shows how Nop10 buttresses the activemore » site of Cbf5, and it reveals two basic troughs that bidirectionally extend the active site cleft. Mutagenesis results implicate an adjacent basic patch in RNA binding. This tripartite RNA-binding surface may function as a molecular bracket that organizes the multihelical H/ACA and telomerase RNAs.« less

Structure of the Zinc-Bound Amino-Terminal Domain of the NMDA Receptor NR2B Subunit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karakas, E.; Simorowski, N; Furukawa, H

2009-01-01

N-methyl-D-aspartate (NMDA) receptors belong to the family of ionotropic glutamate receptors (iGluRs) that mediate the majority of fast excitatory synaptic transmission in the mammalian brain. One of the hallmarks for the function of NMDA receptors is that their ion channel activity is allosterically regulated by binding of modulator compounds to the extracellular amino-terminal domain (ATD) distinct from the L-glutamate-binding domain. The molecular basis for the ATD-mediated allosteric regulation has been enigmatic because of a complete lack of structural information on NMDA receptor ATDs. Here, we report the crystal structures of ATD from the NR2B NMDA receptor subunit in the zinc-freemore » and zinc-bound states. The structures reveal the overall clamshell-like architecture distinct from the non-NMDA receptor ATDs and molecular determinants for the zinc-binding site, ion-binding sites, and the architecture of the putative phenylethanolamine-binding site.« less

Nanoscale protein architecture of the kidney glomerular basement membrane

PubMed Central

Suleiman, Hani; Zhang, Lei; Roth, Robyn; Heuser, John E; Miner, Jeffrey H; Shaw, Andrey S; Dani, Adish

2013-01-01

In multicellular organisms, proteins of the extracellular matrix (ECM) play structural and functional roles in essentially all organs, so understanding ECM protein organization in health and disease remains an important goal. Here, we used sub-diffraction resolution stochastic optical reconstruction microscopy (STORM) to resolve the in situ molecular organization of proteins within the kidney glomerular basement membrane (GBM), an essential mediator of glomerular ultrafiltration. Using multichannel STORM and STORM-electron microscopy correlation, we constructed a molecular reference frame that revealed a laminar organization of ECM proteins within the GBM. Separate analyses of domains near the N- and C-termini of agrin, laminin, and collagen IV in mouse and human GBM revealed a highly oriented macromolecular organization. Our analysis also revealed disruptions in this GBM architecture in a mouse model of Alport syndrome. These results provide the first nanoscopic glimpse into the organization of a complex ECM. DOI: http://dx.doi.org/10.7554/eLife.01149.001 PMID:24137544

SchNet - A deep learning architecture for molecules and materials

NASA Astrophysics Data System (ADS)

Schütt, K. T.; Sauceda, H. E.; Kindermans, P.-J.; Tkatchenko, A.; Müller, K.-R.

2018-06-01

Deep learning has led to a paradigm shift in artificial intelligence, including web, text, and image search, speech recognition, as well as bioinformatics, with growing impact in chemical physics. Machine learning, in general, and deep learning, in particular, are ideally suitable for representing quantum-mechanical interactions, enabling us to model nonlinear potential-energy surfaces or enhancing the exploration of chemical compound space. Here we present the deep learning architecture SchNet that is specifically designed to model atomistic systems by making use of continuous-filter convolutional layers. We demonstrate the capabilities of SchNet by accurately predicting a range of properties across chemical space for molecules and materials, where our model learns chemically plausible embeddings of atom types across the periodic table. Finally, we employ SchNet to predict potential-energy surfaces and energy-conserving force fields for molecular dynamics simulations of small molecules and perform an exemplary study on the quantum-mechanical properties of C20-fullerene that would have been infeasible with regular ab initio molecular dynamics.

Molecular dynamics simulation analysis of the effect of T790M mutation on epidermal growth factor receptor protein architecture in non-small cell lung carcinoma.

PubMed

Peng, Xiao-Nu; Wang, Jing; Zhang, Wei

2017-08-01

Non-small cell lung cancer etiology and its treatment failure are due to epidermal growth factor receptor (EGFR) kinase domain mutations at amino acid position 790. The mutational change from threonine to methionine at position 790 (T790M) is responsible for tyrosine kinase inhibition failure. Using molecular dynamic simulation, the present study investigated the architectural changes occurring at the atomic scale. The 50-nsec runs using a GROMOS force field for wild-type and mutant EGFR's kinase domains were investigated for contrasting variations using Gromacs inbuilt tools. The adenosine triphosphate binding domain and the active site of EGFR were studied extensively in order to understand the structural changes. All the parameters investigated in the present study revealed considerable changes in the studied structures, and the knowledge gained from this may be used to develop novel kinase inhibitors that will be effective irrespective of the structural alterations in kinase domain.

The Use of 3D Telomere FISH for the Characterization of the Nuclear Architecture in EBV-Positive Hodgkin's Lymphoma.

PubMed

Knecht, Hans; Mai, Sabine

2017-01-01

The 3D nuclear architecture is closely related to cellular functions and chromosomes are organized in distinct territories. Quantitative 3D telomere FISH analysis (3D Q-FISH) and 3D super-resolution imaging (3D-SIM) at a resolution up to 80 nm as well as the recently developed combined quantitative 3D TRF2-telomere immune FISH technique (3D TRF2/Telo-Q-FISH) have substantially contributed to elucidate molecular pathogenic mechanisms of hematological diseases. Here we report the methods we applied to uncover major molecular steps involved in the pathogenesis of EBV-associated Hodgkin's lymphoma. These methods allowed us to identify the EBV-encoded oncoprotein LMP1 as a key element in the formation of Hodgkin (H-cell) and multinucleated Reed-Sternberg cells (RS-cell), the diagnostic tumor cell of classical Hodgkin's lymphoma (cHL). LMP1 mediates multinuclearity through downregulation of shelterin proteins, in particular telomere repeat binding factor 2 (TRF2).

Long-range allosteric signaling in red light–regulated diguanylyl cyclases

PubMed Central

Gourinchas, Geoffrey; Etzl, Stefan; Göbl, Christoph; Vide, Uršula; Madl, Tobias; Winkler, Andreas

2017-01-01

Nature has evolved an astonishingly modular architecture of covalently linked protein domains with diverse functionalities to enable complex cellular networks that are critical for cell survival. The coupling of sensory modules with enzymatic effectors allows direct allosteric regulation of cellular signaling molecules in response to diverse stimuli. We present molecular details of red light–sensing bacteriophytochromes linked to cyclic dimeric guanosine monophosphate–producing diguanylyl cyclases. Elucidation of the first crystal structure of a full-length phytochrome with its enzymatic effector, in combination with the characterization of light-induced changes in conformational dynamics, reveals how allosteric light regulation is fine-tuned by the architecture and composition of the coiled-coil sensor-effector linker and also the central helical spine. We anticipate that consideration of molecular principles of sensor-effector coupling, going beyond the length of the characteristic linker, and the appreciation of dynamically driven allostery will open up new directions for the design of novel red light–regulated optogenetic tools. PMID:28275738

A 17 GHz molecular rectifier

PubMed Central

Trasobares, J.; Vuillaume, D.; Théron, D.; Clément, N.

2016-01-01

Molecular electronics originally proposed that small molecules sandwiched between electrodes would accomplish electronic functions and enable ultimate scaling to be reached. However, so far, functional molecular devices have only been demonstrated at low frequency. Here, we demonstrate molecular diodes operating up to 17.8 GHz. Direct current and radio frequency (RF) properties were simultaneously measured on a large array of molecular junctions composed of gold nanocrystal electrodes, ferrocenyl undecanethiol molecules and the tip of an interferometric scanning microwave microscope. The present nanometre-scale molecular diodes offer a current density increase by several orders of magnitude compared with that of micrometre-scale molecular diodes, allowing RF operation. The measured S11 parameters show a diode rectification ratio of 12 dB which is linked to the rectification behaviour of the direct current conductance. From the RF measurements, we extrapolate a cut-off frequency of 520 GHz. A comparison with the silicon RF-Schottky diodes, architecture suggests that the RF-molecular diodes are extremely attractive for scaling and high-frequency operation. PMID:27694833

Developing Performance Based Requirements for Open Architecture Design

DTIC Science & Technology

2006-04-30

Åèìáëáíáçå= oÉëÉ~êÅÜ=póãéçëáìã= DEVELOPING PERFORMANCE BASED REQUIREMENTS FOR OPEN ARCHITECTURE DESIGN Published: 30 April 2006 by Brad Naegle...for Open Architecture Design 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f...Ñçê=áåÑçêãÉÇ=ÅÜ~åÖÉ======= = - 174 - = = Developing Performance Based Requirements for Open Architecture Design Presenter: Brad Naegle, Lieutenant

The Yeast Nuclear Pore Complex

PubMed Central

Rout, Michael P.; Aitchison, John D.; Suprapto, Adisetyantari; Hjertaas, Kelly; Zhao, Yingming; Chait, Brian T.

2000-01-01

An understanding of how the nuclear pore complex (NPC) mediates nucleocytoplasmic exchange requires a comprehensive inventory of the molecular components of the NPC and a knowledge of how each component contributes to the overall structure of this large molecular translocation machine. Therefore, we have taken a comprehensive approach to classify all components of the yeast NPC (nucleoporins). This involved identifying all the proteins present in a highly enriched NPC fraction, determining which of these proteins were nucleoporins, and localizing each nucleoporin within the NPC. Using these data, we present a map of the molecular architecture of the yeast NPC and provide evidence for a Brownian affinity gating mechanism for nucleocytoplasmic transport. PMID:10684247

Interaction sorting method for molecular dynamics on multi-core SIMD CPU architecture.

PubMed

Matvienko, Sergey; Alemasov, Nikolay; Fomin, Eduard

2015-02-01

Molecular dynamics (MD) is widely used in computational biology for studying binding mechanisms of molecules, molecular transport, conformational transitions, protein folding, etc. The method is computationally expensive; thus, the demand for the development of novel, much more efficient algorithms is still high. Therefore, the new algorithm designed in 2007 and called interaction sorting (IS) clearly attracted interest, as it outperformed the most efficient MD algorithms. In this work, a new IS modification is proposed which allows the algorithm to utilize SIMD processor instructions. This paper shows that the improvement provides an additional gain in performance, 9% to 45% in comparison to the original IS method.

Molecular building blocks and their architecture in biologically/environmentally compatible soft matter chemical machinery.

PubMed

Toyota, Taro; Banno, Taisuke; Nitta, Sachiko; Takinoue, Masahiro; Nomoto, Tomonori; Natsume, Yuno; Matsumura, Shuichi; Fujinami, Masanori

2014-01-01

This review briefly summarizes recent developments in the construction of biologically/environmentally compatible chemical machinery composed of soft matter. Since environmental and living systems are open systems, chemical machinery must continuously fulfill its functions not only through the influx and generation of molecules but also via the degradation and dissipation of molecules. If the degradation or dissipation of soft matter molecular building blocks and biomaterial molecules/polymers can be achieved, soft matter particles composed of them can be used to realize chemical machinery such as selfpropelled droplets, drug delivery carriers, tissue regeneration scaffolds, protocell models, cell-/tissuemarkers, and molecular computing systems.

Fragment-based drug discovery and its application to challenging drug targets.

PubMed

Price, Amanda J; Howard, Steven; Cons, Benjamin D

2017-11-08

Fragment-based drug discovery (FBDD) is a technique for identifying low molecular weight chemical starting points for drug discovery. Since its inception 20 years ago, FBDD has grown in popularity to the point where it is now an established technique in industry and academia. The approach involves the biophysical screening of proteins against collections of low molecular weight compounds (fragments). Although fragments bind to proteins with relatively low affinity, they form efficient, high quality binding interactions with the protein architecture as they have to overcome a significant entropy barrier to bind. Of the biophysical methods available for fragment screening, X-ray protein crystallography is one of the most sensitive and least prone to false positives. It also provides detailed structural information of the protein-fragment complex at the atomic level. Fragment-based screening using X-ray crystallography is therefore an efficient method for identifying binding hotspots on proteins, which can then be exploited by chemists and biologists for the discovery of new drugs. The use of FBDD is illustrated here with a recently published case study of a drug discovery programme targeting the challenging protein-protein interaction Kelch-like ECH-associated protein 1:nuclear factor erythroid 2-related factor 2. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Effective and efficient detection of pH fluctuations based on ratiometric metallic-ciprofloxacin architectures

NASA Astrophysics Data System (ADS)

Wang, Zhuosen; Gao, Jinwei; Zhang, Kaibo; Mai, Zhihong; Wang, Qianming

2018-07-01

The availability of lanthanide ciprofloxacin complexes and the exploration of efficient new ways to the target species have made fluorescent signals as essential tools for chemical sensing. Both terbium (III) and europium (III) compounds possess easily distinguished, line-like emission bands occurring in the green and red region respectively. Based on the steps of ionizations and the coordination structure changes, the two molecular probes give rise to unique pH-sensitivities at different conditions. The photoluminescence properties of the mixture for the two complexes are demonstrated. At pH from 3 to 6, the Eu(III) emission is found to be less affected and the solution emits blue light in acidic environment (pH = 3). The terbium (III) characteristic luminescence exhibited off-on changes within a narrow pH range (pH = 5-6). Further spectroscopic pH titrations (pH from 6 to 10) are performed and the Eu (III) red emission has been significantly improved. The molecular-based probes have excellent water solubility, negligible cytotoxicity and enough permeability to across cell membrane. Such pH-responsive performance has been carried out for the investigation of intracellular pH measurement and these novel pH indicators were considered to be suitable for detecting bio-medical samples.

High Performance Poly(viologen)-Graphene Nanocomposite Battery Materials with Puff Paste Architecture.

PubMed

Beladi-Mousavi, Seyyed Mohsen; Sadaf, Shamaila; Mahmood, Arsalan Mado; Walder, Lorenz

2017-09-26

Four linear poly(viologens) (PV1, PV2: phenylic, PV3: benzylic, and PV4: aliphatic) in tight molecular contact with reduced graphene oxide (rGO), that is, PV@rGO, were prepared and used as anodic battery materials. These composites show exceptionally high, areal, volumetric, and current densities, for example, PV1@rGO composites (with 15 wt % rGO, corresponding to 137 mAh g -1 ) show 13.3 mAh cm -2 at 460 μm and 288 mAh cm -3 with 98% Coulombic efficiency at current densities up to 1000 A g -1 , better than any reported organic materials. These remarkable performances are based on (i) molecular self-assembling of PVs on individual GO sheets yielding colloidal PV@GO and (ii) efficient GO/rGO transformation electrocatalyzed by PVs. Ion breathing during charging/discharging was studied by electrochemical quartz crystal microbalance and electrochemical atomic force microscopy revealing an absolute reversible and strongly anisotropic thickness oscillation of PV1@rGO at a right angle to the macroscopic current collector. It is proposed that such stress-free breathing is the key property for good cyclability of the battery material. The anisotropy is related to a puff paste architecture of rGO sheets parallel to the macroscopic current collector. A thin graphite sheet electrode with an areal capacity of 1.23 mAh cm -2 is stable over 200 bending cycles, making the material applicable for wearable electronics. The polymer acts as a lubricant between the rGO layers if shearing forces are active.

The molecular architecture of QdtA, a sugar 3,4-ketoisomerase from Thermoanaerobacterium thermosaccharolyticum.

PubMed

Thoden, James B; Holden, Hazel M

2014-06-01

Unusual di- and trideoxysugars are often found on the O-antigens of Gram-negative bacteria, on the S-layers of Gram-positive bacteria, and on various natural products. One such sugar is 3-acetamido-3,6-dideoxy-D-glucose. A key step in its biosynthesis, catalyzed by a 3,4-ketoisomerase, is the conversion of thymidine diphosphate (dTDP)-4-keto-6-deoxyglucose to dTDP-3-keto-6-deoxyglucose. Here we report an X-ray analysis of a 3,4-ketoisomerase from Thermoanaerobacterium thermosaccharolyticum. For this investigation, the wild-type enzyme, referred to as QdtA, was crystallized in the presence of dTDP and its structure solved to 2.0-Å resolution. The dimeric enzyme adopts a three-dimensional architecture that is characteristic for proteins belonging to the cupin superfamily. In order to trap the dTDP-4-keto-6-deoxyglucose substrate into the active site, a mutant protein, H51N, was subsequently constructed, and the structure of this protein in complex with the dTDP-sugar ligand was solved to 1.9-Å resolution. Taken together, the structures suggest that His 51 serves as a catalytic base, that Tyr 37 likely functions as a catalytic acid, and that His 53 provides a proton shuttle between the C-3' hydroxyl and the C-4' keto group of the hexose. This study reports the first three-dimensional structure of a 3,4-ketoisomerase in complex with its dTDP-sugar substrate and thus sheds new molecular insight into this fascinating class of enzymes. © 2014 The Protein Society.

New concept of aging care architecture landscape design based on sustainable development

NASA Astrophysics Data System (ADS)

Xu, Ying

2017-05-01

As the aging problem becoming serious in China, Aging care is now one of the top issuer in front of all of us. Lots of private and public aging care architecture and facilities have been built. At present, we only pay attention to the architecture design and interior design scientific, ecological and sustainable design on aged care architecture landscape. Based on the social economy, population resources, mutual coordination and development of the environment, taking the elderly as the special group, this paper follows the principles of the sustainable development, conducts the comprehensive design planning of aged care landscape architecture and makes a deeper understanding and exploration through changing the form of architectural space, ecological landscape planting, new materials and technology, ecological energy utilization.

Two color high operating temperature HgCdTe photodetectors grown by molecular beam epitaxy on silicon substrates

NASA Astrophysics Data System (ADS)

Velicu, S.; Bommena, R.; Morley, M.; Zhao, J.; Fahey, S.; Cowan, V.; Morath, C.

2013-09-01

The development of a broadband IR focal plane array poses several challenges in the area of detector design, material, device physics, fabrication process, hybridization, integration and testing. The purpose of our research is to address these challenges and demonstrate a high-performance IR system that incorporates a HgCdTe-based detector array with high uniformity and operability. Our detector architecture, grown using molecular beam epitaxy (MBE), is vertically integrated, leading to a stacked detector structure with the capability to simultaneously detect in two spectral bands. MBE is the method of choice for multiplelayer HgCdTe growth because it produces material of excellent quality and allows composition and doping control at the atomic level. Such quality and control is necessary for the fabrication of multicolor detectors since they require advanced bandgap engineering techniques. The proposed technology, based on the bandgap-tunable HgCdTe alloy, has the potential to extend the broadband detector operation towards room temperature. We present here our modeling, MBE growth and device characterization results, demonstrating Auger suppression in the LWIR band and diffusion limited behavior in the MWIR band.

Fabrication and Characterization of a Novel Nanodendrite-based Electrochemical Sensor for the Detection of Disease Biomarkers

NASA Astrophysics Data System (ADS)

Connolly, Timothy; Archibald, Michelle M.; Nesbitt, Nathan T.; Rossi, Matthew; Glover, Jennifer A.; Burns, Michael J.; Naughton, Michael J.; Chiles, Thomas C.

2014-03-01

Technologies to detect early stage cancer would provide significant benefit to cancer disease patients. Clinical measurement of biomarkers offers the promise of a noninvasive and cost effective screening for early stage detection. We are currently developing a novel 3-dimensional nanopillar dendrite biosensor array for the detection of human cancer biomarkers (e . g . CA-125 for early-stage ovarian cancer) in serum and other fluids. Here, we describe a nanoscale 3D architecture that can afford molecular detection at room temperature. We report our efforts on the development of an all-electronic, ambient temperature, rapid-response dendritic biosensor fabricated by directed electrochemical nanowire assembly (DENA) that achieves molecular-scale sensitivity for protein biomarker based detection. Each sensor is a vertically-oriented nanodendritic array where an electrochemical signal is detected from the oxidation of the redox end-product of an enzyme-linked immunosorbent assay (ELISA). Our results demonstrate the feasibility of using the present nanodendritic array structure as a sensitive device to detect a range of proteins of interest, including disease biomarkers. Supported by NIH (National Cancer Institute and the National Institute of Allergy and Infectious Diseases).

High Performance Electroactive Polymer Actuators Based on Sulfonated Block Copolymers Comprising Ionic Liquids

NASA Astrophysics Data System (ADS)

Kim, Onnuri; Park, Moon Jeong

2015-03-01

Electroactive polymer (EAP) actuators that show reversible deformation under external electric stimulus have attracted great attention toward a range of biomimetic applications such as microsensors and artificial muscles. Key challenges to advance the technologies can be placed on the achievement of fast response time, low driving voltage, and durable operation in air. In present study, we are motivated to solve these issues by employing self-assembled block copolymers containing ionic liquids (ILs) as polymer layers in the actuator based on knowledge of factors affecting electromechanical properties of actuators. By controlling the block architecture and molecular weight of block copolymers, bending strain and durability were controlled in a straightforward manner. It has also been revealed that the type of IL makes impact on the EAP actuator performance by determining ion migration dynamics. Our actuators demonstrated large bending strains (up to 4%) under low voltages of 1-3V, which far exceeds the best performance of other EAP actuators reported in the literature. To underpin the molecular-level understanding of actuation mechanisms underlying the improved performance, we carried out in situ spectroscopy and in situ scattering experiments under actuation.

A comparative analysis of loop heat pipe based thermal architectures for spacecraft thermal control

NASA Technical Reports Server (NTRS)

Pauken, Mike; Birur, Gaj

2004-01-01

Loop Heat Pipes (LHP) have gained acceptance as a viable means of heat transport in many spacecraft in recent years. However, applications using LHP technology tend to only remove waste heat from a single component to an external radiator. Removing heat from multiple components has been done by using multiple LHPs. This paper discusses the development and implementation of a Loop Heat Pipe based thermal architecture for spacecraft. In this architecture, a Loop Heat Pipe with multiple evaporators and condensers is described in which heat load sharing and thermal control of multiple components can be achieved. A key element in using a LHP thermal architecture is defining the need for such an architecture early in the spacecraft design process. This paper describes an example in which a LHP based thermal architecture can be used and how such a system can have advantages in weight, cost and reliability over other kinds of distributed thermal control systems. The example used in this paper focuses on a Mars Rover Thermal Architecture. However, the principles described here are applicable to Earth orbiting spacecraft as well.

Distributed Computing Architecture for Image-Based Wavefront Sensing and 2 D FFTs

NASA Technical Reports Server (NTRS)

Smith, Jeffrey S.; Dean, Bruce H.; Haghani, Shadan

2006-01-01

Image-based wavefront sensing (WFS) provides significant advantages over interferometric-based wavefi-ont sensors such as optical design simplicity and stability. However, the image-based approach is computational intensive, and therefore, specialized high-performance computing architectures are required in applications utilizing the image-based approach. The development and testing of these high-performance computing architectures are essential to such missions as James Webb Space Telescope (JWST), Terrestial Planet Finder-Coronagraph (TPF-C and CorSpec), and Spherical Primary Optical Telescope (SPOT). The development of these specialized computing architectures require numerous two-dimensional Fourier Transforms, which necessitate an all-to-all communication when applied on a distributed computational architecture. Several solutions for distributed computing are presented with an emphasis on a 64 Node cluster of DSPs, multiple DSP FPGAs, and an application of low-diameter graph theory. Timing results and performance analysis will be presented. The solutions offered could be applied to other all-to-all communication and scientifically computationally complex problems.

SME2EM: Smart mobile end-to-end monitoring architecture for life-long diseases.

PubMed

Serhani, Mohamed Adel; Menshawy, Mohamed El; Benharref, Abdelghani

2016-01-01

Monitoring life-long diseases requires continuous measurements and recording of physical vital signs. Most of these diseases are manifested through unexpected and non-uniform occurrences and behaviors. It is impractical to keep patients in hospitals, health-care institutions, or even at home for long periods of time. Monitoring solutions based on smartphones combined with mobile sensors and wireless communication technologies are a potential candidate to support complete mobility-freedom, not only for patients, but also for physicians. However, existing monitoring architectures based on smartphones and modern communication technologies are not suitable to address some challenging issues, such as intensive and big data, resource constraints, data integration, and context awareness in an integrated framework. This manuscript provides a novel mobile-based end-to-end architecture for live monitoring and visualization of life-long diseases. The proposed architecture provides smartness features to cope with continuous monitoring, data explosion, dynamic adaptation, unlimited mobility, and constrained devices resources. The integration of the architecture׳s components provides information about diseases׳ recurrences as soon as they occur to expedite taking necessary actions, and thus prevent severe consequences. Our architecture system is formally model-checked to automatically verify its correctness against designers׳ desirable properties at design time. Its components are fully implemented as Web services with respect to the SOA architecture to be easy to deploy and integrate, and supported by Cloud infrastructure and services to allow high scalability, availability of processes and data being stored and exchanged. The architecture׳s applicability is evaluated through concrete experimental scenarios on monitoring and visualizing states of epileptic diseases. The obtained theoretical and experimental results are very promising and efficiently satisfy the proposed architecture׳s objectives, including resource awareness, smart data integration and visualization, cost reduction, and performance guarantee. Copyright © 2015 Elsevier Ltd. All rights reserved.

Branchpoint expansion in a fully complementary three-way DNA junction.

PubMed

Sabir, Tara; Toulmin, Anita; Ma, Long; Jones, Anita C; McGlynn, Peter; Schröder, Gunnar F; Magennis, Steven W

2012-04-11

Branched nucleic acid molecules serve as key intermediates in DNA replication, recombination, and repair; architectural elements in RNA; and building blocks and functional components for nanoscience applications. Using a combination of high-resolution single-molecule FRET, time-resolved spectroscopy, and molecular modeling, we have probed the local and global structure of a DNA three-way junction (3WJ) in solution. We found that it adopts a Y-shaped, pyramidal structure, in which the bases adjacent to the branchpoint are unpaired, despite the full Watson-Crick complementarity of the molecule. The unpairing allows a nanoscale cavity to form at the junction center. Our structure accounts for earlier observations made of the structure, flexibility, and reactivity of 3WJs. We anticipate that these results will guide the development of new DNA-based supramolecular receptors and nanosystems. © 2012 American Chemical Society

Open architecture design and approach for the Integrated Sensor Architecture (ISA)

NASA Astrophysics Data System (ADS)

Moulton, Christine L.; Krzywicki, Alan T.; Hepp, Jared J.; Harrell, John; Kogut, Michael

2015-05-01

Integrated Sensor Architecture (ISA) is designed in response to stovepiped integration approaches. The design, based on the principles of Service Oriented Architectures (SOA) and Open Architectures, addresses the problem of integration, and is not designed for specific sensors or systems. The use of SOA and Open Architecture approaches has led to a flexible, extensible architecture. Using these approaches, and supported with common data formats, open protocol specifications, and Department of Defense Architecture Framework (DoDAF) system architecture documents, an integration-focused architecture has been developed. ISA can help move the Department of Defense (DoD) from costly stovepipe solutions to a more cost-effective plug-and-play design to support interoperability.

A knowledge-base generating hierarchical fuzzy-neural controller.

PubMed

Kandadai, R M; Tien, J M

1997-01-01

We present an innovative fuzzy-neural architecture that is able to automatically generate a knowledge base, in an extractable form, for use in hierarchical knowledge-based controllers. The knowledge base is in the form of a linguistic rule base appropriate for a fuzzy inference system. First, we modify Berenji and Khedkar's (1992) GARIC architecture to enable it to automatically generate a knowledge base; a pseudosupervised learning scheme using reinforcement learning and error backpropagation is employed. Next, we further extend this architecture to a hierarchical controller that is able to generate its own knowledge base. Example applications are provided to underscore its viability.

Equilibrating high-molecular-weight symmetric and miscible polymer blends with hierarchical back-mapping.

PubMed

Ohkuma, Takahiro; Kremer, Kurt; Daoulas, Kostas

2018-05-02

Understanding properties of polymer alloys with computer simulations frequently requires equilibration of samples comprised of microscopically described long molecules. We present the extension of an efficient hierarchical backmapping strategy, initially developed for homopolymer melts, to equilibrate high-molecular-weight binary blends. These mixtures present significant interest for practical applications and fundamental polymer physics. In our approach, the blend is coarse-grained into models representing polymers as chains of soft blobs. Each blob stands for a subchain with N b microscopic monomers. A hierarchy of blob-based models with different resolution is obtained by varying N b . First the model with the largest N b is used to obtain an equilibrated blend. This configuration is sequentially fine-grained, reinserting at each step the degrees of freedom of the next in the hierarchy blob-based model. Once the blob-based description is sufficiently detailed, the microscopic monomers are reinserted. The hard excluded volume is recovered through a push-off procedure and the sample is re-equilibrated with molecular dynamics (MD), requiring relaxation on the order of the entanglement time. For the initial method development we focus on miscible blends described on microscopic level through a generic bead-spring model, which reproduces hard excluded volume, strong covalent bonds, and realistic liquid density. The blended homopolymers are symmetric with respect to molecular architecture and liquid structure. To parameterize the blob-based models and validate equilibration of backmapped samples, we obtain reference data from independent hybrid simulations combining MD and identity exchange Monte Carlo moves, taking advantage of the symmetry of the blends. The potential of the backmapping strategy is demonstrated by equilibrating blend samples with different degree of miscibility, containing 500 chains with 1000 monomers each. Equilibration is verified by comparing chain conformations and liquid structure in backmapped blends with the reference data. Possible directions for further methodological developments are discussed.

Equilibrating high-molecular-weight symmetric and miscible polymer blends with hierarchical back-mapping

NASA Astrophysics Data System (ADS)

Ohkuma, Takahiro; Kremer, Kurt; Daoulas, Kostas

2018-05-01

Understanding properties of polymer alloys with computer simulations frequently requires equilibration of samples comprised of microscopically described long molecules. We present the extension of an efficient hierarchical backmapping strategy, initially developed for homopolymer melts, to equilibrate high-molecular-weight binary blends. These mixtures present significant interest for practical applications and fundamental polymer physics. In our approach, the blend is coarse-grained into models representing polymers as chains of soft blobs. Each blob stands for a subchain with N b microscopic monomers. A hierarchy of blob-based models with different resolution is obtained by varying N b. First the model with the largest N b is used to obtain an equilibrated blend. This configuration is sequentially fine-grained, reinserting at each step the degrees of freedom of the next in the hierarchy blob-based model. Once the blob-based description is sufficiently detailed, the microscopic monomers are reinserted. The hard excluded volume is recovered through a push-off procedure and the sample is re-equilibrated with molecular dynamics (MD), requiring relaxation on the order of the entanglement time. For the initial method development we focus on miscible blends described on microscopic level through a generic bead-spring model, which reproduces hard excluded volume, strong covalent bonds, and realistic liquid density. The blended homopolymers are symmetric with respect to molecular architecture and liquid structure. To parameterize the blob-based models and validate equilibration of backmapped samples, we obtain reference data from independent hybrid simulations combining MD and identity exchange Monte Carlo moves, taking advantage of the symmetry of the blends. The potential of the backmapping strategy is demonstrated by equilibrating blend samples with different degree of miscibility, containing 500 chains with 1000 monomers each. Equilibration is verified by comparing chain conformations and liquid structure in backmapped blends with the reference data. Possible directions for further methodological developments are discussed.

EFFECTS OF MOLECULAR ARCHITECTURE ON TWO-STEP MELT-SPUN POLY(LACTIC ACID) FIBERS. (R826733)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

CHEMISTRY, A GUIDE FOR TEACHERS.

ERIC Educational Resources Information Center

WHEELER, HUBERT

THE VOLUME INCLUDES AN INTRODUCTION, THE COURSE CONTENT IN CHEMISTRY, AND FIVE APPENDIXES OF USEFUL INFORMATION. THE CHEMISTRY COURSE CONTENT IS FURTHER SUBDIVIDED INTO FIVE SECTIONS--(1) THE OVERVIEW, (2) CHEMICAL REACTIONS, (3) CHEMICAL BONDING AND MOLECULAR ARCHITECTURE, (4) DESCRIPTIVE CHEMISTRY, AND (5) ADVANCED CHEMISTRY. EACH OF THE FIVE…

Layer-by-Layer Enabled Nanomaterials for Chemical Sensing and Energy Conversion

NASA Astrophysics Data System (ADS)

Paterno, Leonardo G.; Soler, Maria A. G.

2013-06-01

The layer-by-layer (LbL) technique is a wet chemical method for the assembly of ultrathin films, with thicknesses up to 100 nm. This method is based on the successive transfer of molecular layers to a solid substrate that is dipped into cationic and anionic solutions in an alternating fashion. The adsorption is mainly driven by electrostatic interactions so that many molecular and nanomaterial systems can be engineered under this method. Moreover, it is inexpensive, can be easily performed, and does not demand sophisticated equipment or clean rooms. The most explored use of the LbL technique is to build up molecular devices for chemical sensing and energy conversion. Both applications require ultrathin films where specific elements must be organized with high control of thickness and spatial distribution, preferably in the nanolength and mesolength scales. In chemical sensors, the LbL technique is employed to assemble specific sensoactive materials such as conjugated polymers, enzymes, and immunological elements onto appropriated electrodes. Molecular recognition events are thus transduced by the assembled sensoactive layer. In energy-conversion devices, the LbL technique can be employed to fabricate different device's parts including electrodes, active layers, and auxiliary layers. In both applications, the devices' performance can be fully modulated and improved by simply varying film thickness and molecular architecture. The present review article highlights the main features of the LbL technique and provides a brief description of different (bio)chemical sensors, solar cells, and organic light-emitting diodes enabled by the LbL approach.

Self assembled monolayers on silicon for molecular electronics.

PubMed

Aswal, D K; Lenfant, S; Guerin, D; Yakhmi, J V; Vuillaume, D

2006-05-24

We present an overview of various aspects of the self-assembly of organic monolayers on silicon substrates for molecular electronics applications. Different chemical strategies employed for grafting the self-assembled monolayers (SAMs) of alkanes having different chain lengths on native oxide of Si or on bare Si have been reviewed. The utility of different characterization techniques in determination of the thickness, molecular ordering and orientation, surface coverage, growth kinetics and chemical composition of the SAMs has been discussed by choosing appropriate examples. The metal counterelectrodes are an integral part of SAMs for measuring their electrical properties as well as using them for molecular electronic devices. A brief discussion on the variety of options available for the deposition of metal counterelectrodes, that is, soft metal contacts, vapor deposition and soft lithography, has been presented. Various theoretical models, namely, tunneling (direct and Fowler-Nordheim), thermionic emission, Poole-Frenkel emission and hopping conduction, used for explaining the electronic transport in dielectric SAMs have been outlined and, some experimental data on alkane SAMs have been analyzed using these models. It has been found that short alkyl chains show excellent agreement with tunneling models; while more experimental data on long alkyl chains are required to understand their transport mechanism(s). Finally, the concepts and realization of various molecular electronic components, that is, diodes, resonant tunnel diodes, memories and transistors, based on appropriate architecture of SAMs comprising of alkyl chains (sigma- molecule) and conjugated molecules (pi-molecule) have been presented.