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Sample records for biological molecules multi-quantum

  1. Diversity in Biological Molecules

    ERIC Educational Resources Information Center

    Newbury, H. John

    2010-01-01

    One of the striking characteristics of fundamental biological processes, such as genetic inheritance, development and primary metabolism, is the limited amount of variation in the molecules involved. Natural selective pressures act strongly on these core processes and individuals carrying mutations and producing slightly sub-optimal versions of…

  2. Diversity in Biological Molecules

    ERIC Educational Resources Information Center

    Newbury, H. John

    2010-01-01

    One of the striking characteristics of fundamental biological processes, such as genetic inheritance, development and primary metabolism, is the limited amount of variation in the molecules involved. Natural selective pressures act strongly on these core processes and individuals carrying mutations and producing slightly sub-optimal versions of…

  3. Geochemical Origin of Biological Molecules

    NASA Astrophysics Data System (ADS)

    Bassez, Marie-Paule

    2013-04-01

    A model for the geochemical origin of biological molecules is presented. Rocks such as peridotites and basalts, which contain ferromagnesian minerals, evolve in the presence of water. Their hydrolysis is an exothermic reaction which generates heat and a release of H2 and of minerals with modified structures. The hydrogen reacts with the CO2 embedded inside the rock or with the CO2 of the environment to form CO in an hydrothermal process. With the N2 of the environment, and with an activation source arising from cosmic radiation, ferromagnesian rocks might evolve towards the abiotic formation of biological molecules, such as peptide like macromolecules which produce amino acids after acid hydrolysis. The reactions concerned are described. The production of hydrothermal CO is discussed in geological sites containing ferromagnesian silicate minerals and the low intensity of the Earth's magnetic field during Paleoarchaean Era is also discussed. It is concluded that excitation sources arising from cosmic radiation were much more abundant during Paleoarchaean Era and that macromolecular structures of biological relevance might consequently form during Archaean Eon, as a product of the chemical evolution of the rocks and of their mineral contents. This synthesis of abiotically formed biological molecules is consecutively discussed for meteorites and other planets such as Mars. This model for the geochemical origin of biological molecules has first been proposed in 2008 in the context of reactions involving catalysers such as kaolinite [Bassez 2008a] and then presented in conferences and articles [Bassez 2008b, 2009, 2012; Bassez et al. 2009a to 2012b]. BASSEZ M.P. 2008a Synthèse prébiotique dans les conditions hydrothermales, CNRIUT'08, Lyon 29-30/05/2008, Conf. and open access article:http://liris.cnrs.fr/~cnriut08/actes/ 29 mai 11h-12h40. BASSEZ M.P. 2008b Prebiotic synthesis under hydrothermal conditions, ISSOL'08, P2-6, Firenze-Italy, 24-29/08/2008. Poster at the

  4. Exploring biology with small organic molecules.

    PubMed

    Stockwell, Brent R

    2004-12-16

    Small organic molecules have proven to be invaluable tools for investigating biological systems, but there is still much to learn from their use. To discover and to use more effectively new chemical tools to understand biology, strategies are needed that allow us to systematically explore 'biological-activity space'. Such strategies involve analysing both protein binding of, and phenotypic responses to, small organic molecules. The mapping of biological-activity space using small molecules is akin to mapping the stars--uncharted territory is explored using a system of coordinates that describes where each new feature lies.

  5. Exploring biology with small organic molecules

    PubMed Central

    Stockwell, Brent R.

    2011-01-01

    Small organic molecules have proven to be invaluable tools for investigating biological systems, but there is still much to learn from their use. To discover and to use more effectively new chemical tools to understand biology, strategies are needed that allow us to systematically explore ‘biological-activity space’. Such strategies involve analysing both protein binding of, and phenotypic responses to, small organic molecules. The mapping of biological-activity space using small molecules is akin to mapping the stars — uncharted territory is explored using a system of coordinates that describes where each new feature lies. PMID:15602550

  6. Biological mechanisms, one molecule at a time.

    PubMed

    Tinoco, Ignacio; Gonzalez, Ruben L

    2011-06-15

    The last 15 years have witnessed the development of tools that allow the observation and manipulation of single molecules. The rapidly expanding application of these technologies for investigating biological systems of ever-increasing complexity is revolutionizing our ability to probe the mechanisms of biological reactions. Here, we compare the mechanistic information available from single-molecule experiments with the information typically obtained from ensemble studies and show how these two experimental approaches interface with each other. We next present a basic overview of the toolkit for observing and manipulating biology one molecule at a time. We close by presenting a case study demonstrating the impact that single-molecule approaches have had on our understanding of one of life's most fundamental biochemical reactions: the translation of a messenger RNA into its encoded protein by the ribosome.

  7. Biological mechanisms, one molecule at a time

    PubMed Central

    Tinoco, Ignacio; Gonzalez, Ruben L.

    2011-01-01

    The last 15 years have witnessed the development of tools that allow the observation and manipulation of single molecules. The rapidly expanding application of these technologies for investigating biological systems of ever-increasing complexity is revolutionizing our ability to probe the mechanisms of biological reactions. Here, we compare the mechanistic information available from single-molecule experiments with the information typically obtained from ensemble studies and show how these two experimental approaches interface with each other. We next present a basic overview of the toolkit for observing and manipulating biology one molecule at a time. We close by presenting a case study demonstrating the impact that single-molecule approaches have had on our understanding of one of life's most fundamental biochemical reactions: the translation of a messenger RNA into its encoded protein by the ribosome. PMID:21685361

  8. Biological signaling by small inorganic molecules.

    PubMed

    Basudhar, Debashree; Ridnour, Lisa A; Cheng, Robert; Kesarwala, Aparna H; Heinecke, Julie; Wink, David A

    2016-01-01

    Small redox active molecules such as reactive nitrogen and oxygen species and hydrogen sulfide have emerged as important biological mediators that are involved in various physiological and pathophysiological processes. Advancement in understanding of cellular mechanisms that tightly regulate both generation and reactivity of these molecules is central to improved management of various disease states including cancer and cardiovascular dysfunction. Imbalance in the production of redox active molecules can lead to damage of critical cellular components such as cell membranes, proteins and DNA and thus may trigger the onset of disease. These small inorganic molecules react independently as well as in a concerted manner to mediate physiological responses. This review provides a general overview of the redox biology of these key molecules, their diverse chemistry relevant to physiological processes and their interrelated nature in cellular signaling.

  9. Halogen bonds in biological molecules

    PubMed Central

    Auffinger, Pascal; Hays, Franklin A.; Westhof, Eric; Ho, P. Shing

    2004-01-01

    Short oxygen–halogen interactions have been known in organic chemistry since the 1950s and recently have been exploited in the design of supramolecular assemblies. The present survey of protein and nucleic acid structures reveals similar halogen bonds as potentially stabilizing inter- and intramolecular interactions that can affect ligand binding and molecular folding. A halogen bond in biomolecules can be defined as a short CX···OY interaction (CX is a carbon-bonded chlorine, bromine, or iodine, and OY is a carbonyl, hydroxyl, charged carboxylate, or phosphate group), where the X···O distance is less than or equal to the sums of the respective van der Waals radii (3.27 Å for Cl···O, 3.37Å for Br···O, and 3.50 Å for I···O) and can conform to the geometry seen in small molecules, with the CX···O angle ≈165° (consistent with a strong directional polarization of the halogen) and the X···OY angle ≈120°. Alternative geometries can be imposed by the more complex environment found in biomolecules, depending on which of the two types of donor systems are involved in the interaction: (i) the lone pair electrons of oxygen (and, to a lesser extent, nitrogen and sulfur) atoms or (ii) the delocalized π -electrons of peptide bonds or carboxylate or amide groups. Thus, the specific geometry and diversity of the interacting partners of halogen bonds offer new and versatile tools for the design of ligands as drugs and materials in nanotechnology. PMID:15557000

  10. Auxin biology revealed by small molecules.

    PubMed

    Ma, Qian; Robert, Stéphanie

    2014-05-01

    The plant hormone auxin regulates virtually every aspect of plant growth and development and unraveling its molecular and cellular modes of action is fundamental for plant biology research. Chemical genomics is the use of small molecules to modify protein functions. This approach currently rises as a powerful technology for basic research. Small compounds with auxin-like activities or affecting auxin-mediated biological processes have been widely used in auxin research. They can serve as a tool complementary to genetic and genomic methods, facilitating the identification of an array of components modulating auxin metabolism, transport and signaling. The employment of high-throughput screening technologies combined with informatics-based chemical design and organic chemical synthesis has since yielded many novel small molecules with more instantaneous, precise and specific functionalities. By applying those small molecules, novel molecular targets can be isolated to further understand and dissect auxin-related pathways and networks that otherwise are too complex to be elucidated only by gene-based methods. Here, we will review examples of recently characterized molecules used in auxin research, highlight the strategies of unraveling the mechanisms of these small molecules and discuss future perspectives of small molecule applications in auxin biology. © 2013 Scandinavian Plant Physiology Society.

  11. Single molecule thermodynamics in biological motors.

    PubMed

    Taniguchi, Yuichi; Karagiannis, Peter; Nishiyama, Masayoshi; Ishii, Yoshiharu; Yanagida, Toshio

    2007-04-01

    Biological molecular machines use thermal activation energy to carry out various functions. The process of thermal activation has the stochastic nature of output events that can be described according to the laws of thermodynamics. Recently developed single molecule detection techniques have allowed each distinct enzymatic event of single biological machines to be characterized providing clues to the underlying thermodynamics. In this study, the thermodynamic properties in the stepping movement of a biological molecular motor have been examined. A single molecule detection technique was used to measure the stepping movements at various loads and temperatures and a range of thermodynamic parameters associated with the production of each forward and backward step including free energy, enthalpy, entropy and characteristic distance were obtained. The results show that an asymmetry in entropy is a primary factor that controls the direction in which the motor will step. The investigation on single molecule thermodynamics has the potential to reveal dynamic properties underlying the mechanisms of how biological molecular machines work.

  12. Proteomics: from single molecules to biological pathways.

    PubMed

    Langley, Sarah R; Dwyer, Joseph; Drozdov, Ignat; Yin, Xiaoke; Mayr, Manuel

    2013-03-15

    The conventional reductionist approach to cardiovascular research investigates individual candidate factors or linear signalling pathways but ignores more complex interactions in biological systems. The advent of molecular profiling technologies that focus on a global characterization of whole complements allows an exploration of the interconnectivity of pathways during pathophysiologically relevant processes, but has brought about the issue of statistical analysis and data integration. Proteins identified by differential expression as well as those in protein-protein interaction networks identified through experiments and through computational modelling techniques can be used as an initial starting point for functional analyses. In combination with other '-omics' technologies, such as transcriptomics and metabolomics, proteomics explores different aspects of disease, and the different pillars of observations facilitate the data integration in disease-specific networks. Ultimately, a systems biology approach may advance our understanding of cardiovascular disease processes at a 'biological pathway' instead of a 'single molecule' level and accelerate progress towards disease-modifying interventions.

  13. Electron Correlation Effects in Biological Molecules

    NASA Astrophysics Data System (ADS)

    Cox, D. L.; Endres, R.; Kulkarni, R. V.; Labute, M.; Singh, R. R. P.

    2002-07-01

    Allosteric (conformation changing) proteins with transition metal atoms are at the heart of much important biological function (e.g., myoglobin hemoglobin used for storing and transporting oxygen in the bloodstream). In the case of myoglobin and hemoglobin, oxygen ligation to the iron center induces a spin crossover (high to low) coupled to a structural change; apart from the role of Hunds' exchange in the spin crossover, electron interaction effects have been ignored. We argue that the spin crossover/structure change observed in the similarly structured but far simpler cobalt valence tautomer molecules1 necessitates an inclusion of underscreened Kondo like correlations for a complete description of the energetics of the transition and dynamics, e.g., for x-ray absorption data. We carry this study out with Varma-Yafet-Gunnarsson-Schonhammer wave functions, which, in chemistry language, are basis set restricted configuration interaction in character. We briefly review the applicability of such wave functions to the description of the putative Kondo molecules cerocene (Ce[(CH)5]2) and ytterbocene bipyridine (Yb[(CH)5]2(bipy)) and to the problem of electron transfer in biological molecules and organic conductors, where anomalous long range tunneling may occur.

  14. Electron Correlation Effects in Biological Molecules

    NASA Astrophysics Data System (ADS)

    Cox, D. L.; Endres, R.; Kulkarni, R. V.; Labute, M.; Singh, R. R. P.

    Allosteric (conformation changing) proteins with transition metal atoms are at the heart of much important biological function (e.g., myoglobin hemoglobin used for storing and transporting oxygen in the bloodstream). In the case of myoglobin and hemoglobin, oxygen ligation to the iron center induces a spin crossover (high to low) coupled to a structural change; apart from the role of Hunds' exchange in the spin crossover, electron interaction effects have been ignored. We argue that the spin crossover/structure change observed in the similarly structured but far simpler cobalt valence tautomer molecules1 necessitates an inclusion of underscreened Kondo like correlations for a complete description of the energetics of the transition and dynamics, e.g., for x-ray absorption data. We carry this study out with Varma-Yafet-Gunnarsson-Schonhammer wave functions, which, in chemistry language, are basis set restricted configuration interaction in character. We briefly review the applicability of such wave functions to the description of the putative Kondo molecules cerocene (Ce[(CH)5]2) and ytterbocene bipyridine (Yb[(CH)5]2(bipy)) and to the problem of electron transfer in biological molecules and organic conductors, where anomalous long range tunneling may occur. Research supported by the U.S. Department of Energy, Office of Science, Basic Energy Sciences, Division of Materials Research.

  15. From molecules to dynamic biological communities.

    PubMed

    McDonald, Daniel; Vázquez-Baeza, Yoshiki; Walters, William A; Caporaso, J Gregory; Knight, Rob

    2013-03-01

    Microbial ecology is flourishing, and in the process, is making contributions to how the ecology and biology of large organisms is understood. Ongoing advances in sequencing technology and computational methods have enabled the collection and analysis of vast amounts of molecular data from diverse biological communities. While early studies focused on cataloguing microbial biodiversity in environments ranging from simple marine ecosystems to complex soil ecologies, more recent research is concerned with community functions and their dynamics over time. Models and concepts from traditional ecology have been used to generate new insight into microbial communities, and novel system-level models developed to explain and predict microbial interactions. The process of moving from molecular inventories to functional understanding is complex and challenging, and never more so than when many thousands of dynamic interactions are the phenomena of interest. We outline the process of how epistemic transitions are made from producing catalogues of molecules to achieving functional and predictive insight, and show how those insights not only revolutionize what is known about biological systems but also about how to do biology itself. Examples will be drawn primarily from analyses of different human microbiota, which are the microbial consortia found in and on areas of the human body, and their associated microbiomes (the genes of those communities). Molecular knowledge of these microbiomes is transforming microbiological knowledge, as well as broader aspects of human biology, health and disease.

  16. Single molecule measurements and biological motors.

    PubMed

    Knight, Alex E; Mashanov, Gregory; Molloy, Justin E

    2005-12-01

    Recent technological advances in lasers and optical detectors have enabled a variety of new, single molecule technologies to be developed. Using intense and highly collimated laser light sources in addition to super-sensitive cameras, the fluorescence of single fluorophores can now be imaged in aqueous solution. Also, laser optical tweezers have enabled the piconewton forces produced by pair of interacting biomolecules to be measured directly. However, for a researcher new to the field to begin to use such techniques in their own research might seem a daunting prospect. Most of the equipment that is in use is custom-built. However, most of the equipment is essence fairly simple and the aim of this article is to provide an entry point to the field for a newcomer. It focuses mainly on those practical aspects which are not particularly well covered in the literature, and aims to provide an overview of the field as a whole with references and web links to more detailed sources elsewhere. Indeed, the opportunity to publish an article such as this on the Internet affords many new opportunities (and more space!) for presenting scientific ideas and information. For example, we have illustrated the nature of optical trap data with an interactive Java simulation; provided links to relevant web sites and technical documents, and included a large number of colour figures and plots. Our group's research focuses on molecular motors, and the bias of this article reflects this. It turns out that molecular motors have been a paradigm (or prototype) for single molecule research and the field has seen a rapid development in the techniques. It is hoped that the methods described here will be broadly applicable to other biological systems.

  17. Fast dynamics in molecules of biological interest

    NASA Astrophysics Data System (ADS)

    Faurskov Nielsen, O.; Jacobsen, K. L.; Westh, P.; Radovic, T.; Due Larsen, B.; Christensen, D. H.

    2001-10-01

    Isotopic substitution is used in cw-Raman studies of fast dynamics in molecules of biological interest. Simple liquid amides are considered as model systems for hydrogen bonding in peptides and proteins. Collectivity of amide I modes is studied by resonance energy transfer (RET) and coalescence of bands in mixtures of isotopomers (CBMI). A 1:1 mixture of HC 16OND 2 and HC 18OND 2 shows only one amide I band with a peak maximum between those observed for each of the pure isotopomers. Dilution studies of this mixture in D 2O show that the collective effects disappear in diluted solutions, where two bands are observed, one from each isotopomer. This is confirmed by dilution experiments performed on HC 16OND 2 in D 2O. Raman spectroscopy is a fast experimental technique reflecting the fast molecular dynamics on a picosecond and faster time scale. Future aspects of the collectivity of vibrational modes in peptides and proteins are mentioned. In this context a vibrational coupling between the amide I modes and the bending mode of water may be important. A comparison between low-frequency Raman and thermodynamic studies of water/lysozyme mixtures seems promising in terms of the difference between protein bound water and the formation of water clusters.

  18. Computer Modelling of Biological Molecules: Free Resources on the Internet.

    ERIC Educational Resources Information Center

    Millar, Neil

    1996-01-01

    Describes a three-dimensional computer modeling system for biological molecules which is suitable for sixth-form teaching. Consists of the modeling program "RasMol" together with structure files of proteins, DNA, and small biological molecules. Describes how the whole system can be downloaded from various sites on the Internet.…

  19. Computer Modelling of Biological Molecules: Free Resources on the Internet.

    ERIC Educational Resources Information Center

    Millar, Neil

    1996-01-01

    Describes a three-dimensional computer modeling system for biological molecules which is suitable for sixth-form teaching. Consists of the modeling program "RasMol" together with structure files of proteins, DNA, and small biological molecules. Describes how the whole system can be downloaded from various sites on the Internet.…

  20. Advancing Biological Understanding and Therapeutics Discovery with Small Molecule Probes

    PubMed Central

    Schreiber, Stuart L.; Kotz, Joanne D.; Li, Min; Aubé, Jeffrey; Austin, Christopher P.; Reed, John C.; Rosen, Hugh; White, E. Lucile; Sklar, Larry A.; Lindsley, Craig W.; Alexander, Benjamin R.; Bittker, Joshua A.; Clemons, Paul A.; de Souza, Andrea; Foley, Michael A.; Palmer, Michelle; Shamji, Alykhan F.; Wawer, Mathias J.; McManus, Owen; Wu, Meng; Zou, Beiyan; Yu, Haibo; Golden, Jennifer E.; Schoenen, Frank J.; Simeonov, Anton; Jadhav, Ajit; Jackson, Michael R.; Pinkerton, Anthony B.; Chung, Thomas D.Y.; Griffin, Patrick R.; Cravatt, Benjamin F.; Hodder, Peter S.; Roush, William R.; Roberts, Edward; Chung, Dong-Hoon; Jonsson, Colleen B.; Noah, James W.; Severson, William E.; Ananthan, Subramaniam; Edwards, Bruce; Oprea, Tudor I.; Conn, P. Jeffrey; Hopkins, Corey R.; Wood, Michael R.; Stauffer, Shaun R.; Emmitte, Kyle A.

    2015-01-01

    Small-molecule probes can illuminate biological processes and aid in the assessment of emerging therapeutic targets by perturbing biological systems in a manner distinct from other experimental approaches. Despite the tremendous promise of chemical tools for investigating biology and disease, small-molecule probes were unavailable for most targets and pathways as recently as a decade ago. In 2005, the U.S. National Institutes of Health launched the decade-long Molecular Libraries Program with the intent of innovating in and broadening access to small-molecule science. This Perspective describes how novel small-molecule probes identified through the program are enabling the exploration of biological pathways and therapeutic hypotheses not otherwise testable. These experiences illustrate how small-molecule probes can help bridge the chasm between biological research and the development of medicines, but also highlight the need to innovate the science of therapeutic discovery. PMID:26046436

  1. Microfluidics for biological measurements with single-molecule resolution.

    PubMed

    Streets, Aaron M; Huang, Yanyi

    2014-02-01

    Single-molecule approaches in biology have been critical in studies ranging from the examination of physical properties of biological macromolecules to the extraction of genetic information from DNA. The variation intrinsic to many biological processes necessitates measurements with single-molecule resolution in order to accurately recapitulate population distributions. Microfluidic technology has proven to be useful in the facilitation and even enhancement of single-molecule studies because of the precise liquid handling, small volume manipulation, and high throughput capabilities of microfluidic devices. In this review we survey the microfluidic "toolbox" available to the single-molecule specialist and summarize some recent biological applications of single-molecule detection on chip. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Mathematical models in biology: from molecules to life.

    PubMed

    Kaznessis, Yiannis N

    2011-01-01

    A vexing question in the biological sciences is the following: can biological phenotypes be explained with mathematical models of molecules that interact according to physical laws? At the crux of the matter lies the doubt that humans can develop physically faithful mathematical representations of living organisms. We discuss advantages that synthetic biological systems confer that may help us describe life's distinctiveness with tractable mathematics that are grounded on universal laws of thermodynamics and molecular biology. Copyright © 2011 John Wiley & Sons, Inc.

  3. Mathematical models in biology: from molecules to life

    PubMed Central

    Kaznessis, Yiannis N.

    2011-01-01

    A vexing question in the biological sciences is the following: can biological phenotypes be explained with mathematical models of molecules that interact according to physical laws? At the crux of the matter lies the doubt that humans can develop physically faithful mathematical representations of living organisms. We discuss advantages that synthetic biological systems confer that may help us describe life’s distinctiveness with tractable mathematics that are grounded on universal laws of thermodynamics and molecular biology. PMID:21472998

  4. Computer display and manipulation of biological molecules

    NASA Technical Reports Server (NTRS)

    Coeckelenbergh, Y.; Macelroy, R. D.; Hart, J.; Rein, R.

    1978-01-01

    This paper describes a computer model that was designed to investigate the conformation of molecules, macromolecules and subsequent complexes. Utilizing an advanced 3-D dynamic computer display system, the model is sufficiently versatile to accommodate a large variety of molecular input and to generate data for multiple purposes such as visual representation of conformational changes, and calculation of conformation and interaction energy. Molecules can be built on the basis of several levels of information. These include the specification of atomic coordinates and connectivities and the grouping of building blocks and duplicated substructures using symmetry rules found in crystals and polymers such as proteins and nucleic acids. Called AIMS (Ames Interactive Molecular modeling System), the model is now being used to study pre-biotic molecular evolution toward life.

  5. Computer display and manipulation of biological molecules

    NASA Technical Reports Server (NTRS)

    Coeckelenbergh, Y.; Macelroy, R. D.; Hart, J.; Rein, R.

    1978-01-01

    This paper describes a computer model that was designed to investigate the conformation of molecules, macromolecules and subsequent complexes. Utilizing an advanced 3-D dynamic computer display system, the model is sufficiently versatile to accommodate a large variety of molecular input and to generate data for multiple purposes such as visual representation of conformational changes, and calculation of conformation and interaction energy. Molecules can be built on the basis of several levels of information. These include the specification of atomic coordinates and connectivities and the grouping of building blocks and duplicated substructures using symmetry rules found in crystals and polymers such as proteins and nucleic acids. Called AIMS (Ames Interactive Molecular modeling System), the model is now being used to study pre-biotic molecular evolution toward life.

  6. First molecules, biological chirality, origin(s) of life.

    PubMed

    Caglioti, Luciano; Micskei, Károly; Pályi, Gyula

    2011-01-01

    Origin(s) of biological chirality appear(s) to be intimately connected to origin(s) of life. Prebiotic evolution toward these important turning points can be traced back to single chiral molecules. These can be small (monomeric) units as amino acids or monosaccharides or oligomers as oligo-RNA type molecules. Earlier speculations about these two kinds of entries to biological chirality are critically reviewed.

  7. Photoactive molecules for applications in molecular imaging and cell biology.

    PubMed

    Shao, Qing; Xing, Bengang

    2010-08-01

    Photoactive technology has proven successful for non-invasive regulation of biological activities and processes in living cells. With the light-directed generation of biomaterials or signals, mechanisms in cell biology can be investigated at the molecular level with spatial and temporal resolution. In this tutorial review, we aim to introduce the important applications of photoactive molecules for elucidating cell biology on aspects of protein engineering, fluorescence labelling, gene regulation and cell physiological functions.

  8. Perspective: Mechanochemistry of biological and synthetic molecules

    NASA Astrophysics Data System (ADS)

    Makarov, Dmitrii E.

    2016-01-01

    Coupling of mechanical forces and chemical transformations is central to the biophysics of molecular machines, polymer chemistry, fracture mechanics, tribology, and other disciplines. As a consequence, the same physical principles and theoretical models should be applicable in all of those fields; in fact, similar models have been invoked (and often repeatedly reinvented) to describe, for example, cell adhesion, dry and wet friction, propagation of cracks, and action of molecular motors. This perspective offers a unified view of these phenomena, described in terms of chemical kinetics with rates of elementary steps that are force dependent. The central question is then to describe how the rate of a chemical transformation (and its other measurable properties such as the transition path) depends on the applied force. I will describe physical models used to answer this question and compare them with experimental measurements, which employ single-molecule force spectroscopy and which become increasingly common. Multidimensionality of the underlying molecular energy landscapes and the ensuing frequent misalignment between chemical and mechanical coordinates result in a number of distinct scenarios, each showing a nontrivial force dependence of the reaction rate. I will discuss these scenarios, their commonness (or its lack), and the prospects for their experimental validation. Finally, I will discuss open issues in the field.

  9. Perspective: Mechanochemistry of biological and synthetic molecules.

    PubMed

    Makarov, Dmitrii E

    2016-01-21

    Coupling of mechanical forces and chemical transformations is central to the biophysics of molecular machines, polymer chemistry, fracture mechanics, tribology, and other disciplines. As a consequence, the same physical principles and theoretical models should be applicable in all of those fields; in fact, similar models have been invoked (and often repeatedly reinvented) to describe, for example, cell adhesion, dry and wet friction, propagation of cracks, and action of molecular motors. This perspective offers a unified view of these phenomena, described in terms of chemical kinetics with rates of elementary steps that are force dependent. The central question is then to describe how the rate of a chemical transformation (and its other measurable properties such as the transition path) depends on the applied force. I will describe physical models used to answer this question and compare them with experimental measurements, which employ single-molecule force spectroscopy and which become increasingly common. Multidimensionality of the underlying molecular energy landscapes and the ensuing frequent misalignment between chemical and mechanical coordinates result in a number of distinct scenarios, each showing a nontrivial force dependence of the reaction rate. I will discuss these scenarios, their commonness (or its lack), and the prospects for their experimental validation. Finally, I will discuss open issues in the field.

  10. Perspective: Mechanochemistry of biological and synthetic molecules

    SciTech Connect

    Makarov, Dmitrii E.

    2016-01-21

    Coupling of mechanical forces and chemical transformations is central to the biophysics of molecular machines, polymer chemistry, fracture mechanics, tribology, and other disciplines. As a consequence, the same physical principles and theoretical models should be applicable in all of those fields; in fact, similar models have been invoked (and often repeatedly reinvented) to describe, for example, cell adhesion, dry and wet friction, propagation of cracks, and action of molecular motors. This perspective offers a unified view of these phenomena, described in terms of chemical kinetics with rates of elementary steps that are force dependent. The central question is then to describe how the rate of a chemical transformation (and its other measurable properties such as the transition path) depends on the applied force. I will describe physical models used to answer this question and compare them with experimental measurements, which employ single-molecule force spectroscopy and which become increasingly common. Multidimensionality of the underlying molecular energy landscapes and the ensuing frequent misalignment between chemical and mechanical coordinates result in a number of distinct scenarios, each showing a nontrivial force dependence of the reaction rate. I will discuss these scenarios, their commonness (or its lack), and the prospects for their experimental validation. Finally, I will discuss open issues in the field.

  11. High-resolution waveguide THz spectroscopy of biological molecules.

    PubMed

    Laman, N; Harsha, S Sree; Grischkowsky, D; Melinger, Joseph S

    2008-02-01

    Low-frequency vibrational modes of biological molecules consist of intramolecular modes, which are dependent on the molecule as a whole, as well as intermolecular modes, which arise from hydrogen-bonding interactions and van der Waals forces. Vibrational modes thus contain important information about conformation dynamics of biological molecules, and can also be used for identification purposes. However, conventional Fourier transform infrared spectroscopy and terahertz time-domain spectroscopy (THz-TDS) often result in broad, overlapping features that are difficult to distinguish. The technique of waveguide THz-TDS has been recently developed, resulting in sharper features. For this technique, an ordered polycrystalline film of the molecule is formed on a metal sample plate. This plate is incorporated into a metal parallel-plate waveguide and probed via waveguide THz-TDS. The planar order of the film reduces the inhomogeneous broadening, and cooling of the samples to 77K reduces the homogenous broadening. This combination results in the line-narrowing of THz vibrational modes, in some cases to an unprecedented degree. Here, this technique has been demonstrated with seven small biological molecules, thymine, deoxycytidine, adenosine, D-glucose, tryptophan, glycine, and L-alanine. The successful demonstration of this technique shows the possibilities and promise for future studies of internal vibrational modes of large biological molecules.

  12. Chemical biology of antigen presentation by MHC molecules.

    PubMed

    van Kasteren, Sander I; Overkleeft, Hermen; Ovaa, Huib; Neefjes, Jacques

    2014-02-01

    MHC class I and MHC class II molecules present peptides to the immune system to drive proper T cell responses. Pharmacological modulation of T-cell responses can offer treatment options for a range of immune-related diseases. Pharmacological downregulation of MHC molecules may find application in treatment of auto-immunity and transplantation rejection while pharmacological activation of antigen presentation would support immune responses to infection and cancer. Since the cell biology of MHC class I and MHC class II antigen presentation is understood in great detail, many potential targets for manipulation have been defined over the years. Here, we discuss how antigen presentation by MHC molecules can be modulated by pharmacological agents and how chemistry can further support the study of antigen presentation in general. The chemical biology of antigen presentation by MHC molecules shows surprising options for immune modulation and the development of future therapies. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Caenorhabditis elegans chemical biology: lessons from small molecules

    USDA-ARS?s Scientific Manuscript database

    How can we complement Caenorhabditis elegans genomics and proteomics with a comprehensive structural and functional annotation of its metabolome? Several lines of evidence indicate that small molecules of largely undetermined structure play important roles in C. elegans biology, including key pathw...

  14. On the biological activity of drug molecules: Busulfan and nabumetone

    NASA Astrophysics Data System (ADS)

    Novak, Igor; Kovač, Branka

    2010-10-01

    The electronic structures of drug molecules busulfan (BSU) and nabumetone (NAB) have been investigated by HeI and HeII UV photoelectron spectroscopy (UPS), quantum chemical calculations and virtual docking studies. Their biological activities are discussed in the framework of their electronic and molecular structures, reactivity and drug-enzyme binding.

  15. Photodissociation mass spectrometry: New tools for characterization of biological molecules

    PubMed Central

    Brodbelt, Jennifer S.

    2014-01-01

    Photodissociation mass spectrometry combines the ability to activate and fragment ions using photons with the sensitive detection of the resulting product ions by mass spectrometry. The resulting combination affords a versatile tool for characterization of biological molecules. The scope and breadth of photodissociation mass spectrometry have increased substantially over the past decade as new research groups have entered the field and developed a number of innovative applications that illustrate the ability of photodissociation to produce rich fragmentation patterns, to cleave bonds selectively, and to target specific molecules based on incorporation of chromophores. This review focuses on many of the key developments in photodissociation mass spectrometry over the past decade with a particular emphasis on its applications to biological molecules. PMID:24481009

  16. GaAs/InAs Multi Quantum Well Solar Cell

    DTIC Science & Technology

    2012-12-01

    4. TITLE AND SUBTITLE GaAs /InAs MULTI QUANTUM WELL SOLAR CELL 5. FUNDING NUMBERS 6. AUTHOR(S) Evangelos Koletsios 7. PERFORMING ORGANIZATION NAME... GaAs /InAs MULTI QUANTUM WELL SOLAR CELL Evangelos Koletsios Lieutenant, Hellenic Navy B.S., Hellenic Naval Academy, 2001 Submitted in...similar, such as a GaAs crystal, which is mainly used in solar cells and it is described as a direct bandgap semiconductor. On the other hand, for

  17. Multi-quantum-well electroabsorption modulators

    NASA Astrophysics Data System (ADS)

    Piprek, Joachim; Chiu, Yijen; Bowers, John E.

    2002-06-01

    Electroabsorption modulators (EAMs) based on the quantum confined Stark effect have advantages in applications that require high speed, low drive voltage, and high extinction ratio. They are promising devices for external signal modulation in high-bandwidth optical communication systems. EAMs can be integrated with other devices like laser diodes, semiconductor optical amplifiers, and mode transformers. We have previously fabricated InGaAsP/InP multi-quantum well EAMs with a bandwidth of 25 GHz and a drive voltage of 1.2 V and 20 dB extinction ratio. Further optimization of our devices requires a detailed analysis of internal physical processes and their interaction. In this paper, we employ a two-dimensional electro-optic device model to analyze our EAMs. The model self-consistently combines kp bandstructure and absorption calculations with a carrier drift-diffusion model and optical waveguiding. The required low polarization sensitivity of EAMs leads to strong valence band mixing so that usual effective mass models cannot be applied. Optical transmission characteristics are calculated which are in good agreement with measurements. Modulation efficiency and linearity are analyzed in detail. Optimum operation voltages are identified.

  18. Energy landscape exploration of the folding processes of biological molecules

    NASA Astrophysics Data System (ADS)

    Engel, Megan Clare

    For decades, scientists from every discipline have struggled to understand the mechanism of biological self-assembly, which allows proteins and nucleic acids to fold reliably into functional three-dimensional structures. Such an understanding may hold the key to eliminating diseases such as Alzheimer's and Parkinson's and to effective protein engineering. The current best framework for describing biological folding processes is that of statistical mechanical energy landscape theory, and one of the most promising experimental techniques for exploring molecular energy landscapes is single molecule force spectroscopy (SMFS), in which molecules are mechanically denatured. Theoretical advances have enabled the extraction of complete energy landscape profiles from SMFS data. Here, SMFS experiments performed using laser optical tweezers are analyzed to yield the first ever full landscape profile for an RNA pseudoknot. Further, a promising novel landscape reconstruction technique is validated for the first time using experimental data from a DNA hairpin.

  19. Pulse requirements for electron diffraction imaging of single biological molecules

    SciTech Connect

    Hau-Riege, S; London, R; Chapman, H

    2004-10-20

    The pulse requirements for electron diffraction imaging of single biological molecules are calculated. We find that the electron fluence and pulse length requirements imposed by the damage limit and by the need to classify the diffraction patterns according to their angular orientation cannot be achieved with today's electron beam technology. A simple analytical model shows that the pulse requirements cannot be achieved due to beam broadening due to spacecharge effects.

  20. Electron scattering from molecules and molecular aggregates of biological relevance

    NASA Astrophysics Data System (ADS)

    Gorfinkiel, Jimena D.; Ptasinska, Sylwia

    2017-09-01

    In this Topical Review we survey the current state of the art in the study of low energy electron collisions with biologically relevant molecules and molecular clusters. We briefly describe the methods and techniques used in the investigation of these processes and summarise the results obtained so far for DNA constituents and their model compounds, amino acids, peptides and other biomolecules. The applications of the data obtained is briefly described as well as future required developments.

  1. Method for imaging informational biological molecules on a semiconductor substrate

    NASA Technical Reports Server (NTRS)

    Coles, L. Stephen (Inventor)

    1994-01-01

    Imaging biological molecules such as DNA at rates several times faster than conventional imaging techniques is carried out using a patterned silicon wafer having nano-machined grooves which hold individual molecular strands and periodically spaced unique bar codes permitting repeatably locating all images. The strands are coaxed into the grooves preferably using gravity and pulsed electric fields which induce electric charge attraction to the molecular strands in the bottom surfaces of the grooves. Differential imaging removes substrate artifacts.

  2. NMR studies of electrostatic potential distribution around biologically important molecules.

    PubMed Central

    Likhtenshtein, G I; Adin, I; Novoselsky, A; Shames, A; Vaisbuch, I; Glaser, R

    1999-01-01

    A new experimental approach has been developed to study the distribution of local electrostatic potential around specific protons in biologically important molecules. The approach is the development of a method denoted as "spin label/spin probe," which was proposed by one of us (. Mol. Biol. 6:498-507). The proposed method is based upon the quantitative measurement of the contribution of differently charged nitroxide probes to the spin lattice relaxation rate (1/T1) of protons in the molecule of interest, followed by calculation of local electrostatic potential using the classical Debye equation. In parallel, the theoretical calculation of potential distribution with the use of the MacSpartan Plus 1.0 program has been performed. Application of the method to solutions of simple organic molecules (aliphatic and aromatic alcohols, aliphatic carboxylates (propionate anion), and protonated ethyl amine and imidazole) allowed us to estimate the effective potential around the molecules under investigation. These were found to be in good agreement with theoretically expected values. This technique was then applied to zwitterionic amino acids bearing neutral and charged side chains (glycine, lysine, histidine, and aspartic acid). The reliability of the general approach is proved by the data presented in this paper. Application of this new methodology can afford insight into the biochemical significance of electrostatic effects in biological systems. PMID:10388770

  3. Complex molecules in galactic dust cores: Biologically interesting molecules and dust chemistry

    NASA Astrophysics Data System (ADS)

    Liu, Shen-Yuan

    2000-06-01

    The astronomical study of molecules has been an essential research field since the development of radio astronomy. Presently nearly 120 molecules have been identified in interstellar and circumstellar environments. The complexity of molecular species, and particularly organic molecules, that can be synthesized in the interstellar medium (ISM) leads to one interesting and important subfield in interstellar molecular studies, namely, the search and study for molecules of possible biological interest. Observationally, complex and most saturated molecules are observed exclusively toward compact hot, dense regions, often called ``hot cores'', in molecular clouds. To account for the observed amount of saturated organic molecules, interstellar dust particles play an important role. It has often been suggested that solid state reactions on grain surfaces provide an efficient way to synthesis saturated organic molecules. The objective of this study is to obtain observational data on biologically interesting molecules and to study important complex interstellar molecules. Since hot molecular cores are inherently compact, interferometric observations are therefore an ideal approach to study these sources. All our observations were all made with the Berkeley-Illinois-Maryland-Association (BIMA) Array. We conducted the first survey of formic acid (HCOOH) with an interferometric array, and identified at least three sources. HCOOH is found with column densities above 1015 cm-2 in these sources. The correlation between HCOOH and HCOOCH3 emission implies a surface chemistry origin of HCOOH. Details of the results are given in Chapter 2. Meanwhile, we continued to search for molecules of biological interest, namely urea, acetic acid, and glycine. In Chapter 3, the results of column density limits set by our observations are discussed. We have also investigated properties of individual hot molecular cores. It is very important to obtain the physical and chemical properties of these

  4. Target identification for biologically active small molecules using chemical biology approaches.

    PubMed

    Lee, Heesu; Lee, Jae Wook

    2016-09-01

    The identification and validation of the targets of biologically active molecules is an important step in the field of chemical biology. While recent advances in proteomic and genomic technology have accelerated this identification process, the discovery of small molecule targets remains the most challenging step. A general method for the identification of these small molecule targets has not yet been established. To overcome the difficulty in target identification, new technology derived from the fields of genomics, proteomics, and bioinformatics has been developed. To date, pull-down methods using small molecules immobilized on a solid support followed by mass spectrometry have been the most successful approach. Here, we discuss current procedures for target identification. We also review the most recent target identification approaches and present several examples that illustrate advanced target identification technology.

  5. Evidence of disorder in biological molecules from single molecule pulling experiments.

    PubMed

    Hyeon, Changbong; Hinczewski, Michael; Thirumalai, D

    2014-04-04

    Heterogeneity in biological molecules, resulting in molecule-to-molecule variations in their dynamics and function, is an emerging theme. To elucidate the consequences of heterogeneous behavior at the single molecule level, we propose an exactly solvable model in which the unfolding rate due to mechanical force depends parametrically on an auxiliary variable representing an entropy barrier arising from fluctuations in internal dynamics. When the rate of fluctuations--a measure of dynamical disorder--is comparable to or smaller than the rate of force-induced unbinding, we show that there are two experimentally observable consequences: nonexponential survival probability at constant force, and a heavy-tailed rupture force distribution at constant loading rate. By fitting our analytical expressions to data from single molecule pulling experiments on proteins and DNA, we quantify the extent of disorder. We show that only by analyzing data over a wide range of forces and loading rates can the role of disorder due to internal dynamics be quantitatively assessed.

  6. Tracking electrons in biological macromolecules: from ensemble to single molecule.

    PubMed

    Tabares, Leandro C; Gupta, Ankur; Aartsma, Thijs J; Canters, Gerard W

    2014-08-06

    Nature utilizes oxido-reductases to cater to the energy demands of most biochemical processes in respiratory species. Oxido-reductases are capable of meeting this challenge by utilizing redox active sites, often containing transition metal ions, which facilitate movement and relocation of electrons/protons to create a potential gradient that is used to energize redox reactions. There has been a consistent struggle by researchers to estimate the electron transfer rate constants in physiologically relevant processes. This review provides a brief background on the measurements of electron transfer rates in biological molecules, in particular Cu-containing enzymes, and highlights the recent advances in monitoring these electron transfer events at the single molecule level or better to say, at the individual event level.

  7. A simple backscattering microscope for fast tracking of biological molecules

    NASA Astrophysics Data System (ADS)

    Sowa, Yoshiyuki; Steel, Bradley C.; Berry, Richard M.

    2010-11-01

    Recent developments in techniques for observing single molecules under light microscopes have helped reveal the mechanisms by which molecular machines work. A wide range of markers can be used to detect molecules, from single fluorophores to micron sized markers, depending on the research interest. Here, we present a new and simple objective-type backscattering microscope to track gold nanoparticles with nanometer and microsecond resolution. The total noise of our system in a 55 kHz bandwidth is ˜0.6 nm per axis, sufficient to measure molecular movement. We found our backscattering microscopy to be useful not only for in vitro but also for in vivo experiments because of lower background scattering from cells than in conventional dark-field microscopy. We demonstrate the application of this technique to measuring the motion of a biological rotary molecular motor, the bacterial flagellar motor, in live Escherichia coli cells.

  8. Single-molecule fluorescence resonance energy transfer in molecular biology.

    PubMed

    Sasmal, Dibyendu K; Pulido, Laura E; Kasal, Shan; Huang, Jun

    2016-12-08

    Single-molecule fluorescence resonance energy transfer (smFRET) is a powerful technique for studying the conformation dynamics and interactions of individual biomolecules. In this review, we describe the concept and principle of smFRET, illustrate general instrumentation and microscopy settings for experiments, and discuss the methods and algorithms for data analysis. Subsequently, we review applications of smFRET in protein conformational changes, ion channel open-close properties, receptor-ligand interactions, nucleic acid structure regulation, vesicle fusion, and force induced conformational dynamics. Finally, we discuss the main limitations of smFRET in molecular biology.

  9. Using cheminformatics for the identification of biological functions of small molecules in metabolic pathway.

    PubMed

    Niu, Bing; Lu, Wencong

    2013-01-01

    Small molecules are involved in metabolic pathways responsible for many biological activities. Therefore it is essential to study them to uncover the unknown biological function of highly complex living systems. It is a crucial step in modern drug discovery to correctly and effectively discover small molecules' biological function since small molecules are related to many protein functions and biological processes. This paper presents the application of cheminformatics approaches in predicting small molecule's (ligand's) biological function in metabolic pathway. Many examples of success in identification and prediction in the area of small molecule metabolic pathway mapping and small molecule-protein interaction prediction have been discussed.

  10. Characterization of Biological Molecules with Time-Domain Terahertz Spectroscopy

    NASA Astrophysics Data System (ADS)

    Bechel, Meagan; Deibel, Jason; Hussian, Saber; Smith, Stanley; Ganti, Sayta; Moulton, Michael

    2010-10-01

    Terahertz (THz) spectroscopy is distinctly appealing for characterization of biological molecules because many biological compounds have vibrational modes within the THz range. These vibrational modes often lead to a unique spectrum for each substance, allowing easy differentiation. The aim of this study is to utilize time-domain terahertz spectroscopy to calculate the frequency-dependent absorption coefficient and refractive index for several amino acids and proteins, including bovine and human serum albumin, glycine, and L- and D-histidine. The histidine study seeks to investigate the optical isomer differention capabilities of THz spectroscopy. It is also hoped that the characterization of proteins will lead to further studies examining the conformational changes related to disease detection.

  11. The Central Symbiosis of Molecular Biology: Molecules in Mutualism.

    PubMed

    Lanier, Kathryn A; Petrov, Anton S; Williams, Loren Dean

    2017-08-07

    As illustrated by the mitochondrion and the eukaryotic cell, little in biology makes sense except in light of mutualism. Mutualisms are persistent, intimate, and reciprocal exchanges; an organism proficient in obtaining certain benefits confers those on a partner, which reciprocates by conferring different benefits. Mutualisms (i) increase fitness, (ii) inspire robustness, (iii) are resilient and resistant to change, (iv) sponsor co-evolution, (v) foster innovation, and (vi) involve partners that are distantly related with contrasting yet complementary proficiencies. Previous to this work, mutualisms were understood to operate on levels of cells, organisms, ecosystems, and even societies and economies. Here, the concepts of mutualism are extended to molecules and are seen to apply to the relationship between RNA and protein. Polynucleotide and polypeptide are Molecules in Mutualism. RNA synthesizes protein in the ribosome and protein synthesizes RNA in polymerases. RNA and protein are codependent, and trade proficiencies. Protein has proficiency in folding into complex three-dimensional states, contributing enzymes, fibers, adhesives, pumps, pores, switches, and receptors. RNA has proficiency in direct molecular recognition, achieved by complementary base pairing interactions, which allow it to maintain, record, and transduce information. The large phylogenetic distance that characterizes partnerships in organismal mutualism has close analogy with large distance in chemical space between RNA and protein. The RNA backbone is anionic and self-repulsive and cannot form hydrophobic structural cores. The protein backbone is neutral and cohesive and commonly forms hydrophobic cores. Molecules in Mutualism extends beyond RNA and protein. A cell is a consortium of molecules in which nucleic acids, proteins, polysaccharides, phospholipids, and other molecules form a mutualism consortium that drives metabolism and replication. Analogies are found in systems such as

  12. Imaging biological molecules with single molecule sensitivity using near-field scanning optical microscopy

    SciTech Connect

    Ambrose, W.P.; Affleck, R.L.; Goodwin, P.M.; Keller, R.A.; Martin, J.C.; Petty, J.T.; Schecker, J.A.; Wu, Ming

    1995-12-01

    We have developed a near-field scanning optical microscope with the sensitivity to detect single fluorescent molecules. Our microscope is based on scanning a sample under a tapered and metal coated fiber optic probe and has an illumination-aperture diameter as small as 100 nm. The microscope simultaneously acquires a shear force image with a height noise of {approximately} 1 nm. We have used this system to demonstrate the detection of single molecules of Rhodamine-6G on silica. In this paper, we explore the use of NSOM for investigations of biological molecules. We have prepared and imaged double-stranded DNA intercalated with thiazole orange homodimer (TOTO); single chromosomes stained with propidium iodide; and {beta}-phycoerythrin proteins on dry, borosilicate-glass surfaces. At very dilute coverages, isolated fluorescent spots are observed for the un-intercalated TOTO dye and for {beta}-phycoerythrin. These fluorescent spots exhibit-emission intensity fluctuations and abrupt bleaching transitions, similar to the intensity behavior observed previously for single Rhodamine 6G molecules on silica.

  13. Small molecule screening at Helmholtz Zentrum München - from biology to molecules.

    PubMed

    Schorpp, Kenji; Hadian, Kamyar

    2014-03-01

    Within the last few years the Helmholtz Zentrum München has established several initiatives enabling the translation of basic research results into discovery of novel small molecules that affect pathomechanisms of chronic and complex diseases. Here, one of the main operations is the Assay Development and Screening Platform (ADSP) that has state-of-the-art equipment for compound screening and provides knowledge in a variety of biochemical or cell-based phenotypic assays. In particular, ADSP has a strong focus on complex assays such as high-content screening in stem cells that are likely to provide an innovative approach complementary to biochemical assays for the discovery of novel small molecules modulating key biological processes.

  14. The 7th Japan-Korea chemical biology symposium: chemical biology of natural bioactive molecules.

    PubMed

    Pandey, Ramesh Prasad; Kwon, Ho Jeong; Ahn, Jong Seog; Osada, Hiroyuki; Sohng, Jae Kyung

    2014-05-16

    Natural bioactive molecules possess supreme chemical diversity and drug-like properties and are an important source for drug lead compounds. At the seventh Japan-Korea Chemical Biology Symposium at Jeju Island, Korea, chemical biologists from Korea and Japan highlighted the remarkable features of natural products and their significance.

  15. Interferometric observations of large biologically interesting interstellar and cometary molecules

    PubMed Central

    Snyder, Lewis E.

    2006-01-01

    Interferometric observations of high-mass regions in interstellar molecular clouds have revealed hot molecular cores that have substantial column densities of large, partly hydrogen-saturated molecules. Many of these molecules are of interest to biology and thus are labeled “biomolecules.” Because the clouds containing these molecules provide the material for star formation, they may provide insight into presolar nebular chemistry, and the biomolecules may provide information about the potential of the associated interstellar chemistry for seeding newly formed planets with prebiotic organic chemistry. In this overview, events are outlined that led to the current interferometric array observations. Clues that connect this interstellar hot core chemistry to the solar system can be found in the cometary detection of methyl formate and the interferometric maps of cometary methanol. Major obstacles to understanding hot core chemistry remain because chemical models are not well developed and interferometric observations have not been very sensitive. Differentiation in the molecular isomers glycolaldehdye, methyl formate, and acetic acid has been observed, but not explained. The extended source structure for certain sugars, aldehydes, and alcohols may require nonthermal formation mechanisms such as shock heating of grains. Major advances in understanding the formation chemistry of hot core species can come from observations with the next generation of sensitive, high-resolution arrays. PMID:16894168

  16. Interferometric observations of large biologically interesting interstellar and cometary molecules.

    PubMed

    Snyder, Lewis E

    2006-08-15

    Interferometric observations of high-mass regions in interstellar molecular clouds have revealed hot molecular cores that have substantial column densities of large, partly hydrogen-saturated molecules. Many of these molecules are of interest to biology and thus are labeled "biomolecules." Because the clouds containing these molecules provide the material for star formation, they may provide insight into presolar nebular chemistry, and the biomolecules may provide information about the potential of the associated interstellar chemistry for seeding newly formed planets with prebiotic organic chemistry. In this overview, events are outlined that led to the current interferometric array observations. Clues that connect this interstellar hot core chemistry to the solar system can be found in the cometary detection of methyl formate and the interferometric maps of cometary methanol. Major obstacles to understanding hot core chemistry remain because chemical models are not well developed and interferometric observations have not been very sensitive. Differentiation in the molecular isomers glycolaldehdye, methyl formate, and acetic acid has been observed, but not explained. The extended source structure for certain sugars, aldehydes, and alcohols may require nonthermal formation mechanisms such as shock heating of grains. Major advances in understanding the formation chemistry of hot core species can come from observations with the next generation of sensitive, high-resolution arrays.

  17. Single-molecule experiments in biological physics: methods and applications.

    PubMed

    Ritort, F

    2006-08-16

    I review single-molecule experiments (SMEs) in biological physics. Recent technological developments have provided the tools to design and build scientific instruments of high enough sensitivity and precision to manipulate and visualize individual molecules and measure microscopic forces. Using SMEs it is possible to manipulate molecules one at a time and measure distributions describing molecular properties, characterize the kinetics of biomolecular reactions and detect molecular intermediates. SMEs provide additional information about thermodynamics and kinetics of biomolecular processes. This complements information obtained in traditional bulk assays. In SMEs it is also possible to measure small energies and detect large Brownian deviations in biomolecular reactions, thereby offering new methods and systems to scrutinize the basic foundations of statistical mechanics. This review is written at a very introductory level, emphasizing the importance of SMEs to scientists interested in knowing the common playground of ideas and the interdisciplinary topics accessible by these techniques. The review discusses SMEs from an experimental perspective, first exposing the most common experimental methodologies and later presenting various molecular systems where such techniques have been applied. I briefly discuss experimental techniques such as atomic-force microscopy (AFM), laser optical tweezers (LOTs), magnetic tweezers (MTs), biomembrane force probes (BFPs) and single-molecule fluorescence (SMF). I then present several applications of SME to the study of nucleic acids (DNA, RNA and DNA condensation) and proteins (protein-protein interactions, protein folding and molecular motors). Finally, I discuss applications of SMEs to the study of the nonequilibrium thermodynamics of small systems and the experimental verification of fluctuation theorems. I conclude with a discussion of open questions and future perspectives.

  18. Novel nuclear magnetic resonance techniques for studying biological molecules

    SciTech Connect

    Laws, David Douglas

    2000-06-01

    Over the fifty-five year history of Nuclear Magnetic Resonance (NMR), considerable progress has been made in the development of techniques for studying the structure, function, and dynamics of biological molecules. The majority of this research has involved the development of multi-dimensional NMR experiments for studying molecules in solution, although in recent years a number of groups have begun to explore NMR methods for studying biological systems in the solid-state. Despite this new effort, a need still exists for the development of techniques that improve sensitivity, maximize information, and take advantage of all the NMR interactions available in biological molecules. In this dissertation, a variety of novel NMR techniques for studying biomolecules are discussed. A method for determining backbone (Φ/Ψ) dihedral angles by comparing experimentally determined 13Ca, chemical-shift anisotropies with theoretical calculations is presented, along with a brief description of the theory behind chemical-shift computation in proteins and peptides. The utility of the Spin-Polarization Induced Nuclear Overhauser Effect (SPINOE) to selectively enhance NMR signals in solution is examined in a variety of systems, as are methods for extracting structural information from cross-relaxation rates that can be measured in SPINOE experiments. Techniques for the production of supercritical and liquid laser-polarized xenon are discussed, as well as the prospects for using optically pumped xenon as a polarizing solvent. In addition, a detailed study of the structure of PrP 89-143 is presented. PrP 89-143 is a 54 residue fragment of the prion proteins which, upon mutation and aggregation, can induce prion diseases in transgenic mice. Whereas the structure of the wild-type PrP 89-143 is a generally unstructured mixture of α-helical and β-sheet conformers in the solid state, the aggregates formed from the PrP 89-143 mutants appear to be mostly β-sheet.

  19. Myricetin: A Dietary Molecule with Diverse Biological Activities.

    PubMed

    Semwal, Deepak Kumar; Semwal, Ruchi Badoni; Combrinck, Sandra; Viljoen, Alvaro

    2016-02-16

    Myricetin is a common plant-derived flavonoid and is well recognised for its nutraceuticals value. It is one of the key ingredients of various foods and beverages. The compound exhibits a wide range of activities that include strong anti-oxidant, anticancer, antidiabetic and anti-inflammatory activities. It displays several activities that are related to the central nervous system and numerous studies have suggested that the compound may be beneficial to protect against diseases such as Parkinson's and Alzheimer's. The use of myricetin as a preserving agent to extend the shelf life of foods containing oils and fats is attributed to the compound's ability to protect lipids against oxidation. A detailed search of existing literature revealed that there is currently no comprehensive review available on this important molecule. Hence, the present work includes the history, synthesis, pharmaceutical applications and toxicity studies of myricetin. This report also highlights structure-activity relationships and mechanisms of action for various biological activities.

  20. Chromatography and mass spectrometry of prebiological and biological molecules

    NASA Astrophysics Data System (ADS)

    Navale, Vivek

    The detection and identification of prebiological and biological molecules are of importance for understanding chemical and biological processes occurring within the solar system. Molecular mass measurements, peptide mapping, and disulfide bond analysis of enzymes and recombinant proteins are important in the development of therapeutic drugs for human diseases. Separation of hydrocarbons (C1 to C6) and nitriles was achieved by 14%-cyanopropylphenyl-86%- dimethylpolysiloxane (CPPS-DMPS) stationary phase in a narrow bore metal capillary column. The calculation of modeling numbers enabled the differentiation of the C4 hydrocarbon isomers of 1-butene (cis and trans). The modeled retention time values for benzene, toluene, xylene, acetonitrile, propane, and propene nitriles were in good agreement with the measurements. The separation of C2 hydrocarbons (ethane and ethene) from predominantly N2 matrix was demonstrated for the first time on wall coated narrow bore low temperature glassy carbon column. Identification and accurate mass measurements of pepsin, an enzymatic protein with less number of basic amino acid residues were successfully demonstrated by matrix- assisted laser desorption ionization mass spectrometry (MALDI-MS). The molecular mass of pepsin was found to be 34,787 Da. Several decomposition products of pepsin, in m/z range of 3,500 to 4,700 were identified. Trypsin, an important endopeptidase enzyme had a mass of 46829.7 Da. Lower mass components with m/z 8047.5, 7776.6, 5722, 5446.2 and 5185 Da were also observed in trypsin spectrum. Both chemokine and growth factor recombinant proteins were mass analyzed as 8848.1 ± 3.5 and 16178.52 ± 4.1 Da, respectively. The accuracy of the measurements was in the range of 0.01 to 0.02%. Reduction and alkylation experiments on the chemokine showed the presence of six cysteines and three disulfide bonds. The two cysteines of the growth factor contained the free sulfhydryl groups and the accurate average mass of the

  1. Photochemical patterning of biological molecules inside a glass capillary.

    PubMed

    Balakirev, Maxim Y; Porte, Stéphanie; Vernaz-Gris, Maud; Berger, Michel; Arié, Jean-Philippe; Fouqué, Brigitte; Chatelain, François

    2005-09-01

    A simple way for photochemical patterning of biological molecules onto the inner wall of fused-silica capillary is described. The method is based on a modification of the inner capillary surface with photoactive benzophenone (BP) derivative. The UV irradiation at 365 nm of the capillary filled with a sample solution results in cross-linking of the solutes to the BP moiety via a stable covalent bond. As a proof of concept, oligonucleotides and proteins were arrayed inside the capillary using an inverted microscope as an irradiation device. We demonstrated that the capillary arrays produced in this way are functional and could be used in different bioassays including DNA hybridization, protein interaction studies, and immunoassays. Having a sensitivity comparable to the fluorophore-based assays in a planar format, the capillary array possesses several advantages including submicroliter sample volume and a short assay time. The capillary format should therefore be considered as a possible alternative to a planar format in a number of low-density array applications such as mutation detection and diagnostic immunoassays.

  2. Myricetin: A Dietary Molecule with Diverse Biological Activities

    PubMed Central

    Semwal, Deepak Kumar; Semwal, Ruchi Badoni; Combrinck, Sandra; Viljoen, Alvaro

    2016-01-01

    Myricetin is a common plant-derived flavonoid and is well recognised for its nutraceuticals value. It is one of the key ingredients of various foods and beverages. The compound exhibits a wide range of activities that include strong anti-oxidant, anticancer, antidiabetic and anti-inflammatory activities. It displays several activities that are related to the central nervous system and numerous studies have suggested that the compound may be beneficial to protect against diseases such as Parkinson’s and Alzheimer’s. The use of myricetin as a preserving agent to extend the shelf life of foods containing oils and fats is attributed to the compound’s ability to protect lipids against oxidation. A detailed search of existing literature revealed that there is currently no comprehensive review available on this important molecule. Hence, the present work includes the history, synthesis, pharmaceutical applications and toxicity studies of myricetin. This report also highlights structure-activity relationships and mechanisms of action for various biological activities. PMID:26891321

  3. Voltammetric detection of biological molecules using chopped carbon fiber.

    PubMed

    Sugawara, Kazuharu; Yugami, Asako; Kojima, Akira

    2010-01-01

    Voltammetric detection of biological molecules was carried out using chopped carbon fibers produced from carbon fiber reinforced plastics that are biocompatible and inexpensive. Because chopped carbon fibers normally are covered with a sizing agent, they are difficult to use as an electrode. However, when the surface of a chopped carbon fiber was treated with ethanol and hydrochloric acid, it became conductive. To evaluate the functioning of chopped carbon fibers, voltammetric measurements of [Fe(CN)(6)](3-) were carried out. Redoxes of FAD, ascorbic acid and NADH as biomolecules were recorded using cyclic voltammetry. The sizing agents used to bundle the fibers were epoxy, polyamide and polyurethane resins. The peak currents were the greatest when using the chopped carbon fibers that were created with epoxy resins. When the electrode response of the chopped carbon fibers was compared with that of a glassy carbon electrode, the peak currents and the reversibility of the electrode reaction were sufficient. Therefore, the chopped carbon fibers will be useful as disposable electrodes for the sensing of biomolecules.

  4. Progress in Small Molecule and Biologic Therapeutics Targeting Ghrelin Signaling.

    PubMed

    McGovern, Kayleigh R; Darling, Joseph E; Hougland, James L

    2016-01-01

    Ghrelin is a circulating peptide hormone involved in regulation of a wide array of physiological processes. As an endogenous ligand for growth hormone secretagogue receptor (GHSR1a), ghrelin is responsible for signaling involved in energy homeostasis, including appetite stimulation, glucose metabolism, insulin signaling, and adiposity. Ghrelin has also been implicated in modulation of several neurological processes. Dysregulation of ghrelin signaling is implicated in diseases related to these pathways, including obesity, type II diabetes, and regulation of appetite and body weight in patients with Prader-Willi syndrome. Multiple steps in the ghrelin signaling pathway are available for targeting in the development of therapeutics for these diseases. Agonists and antagonists of GHS-R1a have been widely studied and have shown varying levels of effectiveness within ghrelin-related physiological pathways. Agents targeting ghrelin directly, either through depletion of ghrelin levels in circulation or inhibitors of ghrelin O-acyltransferase whose action is required for ghrelin to become biologically active, are receiving increasing attention as potential therapeutic options. We discuss the approaches utilized to target ghrelin signaling and highlight the current challenges toward developing small-molecule agents as potential therapeutics for ghrelin-related diseases.

  5. Single-molecule biophysics: at the interface of biology, physics and chemistry.

    PubMed

    Deniz, Ashok A; Mukhopadhyay, Samrat; Lemke, Edward A

    2008-01-06

    Single-molecule methods have matured into powerful and popular tools to probe the complex behaviour of biological molecules, due to their unique abilities to probe molecular structure, dynamics and function, unhindered by the averaging inherent in ensemble experiments. This review presents an overview of the burgeoning field of single-molecule biophysics, discussing key highlights and selected examples from its genesis to our projections for its future. Following brief introductions to a few popular single-molecule fluorescence and manipulation methods, we discuss novel insights gained from single-molecule studies in key biological areas ranging from biological folding to experiments performed in vivo.

  6. Single-molecule tools for enzymology, structural biology, systems biology and nanotechnology: an update.

    PubMed

    Widom, Julia R; Dhakal, Soma; Heinicke, Laurie A; Walter, Nils G

    2014-11-01

    Toxicology is the highly interdisciplinary field studying the adverse effects of chemicals on living organisms. It requires sensitive tools to detect such effects. After their initial implementation during the 1990s, single-molecule fluorescence detection tools were quickly recognized for their potential to contribute greatly to many different areas of scientific inquiry. In the intervening time, technical advances in the field have generated ever-improving spatial and temporal resolution and have enabled the application of single-molecule fluorescence to increasingly complex systems, such as live cells. In this review, we give an overview of the optical components necessary to implement the most common versions of single-molecule fluorescence detection. We then discuss current applications to enzymology and structural studies, systems biology, and nanotechnology, presenting the technical considerations that are unique to each area of study, along with noteworthy recent results. We also highlight future directions that have the potential to revolutionize these areas of study by further exploiting the capabilities of single-molecule fluorescence microscopy.

  7. Single molecule tools for enzymology, structural biology, systems biology and nanotechnology: an update

    PubMed Central

    Widom, Julia R.; Dhakal, Soma; Heinicke, Laurie A.; Walter, Nils G.

    2015-01-01

    Toxicology is the highly interdisciplinary field studying the adverse effects of chemicals on living organisms. It requires sensitive tools to detect such effects. After their initial implementation during the 1990s, single-molecule fluorescence detection tools were quickly recognized for their potential to contribute greatly to many different areas of scientific inquiry. In the intervening time, technical advances in the field have generated ever-improving spatial and temporal resolution, and have enabled the application of single-molecule fluorescence to increasingly complex systems, such as live cells. In this review, we give an overview of the optical components necessary to implement the most common versions of single-molecule fluorescence detection. We then discuss current applications to enzymology and structural studies, systems biology, and nanotechnology, presenting the technical considerations that are unique to each area of study, along with noteworthy recent results. We also highlight future directions that have the potential to revolutionize these areas of study by further exploiting the capabilities of single-molecule fluorescence microscopy. PMID:25212907

  8. Sustainable production of biologically active molecules of marine based origin.

    PubMed

    Murray, Patrick M; Moane, Siobhan; Collins, Catherine; Beletskaya, Tanya; Thomas, Olivier P; Duarte, Alysson W F; Nobre, Fernando S; Owoyemi, Ifeloju O; Pagnocca, Fernando C; Sette, L D; McHugh, Edward; Causse, Eric; Pérez-López, Paula; Feijoo, Gumersindo; Moreira, Ma T; Rubiolo, Juan; Leirós, Marta; Botana, Luis M; Pinteus, Susete; Alves, Celso; Horta, André; Pedrosa, Rui; Jeffryes, Clayton; Agathos, Spiros N; Allewaert, Celine; Verween, Annick; Vyverman, Wim; Laptev, Ivan; Sineoky, Sergei; Bisio, Angela; Manconi, Renata; Ledda, Fabio; Marchi, Mario; Pronzato, Roberto; Walsh, Daniel J

    2013-09-25

    The marine environment offers both economic and scientific potential which are relatively untapped from a biotechnological point of view. These environments whilst harsh are ironically fragile and dependent on a harmonious life form balance. Exploitation of natural resources by exhaustive wild harvesting has obvious negative environmental consequences. From a European industry perspective marine organisms are a largely underutilised resource. This is not due to lack of interest but due to a lack of choice the industry faces for cost competitive, sustainable and environmentally conscientious product alternatives. Knowledge of the biotechnological potential of marine organisms together with the development of sustainable systems for their cultivation, processing and utilisation are essential. In 2010, the European Commission recognised this need and funded a collaborative RTD/SME project under the Framework 7-Knowledge Based Bio-Economy (KBBE) Theme 2 Programme 'Sustainable culture of marine microorganisms, algae and/or invertebrates for high value added products'. The scope of that project entitled 'Sustainable Production of Biologically Active Molecules of Marine Based Origin' (BAMMBO) is outlined. Although the Union is a global leader in many technologies, it faces increasing competition from traditional rivals and emerging economies alike and must therefore improve its innovation performance. For this reason innovation is placed at the heart of a European Horizon 2020 Strategy wherein the challenge is to connect economic performance to eco performance. This article provides a synopsis of the research activities of the BAMMBO project as they fit within the wider scope of sustainable environmentally conscientious marine resource exploitation for high-value biomolecules. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Shining the spotlight on functional molecular complexes: The new science of single-molecule cell biology.

    PubMed

    Leake, Mark C

    2010-09-01

    Single-molecule research is emerging as one of the fastest growing fields within the biosciences. Historically, most of the techniques employed have operated largely in the world of the test tube in which the components of the biological system under investigation have been extracted and purified from cells to reduce them to just the key ingredients under study, and this research has involved novel, pioneering methods of biophysics to obtain single-molecule measurements. What has emerged recently is the technical ability to now perform key single-molecule experiments whilst retaining the native biological context-namely to do single-molecule experiments on functional living cells. This presents essentially a new science of "single-molecule cell biology", which combines classical cell biology approaches with modern single-molecule biophysics. Here, key recent studies which have pushed back the boundaries of this field are discussed.

  10. Single molecule experimentation in biological physics: exploring the living component of soft condensed matter one molecule at a time.

    PubMed

    Harriman, O L J; Leake, M C

    2011-12-21

    The soft matter of biological systems consists of mesoscopic length scale building blocks, composed of a variety of different types of biological molecules. Most single biological molecules are so small that 1 billion would fit on the full-stop at the end of this sentence, but collectively they carry out the vital activities in living cells whose length scale is at least three orders of magnitude greater. Typically, the number of molecules involved in any given cellular process at any one time is relatively small, and so real physiological events may often be dominated by stochastics and fluctuation behaviour at levels comparable to thermal noise, and are generally heterogeneous in nature. This challenging combination of heterogeneity and stochasticity is best investigated experimentally at the level of single molecules, as opposed to more conventional bulk ensemble-average techniques. In recent years, the use of such molecular experimental approaches has become significantly more widespread in research laboratories around the world. In this review we discuss recent experimental approaches in biological physics which can be applied to investigate the living component of soft condensed matter to a precision of a single molecule. © 2011 IOP Publishing Ltd Printed in the UK & the USA

  11. Vibrational self-consistent field calculations for spectroscopy of biological molecules: new algorithmic developments and applications.

    PubMed

    Roy, Tapta Kanchan; Gerber, R Benny

    2013-06-28

    This review describes the vibrational self-consistent field (VSCF) method and its other variants for computing anharmonic vibrational spectroscopy of biological molecules. The superiority and limitations of this algorithm are discussed with examples. The spectroscopic accuracy of the VSCF method is compared with experimental results and other available state-of-the-art algorithms for various biologically important systems. For large biological molecules with many vibrational modes, the scaling of computational effort is investigated. The accuracy of the vibrational spectra of biological molecules using the VSCF approach for different electronic structure methods is also assessed. Finally, a few open problems and challenges in this field are discussed.

  12. The aims of systems biology: between molecules and organisms.

    PubMed

    Noble, D

    2011-05-01

    The systems approach to biology has a long history. Its recent rapid resurgence at the turn of the century reflects the problems encountered in interpreting the sequencing of the genome and the failure of that immense achievement to provide rapid and direct solutions to major multi-factorial diseases. This paper argues that systems biology is necessarily multilevel and that there is no privileged level of causality in biological systems. It is an approach rather than a separate discipline. Functionality arises from biological networks that interact with the genome, the environment and the phenotype. This view of biology is very different from the gene-centred views of neo-Darwinism and molecular biology. In neuroscience, the systems approach leads naturally to 2 important conclusions: first, that the idea of 'programs' in the brain is confusing, and second, that the self is better interpreted as a process than as an object. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Intersubband optical transients in multi-quantum-well structures

    NASA Astrophysics Data System (ADS)

    Luc, F.; Rosencher, E.; Bois, Ph.

    1993-05-01

    We show that optical transients due to the intersubband photoionization of the electrons from quantum wells may be observed by inserting a multi-quantum-well structure in the space-charge layer of a Schottky diode. This method provides a direct measurement of the photoionization cross section of a quantum well. The escape probability of the photoexcited electron from the quantum well can thus be unambiguously deduced. Its variation with the electric field may be described by a simple model based on the statistical fluctuation of the quantum-well width.

  14. Ferroelectric tunnel junctions with multi-quantum well structures

    SciTech Connect

    Ma, Zhijun; Zhang, Tianjin; Liang, Kun; Qi, Yajun; Wang, Duofa; Wang, Jinzhao; Jiang, Juan

    2014-06-02

    Ferroelectric tunnel junctions (FTJs) with multi-quantum well structures are proposed and the tunneling electroresistance (TER) effect is investigated theoretically. Compared with conventional FTJs with monolayer ferroelectric barriers, FTJs with single-well structures provide TER ratio improvements of one order of magnitude, while FTJs with optimized multi-well structures can enhance this improvement by another order of magnitude. It is believed that the increased resonant tunneling strength combined with appropriate asymmetry in these FTJs contributes to the improvement. These studies may help to fabricate FTJs with large TER ratio experimentally and put them into practice.

  15. Proteoglycans and more – from molecules to biology

    PubMed Central

    Heinegård, Dick

    2009-01-01

    In this article the organization and functional details of the extracellular matrix, with particular focus on cartilage, are described. All tissues contain a set of molecules that are arranged to contribute structural elements. Examples are fibril-forming collagens forming major fibrillar networks in most tissues. The assembly process is regulated by a number of proteins (thrombospondins, LRR-proteins, matrilins and other collagens) that can bind to the collagen molecule and in many cases remain bound to the formed fibre providing additional stability and enhancing networking to other structural networks. One such network is formed by collagen VI molecules assembled to beaded filaments in the matrix catalysed by interactions with small proteoglycans of the LRR-family, which remain bound to the filament providing for interactions via a linker of a matrilin to other matrix constituents like collagen fibres and the large proteoglycans, e.g. aggrecan in cartilage. Aggrecan is contributing an extreme anionic charge density to the extracellular matrix, which by osmotic effects leads to water retention and strive to swelling, resisted by the tensile properties of the collagen fibres. Aggrecan is bound via one end to hyaluronan, including such molecules retained at the cell surface, to form very large molecular entities that interact with other constituents of the matrix, e.g. fibulins that can form their own network. Other important interactions are those with cell surface receptors such as integrins, heparan sulphfate proteoglycans, hyaluronan receptors and others. Many of the molecules with an ability to interact with these receptors can also bind to molecules in the matrix and provide a bridge from the matrix to the cell and induce various responses. In pathology, there is an imbalance in matrix turnover with often excessive proteolytic breakdown. This results in the formation of protein fragments, where cleavage provides information on the active enzyme. Those

  16. Semiconductor Quantum Rods as Single Molecule FluorescentBiological Labels

    SciTech Connect

    Fu, Aihua; Gu, Weiwei; Boussert, Benjamine; Koski, Kristie; Gerion, Daniele; Manna, Liberato; Le Gros, Mark; Larabell, Carolyn; Alivisatos, A. Paul

    2006-05-29

    In recent years, semiconductor quantum dots have beenapplied with great advantage in a wide range of biological imagingapplications. The continuing developments in the synthesis of nanoscalematerials and specifically in the area of colloidal semiconductornanocrystals have created an opportunity to generate a next generation ofbiological labels with complementary or in some cases enhanced propertiescompared to colloidal quantum dots. In this paper, we report thedevelopment of rod shaped semiconductor nanocrystals (quantum rods) asnew fluorescent biological labels. We have engineered biocompatiblequantum rods by surface silanization and have applied them fornon-specific cell tracking as well as specific cellular targeting. Theproperties of quantum rods as demonstrated here are enhanced sensitivityand greater resistance for degradation as compared to quantum dots.Quantum rods have many potential applications as biological labels insituations where their properties offer advantages over quantumdots.

  17. Biological Molecules for the Regeneration of the Pulp-Dentin Complex.

    PubMed

    Kim, Sahng G

    2017-01-01

    Regenerative endodontic treatment has yielded excellent clinical outcomes, but only several animal studies have shown the robust regeneration of the pulp-dentin complex. The biological molecules, if properly delivered, can enkindle regeneration of dental pulp and dentin rather than repair with tissues of periodontal origin. This review details the biological significance of regenerating the pulp-dentin complex, the effects of biological cues in pulp regeneration, and the delivery strategies of biological molecules to enhance the outcomes of regenerative endodontic therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Experimental and computational characterization of biological liquid crystals: a review of single-molecule bioassays.

    PubMed

    Eom, Kilho; Yang, Jaemoon; Park, Jinsung; Yoon, Gwonchan; Soo Sohn, Young; Park, Shinsuk; Yoon, Dae Sung; Na, Sungsoo; Kwon, Taeyun

    2009-09-10

    Quantitative understanding of the mechanical behavior of biological liquid crystals such as proteins is essential for gaining insight into their biological functions, since some proteins perform notable mechanical functions. Recently, single-molecule experiments have allowed not only the quantitative characterization of the mechanical behavior of proteins such as protein unfolding mechanics, but also the exploration of the free energy landscape for protein folding. In this work, we have reviewed the current state-of-art in single-molecule bioassays that enable quantitative studies on protein unfolding mechanics and/or various molecular interactions. Specifically, single-molecule pulling experiments based on atomic force microscopy (AFM) have been overviewed. In addition, the computational simulations on single-molecule pulling experiments have been reviewed. We have also reviewed the AFM cantilever-based bioassay that provides insight into various molecular interactions. Our review highlights the AFM-based single-molecule bioassay for quantitative characterization of biological liquid crystals such as proteins.

  19. Acquisition of a Circular Dichroism Spectrometer to Study Biological Molecules at Interfaces

    DTIC Science & Technology

    2016-02-10

    02-2016 15-Jul-2014 14-Jan-2016 Final Report: Acquisition of a Circular Dichroism Spectrometer to Study Biological Molecules at Interfaces The views...Circular Dichroism Spectrometer to Study Biological Molecules at Interfaces Report Title We have made substantial progress in the design, implementation, and...1 Grant Information Award Number W911NF-14-1-0413 Title of Research Acquisition of a Circular Dichroism (CD) Spectrometer to Study

  20. Detection of biological molecules using chemical amplification and optical sensors

    SciTech Connect

    Antwerp, W.P. van; Mastrototaro, J.J.

    2000-01-04

    Methods are provided for the determination of the concentration of biological levels of polyhydroxylated compounds, particularly glucose. The methods utilize an amplification system that is an analyte transducer immobilized in a polymeric matrix, where the system is implantable and biocompatible. Upon interrogation by an optical system, the amplification system produces a signal capable of detection external to the skin of the patient. Quantitation of the analyte of interest is achieved by measurement of the emitted signal.

  1. Detection of biological molecules using chemical amplification and optical sensors

    DOEpatents

    Van Antwerp, William Peter; Mastrototaro, John Joseph

    2004-10-12

    Methods are provided for the determination of the concentration of biological levels of polyhydroxylated compounds, particularly glucose. The methods utilize an amplification system that is an analyte transducer immobilized in a polymeric matrix, where the system is implantable and biocompatible. Upon interrogation by an optical system, the amplification system produces a signal capable of detection external to the skin of the patient. Quantitation of the analyte of interest is achieved by measurement of the emitted signal.

  2. Detection of biological molecules using chemical amplification and optical sensors

    DOEpatents

    Van Antwerp, William Peter; Mastrototaro, John Joseph

    2000-01-01

    Methods are provided for the determination of the concentration of biological levels of polyhydroxylated compounds, particularly glucose. The methods utilize an amplification system that is an analyte transducer immobilized in a polymeric matrix, where the system is implantable and biocompatible. Upon interrogation by an optical system, the amplification system produces a signal capable of detection external to the skin of the patient. Quantitation of the analyte of interest is achieved by measurement of the emitted signal.

  3. Chemokines as effector and target molecules in vascular biology.

    PubMed

    Sozzani, Silvano; Del Prete, Annalisa; Bonecchi, Raffaella; Locati, Massimo

    2015-08-01

    Chemokines are key mediators of inflammation. In pathological tissues, the main roles of chemokines are to regulate leucocyte accumulation through the activation of oriented cell migration and the activation of limited programs of gene transcription. Through these activities, chemokines exert many crucial functions, including the regulation of angiogenesis. The 'chemokine system' is tightly regulated at several levels, such as the post-transcriptional processing of ligands, the regulation of the expression and function of the receptors and through the expression of molecules known as 'atypical chemokine receptors', proteins that function as chemokine scavenging and presenting molecules. Several experimental evidence obtained in vitro, in animal models and in human studies, has defined a crucial role of chemokines in cardiovascular diseases. An intense area of research is currently exploring the possibility to develop new effective therapeutic strategies through the identification of chemokine receptor antagonists. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

  4. Insights into adhesion biology using single-molecule localization microscopy.

    PubMed

    Tabarin, Thibault; Pageon, Sophie V; Bach, Cuc T T; Lu, Yong; O'Neill, Geraldine M; Gooding, J Justin; Gaus, Katharina

    2014-03-17

    Focal adhesions are complex multi-protein structures that mediate cell adhesion and cell migration in multicellular organisms. Most of the protein components involved in focal adhesion formation have been identified, but a major challenge remains: determination of the spatial and temporal dynamics of adhesion proteins in order to understand the molecular mechanisms of adhesion assembly, maturation, signal regulation, and disassembly. Progress in this field has been hampered by the limited resolution of fluorescence microscopy. Recent advances have led to the development of super-resolution techniques including single-molecule localization microscopy (SMLM). Here, we discuss how the application of these techniques has revealed important new insights into focal adhesion structure and dynamics, including the first description of the three-dimensional nano-architecture of focal adhesions and of the dynamic exchange of integrins in focal adhesions. Hence, SMLM has contributed to the refinement of existing models of adhesions as well as the establishment of novel models, thereby opening new research directions. With current improvements in SMLM instrumentation and analysis, it has become possible to study cellular adhesions at the single-molecule level. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Challenges of general safety evaluations of biologics compared to small molecule pharmaceuticals in animal models.

    PubMed

    Dixit, Rakesh; Iciek, Laurie A; McKeever, Kathleen; Ryan, Patricia Clare

    2010-01-01

    The prediction of human toxicity by employing animal models for nonclinical safety evaluation of pharmaceuticals poses numerous challenges. Each type, biologics, vaccines and small molecules, has unique features, which may impact the ability to effectively assess safety. The importance of taking a case-by-case approach is highlighted in this review of the challenges encountered in general safety evaluations for biologics and vaccines compared to small molecules. The reader will gain insights in specific issues related to building a successful predictive nonclinical safety program for biologics. While there is fair concordance for small molecules, animal models used for the safety evaluation of biologics may have limitations with regard to human relevance. For small molecules, this is commonly because of differences in metabolism profiles or off-target effects. For biologics, which are highly targeted molecules, it may be because of differences in physiological processes or biologic pathways that limit pharmacologic relevance. For vaccines or immunomodulatory biologics, it may be related to the complexities of modeling the human immune system in a nonhuman species. While international guidances are available to govern the nonclinical safety assessment process for human pharmaceuticals (such as ICH M3), in many instances a case-by-case approach is employed for novel agents.

  6. SINGLE MOLECULE APPROACHES TO BIOLOGY, 2010 GORDON RESEARCH CONFERENCE, JUNE 27-JULY 2, 2010, ITALY

    SciTech Connect

    Professor William Moerner

    2010-07-09

    The 2010 Gordon Conference on Single-Molecule Approaches to Biology focuses on cutting-edge research in single-molecule science. Tremendous technical developments have made it possible to detect, identify, track, and manipulate single biomolecules in an ambient environment or even in a live cell. Single-molecule approaches have changed the way many biological problems are addressed, and new knowledge derived from these approaches continues to emerge. The ability of single-molecule approaches to avoid ensemble averaging and to capture transient intermediates and heterogeneous behavior renders them particularly powerful in elucidating mechanisms of biomolecular machines: what they do, how they work individually, how they work together, and finally, how they work inside live cells. The burgeoning use of single-molecule methods to elucidate biological problems is a highly multidisciplinary pursuit, involving both force- and fluorescence-based methods, the most up-to-date advances in microscopy, innovative biological and chemical approaches, and nanotechnology tools. This conference seeks to bring together top experts in molecular and cell biology with innovators in the measurement and manipulation of single molecules, and will provide opportunities for junior scientists and graduate students to present their work in poster format and to exchange ideas with leaders in the field. A number of excellent poster presenters will be selected for short oral talks. Topics as diverse as single-molecule sequencing, DNA/RNA/protein interactions, folding machines, cellular biophysics, synthetic biology and bioengineering, force spectroscopy, new method developments, superresolution imaging in cells, and novel probes for single-molecule imaging will be on the program. Additionally, the collegial atmosphere of this Conference, with programmed discussion sessions as well as opportunities for informal gatherings in the afternoons and evenings in the beauty of the Il Ciocco site in

  7. Spatial Simulations in Systems Biology: From Molecules to Cells

    PubMed Central

    Klann, Michael; Koeppl, Heinz

    2012-01-01

    Cells are highly organized objects containing millions of molecules. Each biomolecule has a specific shape in order to interact with others in the complex machinery. Spatial dynamics emerge in this system on length and time scales which can not yet be modeled with full atomic detail. This review gives an overview of methods which can be used to simulate the complete cell at least with molecular detail, especially Brownian dynamics simulations. Such simulations require correct implementation of the diffusion-controlled reaction scheme occurring on this level. Implementations and applications of spatial simulations are presented, and finally it is discussed how the atomic level can be included for instance in multi-scale simulation methods. PMID:22837728

  8. Spatial simulations in systems biology: from molecules to cells.

    PubMed

    Klann, Michael; Koeppl, Heinz

    2012-01-01

    Cells are highly organized objects containing millions of molecules. Each biomolecule has a specific shape in order to interact with others in the complex machinery. Spatial dynamics emerge in this system on length and time scales which can not yet be modeled with full atomic detail. This review gives an overview of methods which can be used to simulate the complete cell at least with molecular detail, especially Brownian dynamics simulations. Such simulations require correct implementation of the diffusion-controlled reaction scheme occurring on this level. Implementations and applications of spatial simulations are presented, and finally it is discussed how the atomic level can be included for instance in multi-scale simulation methods.

  9. Detection of biological molecules using chemical amplification and optical sensors

    DOEpatents

    Van Antwerp, William Peter; Mastrototaro, John Joseph

    2001-01-01

    Methods are provided for the determination of the concentration of biological levels of polyhydroxylated compounds, particularly glucose. The methods utilize an amplification system that is an analyte transducer immobilized in a polymeric matrix, where the system is implantable and biocompatible. Upon interrogation by an optical system, the amplification system produces a signal capable of detection external to the skin of the patient. Quantitation of the analyte of interest is achieved by measurement of the emitted signal. Specifically, the analyte transducer immobilized in a polymeric matrix can be a boronic acid moiety.

  10. Electrochemically etched nanoporous silicon membrane for separation of biological molecules in mixture

    NASA Astrophysics Data System (ADS)

    Burham, Norhafizah; Azlan Hamzah, Azrul; Yunas, Jumril; Yeop Majlis, Burhanuddin

    2017-07-01

    This paper presents a technique for separating biological molecules in mixture using nanoporous silicon membrane. Nanopores were formed using electrochemical etching process (ECE) by etching a prefabricated silicon membrane in hydrofluoric acid (HF) and ethanol, and then directly bonding it with PDMS to form a complete filtration system for separating biological molecules. Tygon S3™ tubings were used as fluid interconnection between PDMS molds and silicon membrane during testing. Electrochemical etching parameters were manipulated to control pore structure and size. In this work, nanopores with sizes of less than 50 nm, embedded on top of columnar structures have been fabricated using high current densities and variable HF concentrations. Zinc oxide was diluted with deionized (DI) water and mixed with biological molecules and non-biological particles, namely protein standard, serum albumin and sodium chloride. Zinc oxide particles were trapped on the nanoporous silicon surface, while biological molecules of sizes up to 12 nm penetrated the nanoporous silicon membrane. The filtered particles were inspected using a Zetasizer Nano SP for particle size measurement and count. The Zetasizer Nano SP results revealed that more than 95% of the biological molecules in the mixture were filtered out by the nanoporous silicon membrane. The nanoporous silicon membrane fabricated in this work is integratable into bio-MEMS and Lab-on-Chip components to separate two or more types of biomolecules at once. The membrane is especially useful for the development of artificial kidney.

  11. Modal reduction of mathematical models of biological molecules

    SciTech Connect

    Li Aiqin . E-mail: aiqin.li@duke.edu; Dowell, Earl H. . E-mail: dowell@ee.duke.edu

    2006-01-01

    This paper reports a detailed study of modal reduction based on either linear normal mode (LNM) analysis or proper orthogonal decomposition (POD) for modeling a single {alpha}-D-glucopyranose monomer as well as a chain of monomers attached to a moving atomic force microscope (AFM) under harmonic excitations. Also a modal reduction method combining POD and component modal synthesis is developed. The accuracy and efficiency of these methods are reported. The focus of this study is to determine to what extent these methods can reduce the time and cost of molecular modeling and simultaneously provide the required accuracy. It has been demonstrated that a linear reduced order model is valid for small amplitude excitation and low frequency excitation. It is found that a nonlinear reduced order model based on POD modes provides a good approximation even for large excitation while the nonlinear reduced order model using linear eigenmodes as the basis vectors is less effective for modeling molecules with a strong nonlinearity. The reduced order model based on component modal synthesis using POD modes for each component also gives a good approximation. With the reduction in the dimension of the system using these methods the computational time and cost can be reduced significantly.

  12. Cellular and System Biology of Memory: Timing, Molecules, and Beyond.

    PubMed

    Korte, Martin; Schmitz, Dietmar

    2016-04-01

    The storage of information in the mammalian nervous systems is dependent on a delicate balance between change and stability of neuronal networks. The induction and maintenance of processes that lead to changes in synaptic strength to a multistep process which can lead to long-lasting changes, which starts and ends with a highly choreographed and perfectly timed dance of molecules in different cell types of the central nervous system. This is accompanied by synchronization of specific networks, resulting in the generation of characteristic "macroscopic" rhythmic electrical fields, whose characteristic frequencies correspond to certain activity and information-processing states of the brain. Molecular events and macroscopic fields influence each other reciprocally. We review here cellular processes of synaptic plasticity, particularly functional and structural changes, and focus on timing events that are important for the initial memory acquisition, as well as mechanisms of short- and long-term memory storage. Then, we cover the importance of epigenetic events on the long-time range. Furthermore, we consider how brain rhythms at the network level participate in processes of information storage and by what means they participating in it. Finally, we examine memory consolidation at the system level during processes of sleep.

  13. Uncovering the basis for nonideal behavior of biological molecules.

    PubMed

    Rösgen, Jörg; Pettitt, Bernard Montgomery; Bolen, David Wayne

    2004-11-16

    The molecular origin of the nonideal behavior for concentrated binary solutions of biochemical compounds is examined. The difference between activities expressed in the molar and molal conventions can be large. Considering the range from dilute to concentrated, we show that molar activity coefficients can be represented by simple but rigorous equations involving between one and three parameters only. We derive a universal relationship interconverting the scales of molarity and molality without requiring the density of the solution. The equations are developed from first principles using a statistical thermodynamic theory of molar activity coefficients. It is shown how to express activity coefficients in different concentration scales, and the advantages and disadvantages of using certain scales are discussed and compared with the experimental data. Several classes of biochemically relevant compounds, many of which are naturally occurring osmolytes, are discussed: six saccharides (glucose, xylose, maltose, mannose, raffinose, and sucrose), four polyols (glycerol, mannitol, erythritol, and sorbitol), five amino acids (glycine, alanine, sarcosine, glycine betaine, and proline), and urea. Of the 16 solutes, 10 could be described in terms of a single parameter that is due to pure first-order effects (packing, hydration, or space limitation). The remaining six exhibit significant second-order effects (solute-solute interactions) and require two additional parameters, one typically identified with the volume occupied per solute molecule in the pure solute (crystal or liquid) and the other with a self-association constant. The activity coefficients of the osmolytes roughly display the rank order found with respect to their ability to stabilize proteins. These findings are discussed in terms of the physical principles that give rise to the activity coefficients.

  14. Surface functionalization of bioactive glasses with natural molecules of biological significance, Part I: Gallic acid as model molecule

    NASA Astrophysics Data System (ADS)

    Zhang, Xin; Ferraris, Sara; Prenesti, Enrico; Verné, Enrica

    2013-12-01

    Gallic acid (3,4,5-trihydroxybenzoic acid, GA) and its derivatives are a group of biomolecules (polyphenols) obtained from plants. They have effects which are potentially beneficial to heath, for example they are antioxidant, anticarcinogenic and antibacterial, as recently investigated in many fields such as medicine, food and plant sciences. The main drawbacks of these molecules are both low stability and bioavailability. In this research work the opportunity to graft GA to bioactive glasses is investigated, in order to deliver the undamaged biological molecule into the body, using the biomaterial surfaces as a localized carrier. GA was considered for functionalization since it is a good model molecule for polyphenols and presents several interesting biological activities, like antibacterial, antioxidant and anticarcinogenic properties. Two different silica based bioactive glasses (SCNA and CEL2), with different reactivity, were employed as substrates. UV photometry combined with the Folin&Ciocalteu reagent was adopted to test the concentration of GA in uptake solution after functionalization. This test verified how much GA consumption occurred with surface modification and it was also used on solid samples to test the presence of GA on functionalized glasses. XPS and SEM-EDS techniques were employed to characterize the modification of material surface properties and functional group composition before and after functionalization.

  15. Surface and biological activity of sophorolipid molecules produced by Wickerhamiella domercqiae var. sophorolipid CGMCC 1576.

    PubMed

    Ma, Xiaojing; Li, Hui; Song, Xin

    2012-06-15

    This work investigated the surface and biological activity of lactonic and acidic sophorolipid (SL) molecules differing in the acetylation degree of sophorose, carbon chain length and unsaturation degree of the fatty acid moiety. Six different SL molecules were prepared from crude SLs produced by Wickerhamiella domercqiae var. sophorolipid CGMCC 1576. The structures of the selected SL molecules were elucidated by MS and GC/MS. The surface properties of SLs including critical micelle concentration (CMC), minimum surface tension (Min. S.T.) and emulsification capacity to hydrocarbon and vegetable oils were studied, and the results demonstrated that SL molecules with different structures exhibited quite different surface properties. Cytotoxicities of different SL molecules to Chang liver cells determined by the MTT (3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide) method showed the effect of chemical structure of the SLs on their biological activities. Biodegradability of these SL molecules was tested using the river-water die-away method. The differences of surface and biological activity in different SL molecules will be of benefit for the applications of these SLs in specific fields such as the detergent, petroleum, pharmaceutical and environment industries. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Connecting synthetic chemistry decisions to cell and genome biology using small-molecule phenotypic profiling

    PubMed Central

    Wagner, Bridget K.; Clemons, Paul A.

    2009-01-01

    Discovering small-molecule modulators for thousands of gene products requires multiple stages of biological testing, specificity evaluation, and chemical optimization. Many cellular profiling methods, including cellular sensitivity, gene-expression, and cellular imaging, have emerged as methods to assess the functional consequences of biological perturbations. Cellular profiling methods applied to small-molecule science provide opportunities to use complex phenotypic information to prioritize and optimize small-molecule structures simultaneously against multiple biological endpoints. As throughput increases and cost decreases for such technologies, we see an emerging paradigm of using more information earlier in probe- and drug-discovery efforts. Moreover, increasing access to public datasets makes possible the construction of “virtual” profiles of small-molecule performance, even when multiplexed measurements were not performed or when multidimensional profiling was not the original intent. We review some key conceptual advances in small-molecule phenotypic profiling, emphasizing connections to other information, such as protein-binding measurements, genetic perturbations, and cell states. We argue that to maximally leverage these measurements in probe and drug discovery requires a fundamental connection to synthetic chemistry, allowing the consequences of synthetic decisions to be described in terms of changes in small-molecule profiles. Mining such data in the context of chemical structure and synthesis strategies can inform decisions about chemistry procurement and library development, leading to optimal small-molecule screening collections. PMID:19825513

  17. Target deconvolution of bioactive small molecules: the heart of chemical biology and drug discovery.

    PubMed

    Jung, Hye Jin; Kwon, Ho Jeong

    2015-09-01

    Identification of the target proteins of bioactive small molecules isolated from phenotypic screens plays an important role in chemical biology and drug discovery. However, discovering the targets of small molecules is often the most challenging and time-consuming step for chemical biology researchers. To overcome the bottlenecks in target identification, many new approaches based on genomics, proteomics, and bioinformatics technologies have been developed. Here, we provide an overview of the current major methodologies for target deconvolution of bioactive small molecules. To obtain an integrated view of the mechanisms of action of small molecules, we propose a systematic approach that involves the combination of multi-omics-based target identification and validation and preclinical target validation.

  18. From physics to biology: A journey through science accompanying the hydrogen bond and the water molecule

    NASA Astrophysics Data System (ADS)

    Maréchal, Y.

    2008-05-01

    The ubiquity of the hydrogen bond in many various scientific domains comes for a great part from its fundamental geometrical, thermodynamical and dynamical properties, but also owes much to the existence of such an exceptional molecule as the water molecule H 2O. Illustrative examples of up to date problems that are picked in various different scientific fields that extend from physics to biology and strongly involve H-bonds and/or the water molecule are examined. They hopefully show that if science is to propose solutions to newly arising problems humanity has to face, it absolutely needs knowing more about the subtle properties of hydrogen bonds and the often ignored crucial roles of water molecules. The interest of teaching more than is up to now done hydrogen bonds in university courses of physics, chemistry or molecular biology is stressed as a conclusion.

  19. A method to label biological molecules with dsDNA coated gold nanoparticles.

    PubMed

    Xing, Ming; Li, Fangliang; Dong, Yingshan; Yu, Zhenxiang; Chen, Xia

    2015-03-01

    We described a new method to label biological molecules using gold nanoparticles (GNPs) and double stranded DNA. Researchers can conveniently label their own samples with GNPs using this method. The label is based on dsDNA with a 93.5% coverage of GNPs (dsDNA:GNP = 303:1). Antigens, streptavidin and biotin were labeled on GNPs and the success of the method was investigated with agarose gel electrophoresis, laser particle size analysis and ultraviolet spectrophotometry. These analyses confirmed that biological molecules were successfully bound to the GNPs. These molecules retained their biological activity and were able to detect targets on PVDF and NC membranes with excellent selectivity and low levels of background. Modified GNPs were also able to detect targets on nylon membranes, but with some degree of false positives. The maximum limit of detection was 25 ng proteins.

  20. Interrogating Biology with Force: Single Molecule High-Resolution Measurements with Optical Tweezers

    PubMed Central

    Capitanio, Marco; Pavone, Francesco S.

    2013-01-01

    Single molecule force spectroscopy methods, such as optical and magnetic tweezers and atomic force microscopy, have opened up the possibility to study biological processes regulated by force, dynamics of structural conformations of proteins and nucleic acids, and load-dependent kinetics of molecular interactions. Among the various tools available today, optical tweezers have recently seen great progress in terms of spatial resolution, which now allows the measurement of atomic-scale conformational changes, and temporal resolution, which has reached the limit of the microsecond-scale relaxation times of biological molecules bound to a force probe. Here, we review different strategies and experimental configurations recently developed to apply and measure force using optical tweezers. We present the latest progress that has pushed optical tweezers’ spatial and temporal resolution down to today’s values, discussing the experimental variables and constraints that are influencing measurement resolution and how these can be optimized depending on the biological molecule under study. PMID:24047980

  1. Group-10 metal complexes of biological molecules and related ligands: structural and functional properties.

    PubMed

    Shimazaki, Yuichi; Yamauchi, Osamu

    2012-09-01

    The complexes of group-10 metals, Ni, Pd, and Pt, with biological molecules and related ligands have been attracting increasing attention in recent years due to their reactivities and functions, such as catalysts and drugs, and their biological relevance. The well-defined structures and kinetic inertness especially of Pt complexes have been used as the sites for weak interactions with other molecules. The Ni complexes have been reported as models not only for Ni enzymes but also for other metalloenzyme active sites for deeper understanding of the reactivities such as oxygen activations and detailed electronic structures. Pd Complexes are widely known for their catalytic activities in conversions of various organic molecules including useful biological molecules, such as Suzuki-Miyaura cross-coupling, while Pt complexes have been intensively studied for their antitumor activities. We focus in this review on our recent results on weak interactions and reactivities of the group-10 metal complexes with biological molecules and related compounds, and discuss their structural features and some new properties pointing to functional possibilities. Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.

  2. Experimental approaches for addressing fundamental biological questions in living, functioning cells with single molecule precision.

    PubMed

    Lenn, Tchern; Leake, Mark C

    2012-06-01

    In recent years, single molecule experimentation has allowed researchers to observe biological processes at the sensitivity level of single molecules in actual functioning, living cells, thereby allowing us to observe the molecular basis of the key mechanistic processes in question in a very direct way, rather than inferring these from ensemble average data gained from traditional molecular and biochemical techniques. In this short review, we demonstrate the impact that the application of single molecule bioscience experimentation has had on our understanding of various cellular systems and processes, and the potential that this approach has for the future to really address very challenging and fundamental questions in the life sciences.

  3. The evolving biology of small molecules: controlling cell fate and identity.

    PubMed

    Efe, Jem A; Ding, Sheng

    2011-08-12

    Small molecules have been playing important roles in elucidating basic biology and treatment of a vast number of diseases for nearly a century, making their use in the field of stem cell biology a comparatively recent phenomenon. Nonetheless, the power of biology-oriented chemical design and synthesis, coupled with significant advances in screening technology, has enabled the discovery of a growing number of small molecules that have improved our understanding of stem cell biology and allowed us to manipulate stem cells in unprecedented ways. This review focuses on recent small molecule studies of (i) the key pathways governing stem cell homeostasis, (ii) the pluripotent stem cell niche, (iii) the directed differentiation of stem cells, (iv) the biology of adult stem cells, and (v) somatic cell reprogramming. In a very short period of time, small molecules have defined a perhaps universally attainable naive ground state of pluripotency, and are facilitating the precise, rapid and efficient differentiation of stem cells into somatic cell populations relevant to the clinic. Finally, following the publication of numerous groundbreaking studies at a pace and consistency unusual for a young field, we are closer than ever to completely eliminating the need for genetic modification in reprogramming.

  4. Reverse pharmacognosy: identifying biological properties for plants by means of their molecule constituents: application to meranzin.

    PubMed

    Do, Quoc-Tuan; Lamy, Cécile; Renimel, Isabelle; Sauvan, Nancy; André, Patrice; Himbert, Franck; Morin-Allory, Luc; Bernard, Philippe

    2007-10-01

    Reverse pharmacognosy aims at finding biological targets for natural compounds by virtual or real screening and identifying natural resources that contain the active molecules. We report herein a study focused on the identification of biological properties of meranzin, a major component isolated from Limnocitrus littoralis (Miq.) Swingle. Selnergy, an IN SILICO biological profiling software, was used to identify putative binding targets of meranzin. Among the 400 screened proteins, 3 targets were selected: COX1, COX2 and PPARgamma. Binding tests were realised for these 3 protein candidates, as well as two negative controls. The predictions made by Selnergy were consistent with the experimental results, meaning that these 3 targets can be modulated by an extract containing this compound in a suitable concentration. These results demonstrate that reverse pharmacognosy and its inverse docking component is a powerful tool to identify biological properties for natural molecules and hence for plants containing these compounds.

  5. Evidence for formation of multi-quantum dots in hydrogenated graphene

    PubMed Central

    2012-01-01

    We report the experimental evidence for the formation of multi-quantum dots in a hydrogenated single-layer graphene flake. The existence of multi-quantum dots is supported by the low-temperature measurements on a field effect transistor structure device. The resulting Coulomb blockade diamonds shown in the color scale plot together with the number of Coulomb peaks exhibit the characteristics of the so-called ‘stochastic Coulomb blockade’. A possible explanation for the formation of the multi-quantum dots, which is not observed in pristine graphene to date, was attributed to the impurities and defects unintentionally decorated on a single-layer graphene flake which was not treated with the thermal annealing process. Graphene multi-quantum dots developed around impurities and defect sites during the hydrogen plasma exposure process. PMID:22898058

  6. Experimental and Computational Characterization of Biological Liquid Crystals: A Review of Single-Molecule Bioassays

    PubMed Central

    Eom, Kilho; Yang, Jaemoon; Park, Jinsung; Yoon, Gwonchan; Soo Sohn, Young; Park, Shinsuk; Yoon, Dae Sung; Na, Sungsoo; Kwon, Taeyun

    2009-01-01

    Quantitative understanding of the mechanical behavior of biological liquid crystals such as proteins is essential for gaining insight into their biological functions, since some proteins perform notable mechanical functions. Recently, single-molecule experiments have allowed not only the quantitative characterization of the mechanical behavior of proteins such as protein unfolding mechanics, but also the exploration of the free energy landscape for protein folding. In this work, we have reviewed the current state-of-art in single-molecule bioassays that enable quantitative studies on protein unfolding mechanics and/or various molecular interactions. Specifically, single-molecule pulling experiments based on atomic force microscopy (AFM) have been overviewed. In addition, the computational simulations on single-molecule pulling experiments have been reviewed. We have also reviewed the AFM cantilever-based bioassay that provides insight into various molecular interactions. Our review highlights the AFM-based single-molecule bioassay for quantitative characterization of biological liquid crystals such as proteins. PMID:19865530

  7. A semantic web ontology for small molecules and their biological targets.

    PubMed

    Choi, Jooyoung; Davis, Melissa J; Newman, Andrew F; Ragan, Mark A

    2010-05-24

    A wide range of data on sequences, structures, pathways, and networks of genes and gene products is available for hypothesis testing and discovery in biological and biomedical research. However, data describing the physical, chemical, and biological properties of small molecules have not been well-integrated with these resources. Semantically rich representations of chemical data, combined with Semantic Web technologies, have the potential to enable the integration of small molecule and biomolecular data resources, expanding the scope and power of biomedical and pharmacological research. We employed the Semantic Web technologies Resource Description Framework (RDF) and Web Ontology Language (OWL) to generate a Small Molecule Ontology (SMO) that represents concepts and provides unique identifiers for biologically relevant properties of small molecules and their interactions with biomolecules, such as proteins. We instanced SMO using data from three public data sources, i.e., DrugBank, PubChem and UniProt, and converted to RDF triples. Evaluation of SMO by use of predetermined competency questions implemented as SPARQL queries demonstrated that data from chemical and biomolecular data sources were effectively represented and that useful knowledge can be extracted. These results illustrate the potential of Semantic Web technologies in chemical, biological, and pharmacological research and in drug discovery.

  8. Unintended consequences? Water molecules at biological and crystallographic protein-protein interfaces.

    PubMed

    Ahmed, Mostafa H; Habtemariam, Mesay; Safo, Martin K; Scarsdale, J Neel; Spyrakis, Francesca; Cozzini, Pietro; Mozzarelli, Andrea; Kellogg, Glen E

    2013-12-01

    The importance of protein-protein interactions (PPIs) is becoming increasingly appreciated, as these interactions lie at the core of virtually every biological process. Small molecule modulators that target PPIs are under exploration as new therapies. One of the greatest obstacles faced in crystallographically determining the 3D structures of proteins is coaxing the proteins to form "artificial" PPIs that lead to uniform crystals suitable for X-ray diffraction. This work compares interactions formed naturally, i.e., "biological", with those artificially formed under crystallization conditions or "non-biological". In particular, a detailed analysis of water molecules at the interfaces of high-resolution (≤2.30 Å) X-ray crystal structures of protein-protein complexes, where 140 are biological protein-protein complex structures and 112 include non-biological protein-protein interfaces, was carried out using modeling tools based on the HINT forcefield. Surprisingly few and relatively subtle differences were observed between the two types of interfaces: (i) non-biological interfaces are more polar than biological interfaces, yet there is better organized hydrogen bonding at the latter; (ii) biological associations rely more on water-mediated interactions with backbone atoms compared to non-biological associations; (iii) aromatic/planar residues play a larger role in biological associations with respect to water, and (iv) Lys has a particularly large role at non-biological interfaces. A support vector machines (SVMs) classifier using descriptors from this study was devised that was able to correctly classify 84% of the two interface types. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. SERS of whole-cell bacteria and trace levels of biological molecules

    NASA Astrophysics Data System (ADS)

    Guzelian, Andrew A.; Sylvia, James M.; Janni, James A.; Clauson, Susan L.; Spencer, Kevin M.

    2002-02-01

    Through its several orders of magnitude signal enhancement over normal Raman, surface-enhanced Raman spectroscopy (SERS) provides an opportunity to extend the benefits of vibrational spectroscopy to trace level detection. SERS in particular holds great potential for biological sensing due to the weak Raman bands of water and the reduction in fluorescence backgrounds from interactions of the analyte with the metal SERS substrate. This work examines the trace level detection of biological molecules and oligomers such as amino acids, peptides, and oligonucleotides as well as the detection of whole cell bacteria. The SERS substrates employed are electrochemically roughened gold. The biological molecules show well-resolved and intense bands that are an effective spectral signature; these bands also persist in corresponding oligomeric compounds. Spectra from whole cell bacteria have been obtained for several species, including gram-positive and gram-negative strains. Viable and nonviable cells have also been examined and significant spectral differences are observed. The results show the potential for using SERS as an analytical tool for the identification of biological molecules and microorganisms with applications in biological agent detection, food and water monitoring, and the search for signs of extraterrestrial life.

  10. Principles of Single-Molecule Manipulation and its Application in Biological Physics

    NASA Astrophysics Data System (ADS)

    Chen, Wei-Hung; Wilson, Jonathan D.; Wijeratne, Sithara S.; Southmayd, Sarah A.; Lin, Kuan-Jiuh; Kiang, Ching-Hwa

    Recent advances in nanoscale manipulation and piconewton force detection provide a unique tool for studying the mechanical and thermodynamic properties of biological molecules and complexes at the single-molecule level. Detailed equilibrium and dynamics information on proteins and DNA have been revealed by single-molecule manipulation and force detection techniques. The atomic force microscope (AFM) and optical tweezers have been widely used to quantify the intra- and inter-molecular interactions of many complex biomolecular systems. In this article, we describe the background, analysis, and applications of these novel techniques. Experimental procedures that can serve as a guide for setting up a single-molecule manipulation system using the AFM are also presented.

  11. Sensors and Biosensors for the Determination of Small Molecule Biological Toxins

    PubMed Central

    Wang, Xiang-Hong; Wang, Shuo

    2008-01-01

    The following review of sensors and biosensors focuses on the determination of commonly studied small molecule biological toxins, including mycotoxins and small molecule neurotoxins. Because of the high toxicity of small molecule toxins, an effective analysis technique for determining their toxicity is indispensable. Sensors and biosensors have emerged as sensitive and rapid techniques for toxicity analysis in the past decade. Several different sensors for the determination of mycotoxins and other small molecule neurotoxins have been reported in the literature, and many of these sensors such as tissue biosensors, enzyme sensors, optical immunosensors, electrochemical sensors, quartz crystal sensors, and surface plasmon resonance biosensors are reviewed in this paper. Sensors are a practical and convenient monitoring tool in the area of routine analysis, and their specificity, sensitivity, reproducibility and analysis stability should all be improved in future work. In addition, accuracy field portable sensing devices and multiplexing analysis devices will be important requirement for the future. PMID:27873857

  12. Suppression and enhancement of non-native molecules within biological systems

    NASA Astrophysics Data System (ADS)

    Jones, E. A.; Lockyer, N. P.; Vickerman, J. C.

    2006-07-01

    With the aim of evaluating the potential of SIMS to provide molecular information from small molecules within biological systems, here we investigate the effect of different biological compounds as they act as matrices. The results highlight the fact that the chemical environment of a molecule can have a significant effect on its limit of detection. This has implications for the imaging of drugs and xenobiotics in tissue sections and other biological matrices. A 1:1 mixture of the organic acid 2,4,6-trihydroxyacetophenone and the dipeptide valine-valine demonstrates that almost complete suppression of the [M + H] + ion of one compound can be caused by the presence of a compound of higher proton affinity. The significance of this is highlighted when two similar drug molecules, atropine (a neutral molecule) and ipratropium bromide (a quaternary nitrogen containing salt) are mixed with brain homogenate. The atropine [M + H] + ion shows significant suppression whilst the [M - Br] + of ipratopium bromide is detected at an intensity that can be rationalised by its decreased surface concentration. By investigating the effect of two abundant tissue lipids, cholesterol and dipalmitoylphosphatidyl choline (DPPC), on the atropine [M + H] + signal detected in mixtures with these lipids we see that the DPPC has a strong suppressing effect, which may be attributed to gas phase proton transfer.

  13. Multicomponent redox catalysts for reduction of large biological molecules using molecular hydrogen as the reductant

    SciTech Connect

    Chao, S.; Simon, R.A.; Mallouk, T.E.; Wrighton, M.S.

    1988-03-30

    One-electron reduction of the large biological molecules horse heart cytochrome c, sperm whale myoglobin, and horseradish peroxidase using H/sub 2/ as the reductant can be catalyzed by two-component, high surface area heterogeneous catalysts. The catalysts can be prepared by first functionalizing high surface area SiO/sub 2/ with a polycationic polymer into which is dispersed MCl/sub 4//sup 2 -/ (M = Pd, Pt). Reduction with H/sub 2/ yields elemental Pd or Pt dispersed in the polymer. The particles are finally functionalized with a redox polymer derived from hydrolysis of Si(OR)/sub 3/ groups of an N,N'-dialkyl-4,4'-bipyridinium- or from a cobalticenium-based monomer. The two components of the heterogeneous catalysts are the buried noble metal capable of activating the H/sub 2/ and the redox polymer, which can equilibrate both with the noble metal and with the large biological molecule. Reduction of the large biological molecules in aqueous solution can be effected at room temperature and 1 atm H/sub 2/ using the catalysts under conditions where the biological materials would not be reducible with H/sub 2/ alone or when the noble metal alone would be used as the catalyst.

  14. Modulation of Host Biology by Pseudomonas aeruginosa Quorum Sensing Signal Molecules: Messengers or Traitors

    PubMed Central

    Liu, Yi-Chia; Chan, Kok-Gan; Chang, Chien-Yi

    2015-01-01

    Bacterial cells sense their population density and respond accordingly by producing various signal molecules to the surrounding environments thereby trigger a plethora of gene expression. This regulatory pathway is termed quorum sensing (QS). Plenty of bacterial virulence factors are controlled by QS or QS-mediated regulatory systems and QS signal molecules (QSSMs) play crucial roles in bacterial signaling transduction. Moreover, bacterial QSSMs were shown to interfere with host cell signaling and modulate host immune responses. QSSMs not only regulate the expression of bacterial virulence factors but themselves act in the modulation of host biology that can be potential therapeutic targets. PMID:26617576

  15. Modulation of Host Biology by Pseudomonas aeruginosa Quorum Sensing Signal Molecules: Messengers or Traitors.

    PubMed

    Liu, Yi-Chia; Chan, Kok-Gan; Chang, Chien-Yi

    2015-01-01

    Bacterial cells sense their population density and respond accordingly by producing various signal molecules to the surrounding environments thereby trigger a plethora of gene expression. This regulatory pathway is termed quorum sensing (QS). Plenty of bacterial virulence factors are controlled by QS or QS-mediated regulatory systems and QS signal molecules (QSSMs) play crucial roles in bacterial signaling transduction. Moreover, bacterial QSSMs were shown to interfere with host cell signaling and modulate host immune responses. QSSMs not only regulate the expression of bacterial virulence factors but themselves act in the modulation of host biology that can be potential therapeutic targets.

  16. Single-molecule FRET and crosslinking studies in structural biology enabled by noncanonical amino acids.

    PubMed

    Tyagi, Swati; Lemke, Edward A

    2015-06-01

    Contemporary structural biology research promises more than just static snap-shots of molecular machineries. This goal is not just facilitated by combining different structural biology techniques, but also by new tools from the field of protein and genetic engineering, as well as from chemistry. Genetic encoding of noncanonical amino acids (ncAAs) through codon-suppression technology provides an excellent opportunity to probe biomolecules using different structural biology methods. In this article, we review the applications of ncAA incorporation into proteins for determining structural information through various techniques with the main focus on crosslinking mass spectrometry and single-molecule FRET-based techniques. Furthermore, advances and limitations of the incorporation of multiple ncAAs are discussed, with respect to design of an ideal host organism for modern and integrative structural biology research.

  17. Pragmatic turn in biology: From biological molecules to genetic content operators

    PubMed Central

    Witzany, Guenther

    2014-01-01

    Erwin Schrödinger‘s question “What is life?” received the answer for decades of “physics + chemistry”. The concepts of Alain Turing and John von Neumann introduced a third term: “information”. This led to the understanding of nucleic acid sequences as a natural code. Manfred Eigen adapted the concept of Hammings “sequence space”. Similar to Hilbert space, in which every ontological entity could be defined by an unequivocal point in a mathematical axiomatic system, in the abstract ”sequence space” concept each point represents a unique syntactic structure and the value of their separation represents their dissimilarity. In this concept molecular features of the genetic code evolve by means of self-organisation of matter. Biological selection determines the fittest types among varieties of replication errors of quasi-species. The quasi-species concept dominated evolution theory for many decades. In contrast to this, recent empirical data on the evolution of DNA and its forerunners, the RNA-world and viruses indicate cooperative agent-based interactions. Group behaviour of quasi-species consortia constitute de novo and arrange available genetic content for adaptational purposes within real-life contexts that determine epigenetic markings. This review focuses on some fundamental changes in biology, discarding its traditional status as a subdiscipline of physics and chemistry. PMID:25225596

  18. Pragmatic turn in biology: From biological molecules to genetic content operators.

    PubMed

    Witzany, Guenther

    2014-08-26

    Erwin Schrödinger's question "What is life?" received the answer for decades of "physics + chemistry". The concepts of Alain Turing and John von Neumann introduced a third term: "information". This led to the understanding of nucleic acid sequences as a natural code. Manfred Eigen adapted the concept of Hammings "sequence space". Similar to Hilbert space, in which every ontological entity could be defined by an unequivocal point in a mathematical axiomatic system, in the abstract "sequence space" concept each point represents a unique syntactic structure and the value of their separation represents their dissimilarity. In this concept molecular features of the genetic code evolve by means of self-organisation of matter. Biological selection determines the fittest types among varieties of replication errors of quasi-species. The quasi-species concept dominated evolution theory for many decades. In contrast to this, recent empirical data on the evolution of DNA and its forerunners, the RNA-world and viruses indicate cooperative agent-based interactions. Group behaviour of quasi-species consortia constitute de novo and arrange available genetic content for adaptational purposes within real-life contexts that determine epigenetic markings. This review focuses on some fundamental changes in biology, discarding its traditional status as a subdiscipline of physics and chemistry.

  19. Self-Assembled Fluorescent Nanoparticles from π-Conjugated Small Molecules: En Route to Biological Applications.

    PubMed

    Schill, Jurgen; Schenning, Albertus P H J; Brunsveld, Luc

    2015-07-01

    Since the development of supramolecular chemical biology, self-organised nano-architectures have been widely explored in a variety of biomedical applications. Functionalized synthetic molecules with the ability of non-covalent assembly in an aqueous environment are typically able to interact with biological systems and are therefore especially interesting for their use in theranostics. Nanostructures based on π-conjugated oligomers are particularly promising as theranostic platforms as they bear outstanding photophysical properties as well as drug loading capabilities. This Feature Article provides an overview on the recent advances in the self-assembly of intrinsically fluorescent nanoparticles from π-conjugated small molecules such as fluorene or perylene based chromophores for biomedical applications. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. The corrosion inhibition of iron and aluminum by various naturally occurring biological molecules

    SciTech Connect

    McCafferty, E.; Hansen, D.C.

    1995-12-31

    Biological polymers that exhibit a strong affinity for metal surfaces are increasingly becoming the focus of research toward the development of environmentally friendly corrosion inhibitors. This paper deals with the use of various naturally occurring organic molecules as corrosion inhibitors for iron or aluminum. Among the organic molecules considered are catecholate and hydroxamate siderophores isolated from bacteria, the adhesive protein from the blue mussel Mytilus edulis L, and caffeic acid and chlorogenic acid. FTIR analysis, anodic polarization curves, and AC impedance measurements were used to determine the adsorption and effectiveness of the various organic molecules as corrosion inhibitors. Parabactin, a catecholate siderophore, was effective in inhibiting both the corrosion of iron in hydrochloric acid and the pitting of aluminum in 0.1 M sodium chloride. The adhesive protein from the blue mussel was also effective in inhibiting the pitting of aluminum.

  1. Graphene as a transparent conductive support for studying biological molecules by transmission electron microscopy

    SciTech Connect

    Nair, R. R.; Anissimova, S.; Novoselov, K. S.; Blake, P.; Blake, J. R.; Geim, A. K.; Zan, R.; Bangert, U.; Golovanov, A. P.; Morozov, S. V.; Latychevskaia, T.

    2010-10-11

    We demonstrate the application of graphene as a support for imaging individual biological molecules in transmission electron microscope (TEM). A simple procedure to produce free-standing graphene membranes has been designed. Such membranes are extremely robust and can support practically any submicrometer object. Tobacco mosaic virus has been deposited on graphene samples and observed in a TEM. High contrast has been achieved even though no staining has been applied.

  2. Structure-property relationship of quinuclidinium surfactants--Towards multifunctional biologically active molecules.

    PubMed

    Skočibušić, Mirjana; Odžak, Renata; Štefanić, Zoran; Križić, Ivana; Krišto, Lucija; Jović, Ozren; Hrenar, Tomica; Primožič, Ines; Jurašin, Darija

    2016-04-01

    Motivated by diverse biological and pharmacological activity of quinuclidine and oxime compounds we have synthesized and characterized novel class of surfactants, 3-hydroxyimino quinuclidinium bromides with different alkyl chains lengths (CnQNOH; n=12, 14 and 16). The incorporation of non conventional hydroxyimino quinuclidinium headgroup and variation in alkyl chain length affects hydrophilic-hydrophobic balance of surfactant molecule and thereby physicochemical properties important for its application. Therefore, newly synthesized surfactants were characterized by the combination of different experimental techniques: X-ray analysis, potentiometry, electrical conductivity, surface tension and dynamic light scattering measurements, as well as antimicrobial susceptibility tests. Comprehensive investigation of CnQNOH surfactants enabled insight into structure-property relationship i.e., way in which the arrangement of surfactant molecules in the crystal phase correlates with their solution behavior and biologically activity. The synthesized CnQNOH surfactants exhibited high adsorption efficiency and relatively low critical micelle concentrations. In addition, all investigated compounds showed very potent and promising activity against Gram-positive and clinically relevant Gram-negative bacterial strains compared to conventional antimicrobial agents: tetracycline and gentamicin. The overall results indicate that bicyclic headgroup with oxime moiety, which affects both hydrophilicity and hydrophobicity of CnQNOH molecule in addition to enabling hydrogen bonding, has dominant effect on crystal packing and physicochemical properties. The unique structural features of cationic surfactants with hydroxyimino quinuclidine headgroup along with diverse biological activity have made them promising structures in novel drug discovery. Obtained fundamental understanding how combination of different functionalities in a single surfactant molecule affects its physicochemical

  3. Gold nanoparticle wire and integrated wire array for electronic detection of chemical and biological molecules

    DOE PAGES

    Diao, J. J.; Cao, Qing

    2011-03-30

    Nanoparticle wire and integrated nanoparticle wire array have been prepared through a green technique: discontinuous vertical evaporation-driven colloidal deposition. The conducting gold nanoparticle wire made by this technique shows ability for the sensitive electronic detection of chemical and biological molecules due to its high surface to volume ratio. In addition, we also demonstrate a potential usage of integrated gold nanoparticle wire array for the localized detection.

  4. In vivo diffusion MRS investigation of non-water molecules in biological tissues.

    PubMed

    Cao, Peng; Wu, Ed X

    2017-03-01

    Diffusion MRS of non-water molecules offers great potential in directly revealing various tissue microstructures and physiology at both cellular and subcellular levels. In brain, (1) H diffusion MRS has been demonstrated as a new tool for probing normal tissue microstructures and their pathological changes. In skeletal muscle, (1) H diffusion MRS could characterize slow and restricted intramyocellular lipid diffusion, providing a sensitive marker for metabolic alterations, while (31) P diffusion MRS can measure ATP and PCr diffusion, which may reflect the capacity of cellular energy transport, complementing the information from frequently used (31) P MRS in muscle. In intervertebral disk, (1) H diffusion MRS can directly monitor extracellular matrix integrity by quantifying the mobility of macromolecules such as proteoglycans and collagens. In tumor tissue, (13) C diffusion MRS could probe intracellular glycolytic metabolism, while (1) H diffusion MRS may separate the spectrally overlapped lactate and lipid resonances. In this review, recent diffusion MRS studies of these biologically relevant non-water molecules under normal and diseased conditions will be presented. Technical considerations for diffusion MRS experiments will be discussed. With advances in MRI hardware and diffusion methodology, diffusion MRS of non-water molecules is expected to provide increasingly valuable and biologically specific information on tissue microstructures and physiology, complementing the traditional diffusion MRI of small and ubiquitous water molecules. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  5. Vibrational spectroscopy and the development of new force fields for biological molecules.

    PubMed

    Gerber, R B; Chaban, G M; Gregurick, S K; Brauer, B

    2003-03-01

    The role of vibrational spectroscopy in the testing of force fields of biological molecules and in the determination of improved force fields is discussed. Analysis shows that quantitative testing of potential energy surfaces by comparison with spectroscopic data generally requires calculations that include anharmonic couplings between different vibrational modes. Applications of the vibrational self-consistent field (VSCF) method to calculations of spectroscopy of biological molecules are presented, and comparison with experiment is used to determine the merits and flaws of various types of force fields. The main conclusions include the following: (1) Potential surfaces from ab initio methods at the level of MP2 yield very satisfactory agreement with spectroscopic experimental data. (2) By the test of spectroscopy, ab initio force fields are considerably superior to the standard versions of force fields such as AMBER or OPLS. (3) Much of the spectroscopic weakness of AMBER and OPLS is due to incorrect description of anharmonic coupling between different vibrational modes. (4) Potential surfaces of the QM/MM (Quantum Mechanics/Molecular Mechanics) type, and potentials based on improved versions of semi-empirical electronic structure theory, which are feasible for large biological molecules, yield encouraging results by the test of vibrational spectroscopy.

  6. Interrogating biology with force: single molecule high-resolution measurements with optical tweezers.

    PubMed

    Capitanio, Marco; Pavone, Francesco S

    2013-09-17

    Single molecule force spectroscopy methods, such as optical and magnetic tweezers and atomic force microscopy, have opened up the possibility to study biological processes regulated by force, dynamics of structural conformations of proteins and nucleic acids, and load-dependent kinetics of molecular interactions. Among the various tools available today, optical tweezers have recently seen great progress in terms of spatial resolution, which now allows the measurement of atomic-scale conformational changes, and temporal resolution, which has reached the limit of the microsecond-scale relaxation times of biological molecules bound to a force probe. Here, we review different strategies and experimental configurations recently developed to apply and measure force using optical tweezers. We present the latest progress that has pushed optical tweezers' spatial and temporal resolution down to today's values, discussing the experimental variables and constraints that are influencing measurement resolution and how these can be optimized depending on the biological molecule under study. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  7. Shaping Small Bioactive Molecules to Untangle Their Biological Function: A Focus on Fluorescent Plant Hormones.

    PubMed

    Lace, Beatrice; Prandi, Cristina

    2016-08-01

    Modern biology overlaps with chemistry in explaining the structure and function of all cellular processes at the molecular level. Plant hormone research is perfectly located at the interface between these two disciplines, taking advantage of synthetic and computational chemistry as a tool to decipher the complex biological mechanisms regulating the action of plant hormones. These small signaling molecules regulate a wide range of developmental processes, adapting plant growth to ever changing environmental conditions. The synthesis of small bioactive molecules mimicking the activity of endogenous hormones allows us to unveil many molecular features of their functioning, giving rise to a new field, plant chemical biology. In this framework, fluorescence labeling of plant hormones is emerging as a successful strategy to track the fate of these challenging molecules inside living organisms. Thanks to the increasing availability of new fluorescent probes as well as advanced and innovative imaging technologies, we are now in a position to investigate many of the dynamic mechanisms through which plant hormones exert their action. Such a deep and detailed comprehension is mandatory for the development of new green technologies for practical applications. In this review, we summarize the results obtained so far concerning the fluorescent labeling of plant hormones, highlighting the basic steps leading to the design and synthesis of these compelling molecular tools and their applications.

  8. Recent Advances in Biological Single-Molecule Applications of Optical Tweezers and Fluorescence Microscopy.

    PubMed

    Hashemi Shabestari, M; Meijering, A E C; Roos, W H; Wuite, G J L; Peterman, E J G

    2017-01-01

    Over the past two decades, single-molecule techniques have evolved into robust tools to study many fundamental biological processes. The combination of optical tweezers with fluorescence microscopy and microfluidics provides a powerful single-molecule manipulation and visualization technique that has found widespread application in biology. In this combined approach, the spatial (~nm) and temporal (~ms) resolution, as well as the force scale (~pN) accessible to optical tweezers is complemented with the power of fluorescence microscopy. Thereby, it provides information on the local presence, identity, spatial dynamics, and conformational dynamics of single biomolecules. Together, these techniques allow comprehensive studies of, among others, molecular motors, protein-protein and protein-DNA interactions, biomolecular conformational changes, and mechanotransduction pathways. In this chapter, recent applications of fluorescence microscopy in combination with optical trapping are discussed. After an introductory section, we provide a description of instrumentation together with the current capabilities and limitations of the approaches. Next we summarize recent studies that applied this combination of techniques in biological systems and highlight some representative biological assays to mark the exquisite opportunities that optical tweezers combined with fluorescence microscopy provide. © 2017 Elsevier Inc. All rights reserved.

  9. Transport and Stability of Biological Molecules in Surfactant-Alginate Composite Hydrogels

    PubMed Central

    Stoppel, Whitney L.; White, Joseph C.; Horava, Sarena D.; Bhatia, Surita R.; Roberts, Susan C.

    2013-01-01

    Obstructed transport of biological molecules can result in improper release of pharmaceuticals or biologics from biomedical devices. Recent studies have shown that nonionic surfactants, such as Pluronic® F68 (F68), positively alter biomaterial properties, such as mesh size and microcapsule diameter. To further understand the effect of F68 (incorporated at concentrations well above the critical micelle concentration (CMC)) in traditional biomaterials, the transport properties of BSA and riboflavin were investigated in F68-alginate composite hydrogels. Results indicate that small molecule transport (represented by riboflavin) was not significantly hindered by F68 in homogeneously crosslinked hydrogels (up to an 11% decrease in loading capacity and 14% increase in effective diffusion coefficient, Deff), while protein transport in homogeneously crosslinked hydrogels (represented by BSA) was significantly affected (up to a 43% decrease in loading capacity and 40% increase in Deff). For inhomogeneously crosslinked hydrogels (CaCl2 or BaCl2 gelation), the Deff increased up to 50% and 83% for small molecule and proteins, respectively. Variation in the alginate gelation method was shown to affect transport through measurable changes in swelling ratio (30% decrease) and observable changes in crosslinking structure as well as up to a 3.6 and 11.8-fold difference in Deff for riboflavin and BSA, respectively. The change in protein transport properties is a product of mesh size restrictions (10–25 nm estimated by mechanical properties) and BSA-F68 interaction (DLS). Taken as a whole, these results show that incorporation of a nonionic surfactant at concentrations above the CMC can affect device functionality by impeding the transport of large biological molecules. PMID:21798381

  10. Linear dichroism spectroscopy of gas phase biological molecules embedded in superfluid helium droplets

    NASA Astrophysics Data System (ADS)

    Kong, Wei; Pei, Linsen; Zhang, Jie

    This article presents the current status of gas phase linear dichroism (LD) spectroscopy, including the theoretical background, the experimental technique, and a few examples in the UV/VIS and IR. Orientation and alignment of gas phase samples are achieved using a DC electric field. To reach the necessary degree of alignment, biological molecules vaporized from a heated oven need to be embedded in superfluid helium droplets. Excitation under different polarization directions of the light source relative to the alignment field can then be used to derive the direction of the transition dipole, or the size of the permanent dipole, or both. For biological molecules that have no resonance lines or too many resonance lines, LD offers an additional parameter for spectroscopic assignment and tautomeric and conformational identification. The direction of the vibrational transition dipole is proven more reliable for vibrational and tautomeric assignment than the energy or frequency information, which is often problematic because of its sensitivity to basis sets and calculation methods. Several examples of vibrational LD of nucleic acid bases will be discussed. On the other hand, if a chromophore with a known electronic transition dipole is attached to a biological molecule, as demonstrated in the case of tryptamine, the permanent dipole determined from LD is then representative of the molecular conformation. This method of conformational determination does not rely on detailed spectroscopic assignment, thus it is applicable to molecules that do not have resolvable vibronic bands. However, its application is currently limited to the availability of an effective chromophore, and the search for such a chromophore is an on-going effort.

  11. Bioturbo similarity searching: combining chemical and biological similarity to discover structurally diverse bioactive molecules.

    PubMed

    Wassermann, Anne Mai; Lounkine, Eugen; Glick, Meir

    2013-03-25

    Virtual screening using bioactivity profiles has become an integral part of currently applied hit finding methods in pharmaceutical industry. However, a significant drawback of this approach is that it is only applicable to compounds that have been biologically tested in the past and have sufficient activity annotations for meaningful profile comparisons. Although bioactivity data generated in pharmaceutical institutions are growing on an unprecedented scale, the number of biologically annotated compounds still covers only a minuscule fraction of chemical space. For a newly synthesized compound or an isolated natural product to be biologically characterized across multiple assays, it may take a considerable amount of time. Consequently, this chemical matter will not be included in virtual screening campaigns based on bioactivity profiles. To overcome this problem, we herein introduce bioturbo similarity searching that uses chemical similarity to map molecules without biological annotations into bioactivity space and then searches for biologically similar compounds in this reference system. In benchmark calculations on primary screening data, we demonstrate that our approach generally achieves higher hit rates and identifies structurally more diverse compounds than approaches using chemical information only. Furthermore, our method is able to discover hits with novel modes of inhibition that traditional 2D and 3D similarity approaches are unlikely to discover. Test calculations on a set of natural products reveal the practical utility of the approach for identifying novel and synthetically more accessible chemical matter.

  12. Engineering Bacteria to Search for Specific Concentrations of Molecules by a Systematic Synthetic Biology Design Method.

    PubMed

    Tien, Shin-Ming; Hsu, Chih-Yuan; Chen, Bor-Sen

    2016-01-01

    Bacteria navigate environments full of various chemicals to seek favorable places for survival by controlling the flagella's rotation using a complicated signal transduction pathway. By influencing the pathway, bacteria can be engineered to search for specific molecules, which has great potential for application to biomedicine and bioremediation. In this study, genetic circuits were constructed to make bacteria search for a specific molecule at particular concentrations in their environment through a synthetic biology method. In addition, by replacing the "brake component" in the synthetic circuit with some specific sensitivities, the bacteria can be engineered to locate areas containing specific concentrations of the molecule. Measured by the swarm assay qualitatively and microfluidic techniques quantitatively, the characteristics of each "brake component" were identified and represented by a mathematical model. Furthermore, we established another mathematical model to anticipate the characteristics of the "brake component". Based on this model, an abundant component library can be established to provide adequate component selection for different searching conditions without identifying all components individually. Finally, a systematic design procedure was proposed. Following this systematic procedure, one can design a genetic circuit for bacteria to rapidly search for and locate different concentrations of particular molecules by selecting the most adequate "brake component" in the library. Moreover, following simple procedures, one can also establish an exclusive component library suitable for other cultivated environments, promoter systems, or bacterial strains.

  13. Engineering Bacteria to Search for Specific Concentrations of Molecules by a Systematic Synthetic Biology Design Method

    PubMed Central

    Chen, Bor-Sen

    2016-01-01

    Bacteria navigate environments full of various chemicals to seek favorable places for survival by controlling the flagella’s rotation using a complicated signal transduction pathway. By influencing the pathway, bacteria can be engineered to search for specific molecules, which has great potential for application to biomedicine and bioremediation. In this study, genetic circuits were constructed to make bacteria search for a specific molecule at particular concentrations in their environment through a synthetic biology method. In addition, by replacing the “brake component” in the synthetic circuit with some specific sensitivities, the bacteria can be engineered to locate areas containing specific concentrations of the molecule. Measured by the swarm assay qualitatively and microfluidic techniques quantitatively, the characteristics of each “brake component” were identified and represented by a mathematical model. Furthermore, we established another mathematical model to anticipate the characteristics of the “brake component”. Based on this model, an abundant component library can be established to provide adequate component selection for different searching conditions without identifying all components individually. Finally, a systematic design procedure was proposed. Following this systematic procedure, one can design a genetic circuit for bacteria to rapidly search for and locate different concentrations of particular molecules by selecting the most adequate “brake component” in the library. Moreover, following simple procedures, one can also establish an exclusive component library suitable for other cultivated environments, promoter systems, or bacterial strains. PMID:27096615

  14. Biological carrier molecules of radiopharmaceuticals for molecular cancer imaging and targeted cancer therapy.

    PubMed

    Aerts, A; Impens, N R E N; Gijs, M; D'Huyvetter, M; Vanmarcke, H; Ponsard, B; Lahoutte, T; Luxen, A; Baatout, S

    2014-01-01

    Many tumors express one or more proteins that are either absent or hardly present in normal tissues, and which can be targeted by radiopharmaceuticals for either visualization of tumor cells or for targeted therapy. Radiopharmaceuticals can consist of a radionuclide and a carrier molecule that interacts with the tumor target and as such guides the attached radionuclide to the right spot. Radiopharmaceuticals hold great promise for the future of oncology by providing early, precise diagnosis and better, personalized treatment. Most advanced developments with marketed products are based on whole antibodies or antibody fragments as carrier molecules. However, a substantial number of (pre)clinical studies indicate that radiopharmaceuticals based on other carrier molecules, such as peptides, nonimmunoglobulin scaffolds, or nucleic acids may be valuable alternatives. In this review, we discuss the biological molecules that can deliver radionuclide payloads to tumor cells in terms of their structure, the selection procedure, their (pre)clinical status, and advantages or obstacles to their use in a radiopharmaceutical design. We also consider the plethora of molecular targets existing on cancer cells that can be targeted by radiopharmaceuticals, as well as how to select a radionuclide for a given diagnostic or therapeutic product.

  15. Application of terahertz spectroscopy for characterization of biologically active organic molecules in natural environment

    NASA Astrophysics Data System (ADS)

    Karaliūnas, Mindaugas; Jakštas, Vytautas; Nasser, Kinan E.; Venckevičius, Rimvydas; Urbanowicz, Andrzej; Kašalynas, Irmantas; Valušis, Gintaras

    2016-09-01

    In this work, a comparative research of biologically active organic molecules in its natural environment using the terahertz (THz) time domain spectroscopy (TDS) and Fourier transform spectroscopy (FTS) systems is carried out. Absorption coefficient and refractive index of Nicotiana tabacum L. leaves containing nicotine, Cannabis sativa L. leaves containing tetrahydrocannabinol, and Humulu lupulus L. leaves containing α-acids, active organic molecules that obtain in natural environment, were measured in broad frequency range from 0.1 to 13 THz at room temperature. In the spectra of absorption coefficient the features were found to be unique for N. tabacum, C. sativa and H. lupulus. Moreover, those features can be exploited for identification of C. sativa sex and N. tabacum origin. The refractive index can be also used to characterize different species.

  16. Collective vibrational modes in biological molecules investigated by terahertz time-domain spectroscopy.

    PubMed

    Walther, M; Plochocka, P; Fischer, B; Helm, H; Uhd Jepsen, P

    2002-01-01

    We present well-resolved absorption spectra of biological molecules in the far-IR (FIR) spectral region recorded by terahertz time-domain spectroscopy (THz-TDS). As an illustrative example we discuss the absorption spectra of benzoic acid, its monosubstitutes salicylic acid (2-hydroxy-benzoic acid), 3- and 4-hydroxybenzoic acid, and aspirin (acetylsalicylic acid) in the spectral region between 18 and 150 cm(-1). The spectra exhibit distinct features originating from low-frequency vibrational modes caused by intra- or intermolecular collective motion and lattice modes. Due to the collective origin of the observed modes the absorption spectra are highly sensitive to the overall structure and configuration of the molecules, as well as their environment. The THz-TDS procedure can provide a direct fingerprint of the molecular structure or conformational state of a compound.

  17. Ab Initio Calculations of the Electronic Structures and Biological Functions of Protein Molecules

    NASA Astrophysics Data System (ADS)

    Zheng, Haoping

    The self-consistent cluster-embedding (SCCE) calculation method reduces the computational effort from M3 to about M1 (M is the number of atoms in the system) with precise calculations. Thus the ab initio, all-electron calculation of the electronic structure and biological function of protein molecule has become a reality, which will promote new proteomics considerably. The calculated results of two real protein molecules, the trypsin inhibitor from the seeds of squash Cucurbita maxima (CMTI-I, 436 atoms) and the ascaris trypsin inhibitor (912 atoms, two three-dimensional structures), will be presented in this paper. The reactive sites of the inhibitors are determined and explained. The accuracy of structure determination of the inhibitors are tested theoretically.

  18. Ab Initio Calculations of the Electronic Structures and Biological Functions of Protein Molecules

    NASA Astrophysics Data System (ADS)

    Zheng, Haoping

    2003-04-01

    The self-consistent cluster-embedding (SCCE) calculation method reduces the computational effort from M3 to about M1 (M is the number of atoms in the system) with unchanged calculation precision. So the ab initio, all-electron calculation of the electronic structure and biological function of protein molecule becomes a reality, which will promote new proteomics considerably. The calculated results of two real protein molecules, the trypsin inhibitor from the seeds of squash Cucurbita maxima (CMTI-I, 436 atoms) and the Ascaris trypsin inhibitor (912 atoms, two three-dimensional structures), are presented. The reactive sites of the inhibitors are determined and explained. The precision of structure determination of inhibitors are tested theoretically.

  19. An Unbiased Cell Morphology–Based Screen for New, Biologically Active Small Molecules

    PubMed Central

    Tanaka, Masahiro; Bateman, Raynard; Rauh, Daniel; Vaisberg, Eugeni; Ramachandani, Shyam; Zhang, Chao; Hansen, Kirk C; Burlingame, Alma L; Trautman, Jay K; Adams, Cynthia L

    2005-01-01

    We have implemented an unbiased cell morphology–based screen to identify small-molecule modulators of cellular processes using the Cytometrix (TM) automated imaging and analysis system. This assay format provides unbiased analysis of morphological effects induced by small molecules by capturing phenotypic readouts of most known classes of pharmacological agents and has the potential to read out pathways for which little is known. Four human-cancer cell lines and one noncancerous primary cell type were treated with 107 small molecules comprising four different protein kinase–inhibitor scaffolds. Cellular phenotypes induced by each compound were quantified by multivariate statistical analysis of the morphology, staining intensity, and spatial attributes of the cellular nuclei, microtubules, and Golgi compartments. Principal component analysis was used to identify inhibitors of cellular components not targeted by known protein kinase inhibitors. Here we focus on a hydroxyl-substituted analog (hydroxy-PP) of the known Src-family kinase inhibitor PP2 because it induced cell-specific morphological features distinct from all known kinase inhibitors in the collection. We used affinity purification to identify a target of hydroxy-PP, carbonyl reductase 1 (CBR1), a short-chain dehydrogenase-reductase. We solved the X-ray crystal structure of the CBR1/hydroxy-PP complex to 1.24 Å resolution. Structure-based design of more potent and selective CBR1 inhibitors provided probes for analyzing the biological function of CBR1 in A549 cells. These studies revealed a previously unknown function for CBR1 in serum-withdrawal-induced apoptosis. Further studies indicate CBR1 inhibitors may enhance the effectiveness of anticancer anthracyclines. Morphology-based screening of diverse cancer cell types has provided a method for discovering potent new small-molecule probes for cell biological studies and anticancer drug candidates. PMID:15799708

  20. Single ionization and capture cross sections from biological molecules by bare projectile impact*

    NASA Astrophysics Data System (ADS)

    Quinto, Michele A.; Monti, Juan M.; Montenegro, Pablo D.; Fojón, Omar A.; Champion, Christophe; Rivarola, Roberto D.

    2017-02-01

    We report calculations on single differential and total cross sections for single ionization and single electron capture from biological targets, namely, vapor water and DNA nucleobasese molecules, by bare projectile impact: H+, He2+, and C6+. They are performed within the Continuum Distorted Wave - Eikonal Initial State approximation and compared to several existing experimental data. This study is oriented to the obtention of a reliable set of theoretical data to be used as input in a Monte Carlo code destined to micro- and nano- dosimetry.

  1. Pulse requirements for x-ray diffraction imaging of single biological molecules

    SciTech Connect

    Hau-Riege, S; London, R; Huldt, G; Chapman, H

    2005-01-05

    It has been suggested that x-ray free electron lasers will enable single-particle diffraction imaging of biological molecules. In this paper we present a model to estimate the required pulse parameters based on a trade-off between minimizing image degradation due to damage and maximizing the image signal-to-noise ratio. We discuss several means to alleviate the photon requirements, and compare the requirements with existing or planned x-ray sources such as short-pulse x-ray free-electron lasers.

  2. Concepts of neuroendocrine cardiology and neuroendocrine immunology, chemistry and biology of signal molecules.

    PubMed

    Galoyan, Armen

    2010-12-01

    Discovery of neurosecretion of cardioactive neurohormones produced by hypothalamic nuclei (NSO and NPV), as well as the biosynthesis of several immunomodulators (signal molecules of the neuroendocrine immune system of brain), deciphering of their chemical structure and study of their biological properties led to the foundation of two important trends of neurobiology: neuroendocrine immunology and cardiology. Hormone formation by atrium ganglionary nerve cells and auriculum establishment of neurohumoral interactions between hypothalamic and atrium neurosecretion indicated the existence of the system neuroendocrine hypothalamus--endocrine heart. Study of their biological properties promoted creation of powerful neurohormonal preparations for the treatment of immune, cardio-vascular, neurodegenerative, infectious and tumor diseases. Concepts suggested by us on neuroendocrine cardiology and immunology, create large perspectives for development of the theory and its implementation in medicine.

  3. Long noncoding RNAs: Novel molecules in cardiovascular biology, disease and regeneration.

    PubMed

    Hou, Jingying; Zhou, Changqing; Long, Huibao; Zheng, Shaoxin; Guo, Tianzhu; Wu, Quanhua; Wu, Hao; Zhong, Tingting; Wang, Tong

    2016-06-01

    Remarkable breakthroughs made in genomic technologies have facilitated the discovery of thousands of novel transcripts that do not template protein synthesis. Numerous RNAs termed as long noncoding RNAs (lncRNAs) generated from this pervasive transcription function vividly in gene regulatory networks and a variety of biological and cellular processes. Here, we make a brief description of the known and putative functions of lncRNAs in cardiovascular biology and disease. The association between lncRNAs and stem cells mediated cardiomyocytes differentiation and neovascularization is discussed then. It will provide a new clue for further studies on these novel molecules in cardiovascular disease and bring bright prospects for their future applications in cardiac regenerative medicine. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. MS-based metabolomics facilitates the discovery of in vivo functional small molecules with a diversity of biological contexts.

    PubMed

    Yan, Leyu; Nie, Wenna; Parker, Tony; Upton, Zee; Lu, Haitao

    2013-10-01

    In vivo small molecules as necessary intermediates are involved in numerous critical metabolic pathways and biological processes associated with many essential biological functions and events. There is growing evidence that MS-based metabolomics is emerging as a powerful tool to facilitate the discovery of functional small molecules that can better our understanding of development, infection, nutrition, disease, toxicity, drug therapeutics, gene modifications and host-pathogen interaction from metabolic perspectives. However, further progress must still be made in MS-based metabolomics because of the shortcomings in the current technologies and knowledge. This technique-driven review aims to explore the discovery of in vivo functional small molecules facilitated by MS-based metabolomics and to highlight the analytic capabilities and promising applications of this discovery strategy. Moreover, the biological significance of the discovery of in vivo functional small molecules with different biological contexts is also interrogated at a metabolic perspective.

  5. A chemical screen for biological small molecule-RNA conjugates reveals CoA-linked RNA.

    PubMed

    Kowtoniuk, Walter E; Shen, Yinghua; Heemstra, Jennifer M; Agarwal, Isha; Liu, David R

    2009-05-12

    Compared with the rapidly expanding set of known biological roles for RNA, the known chemical diversity of cellular RNA has remained limited primarily to canonical RNA, 3'-aminoacylated tRNAs, nucleobase-modified RNAs, and 5'-capped mRNAs in eukaryotes. We developed two methods to detect in a broad manner chemically labile cellular small molecule-RNA conjugates. The methods were validated by the detection of known tRNA and rRNA modifications. The first method analyzes small molecules cleaved from RNA by base or nucleophile treatment. Application to Escherichia coli and Streptomyces venezuelae RNA revealed an RNA-linked hydroxyfuranone or succinyl ester group, in addition to a number of other putative small molecule-RNA conjugates not previously reported. The second method analyzes nuclease-generated mononucleotides before and after treatment with base or nucleophile and also revealed a number of new putative small molecule-RNA conjugates, including 3'-dephospho-CoA and its succinyl-, acetyl-, and methylmalonyl-thioester derivatives. Subsequent experiments established that these CoA species are attached to E. coli and S. venezuelae RNA at the 5' terminus. CoA-linked RNA cannot be generated through aberrant transcriptional initiation by E. coli RNA polymerase in vitro, and CoA-linked RNA in E. coli is only found among smaller (approximately < 200 nucleotide) RNAs that have yet to be identified. These results provide examples of small molecule-RNA conjugates and suggest that the chemical diversity of cellular RNA may be greater than previously understood.

  6. Quantitative evaluations of mechanisms of radiofrequency interactions with biological molecules and processes.

    PubMed

    Sheppard, Asher R; Swicord, Mays L; Balzano, Quirino

    2008-10-01

    The complexity of interactions of electromagnetic fields up to 10(12) Hz with the ions, atoms, and molecules of biological systems has given rise to a large number of established and proposed biophysical mechanisms applicable over a wide range of time and distance scales, field amplitudes, frequencies, and waveforms. This review focuses on the physical principles that guide quantitative assessment of mechanisms applicable for exposures at or below the level of endogenous electric fields associated with development, wound healing, and excitation of muscles and the nervous system (generally, 1 to 10(2) V m(-1)), with emphasis on conditions where temperature increases are insignificant (<1 K). Experiment and theory demonstrate possible demodulation at membrane barriers for frequencies < or =10 MHz, but not at higher frequencies. Although signal levels somewhat below system noise can be detected, signal-to-noise ratios substantially less than 0.1 cannot be overcome by cooperativity, signal averaging, coherent detection, or by nonlinear dynamical systems. Sensory systems and possible effects on biological magnetite suggest paradigms for extreme sensitivity at lower frequencies, but there are no known radiofrequency (RF) analogues. At the molecular level, vibrational modes are so overdamped by water molecules that excitation of molecular modes below the far infrared cannot occur. Two RF mechanisms plausibly may affect biological matter under common exposure conditions. For frequencies below approximately 150 MHz, shifts in the rate of chemical reactions can be mediated by radical pairs and, at all frequencies, dielectric and resistive heating can raise temperature and increase the entropy of the affected biological system.

  7. Single Fluorescent Molecules as Nano-Illuminators for Biological Structure and Function

    NASA Astrophysics Data System (ADS)

    Moerner, W. E.

    2011-03-01

    Since the first optical detection and spectroscopy of a single molecule in a solid (Phys. Rev. Lett. {62}, 2535 (1989)), much has been learned about the ability of single molecules to probe local nanoenvironments and individual behavior in biological and nonbiological materials in the absence of ensemble averaging that can obscure heterogeneity. Because each single fluorophore acts a light source roughly 1 nm in size, microscopic imaging of individual fluorophores leads naturally to superlocalization, or determination of the position of the molecule with precision beyond the optical diffraction limit, simply by digitization of the point-spread function from the single emitter. For example, the shape of single filaments in a living cell can be extracted simply by allowing a single molecule to move through the filament (PNAS {103}, 10929 (2006)). The addition of photoinduced control of single-molecule emission allows imaging beyond the diffraction limit (super-resolution) and a new array of acronyms (PALM, STORM, F-PALM etc.) and advances have appeared. We have used the native blinking and switching of a common yellow-emitting variant of green fluorescent protein (EYFP) reported more than a decade ago (Nature {388}, 355 (1997)) to achieve sub-40 nm super-resolution imaging of several protein structures in the bacterium Caulobacter crescentus: the quasi-helix of the actin-like protein MreB (Nat. Meth. {5}, 947 (2008)), the cellular distribution of the DNA binding protein HU (submitted), and the recently discovered division spindle composed of ParA filaments (Nat. Cell Biol. {12}, 791 (2010)). Even with these advances, better emitters would provide more photons and improved resolution, and a new photoactivatable small-molecule emitter has recently been synthesized and targeted to specific structures in living cells to provide super-resolution images (JACS {132}, 15099 (2010)). Finally, a new optical method for extracting three-dimensional position information based on

  8. A Synthetic Biology Project - Developing a single-molecule device for screening drug-target interactions.

    PubMed

    Firman, Keith; Evans, Luke; Youell, James

    2012-07-16

    This review describes a European-funded project in the area of Synthetic Biology. The project seeks to demonstrate the application of engineering techniques and methodologies to the design and construction of a biosensor for detecting drug-target interactions at the single-molecule level. Production of the proteins required for the system followed the principle of previously described "bioparts" concepts (a system where a database of biological parts - promoters, genes, terminators, linking tags and cleavage sequences - is used to construct novel gene assemblies) and cassette-type assembly of gene expression systems (the concept of linking different "bioparts" to produce functional "cassettes"), but problems were quickly identified with these approaches. DNA substrates for the device were also constructed using a cassette-system. Finally, micro-engineering was used to build a magnetoresistive Magnetic Tweezer device for detection of single molecule DNA modifying enzymes (motors), while the possibility of constructing a Hall Effect version of this device was explored. The device is currently being used to study helicases from Plasmodium as potential targets for anti-malarial drugs, but we also suggest other potential uses for the device. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  9. Biological signaling by carbon monoxide and carbon monoxide-releasing molecules.

    PubMed

    Motterlini, Roberto; Foresti, Roberta

    2017-03-01

    Carbon monoxide (CO) is continuously produced in mammalian cells during the degradation of heme. It is a stable gaseous molecule that reacts selectively with transition metals in a specific redox state, and these characteristics restrict the interaction of CO with defined biological targets that transduce its signaling activity. Because of the high affinity of CO for ferrous heme, these targets can be grouped into heme-containing proteins, representing a large variety of sensors and enzymes with a series of diverse function in the cell and the organism. Despite this notion, progress in identifying which of these targets are selective for CO has been slow and even the significance of elevated carbonmonoxy hemoglobin, a classical marker used to diagnose CO poisoning, is not well understood. This is also due to the lack of technologies capable of assessing in a comprehensive fashion the distribution and local levels of CO between the blood circulation, the tissue, and the mitochondria, one of the cellular compartments where CO exerts its signaling or detrimental effects. Nevertheless, the use of CO gas and CO-releasing molecules as pharmacological approaches in models of disease has provided new important information about the signaling properties of CO. In this review we will analyze the most salient effects of CO in biology and discuss how the binding of CO with key ferrous hemoproteins serves as a posttranslational modification that regulates important processes as diverse as aerobic metabolism, oxidative stress, and mitochondrial bioenergetics. Copyright © 2017 the American Physiological Society.

  10. Interstellar Chemistry Special Feature: Interferometric observations of large biologically interesting interstellar and cometary molecules

    NASA Astrophysics Data System (ADS)

    Snyder, Lewis E.

    2006-08-01

    Interferometric observations of high-mass regions in interstellar molecular clouds have revealed hot molecular cores that have substantial column densities of large, partly hydrogen-saturated molecules. Many of these molecules are of interest to biology and thus are labeled "biomolecules." Because the clouds containing these molecules provide the material for star formation, they may provide insight into presolar nebular chemistry, and the biomolecules may provide information about the potential of the associated interstellar chemistry for seeding newly formed planets with prebiotic organic chemistry. In this overview, events are outlined that led to the current interferometric array observations. Clues that connect this interstellar hot core chemistry to the solar system can be found in the cometary detection of methyl formate and the interferometric maps of cometary methanol. Major obstacles to understanding hot core chemistry remain because chemical models are not well developed and interferometric observations have not been very sensitive. Differentiation in the molecular isomers glycolaldehdye, methyl formate, and acetic acid has been observed, but not explained. The extended source structure for certain sugars, aldehydes, and alcohols may require nonthermal formation mechanisms such as shock heating of grains. Major advances in understanding the formation chemistry of hot core species can come from observations with the next generation of sensitive, high-resolution arrays. biomolecules | comets | chemistry

  11. High throughput extraction of plant, marine and fungal specimens for preservation of biologically active molecules.

    PubMed

    McCloud, Thomas G

    2010-06-24

    The Developmental Therapeutics Program (DTP) of the U.S. National Cancer Institute (NCI), at its NCI-Frederick facility, has built perhaps the largest and most diverse natural products screening library in the world for drug discovery. Composed of plant, marine organism and microbial extracts, it currently contains in excess of 230,000 unique materials. From the inception of this program to identify new anticancer chemotherapeutics from natural products sources in 1987, two extracts have been sequentially prepared from each specimen: one produced by organic solvent extraction, which yields a complex material that contains non- to moderately polar small molecules, and a water-soluble extract, a milieu largely unexplored for useful drugs in earlier years, which contains polar small to medium-sized molecules. Plant specimens and microbial ferments are extracted by modified traditional methods, while the method developed to produce extracts from marine organisms is unique and very different from that used by marine natural products chemists previously, but again yields both an organic solvent soluble and a water soluble material for inclusion into the screening library. Details of high throughput extract production for preservation of biologically active molecules are presented.

  12. Next generation techniques in the high resolution spectroscopy of biologically relevant molecules.

    PubMed

    Neill, Justin L; Douglass, Kevin O; Pate, Brooks H; Pratt, David W

    2011-04-28

    Recent advances in the technology of test and measurement equipment driven by the computer and telecommunications industries have made possible the development of a new broadband, Fourier-transform microwave spectrometer that operates on principles similar to FTNMR. This technique uses a high sample-rate arbitrary waveform generator to construct a phase-locked chirped microwave pulse that gives a linear frequency sweep over a wide frequency range in 1 μs. The chirped pulse efficiently polarizes the molecular sample at all frequencies lying within this band. The subsequent free induction decay of this polarization is measured with a high-speed digitizer and then fast Fourier-transformed to yield a broadband, frequency-resolved rotational spectrum, spanning up to 11.5 GHz and containing lines that are as narrow as 100 kHz. This new technique is called chirped-pulse Fourier transform microwave (CP-FTMW) spectroscopy. The technique offers the potential to determine the structural and dynamical properties of very large molecules solely from fully resolved pure rotational spectra. FTMW double resonance techniques employing a low-resolution UV laser facilitate an easy assignment of overlapping spectra produced by different conformers in the sample. Of particular interest are the energy landscapes of conformationally flexible molecules of biological importance, including studies of their interaction with solvent and/or other weakly bound molecules. An example is provided from the authors' work on p-methoxyphenethylamine, a neurotransmitter, and its complexes with water.

  13. Molecules in interstellar clouds. [physical and chemical conditions of star formation and biological evolution

    NASA Technical Reports Server (NTRS)

    Irvine, W. M.; Hjalmarson, A.; Rydbeck, O. E. H.

    1981-01-01

    The physical conditions and chemical compositions of the gas in interstellar clouds are reviewed in light of the importance of interstellar clouds for star formation and the origin of life. The Orion A region is discussed as an example of a giant molecular cloud where massive stars are being formed, and it is pointed out that conditions in the core of the cloud, with a kinetic temperature of about 75 K and a density of 100,000-1,000,000 molecules/cu cm, may support gas phase ion-molecule chemistry. The Taurus Molecular Clouds are then considered as examples of cold, dark, relatively dense interstellar clouds which may be the birthplaces of solar-type stars and which have been found to contain the heaviest interstellar molecules yet discovered. The molecular species identified in each of these regions are tabulated, including such building blocks of biological monomers as H2O, NH3, H2CO, CO, H2S, CH3CN and H2, and more complex species such as HCOOCH3 and CH3CH2CN.

  14. Electron Momentum Spectroscopy and Its Applications to Molecules of Biological Interest

    NASA Astrophysics Data System (ADS)

    Wang, Feng

    2007-11-01

    Energy and wave function are the heart and soul of Schrödinger quantum mechanics. Electron momentum spectroscopy (EMS) so far provides the most stringent test for quantum mechanical models (theory, basis sets and the combination of both) through observables such as binding energy spectra and Dyson orbital momentum distributions. The capability of EMS to measure Dyson orbitals of a molecule as momentum distributions provides a unique opportunity to assess the models of quantum mechanics based on orbitals, rather than on energy dominated (mostly isotropic) properties. Recently, the author introduced a technique called dual space analysis (DSA), which is based on EMS and quantum mechanics to analyze orbital based information in the more familiar position space as well as the less familiar momentum space. In this article, the development of EMS and DSA is reviewed through the applications to molecules of biological interest such as amino acids, nucleic acid bases and recently nucleosides. The emphasis is the applications of DSA to study isomerization processes and chemical bonding mechanisms of these molecules.

  15. Second-harmonic generation for studying structural motion of biological molecules in real time and space.

    PubMed

    Salafsky, Joshua S

    2007-11-14

    SHG and sum-frequency generation (SFG) are surface-selective, nonlinear optical techniques whose ability to measure the average tilt angle of molecules on surfaces is well known in non-biological systems. By labeling molecules with a second-harmonic-active dye probe, SHG detection is extended to any biological molecule. The method has been used in previous work to detect biomolecules at an interface and their ligand-induced conformational changes. Here I demonstrate that SHG can be used to study structural motion quantitatively using a probe placed at a specific site (Cys-77) in adenylate kinase, a protein. The protein is also labeled non-site-specifically via amines. Labeled protein is absorbed to a surface and a baseline SH signal is measured. Upon introducing ATP, AMP or a specific inhibitor, AP(5)A, the baseline signal changes depending on the ligand and the labeling site. In particular, a substantial change in SH intensity is produced upon binding ATP to the amine-labeled protein, consistent with the X-ray crystal structures. In contrast, SHG polarization measurements are used to quantitatively determine that no rotation occurs at site Cys-77, in agreement with the lack of motion observed at this site in the X-ray crystal structures. A method for building a global map of conformational change in real time and space is proposed using a set of probes placed at different sites in a biomolecule. For this purpose, SH-active unnatural amino acids are attractive complements to exogenous labels.

  16. Electron transfer behaviour of biological macromolecules towards the single-molecule level

    NASA Astrophysics Data System (ADS)

    Zhang, Jingdong; Grubb, Mikala; Hansen, Allan G.; Kuznetsov, Alexander M.; Boisen, Anja; Wackerbarth, Hainer; Ulstrup, Jens

    2003-05-01

    Redox metalloproteins immobilized on metallic surfaces in contact with aqueous biological media are important in many areas of pure and applied sciences. Redox metalloprotein films are currently being addressed by new approaches where biotechnology including modified and synthetic proteins is combined with state-of-the-art physical electrochemistry with emphasis on single-crystal, atomically planar electrode surfaces, in situ scanning tunnelling microscopy (STM) and other surface techniques. These approaches have brought bioelectrochemistry important steps forward towards the nanoscale and single-molecule levels. We discuss here these advances with reference to two specific redox metalloproteins, the blue single-copper protein Pseudomonas aeruginosa azurin and the single-haem protein Saccharomyces cerevisiae yeast cytochrome c, and a short oligonucleotide. Both proteins can be immobilized on Au(111) by chemisorption via exposed sulfur-containing residues. Voltammetric, interfacial capacitance, x-ray photoelectron spectroscopy and microcantilever sensor data, together with in situ STM with single-molecule resolution, all point to a coherent view of monolayer organization with protein electron transfer (ET) function retained. In situ STM can also address the microscopic mechanisms for electron tunnelling through the biomolecules and offers novel notions such as coherent multi-ET between the substrate and tip via the molecular redox levels. This differs in important respects from electrochemical ET at a single metal/electrolyte interface. Similar data for a short oligonucleotide immobilized on Au(111) show that oligonucleotides can be characterized with comparable detail, with novel perspectives for addressing DNA electronic conduction mechanisms and for biological screening towards the single-molecule level.

  17. Microtechnology meets systems biology: the small molecules of metabolome as next big targets.

    PubMed

    Wurm, M; Schöpke, B; Lutz, D; Müller, J; Zeng, A-P

    2010-08-20

    One of the key objectives of systems biology is to study and control biological processes in terms of interactions of components at different molecular levels. Advances in genome sequencing, transcriptomics and proteomics have paved the way for a systemic analysis of cellular processes at gene and protein levels. However, tools are still missing for a reliable and systemic analysis of the small molecules inside cells, the so-called metabolome. Due to the generally very low concentration, high turn-over rate and chemical diversity of metabolites their quantification under physiological, in vivo and dynamic conditions presents major challenges and the missing link for a real systems biology approach on the way from genome to cellular function. To this end, microfluidics can play an important role owing to its unique characteristics such as highly spatial and temporal resolution of sample treatment and analysis. Despite impressive progresses in microtechnology in recent years, many of the microfluidic studies or devices remain at the level of proof-of-principle and have been seldom applied to the real world of metabolomic analysis. In this review article, we first present the major obstacles and challenges for determining in vivo metabolite dynamics in complex biological systems. The progresses in microfluidics, their characteristics and possible applications to solving some of the compelling problems in metabolomic analysis are then discussed. Emphases are put on pinpointing the deficits of the presently available devices and technologies and directions for further development to fulfill the special need of systems biology. Copyright 2010 Elsevier B.V. All rights reserved.

  18. TOPICAL REVIEW: Single-molecule experiments in biological physics: methods and applications

    NASA Astrophysics Data System (ADS)

    Ritort, F.

    2006-08-01

    I review single-molecule experiments (SMEs) in biological physics. Recent technological developments have provided the tools to design and build scientific instruments of high enough sensitivity and precision to manipulate and visualize individual molecules and measure microscopic forces. Using SMEs it is possible to manipulate molecules one at a time and measure distributions describing molecular properties, characterize the kinetics of biomolecular reactions and detect molecular intermediates. SMEs provide additional information about thermodynamics and kinetics of biomolecular processes. This complements information obtained in traditional bulk assays. In SMEs it is also possible to measure small energies and detect large Brownian deviations in biomolecular reactions, thereby offering new methods and systems to scrutinize the basic foundations of statistical mechanics. This review is written at a very introductory level, emphasizing the importance of SMEs to scientists interested in knowing the common playground of ideas and the interdisciplinary topics accessible by these techniques. The review discusses SMEs from an experimental perspective, first exposing the most common experimental methodologies and later presenting various molecular systems where such techniques have been applied. I briefly discuss experimental techniques such as atomic-force microscopy (AFM), laser optical tweezers (LOTs), magnetic tweezers (MTs), biomembrane force probes (BFPs) and single-molecule fluorescence (SMF). I then present several applications of SME to the study of nucleic acids (DNA, RNA and DNA condensation) and proteins (protein-protein interactions, protein folding and molecular motors). Finally, I discuss applications of SMEs to the study of the nonequilibrium thermodynamics of small systems and the experimental verification of fluctuation theorems. I conclude with a discussion of open questions and future perspectives.

  19. Unraveling retrograde signaling pathways: finding candidate signaling molecules via metabolomics and systems biology driven approaches.

    PubMed

    Caldana, Camila; Fernie, Alisdair R; Willmitzer, Lothar; Steinhauser, Dirk

    2012-01-01

    A tight coordination of biological processes between cellular compartments and organelles is crucial for the survival of any eukaryotic organism. According to cellular requirements, signals can be generated within organelles, such as chloroplasts and mitochondria, modulating the nuclear gene expression in a process called retrograde signaling. Whilst many research efforts have been focused on dissecting retrograde signaling pathways using biochemical and genetics approaches, metabolomics and systems biology driven studies have illustrated their great potential for hypotheses generation and for dissecting signaling networks in a rather unbiased or untargeted fashion. Recently, integrative genomics approaches, in which correlation analysis has been applied on transcript and metabolite profiling data of Arabidopsis thaliana, revealed the identification of metabolites which are putatively acting as mediators of nuclear gene expression. Complimentary, the continuous technological developments in the field of metabolomics per se has further demonstrated its potential as a very suitable readout to unravel metabolite-mediated signaling processes. As foundation for these studies here we outline and discuss recent advances in elucidating retrograde signaling molecules and pathways with an emphasis on metabolomics and systems biology driven approaches.

  20. Single Molecule Detection in Living Biological Cells using Carbon Nanotube Optical Probes

    NASA Astrophysics Data System (ADS)

    Strano, Michael

    2009-03-01

    Nanoscale sensing elements offer promise for single molecule analyte detection in physically or biologically constrained environments. Molecular adsorption can be amplified via modulation of sharp singularities in the electronic density of states that arise from 1D quantum confinement [1]. Single-walled carbon nanotubes (SWNT), as single molecule optical sensors [2-3], offer unique advantages such as photostable near-infrared (n-IR) emission for prolonged detection through biological media, single-molecule sensitivity and, nearly orthogonal optical modes for signal transduction that can be used to identify distinct classes of analytes. Selective binding to the SWNT surface is difficult to engineer [4]. In this lecture, we will briefly review the immerging field of fluorescent diagnostics using band gap emission from SWNT. In recent work, we demonstrate that even a single pair of SWNT provides at least four optical modes that can be modulated to uniquely fingerprint chemical agents by the degree to which they alter either the emission band intensity or wavelength. We validate this identification method in vitro by demonstrating detection and identification of six genotoxic analytes, including chemotherapeutic drugs and reactive oxygen species (ROS), which are spectroscopically differentiated into four distinct classes. We also demonstrate single-molecule sensitivity in detecting hydrogen peroxide, one of the most common genotoxins and an important cellular signal. Finally, we employ our sensing and fingerprinting method of these analytes in real time within live 3T3 cells, demonstrating the first multiplexed optical detection from a nanoscale biosensor and the first label-free tool to optically discriminate between genotoxins. We will also discuss our recent efforts to fabricate biomedical sensors for real time detection of glucose and other important physiologically relevant analytes in-vivo. The response of embedded SWNT in a swellable hydrogel construct to

  1. Challenges of biological sample preparation for SIMS imaging of elements and molecules at subcellular resolution

    NASA Astrophysics Data System (ADS)

    Chandra, Subhash

    2008-12-01

    Secondary ion mass spectrometry (SIMS) based imaging techniques capable of subcellular resolution characterization of elements and molecules are becoming valuable tools in many areas of biology and medicine. Due to high vacuum requirements of SIMS, the live cells cannot be analyzed directly in the instrument. The sample preparation, therefore, plays a critical role in preserving the native chemical composition for SIMS analysis. This work focuses on the evaluation of frozen-hydrated and frozen freeze-dried sample preparations for SIMS studies of cultured cells with a CAMECA IMS-3f dynamic SIMS ion microscope instrument capable of producing SIMS images with a spatial resolution of 500 nm. The sandwich freeze-fracture method was used for fracturing the cells. The complimentary fracture planes in the plasma membrane were characterized by field-emission secondary electron microscopy (FESEM) in the frozen-hydrated state. The cells fractured at the dorsal surface were used for SIMS analysis. The frozen-hydrated SIMS analysis of individual cells under dynamic primary ion beam (O 2+) revealed local secondary ion signal enhancements correlated with the water image signals of 19(H 3O) +. A preferential removal of water from the frozen cell matrix in the Z-axis was also observed. These complications render the frozen-hydrated sample type less desirable for subcellular dynamic SIMS studies. The freeze-drying of frozen-hydrated cells, either inside the instrument or externally in a freeze-drier, allowed SIMS imaging of subcellular chemical composition. Morphological evaluations of fractured freeze-dried cells with SEM and confocal laser scanning microscopy (CLSM) revealed well-preserved mitochondria, Golgi apparatus, and stress fibers. SIMS analysis of fractured freeze-dried cells revealed well-preserved chemical composition of even the most highly diffusible ions like K + and Na + in physiologically relevant concentrations. The high K-low Na signature in individual cells

  2. Small molecules unravel complex interplay between auxin biology and endomembrane trafficking.

    PubMed

    Doyle, Siamsa M; Vain, Thomas; Robert, Stéphanie

    2015-08-01

    The establishment and maintenance of controlled auxin gradients within plant tissues are essential for a multitude of developmental processes. Auxin gradient formation is co-ordinated via local biosynthesis and transport. Cell to cell auxin transport is facilitated and precisely regulated by complex endomembrane trafficking mechanisms that target auxin carrier proteins to their final destinations. In turn, auxin and cross-talk with other phytohormones regulate the endomembrane trafficking of auxin carriers. Dissecting such rapid and complicated processes is challenging for classical genetic experiments due to trafficking pathway diversity, gene functional redundancy, and lethality in loss-of-function mutants. Many of these difficulties can be bypassed via the use of small molecules to modify or disrupt the function or localization of proteins. Here, we will review examples of the knowledge acquired by the use of such chemical tools in this field, outlining the advantages afforded by chemical biology approaches.

  3. Extension of in vivo half-life of biologically active molecules by XTEN protein polymers.

    PubMed

    Podust, Vladimir N; Balan, Sibu; Sim, Bee-Cheng; Coyle, Michael P; Ernst, Ulrich; Peters, Robert T; Schellenberger, Volker

    2016-10-28

    XTEN™ is a class of unstructured hydrophilic, biodegradable protein polymers designed to increase the half-lives of therapeutic peptides and proteins. XTEN polymers and XTEN fusion proteins are typically expressed in Escherichia coli and purified by conventional protein chromatography as monodisperse polypeptides of exact length and sequence. Unstructured XTEN polypeptides have hydrodynamic volumes significantly larger than typical globular proteins of similar mass, thus imparting a bulking effect to the therapeutic payloads attached to them. Since their invention, XTEN polypeptides have been utilized to extend the half-lives of a variety of peptide- and protein-based therapeutics. Multiple clinical and preclinical studies and related drug discovery and development efforts are in progress. This review details the most current understanding of physicochemical properties and biological behavior of XTEN and XTENylated molecules. Additionally, the development path and status of several advanced drug discovery and development efforts are highlighted.

  4. Higher sensitivity secondary ion mass spectrometry of biological molecules for high resolution, chemically specific imaging.

    PubMed

    McDonnell, Liam A; Heeren, Ron M A; de Lange, Robert P J; Fletcher, Ian W

    2006-09-01

    To expand the role of high spatial resolution secondary ion mass spectrometry (SIMS) in biological studies, numerous developments have been reported in recent years for enhancing the molecular ion yield of high mass molecules. These include both surface modification, including matrix-enhanced SIMS and metal-assisted SIMS, and polyatomic primary ions. Using rat brain tissue sections and a bismuth primary ion gun able to produce atomic and polyatomic primary ions, we report here how the sensitivity enhancements provided by these developments are additive. Combined surface modification and polyatomic primary ions provided approximately 15.8 times more signal than using atomic primary ions on the raw sample, whereas surface modification and polyatomic primary ions yield approximately 3.8 and approximately 8.4 times more signal. This higher sensitivity is used to generate chemically specific images of higher mass biomolecules using a single molecular ion peak.

  5. Surface-enhanced Raman spectroscopy at single-molecule scale and its implications in biology.

    PubMed

    Wang, Yuling; Irudayaraj, Joseph

    2013-02-05

    Single-molecule (SM) spectroscopy has been an exciting area of research offering significant promise and hope in the field of sensor development to detect targets at ultra-low levels down to SM resolution. To the experts and developers in the field of surface-enhanced Raman spectroscopy (SERS), this has often been a challenge and a significant opportunity for exploration. Needless to say, the opportunities and excitement of this multidisciplinary area impacts span the fields of physics, chemistry and engineering, along with a significant thrust in applications constituting areas in medicine, biology, environment and agriculture among others. In this review, we will attempt to provide a quick snapshot of the basics of SM-SERS, nanostructures and devices that can enable SM Raman measurement. We will conclude with a discussion on SERS implications in biomedical sciences.

  6. In situ sensing and manipulation of molecules in biological samples using a nanorobotic system.

    PubMed

    Li, Guangyong; Xi, Ning; Wang, Donna H

    2005-03-01

    Atomic force microscopy (AFM) is a powerful and widely used imaging technique that can visualize single molecules both in air and solution. Using the AFM tip as an end-effector, an atomic force microscope can be modified into a nanorobot that can manipulate objects in nanoscale. By functionalizing the AFM tip with specific antibodies, the nanorobot is able to identify specific types of receptors on cells' membrane. It is similar to the fluorescent optical microscopy but with higher resolution. By locally updating the AFm image based on interaction force infromation and objects' model during nanomanipulation, real-time visual feedback is obtained through the augmented reality interface. The development of the AFM-based nanorobotic system will enable us to simultaneously conduct in situ imaging, sensing, and manipulation at nanometer scale (eg, protein and DNA levels). This new technology opens a promising way to individually study the function of biological system in molecular level.

  7. The subcellular distribution of small molecules: from pharmacokinetics to synthetic biology.

    PubMed

    Zheng, Nan; Tsai, Hobart Ng; Zhang, Xinyuan; Rosania, Gus R

    2011-10-03

    The systemic pharmacokinetics and pharmacodynamics of small molecules are determined by subcellular transport phenomena. Although approaches used to study the subcellular distribution of small molecules have gradually evolved over the past several decades, experimental analysis and prediction of cellular pharmacokinetics remains a challenge. In this review, we survey the progress of subcellular distribution research since the 1960s, with a focus on the advantages, disadvantages and limitations of the various experimental techniques. Critical review of the existing body of knowledge points to many opportunities to advance the rational design of organelle-targeted chemical agents. These opportunities include (1) development of quantitative, non-fluorescence-based, whole cell methods and techniques to measure the subcellular distribution of chemical agents in multiple compartments; (2) exploratory experimentation with nonspecific transport probes that have not been enriched with putative, organelle-targeting features; (3) elaboration of hypothesis-driven, mechanistic and modeling-based approaches to guide experiments aimed at elucidating subcellular distribution and transport; and (4) introduction of revolutionary conceptual approaches borrowed from the field of synthetic biology combined with cutting edge experimental strategies. In our laboratory, state-of-the-art subcellular transport studies are now being aimed at understanding the formation of new intracellular membrane structures in response to drug therapy, exploring the function of drug-membrane complexes as intracellular drug depots, and synthesizing new organelles with extraordinary physical and chemical properties.

  8. Biological response of HeLa cells to gold nanoparticles coated with organic molecules.

    PubMed

    Cardoso Avila, P E; Rangel Mendoza, A; Pichardo Molina, J L; Flores Villavicencio, L L; Castruita Dominguez, J P; Chilakapati, M K; Sabanero Lopez, M

    2017-08-01

    In this work, gold nanospheres functionalized with low weight organic molecules (4-aminothiphenol and cysteamine) were synthesized in a one-step method for their in vitro cytotoxic evaluation on HeLa cells. To enhance the biocompatibility of the cysteamine-capped GNPs, BSA was used due to its broad PH stability and high binding affinity to gold nanoparticles. Besides, the widely reported silica coated gold nanorods were tested here to contrast their toxic response against our nanoparticles coated with organic molecules. Our results shown, the viability measured at 1.9×10(-5)M did not show significant differences against negative controls for all the samples; however, the metabolic activity of HeLa cells dropped when they were exposed to silica gold nanorods in the range of concentrations from 2.9×10(-7)M to 3.0×10(-4)M, while in the cases of gold nanospheres, we found that only at concentrations below 1.9×10(-5)M metabolic activity was normal. Our preliminary results did not indicate any perceivable harmful toxicity to cell membrane, cytoskeleton or nucleus due to our nanospheres at 1.9×10(-5)M. Additional test should be conducted in order to ensure a safe use of them for biological applications, and to determine the extent of possible damage. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Documenting and harnessing the biological potential of molecules in Distributed Drug Discovery (D3) virtual catalogs.

    PubMed

    Abraham, Milata M; Denton, Ryan E; Harper, Richard W; Scott, William L; O'Donnell, Martin J; Durrant, Jacob D

    2017-04-28

    Virtual molecular catalogs have limited utility if member compounds are (i) difficult to synthesize or (ii) unlikely to have biological activity. The Distributed Drug Discovery (D3) program addresses the synthesis challenge by providing scientists with a free virtual D3 catalog of 73,024 easy-to-synthesize N-acyl unnatural α-amino acids, their methyl esters, and primary amides. The remaining challenge is to document and exploit the bioactivity potential of these compounds. In the current work, a search process is described that retrospectively identifies all virtual D3 compounds classified as bioactive hits in PubChem-cataloged experimental assays. The results provide insight into the broad range of drug-target classes amenable to inhibition and/or agonism by D3-accessible molecules. To encourage computer-aided drug discovery centered on these compounds, a publicly available virtual database of D3 molecules prepared for use with popular computer docking programs is also presented. © 2017 John Wiley & Sons A/S.

  10. Semiexperimental equilibrium structures for building blocks of organic and biological molecules: the B2PLYP route.

    PubMed

    Penocchio, Emanuele; Piccardo, Matteo; Barone, Vincenzo

    2015-10-13

    The B2PLYP double hybrid functional, coupled with the correlation-consistent triple-ζ cc-pVTZ (VTZ) basis set, has been validated in the framework of the semiexperimental (SE) approach for deriving accurate equilibrium structures of molecules containing up to 15 atoms. A systematic comparison between new B2PLYP/VTZ results and several equilibrium SE structures previously determined at other levels, in particular B3LYP/SNSD and CCSD(T) with various basis sets, has put in evidence the accuracy and the remarkable stability of such model chemistry for both equilibrium structures and vibrational corrections. New SE equilibrium structures for phenylacetylene, pyruvic acid, peroxyformic acid, and phenyl radical are discussed and compared with literature data. Particular attention has been devoted to the discussion of systems for which lack of sufficient experimental data prevents a complete SE determination. In order to obtain an accurate equilibrium SE structure for these situations, the so-called templating molecule approach is discussed and generalized with respect to our previous work. Important applications are those involving biological building blocks, like uracil and thiouracil. In addition, for more general situations the linear regression approach has been proposed and validated.

  11. Aqueous Phase Separation as a Possible Route to Compartmentalization of Biological Molecules

    PubMed Central

    2012-01-01

    How could the incredible complexity of modern cells evolve from something simple enough to have appeared in a primordial soup? This enduring question has sparked the interest of researchers since Darwin first considered his theory of natural selection. Organic molecules, even potentially functional molecules including peptides and nucleotides, can be produced abiotically. Amphiphiles such as surfactants and lipids display remarkable self-assembly processes including the spontaneous formation of vesicles resembling the membranes of living cells. Nonetheless, numerous questions remain. Given the presumably dilute concentrations of macromolecules in the prebiotic pools where the earliest cells are thought to have appeared, how could the necessary components become concentrated and encapsulated within a semipermeable membrane? What would drive the further structural complexity that is a hallmark of modern living systems? The interior of modern cells is subdivided into microcompartments such as the nucleoid of bacteria or the organelles of eukaryotic cells. Even within what at first appears to be a single compartment, for example, the cytoplasm or nucleus, chemical composition is often nonuniform, containing gradients, macromolecular assemblies, and/or liquid droplets. What might the internal structure of intermediate evolutionary forms have looked like? The nonideal aqueous solution chemistry of macromolecules offers an attractive possible answer to these questions. Aqueous polymer solutions will form multiple coexisting thermodynamic phases under a variety of readily accessible conditions. In this Account, we describe aqueous phase separation as a model system for biological compartmentalization in both early and modern cells, with an emphasis on systems that have been encapsulated within a lipid bilayer. We begin with an introduction to aqueous phase separation and discuss how this phenomenon can lead to microcompartmentalization and could facilitate biopolymer

  12. Aqueous phase separation as a possible route to compartmentalization of biological molecules.

    PubMed

    Keating, Christine D

    2012-12-18

    How could the incredible complexity of modern cells evolve from something simple enough to have appeared in a primordial soup? This enduring question has sparked the interest of researchers since Darwin first considered his theory of natural selection. Organic molecules, even potentially functional molecules including peptides and nucleotides, can be produced abiotically. Amphiphiles such as surfactants and lipids display remarkable self-assembly processes including the spontaneous formation of vesicles resembling the membranes of living cells. Nonetheless, numerous questions remain. Given the presumably dilute concentrations of macromolecules in the prebiotic pools where the earliest cells are thought to have appeared, how could the necessary components become concentrated and encapsulated within a semipermeable membrane? What would drive the further structural complexity that is a hallmark of modern living systems? The interior of modern cells is subdivided into microcompartments such as the nucleoid of bacteria or the organelles of eukaryotic cells. Even within what at first appears to be a single compartment, for example, the cytoplasm or nucleus, chemical composition is often nonuniform, containing gradients, macromolecular assemblies, and/or liquid droplets. What might the internal structure of intermediate evolutionary forms have looked like? The nonideal aqueous solution chemistry of macromolecules offers an attractive possible answer to these questions. Aqueous polymer solutions will form multiple coexisting thermodynamic phases under a variety of readily accessible conditions. In this Account, we describe aqueous phase separation as a model system for biological compartmentalization in both early and modern cells, with an emphasis on systems that have been encapsulated within a lipid bilayer. We begin with an introduction to aqueous phase separation and discuss how this phenomenon can lead to microcompartmentalization and could facilitate biopolymer

  13. Force per cross-sectional area from molecules to muscles: a general property of biological motors.

    PubMed

    Rospars, Jean-Pierre; Meyer-Vernet, Nicole

    2016-07-01

    We propose to formally extend the notion of specific tension, i.e. force per cross-sectional area-classically used for muscles, to quantify forces in molecular motors exerting various biological functions. In doing so, we review and compare the maximum tensions exerted by about 265 biological motors operated by about 150 species of different taxonomic groups. The motors considered range from single molecules and motile appendages of microorganisms to whole muscles of large animals. We show that specific tensions exerted by molecular and non-molecular motors follow similar statistical distributions, with in particular, similar medians and (logarithmic) means. Over the 10(19) mass (M) range of the cell or body from which the motors are extracted, their specific tensions vary as M(α) with α not significantly different from zero. The typical specific tension found in most motors is about 200 kPa, which generalizes to individual molecular motors and microorganisms a classical property of macroscopic muscles. We propose a basic order-of-magnitude interpretation of this result.

  14. Force per cross-sectional area from molecules to muscles: a general property of biological motors

    PubMed Central

    Meyer-Vernet, Nicole

    2016-01-01

    We propose to formally extend the notion of specific tension, i.e. force per cross-sectional area—classically used for muscles, to quantify forces in molecular motors exerting various biological functions. In doing so, we review and compare the maximum tensions exerted by about 265 biological motors operated by about 150 species of different taxonomic groups. The motors considered range from single molecules and motile appendages of microorganisms to whole muscles of large animals. We show that specific tensions exerted by molecular and non-molecular motors follow similar statistical distributions, with in particular, similar medians and (logarithmic) means. Over the 1019 mass (M) range of the cell or body from which the motors are extracted, their specific tensions vary as Mα with α not significantly different from zero. The typical specific tension found in most motors is about 200 kPa, which generalizes to individual molecular motors and microorganisms a classical property of macroscopic muscles. We propose a basic order-of-magnitude interpretation of this result. PMID:27493785

  15. Phosphate ester hydrolysis of biologically relevant molecules by cerium oxide nanoparticles.

    PubMed

    Kuchma, Melissa Hirsch; Komanski, Christopher B; Colon, Jimmie; Teblum, Andrew; Masunov, Artëm E; Alvarado, Beatrice; Babu, Suresh; Seal, Sudipta; Summy, Justin; Baker, Cheryl H

    2010-12-01

    In an effort to characterize the interaction of cerium oxide nanoparticles (CNPs) in biological systems, we explored the reactivity of CNPs with the phosphate ester bonds of p-nitrophenylphosphate (pNPP), ATP, o-phospho-l-tyrosine, and DNA. The activity of the bond cleavage for pNPP at pH 7 is calculated to be 0.860 ± 0.010 nmol p-nitrophenol/min/μg CNPs. Interestingly, when CNPs bind to plasmid DNA, no cleavage products are detected. While cerium(IV) complexes generally exhibit the ability to break phosphorus-oxygen bonds, the reactions we report appear to be dependent on the availability of cerium(III) sites, not cerium(IV) sites. We investigated the dephosphorylation mechanism from the first principles and find the reaction proceeds through inversion of the phosphate group similar to an S(N)2 mechanism. The ability of CNPs to interact with phosphate ester bonds of biologically relevant molecules has important implications for their use as potential therapeutics.

  16. Smell sensing and visualizing based on multi-quantum wells spatial light modulator

    NASA Astrophysics Data System (ADS)

    Tian, Fengchun; Zhao, Zhenzhen; Jia, Pengfei; Liao, Hailin; Chen, Danyu; Liu, Shouqiong

    2014-09-01

    For the existing drawbacks of traditional detecting methods which use gratings or prisms to detect light intensity distribution at each wavelength of polychromatic light, a novel method based on multi-quantum wells spatial light modulator (MQWs-SLM) has been proposed in this paper. In the proposed method, MQWs-SLM serves as a distribution features detector of the signal light. It is on the basis of quantum-confine Stark effect (QCSE) that the vertical applied voltage can change the absorption features of exciton in multi-quantum wells, and further change the distribution features of the readout polychromatic light of MQWs-SLM. It can be not only an universal detecting method, but also especially recommended to use in the Electronic nose system for features detecting of signal light so as to realize smell sensing and visualizing. The feasibility of the proposed method has been confirmed by mathematical modeling and analysis, simulation experiments and research status analysis.

  17. MicroRNA: a small molecule with a big biological impact.

    PubMed

    Zhou, Xiaofeng; Yang, Pan-Chyr

    2012-01-01

    One of the most significant achievements in biological science in the last decade is the discovery of RNA interference (RNAi), a process within living cells that regulates gene expression at post-transcriptional levels. Historically, this process was described by other more generic names, such as co-suppression and post transcriptional gene silencing. Only after the molecular mechanism underlying these apparently unrelated processes was fully understood did it become apparent that they all described the RNAi phenomenon. In 2006, Dr. Andrew Fire and Dr. Craig C. Mello were awarded the Nobel Prize in Physiology or Medicine for their work on RNAi interference. RNAi is an RNA-dependent gene silencing process that is controlled by the RNA-induced silencing complex (RISC) and is initiated by two types of small RNA molecules - microRNA (miRNA) and small interfering RNA (siRNA). However, the function of microRNA appears to be far beyond RNAi alone, including direct interaction with the gene promoter and epigenetic regulation of the DNA methylation and histone modification. By regulating gene expression, miRNAs are likely to be involved in diverse biological activities, such as tumorigenesis, immune response, insulin secretion, neurotransmitter synthesis, and circadian rhythm, to name a few. MicroRNAs are 21-23 nucleotide single stranded RNA molecules found in eukaryotic cells. The first miRNA, lin-4, was characterized in C. elegans in the early 1990s [1]. In the early years, the progress on microRNA research was slow and experienced substantial growing pains. The short length and uniqueness of each microRNA rendered many conventional hybridization based methods ineffective; very small RNAs are difficult to reliably amplify or label without introducing bias. In addition, hybridization-based methods for microRNA profiling relied on probes designed to detect known microRNAs or known microRNA species previously identified by sequencing or homology search. Recent evidence of

  18. On the role of water molecules in the interface between biological systems and polymers.

    PubMed

    Tsuruta, Teiji

    2010-01-01

    The excellent biocompatibility of PMEA was ascribed by Tanaka to the predominant population of intermediate water in the hydrated polymer matrix. The intermediate water concept was examined using the 'nano-plate model' on the basis of new results (by Morita) of a time-resolved IR study on the water sorption process into PMEA. The examination showed that the image picture proposed by Tanaka concerning the role of intermediate water was in consistent with experimental results so far obtained. Morita showed that the intermediate water exhibited a strong peak at 3400 cm(-1) in its IR spectrum. Water sorption profiles of MMA, PEG and PMVE were found to be similar to that of PMEA. It was shown that the biocompatibility of these polymers could be explained by the intermediate water concept. It was also pointed out that PVP and PDMAA have a considerable amount of intermediate water under appropriate circumstances. The PHEMA-water system showed neither clear peak for cold crystallization in DSC chart, nor the strong peak at 3400 cm(-1) in its IR spectrum, because the PHEMA system did not contain enough intermediate water to show similar behavior to PMEA. The hydrated PHEMA matrix contains a stable network structure of water molecules including the nodes of OH groups of its side-chains. In the stable network system, most water molecules should be hydrogen bonded strongly to form non-freezing water, but not intermediate water. The inferior biocompatibility of PHEMA was ascribed to the stable network structure of water molecules. Some of the PHEMA co-polymers, on the other hand, were found to have highly improved biocompatibility. Mechanism for the improvement was discussed in terms of loosening the network structure, which could be brought about by introducing ionic groups or branching to the polymer chains through co-polymerization with appropriate 'key monomers'. The mobility of polymer chains, as well as the population of three kinds of water in polysaccharide molecules in

  19. 2012 SINGLE MOLECULE APPROACHES TO BIOLOGY GORDON RESEARCH CONFERENCE (JULY 15-20, 2012 - MOUNT SNOW RESORT, WEST DOVER VT)

    SciTech Connect

    Fernandez, Julio

    2012-04-20

    Single molecule techniques are rapidly occupying a central role in biological research at all levels. This transition was made possible by the availability and dissemination of robust techniques that use fluorescence and force probes to track the conformation of molecules one at a time, in vitro as well as in live cells. Single-molecule approaches have changed the way many biological problems are studied. These novel techniques provide previously unobtainable data on fundamental biochemical processes that are essential for all forms of life. The ability of single-molecule approaches to avoid ensemble averaging and to capture transient intermediates and heterogeneous behavior renders them particularly powerful in elucidating mechanisms of the molecular systems that underpin the functioning of living cells. Hence, our conference seeks to disseminate the implementation and use of single molecule techniques in the pursuit of new biological knowledge. Topics covered include: Molecular Motors on the Move; Origin And Fate Of Proteins; Physical Principles Of Life; Molecules and Super-resolution Microscopy; Nanoswitches In Action; Active Motion Or Random Diffusion?; Building Blocks Of Living Cells; From Molecular Mechanics To Physiology; Tug-of-war: Force Spectroscopy Of Single Proteins.

  20. Applications of Engineered DNA-Binding Molecules Such as TAL Proteins and the CRISPR/Cas System in Biology Research.

    PubMed

    Fujita, Toshitsugu; Fujii, Hodaka

    2015-09-24

    Engineered DNA-binding molecules such as transcription activator-like effector (TAL or TALE) proteins and the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) (CRISPR/Cas) system have been used extensively for genome editing in cells of various types and species. The sequence-specific DNA-binding activities of these engineered DNA-binding molecules can also be utilized for other purposes, such as transcriptional activation, transcriptional repression, chromatin modification, visualization of genomic regions, and isolation of chromatin in a locus-specific manner. In this review, we describe applications of these engineered DNA-binding molecules for biological purposes other than genome editing.

  1. Single-molecule conformational dynamics of a biologically functional hydroxocobalamin riboswitch.

    PubMed

    Holmstrom, Erik D; Polaski, Jacob T; Batey, Robert T; Nesbitt, David J

    2014-12-03

    Riboswitches represent a family of highly structured regulatory elements found primarily in the leader sequences of bacterial mRNAs. They function as molecular switches capable of altering gene expression; commonly, this occurs via a conformational change in a regulatory element of a riboswitch that results from ligand binding in the aptamer domain. Numerous studies have investigated the ligand binding process, but little is known about the structural changes in the regulatory element. A mechanistic description of both processes is essential for deeply understanding how riboswitches modulate gene expression. This task is greatly facilitated by studying all aspects of riboswitch structure/dynamics/function in the same model system. To this end, single-molecule fluorescence resonance energy transfer (smFRET) techniques have been used to directly observe the conformational dynamics of a hydroxocobalamin (HyCbl) binding riboswitch (env8HyCbl) with a known crystallographic structure.1 The single-molecule RNA construct studied in this work is unique in that it contains all of the structural elements both necessary and sufficient for regulation of gene expression in a biological context. The results of this investigation reveal that the undocking rate constant associated with the disruption of a long-range kissing-loop (KL) interaction is substantially decreased when the ligand is bound to the RNA, resulting in a preferential stabilization of the docked conformation. Notably, the formation of this tertiary KL interaction directly sequesters the Shine-Dalgarno sequence (i.e., the ribosome binding site) via base-pairing, thus preventing translation initiation. These results reveal that the conformational dynamics of this regulatory switch are quantitatively described by a four-state kinetic model, whereby ligand binding promotes formation of the KL interaction. The results of complementary cell-based gene expression experiments conducted in Escherichia coli are highly

  2. Design and Synthesis of Functional Molecules Based on Complexation and Their Biological Applications.

    PubMed

    Hisamatsu, Yosuke

    2016-01-01

     In this review, we introduce the development of supermolecules, host-guest complexes, and metal complexes formed from the combination of non-covalent interactions and/or coordination bonds, as well as their biological applications. An adenine selective host molecule 1 provides a correctly oriented array of complementary hydrogen bonding sites for the adenine nucleobase. Furthermore, the new DDAA (D: hydrogen bond donor, A: hydrogen bond acceptor) module 4 and ADDA module 7 have been developed as quadruple hydrogen-bonding modules. A quadruple zwitterion 8 forms supramolecular gel in dimethyl sulfoxide, driven by the formation of ion-paired dimers between the zwitterionic units. The obtained supramolecular gel exhibits reversible gel-sol transitions in response to both acid, base, and heating. Self-assembly of a dimeric zinc(II) complex, dianion of cyanuric acid (CA) or 5,5-diethylbarbituric acid (Bar), and copper(II) ion (Cu(2+)) in an aqueous solution provides 4 : 4 : 4 and 2 : 2 : 2 supermolecules 10 and 11, respectively. These supermolecules possess Cu2(μ-OH)2 centers, and accelerate the hydrolysis of a phosphate monoester dianion, mono(4-nitrophenyl)phosphate (MNP), at neutral pH. Regioselective substitution reactions of tris-cyclometalated iridium (Ir) complexes at the 5'-position on 2-phenylpyridine type ligands, and their subsequent conversions to a variety of functional groups are described. For example, pH-sensitive Ir complexes having basic functional groups have been developed. Tris-cyclometalated Ir complexes containing cationic peptides, such as Lys-Lys-Gly-Gly (KKGG) peptides, work as inducers and detectors of cancer cell death. Mechanistic studies suggest that the Ir complex interacts with anionic molecules on the cell surface and/or membrane receptors to trigger an intracellular Ca(2+) response, resulting in necrosis accompanied by membrane disruption.

  3. Tailored treatment options for patients with psoriatic arthritis and psoriasis: review of established and new biologic and small molecule therapies.

    PubMed

    Elyoussfi, Sarah; Thomas, Benjamin J; Ciurtin, Coziana

    2016-05-01

    The diverse clinical picture of PsA suggests the need to identify suitable therapies to address the different combinations of clinical manifestations. This review aimed to classify the available biologic agents and new small molecule inhibitors (licensed and nonlicensed) based on their proven efficacy in treating different clinical manifestations associated with psoriasis and PsA. This review presents the level of evidence of efficacy of different biologic treatments and small molecule inhibitors for certain clinical features of treatment of PsA and psoriasis, which was graded in categories I-IV. The literature searches were performed on the following classes of biologic agents and small molecules: TNF inhibitors (adalimumab, etanercept, infliximab, golimumab, certolizumab), anti-IL12/IL23 (ustekinumab), anti-IL17 (secukinumab, brodalumab, ixekizumab), anti-IL6 (tocilizumab), T cell modulators (alefacept, efalizumab, abatacept, itolizumab), B cell depletion therapy (rituximab), phosphodiesterase 4 inhibitor (apremilast) and Janus kinase inhibitor (tofacitinib). A comprehensive table including 17 different biologic agents and small molecule inhibitors previously tested in psoriasis and PsA was generated, including the level of evidence of their efficacy for each of the clinical features included in our review (axial and peripheral arthritis, enthesitis, dactylitis, and nail and skin disease). We also proposed a limited set of recommendations for a sequential biologic treatment algorithm for patients with PsA who failed the first anti-TNF therapy, based on the available literature data. There is good evidence that many of the biologic treatments initially tested in psoriasis are also effective in PsA. Further research into both prognostic biomarkers and patient stratification is required to allow clinicians the possibility to make better use of the various biologic treatment options available. This review showed that there are many potentially new treatments that are

  4. Regulation of drug-metabolizing enzymes in infectious and inflammatory disease: implications for biologics-small molecule drug interactions.

    PubMed

    Mallick, Pankajini; Taneja, Guncha; Moorthy, Bhagavatula; Ghose, Romi

    2017-06-01

    Drug-metabolizing enzymes (DMEs) are primarily down-regulated during infectious and inflammatory diseases, leading to disruption in the metabolism of small molecule drugs (smds), which are increasingly being prescribed therapeutically in combination with biologics for a number of chronic diseases. The biologics may exert pro- or anti-inflammatory effect, which may in turn affect the expression/activity of DMEs. Thus, patients with infectious/inflammatory diseases undergoing biologic/smd treatment can have complex changes in DMEs due to combined effects of the disease and treatment. Areas covered: We will discuss clinical biologics-SMD interaction and regulation of DMEs during infection and inflammatory diseases. Mechanistic studies will be discussed and consequences on biologic-small molecule combination therapy on disease outcome due to changes in drug metabolism will be highlighted. Expert opinion: The involvement of immunomodulatory mediators in biologic-SMDs is well known. Regulatory guidelines recommend appropriate in vitro or in vivo assessments for possible interactions. The role of cytokines in biologic-SMDs has been documented. However, the mechanisms of drug-drug interactions is much more complex, and is probably multi-factorial. Studies aimed at understanding the mechanism by which biologics effect the DMEs during inflammation/infection are clinically important.

  5. Current and Future Perspectives on the Structural Identification of Small Molecules in Biological Systems.

    PubMed

    Dias, Daniel A; Jones, Oliver A H; Beale, David J; Boughton, Berin A; Benheim, Devin; Kouremenos, Konstantinos A; Wolfender, Jean-Luc; Wishart, David S

    2016-12-15

    Although significant advances have been made in recent years, the structural elucidation of small molecules continues to remain a challenging issue for metabolite profiling. Many metabolomic studies feature unknown compounds; sometimes even in the list of features identified as "statistically significant" in the study. Such metabolic "dark matter" means that much of the potential information collected by metabolomics studies is lost. Accurate structure elucidation allows researchers to identify these compounds. This in turn, facilitates downstream metabolite pathway analysis, and a better understanding of the underlying biology of the system under investigation. This review covers a range of methods for the structural elucidation of individual compounds, including those based on gas and liquid chromatography hyphenated to mass spectrometry, single and multi-dimensional nuclear magnetic resonance spectroscopy, and high-resolution mass spectrometry and includes discussion of data standardization. Future perspectives in structure elucidation are also discussed; with a focus on the potential development of instruments and techniques, in both nuclear magnetic resonance spectroscopy and mass spectrometry that, may help solve some of the current issues that are hampering the complete identification of metabolite structure and function.

  6. Current and Future Perspectives on the Structural Identification of Small Molecules in Biological Systems

    PubMed Central

    Dias, Daniel A.; Jones, Oliver A.H.; Beale, David J.; Boughton, Berin A.; Benheim, Devin; Kouremenos, Konstantinos A.; Wolfender, Jean-Luc; Wishart, David S.

    2016-01-01

    Although significant advances have been made in recent years, the structural elucidation of small molecules continues to remain a challenging issue for metabolite profiling. Many metabolomic studies feature unknown compounds; sometimes even in the list of features identified as “statistically significant” in the study. Such metabolic “dark matter” means that much of the potential information collected by metabolomics studies is lost. Accurate structure elucidation allows researchers to identify these compounds. This in turn, facilitates downstream metabolite pathway analysis, and a better understanding of the underlying biology of the system under investigation. This review covers a range of methods for the structural elucidation of individual compounds, including those based on gas and liquid chromatography hyphenated to mass spectrometry, single and multi-dimensional nuclear magnetic resonance spectroscopy, and high-resolution mass spectrometry and includes discussion of data standardization. Future perspectives in structure elucidation are also discussed; with a focus on the potential development of instruments and techniques, in both nuclear magnetic resonance spectroscopy and mass spectrometry that, may help solve some of the current issues that are hampering the complete identification of metabolite structure and function. PMID:27983674

  7. Introducing Bond-Line Organic Structures in High School Biology: An Activity that Incorporates Pleasant-Smelling Molecules

    ERIC Educational Resources Information Center

    Rios, Andro C.; French, Gerald

    2011-01-01

    Chemical education occurs in settings other than just the chemistry classroom. High school biology courses are frequently where students are introduced to organic molecules and their importance to cellular chemistry. However, structural representations are often intimidating because students have not been introduced to the language. As part of a…

  8. Introducing Bond-Line Organic Structures in High School Biology: An Activity that Incorporates Pleasant-Smelling Molecules

    ERIC Educational Resources Information Center

    Rios, Andro C.; French, Gerald

    2011-01-01

    Chemical education occurs in settings other than just the chemistry classroom. High school biology courses are frequently where students are introduced to organic molecules and their importance to cellular chemistry. However, structural representations are often intimidating because students have not been introduced to the language. As part of a…

  9. Affinity of Drugs and Small Biologically Active Molecules to Carbon Nanotubes: A Pharmacodynamics and Nanotoxicity Factor?

    PubMed Central

    Liu, John; Yang, Liu; Hopfinger, Anton J.

    2009-01-01

    The MM-PBSA MD method was used to estimate the affinity, as represented by log kb, of each of a variety of biologically active molecules to a carbon nanotube in an aqueous environment. These ligand-receptor binding simulations were calibrated by first estimating the log kb values for eight ligands to human serum albumin, HSA, whose log kb values have been observed. A validation linear correlation equation was established [R2 = 0.888 Q2 = 0.603] between the observed and estimated log kb values to HSA. This correlation equation was then used to re-scale all MM-PBSA MD log kb values using a carbon nanotube as the receptor. The log kb of the eight HSA ligands, nine polar and/or rigid ligands and six nonpolar and/or flexible ligands to a carbon nanotube were estimated. The range in re-scaled log kb values across this set of 23 ligands is 0.25 to 7.14, essentially seven orders of magnitude. Some ligands, like PGI2, bind in the log kb = 7 range which corresponds to the lower limits of known drugs. Thus, such significant levels of binding of biologically relevant compounds to carbon nanotubes might lead to alterations in the normal pharmacodynamic profiles of these compounds and be a source of toxicity. Ligand binding potency to a carbon nanotube is largely controlled by the shape, polarity/nonpolarity distribution and flexibility of the ligand. HSA ligands exhibit the most limited binding to a carbon nanotube, and they are relatively rigid and of generally spherical shape. Polar and/or rigid ligands bind less strongly to the carbon nanotube, on average, than nonpolar and/or flexible ligands even though the chosen members of both classes of ligands in this study have chain-like shapes that facilitate binding. The introduction of only a few strategically spaced single bonds in the polar and/or rigid ligands markedly increases their binding to a carbon nanotube. PMID:19281188

  10. Affinity of drugs and small biologically active molecules to carbon nanotubes: a pharmacodynamics and nanotoxicity factor?

    PubMed

    Liu, John; Yang, Liu; Hopfinger, Anton J

    2009-01-01

    The MM-PBSA MD method was used to estimate the affinity, as represented by log k(b), of each of a variety of biologically active molecules to a carbon nanotube in an aqueous environment. These ligand-receptor binding simulations were calibrated by first estimating the log k(b) values for eight ligands to human serum albumin, HSA, whose log k(b) values have been observed. A validation linear correlation equation was established [R(2) = 0.888, Q(2) = 0.603] between the observed and estimated log k(b) values to HSA. This correlation equation was then used to rescale all MM-PBSA MD log k(b) values using a carbon nanotube as the receptor. The log k(b) of the eight HSA ligands, nine polar and/or rigid ligands and six nonpolar and/or flexible ligands to a carbon nanotube were estimated. The range in rescaled log k(b) values across this set of 23 ligands is 0.25 to 7.14, essentially 7 orders of magnitude. Some ligands, like PGI2, bind in the log k(b) = 7 range which corresponds to the lower limits of known drugs. Thus, such significant levels of binding of biologically relevant compounds to carbon nanotubes might lead to alterations in the normal pharmacodynamic profiles of these compounds and be a source of toxicity. Ligand binding potency to a carbon nanotube is largely controlled by the shape, polarity/nonpolarity distribution and flexibility of the ligand. HSA ligands exhibit the most limited binding to a carbon nanotube, and they are relatively rigid and of generally spherical shape. Polar and/or rigid ligands bind less strongly to the carbon nanotube, on average, than nonpolar and/or flexible ligands even though the chosen members of both classes of ligands in this study have chainlike shapes that facilitate binding. The introduction of only a few strategically spaced single bonds in the polar and/or rigid ligands markedly increases their binding to a carbon nanotube.

  11. Laser desorption/ionization mass spectrometry for direct profiling and imaging of small molecules from raw biological materials

    SciTech Connect

    Cha, Sangwon

    2008-01-01

    Matrix-assisted laser desorption/ionization(MALDI) mass spectrometry(MS) has been widely used for analysis of biological molecules, especially macromolecules such as proteins. However, MALDI MS has a problem in small molecule (less than 1 kDa) analysis because of the signal saturation by organic matrixes in the low mass region. In imaging MS (IMS), inhomogeneous surface formation due to the co-crystallization process by organic MALDI matrixes limits the spatial resolution of the mass spectral image. Therefore, to make laser desorption/ionization (LDI) MS more suitable for mass spectral profiling and imaging of small molecules directly from raw biological tissues, LDI MS protocols with various alternative assisting materials were developed and applied to many biological systems of interest. Colloidal graphite was used as a matrix for IMS of small molecules for the first time and methodologies for analyses of small metabolites in rat brain tissues, fruits, and plant tissues were developed. With rat brain tissues, the signal enhancement for cerebroside species by colloidal graphite was observed and images of cerebrosides were successfully generated by IMS. In addition, separation of isobaric lipid ions was performed by imaging tandem MS. Directly from Arabidopsis flowers, flavonoids were successfully profiled and heterogeneous distribution of flavonoids in petals was observed for the first time by graphite-assisted LDI(GALDI) IMS.

  12. Silicon-Germanium multi-quantum well photodetectors in the near infrared.

    PubMed

    Onaran, Efe; Onbasli, M Cengiz; Yesilyurt, Alper; Yu, Hyun Yong; Nayfeh, Ammar M; Okyay, Ali K

    2012-03-26

    Single crystal Silicon-Germanium multi-quantum well layers were epitaxially grown on silicon substrates. Very high quality films were achieved with high level of control utilizing recently developed MHAH epitaxial technique. MHAH growth technique facilitates the monolithic integration of photonic functionality such as modulators and photodetectors with low-cost silicon VLSI technology. Mesa structured p-i-n photodetectors were fabricated with low reverse leakage currents of ~10 mA/cm² and responsivity values exceeding 0.1 A/W. Moreover, the spectral responsivity of fabricated detectors can be tuned by applied voltage.

  13. Electrons, Photons, and Force: Quantitative Single-Molecule Measurements from Physics to Biology

    PubMed Central

    2011-01-01

    Single-molecule measurement techniques have illuminated unprecedented details of chemical behavior, including observations of the motion of a single molecule on a surface, and even the vibration of a single bond within a molecule. Such measurements are critical to our understanding of entities ranging from single atoms to the most complex protein assemblies. We provide an overview of the strikingly diverse classes of measurements that can be used to quantify single-molecule properties, including those of single macromolecules and single molecular assemblies, and discuss the quantitative insights they provide. Examples are drawn from across the single-molecule literature, ranging from ultrahigh vacuum scanning tunneling microscopy studies of adsorbate diffusion on surfaces to fluorescence studies of protein conformational changes in solution. PMID:21338175

  14. The Molecule Microscope: A New Instrument for Biological and Biomedical Research

    PubMed Central

    Weaver, James C.; King, John G.

    1973-01-01

    We describe a new instrument, the molecule microscope, which reveals directly spatial variations in the rate of evaporation of molecules from surfaces by using neutral molecules instead of light or charged particles used in existing kinds of microscopes. The surface composition of the sample determines the binding energy of the evaporating molecules and, hence, the rate of evaporation, which also depends on permeability of the sample when the molecules come either from within or from the other side. We show first results obtained with our apparatus, discuss the design of an instrument now under construction with ≈1-μm resolution, and describe briefly some more advanced versions under consideration with ≈100-Å resolution. Images PMID:4542778

  15. Electrons, photons, and force: quantitative single-molecule measurements from physics to biology.

    PubMed

    Claridge, Shelley A; Schwartz, Jeffrey J; Weiss, Paul S

    2011-02-22

    Single-molecule measurement techniques have illuminated unprecedented details of chemical behavior, including observations of the motion of a single molecule on a surface, and even the vibration of a single bond within a molecule. Such measurements are critical to our understanding of entities ranging from single atoms to the most complex protein assemblies. We provide an overview of the strikingly diverse classes of measurements that can be used to quantify single-molecule properties, including those of single macromolecules and single molecular assemblies, and discuss the quantitative insights they provide. Examples are drawn from across the single-molecule literature, ranging from ultrahigh vacuum scanning tunneling microscopy studies of adsorbate diffusion on surfaces to fluorescence studies of protein conformational changes in solution.

  16. Wavy growth onset in strain-balanced InGaAs multi-quantum wells

    NASA Astrophysics Data System (ADS)

    Nasi, L.; Ferrari, C.; Lanzi, A.; Lazzarini, L.; Balboni, R.; Clarke, G.; Mazzer, M.; Rohr, C.; Abbott, P.; Barnham, K. W. J.

    2005-01-01

    Different strain-balanced InGaAs/InGaAs multi-quantum wells (MQWs) were grown on (0 0 1) InP to be used as active layers of thermophotovoltaic devices. Transmission electron microscopy (TEM) and high-resolution X-ray diffraction (HRXRD) were performed to correlate the evolution of the layer interfaces from planar to wavy and the consequent nucleation of extended defects with the well and barrier compositions and thicknesses and the growth temperature. The existence of a critical elastic energy density for the wavy growth onset has been experimentally confirmed by changing both the well and barrier misfit and the multi-quantum well layer thickness. A decrease of the growth temperature shifts the critical energy to higher values. An empirical model to predict the maximum number of layers that can be grown without modulations as a function of the strain energy stored in the MQW period and the growth temperature is presented and successfully applied for the growth of high quality 40 repetitions MQWs with a well misfit of about 1.5%.

  17. Applications of Engineered DNA-Binding Molecules Such as TAL Proteins and the CRISPR/Cas System in Biology Research

    PubMed Central

    Fujita, Toshitsugu; Fujii, Hodaka

    2015-01-01

    Engineered DNA-binding molecules such as transcription activator-like effector (TAL or TALE) proteins and the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) (CRISPR/Cas) system have been used extensively for genome editing in cells of various types and species. The sequence-specific DNA-binding activities of these engineered DNA-binding molecules can also be utilized for other purposes, such as transcriptional activation, transcriptional repression, chromatin modification, visualization of genomic regions, and isolation of chromatin in a locus-specific manner. In this review, we describe applications of these engineered DNA-binding molecules for biological purposes other than genome editing. PMID:26404236

  18. Conformational, spectroscopic and nonlinear optical properties of biologically active N,N-dimethyltryptamine molecule: A theoretical study

    NASA Astrophysics Data System (ADS)

    Öner, Nazmiye; Tamer, Ömer; Avcı, Davut; Atalay, Yusuf

    2014-12-01

    The effective psychoactive properties of N,N-dimethyltryptamine (DMT) known as the near-death molecule have encouraged the imagination of many research disciplines for several decades. Although there is no theoretical study, a number of paper composed by experimental techniques have been reported for DMT molecule. In this study, the molecular modeling of DMT was carried out using B3LYP and HSEh1PBE levels of density functional theory (DFT). Our calculations showed that the energy gap between HOMO and LUMO is low, demonstrating that DMT is a biologically active molecule. Large hyperconjugation interaction energies imply that molecular charge transfer occurs in DMT. Moreover, NLO analysis indicates that DMT can be used an effective NLO material.

  19. Conformational, spectroscopic and nonlinear optical properties of biologically active N,N-dimethyltryptamine molecule: a theoretical study.

    PubMed

    Öner, Nazmiye; Tamer, Ömer; Avcı, Davut; Atalay, Yusuf

    2014-12-10

    The effective psychoactive properties of N,N-dimethyltryptamine (DMT) known as the near-death molecule have encouraged the imagination of many research disciplines for several decades. Although there is no theoretical study, a number of paper composed by experimental techniques have been reported for DMT molecule. In this study, the molecular modeling of DMT was carried out using B3LYP and HSEh1PBE levels of density functional theory (DFT). Our calculations showed that the energy gap between HOMO and LUMO is low, demonstrating that DMT is a biologically active molecule. Large hyperconjugation interaction energies imply that molecular charge transfer occurs in DMT. Moreover, NLO analysis indicates that DMT can be used an effective NLO material.

  20. Ridge InGaAs/InP multi-quantum-well selective growth in nanoscale trenches on Si (001) substrate

    SciTech Connect

    Li, S.; Zhou, X.; Li, M.; Kong, X.; Mi, J.; Wang, M.; Wang, W.; Pan, J.

    2016-01-11

    Metal organic chemical vapor deposition of InGaAs/InP multi-quantum-well in nanoscale V-grooved trenches on Si (001) substrate was studied using the aspect ratio trapping method. A high quality GaAs/InP buffer layer with two convex (111) B facets was selectively grown to promote the highly uniform, single-crystal ridge InP/InGaAs multi-quantum-well structure growth. Material quality was confirmed by transmission electron microscopy and room temperature micro-photoluminescence measurements. This approach shows great promise for the fabrication of photonics devices and nanolasers on Si substrate.

  1. The characterization of the sol-gel encapsulated curcumin as a possible sensor for small biologically important molecules.

    PubMed

    Iwunze, M O; McEwan, D

    2007-05-15

    Curcumin, a known phytochemical antioxidant was found to be useful as a potential sensor for some small biologically important molecules. Hydrogen peroxide, the sodium salt of nitrite (NO2-), hydroxide (OH-), bromide (Br-) and iodide (I-) were observed to quench the fluorescence of sol-gel encapsulated curcumin, which emits radiation at 530 nm when excited at 420 nm. The observed bimolecular quenching constant which is related to the Stern-Volmer quenching constant, KSV, for the species studied in this work was determined by a modified Stern-Volmer relation for molecular surface accessibility, was observed to be specific for each of these anions and correlates quite well with their half-wave potentials, E1/2. The extent of permeability of these molecules through the pores of the sol-gel matrix was determined and they, also, correlated with these molecules' charge densities and sizes. In all the species, the reaction was quite exergonic and the free energy change, DeltaGoET, obtained in each case, suggest an outer-sphere, long range electron transfer mechanism. These observations open up the possible use of curcumin as a sensor for probing and characterizing some relevant bio-molecules in biological systems.

  2. In situ single molecule imaging of cell membranes: linking basic nanotechniques to cell biology, immunology and medicine.

    PubMed

    Pi, Jiang; Jin, Hua; Yang, Fen; Chen, Zheng W; Cai, Jiye

    2014-11-07

    The cell membrane, which consists of a viscous phospholipid bilayer, different kinds of proteins and various nano/micrometer-sized domains, plays a very important role in ensuring the stability of the intracellular environment and the order of cellular signal transductions. Exploring the precise cell membrane structure and detailed functions of the biomolecules in a cell membrane would be helpful to understand the underlying mechanisms involved in cell membrane signal transductions, which could further benefit research into cell biology, immunology and medicine. The detection of membrane biomolecules at the single molecule level can provide some subtle information about the molecular structure and the functions of the cell membrane. In particular, information obtained about the molecular mechanisms and other information at the single molecule level are significantly different from that detected from a large amount of biomolecules at the large-scale through traditional techniques, and can thus provide a novel perspective for the study of cell membrane structures and functions. However, the precise investigations of membrane biomolecules prompts researchers to explore cell membranes at the single molecule level by the use of in situ imaging methods, as the exact conformation and functions of biomolecules are highly controlled by the native cellular environment. Recently, the in situ single molecule imaging of cell membranes has attracted increasing attention from cell biologists and immunologists. The size of biomolecules and their clusters on the cell surface are set at the nanoscale, which makes it mandatory to use high- and super-resolution imaging techniques to realize the in situ single molecule imaging of cell membranes. In the past few decades, some amazing imaging techniques and instruments with super resolution have been widely developed for molecule imaging, which can also be further employed for the in situ single molecule imaging of cell membranes. In

  3. In situ single molecule imaging of cell membranes: linking basic nanotechniques to cell biology, immunology and medicine

    NASA Astrophysics Data System (ADS)

    Pi, Jiang; Jin, Hua; Yang, Fen; Chen, Zheng W.; Cai, Jiye

    2014-10-01

    The cell membrane, which consists of a viscous phospholipid bilayer, different kinds of proteins and various nano/micrometer-sized domains, plays a very important role in ensuring the stability of the intracellular environment and the order of cellular signal transductions. Exploring the precise cell membrane structure and detailed functions of the biomolecules in a cell membrane would be helpful to understand the underlying mechanisms involved in cell membrane signal transductions, which could further benefit research into cell biology, immunology and medicine. The detection of membrane biomolecules at the single molecule level can provide some subtle information about the molecular structure and the functions of the cell membrane. In particular, information obtained about the molecular mechanisms and other information at the single molecule level are significantly different from that detected from a large amount of biomolecules at the large-scale through traditional techniques, and can thus provide a novel perspective for the study of cell membrane structures and functions. However, the precise investigations of membrane biomolecules prompts researchers to explore cell membranes at the single molecule level by the use of in situ imaging methods, as the exact conformation and functions of biomolecules are highly controlled by the native cellular environment. Recently, the in situ single molecule imaging of cell membranes has attracted increasing attention from cell biologists and immunologists. The size of biomolecules and their clusters on the cell surface are set at the nanoscale, which makes it mandatory to use high- and super-resolution imaging techniques to realize the in situ single molecule imaging of cell membranes. In the past few decades, some amazing imaging techniques and instruments with super resolution have been widely developed for molecule imaging, which can also be further employed for the in situ single molecule imaging of cell membranes. In

  4. Case studies in quantitative biology: Biochemistry on a leash and a single-molecule Hershey-Chase experiment

    NASA Astrophysics Data System (ADS)

    Van Valen, David

    2011-12-01

    The last 50 years of biological research has seen a marked increase in the amount of quantitative data that describes living systems. This wealth of data provides a unique opportunity to recast the pictorial level descriptions of biological processes in the language of mathematics, with the hope that such an undertaking will lead to deeper insights into the behavior of living systems. To achieve this end, we have undertaken three case studies in physical biology. In the first case study, we used statistical mechanics and polymer physics to construct a simple model that describes how flexible chains of amino acids, referred to as tethers, influence the information processing properties of signaling proteins. In the second case study, we studied the DNA ejection process of phage lambda in vitro. In particular, we used bulk and single-molecule methods to study the control parameters that govern the force and kinematics of the ejection process in vitro. In the last case study, we studied the DNA ejection process of phage lambda in vivo. We developed an assay that allows real-time monitoring of DNA ejection in vivo at the single-molecule level. We also developed a parallel system that allows the simultaneous visualization of both phage capsids and phage DNA at the single-cell level, constituting a true single-molecule Hershey-Chase experiment. The work described in this thesis outlines new tools, both in theory and experiment, that can be used to study biological systems as well as a paradigm that can be employed to mathematicize the cartoons of biology.

  5. Chemocavity: specific concavity in protein reserved for the binding of biologically functional small molecules.

    PubMed

    Soga, Shinji; Shirai, Hiroki; Kobori, Masato; Hirayama, Noriaki

    2008-08-01

    The idea that there should be a specific site on a protein for a particular functional small molecule is widespread. It is, however, usually not so easy to understand what characteristics of the site determine the binding ability of the functional small molecule. We have focused on the concurrence rate of the 20 standard amino acids at such binding sites. In order to correlate the concurrence rate and the specific binding site, we have analyzed high-quality X-ray structures of complexes between proteins and small molecules. A novel index characterizing the binding site based on the concurrency rate has been introduced. Using this index we have identified that there is a specific concavity designated as a chemocavity where a specific group of small molecules, i.e., canonical molecular group, is highly inclined to be bound. This study has demonstrated that a chemocavity is reserved for a specific canonical molecular group, and the prevalent idea has been confirmed.

  6. Super-resolution imaging with stochastic single-molecule localization: concepts, technical developments, and biological applications.

    PubMed

    Oddone, Anna; Vilanova, Ione Verdeny; Tam, Johnny; Lakadamyali, Melike

    2014-07-01

    Light microscopy has undergone a revolution with the advent of super-resolution microscopy methods that can surpass the diffraction limit. These methods have generated much enthusiasm, in particular with regards to the new possibilities they offer for biological imaging. The recent years have seen a great advancement both in terms of new technological developments and exciting biological applications. Here, we review some of the important milestones in the field and highlight some recent biological applications. © 2014 Wiley Periodicals, Inc.

  7. SASSIE: A program to study intrinsically disordered biological molecules and macromolecular ensembles using experimental scattering restraints

    NASA Astrophysics Data System (ADS)

    Curtis, Joseph E.; Raghunandan, Sindhu; Nanda, Hirsh; Krueger, Susan

    2012-02-01

    A program to construct ensembles of biomolecular structures that are consistent with experimental scattering data are described. Specifically, we generate an ensemble of biomolecular structures by varying sets of backbone dihedral angles that are then filtered using experimentally determined restraints to rapidly determine structures that have scattering profiles that are consistent with scattering data. We discuss an application of these tools to predict a set of structures for the HIV-1 Gag protein, an intrinsically disordered protein, that are consistent with small-angle neutron scattering experimental data. We have assembled these algorithms into a program called SASSIE for structure generation, visualization, and analysis of intrinsically disordered proteins and other macromolecular ensembles using neutron and X-ray scattering restraints. Program summaryProgram title: SASSIE Catalogue identifier: AEKL_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEKL_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GNU General Public License v3 No. of lines in distributed program, including test data, etc.: 3 991 624 No. of bytes in distributed program, including test data, etc.: 826 Distribution format: tar.gz Programming language: Python, C/C++, Fortran Computer: PC/Mac Operating system: 32- and 64-bit Linux (Ubuntu 10.04, Centos 5.6) and Mac OS X (10.6.6) RAM: 1 GB Classification: 3 External routines: Python 2.6.5, numpy 1.4.0, swig 1.3.40, scipy 0.8.0, Gnuplot-py-1.8, Tcl 8.5, Tk 8.5, Mac installation requires aquaterm 1.0 (or X window system) and Xcode 3 development tools. Nature of problem: Open source software to generate structures of disordered biological molecules that subsequently allow for the comparison of computational and experimental results is limiting the use of scattering resources. Solution method: Starting with an all atom model of a protein, for example, users can input

  8. Identification and biological activities of a new antiangiogenic small molecule that suppresses mitochondrial reactive oxygen species

    SciTech Connect

    Kim, Ki Hyun; Park, Ju Yeol; Jung, Hye Jin; Kwon, Ho Jeong

    2011-01-07

    Research highlights: {yields} YCG063 was screened as a new angiogenesis inhibitor which suppresses mitochondrial ROS generation in a phenotypic cell-based screening of a small molecule-focused library. {yields} The compound inhibited in vitro and in vivo angiogenesis in a dose-dependent manner. {yields} This new small molecule tool will provide a basis for a better understanding of angiogenesis driven under hypoxic conditions. -- Abstract: Mitochondrial reactive oxygen species (ROS) are associated with multiple cellular functions such as cell proliferation, differentiation, and apoptosis. In particular, high levels of mitochondrial ROS in hypoxic cells regulate many angiogenesis-related diseases, including cancer and ischemic disorders. Here we report a new angiogenesis inhibitor, YCG063, which suppressed mitochondrial ROS generation in a phenotypic cell-based screening of a small molecule-focused library with an ArrayScan HCS reader. YCG063 suppressed mitochondrial ROS generation under a hypoxic condition in a dose-dependent manner, leading to the inhibition of in vitro angiogenic tube formation and chemoinvasion as well as in vivo angiogenesis of the chorioallantoic membrane (CAM) at non-toxic doses. In addition, YCG063 decreased the expression levels of HIF-1{alpha} and its target gene, VEGF. Collectively, a new antiangiogenic small molecule that suppresses mitochondrial ROS was identified. This new small molecule tool will provide a basis for a better understanding of angiogenesis driven under hypoxic conditions.

  9. Rodent Preclinical Models for Developing Novel Antiarthritic Molecules: Comparative Biology and Preferred Methods for Evaluating Efficacy

    PubMed Central

    Bolon, Brad; Stolina, Marina; King, Caroline; Middleton, Scot; Gasser, Jill; Zack, Debra; Feige, Ulrich

    2011-01-01

    Rodent models of immune-mediated arthritis (RMIA) are the conventional approach to evaluating mechanisms of inflammatory joint disease and the comparative efficacy of antiarthritic agents. Rat adjuvant-induced (AIA), collagen-induced (CIA), and streptococcal cell wall-induced (SCW) arthritides are preferred models of the joint pathology that occurs in human rheumatoid arthritis (RA). Lesions of AIA are most severe and consistent; structural and immunological changes of CIA best resemble RA. Lesion extent and severity in RMIA depends on experimental methodology (inciting agent, adjuvant, etc.) and individual physiologic parameters (age, genetics, hormonal status, etc.). The effectiveness of antiarthritic molecules varies with the agent, therapeutic regimen, and choice of RMIA. All RMIA are driven by overactivity of proinflammatory pathways, but the dominant molecules differ among the models. Hence, as with the human clinical experience, the efficacy of various antiarthritic molecules differs among RMIA, especially when the agent is a specific cytokine inhibitor. PMID:21253435

  10. Single molecule optical measurements of orientation and rotations of biological macromolecules

    PubMed Central

    Shroder, Deborah Y; Lippert, Lisa G; Goldman, Yale E

    2016-01-01

    The subdomains of macromolecules often undergo large orientation changes during their catalytic cycles that are essential for their activity. Tracking these rearrangements in real time opens a powerful window into the link between protein structure and functional output. Site-specific labeling of individual molecules with polarized optical probes and measuring their spatial orientation can give insight into the crucial conformational changes, dynamics, and fluctuations of macromolecules. Here we describe the range of single molecule optical technologies that can extract orientation information from these probes, we review the relevant types of probes and labeling techniques, and we highlight the advantages and disadvantages of these technologies for addressing specific inquiries. PMID:28192292

  11. Single molecule optical measurements of orientation and rotations of biological macromolecules

    NASA Astrophysics Data System (ADS)

    Shroder, Deborah Y.; Lippert, Lisa G.; Goldman, Yale E.

    2016-12-01

    Subdomains of macromolecules often undergo large orientation changes during their catalytic cycles that are essential for their activity. Tracking these rearrangements in real time opens a powerful window into the link between protein structure and functional output. Site-specific labeling of individual molecules with polarized optical probes and measurement of their spatial orientation can give insight into the crucial conformational changes, dynamics, and fluctuations of macromolecules. Here we describe the range of single molecule optical technologies that can extract orientation information from these probes, review the relevant types of probes and labeling techniques, and highlight the advantages and disadvantages of these technologies for addressing specific inquiries.

  12. Monte Carlo simulation of several biologically relevant molecules and zwitterions in water

    NASA Astrophysics Data System (ADS)

    Patuwo, Michael Y.; Bettens, Ryan P. A.

    2012-02-01

    In this work, we study the hydration free energies of butane, zwitterionic alanine, valine, serine, threonine, and asparagine, and two neuraminidase inhibitors by means of Monte Carlo (MC) simulation. The solute molecule, represented in the form of distributed multipoles and modified 6-12 potential, was varied from a non-interacting 'ghost' molecule to its full potential functions in TIP4P water. Intermediate systems with soft-core solute-solvent interaction potentials are simulated separately and then subjected to Bennett's Acceptance ratio (BAR) for the free energy calculation. Hydration shells surrounding the solute particles were used to assess the quality of potential functions.

  13. Chemical biology--identification of small molecule modulators of cellular activity by natural product inspired synthesis.

    PubMed

    Hübel, Katja; Lessmann, Torben; Waldmann, Herbert

    2008-07-01

    The aim of this tutorial review is to introduce the reader to the concept, synthesis and application of natural product-inspired compound collections as an important field in chemical biology. This review will discuss how potentially interesting scaffolds can be identified (structural classification of natural products), synthesized in an appropriate manner (including stereoselective transformations for solid phase-bound compounds) and tested in biological assays (cell-based screening as well as biochemical in vitro assays). These approaches will provide the opportunity to identify new and interesting compounds as well as new targets for chemical biology and medicinal chemistry research.

  14. Expedient construction of small molecule macroarrays via sequential palladium- and copper-mediated reactions and their ex situ biological testing†

    PubMed Central

    Frei, Reto; Breitbach, Anthony S.

    2012-01-01

    We report the highly efficient syntheses of a series of focused libraries in the small molecule macroarray format using Suzuki–Miyaura and copper-catalyzed azide–alkyne cycloaddition (or “click”) reactions. The libraries were based on stilbene and triazole scaffolds, which are known to have a broad range of biological activities, including quorum-sensing (QS) modulation in bacteria. The library products were generated in parallel on the macroarray in extremely short reaction times (~10–20 min) and isolated in excellent purities. Biological testing of one macroarray library post-cleavage (ex situ) revealed several potent agonists of the QS receptor, LuxR, in Vibrio fischeri. These synthetic agonists, in contrast to others that we have reported, were only active in the presence of the native QS signal in V. fischeri, which is suggestive of a different mode of activity. Notably, the results presented herein showcase the ready compatibility of the macroarray platform with chemical reactions that are commonly utilized in small molecule probe and drug discovery today. As such, this work serves to expand the utility of the small molecule macroarray as a rapid and operationally straightforward approach toward the synthesis and screening of bioactive agents. PMID:23198087

  15. Nanometric Gap Structure with a Fluid Lipid Bilayer for the Selective Transport and Detection of Biological Molecules.

    PubMed

    Ando, Koji; Tanabe, Masashi; Morigaki, Kenichi

    2016-08-09

    The biological membrane is a natural biosensing platform that can detect specific molecules with extremely high sensitivity. We developed a biosensing methodology by combining a model biological membrane and a nanometer-sized gap structure on a glass substrate. The model membrane comprised lithographically patterned polymeric and fluid lipid bilayers. The polymeric bilayer was bonded to a poly(dimethylsiloxane) (PDMS) sheet by using an adhesion layer with a defined thickness (lipid vesicles). Extruded lipid vesicles having a biotin moiety on the surface were used as the adhesion layer in conjunction with the biotin-streptavidin linkage. A gap structure was formed between the fluid bilayer and PDMS (nanogap junction). The thickness of the gap structure was several tens of nanometers, as determined by the thickness of the adhesion layer. The nanogap junction acted as a sensitive biosensing platform. From a mixture of proteins (cholera toxin and albumin), the target protein (cholera toxin) was selectively transported into the gap by the specific binding to a glycolipid (GM1) in the fluid bilayer and lateral diffusion. The target protein molecules were then detected with an elevated signal-to-noise ratio due to the reduced background noise in the nanometric gap. The combination of selective transport and reduced background noise drastically enhanced the sensitivity toward the target protein. The nanogap junction should have broad biomedical applications by realizing highly selective and sensitive biosensing in samples having diverse coexisting molecules.

  16. PDMS-glass bonding using grafted polymeric adhesive--alternative process flow for compatibility with patterned biological molecules.

    PubMed

    Beh, Cyrus Weijie; Zhou, Weizhuang; Wang, Tza-Huei

    2012-10-21

    We report a novel modification of silicone elastomer polydimethylsiloxane (PDMS) with a polymer graft that allows interfacial bonding between an elastomer and glass substrate to be performed without exposure of the substrate to harsh treatment conditions, such as oxygen plasma. Organic molecules can thus be patterned within microfluidic channels and still remain functional post-bonding. In addition, after polymer grafting the PDMS can be stored in a desiccator for at least 40 days, and activated upon exposure to acidic buffer for bonding. The bonded devices remain fully bonded in excess of 80 psi driving pressure, with no signs of compromise to the bond integrity. Finally, we demonstrate the compatibility of our method with biological molecules using a proof-of-concept DNA sensing device, in which fluorescently-labelled DNA targets are successfully captured by a patterned probe in a device sealed using our method, while the pattern on a plasma-treated device was completely destroyed. Therefore, this method provides a much-needed alternative bonding process for incorporation of biological molecules in microfluidic devices.

  17. PDMS-Glass bonding using grafted polymeric adhesive - Alternative process flow for compatibility with patterned biological molecules

    PubMed Central

    Beh, Cyrus Weijie; Zhou, Weizhuang

    2013-01-01

    We report a novel modification of silicone elastomer, polydimethylsiloxane (PDMS) with a polymer graft that allows interfacial bonding between elastomer and glass substrate to be performed without exposure of said substrate to harsh treatment conditions like oxygen plasma. Organic molecules can thus be patterned within microfluidic channels and still remain functional post-bonding. In addition, after polymer grafting the PDMS can be stored in a desiccator for at least 40 days, and activated upon exposure to acidic buffer for bonding. The bonded devices remain fully bonded in excess of 80 psi driving pressure, with no signs of compromise to the bond integrity. Finally, we demonstrate the compatibility of our method with biological molecules using a proof-of-concept DNA sensing device, in which fluorescently-labelled DNA targets are successfully captured by a patterned probe in a device sealed using our method, while the pattern on a plasma-treated device was completely destroyed. Therefore, this method provides a much-needed alternative bonding process for incorporation of biological molecules in microfluidic devices. PMID:22858861

  18. Unequal Activities of Enantiomers via Biological Receptors: Examples of Chiral Drug, Pesticide, and Fragrance Molecules

    ERIC Educational Resources Information Center

    Mannschreck, Albrecht; Kiesswetter, Roland; von Angerer, Erwin

    2007-01-01

    A molecule coming from outside an organism can form a ligand-receptor complex. Upon its formation, a message is transmitted, for example, to certain cells. In this way, two enantiomers can emit messages that differ, either quantitatively or qualitatively. In the present article, these facts are taken as a common basis for the actions of chiral…

  19. Unequal Activities of Enantiomers via Biological Receptors: Examples of Chiral Drug, Pesticide, and Fragrance Molecules

    ERIC Educational Resources Information Center

    Mannschreck, Albrecht; Kiesswetter, Roland; von Angerer, Erwin

    2007-01-01

    A molecule coming from outside an organism can form a ligand-receptor complex. Upon its formation, a message is transmitted, for example, to certain cells. In this way, two enantiomers can emit messages that differ, either quantitatively or qualitatively. In the present article, these facts are taken as a common basis for the actions of chiral…

  20. Experimental evidence of hot carriers solar cell operation in multi-quantum wells heterostructures

    SciTech Connect

    Rodière, Jean; Lombez, Laurent; Le Corre, Alain; Durand, Olivier; Guillemoles, Jean-François

    2015-05-04

    We investigated a semiconductor heterostructure based on InGaAsP multi quantum wells (QWs) using optical characterizations and demonstrate its potential to work as a hot carrier cell absorber. By analyzing photoluminescence spectra, the quasi Fermi level splitting Δμ and the carrier temperature are quantitatively measured as a function of the excitation power. Moreover, both thermodynamics values are measured at the QWs and the barrier emission energy. High values of Δμ are found for both transition, and high carrier temperature values in the QWs. Remarkably, the quasi Fermi level splitting measured at the barrier energy exceeds the absorption threshold of the QWs. This indicates a working condition beyond the classical Shockley-Queisser limit.

  1. Nonlinear processes in multi-quantum-well plasmonic metasurfaces: Electromagnetic response, saturation effects, limits, and potentials

    NASA Astrophysics Data System (ADS)

    Gomez-Diaz, J. S.; Tymchenko, M.; Lee, J.; Belkin, M. A.; Alà, Andrea

    2015-09-01

    Nonlinear metasurfaces based on coupling a locally enhanced plasmonic response to intersubband transitions of n -doped multi-quantum-wells (MQWs) can provide second-order susceptibilities orders of magnitude larger than any other nonlinear flat structure measured so far. Here we present a comprehensive theory to characterize the electromagnetic response of nonlinear processes occurring in ultrathin MQW-based plasmonic metasurfaces, providing a homogeneous model that takes phase matching at the unit-cell level and the influence of saturation and losses into account. In addition, the limits imposed by saturation of the MQW transitions on the nonlinear response of these metasurfaces are analytically derived, revealing useful guidelines to design devices with enhanced performance. Our approach is first validated using experimental data and then applied to theoretically investigate novel designs able to achieve significant second-harmonic generation efficiency in the infrared frequency band.

  2. Integration of biological ion channels onto optically addressable micro-fluidic electrode arrays for single molecule characterization.

    SciTech Connect

    Brozik, Susan Marie; Frink, Laura J. Douglas; Bachand, George David; Keller, David J.; Patrick, Elizabeth L.; Marshall, Jason A.; Ortiz, Theodore P.; Meyer, Lauren A.; Davis, Ryan W.; Brozik, James A.; Flemming, Jeb Hunter

    2004-12-01

    The challenge of modeling the organization and function of biological membranes on a solid support has received considerable attention in recent years, primarily driven by potential applications in biosensor design. Affinity-based biosensors show great promise for extremely sensitive detection of BW agents and toxins. Receptor molecules have been successfully incorporated into phospholipid bilayers supported on sensing platforms. However, a collective body of data detailing a mechanistic understanding of membrane processes involved in receptor-substrate interactions and the competition between localized perturbations and delocalized responses resulting in reorganization of transmembrane protein structure, has yet to be produced. This report describes a systematic procedure to develop detailed correlation between (recognition-induced) protein restructuring and function of a ligand gated ion channel by combining single molecule fluorescence spectroscopy and single channel current recordings. This document is divided into three sections: (1) reported are the thermodynamics and diffusion properties of gramicidin using single molecule fluorescence imaging and (2) preliminary work on the 5HT{sub 3} serotonin receptor. Thirdly, we describe the design and fabrication of a miniaturized platform using the concepts of these two technologies (spectroscopic and single channel electrochemical techniques) for single molecule analysis, with a longer term goal of using the physical and electronic changes caused by a specific molecular recognition event as a transduction pathway in affinity based biosensors for biotoxin detection.

  3. The lifetime of the soliton in the improved Davydov model at the biological temperature 300 K for protein molecules

    NASA Astrophysics Data System (ADS)

    Xiao-feng, Pang

    We study the effects of quantum fluctuations and thermal perturbations on the lifetime of the soliton in the improved Davydov model proposed by us with two-quanta and with an added interaction. By using quantum perturbation theory, we compute the soliton lifetime for a wide ranges of parameter values relevant for protein molecules. The lifetime of the new soliton at the biological temperature 300 K is of the order of 10-10 second or τ/τ>= 500 for parameters appropriate to α-helical protein molecules. This shows clearly that the new soliton in the improved model is a viable mechanism for the bio-energy transport in the α-helix region of proteins.

  4. Coulomb explosion and binary encounter processes in collisions between slow ions and small molecules of biological interest

    SciTech Connect

    Juhasz, Z.; Sulik, B.

    2008-12-08

    In this work we study the ion impact induced fragmentation of small molecules, which are relevant for radiation damage studies in biological tissues. We present double differential ion emission yields for collisions of N{sup 6+} ions with water and methane molecules at 15 and 30 keV impact energies. The angular distribution of the fragment ions shows post-collision and nucleus-nucleus binary collision effects. In the multiple capture energy range, a strong interplay is indicated between the Coulomb explosion and the binary collision mechanisms. In the energy region, where triple capture is dominant, an unexpected angular distribution was found for water fragments, which may be attributed to orientation sensitivity of some of the capture channels. Such processes are relevant for astrophysics and radiation therapy.

  5. Effect of co-existing biologically relevant molecules and ions on DNA photocleavage caused by pyrene and its derivatives.

    PubMed

    Wang, Shuguang; Yu, Hongtao

    2005-04-01

    Inorganic ions, coenzymes, amino acids, and saccharides could co-exist with toxic environmental chemicals, such as polycyclic aromatic hydrocarbons (PAHs), in the cell. The presence of these co-existing chemicals can modulate the toxicity of the PAHs. One of the genotoxic effects by PAHs is light-induced cleavage, or photocleavage, of DNA. The effect of inorganic ions I-, Na+, Ca2+, Mg2+, Fe3+, Mn2+, Cu2+, and Zn2+ and biological molecules riboflavin, histidine, mannitol, nicotinamide adenine dinucleotide (NAD), glutathione, and glutamic acid on the DNA photocleavage by pyrene, 1-hydroxypyrene (1-HP), and 1-aminopyrene (1-AP), is studied. The non-transition metal ions Na+, Ca2+, and Mg2+, usually have very little inhibitory effects, while the transition metal ions Fe3+, Cu2+, and Zn2+ enhance, Mn2+ inhibits the DNA photocleavage. The effect by biological molecules is complex, depending on the photochemical reaction mechanisms of the compounds tested (1-AP, 1-HP and pyrene) and on the chemical nature of the added biological molecules. Riboflavin, histidine, and mannitol enhance DNA photocleavage by all three compounds, except that mannitol has no effect on the photocleavage of DNA by pyrene. Glutathione inhibits the DNA photocleavage by 1-AP and 1-HP, but has no effect on that by pyrene. NAD enhances the DNA photocleavage by 1-AP, but has no effect on that by 1-HP and pyrene. Glutamic acid enhances the DNA photocleavage by 1-AP and pyrene, but inhibits that by 1-HP. These results show that the co-existing chemicals may have a profound effect on the toxicity of PAHs, or possibly on the toxicity of many other chemicals. Therefore, if one studies the toxic effects of PAHs or other toxic chemicals, the effect of the co-existing chemicals or ions needs to be considered.

  6. Normal Mode Flexible Fitting of High-Resolution Structures of Biological Molecules Toward SAXS Data

    PubMed Central

    Gorba, Christian; Tama, Florence

    2010-01-01

    We present a method to reconstruct a three-dimensional protein structure from an atomic pair distribution function derived from the scattering intensity profile from SAXS data by flexibly fitting known x-ray structures. This method uses a linear combination of low-frequency normal modes from an elastic network description of the molecule in an iterative manner to deform the structure to conform optimally to the target pair distribution function derived from SAXS data. For computational efficiency, the protein and water molecules included in the protein first hydration shell are coarse-grained. In this paper, we demonstrate the validity of our coarse-graining approach to study SAXS data. Illustrative results of our flexible fitting studies on simulated SAXS data from five different proteins are presented. PMID:20634984

  7. Studies of the dynamics of biological macromolecules using Au nanoparticle-DNA artificial molecules.

    PubMed

    Chen, Qian; Smith, Jessica M; Rasool, Haider I; Zettl, Alex; Alivisatos, A Paul

    2014-01-01

    The recent development of graphene liquid cells, a nanoscale version of liquid bubble wrap, is a breakthrough for in situ liquid phase electron microscopy (EM). Using ultrathin graphene sheets as the liquid sample container, graphene liquid cells have allowed the unprecedented atomic resolution observation of solution phase growth and dynamics of nanocrystals. Here we explore the potential of this technique to probe nanoscale structure and dynamics of biomolecules in situ, using artificial Au nanoparticle-DNA artificial molecules as model systems. The interactions of electrons with both the artificial molecules and the liquid environment have been demonstrated and discussed, revealing both the opportunities and challenges of using graphene liquid cell EM as a new method of bio-imaging.

  8. High-throughput, dual probe biological assays based on single molecule detection

    DOEpatents

    Hollars, Christopher W.; Huser, Thomas R.; Lane, Stephen M.; Balhorn, Rodney L.; Bakajin, Olgica; Darrow, Christopher; Satcher, Jr., Joe H.

    2006-07-11

    A method and apparatus with the sensitivity to detect and identify single target molecules through the localization of dual, fluorescently labeled probe molecules. This can be accomplished through specific attachment of the taget to a surface or in a two-dimensional (2D) flowing fluid sheet having approximate dimensions of 0.5 .mu.m.times.100 .mu.m.times.100 .mu.m. A device using these methods would have 10.sup.3 10.sup.4 greater throughput than previous one-dimensional (1D) micro-stream devices having 1 .mu.m.sup.3 interrogation volumes and would for the first time allow immuno- and DNA assays at ultra-low (femtomolar) concentrations to be performed in short time periods (.about.10 minutes). The use of novel labels (such as metal or semiconductor nanoparticles) may be incorporated to further extend the sensitivity possibly into the attomolar range.

  9. Ncm, a Photolabile Group for Preparation of Caged Molecules: Synthesis and Biological Application

    PubMed Central

    Muralidharan, Sukumaran; Dirda, Nathaniel D. A.; Katz, Elizabeth J.; Tang, Cha-Min; Bandyopadhyay, Sharba; Kanold, Patrick O.

    2016-01-01

    Ncm, 6-nitrocoumarin-7-ylmethyl, is a photolabile protective group useful for making “caged” molecules. Ncm marries the reliable photochemistry of 2-nitrobenzyl systems with the excellent stability and spectroscopic properties of the coumarin chromophore. From simple, commercially available starting materials, preparation of Ncm and its caged derivatives is both quick and easy. Photorelease of Ncm-caged molecules occurs on the microsecond time scale, with quantum efficiencies of 0.05–0.08. We report the synthesis and physical properties of Ncm and its caged derivatives. The utility of Ncm-caged glutamate for neuronal photostimulation is demonstrated in cultured hippocampal neurons and in brain slice preparations. PMID:27695074

  10. Solid-State ¹⁷O NMR studies of organic and biological molecules: Recent advances and future directions.

    PubMed

    Wu, Gang

    2016-02-01

    This Trends article highlights the recent advances published between 2012 and 2015 in solid-state (17)O NMR for organic and biological molecules. New developments in the following areas are described: (1) new oxygen-containing functional groups, (2) metal organic frameworks, (3) pharmaceuticals, (4) probing molecular motion in organic solids, (5) dynamic nuclear polarization, and (6) paramagnetic coordination compounds. For each of these areas, the author offers his personal views on important problems to be solved and possible future directions. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Mass spectrometry imaging of small molecules in biological tissues using graphene oxide as a matrix.

    PubMed

    Zhou, Dan; Guo, Shuai; Zhang, Mo; Liu, Yujie; Chen, Tianjing; Li, Zhili

    2017-04-15

    With the development of matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI), molecular interrogation of tissue sections over a wide mass range has become feasible, but small molecule analysis is still far from being fully reached due to the limited sensitivity and matrix interference. Herein, graphene oxide (GO) is used as a MALDI matrix to image small molecules in tissues in negative ion mode. Finally, 212 of molecules including 190 of lipids and 22 of low molecular weight metabolites were detected and spatially visualized in mouse brain tissue sections without the interference of matrix ions/clusters, and the structures of 69 of the lipids were confirmed by using in situ tandem mass spectrometry. A further application of GO matrix could reveal distinct spatio-molecular signatures in viable and necrotic tumor regions derived from a mouse breast cancer tissue. In addition, GO as a MALDI matrix has exhibited a better performance in MSI of lipids relative to N-(1-naphthyl) ethylenediamine dihydrochloride and 9-aminoacridine. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Mapping the Importance of Four Factors in Creating Monovalent Ion Selectivity in Biological Molecules

    PubMed Central

    Thomas, Michael; Jayatilaka, Dylan; Corry, Ben

    2011-01-01

    The ability of macrocycles, enzymes, ion channels, transporters, and DNA to differentiate among ion types is often crucial to their function. Using molecular dynamics simulations on both detailed systems and simple models, we quantify the importance of several factors which affect the ion selectivity of such molecules, including the number of coordinating ligands, their dipole moment, and their vibrational motion. The information resulting from our model systems is distilled into a series of selectivity maps that can be used to read off the relative free energy associated with binding of different ions, and to provide an estimate of the importance of the various factors. Although our maps cannot capture all elements of real systems, it is remarkable that they produce differential site-binding energies that are in line with experiment and more-detailed simulations for a variety of systems—making them useful for understanding the origins of selective binding and transport. The chemical nature of the coordinating ligands is essential for creating thermodynamic ion selectivity in flexible molecules (such as 18c6), but as the binding site becomes more rigid, the number of ligands (as in ion channels) and the reduction of thermal fluctuations (as in amino-acid transporters) can become important. In the future, our maps could aid in the determination of the local structure from binding energies and assist in the design of novel ion selective molecules. PMID:21190657

  13. Adsorption of biological molecules to a solid support for scanning probe microscopy.

    PubMed

    Müller, D J; Amrein, M; Engel, A

    1997-07-01

    Scanning probe microscopes are now established tools to study the surface structure of biological macromolecules under physiological conditions. Sample preparation methods for this microscopy all have the objective to attach the specimen firmly to a support. Here we analyse the commonly used method of adsorbing biological specimens to freshly cleaved mica. This is facilitated by adjusting the electrolyte concentration and the pH of the buffer solution. Native macromolecular systems absorbed to mica in this way can be reproducibly imaged at submolecular resolution.

  14. Discovery of antiviral molecules for dengue: In silico search and biological evaluation.

    PubMed

    Cabarcas-Montalvo, Maria; Maldonado-Rojas, Wilson; Montes-Grajales, Diana; Bertel-Sevilla, Angela; Wagner-Döbler, Irene; Sztajer, Helena; Reck, Michael; Flechas-Alarcon, Maria; Ocazionez, Raquel; Olivero-Verbel, Jesus

    2016-03-03

    Dengue disease is a global disease that has no effective treatment. The dengue virus (DENV) NS2B/NS3 protease complex is a target for designing specific antivirals due to its importance in viral replication and its high degree of conservation. NS2B/NS3 protease complex structural information was employed to find small molecules that are capable of inhibiting the activity of the enzyme complex. This inhibitory activity was probed with in vitro assays using a fluorescent substrate and the complex NS2B/NS3 obtained by recombinant DNA techniques. HepG2 cells infected with dengue virus serotype 2 were used to test the activity against dengue virus replication. A total of 210,903 small molecules from PubChem were docked in silico to the NS2B/NS3 structure (PDB: 2FOM) to find molecules that were capable of inhibiting this protein complex. Five of the best 500 leading compounds, according to their affinity values (-11.6 and -13.5 kcal/mol), were purchased. The inhibitory protease activity on the recombinant protein and antiviral assays was tested. Chemicals CID 54681617, CID 54692801 and CID 54715399 were strong inhibitors of NS2B/NS3, with IC50 values (μM) and percentages of viral titer reductions of 19.9, 79.9%; 17.5, 69.8%; and 9.1, 73.9%, respectively. Multivariate methods applied to the molecular descriptors showed two compounds that were structurally different from other DENV inhibitors. This discovery opens new possibilities for obtaining drug candidates against Dengue virus. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  15. The RCSB PDB “Molecule of the Month”: Inspiring a Molecular View of Biology

    PubMed Central

    Goodsell, David S.; Dutta, Shuchismita; Zardecki, Christine; Voigt, Maria; Berman, Helen M.; Burley, Stephen K.

    2015-01-01

    The Research Collaboratory for Structural Bioinformatics (RCSB) Molecule of the Month series provides a curated introduction to the 3-D biomolecular structures available in the Protein Data Bank archive and the tools that are available at the RCSB website for accessing and exploring them. A variety of educational materials, such as articles, videos, posters, hands-on activities, lesson plans, and curricula, build on this series for use in a variety of educational settings as a general introduction to key topics, such as enzyme action, protein synthesis, and viruses. The series and associated educational materials are freely available at www.rcsb.org. PMID:25942442

  16. The RCSB PDB "Molecule of the Month": Inspiring a Molecular View of Biology.

    PubMed

    Goodsell, David S; Dutta, Shuchismita; Zardecki, Christine; Voigt, Maria; Berman, Helen M; Burley, Stephen K

    2015-05-01

    The Research Collaboratory for Structural Bioinformatics (RCSB) Molecule of the Month series provides a curated introduction to the 3-D biomolecular structures available in the Protein Data Bank archive and the tools that are available at the RCSB website for accessing and exploring them. A variety of educational materials, such as articles, videos, posters, hands-on activities, lesson plans, and curricula, build on this series for use in a variety of educational settings as a general introduction to key topics, such as enzyme action, protein synthesis, and viruses. The series and associated educational materials are freely available at www.rcsb.org.

  17. Late-Stage Diversification of Biologically Active Molecules via Chemoenzymatic C-H Functionalization.

    PubMed

    Durak, Landon J; Payne, James T; Lewis, Jared C

    2016-03-04

    Engineered variants of rebeccamycin halogenase were used to selectively halogenate a number of biologically active aromatic compounds. Subsequent Pd-catalyzed cross-coupling reactions on the crude extracts of these reactions were used to install aryl, amine, and ether substituents at the halogenation site. This simple, chemoenzymatic method enables non-directed functionalization of C-H bonds on a range of substrates to provide access to derivatives that would be challenging or inefficient to prepare by other means.

  18. Detection of biological molecules using boronate-based chemical amplification and optical sensors

    DOEpatents

    Van Antwerp, William Peter; Mastrototaro, John Joseph; Lane, Stephen M.; Satcher, Jr., Joe H.; Darrow, Christopher B.; Peyser, Thomas A.; Harder, Jennifer

    2004-06-15

    Methods are provided for the determination of the concentration of biological levels of polyhydroxylated compounds, particularly glucose. The methods utilize an amplification system that is an analyte transducer immobilized in a polymeric matrix, where the system is implantable and biocompatible. Upon interrogation by an optical system, the amplification system produces a signal capable of detection external to the skin of the patient. Quantitation of the analyte of interest is achieved by measurement of the emitted signal.

  19. Detection of biological molecules using boronate-based chemical amplification and optical sensors

    DOEpatents

    Van Antwerp, William Peter; Mastrototaro, John Joseph; Lane, Stephen M.; Satcher, Jr., Joe H.; Darrow, Christopher B.; Peyser, Thomas A.; Harder, Jennifer

    1999-01-01

    Methods are provided for the determination of the concentration of biological levels of polyhydroxylated compounds, particularly glucose. The methods utilize an amplification system that is an analyte transducer immobilized in a polymeric matrix, where the system is implantable and biocompatible. Upon interrogation by an optical system, the amplification system produces a signal capable of detection external to the skin of the patient. Quantitation of the analyte of interest is achieved by measurement of the emitted signal.

  20. Topology simplification: Important biological phenomenon or evolutionary relic?. Comment on "Disentangling DNA molecules" by Alexander Vologodskii

    NASA Astrophysics Data System (ADS)

    Bates, Andrew D.; Maxwell, Anthony

    2016-09-01

    The review, Disentangling DNA molecules[1], gives an excellent technical description of the phenomenon of topology simplification (TS) by type IIA DNA topoisomerases (topos). In the 20 years since its discovery [2], this effect has attracted a good deal of attention, probably because of its apparently magical nature, and because it seemed to offer a solution to the conundrum that all type II topos rely on ATP hydrolysis, but only bacterial DNA gyrases were known to transduce the free energy of hydrolysis into torsion (supercoiling) in the DNA. It made good sense to think that the other enzymes are using the energy to reduce the level of supercoiling, knotting, and particularly decatenation (unlinking), below equilibrium, since the key activity of the non-supercoiling topos is the removal of links between daughter chromosomes [3]. As Vologodskii discusses [1], there have been a number of theoretical models developed to explain how the local effect of a type II topo can influence the global level of knotting and catenation in large DNA molecules, and he explains how features of two of the most successful models (bent G segment and hooked juxtapositions) may be combined to explain the magnitude of the effect and overcome a kinetic problem with the hooked juxtaposition model.

  1. Crystallography Without Crystals: Determining the Structure of Individual Biological Molecules and Nanoparticles

    ScienceCinema

    Ourmazd, Abbas [University of Wisconsin, Milwaukee, Wisconsin, USA

    2016-07-12

    Ever shattered a valuable vase into 10 to the 6th power pieces and tried to reassemble it under a light providing a mean photon count of 10 minus 2 per detector pixel with shot noise? If you can do that, you can do single-molecule crystallography. This talk will outline how this can be done in principle. In more technical terms, the talk will describe how the combination of scattering physics and Bayesian algorithms can be used to reconstruct the 3-D diffracted intensity distribution from a collection of individual 2-D diffiraction patterns down to a mean photon count of 10 minus 2 per pixel, the signal level anticipated from the Linac Coherent Light Source, and hence determine the structure of individual macromolecules and nanoparticles.

  2. Crystallography Without Crystals: Determining the Structure of Individual Biological Molecules and Nanoparticles

    SciTech Connect

    Ourmazd, Abbas

    2008-03-05

    Ever shattered a valuable vase into 10 to the 6th power pieces and tried to reassemble it under a light providing a mean photon count of 10 minus 2 per detector pixel with shot noise? If you can do that, you can do single-molecule crystallography. This talk will outline how this can be done in principle. In more technical terms, the talk will describe how the combination of scattering physics and Bayesian algorithms can be used to reconstruct the 3-D diffracted intensity distribution from a collection of individual 2-D diffiraction patterns down to a mean photon count of 10 minus 2 per pixel, the signal level anticipated from the Linac Coherent Light Source, and hence determine the structure of individual macromolecules and nanoparticles.

  3. Design, synthesis and biological activity of novel molecules designed to target PARP and DNA.

    PubMed

    Goodfellow, Elliot; Senhaji Mouhri, Zhor; Williams, Christopher; Jean-Claude, Bertrand J

    2017-02-01

    In order to enhance the cytotoxic potential of poly(ADP-ribose) polymerase (PARP) inhibitors in BRCA1 or 2 deficient tumours, we designed a series of molecules containing a 1,2,3-triazene moiety tethered to a PARP targeting scaffold. A cell-based selectivity assay involving a BRCA2-deficient Chinese hamster cell line and its corresponding BRCA2 wild type transfectant, was used to predict the PARP targeting potential of the latter agents. The results showed that adding a DNA damaging function to the PARP inhibitors decreased but did not abrogate the selective targeting of the BRCA2-deficient cells. The DNA damaging moiety augmented the potency in BRCA2 deficient cells by 2-20 fold. The most selective dual PARP-DNA targeting agent 14b was found to possess dual DNA and PARP targeting properties.

  4. Role of ATP as a Key Signaling Molecule Mediating Radiation-Induced Biological Effects.

    PubMed

    Kojima, Shuji; Ohshima, Yasuhiro; Nakatsukasa, Hiroko; Tsukimoto, Mitsutoshi

    2017-01-01

    Adenosine triphosphate (ATP) serves as a signaling molecule for adaptive responses to a variety of cytotoxic agents and plays an important role in mediating the radiation stress-induced responses that serve to mitigate or repair the injurious effects of γ radiation on the body. Indeed, low doses of radiation may have a net beneficial effect by activating a variety of protective mechanisms, including antitumor immune responses. On the other hand, ATP signaling may be involved in the radiation resistance of cancer cells. Here, focusing on our previous work, we review the evidence that low-dose γ irradiation (0.25-0.5 Gy) induces release of extracellular ATP, and that the released ATP mediates multiple radiation-induced responses, including increased intracellular antioxidant synthesis, cell-mediated immune responses, induction of DNA damage repair systems, and differentiation of regulatory T cells.

  5. Role of ATP as a Key Signaling Molecule Mediating Radiation-Induced Biological Effects

    PubMed Central

    Ohshima, Yasuhiro; Nakatsukasa, Hiroko; Tsukimoto, Mitsutoshi

    2017-01-01

    Adenosine triphosphate (ATP) serves as a signaling molecule for adaptive responses to a variety of cytotoxic agents and plays an important role in mediating the radiation stress-induced responses that serve to mitigate or repair the injurious effects of γ radiation on the body. Indeed, low doses of radiation may have a net beneficial effect by activating a variety of protective mechanisms, including antitumor immune responses. On the other hand, ATP signaling may be involved in the radiation resistance of cancer cells. Here, focusing on our previous work, we review the evidence that low-dose γ irradiation (0.25-0.5 Gy) induces release of extracellular ATP, and that the released ATP mediates multiple radiation-induced responses, including increased intracellular antioxidant synthesis, cell-mediated immune responses, induction of DNA damage repair systems, and differentiation of regulatory T cells. PMID:28250717

  6. Multi-Quantum Well Structures to Improve the Performance of Multijunction Solar Cells

    NASA Astrophysics Data System (ADS)

    Samberg, Joshua Paul

    Current, lattice matched triple junction solar cell efficiency is approximately 44% at a solar concentration of 942x. Higher efficiency for such cells can be realized with the development of a 1eV bandgap material lattice matched to Ge. One of the more promising materials for this application is that of the InGaAs/GaAsP multi-quantum well (MQW) structure. By inserting a stress/strain-balanced InGaAs/GaAsP MQW structure into the iregion of a GaAs p-i-n diode, the absorption edge of the p-i-n diode can be red shifted with respect to that of a standard GaAs p-n diode. Compressive stress in the InGaAs wells are balanced via GaAsP barriers subjected to tensile stress. Individually, the InGaAs and GaAsP layers are grown below their critical layer thickness to prevent the formation of misfit and threading dislocations. Until recently InGaAs/GaAsP MQWs have been somewhat hindered by their usage of low phosphorus-GaAsP barriers. Presented within is the development of a high-P composition GaAsP and the merits for using such a high composition of phosphorus are discussed. It is believed that these barriers represent the highest phosphorus content to date in such a structure. By using high composition GaAsP the carriers are collected via tunneling (for barriers .30A) as opposed to thermionic emission. Thus, by utilizing thin, high content GaAsP barriers one can increase the percentage of the intrinsic region in a p-i-n structure that is comprised of the InGaAs well in addition to increasing the number of periods that can be grown for a given depletion width. However, standard MQWs of this type inherently possess undesirable compressive strain and quantum size effects (QSE) that cause the optical absorption of the InGaAs wells to blue shift. To circumvent these deleterious QSEs stress balanced, pseudomorphic InGaAs/GaAsP staggered MQWs were developed. Tunneling is still a viable mode for carrier transport in the staggered MQW structures. GaAs interfacial layers within the multi-quantum

  7. [Recent progress in the theoretical studies of structure, function, and reaction of biological molecules].

    PubMed

    Hirao, Hajime; Morokuma, Keiji

    2011-01-01

    Essential biomolecular functions often involve electron-related events such as chemical reactions and photoluminescence phenomena. Theoretical description of such electronic processes requires the use of quantum mechanics (QM), but the number of atoms that can be handled with QM is usually smaller than the number of atoms present in a single protein. A reasonable strategy is therefore to give priority to a few tens or hundreds of atoms in the system and deal with them quantum mechanically. Lower-priority atoms influence the event occurring in the higher-priority area; therefore, their effect should also be taken into account. Under these circumstances, a reasonable approach is to apply two or more different theoretical methods to differently prioritized subsystems. QM can be combined, for example, with less accurate yet much less demanding molecular mechanics (MM). Our own N-layered integrated molecular orbital and molecular mechanics (ONIOM) method allows for such hybrid calculations, and our group has been applying it to a wide range of biology-related problems. In this paper, we briefly explain the theoretical background and the procedure for the theoretical investigation of biological systems. Subsequently, we provide an overview of some of our recent studies of metalloenzymes and photobiology-related problems.

  8. Stable organic field-effect transistors for continuous and nondestructive sensing of chemical and biologically relevant molecules in aqueous environment.

    PubMed

    Yun, Minseong; Sharma, Asha; Fuentes-Hernandez, Canek; Hwang, Do Kyung; Dindar, Amir; Singh, Sanjeev; Choi, Sangmoo; Kippelen, Bernard

    2014-02-12

    The use of organic field-effect transistors (OFETs) as sensors in aqueous media has gained increased attention for environmental monitoring and medical diagnostics. However, stable operation of OFETs in aqueous media is particularly challenging because of electrolytic hydrolysis of water, high ionic conduction through the analyte, and irreversible damage of organic semiconductors when exposed to water. To date, OFET sensors have shown the capability of label-free sensing of various chemical/biological species, but they could only be used once because their operational stability and lifetime while operating in aqueous environments has been poor, and their response times typically slow. Here, we report on OFETs with unprecedented water stability. These OFETs are suitable for the implementation of reusable chemical/biological sensors because they primarily respond to charged species diluted in an aqueous media by rapidly shifting their threshold voltage. These OFET sensors present stable current baselines and saturated signals which are ideal for detection of low concentration of small or large molecules that alter the pH of an aqueous environment. The overall response of these OFET sensors paves the way for the development of continuous chemical/biological nondestructive sensor applications in aqueous media.

  9. Analyzing free zinc(II) ion concentrations in cell biology with fluorescent chelating molecules.

    PubMed

    Maret, Wolfgang

    2015-02-01

    Essential metal ions are tightly controlled in biological systems. An understanding of metal metabolism and homeostasis is being developed from quantitative information of the sizes, concentrations, and dynamics of cellular and subcellular metal ion pools. In the case of human zinc metabolism, minimally 24 proteins of two zinc transporter families and a dozen metallothioneins participate in cellular uptake, extrusion, and re-distribution among cellular compartments. Significantly, zinc(ii) ions are now considered signaling ions in intra- and intercellular communication. Such functions require transients of free zinc ions. It is experimentally quite challenging to distinguish zinc that is protein-bound from zinc that is not bound to proteins. Measurement of total zinc is relatively straightforward with analytical techniques such as atomic absorption/emission spectroscopy or inductively coupled plasma mass spectrometry. Total zinc concentrations of human cells are 200-300 μM. In contrast, the pool of non-protein bound zinc is mostly examined with fluorescence microscopy/spectroscopy. There are two widely applied fluorescence approaches, one employing low molecular weight chelating agents ("probes") and the other metal-binding proteins ("sensors"). The protein sensors, such as the CALWY, Zap/ZifCY, and carbonic anhydrase-based sensors, can be genetically encoded and have certain advantages in terms of controlling intracellular concentration, localization, and calibration. When employed correctly, both probes and sensors can establish qualitative differences in free zinc ion concentrations. However, when quantitative information is sought, the assumptions underlying the applications of probes and sensors must be carefully examined and even then measured pools of free zinc ions remain methodologically defined. A consensus is building that the steady-state free zinc ion concentrations in the cytosol are in the picomolar range but there is no consensus on their

  10. Energy band design for p-type tensile strained Si/SiGe multi-quantum well infrared photodetector

    NASA Astrophysics Data System (ADS)

    Li, Jin-tao; Chen, Song-yan; Qi, Dong-feng; Huang, Wei; Li, Cheng; Lai, Hong-kai

    2011-05-01

    The band structure of the confined states is calculated for Si/SiGe multi-quantum well infrared photodetector (M-QWIP). The influence of the Ge component in pseudosubstrate on the energy band structure of Si/Si{in0.54}Ge{in0.46} multi-quantum wells (MQWs) is investigated. It is found that the high energy levels in the MQWs move up while the low energy levels move down as the Ge component in pseudosubstrate increases. The influence of the barrier width on the energy band structure of MQWs is also studied based on the 6 × 6 k·p method. The results show that the Si barrier between 5 nm and 10 nm is optimized to enhance the intersubband absorption in the MQWs.

  11. The Origin of Universal Scaling Laws in Biology from Molecules and Cells to Whales

    NASA Astrophysics Data System (ADS)

    West, Geoffrey B.

    1999-10-01

    Even though biological systems are the most complex physical systems known, they satisfy remarkably simple scaling laws. For example, metabolic rate (the power needed to sustain life) scales like the -power of mass over 26 orders of magnitude ranging from the molecular respiratory complex within mitochondria up through the smallest unicellular organism (mycoplasma) to the largest animals (whales) and plants (giant sequoia). Other scaling laws relate how organismal features change with size over many orders of magnitude; these include time-scales (such as lifespan and heart-rate) and sizes (such as the radius of a tree trunk or the aorta). All of these can be expressed as power laws with exponents which are typically simple multiples of . Their phenomenology will be discussed and a quantitative, unified model presented that can explain their origin, including that of the universal -power.

  12. Directed Evolution of RebH for Site Selective Halogenation of Large, Biologically Active Molecules**

    PubMed Central

    Payne, James T.; Poor, Catherine B.

    2015-01-01

    We recently characterized the substrate scope of wild-type RebH and evolved variants of this enzyme with improved stability for biocatalysis. The substrate scopes of both RebH and the stabilized variants, however, are limited primarily to compounds similar in size to tryptophan. We have now used a substrate walking approach to further evolve RebH variants with expanded substrate scope. Two particularly notable variants were identified: 3-SS, which provides high conversion of tricyclic tryptoline derivatives; and 4-V, which accepts a broad range of large indoles and carbazoles. This constitutes the first reported use of directed evolution to enable functionalization of substrates not accepted by wild-type RebH and demonstrates the utility of RebH variants for site-selective halogenation of biologically active compounds. PMID:25678465

  13. Fluid Flows and Their Role in the Regulation of Biological Molecules in the Bloodstream

    NASA Astrophysics Data System (ADS)

    Sing, Charles; Alexander-Katz, Alfredo

    2010-03-01

    We use computer simulations to elucidate the physics underlying blood clotting mechanisms. A straightforward and general model for the behavior of proteins such as von Willebrand Factor (vWF) under various flow conditions has been developed. The particular case of vWF is considered in depth, since it demonstrates the counter-intuitive behavior of adsorbing to a surface at higher flow rates. We use the globule-stretch transition of a collapsed polymer to explain this phenomenon, and have identified the conditions necessary to induce this transition. We have also developed a theory to explain the mechanism of this transition, which is based on the nucleation and growth of large thermal protrusions. Upon the consideration of the specific length and time scales present under biological conditions, it is apparent that vWF is strongly regulated by elongational flows. We can show how phenomena from the molecular to physiological levels are supplemented by this understanding of vWF function.

  14. Detection of nerve agents and biological molecules using embedded piezoresistive microcantilever sensors.

    NASA Astrophysics Data System (ADS)

    Porter, Timothy; Vail, Tim; Wooley, Amanda

    2008-03-01

    Embedded piezoresistive microcantilever (EPM) sensors have been used in the detection of a variety of analyte species. EPM sensors utilize a tiny piezoresistive microcantilever partially embedded into a sensing material to produce a sensing element that is compact, simple, resistant to movement and shock, and suitable for remote sensing applications. In the current project, we have used sensing materials comprised of an immobilizing polymer functionalized with either target enzymes or antibodies to detect two biological agents, bacillus globigi (BG) and Diisopropyl fluorophosphate (DFP). DFP is an organophosphate used as a simulant for organophosphate nerve agents, while BG is a large bacterial spore used as a simulant for other bacterial spores such as bacillus anthracis. Sensing results are presented for both types of EPM sensors.

  15. Design, Synthesis, and Biological Evaluation of Novel Selenium (Se-NSAID) Molecules as Anticancer Agents.

    PubMed

    Plano, Daniel; Karelia, Deepkamal N; Pandey, Manoj K; Spallholz, Julian E; Amin, Shantu; Sharma, Arun K

    2016-03-10

    The synthesis and anticancer evaluation of novel selenium-nonsteroidal anti-inflammatory drug (Se-NSAID) hybrid molecules are reported. The Se-aspirin analogue 8 was identified as the most effective agent in reducing the viability of different cancer cell lines, particularly colorectal cancer (CRC) cells, was more selective toward cancer cells than normal cells, and was >10 times more potent than 5-FU, the current therapy for CRC. Compound 8 inhibits CRC growth via the inhibition of the cell cycle in G1 and G2/M phases and reduces the cell cycle markers like cyclin E1 and B1 in a dose dependent manner; the inhibition of the cell cycle may be dependent on the ability of 8 to induce p21 expression. Furthermore, 8 induces apoptosis by activating caspase 3/7 and PARP cleavage, and its longer exposure causes increase in intracellular ROS levels in CRC cells. Taken together, 8 has the potential to be developed further as a chemotherapeutic agent for CRC.

  16. Biology of HLA-G in cancer: a candidate molecule for therapeutic intervention?

    PubMed Central

    Amiot, Laurence; Ferrone, Soldano; Grosse-Wilde, Hans; Seliger, Barbara

    2012-01-01

    Although the expression of the non-classical HLA class I molecule HLA-G was first reported to be restricted to the fetal–maternal interface on the extravillous cytotrophoblasts, the distribution of HLA-G in normal tissues appears broader than originally described. HLA-G expression was found in embryonic tissues, in adult immune privileged organs, and in cells of the hematopoietic lineage. More interestingly, under pathophysiological conditions HLA-G antigens may be expressed on various types of malignant cells suggesting that HLA-G antigen expression is one strategy used by tumor cells to escape immune surveillance. In this article, we will focus on HLA-G expression in cancers of distinct histology and its association with the clinical course of diseases, on the underlying molecular mechanisms of impaired HLA-G expression, on the immune tolerant function of HLA-G in tumors, and on the use of membrane-bound and soluble HLA-G as a diagnostic or prognostic biomarker to identify tumors and to monitor disease stage, as well as on the use of HLA-G as a novel therapeutic target in cancer. PMID:21063893

  17. Detecting and Identifying Organic Molecules in Space - The AstroBiology Explorer (ABE) MIDEX Mission Concept

    NASA Technical Reports Server (NTRS)

    Sandford, Scott A.

    2001-01-01

    Infrared spectroscopy in the 2.5-16 micron (4000-625/cm) range is a principle means by which organic compounds are detected and identified in space. Ground-based, airborne, and spaceborne IR spectral studies have already demonstrated that a significant fraction of the carbon in the interstellar medium (ISM) resides in the form of complex organic molecular species. Unfortunately, neither the distribution of these materials nor their genetic and evolutionary relationships with each other or their environments are well understood. The Astrobiology Explorer (ABE) is a MIDEX (Medium-class Explorer) mission concept currently under study at NASA's Ames Research Center in collaboration with Ball Aerospace and Technologies Corporation. ABE will conduct IR spectroscopic observations to address outstanding important problems in astrobiology, astrochemistry, and astrophysics. The core observational program would make fundamental scientific progress in understanding (1) the evolution of ices and organic matter in dense molecular clouds and young forming stellar systems, (2) the chemical evolution of organic molecules in the ISM as they transition from AGB outflows to planetary nebulae to the general diffuse ISM to H II regions and dense clouds, (3) the distribution of organics in the diffuse ISM, (4) the nature of organics in the Solar System (in comets, asteroids, satellites), and (5) the nature and distribution of organics in local galaxies. Both the scientific goals of the mission and how they would be achieved will be discussed.

  18. Detecting and Identifying Organic Molecules in Space: The AstroBiology Explorer (ABE) MIDEX Mission Concept

    NASA Technical Reports Server (NTRS)

    Sandford, Scott A.; DeVincenzi, Donald (Technical Monitor)

    2001-01-01

    Infrared spectroscopy in the 2.5-16 microns (4000-625/cm) range is a principle means by which organic compounds are detected and identified in space. Ground-based, airborne, and spaceborne IR spectral studies have already demonstrated that a significant fraction of the carbon in the interstellar medium (ISM) resides in the form of complex organic molecular species. Unfortunately, neither the distribution of these materials nor their genetic and evolutionary relationships with each other or their environments are well understood. The Astrobiology Explorer (ABE) is a MIDEX (Medium-class Explorer) mission concept currently under study at NASA's Ames Research Center in collaboration with Ball Aerospace and Technologies Corporation. ABE will conduct IR spectroscopic observations to address outstanding important problems in astrobiology, astrochemistry, and astrophysics. The core observational program would make fundamental scientific progress in understanding (1) the evolution of ices and organic matter in dense molecular clouds and young forming stellar systems, (2) the chemical evolution of organic molecules in the ISM as they transition from AGB outflows to planetary nebulae to the general diffuse ISM to H II regions and dense clouds, (3) the distribution of organics in the diffuse ISM, (4) the nature of organics in the Solar System (in comets, asteroids, satellites), and (5) the nature and distribution of organics in local galaxies. Both the scientific goals of the mission and how they would be achieved will be discussed.

  19. Identifying Organic Molecules in Space: The AstroBiology Explorer (ABE) MIDEX Mission Concept

    NASA Technical Reports Server (NTRS)

    Sandford, Scott A.; Allamandola, Louis; Bregman, Jesse; Ennico, Kimberly; Greene, Thomas; Hudgins, Douglas; Strecker, Donald; DeVincenzi, Donald (Technical Monitor)

    2001-01-01

    Infrared spectroscopy in the 2.5-16 micron range is a principle means by which organic compounds are detected and identified in space. Ground-based, airborne, and spaceborne IR spectral studies have already demonstrated that a significant fraction of the carbon in the interstellar medium (ISM) resides in the form of complex organic molecular species. Unfortunately, neither the distribution of these materials nor their genetic and evolutionary relationships with each other or their environments are well understood. The Astrobiology Explorer (ABE) is a MIDEX mission concept currently under study at NASA's Ames Research Center in collaboration with Ball Aerospace and Technologies Corporation. ABE will conduct IR spectroscopic observations to address outstanding important problems in astrobiology, astrochemistry, and astrophysics. The core observational program would make fundamental scientific progress in understanding (1) the evolution of ices and organic matter in dense molecular clouds and young forming stellar systems, (2) the chemical evolution of organic molecules in the ISM as they transition from AGB outflows to planetary nebulae to the general diffuse ISM to H II regions and dense clouds, (3) the distribution of organics in the diffuse ISM, (4) the nature of organics in the Solar System (in comets, asteroids, satellites), and (5) the nature and distribution of organics in local galaxies. The technical considerations of achieving these science objectives in a MIDEX-sized mission will be described.

  20. Identifying Organic Molecules in Space - The AstroBiology Explorer (ABE) MIDEX Mission Concept

    NASA Astrophysics Data System (ADS)

    Sandford, S. A.; Allamandola, L. J.; Bregman, J.; Ennico, K.; Greene, T.; Hudgins, D.; Strecker, D.

    2001-05-01

    Infrared spectroscopy in the 2.5-16 micron range is a principle means by which organic compounds can be detected and identified in space via their vibrational transitions. Ground-based, airborne, and spaceborne IR spectral studies have already demonstrated that a significant fraction of the carbon in the interstellar medium (ISM) resides in the form of complex organic molecular species. Unfortunately, neither the distribution of these materials nor their genetic and evolutionary relationships with each other or their environments are well understood. The Astrobiology Explorer (ABE) is a MIDEX mission concept currently under study at NASA's Ames Research Center in collaboration with Ball Aerospace and Technologies Corporation. ABE will conduct IR spectroscopic observations to address outstanding important problems in astrobiology, astrochemistry, and astrophysics. The core observational program would make fundamental scientific progress in understanding (1) the evolution of ices and organic matter in dense molecular clouds and young forming stellar systems, (2) the chemical evolution of organic molecules in the ISM as they transition from AGB outflows to planetary nebulae to the general diffuse ISM to HII regions and dense clouds, (3) the distribution of organics in the diffuse ISM, (4) the nature of organics in the Solar System (in comets, asteroids, satellites), and (5) the nature and distribution of organics in local galaxies. The technical considerations of achieving these science objectives in a MIDEX-sized mission will be presented.

  1. Probing autoinducer-2 based quorum sensing: the biological consequences of molecules unable to traverse equilibrium states.

    PubMed

    Tsuchikama, Kyoji; Lowery, Colin A; Janda, Kim D

    2011-09-02

    Bacteria have developed a cell-to-cell communication system, termed quorum sensing (QS), which allows for the population-dependent coordination of their behavior via the exchange of chemical signals. Autoinducer-2 (AI-2), a class of QS signals derived from 4,5-dihydroxy-2,3-pentandione (DPD), has been revealed as a universal signaling molecule in a variety of bacterial species. In spite of considerable interest, the study of putative AI-2 based QS systems remains a challenging topic in part due to the rapid interconversion between the linear and cyclic forms of DPD. Herein, we report the design and development of efficient syntheses of carbocyclic analogues of DPD, which are locked in the cyclic form. The synthetic analogues were evaluated for the modulation of AI-2-based QS in Vibrio harveyi and Salmonella typhimurium. No agonists were uncovered in either V. harveyi or S. typhimurium assay, whereas weak to moderate antagonists were found against V. harveyi. On the basis of NMR analyses and DFT calculations, the heterocyclic oxygen atom within DPD appears necessary to promote hydration at the C3 position of cyclic DPD to afford the active tetrahydroxy species. These results also shed light on the interaction between the heterocyclic oxygen atom and receptor proteins as well as the importance of the linear form and dynamic equilibrium of DPD as crucial requirements for activation of AI-2 based QS circuits.

  2. Exploring the reactivity of retinol radical cation toward organic and biological molecules: A laser flash photolysis study.

    PubMed

    El-Agamey, Ali; Melø, Thor B; Sliwka, Hans-Richard

    2017-05-01

    Vitamin A (retinol) and various natural retinoids are essential for life. Under oxidative conditions, vitamin A radical cation (RET(+)) can be formed. Many deleterious effects were reported about the formation of carotenoid radical cations in biological environments, on the other hand, little is known about the consequences of the RET(+) formation in these environments. Therefore, it is important to explore the reactivity of RET(+) toward various biological substrates. Here, we employed nanosecond laser flash photolysis (LFP) to generate RET(+) (λmax=580nm in methanol) and examine its reactivity toward a wide range of biological molecules including amino acids, vitamins, carotenoids, naturally-occurring phenols, neurotransmitters such as catecholamines, wide range of phenol derivatives and some selected electron-donors. The results show that the reactivity of RET(+) toward various substrates is strongly dependent on the polarity of solvent. In addition, RET(+) is able to oxidize amino acids, which subsequently can lead to protein damage. However, the presence of vitamins (vitamins E and C), carotenoids and naturally-occurring phenols (e.g. resveratrol, vanillin, dopamine hydrochloride and l-Dopa) can inhibit the damaging effect of retinol(+) by reducing it back to retinol. Vitamin E and carotenoids are the most efficient quenchers for the RET(+) (diffusion-controlled reactions). Importantly, our results clearly indicate that the reactivity of RET(+) is as strong as that of the powerful trichloromethylperoxyl radical (CCl3O2). Thereby, formation of RET(+) in biological media is expected to induce bio-damage. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Biological functions of hCG and hCG-related molecules

    PubMed Central

    2010-01-01

    Background hCG is a term referring to 4 independent molecules, each produced by separate cells and each having completely separate functions. These are hCG produced by villous syncytiotrophoblast cells, hyperglycosylated hCG produced by cytotrophoblast cells, free beta-subunit made by multiple primary non-trophoblastic malignancies, and pituitary hCG made by the gonadotrope cells of the anterior pituitary. Results and discussion hCG has numerous functions. hCG promotes progesterone production by corpus luteal cells; promotes angiogenesis in uterine vasculature; promoted the fusion of cytotrophoblast cell and differentiation to make syncytiotrophoblast cells; causes the blockage of any immune or macrophage action by mother on foreign invading placental cells; causes uterine growth parallel to fetal growth; suppresses any myometrial contractions during the course of pregnancy; causes growth and differentiation of the umbilical cord; signals the endometrium about forthcoming implantation; acts on receptor in mother's brain causing hyperemesis gravidarum, and seemingly promotes growth of fetal organs during pregnancy. Hyperglycosylated hCG functions to promote growth of cytotrophoblast cells and invasion by these cells, as occurs in implantation of pregnancy, and growth and invasion by choriocarcinoma cells. hCG free beta-subunit is produced by numerous non-trophoblastic malignancies of different primaries. The detection of free beta-subunit in these malignancies is generally considered a sign of poor prognosis. The free beta-subunit blocks apoptosis in cancer cells and promotes the growth and malignancy of the cancer. Pituitary hCG is a sulfated variant of hCG produced at low levels during the menstrual cycle. Pituitary hCG seems to mimic luteinizing hormone actions during the menstrual cycle. PMID:20735820

  4. Absorption into fluorescence. A method to sense biologically relevant gas molecules

    NASA Astrophysics Data System (ADS)

    Strianese, Maria; Varriale, Antonio; Staiano, Maria; Pellecchia, Claudio; D'Auria, Sabato

    2011-01-01

    In this work we present an innovative optical sensing methodology based on the use of biomolecules as molecular gating nano-systems. Here, as an example, we report on the detection ofanalytes related to climate change. In particular, we focused our attention on the detection ofnitric oxide (NO) and oxygen (O2). Our methodology builds on the possibility of modulating the excitation intensity of a fluorescent probe used as a transducer and a sensor molecule whose absorption is strongly affected by the binding of an analyte of interest used as a filter. The two simple conditions that have to be fulfilled for the method to work are: (a) the absorption spectrum of the sensor placed inside the cuvette, and acting as the recognition element for the analyte of interest, should strongly change upon the binding of the analyte and (b) the fluorescence dye transducer should exhibit an excitation band which overlaps with one or more absorption bands of the sensor. The absorption band of the sensor affected by the binding of the specific analyte should overlap with the excitation band of the transducer. The high sensitivity of fluorescence detection combined with the use of proteins as highly selective sensors makes this method a powerful basis for the development of a new generation of analytical assays. Proof-of-principle results showing that cytochrome c peroxidase (CcP) for NO detection and myoglobin (Mb) for O2 detection can be successfully used by exploiting our new methodology are reported. The proposed technology can be easily expanded to the determination of different target analytes.

  5. Absorption into fluorescence. A method to sense biologically relevant gas molecules.

    PubMed

    Strianese, Maria; Varriale, Antonio; Staiano, Maria; Pellecchia, Claudio; D'Auria, Sabato

    2011-01-01

    In this work we present an innovative optical sensing methodology based on the use of biomolecules as molecular gating nano-systems. Here, as an example, we report on the detection of analytes related to climate change. In particular, we focused our attention on the detection of nitric oxide (NO) and oxygen (O2). Our methodology builds on the possibility of modulating the excitation intensity of a fluorescent probe used as a transducer and a sensor molecule whose absorption is strongly affected by the binding of an analyte of interest used as a filter. The two simple conditions that have to be fulfilled for the method to work are: (a) the absorption spectrum of the sensor placed inside the cuvette, and acting as the recognition element for the analyte of interest, should strongly change upon the binding of the analyte and (b) the fluorescence dye transducer should exhibit an excitation band which overlaps with one or more absorption bands of the sensor. The absorption band of the sensor affected by the binding of the specific analyte should overlap with the excitation band of the transducer. The high sensitivity of fluorescence detection combined with the use of proteins as highly selective sensors makes this method a powerful basis for the development of a new generation of analytical assays. Proof-of-principle results showing that cytochrome c peroxidase (CcP) for NO detection and myoglobin (Mb) for O2 detection can be successfully used by exploiting our new methodology are reported. The proposed technology can be easily expanded to the determination of different target analytes.

  6. Quantum well intermixing and radiation effects in InGaN/GaN multi quantum wells

    NASA Astrophysics Data System (ADS)

    Lorenz, K.; Redondo-Cubero, A.; Lourenço, M. B.; Sequeira, M. C.; Peres, M.; Freitas, A.; Alves, L. C.; Alves, E.; Leitão, M. P.; Rodrigues, J.; Ben Sedrine, N.; Correia, M. R.; Monteiro, T.

    2016-02-01

    Compositional grading of InGaN/GaN multi quantum wells (QWs) was proposed to mitigate polarization effects and Auger losses in InGaN-based light emitting diodes [K. P. O'Donnell et al., Phys. Status Solidi RRL 6 (2012) 49]. In this paper we are reviewing our recent attempts on achieving such gradient via quantum well intermixing. Annealing up to 1250 °C resulted in negligible interdiffusion of QWs and barriers revealing a surprising thermal stability well above the typical MOCVD growth temperatures. For annealing at 1400 °C results suggest a decomposition of the QWs in regions with high and low InN content. The defect formation upon nitrogen implantation was studied in detail. Despite strong dynamic annealing effects, which keep structural damage low, the created defects strongly quench the QW luminescence even for low implantation fluences. This degradation could not be reversed during thermal annealing and is hampering the use of implantation induced quantum well intermixing in InGaN/GaN structures.

  7. Investigation of temperature-dependent photoluminescence in multi-quantum wells

    PubMed Central

    Fang, Yutao; Wang, Lu; Sun, Qingling; Lu, Taiping; Deng, Zhen; Ma, Ziguang; Jiang, Yang; Jia, Haiqiang; Wang, Wenxin; Zhou, Junming; Chen, Hong

    2015-01-01

    Photoluminescence (PL) is a nondestructive and powerful method to investigate carrier recombination and transport characteristics in semiconductor materials. In this study, the temperature dependences of photoluminescence of GaAs-AlxGa1-xAs multi-quantum wells samples with and without p-n junction were measured under both resonant and non-resonant excitation modes. An obvious increase of photoluminescence(PL) intensity as the rising of temperature in low temperature range (T < 50 K), is observed only for GaAs-AlxGa1-xAs quantum wells sample with p-n junction under non-resonant excitation. The origin of the anomalous increase of integrated PL intensity proved to be associated with the enhancement of carrier drifting because of the increase of carrier mobility in the temperature range from 15 K to 100 K. For non-resonant excitation, carriers supplied from the barriers will influence the temperature dependence of integrated PL intensity of quantum wells, which makes the traditional methods to acquire photoluminescence characters from the temperature dependence of integrated PL intensity unavailable. For resonant excitation, carriers are generated only in the wells and the temperature dependence of integrated PL intensity is very suitable to analysis the photoluminescence characters of quantum wells. PMID:26228734

  8. Investigation of temperature-dependent photoluminescence in multi-quantum wells.

    PubMed

    Fang, Yutao; Wang, Lu; Sun, Qingling; Lu, Taiping; Deng, Zhen; Ma, Ziguang; Jiang, Yang; Jia, Haiqiang; Wang, Wenxin; Zhou, Junming; Chen, Hong

    2015-07-31

    Photoluminescence (PL) is a nondestructive and powerful method to investigate carrier recombination and transport characteristics in semiconductor materials. In this study, the temperature dependences of photoluminescence of GaAs-AlxGa1-xAs multi-quantum wells samples with and without p-n junction were measured under both resonant and non-resonant excitation modes. An obvious increase of photoluminescence(PL) intensity as the rising of temperature in low temperature range (T < 50 K), is observed only for GaAs-AlxGa1-xAs quantum wells sample with p-n junction under non-resonant excitation. The origin of the anomalous increase of integrated PL intensity proved to be associated with the enhancement of carrier drifting because of the increase of carrier mobility in the temperature range from 15 K to 100 K. For non-resonant excitation, carriers supplied from the barriers will influence the temperature dependence of integrated PL intensity of quantum wells, which makes the traditional methods to acquire photoluminescence characters from the temperature dependence of integrated PL intensity unavailable. For resonant excitation, carriers are generated only in the wells and the temperature dependence of integrated PL intensity is very suitable to analysis the photoluminescence characters of quantum wells.

  9. Investigation of carrier collection in multi-quantum well solar cells by luminescence spectra analysis

    NASA Astrophysics Data System (ADS)

    Delamarre, Amaury; Fujii, Hiromasa; Watanabe, Kentaroh; Guillemoles, Jean-François; Nakano, Yoshiaki; Sugiyama, Masakazu

    2015-03-01

    Multi-Quantum well solar cells (MQWSC) have been shown to present several advantages, among which are low dark currents and tunable bandgaps. They are especially suited for implementation in multi-junction cells, and are highly promising for absorbers in Hot Carrier Solar Cells (HCSC). Such applications require high concentration ratio, which arises the issue of collection efficiency. Whereas it is usually considered that collection in MQW is very close to unity at one sun, it has been shown to not be the case under high concentration at the maximum power point. We propose in this work to take advantage of the luminescence spectral variation to investigate the depth collection efficiency. In order to validate the model, a series of strain compensated InGaAs/GaAsP MQW solar cells with intentional variation of the MQW doping concentration are grown. This has the effect of switching the space charge region position and width as well as the electric field intensity. Recording the luminescence spectra at various illumination intensities and applied voltages, we show that the in-depth quasi-Fermi level splitting and thus collection properties can be probed. Other measurements (EQE, luminescence intensity variation) are shown to be consistent with these results. Regarding their use as HCSC, the luminescence of MQW solar cells has been mainly used so far for investigating the quasi-Fermi level splitting and the temperature. Our results improve our understanding by adding information on carrier transport.

  10. Radiation response of multi-quantum well solar cells: Electron-beam-induced current analysis

    NASA Astrophysics Data System (ADS)

    Maximenko, S. I.; Lumb, M. P.; Hoheisel, R.; Gonzalez, M.; Scheiman, D. A.; Messenger, S. R.; Tibbits, T. N. D.; Imaizumi, M.; Ohshima, T.; Sato, S. I.; Jenkins, P. P.; Walters, R. J.

    2015-12-01

    Solar cells utilizing multi-quantum well (MQW) structures are considered promising candidate materials for space applications. An open question is how well these structures can resist the impact of particle irradiation. The aim of this work is to provide feedback about the radiation response of In0.01Ga0.99As solar cells grown on Ge with MQWs incorporated within the i-region of the device. In particular, the local electronic transport properties of the MQW i-regions of solar cells subjected to electron and proton irradiation were evaluated experimentally using the electron beam induced current (EBIC) technique. The change in carrier collection distribution across the MQW i-region was analyzed using a 2D EBIC diffusion model in conjunction with numerical modeling of the electrical field distribution. Both experimental and simulated findings show carrier removal and type conversion from n- to p-type in MQW i-region at a displacement damage dose as low as ˜6.06-9.88 × 109 MeV/g. This leads to a redistribution of the electric field and significant degradation in charge carrier collection.

  11. Radiation response of multi-quantum well solar cells: Electron-beam-induced current analysis

    SciTech Connect

    Maximenko, S. I. Scheiman, D. A.; Jenkins, P. P.; Walters, R. J.; Lumb, M. P.; Hoheisel, R.; Gonzalez, M.; Messenger, S. R.; Tibbits, T. N. D.; Imaizumi, M.; Ohshima, T.; Sato, S. I.

    2015-12-28

    Solar cells utilizing multi-quantum well (MQW) structures are considered promising candidate materials for space applications. An open question is how well these structures can resist the impact of particle irradiation. The aim of this work is to provide feedback about the radiation response of In{sub 0.01}Ga{sub 0.99}As solar cells grown on Ge with MQWs incorporated within the i-region of the device. In particular, the local electronic transport properties of the MQW i-regions of solar cells subjected to electron and proton irradiation were evaluated experimentally using the electron beam induced current (EBIC) technique. The change in carrier collection distribution across the MQW i-region was analyzed using a 2D EBIC diffusion model in conjunction with numerical modeling of the electrical field distribution. Both experimental and simulated findings show carrier removal and type conversion from n- to p-type in MQW i-region at a displacement damage dose as low as ∼6.06–9.88 × 10{sup 9} MeV/g. This leads to a redistribution of the electric field and significant degradation in charge carrier collection.

  12. Intermolecular hydrogen bonds in hetero-complexes of biologically active aromatic molecules probed by the methods of vibrational spectroscopy

    NASA Astrophysics Data System (ADS)

    Semenov, M. A.; Blyzniuk, Iu. N.; Bolbukh, T. V.; Shestopalova, A. V.; Evstigneev, M. P.; Maleev, V. Ya.

    2012-09-01

    By the methods of vibrational spectroscopy (Infrared and Raman) the investigation of the hetero-association of biologically active aromatic compounds: flavin-mononucleotide (FMN), ethidium bromide (EB) and proflavine (PRF) was performed in aqueous solutions. It was shown that between the functional groups (Cdbnd O and NH2) the intermolecular hydrogen bonds are formed in the hetero-complexes FMN-EB and FMN-PRF, additionally stabilizing these structures. An estimation of the enthalpy of Н-bonding obtained from experimental shifts of carbonyl vibrational frequencies has shown that the H-bonds do not dominate in the magnitude of experimentally measured total enthalpy of the hetero-association reactions. The main stabilization is likely due to intermolecular interactions of the molecules in these complexes and their interaction with water environment.

  13. Evolution of conformational changes in the dynamics of small biological molecules: a hybrid MD/RRK approach.

    PubMed

    Segev, Elad; Grumbach, Mikael; Gerber, Robert Benny

    2006-11-14

    The dynamics of long timescale evolution of conformational changes in small biological molecules is described by a hybrid molecular dynamics/RRK algorithm. The approach employs classical trajectories for transitions between adjacent structures separated by a low barrier, and the classical statistical RRK approximation when the barrier involved is high. In determining the long-time dynamics from an initial structure to a final structure of interest, an algorithm is introduced for determining the most efficient pathways (sequence of the intermediate conformers). This method uses the Dijkstra algorithm for finding optimal paths on networks. Three applications of the method using an AMBER force field are presented: a detailed study of conformational transitions in a blocked valine dipeptide; a multiple reaction path study of the blocked valine tripeptide; and the evolution in time from the beta hairpin to alpha helix structure of a blocked alanine hexapeptide. Advantages and limitations of the method are discussed in light of the results.

  14. Intermolecular hydrogen bonds in hetero-complexes of biologically active aromatic molecules probed by the methods of vibrational spectroscopy.

    PubMed

    Semenov, M A; Blyzniuk, Iu N; Bolbukh, T V; Shestopalova, A V; Evstigneev, M P; Maleev, V Ya

    2012-09-01

    By the methods of vibrational spectroscopy (Infrared and Raman) the investigation of the hetero-association of biologically active aromatic compounds: flavin-mononucleotide (FMN), ethidium bromide (EB) and proflavine (PRF) was performed in aqueous solutions. It was shown that between the functional groups (CO and NH(2)) the intermolecular hydrogen bonds are formed in the hetero-complexes FMN-EB and FMN-PRF, additionally stabilizing these structures. An estimation of the enthalpy of Н-bonding obtained from experimental shifts of carbonyl vibrational frequencies has shown that the H-bonds do not dominate in the magnitude of experimentally measured total enthalpy of the hetero-association reactions. The main stabilization is likely due to intermolecular interactions of the molecules in these complexes and their interaction with water environment.

  15. In vivo biochemistry: Applications for small molecule biosensors in plant biology

    PubMed Central

    Jones, Alexander; Grossmann, Guido; Danielson, Jonas Å.H.; Sosso, Davide; Chen, Li-Qing; Ho, Cheng Hsun; Frommer, Wolf B.

    2013-01-01

    Summary Revolutionary new technologies, namely in the areas of DNA sequencing and molecular imaging, continue to impact new discoveries in plant science and beyond. For decades we have been able to determine properties of enzymes, receptors and transporters in vitro or in heterologous systems, and more recently been able to analyze their regulation at the transcriptional level, use GFP reporters to obtain insights into cellular and subcellular localization, and measure ion and metabolite levels with unprecedented precision using mass spectrometry. However, we lack key information on location and dynamics of the substrates of enzymes, receptors and transporters, and on the regulation of these proteins in their cellular environment. Such information can now be obtained by transitioning from in vitro to in vivo biochemistry using biosensors. Genetically encoded fluorescent protein-based sensors for ion and metabolite dynamics provide highly resolved spatial and temporal information, and are complemented by sensors for pH, redox, voltage, and tension. They serve as powerful tools for identifying missing processes (e.g. glucose transport across ER membranes), components (e.g. SWEET sugar transporters for cellular sugar efflux), and signaling networks (e.g. from systematic screening of mutants that affect sugar transport or cytosolic and vacuolar pH). Combined with the knowledge of properties of enzymes and transporters and their interactions with the regulatory machinery, biosensors promise to be key diagnostic tools for systems and synthetic biology. PMID:23587939

  16. In vivo biochemistry: applications for small molecule biosensors in plant biology.

    PubMed

    Jones, Alexander M; Grossmann, Guido; Danielson, Jonas Åh; Sosso, Davide; Chen, Li-Qing; Ho, Cheng-Hsun; Frommer, Wolf B

    2013-06-01

    Revolutionary new technologies, namely in the areas of DNA sequencing and molecular imaging, continue to impact new discoveries in plant science and beyond. For decades we have been able to determine properties of enzymes, receptors and transporters in vitro or in heterologous systems, and more recently been able to analyze their regulation at the transcriptional level, to use GFP reporters for obtaining insights into cellular and subcellular localization, and tp measure ion and metabolite levels with unprecedented precision using mass spectrometry. However, we lack key information on the location and dynamics of the substrates of enzymes, receptors and transporters, and on the regulation of these proteins in their cellular environment. Such information can now be obtained by transitioning from in vitro to in vivo biochemistry using biosensors. Genetically encoded fluorescent protein-based sensors for ion and metabolite dynamics provide highly resolved spatial and temporal information, and are complemented by sensors for pH, redox, voltage, and tension. They serve as powerful tools for identifying missing processes (e.g., glucose transport across ER membranes), components (e.g., SWEET sugar transporters for cellular sugar efflux), and signaling networks (e.g., from systematic screening of mutants that affect sugar transport or cytosolic and vacuolar pH). Combined with the knowledge of properties of enzymes and transporters and their interactions with the regulatory machinery, biosensors promise to be key diagnostic tools for systems and synthetic biology. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Identifying Organic Molecules in Space - The AstroBiology Explorer (ABE) Mission Concept

    NASA Astrophysics Data System (ADS)

    Ennico, K. A.; Sandford, S. A.; Allamandola, L. J.; Bregman, J. D.; Cohen, M.; Cruikshank, D. P.; Dumas, C.; Greene, T. P.; Hudgins, D. M.; Kwok, S.; Lord, S. D.; Madden, S. C.; McCreight, C. R.; Roellig, T. L.; Strecker, D. W.; Tielens, A. G.; Werner, M. W.; Wilmoth, K. L.

    2003-12-01

    The AstroBiology Explorer (ABE) mission concept consists of a modest dedicated space observatory having a 60 cm class primary mirror cooled to T < 50 K equipped with a modest resolution cross-dispersed spectrometers having cooled large format near- and mid-infrared detector arrays. Such as system would be capable of addressing outstanding problems in Astrochemistry and Astrophysics that are particularly relevant to Astrobiology and addressable via astronomical observation. This mission's observationsal program would make fundamental scientific progress in establishing the nature, distribution, formation and evolution of organic and other molecular materials in the following extraterrestrial environments: 1 The Outflow of Dying Stars 2 The Diffuse Interstellar Medium 3 Dense Molecular Clouds, Star Formation Regions, and Young Stellar/Planetary Systems 4 Planets, Satellites, and Small Bodies within the Solar System, and 5 Interstellar Media of Other Galaxies ABE could make fundamental progress in all of these areas by conducting a 1 to 2 year mission to obtain a coordinated set of infrared spectroscopic observations over the 2.5-20 micron spectral range at a spectral resolution of R > 2500 of about 1500 galaxies, stars, planetary nebulae, young stellar objects, and solar system objects.

  18. Identifying organic molecules in space: the AstroBiology Explorer (ABE) mission concept

    NASA Astrophysics Data System (ADS)

    Ennico, Kimberly A.; Sandford, Scott A.

    2004-10-01

    The AstroBiology Explorer (ABE) mission concept consists of a dedicated space observatory having a 60 cm class primary mirror cooled to T < 50 K equipped with medium resolution cross-dispersed spectrometers having cooled large format near- and mid-infrared detector arrays. Such a system would be capable of addressing outstanding problems in Astrochemistry and Astrophysics that are particularly relevant to Astrobiology and addressable via astronomical observation. The mission's observational program would make fundamental scientific progress in establishing the nature, distribution, formation and evolution of organic and other molecular materials in the following extra-terrestrial environments: 1) The Outflow of Dying Stars, 2) The Diffuse Interstellar Medium, 3) Dense Molecular Clouds, Star Formation Regions, and Young Stellar/Planetary Systems, 4) Planets, Satellites, and Small Bodies within the Solar System, and 5) The Interstellar Media of Other Galaxies. ABE could make fundamental progress in all of these areas by conducting a 1 to 2 year mission to obtain a coordinated set of infrared spectroscopic observations over the 2.5-20 micron spectral range at a spectral resolution of R > 2000 of about 1500 objects including galaxies, stars, planetary nebulae, young stellar objects, and solar system objects.

  19. Identifying Organic Molecules in Space: The AstroBiology Explorer (ABE) Mission Concept

    NASA Technical Reports Server (NTRS)

    Ennico, Kimberly; Sandford, S.; Allamandola, L.; Bregman, J.; Cohen, M.; Cruikshank, D.; Dumas, C.; Greene, T.; Hudgins, D.; Kwok, S.

    2004-01-01

    The AstroBiology Explorer (ABE) mission concept consists of a modest dedicated space observatory having a 60 cm class primary mirror cooled to T less than 50 K equipped with medium resolution cross-dispersed spectrometers having cooled large format near- and mid-infrared detector arrays. Such a system would be capable of addressing outstanding problems in Astrochemistry and Astrophysics that are particularly relevant to Astrobiology and addressable via astronomical observation. The mission's observaticxiai program woiild make fundamental scieztific: prngress in establishing the nature, distribution, formation and evolution of organic and other molecular materials in the following extra-terrestrial environments: 1) The Outflow of Dying Stars; 2) The Diffuse Interstellar Medium (DISM); 3) Dense Molecular Clouds, Star Formation Regions, and Young Stellar/Planetary Systems; 4) Planets, Satellites, and Small Bodies within the Solar System; and 5) The Interstellar Media of Other Galaxies ABE could make fundamental progress in all of these area by conducting a 1 to 2 year mission to obtain a coordinated set of infrared spectroscopic observations over the 2.5 - 20 micron spectral range at a spectral resolution of R greater than 2500 of about 1500 galaxies, stars, planetary nebulae, young stellar objects, and solar system objects.

  20. Identifying Organic Molecules in Space: The AstroBiology Explorer (ABE) Mission Concept

    NASA Technical Reports Server (NTRS)

    Ennico, K. A.; Sandford, S. A.; Allamandola, L.; Bregman, J.; Cohen, M.; Cruikshank, D.; Dumas, C.; Greene, T.; Hudgins, D.; Kwok, S.

    2004-01-01

    The AstroBiology Explorer (ABE) mission concept consists of a dedicated space observatory having a 60 cm class primary mirror cooled to T < 50 K equipped with medium resolution cross-dispersed spectrometers having cooled large format near- and mid-infrared detector arrays. Such a system would be capable of addressing outstanding problems in Astrochemistry and Astrophysics that are particularly relevant to Astrobiology and addressable via astronomical observation. The mission s observational program would make fundamental scientific progress in establishing the nature, distribution, formation and evolution of organic and other molecular materials in the following extra-terrestrial environments: 1) The Outflow of Dying Stars, 2) The Diffuse Interstellar Medium, 3) Dense Molecular Clouds, Star Formation Regions, and Young StellarPlanetary Systems, 4) Planets, Satellites, and Small Bodies within the Solar System, and 5 ) The Interstellar Media of Other Galaxies. ABE could make fundamental progress in all of these areas by conducting a 1 to 2 year mission to obtain a coordinated set of infrared spectroscopic observations over the 2.5-20 micron spectral range at a spectral resolution of R > 2000 of about 1500 objects including galaxies, stars, planetary nebulae, young stellar objects, and solar system objects. Keywords: Astrobiology, infrared, Explorers, interstellar organics, telescope, spectrometer, space, infrared detectors

  1. Characterization of the electronic states of the biological relevant SSNO molecule

    NASA Astrophysics Data System (ADS)

    Ayari, Tarek; Hochlaf, Majdi; Mogren Al-Mogren, Muneerah; Francisco, Joseph S.

    2017-02-01

    Using configuration interaction ab initio methods, we investigate the lowest electronic states of doublet and quartet spin multiplicities of SSNO where the one-dimensional cuts of the six-dimensional potential energy surfaces of these electronic states along the stretching and bending coordinates are computed. Mainly, these electronic states are found to be repulsive along the central SN distance. A high density of electronic states is computed even at low excitation energies that may favor their couplings. Therefore, the dynamics of the SSNO electronic states is expected to be very complex. We also characterized the bound electronic states spectroscopically where we derived their equilibrium structures and vibrational frequencies. Our calculations show the importance of taking into account of dynamical correlation, in addition to static correlation, for the accurate description of SSNO electronic excited states and more generally for those of R-NO molecular species. Finally, we highlighted the potential role of SSNO in light-induced NO delivery from SSNO related species in biological media.

  2. Identifying Organic Molecules in Space: The AstroBiology Explorer (ABE) Mission Concept

    NASA Technical Reports Server (NTRS)

    Ennico, Kimberly; Sandford, S.; Allamandola, L.; Bregman, J.; Cohen, M.; Cruikshank, D.; Dumas, C.; Greene, T.; Hudgins, D.; Kwok, S.

    2004-01-01

    The AstroBiology Explorer (ABE) mission concept consists of a modest dedicated space observatory having a 60 cm class primary mirror cooled to T less than 50 K equipped with medium resolution cross-dispersed spectrometers having cooled large format near- and mid-infrared detector arrays. Such a system would be capable of addressing outstanding problems in Astrochemistry and Astrophysics that are particularly relevant to Astrobiology and addressable via astronomical observation. The mission's observaticxiai program woiild make fundamental scieztific: prngress in establishing the nature, distribution, formation and evolution of organic and other molecular materials in the following extra-terrestrial environments: 1) The Outflow of Dying Stars; 2) The Diffuse Interstellar Medium (DISM); 3) Dense Molecular Clouds, Star Formation Regions, and Young Stellar/Planetary Systems; 4) Planets, Satellites, and Small Bodies within the Solar System; and 5) The Interstellar Media of Other Galaxies ABE could make fundamental progress in all of these area by conducting a 1 to 2 year mission to obtain a coordinated set of infrared spectroscopic observations over the 2.5 - 20 micron spectral range at a spectral resolution of R greater than 2500 of about 1500 galaxies, stars, planetary nebulae, young stellar objects, and solar system objects.

  3. From old organisms to new molecules: integrative biology and therapeutic targets in accelerated human ageing.

    PubMed

    Cox, L S; Faragher, R G A

    2007-10-01

    Understanding the basic biology of human ageing is a key milestone in attempting to ameliorate the deleterious consequences of old age. This is an urgent research priority given the global demographic shift towards an ageing population. Although some molecular pathways that have been proposed to contribute to ageing have been discovered using classical biochemistry and genetics, the complex, polygenic and stochastic nature of ageing is such that the process as a whole is not immediately amenable to biochemical analysis. Thus, attempts have been made to elucidate the causes of monogenic progeroid disorders that recapitulate some, if not all, features of normal ageing in the hope that this may contribute to our understanding of normal human ageing. Two canonical progeroid disorders are Werner's syndrome and Hutchinson-Gilford progeroid syndrome (also known as progeria). Because such disorders are essentially phenocopies of ageing, rather than ageing itself, advances made in understanding their pathogenesis must always be contextualised within theories proposed to help explain how the normal process operates. One such possible ageing mechanism is described by the cell senescence hypothesis of ageing. Here, we discuss this hypothesis and demonstrate that it provides a plausible explanation for many of the ageing phenotypes seen in Werner's syndrome and Hutchinson-Gilford progeriod syndrome. The recent exciting advances made in potential therapies for these two syndromes are also reviewed.

  4. Applications of Path Integral Langevin Dynamics to Weakly Bound Clusters and Biological Molecules

    NASA Astrophysics Data System (ADS)

    Ing, Christopher; Hinsen, Conrad; Yang, Jing; Roy, Pierre-Nicholas

    2011-06-01

    We present the use of path integral molecular dynamics (PIMD) in conjunction with the path integral Langevin equation thermostat for sampling systems that exhibit nuclear quantum effects, notably those at low temperatures or those consisting mainly of hydrogen or helium. To test this approach, the internal energy of doped helium clusters are compared with white-noise Langevin thermostatting and high precision path integral monte carlo (PIMC) simulations. We comment on the structural evolution of these clusters in the absence of rotation and exchange as a function of cluster size. To quantify the importance of both rotation and exchange in our PIMD simulation, we compute band origin shifts for (He)_N-CO_2 as a function of cluster size and compare to previously published experimental and theoretical shifts. A convergence study is presented to confirm the systematic error reduction introduced by increasing path integral beads for our implementation in the Molecular Modelling Toolkit (MMTK) software package. Applications to carbohydrates are explored at biological temperatures by calculating both equilibrium and dynamical properties using the methods presented. M. Ceriotti, M. Parrinello, and D. E. Manolopoulos, J Chem Phys 133, 124104. H. Li, N. Blinov, P.-N. Roy, and R. J. L. Roy, J Chem Phys 130, 144305.

  5. Connecting Small Molecules with Similar Assay Performance Profiles Leads to New Biological Hypotheses

    PubMed Central

    Dančík, Vlado; Carrel, Hyman; Bodycombe, Nicole E.; Seiler, Kathleen Petri; Fomina-Yadlin, Dina; Kubicek, Stefan T.; Hartwell, Kimberly; Shamji, Alykhan F.; Wagner, Bridget K.; Clemons, Paul A.

    2017-01-01

    High-throughput screening allows rapid identification of new candidate compounds for biological probe or drug development. Here, we describe a principled method to generate “assay performance profiles” for individual compounds that can serve as a basis for similarity searches and cluster analyses. Our method overcomes three challenges associated with generating robust assay performance profiles: (1) we transform data, allowing us to build profiles from assays having diverse dynamic ranges and variability; (2) we apply appropriate mathematical principles to handle missing data; and (3) we mitigate the fact that loss-of-signal assay measurements may not distinguish between multiple mechanisms that can lead to certain phenotypes (e.g., cell death). Our method connected compounds with similar mechanisms of action, enabling prediction of new targets and mechanisms both for known bioactives and for compounds emerging from new screens. Furthermore, we used Bayesian modeling of promiscuous compounds to distinguish between broadly bioactive and narrowly bioactive compound communities. Several examples illustrate the utility of our method to support mechanism-of-action studies in probe development and target identification projects. PMID:24464433

  6. A ligation-triggered DNAzyme cascade for amplified fluorescence detection of biological small molecules with zero-background signal.

    PubMed

    Lu, Li-Min; Zhang, Xiao-Bing; Kong, Rong-Mei; Yang, Bin; Tan, Weihong

    2011-08-03

    Many types of fluorescent sensing systems have been reported for biological small molecules. Particularly, several methods have been developed for the recognition of ATP or NAD(+), but they only show moderate sensitivity, and they cannot discriminate either ATP or NAD(+) from their respective analogues. We have addressed these limitations and report here a dual strategy which combines split DNAzyme-based background reduction with catalytic and molecular beacon (CAMB)-based amplified detection to develop a ligation-triggered DNAzyme cascade, resulting in ultrahigh sensitivity. First, the 8-17 DNAzyme is split into two separate oligonucleotide fragments as the building blocks for the DNA ligation reaction, thereby providing a zero-background signal to improve overall sensitivity. Next, a CAMB strategy is further employed for amplified signal detection achieved through cycling and regenerating the DNAzyme to realize the true enzymatic multiple turnover (one enzyme catalyzes the cleavage of several substrates) of catalytic beacons. This combination of zero-background signal and signal amplification significantly improves the sensitivity of the sensing systems, resulting in detection limits of 100 and 50 pM for ATP and NAD(+), respectively, much lower than those of previously reported biosensors. Moreover, by taking advantage of the highly specific biomolecule-dependence of the DNA ligation reaction, the developed DNAzyme cascades show significantly high selectivity toward the target cofactor (ATP or NAD(+)), and the target biological small molecule can be distinguished from its analogues. Therefore, as a new and universal platform for the design of DNA ligation reaction-based sensing systems, this novel ligation-triggered DNAzyme cascade method may find a broad spectrum of applications in both environmental and biomedical fields.

  7. Biologically active molecules regulating the IgE antibody system: biochemical and biological comparisons of suppressive factor of allergy (SFA) and enhancing factor of allergy (EFA).

    PubMed

    Katz, D H; Chen, S S; Liu, F T; Bogowitz, C A; Katz, L R

    1984-01-01

    Studies in recent years directed at unraveling the complex regulatory mechanisms controlling IgE antibody production have demonstrated the existence of soluble factors that exert selective regulatory effects on the IgE antibody system. In addition, the demonstration of IgE-specific Fc receptors (FcR epsilon) on B and T lymphocytes, especially after exposure to high concentrations of IgE either in vivo or in vitro, has provided increasingly strong indications of an important role for such cells in the overall control of the IgE system. In our own laboratory, we have been studying soluble regulatory factors known as suppressive factor of allergy (SFA) and enhancing factor of allergy (EFA), which were initially identified by their selective, and opposing, regulatory effects on in vivo IgE responses in inbred mice. More recently, in an in vitro system in which it is possible to induce the de novo expression of FcR epsilon on lymphocytes cultured in the presence of monoclonal IgE, we reported that concomitant exposure of such cultured cells to SFA selectively blocked the induction of FcR epsilon expression. In the present study, we have extended these investigations by making a direct comparison between certain biological properties and biochemical characteristics of SFA and EFA. We found that SFA and EFA can be distinguished biochemically on the basis of size, SFA falling in the range of 30,000 daltons or so, and EFA falling in the range of 15,000 daltons. In examining their biological properties, we unexpectedly found that although SFA-enriched and EFA-enriched fractions exert dramatically distinct biological effects on in vivo IgE antibody synthesis (as implied by their names), the two respective active fractions are totally indistinguishable in their inhibitory effects on IgE-mediated induction of FcR epsilon + lymphocytes in vitro when intact spleen cell populations are exposed to monoclonal IgE. That the active entities in SFA and EFA responsible for inhibition of

  8. BioCompoundML: A General Biofuel Property Screening Tool for Biological Molecules Using Random Forest Classifiers

    DOE PAGES

    Whitmore, Leanne S.; Davis, Ryan W.; McCormick, Robert L.; ...

    2016-09-15

    Screening a large number of biologically derived molecules for potential fuel compounds without recourse to experimental testing is important in identifying understudied yet valuable molecules. Experimental testing, although a valuable standard for measuring fuel properties, has several major limitations, including the requirement of testably high quantities, considerable expense, and a large amount of time. This paper discusses the development of a general-purpose fuel property tool, using machine learning, whose outcome is to screen molecules for desirable fuel properties. BioCompoundML adopts a general methodology, requiring as input only a list of training compounds (with identifiers and measured values) and a listmore » of testing compounds (with identifiers). For the training data, BioCompoundML collects open data from the National Center for Biotechnology Information, incorporates user-provided features, imputes missing values, performs feature reduction, builds a classifier, and clusters compounds. BioCompoundML then collects data for the testing compounds, predicts class membership, and determines whether compounds are found in the range of variability of the training data set. We demonstrate this tool using three different fuel properties: research octane number (RON), threshold soot index (TSI), and melting point (MP). Here we provide measures of its success with these properties using randomized train/test measurements: average accuracy is 88% in RON, 85% in TSI, and 94% in MP; average precision is 88% in RON, 88% in TSI, and 95% in MP; and average recall is 88% in RON, 82% in TSI, and 97% in MP. The receiver operator characteristics (area under the curve) were estimated at 0.88 in RON, 0.86 in TSI, and 0.87 in MP. We also measured the success of BioCompoundML by sending 16 compounds for direct RON determination. Finally, we provide a screen of 1977 hydrocarbons/oxygenates within the 8696 compounds in MetaCyc, identifying compounds with high

  9. Holography and coherent diffraction with low-energy electrons: A route towards structural biology at the single molecule level.

    PubMed

    Latychevskaia, Tatiana; Longchamp, Jean-Nicolas; Escher, Conrad; Fink, Hans-Werner

    2015-12-01

    The current state of the art in structural biology is led by NMR, X-ray crystallography and TEM investigations. These powerful tools however all rely on averaging over a large ensemble of molecules. Here, we present an alternative concept aiming at structural analysis at the single molecule level. We show that by combining electron holography and coherent diffraction imaging estimations concerning the phase of the scattered wave become needless as the phase information is extracted from the data directly and unambiguously. Performed with low-energy electrons the resolution of this lens-less microscope is just limited by the De Broglie wavelength of the electron wave and the numerical aperture, given by detector geometry. In imaging freestanding graphene, a resolution of 2Å has been achieved revealing the 660.000 unit cells of the graphene sheet from a single data set. Once applied to individual biomolecules the method shall ultimately allow for non-destructive imaging and imports the potential to distinguish between different conformations of proteins with atomic resolution.

  10. Characterization of the biological activity of a potent small molecule Hec1 inhibitor TAI-1

    PubMed Central

    2014-01-01

    Background Hec1 (NDC80) is an integral part of the kinetochore and is overexpressed in a variety of human cancers, making it an attractive molecular target for the design of novel anticancer therapeutics. A highly potent first-in-class compound targeting Hec1, TAI-1, was identified and is characterized in this study to determine its potential as an anticancer agent for clinical utility. Methods The in vitro potency, cancer cell specificity, synergy activity, and markers for response of TAI-1 were evaluated with cell lines. Mechanism of action was confirmed with western blotting and immunofluorescent staining. The in vivo potency of TAI-1 was evaluated in three xenograft models in mice. Preliminary toxicity was evaluated in mice. Specificity to the target was tested with a kinase panel. Cardiac safety was evaluated with hERG assay. Clinical correlation was performed with human gene database. Results TAI-1 showed strong potency across a broad spectrum of tumor cells. TAI-1 disrupted Hec1-Nek2 protein interaction, led to Nek2 degradation, induced significant chromosomal misalignment in metaphase, and induced apoptotic cell death. TAI-1 was effective orally in in vivo animal models of triple negative breast cancer, colon cancer and liver cancer. Preliminary toxicity shows no effect on the body weights, organ weights, and blood indices at efficacious doses. TAI-1 shows high specificity to cancer cells and to target and had no effect on the cardiac channel hERG. TAI-1 is synergistic with doxorubicin, topotecan and paclitaxel in leukemia, breast and liver cancer cells. Sensitivity to TAI-1 was associated with the status of RB and P53 gene. Knockdown of RB and P53 in cancer cells increased sensitivity to TAI-1. Hec1-overexpressing molecular subtypes of human lung cancer were identified. Conclusions The excellent potency, safety and synergistic profiles of this potent first-in-class Hec1-targeted small molecule TAI-1 show its potential for clinically utility in anti

  11. From animal to molecule: aspects of the biology of insulin-like growth factors.

    PubMed Central

    Gilmour, R. S.; Prosser, C. G.; Fleet, I. R.; Cocco, L.; Saunders, J. C.; Brown, K. D.; Corps, A. N.

    1988-01-01

    The synthesis of IGF-II mRNA in sheep foetal tissues is considerably higher than IGF-I. IGF-II probably has a paracrine role in the foetus; however it is likely that IGF-I originates mainly from the foetal liver and has an endocrine function. Although in the adult system IGF-I is tightly bound to serum carrier proteins it is potentially biologically active. Galactopoiesis in the goat mammary gland provides a useful model for demonstrating the importance of circulating IGF-I as a mediator of GH action. Ligand-receptor interactions involved in the stimulation of Swiss 3T3 fibroblasts by IGF-I, II and insulin were examined. It was found that the potency of binding to type I receptors was IGF-I greater than IGF-II much greater than insulin by competitive binding assays and chemical cross-linking studies, and that some cell lines secrete an IGF binding protein which is specific for IGF-I and II and which acts as an inhibitor in cellular binding assays. Maximal stimulation of DNA synthesis induced by IGF-I, II and insulin in the presence of synergising mitogens were similar. While the actions of the IGFs were consistent with type I receptor binding insulin appeared to act through its own receptor. The reduction of EGF receptor affinity following the addition of IGF-I and insulin to 3T3 cells may involve a protein kinase that is not sensitive to phorbol esters. 3T3 cell nuclei contain endogenous inositol phospholipids and their corresponding kinases and monoesterases.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 4 Figure 6 PMID:2855464

  12. 2-nitroglycals as powerful glycosyl donors: application in the synthesis of biologically important molecules.

    PubMed

    Schmidt, Richard R; Vankar, Yashwant D

    2008-08-01

    [Reaction: see text]. The biological significance of oligosaccharides and glycoconjugates is profound and wide-ranging. For example, the mucins have attracted attention because of their role in fundamental cellular processes such as fertilization, parasitic infection, inflammation, immune defense, cell growth, and cell-cell adhesion. Increased expression of mucins is implicated in malignant transformation of cells. Antifreeze glycoproteins also are of interest because they are important for the survival of many marine teleost fishes that live in polar and subpolar waters. The synthesis of glycoconjugates requires methods for glycoside bond formation, the most difficult aspect of which is the assembly of monosaccharide building blocks. This Account discusses a valuable addition to the repertoire of methods for glycoconjugate synthesis: an approach that involves 2-nitroglycal concatenation. For a long time, methods for glycosylation via glycosyl donor generation required either an anomeric oxygen exchange reaction or anomeric oxygen retention. In the case of an anomeric oxygen exchange reaction, activation of the glycosyl donors demands a promoter in at least equimolar amounts. However, anomeric oxygen retention, such as base-catalyzed formation of O-glycosyl trichloroacetimidates, can be activated by catalytic amounts of acid or Lewis acid. Alternatively, glycals, which are readily available from sugars, can be an attractive starting material for glycoside bond formation. Their nucleophilic character at C-2 permits reactions with oxygen, nitrogen, and sulfur electrophiles that under high substrate stereocontrol generally lead to three-membered rings; ring opening under acid catalysis furnishes the corresponding glycosides, whichdepending on the electrophile Xare also employed for 2-deoxyglycoside synthesis. Glycals also can be transformed into derivatives that have at C-2 an electron-withdrawing group and are amenable to Michael-type addition. A good example are 2

  13. Competitive behavior of photons contributing to junction voltage jump in narrow band-gap semiconductor multi-quantum-well laser diodes at lasing threshold

    SciTech Connect

    Feng, Liefeng E-mail: lihongru@nankai.edu.cn; Yang, Xiufang; Wang, Cunda; Yao, Dongsheng; Li, Yang; Li, Ding; Hu, Xiaodong; Li, Hongru E-mail: lihongru@nankai.edu.cn

    2015-04-15

    The junction behavior of different narrow band-gap multi-quantum-well (MQW) laser diodes (LDs) confirmed that the jump in the junction voltage in the threshold region is a general characteristic of narrow band-gap LDs. The relative change in the 1310 nm LD is the most obvious. To analyze this sudden voltage change, the threshold region is divided into three stages by I{sub th}{sup l} and I{sub th}{sup u}, as shown in Fig. 2; I{sub th}{sup l} is the conventional threshold, and as long as the current is higher than this threshold, lasing exists and the IdV/dI-I plot drops suddenly; I{sub th}{sup u} is the steady lasing point, at which the separation of the quasi-Fermi levels of electron and holes across the active region (V{sub j}) is suddenly pinned. Based on the evolutionary model of dissipative structure theory, the rate equations of the photons in a single-mode LD were deduced in detail at I{sub th}{sup l} and I{sub th}{sup u}. The results proved that the observed behavior of stimulated emission suddenly substituting for spontaneous emission, in a manner similar to biological evolution, must lead to a sudden increase in the injection carriers in the threshold region, which then causes the sudden increase in the junction voltage in this region.

  14. Gas-phase geometry optimization of biological molecules as a reasonable alternative to a continuum environment description: fact, myth, or fiction?

    PubMed

    Sousa, Sérgio Filipe; Fernandes, Pedro Alexandrino; Ramos, Maria João

    2009-12-31

    Gas-phase optimization of single biological molecules and of small active-site biological models has become a standard approach in first principles computational enzymology. The important role played by the surrounding environment (solvent, enzyme, both) is normally only accounted for through higher-level single point energy calculations performed using a polarizable continuum model (PCM) and an appropriate dielectric constant with the gas-phase-optimized geometries. In this study we analyze this widely used approximation, by comparing gas-phase-optimized geometries with geometries optimized with different PCM approaches (and considering different dielectric constants) for a representative data set of 20 very important biological molecules--the 20 natural amino acids. A total of 323 chemical bonds and 469 angles present in standard amino acid residues were evaluated. The results show that the use of gas-phase-optimized geometries can in fact be quite a reasonable alternative to the use of the more computationally intensive continuum optimizations, providing a good description of bond lengths and angles for typical biological molecules, even for charged amino acids, such as Asp, Glu, Lys, and Arg. This approximation is particularly successful if the protonation state of the biological molecule could be reasonably described in vacuum, a requirement that was already necessary in first principles computational enzymology.

  15. A translational synthetic biology platform for rapid access to gram-scale quantities of novel drug-like molecules.

    PubMed

    Reed, James; Stephenson, Michael J; Miettinen, Karel; Brouwer, Bastiaan; Leveau, Aymeric; Brett, Paul; Goss, Rebecca J M; Goossens, Alain; O'Connell, Maria A; Osbourn, Anne

    2017-07-01

    Plants are an excellent source of drug leads. However availability is limited by access to source species, low abundance and recalcitrance to chemical synthesis. Although plant genomics is yielding a wealth of genes for natural product biosynthesis, the translation of this genetic information into small molecules for evaluation as drug leads represents a major bottleneck. For example, the yeast platform for artemisinic acid production is estimated to have taken >150 person years to develop. Here we demonstrate the power of plant transient transfection technology for rapid, scalable biosynthesis and isolation of triterpenes, one of the largest and most structurally diverse families of plant natural products. Using pathway engineering and improved agro-infiltration methodology we are able to generate gram-scale quantities of purified triterpene in just a few weeks. In contrast to heterologous expression in microbes, this system does not depend on re-engineering of the host. We next exploit agro-infection for quick and easy combinatorial biosynthesis without the need for generation of multi-gene constructs, so affording an easy entrée to suites of molecules, some new-to-nature, that are recalcitrant to chemical synthesis. We use this platform to purify a suite of bespoke triterpene analogs and demonstrate differences in anti-proliferative and anti-inflammatory activity in bioassays, providing proof of concept of this system for accessing and evaluating medicinally important bioactives. Together with new genome mining algorithms for plant pathway discovery and advances in plant synthetic biology, this advance provides new routes to synthesize and access previously inaccessible natural products and analogs and has the potential to reinvigorate drug discovery pipelines. Copyright © 2017. Published by Elsevier Inc.

  16. Regulatory forum opinion piece: differences between protein-based biologic products (biotherapeutics) and chemical entities (small molecules) of relevance to the toxicologic pathologist.

    PubMed

    Leach, Michael W

    2013-01-01

    With the advances in cell culture methodologies and molecular biology that have occurred over the past several decades, biologics have become as common as small molecules within the portfolios of the pharmaceutical industry. Toxicologic pathologists should be aware of some of the fundamental differences between small molecules and biologics. Effects are not always observed in studies following administration of biologics. When findings are observed, the toxicologic pathologist should initially determine whether the effect(s) are mediated (directly or indirectly) via the intended pharmacology, exaggerated pharmacology, an immune response, and/or off target effects. Following this determination, the toxicologic pathologist should provide an assessment regarding the relevance of the findings to the intended clinical population, usually humans. The toxicologic pathologist may also be asked to assess unusual species and models. Given their broad background in physiology and immunology, toxicologic pathologists are uniquely positioned to provide this input to drug development teams.

  17. The effects of biological lubricating molecules on flexor tendon reconstruction in a canine allograft model in vivo.

    PubMed

    Zhao, Chunfeng; Wei, Zhuang; Reisdorf, Ramona L; Thoreson, Andrew R; Jay, Gregory D; Moran, Steven L; An, Kai-Nan; Amadio, Peter C

    2014-05-01

    Using allograft is an attractive alternative for flexor tendon reconstruction because of the lack of donor-site morbidity, and better matching to the intrasynovial environment. The purpose of this study was to use biological lubricant molecules to modify the graft surface to decrease adhesions and improve digit function. Twenty-eight flexor digitorum profundus tendons from the second and fifth digits of 14 dogs were lacerated and repaired to create a model with repair failure and scar digit for tendon reconstruction. Six weeks after the initial operation, the tendons were reconstructed with flexor digitorum profundus allograft tendons obtained from canine cadavers. One graft tendon in each dog was treated with saline as a control and the other was treated with carbodiimide-derivatized hyaluronic acid and gelatin plus lubricin. Six weeks postoperatively, digit function, graft mechanics, and biology were analyzed. Allograft tendons treated with carbodiimide-derivatized hyaluronic acid-lubricin had decreased adhesions at the proximal tendon/graft repair and within the flexor sheath, improved digit function, and increased graft gliding ability. The treatment also reduced the strength at the distal tendon-to-bone repair, but the distal attachment rupture rate was similar for both graft types. Histologic evaluation showed that viable cells migrated to the allograft, but these were limited to the tendon surface. Carbodiimide-derivatized hyaluronic acid-lubricin treatment of tendon allograft improves digit functional outcomes after flexor tendon reconstruction. However, delayed bone-to-tendon healing should be a caution. Furthermore, the cell infiltration into the allograft tendon substance should be a target for future studies, to shorten the allograft self-regeneration period.

  18. Bioorganic chemistry à la baguette: studies on molecular recognition in biological systems using rigid-rod molecules.

    PubMed

    Matile, S

    2001-01-01

    Initial studies using rigid-rod molecules or "baguettes" to address bioorganic topics of current scientific concern are reported. It is illustrated how transmembrane oligo(p-phenylene)s as representative model rods can be tuned to recognize lipid bilayer membranes either by their thickness or polarization. The construction of otherwise problematic hydrogen-bonded chains along transmembrane rods yields "proton wires," which act by a mechanism that is central in bioenergetics but poorly explored by means of synthetic models. Another example focuses on multivalent ligands assembling rigid-rod cell-surface receptors into transmembrane dynamic arene arrays. The potassium transport mediated by these ligand-receptor complexes provides experimental support for the potential biological importances of the controversial cation-pi mechanism. More complex supramolecular architecture is portrayed in the first artificial beta-barrels. It is shown how programmed assembly of toroidal rigid-rod supramolecules in detergent-free water permits control of diameter of the chemical nature of their interior. Reversed rigid-rod beta-barrels are assembled to function as self-assembled ionophores, ion channel models, and transmembrane nanopores. The potential of future intratoroidal chemistry is exemplified by encapsulation and planarization of beta-carotene in water and the construction of transmembrane B-DNA at the center of a second-sphere host-guest complex à al baguette.

  19. Benchmark reaction rates, the stability of biological molecules in water, and the evolution of catalytic power in enzymes.

    PubMed

    Wolfenden, Richard

    2011-01-01

    The rates of enzyme reactions fall within a relatively narrow range. To estimate the rate enhancements produced by enzymes, and their expected affinities for transition state analog inhibitors, it is necessary to measure the rates of the corresponding reactions in water in the absence of a catalyst. This review describes the spontaneous cleavages of C-C, C-H, C-N, C-O, P-O, and S-O bonds in biological molecules, as well as the uncatalyzed reactions that correspond to phosphoryl transfer reactions catalyzed by kinases and to peptidyl transfer in the ribosome. The rates of these reactions, some with half-lives in excess of one million years, span an overall range of 10¹⁹-fold. Moreover, the slowest reactions tend to be most sensitive to temperature, with rates that increase as much as 10⁷-fold when the temperature is raised from 25° to 100°C. That tendency collapses, by many orders of magnitude, the time that would have been required for chemical evolution on a warm earth. If the catalytic effect of primitive enzymes, like that of modern enzymes and many nonenzymatic catalysts, were mainly to reduce a reaction's enthalpy of activation, then the resulting rate enhancement would have increased automatically as the surroundings cooled. By reducing the time required for early chemical evolution in a warm environment, these findings counter the view that not enough time has passed for terrestrial life to have evolved to its present level of complexity.

  20. Periradicular Tissue Responses to Biologically Active Molecules or MTA When Applied in Furcal Perforation of Dogs' Teeth

    PubMed Central

    Zairi, Anna; Lambrianidis, Theodoros; Pantelidou, Ourania; Papadimitriou, Serafim; Tziafas, Dimitrios

    2012-01-01

    The aim of this study was the comparative evaluation of inflammatory reactions and tissue responses to four growth factors, or mineral trioxide aggregate (MTA), or a zinc-oxide-eugenol-based cement (IRM) as controls, when used for the repair of furcal perforations in dogs' teeth. Results showed significantly higher inflammatory cell response in the transforming growth factorβ1 (TGFβ1) and zinc-oxide-eugenol-based cement (IRM) groups and higher rates of epithelial proliferation in the TGFβ1, basic fibroblast growth factor (bFGF), and insulin growth factor-I (IGF-I) groups compared to the MTA. Significantly higher rates of bone formation were found in the control groups compared to the osteogenic protein-1 (OP-1). Significantly higher rates of cementum formation were observed in the IGF-I and bFGF groups compared to the IRM. None of the biologically active molecules can be suggested for repairing furcal perforations, despite the fact that growth factors exerted a clear stimulatory effect on cementum formation and inhibited collagen capsule formation. MTA exhibited better results than the growth factors. PMID:22319529

  1. Utilization of Microwave Spectroscopy to Identify and Probe Reaction Dynamics of Hsno, a Crucial Biological Signaling Molecule

    NASA Astrophysics Data System (ADS)

    Nava, Matthew; Martin-Drumel, Marie-Aline; Stanton, John F.; Cummins, Christopher; McCarthy, Michael C.

    2016-06-01

    Thionitrous acid (HSNO), a potential key intermediate in biological signaling pathways, has been proposed to link NO and H2S biochemistries. Its existence and stability in vivo, however, remain controversial. By means of Fourier-transform microwave spectroscopy, we establish that HSNO is spontaneously formed in high concentration when NO and H2S gases are simply mixed at room temperature in the presence of metallic surfaces. Our measurements reveal that HSNO is formed with high efficiency by the reaction H2S and N2O3 to produce HSNO and HNO2, where N2O3 is a product of NO disproportionation. These studies also suggest that further reaction of HSNO with H2S may form HNO and HSSH. The length of the S--N bond has been derived to high precision from isotopic studies, and is found to be unusually long, 1.84 Å -- the longest S--N bond reported to date for an SNO compound. The present structural and reactivity investigations of this elusive molecule provide a firm fundation to better understand its physiological chemistry and propensity to undergo S--N bond homolysis in vivo.

  2. Prospect of detection and recognition of single biological molecules using ultrafast coherent dynamics in quantum dot-metallic nanoparticle systems

    NASA Astrophysics Data System (ADS)

    Sadeghi, S. M.

    2015-08-01

    Conventional plasmonic sensors are based on the intrinsic resonances of metallic nanoparticles. In such sensors wavelength shift of such resonances are used to detect biological molecules. Recently we introduced ultra-sensitive timedomain nanosensors based on the way variations in the environmental conditions influence coherent dynamics of hybrid systems consisting of metallic nanoparticles and quantum dots. Such dynamics are generated via interaction of these systems with a laser field, generating quantum coherence and coherent exciton-plasmon coupling. These sensors are based on impact of variations of the refractive index of the environment on such dynamics, generating time-dependent changes in the emission of the QDs. In this paper we study the impact of material properties of the metallic nanoparticles on this process and demonstrate the key role played by the design of the quantum dots. We show that Ag nanoparticles, even in a simple spherical shape, may allow these sensors to operate at room temperature, owing to the special properties of quantum dot-metallic nanoparticle systems that may allow coherent effects utilized in such sensors happen in the presence of the ultrafast polarization dephasing of quantum dots.

  3. Supramolecular assembly of biological molecules purified from bovine nerve cells: from microtubule bundles and necklaces to neurofilament networks

    NASA Astrophysics Data System (ADS)

    Needleman, Daniel J.; Jones, Jayna B.; Raviv, Uri; Ojeda-Lopez, Miguel A.; Miller, H. P.; Li, Y.; Wilson, L.; Safinya, C. R.

    2005-11-01

    With the completion of the human genome project, the biosciences community is beginning the daunting task of understanding the structures and functions of a large number of interacting biological macromolecules. Examples include the interacting molecules involved in the process of DNA condensation during the cell cycle, and in the formation of bundles and networks of filamentous actin proteins in cell attachment, motility and cytokinesis. In this proceedings paper we present examples of supramolecular assembly based on proteins derived from the vertebrate nerve cell cytoskeleton. The axonal cytoskeleton in vertebrate neurons provides a rich example of bundles and networks of neurofilaments, microtubules (MTs) and filamentous actin, where the nature of the interactions, structures, and structure-function correlations remains poorly understood. We describe synchrotron x-ray diffraction, electron microscopy, and optical imaging data, in reconstituted protein systems purified from bovine central nervous system, which reveal unexpected structures not predicted by current electrostatic theories of polyelectrolyte bundling, including three-dimensional MT bundles and two-dimensional MT necklaces.

  4. X-ray diffraction simulation of GeSn/Ge multi-quantum wells with kinematic approach

    NASA Astrophysics Data System (ADS)

    Li, Hui; Chang, Chiao; Cheng, Hung-Hsiang

    2017-06-01

    We report an investigation on X-ray diffraction simulation of GeSn/Ge Multi-quantum wells (MQWs) with kinematic approach. X-ray diffraction in (004) ω-2θ scan and (224) reciprocal space mapping are performed for characterization of the MQWs. However, simulation of the diffraction process is imperative for further structural analysis of the MQWs. The compressive strain not only affects the calculation of Sn composition in GeSn wells, but also dramatically affects the symmetry of satellite peaks.

  5. Design of monocrystalline Si/SiGe multi-quantum well microbolometer detector for infrared imaging systems

    NASA Astrophysics Data System (ADS)

    Shafique, Atia; Durmaz, Emre C.; Cetindogan, Barbaros; Yazici, Melik; Kaynak, Mehmet; Kaynak, Canan B.; Gurbuz, Yasar

    2016-05-01

    This paper presents the design, modelling and simulation results of silicon/silicon-germanium (Si/SiGe) multi-quantum well based bolometer detector for uncooled infrared imaging system. The microbolometer is designed to detect light in the long wave length infrared (LWIR) range from 8 to 14 μm with pixel size of 25 x 25 μm. The design optimization strategy leads to achieve the temperature coefficient of resistance (TCR) 4.5%/K with maximum germanium (Ge) concentration of 50%. The design of microbolometer entirely relies on standard CMOS and MEMS processes which makes it suitable candidate for commercial infrared imaging systems.

  6. Dependence of device performance on carrier escape sequence in multi-quantum-well p-i-n solar cells

    NASA Astrophysics Data System (ADS)

    Alemu, A.; Coaquira, J. A. H.; Freundlich, A.

    2006-04-01

    This work is a study relating device performance and carrier escape sequence in a large set of InAsP/InP p-i-n multi-quantum-well solar cells. The devices encompass nearly identical i-region thickness and built-in electric field and present similar absorption threshold energies. The escape sequence of the first confined electron-to-conduction band continuum and heavy/light holes-to-valence band continuum is extracted from the photoluminescence versus temperature analysis and by comparing the measured activation energies to calculated hole/electron well depths and thermionic escape times. Light holes, as expected for most III-V nanostructure systems, are found to be the fastest escaping carriers in all samples. The escape of electrons prior to heavy holes is shown to be a prerequisite to prevent severe open circuit voltage degradation. A possible explanation of the origin of this effect is offered. InP/InAsP multi-quantum-well solar cells with high built-in electric field and fast electronic escape time display better open circuit voltage and performance.

  7. Recent advances in experimental techniques to probe fast excited-state dynamics in biological molecules in the gas phase: dynamics in nucleotides, amino acids and beyond

    PubMed Central

    Staniforth, Michael; Stavros, Vasilios G.

    2013-01-01

    In many chemical reactions, an activation barrier must be overcome before a chemical transformation can occur. As such, understanding the behaviour of molecules in energetically excited states is critical to understanding the chemical changes that these molecules undergo. Among the most prominent reactions for mankind to understand are chemical changes that occur in our own biological molecules. A notable example is the focus towards understanding the interaction of DNA with ultraviolet radiation and the subsequent chemical changes. However, the interaction of radiation with large biological structures is highly complex, and thus the photochemistry of these systems as a whole is poorly understood. Studying the gas-phase spectroscopy and ultrafast dynamics of the building blocks of these more complex biomolecules offers the tantalizing prospect of providing a scientifically intuitive bottom-up approach, beginning with the study of the subunits of large polymeric biomolecules and monitoring the evolution in photochemistry as the complexity of the molecules is increased. While highly attractive, one of the main challenges of this approach is in transferring large, and in many cases, thermally labile molecules into vacuum. This review discusses the recent advances in cutting-edge experimental methodologies, emerging as excellent candidates for progressing this bottom-up approach. PMID:24204191

  8. Recent advances in experimental techniques to probe fast excited-state dynamics in biological molecules in the gas phase: dynamics in nucleotides, amino acids and beyond.

    PubMed

    Staniforth, Michael; Stavros, Vasilios G

    2013-11-08

    In many chemical reactions, an activation barrier must be overcome before a chemical transformation can occur. As such, understanding the behaviour of molecules in energetically excited states is critical to understanding the chemical changes that these molecules undergo. Among the most prominent reactions for mankind to understand are chemical changes that occur in our own biological molecules. A notable example is the focus towards understanding the interaction of DNA with ultraviolet radiation and the subsequent chemical changes. However, the interaction of radiation with large biological structures is highly complex, and thus the photochemistry of these systems as a whole is poorly understood. Studying the gas-phase spectroscopy and ultrafast dynamics of the building blocks of these more complex biomolecules offers the tantalizing prospect of providing a scientifically intuitive bottom-up approach, beginning with the study of the subunits of large polymeric biomolecules and monitoring the evolution in photochemistry as the complexity of the molecules is increased. While highly attractive, one of the main challenges of this approach is in transferring large, and in many cases, thermally labile molecules into vacuum. This review discusses the recent advances in cutting-edge experimental methodologies, emerging as excellent candidates for progressing this bottom-up approach.

  9. Qualitative and quantitative pharmacophore-similarity assessment of anthranilamide-based factor Xa inhibitors: applications on similar molecules with identical biological endpoints.

    PubMed

    Kumar, Sivakumar Prasanth; Rawal, Rakesh M; Pandya, Himanshu A; Jasrai, Yogesh T

    2016-01-01

    It is a conventional practice to exclude molecules with identical biological endpoints to avoid bias in the resulting hypothesis model. Despite the diverse chemical functionalities, the receptor interactions of such molecules are often unexplored. The present study motivates the selection of these molecules diversified by single atom or functional group compared to internal molecules as external set and helps in the understanding of corresponding effects toward receptor interactions and biological endpoints. Applied on anthranilamide-series of factor Xa analogs, the inhibitory activities were correlated (r(2) = 0.99) and validated (q(2) = 0.68) with distance-based pharmacophore descriptors using support vector machine. The selected external set molecules exhibited better prediction accuracy by securing activities less than one residual threshold. The effect on inhibitory activity was assessed by the examination of pharmacophore-similarity and its interactions with key residues of Human factor Xa enzyme using molecular docking approach. Furthermore, qualitative pharmacophore models were developed on the subset of molecular dataset divided as most actives, moderately actives and least actives, to recognize crucial activity governing pharmacophore features. The outcome of this study will bring new insights about the requirements of pharmacophore features and prioritizes its selection in the design and optimization of potent Xa inhibitors.

  10. Prion-like nanofibrils of small molecules (PriSM): A new frontier at the intersection of supramolecular chemistry and cell biology.

    PubMed

    Zhou, Jie; Du, Xuewen; Xu, Bing

    2015-01-01

    Formed by non-covalent interactions and not defined at genetic level, the assemblies of small molecules in biology are complicated and less explored. A common morphology of the supramolecular assemblies of small molecules is nanofibrils, which coincidentally resembles the nanofibrils formed by proteins such as prions. So these supramolecular assemblies are termed as prion-like nanofibrils of small molecules (PriSM). Emerging evidence from several unrelated fields over the past decade implies the significance of PriSM in biology and medicine. This perspective aims to highlight some recent advances of the research on PriSM. This paper starts with description of the intriguing similarities between PriSM and prions, discusses the paradoxical features of PriSM, introduces the methods for elucidating the biological functions of PriSM, illustrates several examples of beneficial aspects of PriSM, and finishes with the promises and current challenges in the research of PriSM. We anticipate that the research of PriSM will contribute to the fundamental understanding at the intersection of supramolecular chemistry and cell biology and ultimately lead to a new paradigm of molecular (or supramolecular) therapeutics for biomedicine.

  11. Encapsulation and Diffraction-Pattern-Correction Methods to Reduce the Effect of Damage in X-Ray Diffraction Imaging of Single Biological Molecules

    SciTech Connect

    Hau-Riege, Stefan P.; London, Richard A.; Chapman, Henry N.; Szoke, Abraham; Timneanu, Nicusor

    2007-05-11

    Short and intense x-ray pulses may be used for atomic-resolution diffraction imaging of single biological molecules. Radiation damage and a low signal-to-noise ratio impose stringent pulse requirements. In this Letter, we describe methods for decreasing the damage and improving the signal by encapsulating the molecule in a sacrificial layer (tamper) that reduces atomic motion and by postprocessing the pulse-averaged diffraction pattern to correct for ionization damage. Simulations show that these methods greatly improve the image quality.

  12. The small molecule C-6 is selectively cytotoxic against breast cancer cells and its biological action is characterized by mitochondrial defects and endoplasmic reticulum stress.

    PubMed

    Vaden, Rachel M; Gligorich, Keith M; Jana, Ranjan; Sigman, Matthew S; Welm, Bryan E

    2014-11-26

    The establishment of drug resistance following treatment with chemotherapeutics is strongly associated with poor clinical outcome in patients, and drugs that target chemoresistant tumors have the potential to increase patient survival. In an effort to identify biological pathways of chemoresistant breast cancers that can be targeted therapeutically, a small molecule screen utilizing metastatic patient-derived breast cancer cells was conducted; from this previous report, the cytotoxic small molecule, C-6, was identified for its ability to selectively kill aggressive breast cancer cells in a caspase-independent manner. Here, we describe the cellular and molecular pathways induced following C-6 treatment in both normal and breast cancer cell lines. Transcriptome analyses and protein expression experiments were used to measure endoplasmic reticulum (ER) stress following C-6 treatment. Studies utilizing transmission electron microscopy and metabolomic profiling were conducted to characterize mitochondrial morphology and function in C-6-treated cells. Oxygen consumption rates and oxidative stress were also measured in breast cancer and normal mammary epithelial cells following treatment with the small molecule. Finally, structural modifications were made to the molecule and potency and cancer selectivity were evaluated. Treatment with C-6 resulted in ER stress in both breast cancer cells and normal mammary epithelial cells. Gross morphological defects were observed in the mitochondria and these aberrations were associated with metabolic imbalances and a diminished capacity for respiration. Following treatment with C-6, oxidative stress was observed in three breast cancer cell lines but not in normal mammary epithelial cells. Finally, synthetic modifications made to the small molecule resulted in the identification of the structural components that contribute to C-6's cancer-selective phenotype. The data reported here implicate mitochondrial and ER stress as a component

  13. Computational models for in-vitro anti-tubercular activity of molecules based on high-throughput chemical biology screening datasets.

    PubMed

    Periwal, Vinita; Kishtapuram, Shireesha; Scaria, Vinod

    2012-03-31

    The emergence of Multi-drug resistant tuberculosis in pandemic proportions throughout the world and the paucity of novel therapeutics for tuberculosis have re-iterated the need to accelerate the discovery of novel molecules with anti-tubercular activity. Though high-throughput screens for anti-tubercular activity are available, they are expensive, tedious and time-consuming to be performed on large scales. Thus, there remains an unmet need to prioritize the molecules that are taken up for biological screens to save on cost and time. Computational methods including Machine Learning have been widely employed to build classifiers for high-throughput virtual screens to prioritize molecules for further analysis. The availability of datasets based on high-throughput biological screens or assays in public domain makes computational methods a plausible proposition for building predictive models. In addition, this approach would save significantly on the cost, effort and time required to run high throughput screens. We show that by using four supervised state-of-the-art classifiers (SMO, Random Forest, Naive Bayes and J48) we are able to generate in-silico predictive models on an extremely imbalanced (minority class ratio: 0.6%) large dataset of anti-tubercular molecules with reasonable AROC (0.6-0.75) and BCR (60-66%) values. Moreover, these models are able to provide 3-4 fold enrichment over random selection. In the present study, we have used the data from in-vitro screens for anti-tubercular activity from a high-throughput screen available in public domain to build highly accurate classifiers based on molecular descriptors of the molecules. We show that Machine Learning tools can be used to build highly effective predictive models for virtual high-throughput screens to prioritize molecules from large molecular libraries.

  14. A novel method developed for estimating mineralization efficiencies and its application in PC and PEC degradations of large molecule biological compounds with unknown chemical formula.

    PubMed

    Li, Guiying; Liu, Xiaolu; An, Taicheng; Wong, Po Keung; Zhao, Huijun

    2016-05-15

    A new method to estimate the photocatalytic (PC) and photoelectrocatalytic (PEC) mineralization efficiencies of large molecule biological compounds with unknown chemical formula in water was firstly developed and experimentally validated. The method employed chemical oxidation under the standard dichromate chemical oxygen demand (COD) conditions to obtain QCOD values of model compounds with unknown chemical formula. The measured QCOD values were used as the reference to replace QCOD values of model compounds for calculation of the mineralization efficiencies (in %) by assuming the obtained QCOD values are the measure of the theoretical charge required for the complete mineralization of organic pollutants. Total organic carbon (TOC) was also employed as a reference to confirm the mineralization capacity of dichromate chemical oxidation. The developed method was applied to determine the degradation extent of model compounds, such as bovine serum albumin (BSA), lecithin and bacterial DNA, by PC and PEC. Incomplete PC mineralization of all large molecule biological compounds was observed, especially for BSA. But the introduction of electrochemical technique into a PC oxidation process could profoundly improve the mineralization efficiencies of model compounds. PEC mineralization efficiencies of bacterial DNA was the highest, while that of lecithin was the lowest. Overall, PEC degradation method was found to be much effective than PC method for all large molecule biological compounds investigated, with PEC/PC mineralization ratios followed an order of BSA > lecithin > DNA.

  15. Effect of potential barrier height on the carrier transport in InGaAs/GaAsP multi-quantum wells and photoelectric properties of laser diode.

    PubMed

    Dong, Hailiang; Sun, Jing; Ma, Shufang; Liang, Jian; Lu, Taiping; Jia, Zhigang; Liu, Xuguang; Xu, Bingshe

    2016-03-07

    The growth and strain-compensation behaviour of InGaAs/GaAsP multi-quantum wells, which were fabricated by metal-organic chemical vapor deposition, have been studied towards the application of these quantum wells in high-power laser diodes. The effect of the height of the potential barrier on the confined level of carrier transport was studied by incorporating different levels of phosphorus content into the GaAsP barrier. The crystal quality and interface roughness of the InGaAs/GaAsP multi-quantum wells with different phosphorus contents were evaluated by high resolution X-ray diffraction and in situ optical surface reflectivity measurements during the growth. The surface morphology and roughness were characterized by atomic force microscopy, which indicates the variation law of surface roughness, terrace width and uniformity with increasing phosphorus content, owing to strain accumulation. Moreover, the defect generation and structural disorder of the multi-quantum wells were investigated by Raman spectroscopy. The optical properties of the multi-quantum wells were characterized by photoluminescence, which shows that the spectral intensity increases as the phosphorus content increases. The results suggest that more electrons are well bound in InGaAs because of the high potential barrier. Finally, the mechanism of the effect of the height of the potential barrier on laser performance was proposed on the basis of simulation calculations and experimental results.

  16. Breaking the Nanometer Barrier: Progress in Biological Nanoscience, Measured One Molecule at a Time (How a Biophysicist Watches DNA Transcription)

    SciTech Connect

    Block, Stephen

    2006-03-20

    A new field of scientific exploration - single molecule biophysics - is currently reshaping and redefining our understanding of the mechanochemistry of life. The development of laser-based optical traps, or 'optical tweezers,' has allowed for physiological assessments of such precision that bio-molecules can now be measured and studied one at a time. In this colloquium, Professor Block will present findings based on his group's construction of optical trapping instrumentation that has broken the nanometer barrier, allowing researchers to study single-molecule displacements on the Angstrom level. Focusing on RNA polymerase, the motor enzyme responsible for transcribing the genetic code contained in DNA, Block's group has been able to measure, in real time, the motion of a single molecule of RNA polymerase as it moves from base to base along the DNA template.

  17. Carrier dynamics in Ga(NAsP)/Si multi-quantum well heterostructures with varying well thickness

    NASA Astrophysics Data System (ADS)

    Shakfa, M. K.; Woscholski, R.; Gies, S.; Wegele, T.; Wiemer, M.; Ludewig, P.; Jandieri, K.; Baranovskii, S. D.; Stolz, W.; Volz, K.; Heimbrodt, W.; Koch, M.

    2016-05-01

    Time-resolved photoluminescence (TR-PL) measurements have been performed in Ga(NAsP)/(BGa)(AsP) multi-quantum well heterostructures (MQWHs) with different well thicknesses. The studied structures have been pseudomorphically grown on Si substrates by metal organic vapor phase epitaxy (MOVPE) with an N content of about 7%. Experimental results reveal a shortening in the PL decay time with increasing QW thickness, meanwhile, accompanied by a decrease in the PL intensity. We attribute this behavior to an increasing non-radiative recombination rate for broader QWs which arises from an increasing number of defects in the QW material. The emission-energy distribution of the PL decay time is studied at various temperatures. The PL decay time strongly depends on the emission energy at low temperatures and becomes emission-energy-independent close to room temperature. This is discussed in terms of the carrier localization in the studied structures.

  18. Observation of weak carrier localization in green emitting InGaN/GaN multi-quantum well structure

    SciTech Connect

    Mohanta, Antaryami; Wang, Shiang-Fu; Jang, Der-Jun; Young, Tai-Fa; Yeh, Ping-Hung; Ling, Dah-Chin; Lee, Meng-En

    2015-04-14

    Green emitting InGaN/GaN multi-quantum well samples were investigated using transmission electron microscopy, photoluminescence (PL), and time-resolved photoluminescence (TRPL) spectroscopy. Weak carrier localization with characteristic energy of ∼12 meV due to an inhomogeneous distribution of In in the InGaN quantum (QW) layer is observed. The temperature dependence of the PL peak energy exhibits S-shape phenomenon and is comparatively discussed within the framework of the Varshni's empirical formula. The full width at half maximum of the PL emission band shows an increasing-decreasing-increasing behavior with increasing temperature arising from the localized states caused by potential fluctuations. The radiative life time, τ{sub r}, extracted from the TRPL profile shows ∼T{sup 3/2} dependence on temperature above 200 K, which confirms the absence of the effect of carrier localization at room temperature.

  19. Terahertz absorbing AlGaN/GaN multi-quantum-wells: Demonstration of a robust 4-layer design

    NASA Astrophysics Data System (ADS)

    Beeler, M.; Bougerol, C.; Bellet-Amalric, E.; Monroy, E.

    2013-08-01

    We report on AlGaN/GaN multi-quantum-well structures displaying intersubband absorption in the THz spectral range. First, we theoretically analyze the weaknesses of the state-of-the-art GaN-based step-quantum-well architecture from an optoelectronic standpoint. We then propose a modified geometry with improved structural robustness considering the uncertainties associated to the growth. This later structure, consisting of 4-layer quantum wells, has been grown by plasma-assisted molecular-beam epitaxy and characterized structurally and optically. Low temperature absorption of samples with different Si doping levels confirms intersubband transitions in the far-infrared, centred at 28 μm.

  20. Observation of weak carrier localization in green emitting InGaN/GaN multi-quantum well structure

    NASA Astrophysics Data System (ADS)

    Chao, Wen-Ching; Mohanta, Antaryami; Yen, Tsu-Chiang; Chen, Wei-Sheng; Jang, Der-Jun

    Green emitting InGaN/GaN multi-quantum well samples were investigated using photoluminescence (PL) and time-resolved photoluminescence (TRPL) spectroscopy. Weak carrier localization with characteristic energy of ~12 meV due to an inhomogeneous distribution of In in the InGaN quantum well (QW) layer is observed. The temperature dependence of the PL peak energy exhibits S-shape phenomenon and is comparatively discussed within the framework of the Varshni's empirical formula. The full width at half maximum (FWHM) of the PL emission band shows an increasing-decreasing-increasing behavior with increasing temperature arising from the localized states caused by potential fluctuations. The radiative life time, τr, extracted from the TRPL profile shows ~T 3 / 2 dependence on temperature above 200 K, which confirms the absence of the effect of carrier localization at room temperature.

  1. Observation of weak carrier localization in green emitting InGaN/GaN multi-quantum well structure

    NASA Astrophysics Data System (ADS)

    Mohanta, Antaryami; Wang, Shiang-Fu; Young, Tai-Fa; Yeh, Ping-Hung; Ling, Dah-Chin; Lee, Meng-En; Jang, Der-Jun

    2015-04-01

    Green emitting InGaN/GaN multi-quantum well samples were investigated using transmission electron microscopy, photoluminescence (PL), and time-resolved photoluminescence (TRPL) spectroscopy. Weak carrier localization with characteristic energy of ˜12 meV due to an inhomogeneous distribution of In in the InGaN quantum (QW) layer is observed. The temperature dependence of the PL peak energy exhibits S-shape phenomenon and is comparatively discussed within the framework of the Varshni's empirical formula. The full width at half maximum of the PL emission band shows an increasing-decreasing-increasing behavior with increasing temperature arising from the localized states caused by potential fluctuations. The radiative life time, τr, extracted from the TRPL profile shows ˜T3/2 dependence on temperature above 200 K, which confirms the absence of the effect of carrier localization at room temperature.

  2. Room temperature mid-infrared InAsSbN multi-quantum well photodiodes grown by MBE

    NASA Astrophysics Data System (ADS)

    Kesaria, M.; de la Mare, M.; Krier, A.

    2016-11-01

    Room temperature photoresponse in the mid-infrared spectral region is demonstrated from InAsSbN/InAs multi-quantum well photodiodes grown by nitrogen plasma assisted molecular beam epitaxy. The structural quality of the InAsSbN MQWs was ascertained in situ by reflection high energy electron diffraction and ex situ by high resolution x-ray diffraction and photoluminescence measurements. The extended long wavelength photoresponse is identified to originate from the electron-heavy hole (e1-hh1) and electron-light hole (e1-lh1) transitions in the InAsSbN MQW, with a cut off wavelength ~4.20 µm and peak detectivity D *  =  1.25  ×  109 cm Hz1/2 W-1.

  3. Stress influenced trapping processes in Si based multi-quantum well structures and heavy ions implanted Si

    SciTech Connect

    Ciurea, Magdalena Lidia Lazanu, Sorina

    2014-10-06

    Multi-quantum well structures and Si wafers implanted with heavy iodine and bismuth ions are studied in order to evaluate the influence of stress on the parameters of trapping centers. The experimental method of thermostimullatedcurrents without applied bias is used, and the trapping centers are filled by illumination. By modeling the discharge curves, we found in multilayered structures the parameters of both 'normal' traps and 'stress-induced' ones, the last having a Gaussian-shaped temperature dependence of the cross section. The stress field due to the presence of stopped heavy ions implanted into Si was modeled by a permanent electric field. The increase of the strain from the neighborhood of I ions to the neighborhood of Bi ions produces the broadening of some energy levels and also a temperature dependence of the cross sections for all levels.

  4. Fluorogenic small molecules requiring reaction with a specific protein to create a fluorescent conjugate for biological imaging--what we know and what we need to learn.

    PubMed

    Baranczak, Aleksandra; Connelly, Stephen; Liu, Yu; Choi, Sungwook; Grimster, Neil P; Powers, Evan T; Wilson, Ian A; Kelly, Jeffery W

    2014-05-01

    We seek fluorogenic small molecules that generate a fluorescent conjugate signal if and only if they react with a given protein-of-interest (i.e., small molecules for which noncovalent binding to the protein-of-interest is insufficient to generate fluorescence). Consequently, it is the new chemical entity afforded by the generally irreversible reaction between the small molecule and the protein-of-interest that enables the energy of an electron occupying the lowest unoccupied molecular orbital (LUMO) of the chromophore to be given off as a photon instead of being dissipated by nonradiative mechanisms in complex biological environments. This category of fluorogenic small molecules is created by starting with environmentally sensitive fluorophores that are modified by an essential functional group that efficiently quenches the fluorescence until a chemoselective reaction between that functional group and the protein-of-interest occurs, yielding the fluorescent conjugate. Fluorogenic small molecules are envisioned to be useful for a wide variety of applications, including live cell imaging without the requirement for washing steps and pulse-chase kinetic analyses of protein synthesis, trafficking, degradation, etc. Copyright © 2013 Wiley Periodicals, Inc.

  5. The bottom–up approach to defining life: deciphering the functional organization of biological cells via multi-objective representation of biological complexity from molecules to cells

    PubMed Central

    Periyasamy, Sathish; Gray, Alex; Kille, Peter

    2013-01-01

    In silico representation of cellular systems needs to represent the adaptive dynamics of biological cells, recognizing a cell's multi-objective topology formed by temporally cohesive intracellular structures. The design of these models needs to address the hierarchical and concurrent nature of cellular functions and incorporate the ability to self-organize in response to transitions between healthy and pathological phases, and adapt accordingly. The functions of biological systems are constantly progressing, due to the ever changing demands of their environment. Biological systems meet these demands by pursuing objectives, aided by their constituents, giving rise to biological functions. A biological cell is organized into an objective/task hierarchy. These objective hierarchy corresponds to the nested nature of temporally cohesive structures and representing them will facilitate in studying pleiotropy and polygeny by modeling causalities propagating across multiple interconnected intracellular processes. Although biological adaptations occur in physiological, developmental and reproductive timescales, the paper is focused on adaptations that occur within physiological timescales, where the biomolecular activities contributing to functional organization, play a key role in cellular physiology. The paper proposes a multi-scale and multi-objective modeling approach from the bottom–up by representing temporally cohesive structures for multi-tasking of intracellular processes. Further the paper characterizes the properties and constraints that are consequential to the adaptive dynamics in biological cells. PMID:24385968

  6. The bottom-up approach to defining life: deciphering the functional organization of biological cells via multi-objective representation of biological complexity from molecules to cells.

    PubMed

    Periyasamy, Sathish; Gray, Alex; Kille, Peter

    2013-01-01

    In silico representation of cellular systems needs to represent the adaptive dynamics of biological cells, recognizing a cell's multi-objective topology formed by temporally cohesive intracellular structures. The design of these models needs to address the hierarchical and concurrent nature of cellular functions and incorporate the ability to self-organize in response to transitions between healthy and pathological phases, and adapt accordingly. The functions of biological systems are constantly progressing, due to the ever changing demands of their environment. Biological systems meet these demands by pursuing objectives, aided by their constituents, giving rise to biological functions. A biological cell is organized into an objective/task hierarchy. These objective hierarchy corresponds to the nested nature of temporally cohesive structures and representing them will facilitate in studying pleiotropy and polygeny by modeling causalities propagating across multiple interconnected intracellular processes. Although biological adaptations occur in physiological, developmental and reproductive timescales, the paper is focused on adaptations that occur within physiological timescales, where the biomolecular activities contributing to functional organization, play a key role in cellular physiology. The paper proposes a multi-scale and multi-objective modeling approach from the bottom-up by representing temporally cohesive structures for multi-tasking of intracellular processes. Further the paper characterizes the properties and constraints that are consequential to the adaptive dynamics in biological cells.

  7. Hydration Structures and Thermodynamic Properties of Cationized Biologically Relevant Molecules, M+(Indole)(H2O)n (M = Na, K; n = 3-6)

    NASA Astrophysics Data System (ADS)

    Ke, Haochen; Lisy, James

    2015-03-01

    The balance between various noncovalent interactions plays a key role in determining the hydration structures and thermodynamic properties of biologically relevant molecules in biological mediums. Such properties of biologically relevant molecules are closely related to their often unique biological functionalities. The indole moiety is a basic functional group of many important neurotransmitters and hormones and has been used as tractable model for more complex biomolecules. The cationized indole water cluster is a perfect system for the quantitative and systematic study of the competition and cooperation of noncovalent interactions, as electrostatic interactions can be adjusted by introducing different monovalent cations and hydrogen bonding interactions can be adjusted by varying the level of hydration. IRPD spectra with isotopic (H/D) analysis helped unravel the overlapping N-H and O-H stretching modes, a major challenge of earlier studies. Thermodynamic analysis using relative Gibbs free energies, for energy ordering, together with spectral analysis provided unambiguous assignment of spectral features and structural configurations. A systematic hydration model with an in-depth account of noncovalent interactions is presented.

  8. Design, Synthesis, and Biological Evaluation of Coumarin-Triazole Hybrid Molecules as Potential Antitumor and Pancreatic Lipase Agents.

    PubMed

    Kahveci, Bahittin; Yılmaz, Fatih; Menteşe, Emre; Ülker, Serdar

    2017-08-01

    The design, synthesis, and investigation of antitumor and anti-lipase activities of some coumarin-triazole hybrid molecules are reported. The synthesis of these hybrid molecules was performed under microwave irradiation and conventional heating procedures. The newly synthesized hybrid molecules were investigated as inhibitors against four tumor cell lines (BT20 human breast carcinoma, SK-Mel 128 melanoma, DU-145 prostate carcinoma, and A549 lung carcinoma) and porcine pancreatic lipase (PPL). Most of these compounds showed notable antitumor activities against the tested tumor cell lines, and compounds 8i and 8l showed the best anti-lipase activity of 99.30 ± 0.56% and 99.85 ± 1.21%, respectively, at a concentration of 10 μM. © 2017 Deutsche Pharmazeutische Gesellschaft.

  9. Human T-cell lymphotropic virus type 1 (HTLV-1)-induced syncytium formation mediated by vascular cell adhesion molecule-1: evidence for involvement of cell adhesion molecules in HTLV-1 biology.

    PubMed Central

    Hildreth, J E; Subramanium, A; Hampton, R A

    1997-01-01

    While studying the potential role of vascular cell adhesion molecule-1 (VCAM-1) in infection of endothelial cells by human immunodeficiency virus (HIV), we found that VCAM-1 can mediate human T-cell lymphotropic virus type 1 (HTLV-1)-induced syncytium formation. Both expression-vector-encoded and endogenously expressed VCAM-1 supported fusion of uninfected cells with HTLV-1-infected cells. Fusion was obtained with cell lines carrying the HTLV-1 genome and expressing viral proteins but not with an HTLV-1-transformed cell line that does not express viral proteins. In clones of VCAM-1-transfected cells, the degree of syncytium formation observed directly reflected the level of VCAM-1 expression. Syncytium formation between HTLV-1-expressing cells and VCAM-1+ cells could be blocked with antiserum against HTLV-1 gp46 and with a monoclonal antibody (MAb) against VCAM-1. Fusion was not blocked by antiserum against HIV or a MAb against VLA-4, the physiological counter-receptor for VCAM-1. The results indicate that VCAM-1 can serve as an accessory molecule or potential coreceptor for HTLV-1-induced cell fusion and provide direct evidence of a role for cell adhesion molecules in the biology of HTLV-1. PMID:8995639

  10. Specificity and mechanism of action of alpha-helical membrane-active peptides interacting with model and biological membranes by single-molecule force spectroscopy.

    PubMed

    Sun, Shiyu; Zhao, Guangxu; Huang, Yibing; Cai, Mingjun; Shan, Yuping; Wang, Hongda; Chen, Yuxin

    2016-07-01

    In this study, to systematically investigate the targeting specificity of membrane-active peptides on different types of cell membranes, we evaluated the effects of peptides on different large unilamellar vesicles mimicking prokaryotic, normal eukaryotic, and cancer cell membranes by single-molecule force spectroscopy and spectrum technology. We revealed that cationic membrane-active peptides can exclusively target negatively charged prokaryotic and cancer cell model membranes rather than normal eukaryotic cell model membranes. Using Acholeplasma laidlawii, 3T3-L1, and HeLa cells to represent prokaryotic cells, normal eukaryotic cells, and cancer cells in atomic force microscopy experiments, respectively, we further studied that the single-molecule targeting interaction between peptides and biological membranes. Antimicrobial and anticancer activities of peptides exhibited strong correlations with the interaction probability determined by single-molecule force spectroscopy, which illustrates strong correlations of peptide biological activities and peptide hydrophobicity and charge. Peptide specificity significantly depends on the lipid compositions of different cell membranes, which validates the de novo design of peptide therapeutics against bacteria and cancers.

  11. Dynamics of initial ionization events in biological molecules: Formation and fate of free radicals. Final technical report, May 1, 1994--December 31, 1995

    SciTech Connect

    Castleman, A.W. Jr.

    1997-08-01

    Study of early time events following the absorption of electromagnetic radiation in biological systems has potentially significant impact on several areas of importance. In this context, the studies being conducted under this program provided insight into the conformational changes as well as the reactions leading to a variety of transformations that culminate from hydrogen atom and proton transfer events. These studies enabled an investigation of molecular details of structure-function relationships. In a second aspect of the program, investigations were conducted to provide basic underpinning research that contributed to a quantification of the behavior of radionuclides and pollutants associated with advanced energy activities after these materials emanate from their source and become transferred through the environment to the biota and human receptor. The approach to elucidating factors governing the difference between reactions in the gas and condensed phase was to study the initiating steps at progressively higher degrees of cluster aggregation. The author employed ultrafast laser techniques, in combination with selected molecules, carefully prepared in tailored compositions, to investigation the primary mechanisms involved in various molecular functional groups following the absorption of electromagnetic radiation. He also studied various molecules representing chromophores in such biologically important molecules as tyrosine and amines.

  12. Specificity and mechanism of action of alpha-helical membrane-active peptides interacting with model and biological membranes by single-molecule force spectroscopy

    PubMed Central

    Sun, Shiyu; Zhao, Guangxu; Huang, Yibing; Cai, Mingjun; Shan, Yuping; Wang, Hongda; Chen, Yuxin

    2016-01-01

    In this study, to systematically investigate the targeting specificity of membrane-active peptides on different types of cell membranes, we evaluated the effects of peptides on different large unilamellar vesicles mimicking prokaryotic, normal eukaryotic, and cancer cell membranes by single-molecule force spectroscopy and spectrum technology. We revealed that cationic membrane-active peptides can exclusively target negatively charged prokaryotic and cancer cell model membranes rather than normal eukaryotic cell model membranes. Using Acholeplasma laidlawii, 3T3-L1, and HeLa cells to represent prokaryotic cells, normal eukaryotic cells, and cancer cells in atomic force microscopy experiments, respectively, we further studied that the single-molecule targeting interaction between peptides and biological membranes. Antimicrobial and anticancer activities of peptides exhibited strong correlations with the interaction probability determined by single-molecule force spectroscopy, which illustrates strong correlations of peptide biological activities and peptide hydrophobicity and charge. Peptide specificity significantly depends on the lipid compositions of different cell membranes, which validates the de novo design of peptide therapeutics against bacteria and cancers. PMID:27363513

  13. Thermal Stability of the New Soliton Transported Bio-Energy Under Influence of Fluctuations of Characteristic Parameters at Biological Temperature in the Protein Molecules

    NASA Astrophysics Data System (ADS)

    Pang, Xiao-Feng; Zhang, Huai-Wu; Yu, Jia-Feng; Luo, Yu-Hui

    The dynamic behaviors of the new soliton in the improved Davydov model in the protein molecules at biological temperature have been numerically simulated by utilizing the dynamic equations for the bio-energy transport and the Runge-Kutta way. In this simulation the influences of the temperature and structure disorders of the protein molecules on the soliton transporting the bio-energy have been completely considered. We find that the new soliton is quite stable in the cases of motion of a long time of 300 ps and of disorders of the structures of the proteins at biological temperatures of 300 K-320 K. The disorders of the structures contain the disorder of mass sequence of amino acids and the fluctuations of the coupling constant, force constant and dipole- dipole interaction constant and ground state energy of the proteins, designating the features of its structure and interactions between the particles in it. However, the soliton disperses in the cases of higher temperature of 325 K and larger structure disorders. The numerical results show that the new soliton is very robust against the influences of the thermal perturbation and structure disorders at biological temperature 300 K, its lifetime and critical temperature are at least 300 ps at 300 K and 320 K, respectively. These results are also consistent with analytical data.

  14. Mapping protein pockets through their potential small-molecule binding volumes: QSCD applied to biological protein structures

    NASA Astrophysics Data System (ADS)

    Mason, Keith; Patel, Nehal M.; Ledel, Aric; Moallemi, Ciamac C.; Wintner, Edward A.

    2004-01-01

    Previously we demonstrated a method, Quantized Surface Complementarity Diversity (QSCD), of defining molecular diversity by measuring shape and functional complementarity of molecules to a basis set of theoretical target surfaces [Wintner E.A. and Moallemi C.C., J. Med. Chem., 43 (2000) 1993]. In this paper we demonstrate a method of mapping actual protein pockets to the same basis set of theoretical target surfaces, thereby allowing categorization of protein pockets by their properties of shape and functionality. The key step in the mapping is a `dissection' algorithm that breaks any protein pocket into a set of potential small molecule binding volumes. It is these binding volumes that are mapped to the basis set of theoretical target surfaces, thus measuring a protein pocket not as a single surface but as a collection of molecular recognition environments.

  15. Discovery of synthetic small molecules that enhance the number of stomata: C-H functionalization chemistry for plant biology.

    PubMed

    Ziadi, Asraa; Uchida, Naoyuki; Kato, Hiroe; Hisamatsu, Rina; Sato, Ayato; Hagihara, Shinya; Itami, Kenichiro; Torii, Keiko U

    2017-08-24

    The increasing climate changes and global warming are leading to colossal agricultural problems such as abatement of food production and quality. As stomatal development is considered to play a key role in crop plant productivity and water-use efficiency, studying stomatal development is useful for understanding the productivity of plant systems for both natural and agricultural systems. Herein, we report the first-in-class synthetic small molecules enhancing the number of stomata in Arabidopsis thaliana that have been discovered by screening of the chemical library and further optimized by the Pd-catalyzed C-H arylation reaction. The present study shows not only huge potential of small molecules to control the cellular and developmental processes of stomata without using genetically modified plants, but also the power of C-H functionalization chemistry to rapidly identify the optimized compounds.

  16. The Biology and Underlying Mechanisms of Cross-Presentation of Exogenous Antigens on MHC-I Molecules.

    PubMed

    Cruz, Freidrich M; Colbert, Jeff D; Merino, Elena; Kriegsman, Barry A; Rock, Kenneth L

    2017-04-26

    To monitor the health of cells, the immune system tasks antigen-presenting cells with gathering antigens from other cells and bringing them to CD8 T cells in the form of peptides bound to MHC-I molecules. Most cells would be unable to perform this function because they use their MHC-I molecules to exclusively present peptides derived from the cell's own proteins. However, the immune system evolved mechanisms for dendritic cells and some other phagocytes to sample and present antigens from the extracellular milieu on MHC-I through a process called cross-presentation. How this important task is accomplished, its role in health and disease, and its potential for exploitation are the subject of this review.

  17. 1H NMR analysis of complexation of hydrotropic agents nicotinamide and caffeine with aromatic biologically active molecules in aqueous solution

    NASA Astrophysics Data System (ADS)

    Lantushenko, Anastasia O.; Mukhina, Yulia V.; Veselkov, Kyrill A.; Davies, David B.; Veselkov, Alexei N.

    2004-07-01

    NMR spectroscopy has been used to elucidate the molecular mechanism of solubilization action of hydrotropic agents nicotinamide (NA) and caffeine (CAF). Hetero-association of NA with riboflavine-mononucleotide (FMN) and CAF with low soluble in aqueous solution synthetic analogue of antibiotic actinomycin D, actinocyl-bis-(3-dimethylaminopropyl) amine (Actill), has been investigated by 500 MHz 1H NMR spectroscopy. Concentration and temperature dependences of proton chemical shifts have been analysed in terms of a statistical-thermodynamic model of indefinite self- and heteroassociation of aromatic molecules. The obtained results enable to conclude that NA-FMN and CAF-Actill intermolecular complexes are mainly stabilized by the stacking interactions of the aromatic chromophores. Hetero-association of the investigated molecules plays an important role in solubilization of aromatic drugs by hydrotropic agents nicotinamide and caffeine.

  18. Max Delbruck Biological Physics Prize Talk: The Biophysics of Gene Regulation, Studied One Molecule at a Time

    NASA Astrophysics Data System (ADS)

    Block, Steven

    2008-03-01

    Advances have led to a new field, dubbed single molecule biophysics. Prominent among the new technologies is the optical trap, or `optical tweezers.' Sensitive systems for measuring force and displacement in optical traps permit the nanomechanical properties of individual macromolecules to be explored with unprecedented precision, revealing behaviors heretofore obscured by ensemble-based approaches. This talk will focus on some of our current work with single-molecule systems, including transcription by RNA polymerase and structural transitions in nucleic acids. We developed high-resolution instrumentation that has broken the nanometer barrier and is thereby able to detect displacements down to the atomic level, in aqueous buffer at room temperature. Consequently, we can monitor the motions of RNA polymerase molecules in real time as these step from base to base along DNA. On the practical side, base-pair resolution makes it possible to sequence DNA in a new way, based on enzyme motions, and points to new directions in nanoscience. The improved stability afforded by the current generation of optical trapping apparatus has allowed us to reconstruct the complete energy landscapes for folding transitions in nucleic-acid hairpins. Recently, we have turned our attention to the problem of co-transcriptional folding, aptamers, and riboswitches formed in nascent mRNAs, and to the DNA or RNA sequence elements that regulate expression.

  19. Chemical biology based on target-selective degradation of proteins and carbohydrates using light-activatable organic molecules.

    PubMed

    Toshima, Kazunobu

    2013-05-01

    Proteins and carbohydrates play crucial roles in a wide range of biological processes, including serious diseases. The development of novel and innovative methods for selective control of specific proteins and carbohydrates functions has attracted much attention in the field of chemical biology. In this account article, the development of novel chemical tools, which can degrade target proteins and carbohydrates by irradiation with a specific wavelength of light under mild conditions without any additives, is introduced. This novel class of photochemical agents promise bright prospects for finding not only molecular-targeted bioprobes for understanding of the structure-activity relationships of proteins and carbohydrates but also novel therapeutic drugs targeting proteins and carbohydrates.

  20. Analysis of the landscape of biologically-derived pharmaceuticals in Europe: dominant production systems, molecule types on the rise and approval trends.

    PubMed

    Kyriakopoulos, Sarantos; Kontoravdi, Cleo

    2013-02-14

    A thorough sort of the human drugs approved by the European Medicines Agency (EMA) between its establishment in 1995 until June 2012 is presented herein with a focus on biologically-derived pharmaceuticals. Over 200 (33%) of the 640 approved therapeutic drugs are derived from natural sources, produced via recombinant DNA technology, or generated through virus propagation. A breakdown based on production method, type of molecule and therapeutic category is presented. Current EMA approvals demonstrate that mammalian cells are the only choice for glycoprotein drugs, with Chinese hamster ovary cells being the dominant hosts for their production. On the other hand, bacterial cells and specifically Escherichia coli are the dominant hosts for protein-based drugs, followed by the yeast Saccharomyces cerevisiae. The latter is the dominant host for recombinant vaccine production, although egg-based production is still the main platform of vaccine provision. Our findings suggest that the majority of biologically-derived drugs are prescribed for cancer and related conditions, as well as the treatment of diabetes. The approval rate for biologically-derived drugs shows a strong upward trend for monoclonal antibodies and fusion proteins since 2009, while hormones, antibodies and growth factors remain the most populous categories. Despite a clear pathway for the approval of biosimilars set by the EMA and their potential to drive sales growth, we have only found approved biosimilars for three molecules. In 2012 there appears to be a slow-down in approvals, which coincides with a reported decline in the growth rate of biologics sales. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. The AstroBiology Explorer (ABE) MIDEX Mission: Using Infrared Spectroscopy to Identify Organic Molecules in Space

    NASA Technical Reports Server (NTRS)

    Sandford, S. A.

    2002-01-01

    The AstroBiology Explorer (ABE) mission is one of four selected for Phase A Concept Study in NASA's current call for MIDEX class missions. ABE is a cooled space telescope equipped with spectrographs covering the 2.5-20 micron spectral range. The ABE mission is devoted to the detection and identification of organic and related molecular species in space. ABE is currently under study at NASA's Ames Research Center in collaboration with Ball Aerospace.

  2. The AstroBiology Explorer (ABE) MIDEX Mission Concept: Using Infrared Spectroscopy to Identify Organic Molecules in Space

    NASA Astrophysics Data System (ADS)

    Sandford, Scott A.

    2002-11-01

    The AstroBiology Explorer (ABE) mission is one of four selected for Phase A Concept Study in NASA's current call for MIDEX class missions. ABE is a cooled space telescope equipped with spectrographs covering the 2.5-20 micron spectral range. The ABE mission is devoted to the detection and identification of organics and related molecular species in space. ABE is currently under study at NASA's Ames Research Center in collaboration with Ball Aerospace.

  3. Small molecule intercalation with double stranded DNA: implications for normal gene regulation and for predicting the biological efficacy and genotoxicity of drugs and other chemicals.

    PubMed

    Hendry, Lawrence B; Mahesh, Virendra B; Bransome, Edwin D; Ewing, Douglas E

    2007-10-01

    The binding of small molecules to double stranded DNA including intercalation between base pairs has been a topic of research for over 40 years. For the most part, however, intercalation has been of marginal interest given the prevailing notion that binding of small molecules to protein receptors is largely responsible for governing biological function. This picture is now changing with the discovery of nuclear enzymes, e.g. topoisomerases that modulate intercalation of various compounds including certain antitumor drugs and genotoxins. While intercalators are classically flat, aromatic structures that can easily insert between base pairs, our laboratories reported in 1977 that a number of biologically active compounds with greater molecular thickness, e.g. steroid hormones, could fit stereospecifically between base pairs. The hypothesis was advanced that intercalation was a salient feature of the action of gene regulatory molecules. Two parallel lines of research were pursued: (1) development of technology to employ intercalation in the design of safe and effective chemicals, e.g. pharmaceuticals, nutraceuticals, agricultural chemicals; (2) exploration of intercalation in the mode of action of nuclear receptor proteins. Computer modeling demonstrated that degree of fit of certain small molecules into DNA intercalation sites correlated with degree of biological activity but not with strength of receptor binding. These findings led to computational tools including pharmacophores and search engines to design new drug candidates by predicting desirable and undesirable activities. The specific sequences in DNA into which ligands best intercalated were later found in the consensus sequences of genes activated by nuclear receptors implying intercalation was central to their mode of action. Recently, the orientation of ligands bound to nuclear receptors was found to match closely the spatial locations of ligands derived from intercalation into unwound gene sequences

  4. Fabrication of surface enhanced Raman Scattering (SERS) substrates made from nanoparticle printing inks for detection of biological molecules

    NASA Astrophysics Data System (ADS)

    Figueroa, Manuel Alejandro

    Surface enhanced Raman scattering (SERS) has generated great interest as a surface analytical technique because it can produce amplification factors between 108-1012. Silver and gold are the most widely used components as their size and structure allows for light to induce conduction electrons to oscillate locally within the nanoparticle structure. When a molecule lies in the interparticle space between two nanoparticles, highly detailed vibrational information becomes detectable. The objective of this study is to reproducibly fabricate such an arrangement in a nanoparticle substrate while maintaining stability. In this work, nanoparticle printing inks -- colloidal nanoparticles encapsulated by a stabilizing ligand -- are used as the main component of SERS substrates. The ligand shell is partially removed by controlled heating, which reduces spacing between nanoparticles creating a broad distribution of interparticle distances. Similar to fractal aggregates this arrangement allows localized plasmons to naturally resonate over a broad range of spectral frequencies. Microwave absorption is applied as a non-invasive method to sensitively monitor nanoparticle sintering in order to gauge the substrates' tuning for large amplification factors. The global arrangement of nanoparticles has always been difficult to measure during heating through DC resistivity measurements and surface imaging techniques. Microwave absorption occurs in the weak resistive links formed between particles during sintering due to the microwave losses in loosely coupled particles. By placing the substrate in a microwave cavity, absorption can be monitored globally during heating. The largest SERS amplification factors occur at a stage immediately preceding the largest microwave absorption gains. This provides a useful method for determining a thermal window for heating when optimizing SERS substrates. Finally, these optimized SERS substrates are used to detect hyaluronic acid. This complex molecule

  5. Enhanced Light Emission due to Formation of Semi-polar InGaN/GaN Multi-quantum Wells.

    PubMed

    Zhao, Wan-Ru; Weng, Guo-En; Wang, Jian-Yu; Zhang, Jiang-Yong; Liang, Hong-Wei; Sekiguchi, Takashi; Zhang, Bao-Ping

    2015-12-01

    InGaN/GaN multi-quantum wells (MQWs) are grown on (0001) sapphire substrates by metal organic chemical vapor deposition (MOCVD) with special growth parameters to form V-shaped pits simultaneously. Measurements by atomic force microscopy (AFM) and transmission electron microscopy (TEM) demonstrate the formation of MQWs on both (0001) and ([Formula: see text]) side surface of the V-shaped pits. The latter is known to be a semi-polar surface. Optical characterizations together with theoretical calculation enable us to identify the optical transitions from these MQWs. The layer thickness on ([Formula: see text]) surface is smaller than that on (0001) surface, and the energy level in the ([Formula: see text]) semi-polar quantum well (QW) is higher than in the (0001) QW. As the sample temperature is increased from 15 K, the integrated cathodoluminescence (CL) intensity of (0001) MQWs increases first and then decreases while that of the ([Formula: see text]) MQWs decreases monotonically. The integrated photoluminescence (PL) intensity of (0001) MQWs increases significantly from 15 to 70 K. These results are explained by carrier injection from ([Formula: see text]) to (0001) MQWs due to thermal excitation. It is therefore concluded that the emission efficiency of (0001) MQWs at high temperatures can be greatly improved due to the formation of semi-polar MQWs.

  6. Strain dependence of In incorporation in m-oriented GaInN/GaN multi quantum well structures

    SciTech Connect

    Horenburg, Philipp Buß, Ernst Ronald; Rossow, Uwe; Ketzer, Fedor Alexej; Bremers, Heiko; Hangleiter, Andreas

    2016-03-07

    We demonstrate a strong dependence of the indium incorporation efficiency on the strain state in m-oriented GaInN/GaN multi quantum well (MQW) structures. Insertion of a partially relaxed AlInN buffer layer opens up the opportunity to manipulate the strain situation in the MQW grown on top. By lattice-matching this AlInN layer to the c- or a-axis of the underlying GaN, relaxation towards larger a- or smaller c-lattice constants can be induced, respectively. This results in a modified template for the subsequent MQW growth. From X-ray diffraction and photoluminescence measurements, we derive significant effects on the In incorporation efficiency and In concentrations in the quantum well (QW) up to x = 38% without additional accumulation of strain energy in the QW region. This makes strain manipulation a very promising method for growth of high In-containing MQW structures for efficient, long wavelength light-emitting devices.

  7. Modeling of Metal-Insulator-Semiconductor Dualband Si/SiO2 Multi-Quantum Well UV Detectors

    NASA Astrophysics Data System (ADS)

    Rostami, A.; Leilaeioun, M.; Golmohammadi, S.; Rasooli Saghai, H.

    2012-11-01

    This article intends to propose a self-consistent theoretical model for Metal-Insulator-Semiconductor (MIS) dualband Si/SiO2 multi-quantum well (MQW) UV photodetector. Employing this model, general characteristics of MIS UV photodetectors such as dark and photocurrent density-voltage (J-V) curves are simulated. The results reveal that the proposed structure reduces dark current since first the resonant tunneling multi-barrier is designed such that the electron tunneling probability is unity at energies coincident with the peak detection wavelength, and secondly, tunneling significantly decreases at energies which are smaller than this optimum value and accordingly, transport of carriers contributing to the dark current, which have broad energy distribution at high temperatures, is inhibited. Moreover, the article demonstrates that the proposed structure can detect two individual x wavelengths in the UV range, simultaneously. The related absorption and responsivity curves are obtained and depicted. Defects in the SiO2 barriers are simulated indirectly by varying the electron effective tunneling mass in SiO2. Reductions in the SiO2 electron effective tunneling mass lead to an increase in dark current of the device.

  8. Dilute nitride multi-quantum well multi-junction design: a route to ultra-efficient photovoltaic devices

    NASA Astrophysics Data System (ADS)

    Vijaya, Gopi Krishna; Alemu, Andenet; Freundlich, Alex

    2011-02-01

    The current high-efficiency triple junction (Al)InGaP (1.9eV)/GaAs(1.42eV)/ Ge(0.66eV) design for a solar cell can be improved upon by the use dilute nitrides to include a sub-cell in the 1eV range. Addition of a small percentage of nitrogen to III-V semiconductor alloys (such as GaAsN) enables us to achieve the required bandgap, however these bulk dilute nitride structures suffer from a reduced minority carrier lifetime, decreasing the overall current output. The route suggested herein is to include dilute nitride multi-quantum wells (with thicknesses much lesser than the minority carrier diffusion length) within the intrinsic region of a GaAs subcell. Modeling has been done for this structure to obtain the confined energies of the electrons and holes, as well as the absorption coefficient and thereby the spectral response of the 4-junction cell. The results show that it is possible to achieve with the appropriate current matching, a conversion efficiency of ~40% under AM0 (1 sun) with up to ~18 mAcm-2 short circuit current.

  9. Catalytic enantioselective construction of quaternary stereocenters: assembly of key building blocks for the synthesis of biologically active molecules.

    PubMed

    Liu, Yiyang; Han, Seo-Jung; Liu, Wen-Bo; Stoltz, Brian M

    2015-03-17

    The ever-present demand for drugs with better efficacy and fewer side effects continually motivates scientists to explore the vast chemical space. Traditionally, medicinal chemists have focused much attention on achiral or so-called "flat" molecules. More recently, attention has shifted toward molecules with stereogenic centers since their three-dimensional structures represent a much larger fraction of the chemical space and have a number of superior properties compared with flat aromatic compounds. Quaternary stereocenters, in particular, add greatly to the three-dimensionality and novelty of the molecule. Nevertheless, synthetic challenges in building quaternary stereocenters have largely prevented their implementation in drug discovery. The lack of effective and broadly general methods for enantioselective formation of quaternary stereocenters in simple molecular scaffolds has prompted us to investigate new chemistry and develop innovative tools and solutions. In this Account, we describe three approaches to constructing quaternary stereocenters: nucleophilic substitution of 3-halooxindoles, conjugate addition of boronic acids to cyclic enones, and allylic alkylation of enolates. In the first approach, malonic ester nucleophiles attack electrophilic 3-halooxindoles, mediated by a copper(II)-bisoxazoline catalyst. A variety of oxindoles containing a benzylic quaternary stereocenter can be accessed through this method. However, it is only applicable to the specialized 3,3-disubstituted oxindole system. To access benzylic quaternary stereocenters in a more general context, we turned our attention to the enantioselective conjugate addition of carbon nucleophiles to α,β-unsaturated carbonyl acceptors. We discovered that in the presence of catalytic palladium-pyridinooxazoline complex, arylboronic acids add smoothly to β-substituted cyclic enones to furnish ketones with a β-benzylic quaternary stereocenter in high yields and enantioselectivities. The reaction is

  10. A rapid means of separating A14-/sup 125/I-insulin from heterogeneously labeled insulin molecules for biologic studies

    SciTech Connect

    Stentz, F.B.; Wright, R.K.; Kitabchi, A.E.

    1982-12-01

    We have used two methods for the preparation of a highly homogeneous insulin with high specific activity. After iodination with chloramine T, the labeled peptides were retained on a disposable Sep Pak cartridge and subsequently eluted. The eluted labeled insulins were further purified by either DEAE cellulose or high performance liquid chromatography (HPLC) to separate A14-/sup 125/I- from A19-/sup 125/I-insulin. Both methods of chromatography were effective, but HPLC offered the advantage of better resolution in less time and higher yields of A14-/sup 125/I-insulin, which is suitable for biologic studies in various target tissues.

  11. Surface functionalization of bioactive glasses with natural molecules of biological significance, part II: Grafting of polyphenols extracted from grape skin

    NASA Astrophysics Data System (ADS)

    Zhang, Xin; Ferraris, Sara; Prenesti, Enrico; Verné, Enrica

    2013-12-01

    Polyphenols, as one of the most important family of phytochemicals protective substances from grape fruit, possess various biological activities and health-promoting benefits, for example: inhibition of some degenerative diseases, cardiovascular diseases and certain types of cancers, reduction of plasma oxidative stress and slowing aging. The combination of polyphenols and biomaterials may have good potential to reach good bioavailability and controlled release, as well as to give biological signaling properties to the biomaterial surfaces. In this research, conventional solvent extraction was developed for obtaining polyphenols from dry grape skins. The Folin&Ciocalteu method was used to determine the amount of total polyphenols in the extracts. Surface functionalization of two bioactive glasses (SCNA and CEL2) was performed by grafting the extracted polyphenols on their surfaces. The effectiveness of the functionalization was tested by UV spectroscopy, which analyzes the amount of polyphenols in the uptake solution (before and after functionalization) and on solid samples, and XPS, which analyzes the presence of phenols on the material surface.

  12. Adsorption of small biological molecules on silica from diluted aqueous solutions: Quantitative characterization and implications to the Bernal's hypothesis

    NASA Astrophysics Data System (ADS)

    Basiuk, Vladimir A.; Gromovoy, Taras Yu.; Khil'Chevskaya, Elena G.

    1995-08-01

    To describe quantitatively the adsorption of prebiotically important compounds of low molecular weight (amino acids, short linear peptides, cyclic dipeptides, the Krebs's cycle and other carboxylic acids, nucleosides and related phosphates) on silica surface from diluted neutral aqueous solutions, equilibrium constants (K) and free energies (-ΔG) of adsorption were determined from the retention values measured by means of high-performance liquid chromatography on a silica gel column and from the isotherms measured under static conditions. For most carboxylic acids (including amino acids and linear peptides) -ΔG values were negative and K<1, thus showing very weak adsorption. Cyclic dipeptides (2,5-piperazinediones) exhibited higher adsorbability; -ΔG>0 and K>1 were found for most of them. Influence of the structure of α-substituent on the adsorbability is analyzed. A linear dependence of -ΔG on the number of aliphatic carbon atoms in a sorbate molecule was found for the series of aliphatic bifunctional amino acids, related dipeptides and 2,5-piperazinediones, as well as for the row from glycine to triglycyl glycine. The adsorption of nucleosides and their phosphates is characterized by much higherK and -ΔG values (of the order of 102 and 104, respectively). The adsorption data available from our work and literature are summarized and discussed with implications to the Bernal's hypothesis on the roles of solid surfaces in the prebiotic formation of biopolymers from monomeric ‘building blocks’.

  13. Polyether ionophores: broad-spectrum and promising biologically active molecules for the control of drug-resistant bacteria and parasites

    PubMed Central

    Kevin, Dion A; Meujo, Damaris AF; Hamann, Mark T

    2016-01-01

    Background As multidrug-resistant (MDR) pathogens continue to emerge, there is a substantial amount of pressure to identify new drug candidates. Carboxyl polyethers, also referred to as polyether antibiotics, are a unique class of compounds with outstanding potency against a variety of critical infectious disease targets including protozoa, bacteria and viruses. The characteristics of these molecules that are of key interest are their selectivity and high potency against several MDR etiological agents. Objective Although many studies have been published about carboxyl polyether antibiotics, there are no recent reviews of this class of drugs. The purpose of this review is to provide the reader with an overview of the spectrum of activity of polyether antibiotics, their mechanism of action, toxicity and potential as drug candidates to combat drug-resistant infectious diseases. Conclusion Polyether ionophores show a high degree of promise for the potential control of drug-resistant bacterial and parasitic infections. Despite the long history of use of this class of drugs, very limited medicinal chemistry and drug optimization studies have been reported, thus leaving the door open to these opportunities in the future. Scifinder and PubMed were the main search engines used to locate articles relevant to the topic presented in the present review. Keywords used in our search were specific names of each of the 88 compounds presented in the review as well as more general terms such as polyethers, ionophores, carboxylic polyethers and polyether antibiotics. PMID:23480512

  14. Small-molecule inhibitors of 25-hydroxyvitamin D-24-hydroxylase (CYP24A1): synthesis and biological evaluation.

    PubMed

    Ferla, Salvatore; Aboraia, Ahmed S; Brancale, Andrea; Pepper, Christopher J; Zhu, Jinge; Ochalek, Justin T; DeLuca, Hector F; Simons, Claire

    2014-09-25

    The synthesis of imidazole styrylbenzamide, tert-butyl styrylimidazole, and tert-butyl styrylsulfonate derivatives is described. Evaluation of binding affinity and inhibitory activity against CYP24A1 identified the imidazole styrylbenzamides as potent inhibitors of CYP24A1, having selectivity with respect to CYP27B1 comparable with or greater than that of the standard ketoconazole. Further evaluation of the 3,5-dimethoxy and 3,4,5-trimethoxy derivatives in chronic lymphocytic leukemia cells revealed that co-treatment of 1α,25-dihydroxyvitamin D3 plus inhibitor coordinately upregulated GADD45α and CDKN1A. Docking experiments on the inhibitors in the CYP24A1 enzyme active site suggest the compounds reach the active site through the vitamin D access tunnel and are exposed to multiple hydrophobic residues. The imidazole styrylbenzamides are optimally positioned to allow interaction of the imidazole with the heme, and, in the case of the methoxy derivatives, a hydrogen bond between the 3-methoxy group and Gln82 stabilizes the molecule in a favorable active conformation.

  15. Investigating how the attributes of self-associated drug complexes influence the passive transport of molecules through biological membranes.

    PubMed

    Inacio, R; Barlow, D; Kong, X; Keeble, J; Jones, S A

    2016-05-01

    Relatively little is known about how drug self-association influences absorption into the human body. This study presented two hydrophobic membranes with a series of solutions containing different types of tetracaine aggregates with the aim of understanding how the attributes of supramolecular aggregate formation influenced passive membrane transport. The data showed that aqueous solutions of the unprotonated form of tetracaine displayed a significantly higher (p<0.05) passive membrane transport compared to solutions with mixtures of the unprotonated and protonated drug microspecies (e.g. transport through the skin was 0.96±0.31μgcm(-2)min(-1) and 1.59±0.26μgcm(-2)min(-1) respectively). However, despite an enhanced rate of drug transport and a better membrane partitioning the unionised molecules showed a significantly longer (p<0.05) lag time to membrane penetration compared solutions rich in the ionised microspecies. Analytical characterisation of the solutions applied to the apical surface of the membranes in the transport studies showed that larger tetracaine aggregates with smaller surface charge gave rise to the longer lag times. These large aggregates demonstrated more extensive intermolecular bonding and therefore, it was suggest that it was the enhanced propensity of the unionised species to form tightly bound drug aggregates that caused the delay in the membrane penetration.

  16. A modified electronegativity equalization method for fast and accurate calculation of atomic charges in large biological molecules.

    PubMed

    Ouyang, Yongzhong; Ye, Fei; Liang, Yizeng

    2009-08-07

    To further extend the EEM approach to improve its accuracy, a new approach, in which the different connectivities and hybridized states are introduced to represent the different chemical environments, has been developed. The C, O and N atoms are distinguished between different hybridized states. Different states of hydrogen atoms are defined according to their different connectivities. Furthermore, the sp(2) carbons in the aromatic rings are also separated from the other sp(2) carbons. Geometries and NPA charges are calculated at the B3LYP/6-31G* level, and the effective electronegativity and hardness values could be calibrated with the help of a training set of 141 organic molecules using the Differential Evolution (DE) algorithm. The quality of the modified EEM charges is evaluated by comparison with the B3LYP/6-31G* charges calculated for a series of polypeptides, not contained in the training set. For further comparison, the atomic parameters of the original EEM without including chemical environments are recalibrated under the same conditions. It is found that the accuracy of the modified EEM method improves significantly as compared to that of the original EEM method.

  17. Search for biochemical fossils on earth and non-biological organic molecules on Jupiter, Saturn and Titan

    NASA Astrophysics Data System (ADS)

    Nagy, Bartholomew

    1982-07-01

    Recognizable remnants of ancient biochemicals may survive under mild/moderate geological environments. Acyclic isoprenoid hydrocarbons, cyclic hydrocarbons with terpenoid carbon skeletons (e.g. hopanes) and vanadyl and nickel porphyrins have been isolated from organic matter, including petroleum, in Phanerozoic sedimentary rocks. Remnants of lignin have also been found. Usually, carbohydrates do not survive long; they degrade and/or react with other organic substances to form macromolecular matter. Proteins, e.g. apparently those in dinosaur bone collagen, break down relatively rapidly. Life arose during the Precambrian and potential biochemical fossils, e.g. n-alkanes, 2,5-dimethylfuran have been isolated from Precambrian kerogens. Traces of hydrocarbons, NH3, PH3 occur on Jupiter and Saturn. Hydrocarbons, N2 and HCN, the latter a key intermediary in the laboratory abiological syntheses of amino acids and nucleic acid bases, are present on Titan where life could not have evolved. Precursor abiological organic molecules of some complexity may have been synthesized on Titan and the Jovian planets.

  18. Investigating how the attributes of self-associated drug complexes influence the passive transport of molecules through biological membranes

    PubMed Central

    Inacio, R.; Barlow, D.; Kong, X.; Keeble, J.; Jones, S.A.

    2016-01-01

    Relatively little is known about how drug self-association influences absorption into the human body. This study presented two hydrophobic membranes with a series of solutions containing different types of tetracaine aggregates with the aim of understanding how the attributes of supramolecular aggregate formation influenced passive membrane transport. The data showed that aqueous solutions of the unprotonated form of tetracaine displayed a significantly higher (p < 0.05) passive membrane transport compared to solutions with mixtures of the unprotonated and protonated drug microspecies (e.g. transport through the skin was 0.96 ± 0.31 μg cm−2 min−1 and 1.59 ± 0.26 μg cm−2 min−1 respectively). However, despite an enhanced rate of drug transport and a better membrane partitioning the unionised molecules showed a significantly longer (p < 0.05) lag time to membrane penetration compared solutions rich in the ionised microspecies. Analytical characterisation of the solutions applied to the apical surface of the membranes in the transport studies showed that larger tetracaine aggregates with smaller surface charge gave rise to the longer lag times. These large aggregates demonstrated more extensive intermolecular bonding and therefore, it was suggest that it was the enhanced propensity of the unionised species to form tightly bound drug aggregates that caused the delay in the membrane penetration. PMID:26965142

  19. The AstroBiology Explorer (ABE) MIDEX Mission Concept: Using Infrared Spectroscopy to Identify Organic Molecules in Space

    NASA Technical Reports Server (NTRS)

    Sandford, Scott A.; Vincenzi, Donald (Technical Monitor)

    2002-01-01

    One of the principal means by which organic compounds are detected and identified in space is by infrared spectroscopy. Past IR studies (telescopic and laboratory) have demonstrated that much of the carbon in the interstellar medium (ISM) is in complex organic species of a variety of types, but the distribution, abundance, and evolutionary relationships of these materials are not well understood. The Astrobiology Explorer (ABE) is a MIDEAST mission concept designed to conduct IR spectroscopic observations to detect and identify these materials to address outstanding important problems in astrobiology, astrochemistry, and astrophysics. Systematic studies include the observation of planetary nebulae and stellar outflows, protostellar objects, Solar System Objects, and galaxies, and multiple lines of sight through dense molecular clouds and the diffuse ISM. ABE will also search for evidence of D enrichment in complex molecules in all these environments. The mission is currently under study at NASA's Ames Research Center in collaboration with Ball Aerospace and Technologies Corp. ABE is a cryogenically-cooled 60 cm diameter space telescope equipped with 3 cryogenic cross-dispersed spectrographs that share a single common slit. The 3 spectrometers each measure single spectral octaves (2.5-5, 5-10, 10-20 microns) and together cover the entire 2.5 - 20 micron region simultaneously. The spectrometers use state-of-the-art 1024x1024 pixel detectors, with a single InSb array for the 2.5-5 micron region and two Si:As arrays for the 5-10 and 10-20 micron regions. The spectral resolution is wavelength dependent but is greater than 2000 across the entire spectral range. ABE would operate in a heliocentric, Earth drift-away orbit and is designed to take maximum advantage of this environment for cooling, thermal stability, and mission lifetime. ABE would have a core science mission lasting approximately 1.5 years.

  20. Design, facile synthesis and biological evaluations of novel pyrano[3,2-a]phenazine hybrid molecules as antitumor agents.

    PubMed

    Lu, Yuanyuan; Yan, Yuru; Wang, Linlin; Wang, Xiaobing; Gao, Jing; Xi, Tao; Wang, Zhixiang; Jiang, Feng

    2017-02-15

    A series of novel pyrano[3,2-a]phenazine derivatives (1a-1r and 2a-2q), designed as hybrid molecules of phenazine and pyran pharmocophores, were facilely synthesized in two steps with 77-93% overall yields in this study. Cytotoxic evaluation indicates that many compounds exhibited cytotoxicity against HCT116, MCF7, HepG2 and A549 cancer cell lines in vitro, in which compounds 1c, 1i, 2e, and 2l were found to have excellent antiproliferative activity against the HepG2 cancer cell line. Thus, inhibitory effect of subcutaneously implanted xenografted mice in vivo (H22H8D8 cells) of the four compounds as well as topoisomerase I and IIα inhibitory activities in vitro (HepG2 cells) were determined. Significantly, compound 1i showed more potent than positive control drug both in vivo and in vitro. Further mechanism studies against HepG2 cells in vitro revealed that compound 1i up-regulated the expression of both p53 and p21, which inhibited the expression of both cyclin B and CDK1, and arrested HepG2 cells in the G2/M phase. Concomitantly, after treating with compound 1i, Bax/Bcl-2 ratio was significantly increased, the cytochrome C was released from mitochondria to cytosol, and the cleavage of caspase-3 and caspase-9 expression levels were both increased. Together, all these evidences implicated that compound 1i acts as topoisomerase I and IIα dual inhibitor, cell cycle arrester and apoptosis inducer against HepG2 cells.

  1. The AstroBiology Explorer (ABE) MIDEX Mission Concept: Using Infrared Spectroscopy to Identify Organic Molecules in Space

    NASA Technical Reports Server (NTRS)

    Sandford, Scott A.; Vincenzi, Donald (Technical Monitor)

    2002-01-01

    One of the principal means by which organic compounds are detected and identified in space is by infrared spectroscopy. Past IR studies (telescopic and laboratory) have demonstrated that much of the carbon in the interstellar medium (ISM) is in complex organic species of a variety of types, but the distribution, abundance, and evolutionary relationships of these materials are not well understood. The Astrobiology Explorer (ABE) is a MIDEAST mission concept designed to conduct IR spectroscopic observations to detect and identify these materials to address outstanding important problems in astrobiology, astrochemistry, and astrophysics. Systematic studies include the observation of planetary nebulae and stellar outflows, protostellar objects, Solar System Objects, and galaxies, and multiple lines of sight through dense molecular clouds and the diffuse ISM. ABE will also search for evidence of D enrichment in complex molecules in all these environments. The mission is currently under study at NASA's Ames Research Center in collaboration with Ball Aerospace and Technologies Corp. ABE is a cryogenically-cooled 60 cm diameter space telescope equipped with 3 cryogenic cross-dispersed spectrographs that share a single common slit. The 3 spectrometers each measure single spectral octaves (2.5-5, 5-10, 10-20 microns) and together cover the entire 2.5 - 20 micron region simultaneously. The spectrometers use state-of-the-art 1024x1024 pixel detectors, with a single InSb array for the 2.5-5 micron region and two Si:As arrays for the 5-10 and 10-20 micron regions. The spectral resolution is wavelength dependent but is greater than 2000 across the entire spectral range. ABE would operate in a heliocentric, Earth drift-away orbit and is designed to take maximum advantage of this environment for cooling, thermal stability, and mission lifetime. ABE would have a core science mission lasting approximately 1.5 years.

  2. Preface - From molecules to molecular materials, biological molecular systems and nanostructures: A collection of contributions presented at the XIIIth International Conference on Molecular Spectroscopy

    NASA Astrophysics Data System (ADS)

    Ratajczak, Henryk; Drozd, Marek; Fausto, Rui

    2016-12-01

    This volume contains a series of selected contributions presented at the XIIIth International Conference on Molecular Spectroscopy (ICMS): "From Molecules to Molecular Materials, Biological Molecular Systems and Nanostructures" held in Wrocław, Poland, 9-12 September 2015, under the auspices of the Mayor of Wrocław and the European Academy of Sciences, Arts and Humanities. Wrocław was chosen not accidentally as venue for the conference. With more than a thousand years of history, Wrocław is the location of one of the oldest universities in Central Europe. Being a place where education and science play major roles in the daily life of its inhabitants, Wrocław is also a privileged center for spectroscopy in Poland.

  3. The biological role of the unique molecule RCAS1: a bioactive marker that induces connective tissue remodeling and lymphocyte apoptosis.

    PubMed

    Sonoda, Kenzo; Miyamoto, Shingo; Nakashima, Manabu; Wake, Norio

    2008-01-01

    RCAS1 is a receptor-binding cancer antigen which is expressed on human uterine cervical adenocarcinoma cell line (SiSo). Finding a correlation between the expression of this gene and the overall survival of patients with 14 different types of cancer points to the clinical significance of this gene. Moreover, the expression RCAS1 correlates with other clinicopathological parameters including the histological type of cancer, its differentiation, tumor size, clinical stage, the depth of invasion, lymphovascular space involvement, lymph node metastasis, and positive peritoneal cytological results. RCAS1 can induce apoptosis in peripheral lymphocytes in vitro as well as in an increased number of apoptotic tumor-infiltrating lymphocytes. RCAS1 is also believed to contribute to the escape of tumor cells from immune surveillance. RCAS1 is secreted via ectodomain shedding, and its expression is related to changes in the characteristics of the extracellular matrix and to a reduced number of vimentin-positive tumor stromal cells, findings that suggest that RCAS1 may induce connective tissue remodeling. The concentration of RCAS1 in serum or pleural effusions has been found to be significantly higher in patients with several different types of cancer as compared to normal controls. Together, the available data shows that RCAS1 may have value as a biomarker for monitoring therapeutic efficacy. Further exploration of the biological function of RCAS1 should help in the development of new therapeutic strategies against human malignancies.

  4. Single molecule analysis of a red fluorescent RecA protein reveals a defect in nucleoprotein filament nucleation that relates to its reduced biological functions.

    PubMed

    Handa, Naofumi; Amitani, Ichiro; Gumlaw, Nathan; Sandler, Steven J; Kowalczykowski, Stephen C

    2009-07-10

    Fluorescent fusion proteins are exceedingly useful for monitoring protein localization in situ or visualizing protein behavior at the single molecule level. Unfortunately, some proteins are rendered inactive by the fusion. To circumvent this problem, we fused a hyperactive RecA protein (RecA803 protein) to monomeric red fluorescent protein (mRFP1) to produce a functional protein (RecA-RFP) that is suitable for in vivo and in vitro analysis. In vivo, the RecA-RFP partially restores UV resistance, conjugational recombination, and SOS induction to recA(-) cells. In vitro, the purified RecA-RFP protein forms a nucleoprotein filament whose k(cat) for single-stranded DNA-dependent ATPase activity is reduced approximately 3-fold relative to wild-type protein, and which is largely inhibited by single-stranded DNA-binding protein. However, RecA protein is also a dATPase; dATP supports RecA-RFP nucleoprotein filament formation in the presence of single-stranded DNA-binding protein. Furthermore, as for the wild-type protein, the activities of RecA-RFP are further enhanced by shifting the pH to 6.2. As a consequence, RecA-RFP is proficient for DNA strand exchange with dATP or at lower pH. Finally, using single molecule visualization, RecA-RFP was seen to assemble into a continuous filament on duplex DNA, and to extend the DNA approximately 1.7-fold. Consistent with its attenuated activities, RecA-RFP nucleates onto double-stranded DNA approximately 3-fold more slowly than the wild-type protein, but still requires approximately 3 monomers to form the rate-limited nucleus needed for filament assembly. Thus, RecA-RFP reveals that its attenuated biological functions correlate with a reduced frequency of nucleoprotein filament nucleation at the single molecule level.

  5. Second-harmonic generation of biological interfaces: probing the membrane protein bacteriorhodopsin and imaging membrane potential around GFP molecules at specific sites in neuronal cells of C. elegans

    NASA Astrophysics Data System (ADS)

    Lewis, Aaron; Khatchatouriants, Artium; Treinin, Millet; Chen, Zhongping; Peleg, Gadi; Friedman, Noga; Bouevitch, Oleg; Rothman, Zvi; Loew, Leslie; Sheres, Mordechai

    1999-07-01

    Second-harmonic generation (SHG) is applied to problems of probing membrane proteins and functionally imaging around selective sites and at single molecules in biological membranes. The membrane protein bacteriorhodopsin (bR) has been shown to have large second-harmonic (SH) intensities that are modulated by protein/retinylidene chromophore interactions. The nonlinear optical properties of model compounds, which simulate these protein chromophore interactions in retinal proteins, are studied in this work by surface SHG and by hyper-Rayleigh scattering. Our results indicate that non-conjugated charges and hydrogen bonding effects have a large effect on the molecular hyperpolarizability of the retinal chromophore. However, mbR, the model system studies suggest that polarizable amino acids strongly affect the vertically excited state of the retinylidene chromophore and appear to play the major role in the observed protein enhancement (>50%) of the retinylidene chromophore molecular hyperpolarizability and associated induced dipole. Furthermore, the data provide insights on emulating these interactions for the design of organic nonlinear optical materials. Our studies have also led to the development of dyes with large SH intensities that can be embedded in cell membranes and can functionally image membrane potential. Single molecules of such dyes in selected single molecular regions of a cell membrane have been detected. SHG from green fluorescent protein (GFP) selectively expressed in concert with a specific protein in neuronal cells in a transgenic form of the worm C. elegans is also reported. The membrane potential around the GFP molecules expressed in these cells has been imaged with SHG in live animals.

  6. Systems biology network-based discovery of a small molecule activator BL-AD008 targeting AMPK/ZIPK and inducing apoptosis in cervical cancer

    PubMed Central

    Tong, Xupeng; Zhang, Jin; Zhang, Yonghui; Ouyang, Liang; Liu, Bo; Huang, Jian

    2015-01-01

    The aim of this study was to discover a small molecule activator BL-AD008 targeting AMPK/ZIPK and inducing apoptosis in cervical cancer. In this study, we systematically constructed the global protein-protein interaction (PPI) network and predicted apoptosis-related protein connections by the Naïve Bayesian model. Then, we identified some classical apoptotic PPIs and other previously unrecognized PPIs between apoptotic kinases, such as AMPK and ZIPK. Subsequently, we screened a series of candidate compounds targeting AMPK/ZIPK, synthesized some compounds and eventually discovered a novel dual-target activator (BL-AD008). Moreover, we found BL-AD008 bear remarkable anti-proliferative activities toward cervical cancer cells and could induce apoptosis by death-receptor and mitochondrial pathways. Additionally, we found that BL-AD008-induced apoptosis was affected by the combination of AMPK and ZIPK. Then, we found that BL-AD008 bear its anti-tumor activities and induced apoptosis by targeting AMPK/ZIPK in vivo. In conclusion, these results demonstrate the ability of systems biology network to identify some key apoptotic kinase targets AMPK and ZIPK; thus providing a dual-target small molecule activator (BL-AD008) as a potential new apoptosis-modulating drug in future cervical cancer therapy. PMID:25797270

  7. Artemether Combined with shRNA Interference of Vascular Cell Adhesion Molecule-1 Significantly Inhibited the Malignant Biological Behavior of Human Glioma Cells

    PubMed Central

    Wang, Ping; Xue, Yi-Xue; Yao, Yi-Long; Yu, Bo; Liu, Yun-Hui

    2013-01-01

    Artemether is the derivative extracted from Chinese traditional herb and originally used for malaria. Artemether also has potential therapeutic effects against tumors. Vascular cell adhesion molecule-1 (VCAM-1) is an important cell surface adhesion molecule associated with malignancy of gliomas. In this work, we investigated the role and mechanism of artemether combined with shRNA interference of VCAM-1 (shRNA-VCAM-1) on the migration, invasion and apoptosis of glioma cells. U87 human glioma cells were treated with artemether at various concentrations and shRNA interfering technology was employed to silence the expression of VCAM-1. Cell viability, migration, invasiveness and apoptosis were assessed with MTT, wound healing, Transwell and Annexin V-FITC/PI staining. The expression of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and phosphorylated Akt (p-Akt) was checked by Western blot assay. Results showed that artemether and shRNA-VCAM-1 not only significantly inhibited the migration, invasiveness and expression of MMP-2/9 and p-Akt, but also promoted the apoptosis of U87 cells. Combined treatment of both displayed the maximum inhibitory effects on the malignant biological behavior of glioma cells. Our work revealed the potential therapeutic effects of artemether and antiVCAM-1 in the treatments of gliomas. PMID:23593320

  8. T cell immunoglobulin and mucin domain-containing molecule 3 on CD14(+) monocytes serves as a novel biological marker for diabetes duration in type 2 diabetes mellitus.

    PubMed

    Yan, Wen-Jiang; Sun, Peng; Wei, Dan-Dan; Wang, Shuang-Xi; Yang, Jing-Jing; Li, Yi-Hui; Zhang, Cheng

    2016-11-01

    Type 2 diabetes is a worldwide disease that is associated with increased rates of obesity and reduced physical activity. Obesity-associated insulin resistance in type 2 diabetes is a disorder in the balance between pro-inflammatory and anti-inflammatory signals. T cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) has been reported as an important regulatory inflammation molecule, and plays a pivotal role in several inflammation-related diseases. Peripheral blood mononuclear cells were obtained from type 2 diabetes patients (n = 31) and healthy donors (n = 18), and Tim-3 expression on peripheral blood mononuclear cells was evaluated by flow cytometry. We showed the downregulated expression of Tim-3 on CD14(+) monocytes from type 2 diabetes patients. In addition, the upregulated expression of Tim-3 on peripheral CD4(+) T cells and CD8(+) T cells was observed in the present study. The correlation analysis between Tim-3 expression on CD14(+) monocytes and diabetes duration showed the longer diabetes duration time, the lower Tim-3 expression on CD14 monocytes. The present results suggest that Tim-3 might participate in the progression of type 2 diabetes by its negative regulation on these immune cells, and Tim-3 on CD14(+) monocytes serves as a novel biological marker for diabetes duration in type 2 diabetes patients. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  9. FOB-SH: Fragment orbital-based surface hopping for charge carrier transport in organic and biological molecules and materials

    NASA Astrophysics Data System (ADS)

    Spencer, J.; Gajdos, F.; Blumberger, J.

    2016-08-01

    We introduce a fragment orbital-based fewest switches surface hopping method, FOB-SH, designed to efficiently simulate charge carrier transport in strongly fluctuating condensed phase systems such as organic semiconductors and biomolecules. The charge carrier wavefunction is expanded and the electronic Hamiltonian constructed in a set of singly occupied molecular orbitals of the molecular sites that mediate the charge transfer. Diagonal elements of the electronic Hamiltonian (site energies) are obtained from a force field, whereas the off-diagonal or electronic coupling matrix elements are obtained using our recently developed analytic overlap method. We derive a general expression for the exact forces on the adiabatic ground and excited electronic state surfaces from the nuclear gradients of the charge localized electronic states. Applications to electron hole transfer in a model ethylene dimer and through a chain of ten model ethylenes validate our implementation and demonstrate its computational efficiency. On the larger system, we calculate the qualitative behaviour of charge mobility with change in temperature T for different regimes of the intermolecular electronic coupling. For small couplings, FOB-SH predicts a crossover from a thermally activated regime at low temperatures to a band-like transport regime at higher temperatures. For higher electronic couplings, the thermally activated regime disappears and the mobility decreases according to a power law. This is interpreted by a gradual loss in probability for resonance between the sites as the temperature increases. The polaron hopping model solved for the same system gives a qualitatively different result and underestimates the mobility decay at higher temperatures. Taken together, the FOB-SH methodology introduced here shows promise for a realistic investigation of charge carrier transport in complex organic, aqueous, and biological systems.

  10. Manipulation of silver nanoparticles in a droplet for label-free detection of biological molecules using surface-enhanced Raman scattering

    NASA Astrophysics Data System (ADS)

    Çulha, Mustafa; Altunbek, Mine; Keskin, Sercan; Saatçi, Deniz

    2011-03-01

    Detection and identification of biomacromolecules is of critical importance in many fields ranging from biotechnology to medicine. Surface-enhanced Raman scattering (SERS) is an emerging technique for the label-free detection and identification of biological molecules and structures with its fingerprinting properties and high sensitivity. However, there are a number of obstacles for its applications for biological macromolecules due to their complexity. In this report, manipulation of microscopic processes in play during the drying of a sessile droplet as a tool to influence the nanoparticle-macromolecule packing, which has dramatic effect on SERS performance, before the SERS acquisition is demonstrated. A process known as the coffee ring phenomenon jams all particles and molecular species to the edges of the droplet during drying. This uncontrolled process has dramatic effects on a SERS experiment, using colloidal metal nanoparticles as substrates, by sweeping everything to the edges and influencing the packing of nanoparticles in the droplet area. A plastic tip was dipped into a drying sample droplet to influence the uncontrolled piling up. A negatively-charged protein, BSA, a positively-charged protein, cytochrom c, and a 20-base long oligonucleotide, were used as model biomacromolecules in this study. While a minimum of one order of magnitude lower concentration improvement in detection limit was observed with negatively-charged biomacromolecules, no significant improvement was observed with positively-charged ones compared to a sample droplet left on the surface without any interference. With the demonstrated approach, picomolar-level biomolecular detection using SERS is possible.

  11. Novel Paraoxonase 2-Dependent Mechanism Mediating the Biological Effects of the Pseudomonas aeruginosa Quorum-Sensing Molecule N-(3-Oxo-Dodecanoyl)-l-Homoserine Lactone

    PubMed Central

    Horke, Sven; Xiao, Junhui; Schütz, Eva-Maria; Kramer, Gerald L.; Wilgenbus, Petra; Witte, Ines; Selbach, Moritz

    2015-01-01

    Pseudomonas aeruginosa produces N-(3-oxo-dodecanoyl)-l-homoserine lactone (3OC12), a crucial signaling molecule that elicits diverse biological responses in host cells thought to subvert immune defenses. The mechanism mediating many of these responses remains unknown. The intracellular lactonase paraoxonase 2 (PON2) hydrolyzes and inactivates 3OC12 and is therefore considered a component of host cells that attenuates 3OC12-mediated responses. Here, we demonstrate in cell lines and in primary human bronchial epithelial cells that 3OC12 is rapidly hydrolyzed intracellularly by PON2 to 3OC12 acid, which becomes trapped and accumulates within the cells. Subcellularly, 3OC12 acid accumulated within the mitochondria, a compartment where PON2 is localized. Treatment with 3OC12 caused a rapid PON2-dependent cytosolic and mitochondrial pH decrease, calcium release, and phosphorylation of stress signaling kinases. The results indicate a novel, PON2-dependent intracellular acidification mechanism by which 3OC12 can mediate its biological effects. Thus, PON2 is a central regulator of host cell responses to 3OC12, acting to decrease the availability of 3OC12 for receptor-mediated effects and acting to promote effects, such as calcium release and stress signaling, via intracellular acidification. PMID:26056385

  12. How dependent are molecular and atomic properties on the electronic structure method? Comparison of Hartree-Fock, DFT, and MP2 on a biologically relevant set of molecules.

    PubMed

    Matta, Chérif F

    2010-04-30

    This article compares molecular properties and atomic properties defined by the quantum theory of atoms in molecules (QTAIM) obtained from three underlying levels of theory: MP2(full), density functional theory (DFT) (B3LYP), and Hartree-Fock (H-F). The same basis set (6-311++G(d,p)) has been used throughout the study. The calculations and comparisons were applied to a set of 30 small molecules representing common fragments of biological molecules. The molecular properties investigated are the energies and the electrostatic moments (up to and including the quadrupoles), and the atomic properties include electron populations (and atomic charge), atomic dipolar and quadrupolar polarizations, atomic volumes, and corrected and raw atomic energies. The Cartesian distance between dipole vectors and the Frobenius distance between the quadrupole tensors calculated at the three levels of theory provide a measure of their correlation (or lack thereof). With the exception of energies (atomic and molecular), it is found that both DFT and H-F are in excellent agreement with MP2, especially with regards to the electrostatic mutipoles up to the quadrupoles, but DFT and MP2 agree better in almost all studied properties (with the exception of molecular geometries). QTAIM properties whether obtained from H-F, DFT(B3LYP), or MP2 calculations when used in the construction of empirical correlations with experiment such as quantitative structure-activity-(or property)-relationships (QSAR/QSPR) are equivalent (because the properties calculated at the three levels are very highly correlated among themselves with r(2) typically >0.95, and therefore preserving trends). These results suggest that the massive volume of results that were published in the older literature at the H-F level is valid especially when used to study trends or in QSAR or QSPR studies, and, as long as our test set of molecules is representative, there is no pressing need to re-evaluate them at other levels of theory

  13. Different design of enzyme-triggered CO-releasing molecules (ET-CORMs) reveals quantitative differences in biological activities in terms of toxicity and inflammation.

    PubMed

    Stamellou, E; Storz, D; Botov, S; Ntasis, E; Wedel, J; Sollazzo, S; Krämer, B K; van Son, W; Seelen, M; Schmalz, H G; Schmidt, A; Hafner, M; Yard, B A

    2014-01-01

    Acyloxydiene-Fe(CO)3 complexes can act as enzyme-triggered CO-releasing molecules (ET-CORMs). Their biological activity strongly depends on the mother compound from which they are derived, i.e. cyclohexenone or cyclohexanedione, and on the position of the ester functionality they harbour. The present study addresses if the latter characteristic affects CO release, if cytotoxicity of ET-CORMs is mediated through iron release or inhibition of cell respiration and to what extent cyclohexenone and cyclohexanedione derived ET-CORMs differ in their ability to counteract TNF-α mediated inflammation. Irrespective of the formulation (DMSO or cyclodextrin), toxicity in HUVEC was significantly higher for ET-CORMs bearing the ester functionality at the outer (rac-4), as compared to the inner (rac-1) position of the cyclohexenone moiety. This was paralleled by an increased CO release from the former ET-CORM. Toxicity was not mediated via iron as EC50 values for rac-4 were significantly lower than for FeCl2 or FeCl3 and were not influenced by iron chelation. ATP depletion preceded toxicity suggesting impaired cell respiration as putative cause for cell death. In long-term HUVEC cultures inhibition of VCAM-1 expression by rac-1 waned in time, while for the cyclohexanedione derived rac-8 inhibition seems to increase. NFκB was inhibited by both rac-1 and rac-8 independent of IκBα degradation. Both ET-CORMs activated Nrf-2 and consequently induced the expression of HO-1. This study further provides a rational framework for designing acyloxydiene-Fe(CO)3 complexes as ET-CORMs with differential CO release and biological activities. We also provide a better understanding of how these complexes affect cell-biology in mechanistic terms.

  14. Electron transfer in biological molecules

    SciTech Connect

    Gray, H.B.

    1995-12-01

    Electron-transfer reactions are key stemps in photosynthesis, respiration, drug metabolism, and many other biochemical processes. These reactions commonly occur between protein-bound prosthetic groups that are separated by large molecular distances (often greater than 10 {Angstrom}). Although the electron donors and acceptors are expected to be weakly coupled, the reactions are remarkably fast and proceed with high specificity. Recent work on structurally engineered iron and cooper proteins has shown that the chemical bonds in the intervening medium potentially can control the rates of these electron-transfer reactions.

  15. Fundamental studies of matrix-assisted laser desorption/ionization, using time-of-flight mass spectrometry to identify biological molecules

    SciTech Connect

    Eades, D.; Wruck, D.; Gregg, H.

    1996-11-11

    MALDI MS was developed as a way of getting molecular weight information on small quantities (picomole to femtomole levels) of high-mass, thermally labile macromolecules. While most other analytical MS ionization techniques cause fragmentation, decomposition, or multiple charging, MALDI efficiently places intact macromolecules into the gas phase with little fragmentation or rearrangement. This project had 3 objectives: establish the MALDI capability at LLNL, perform fundamental studies of analyte-matrix interactions, and apply the technique for biochemical research. A retired time-of-flight instrument was adapted for MALDI analyses, relevant parameters influencing the MALDI process were identified for further study (matrix molar absorptivity, sample crystal preparation), and collaborations were established with research groups in the Biology and Biotechnology Research Program at LLNL. In MALDI, the macromolecule of interest is mixed with a high-molar excess (1:100 to 1:10,000) of an organic matrix which readily absorbs energy at the wavelength corresponding to a UV laser. Upon laser irradiation, the matrix absorbs the majority of the energy, causing it to desorb from the surface and gently release the macromolecule into the gas phase with little or no fragmentation. Once in the gas phase, ion-molecule reactions between excited matrix and neutral macromolecules generated ionized analyte species which then can be focused into a MS for detection.

  16. Distance measurements in model Bis-Gd(III) complexes with flexible “bridge”. Emulation of biological molecules having flexible structure with Gd(III) labels attached

    PubMed Central

    Potapov, A.; Song, Y.; Meade, T. J.; Goldfarb, D.; Astashkin, A.V.; Raitsimring, A.

    2010-01-01

    In this work, we continue to explore Gd(III) as a possible spin label for high field Double Electron Electron Resonance (DEER) based distance measurements in biological molecules with flexible geometry. For this purpose, a bis-Gd(III) complex with a flexible “bridge” was used as a model. The distances in the model were expected to be distributed in the range of 5-26 Å, allowing us to probe the shortest limits of accessible distances which were found to be as small as 13 Å. The upper distance limit for these labels was also evaluated and was found to be about 60 Å. Various pulse duration setups can result in apparent differences in the distribution function derived from DEER kinetics due to short distance limit variations. The advantages, such as the ability to perform measurements at cryogenic temperatures and high repetition rates simultaneously, the use of very short pumping and observation pulses without mutual interference, the lack of orientational selectivity, as well as the shortcomings, such as the limited mw operational frequency range and intrinsically smaller amplitude of oscillation related to dipolar interaction as compared with nitroxide spin labels are discussed. Most probably the use of nitroxide and Gd based labels for distance measurements will be complementary depending on the particulars of the problem and the availability of instrumentation. PMID:20418132

  17. Imaging the behavior of molecules in biological systems: breaking the 3D speed barrier with 3D multi-resolution microscopy.

    PubMed

    Welsher, Kevin; Yang, Haw

    2015-01-01

    The overwhelming effort in the development of new microscopy methods has been focused on increasing the spatial and temporal resolution in all three dimensions to enable the measurement of the molecular scale phenomena at the heart of biological processes. However, there exists a significant speed barrier to existing 3D imaging methods, which is associated with the overhead required to image large volumes. This overhead can be overcome to provide nearly unlimited temporal precision by simply focusing on a single molecule or particle via real-time 3D single-particle tracking and the newly developed 3D Multi-resolution Microscopy (3D-MM). Here, we investigate the optical and mechanical limits of real-time 3D single-particle tracking in the context of other methods. In particular, we investigate the use of an optical cantilever for position sensitive detection, finding that this method yields system magnifications of over 3000×. We also investigate the ideal PID control parameters and their effect on the power spectrum of simulated trajectories. Taken together, these data suggest that the speed limit in real-time 3D single particle-tracking is a result of slow piezoelectric stage response as opposed to optical sensitivity or PID control.

  18. Design, synthesis and biological evaluation of estradiol-PEG-linked platinum(II) hybrid molecules: comparative molecular modeling study of three distinct families of hybrids.

    PubMed

    Provencher-Mandeville, Josée; Debnath, Chhanda; Mandal, Sanat K; Leblanc, Valérie; Parent, Sophie; Asselin, Eric; Bérubé, Gervais

    2011-01-01

    The synthesis of a series of 17β-estradiol-platinum(II) hybrid molecules is reported. The hybrids are made of a PEG linking chain of various length and a 2-(2'-aminoethyl)pyridine ligand. They are prepared from estrone in only 5 chemical steps with an overall yield of 22%. The length of the PEG chain does not influence the solubility of the compounds as it remains relatively constant throughout the series. MTT assays showed that the derivative with the longest PEG chain showed the best activity against two human breast cancer cell lines (MCF-7 and MDA-MB-231). The novel PEG-hybrids are also compared in terms of activities with two other families of 17β-estradiol-platinum(II) hybrids that we reported in previous studies. Molecular modeling study performed on a representative member of each family of hybrids reveals distinct molecular interactions with the estrogen receptor α which further corroborates their notably contrasting cytocidal activities on breast cancer cell lines. This study also shows that lipophilicity and the orientation of the tether chain between the estrogenic portion and the platinum(II) core contribute markedly to the biological activity of the various families of hybrids. The most active hybrids are those possessing an alkyl tether chain at position 16β of the steroid nucleus. For example, derivative 3 (p=6) is about 16 times more potent on MCF-7 breast cancer cells than the corresponding 16α-PEG-hybrids (2b) made in this study. Copyright © 2010 Elsevier Inc. All rights reserved.

  19. Mid-infrared electro-luminescence and absorption from AlGaN/GaN-based multi-quantum well inter-subband structures

    SciTech Connect

    Hofstetter, Daniel; Bour, David P.; Kirste, Lutz

    2014-06-16

    We present electro-modulated absorption and electro-luminescence measurements on chirped AlGaN/GaN-based multi-quantum well inter-subband structures grown by metal-organic vapour phase epitaxy. The absorption signal is a TM-polarized, 70 meV wide feature centred at 230 meV. At medium injection current, a 58 meV wide luminescence peak corresponding to an inter-subband transition at 1450 cm{sup −1} (180 meV) is observed. Under high injection current, we measured a 4 meV wide structure peaking at 92.5 meV in the luminescence spectrum. The energy location of this peak is exactly at the longitudinal optical phonon of GaN.

  20. A novel model on time-resolved photoluminescence measurements of polar InGaN/GaN multi-quantum-well structures

    PubMed Central

    Xing, Yuchen; Wang, Lai; Yang, Di; Wang, Zilan; Hao, Zhibiao; Sun, Changzheng; Xiong, Bing; Luo, Yi; Han, Yanjun; Wang, Jian; Li, Hongtao

    2017-01-01

    Based on carrier rate equation, a new model is proposed to explain the non-exponential nature of time-resolved photoluminescence (TRPL) decay curves in the polar InGaN/GaN multi-quantum-well structures. From the study of TRPL curves at different temperatures, it is found that both radiative and non-radiative recombination coefficients vary from low temperature to room temperature. The variation of the coefficients is compatible with the carrier density of states distribution as well as the carrier localization process. These results suggest that there is a novel method to calculate the internal quantum efficiency, which is a complement to the traditional one based on temperature dependent photoluminescence measurement. PMID:28327629

  1. Effect of selective area growth mask width on multi-quantum-well electroabsorption modulated lasers investigated by synchrotron radiation X-ray microprobe

    NASA Astrophysics Data System (ADS)

    Mino, Lorenzo; Agostino, Angelo; Codato, Simone; Martinez-Criado, Gema; Lamberti, Carlo

    2012-08-01

    High performance optoelectronic devices require monolithic integration of different functions at chip level. This is the case of multi-quantum well (MQW) electroabsorption modulated laser (EML), employed in long-distance, high-frequency optical fiber communication applications, which is realized exploiting the selective area growth (SAG) technique. Optimization of the growth parameters is carried out by empirical approaches since a direct characterization of the MQW is not possible with laboratory X-ray sources, owing to the micrometer-variation of composition and thickness inherent to the SAG technique. In this work we combined micrometer-resolved photoluminescence with synchrotron radiation micrometer-resolved X-ray fluorescence to study the effect of different SAG masks on the electronic properties and chemical composition of the SAG MQW EML device.

  2. A facile method for highly uniform GaN-based nanorod light-emitting diodes with InGaN/GaN multi-quantum-wells.

    PubMed

    Park, Hyunik; Baik, Kwang Hyeon; Kim, Jihyun; Ren, Fan; Pearton, Stephen J

    2013-05-20

    We report on a simple and reproducible method for fabricating InGaN/GaN multi-quantum-well (MQW) nanorod light-emitting diodes (LEDs), prepared by combining a SiO2 nanosphere lithography and dry-etch process. Focused-ion-beam (FIB)-deposited Pt was contacted to both ends of the nanorod LEDs, producing bright electroluminescence from the LEDs under forward bias conditions. The turn-on voltage in these nanorod LEDs was higher (13 V) than in companion thin film devices (3 V) and this can be attributed to the high contact resistance between the FIB-deposited Pt and nanorod LEDs and the damage induced by inductively-coupled plasma and Ga + -ions. Our method to obtain uniform MQW nanorod LEDs shows promise for improving the reproducibility of nano-optoelectronics.

  3. Characterization of the InGaN/GaN Multi-Quantum-Wells Light-Emitting Diode Grown on Patterned Sapphire Substrate with Wide Electroluminescence Spectrum

    NASA Astrophysics Data System (ADS)

    Lee, Ah Reum; Jeon, Hunsoo; Lee, Gang-Seok; Ok, Jin-Eun; Jo, Dong-Wan; Kim, Kyoung Hwa; Yi, Sam Nyung; Yang, Min; Ahn, Hyung Soo; Cho, Chae-Ryong; Kim, Suok-Whan; Lee, Jae-Hak; Ha, Hong-Ju

    2011-01-01

    We report the characterization of the InGaN/GaN multi-quantum-well (MQW) light-emitting diode (LED) grown on a patterned sapphire substrate by metal organic chemical vapor deposition (MOCVD) using the selective area growth (SAG) method. The SAG patterns were designed to be circular and their diameters were 700 and 200 μm. After the growth, the InGaN/GaN MQW LED of 200 μm diameter had various crystal facets and a shape similar to volcanic craters, which were not observed in the 700-μm-diameter sample. We obtained an active layer with compositional nonuniformity and superior optical properties. We found wide electroluminescence (EL) spectral peaks near 470, 570, and 600 nm. The distribution of the EL spectrum of the sample was similar to that of a conventional phosphor-converted white LED.

  4. Characterization of the InGaN/GaN Multi-Quantum-Wells Light-Emitting Diode Grown on Patterned Sapphire Substrate with Wide Electroluminescence Spectrum

    NASA Astrophysics Data System (ADS)

    Reum Lee, Ah; Jeon, Hunsoo; Lee, Gang-Seok; Ok, Jin-Eun; Jo, Dong-Wan; Kim, Kyoung Hwa; Yi, Sam Nyung; Yang, Min; Ahn, Hyung Soo; Cho, Chae-Ryong; Kim, Suok-Whan; Lee, Jae-Hak; Ha, Hong-Ju

    2011-01-01

    We report the characterization of the InGaN/GaN multi-quantum-well (MQW) light-emitting diode (LED) grown on a patterned sapphire substrate by metal organic chemical vapor deposition (MOCVD) using the selective area growth (SAG) method. The SAG patterns were designed to be circular and their diameters were 700 and 200 µm. After the growth, the InGaN/GaN MQW LED of 200 µm diameter had various crystal facets and a shape similar to volcanic craters, which were not observed in the 700-µm-diameter sample. We obtained an active layer with compositional nonuniformity and superior optical properties. We found wide electroluminescence (EL) spectral peaks near 470, 570, and 600 nm. The distribution of the EL spectrum of the sample was similar to that of a conventional phosphor-converted white LED.

  5. Optical and structural characteristics of high indium content InGaN/GaN multi-quantum wells with varying GaN cap layer thickness

    SciTech Connect

    Yang, J.; Zhao, D. G. Jiang, D. S.; Chen, P.; Zhu, J. J.; Liu, Z. S.; Le, L. C.; Li, X. J.; He, X. G.; Liu, J. P.; Yang, H.; Zhang, Y. T.; Du, G. T.

    2015-02-07

    The optical and structural properties of InGaN/GaN multi-quantum wells (MQWs) with different thicknesses of low temperature grown GaN cap layers are investigated. It is found that the MQW emission energy red-shifts and the peak intensity decreases with increasing GaN cap layer thickness, which may be partly caused by increased floating indium atoms accumulated at quantum well (QW) surface. They will result in the increased interface roughness, higher defect density, and even lead to a thermal degradation of QW layers. An extra growth interruption introduced before the growth of GaN cap layer can help with evaporating the floating indium atoms, and therefore is an effective method to improve the optical properties of high indium content InGaN/GaN MQWs.

  6. A novel model on time-resolved photoluminescence measurements of polar InGaN/GaN multi-quantum-well structures

    NASA Astrophysics Data System (ADS)

    Xing, Yuchen; Wang, Lai; Yang, Di; Wang, Zilan; Hao, Zhibiao; Sun, Changzheng; Xiong, Bing; Luo, Yi; Han, Yanjun; Wang, Jian; Li, Hongtao

    2017-03-01

    Based on carrier rate equation, a new model is proposed to explain the non-exponential nature of time-resolved photoluminescence (TRPL) decay curves in the polar InGaN/GaN multi-quantum-well structures. From the study of TRPL curves at different temperatures, it is found that both radiative and non-radiative recombination coefficients vary from low temperature to room temperature. The variation of the coefficients is compatible with the carrier density of states distribution as well as the carrier localization process. These results suggest that there is a novel method to calculate the internal quantum efficiency, which is a complement to the traditional one based on temperature dependent photoluminescence measurement.

  7. Optical and structural properties of GaN nanopillar and nanostripe arrays with embedded InGaN /GaN multi-quantum wells

    NASA Astrophysics Data System (ADS)

    Keller, S.; Schaake, C.; Fichtenbaum, N. A.; Neufeld, C. J.; Wu, Y.; McGroddy, K.; David, A.; DenBaars, S. P.; Weisbuch, C.; Speck, J. S.; Mishra, U. K.

    2006-09-01

    GaN nanopillar and nanostripe arrays with embedded InGaN /GaN multi-quantum wells (MQWs) were fabricated by holographic lithography and subsequent reactive ion etching. Etch related damage of the nanostructures was successfully healed through annealing in NH3/N2 mixtures under optimized conditions. The nanopatterned samples exhibited enhanced luminescence in comparison to the planar wafers. X-ray reciprocal space maps recorded around the asymmetric (101¯5) reflection revealed that the MQWs in both nanopillars and nanostripes relaxed after nanopatterning and adopted a larger in-plane lattice constant than the underlying GaN layer. The pillar relaxation process had no measurable effect on the Stokes shift typically observed in MQWs on c-plane GaN, as evaluated by excitation power dependent photoluminescence (PL) measurements. Angular-resolved PL measurements revealed the extraction of guided modes from the nanopillar arrays.

  8. Investigating the origin of efficiency droop by profiling the voltage across the multi-quantum well of an operating light-emitting diode

    SciTech Connect

    Kim, Taewoong; Seong, Tae-Yeon; Kwon, Ohmyoung

    2016-06-06

    Efficiency droop is a phenomenon in which the efficiency of a light-emitting diode (LED) decreases with the increase in current density. To analyze efficiency droop, direct experimental observations on the energy conversion occurring inside the LED is required. Here, we present the measured voltage profiles on the cross section of an operating LED and analyze them with the cross-sectional temperature profiles obtained in a previous study under the same operation conditions. The measured voltage profiles suggest that with increases in the injection current density, electron depletion shifts from the multi-quantum well through an electron blocking layer to the p-GaN region. This is because electron leakage increases with increases in current density.

  9. A novel model on time-resolved photoluminescence measurements of polar InGaN/GaN multi-quantum-well structures.

    PubMed

    Xing, Yuchen; Wang, Lai; Yang, Di; Wang, Zilan; Hao, Zhibiao; Sun, Changzheng; Xiong, Bing; Luo, Yi; Han, Yanjun; Wang, Jian; Li, Hongtao

    2017-03-22

    Based on carrier rate equation, a new model is proposed to explain the non-exponential nature of time-resolved photoluminescence (TRPL) decay curves in the polar InGaN/GaN multi-quantum-well structures. From the study of TRPL curves at different temperatures, it is found that both radiative and non-radiative recombination coefficients vary from low temperature to room temperature. The variation of the coefficients is compatible with the carrier density of states distribution as well as the carrier localization process. These results suggest that there is a novel method to calculate the internal quantum efficiency, which is a complement to the traditional one based on temperature dependent photoluminescence measurement.

  10. Tracking protein function with sodium multi quantum spectroscopy in a 3D-tissue culture based on microcavity arrays.

    PubMed

    Neubauer, Andreas; Nies, Cordula; Schepkin, Victor D; Hu, Ruomin; Malzacher, Matthias; Chacón-Caldera, Jorge; Thiele, David; Gottwald, Eric; Schad, Lothar R

    2017-06-21

    The aim of this study was to observe the effects of strophanthin induced inhibition of the Na-/K-ATPase in liver cells using a magnetic resonance (MR) compatible bioreactor. A microcavity array with a high density three-dimensional cell culture served as a functional magnetic resonance imaging (MRI) phantom for sodium multi quantum (MQ) spectroscopy. Direct contrast enhanced (DCE) MRI revealed the homogenous distribution of biochemical substances inside the bioreactor. NMR experiments using advanced bioreactors have advantages with respect to having full control over a variety of physiological parameters such as temperature, gas composition and fluid flow. Simultaneous detection of single quantum (SQ) and triple quantum (TQ) MR signals improves accuracy and was achieved by application of a pulse sequence with a time proportional phase increment (TQTPPI). The time course of the Na-/K-ATPase inhibition in the cell culture was demonstrated by the corresponding alterations of sodium TQ/SQ MR signals.

  11. Molecule nanoweaver

    DOEpatents

    Gerald, II; Rex, E [Brookfield, IL; Klingler, Robert J [Glenview, IL; Rathke, Jerome W [Homer Glen, IL; Diaz, Rocio [Chicago, IL; Vukovic, Lela [Westchester, IL

    2009-03-10

    A method, apparatus, and system for constructing uniform macroscopic films with tailored geometric assemblies of molecules on the nanometer scale. The method, apparatus, and system include providing starting molecules of selected character, applying one or more force fields to the molecules to cause them to order and condense with NMR spectra and images being used to monitor progress in creating the desired geometrical assembly and functionality of molecules that comprise the films.

  12. An integrated approach of network-based systems biology, molecular docking, and molecular dynamics approach to unravel the role of existing antiviral molecules against AIDS-associated cancer.

    PubMed

    Omer, Ankur; Singh, Poonam

    2017-05-01

    A serious challenge in cancer treatment is to reposition the activity of various already known drug candidates against cancer. There is a need to rewrite and systematically analyze the detailed mechanistic aspect of cellular networks to gain insight into the novel role played by various molecules. Most Human Immunodeficiency Virus infection-associated cancers are caused by oncogenic viruses like Human Papilloma Viruses and Epstein-Bar Virus. As the onset of AIDS-associated cancers marks the severity of AIDS, there might be possible interconnections between the targets and mechanism of both the diseases. We have explored the possibility of certain antiviral compounds to act against major AIDS-associated cancers: Kaposi's Sarcoma, Non-Hodgkin Lymphoma, and Cervical Cancer with the help of systems pharmacology approach that includes screening for targets and molecules through the construction of a series of drug-target and drug-target-diseases network. Two molecules (Calanolide A and Chaetochromin B) and the target "HRAS" were finally screened with the help of molecular docking and molecular dynamics simulation. The results provide novel antiviral molecules against HRAS target to treat AIDS defining cancers and an insight for understanding the pharmacological, therapeutic aspects of similar unexplored molecules against various cancers.

  13. Effects of physiological self-crowding of DNA on shape and biological properties of DNA molecules with various levels of supercoiling

    PubMed Central

    Benedetti, Fabrizio; Japaridze, Aleksandre; Dorier, Julien; Racko, Dusan; Kwapich, Robert; Burnier, Yannis; Dietler, Giovanni; Stasiak, Andrzej

    2015-01-01

    DNA in bacterial chromosomes and bacterial plasmids is supercoiled. DNA supercoiling is essential for DNA replication and gene regulation. However, the density of supercoiling in vivo is circa twice smaller than in deproteinized DNA molecules isolated from bacteria. What are then the specific advantages of reduced supercoiling density that is maintained in vivo? Using Brownian dynamics simulations and atomic force microscopy we show here that thanks to physiological DNA–DNA crowding DNA molecules with reduced supercoiling density are still sufficiently supercoiled to stimulate interaction between cis-regulatory elements. On the other hand, weak supercoiling permits DNA molecules to modulate their overall shape in response to physiological changes in DNA crowding. This plasticity of DNA shapes may have regulatory role and be important for the postreplicative spontaneous segregation of bacterial chromosomes. PMID:25653164

  14. Interstellar molecules

    NASA Technical Reports Server (NTRS)

    Townes, C. H.

    1976-01-01

    Progress in the discovery and study of interstellar molecules is summarized. The 36 molecular species thus far identified in interstellar space are listed in several groups which include simple hydrides, oxides, and sulfides, various derivatives of ammonia, molecules involving linear carbon chains, cyanides, and molecules related in structure to formaldehyde, alcohols, or ethers. Several free radicals are described, the discovery of molecules in external galaxies is discussed, and possible mechanisms for molecular formation are noted. Methods for examining relative isotopic abundances by measuring molecules in interstellar clouds are outlined, mechanisms for the excitation of interstellar molecules are reviewed, and values are presented for the C-12/C-13 abundance ratio in a number of interstellar clouds. The detection of interstellar masers is discussed along with pumping mechanisms and masing transitions in H2CO, CH, OH, and SiO. The nature of dense interstellar clouds is examined in terms of several simple and complex cloud models, with emphasis on multiple condensation models.

  15. Synthesis and in Vivo Biological Evaluation of (68)Ga-Labeled Carbonic Anhydrase IX Targeting Small Molecules for Positron Emission Tomography.

    PubMed

    Sneddon, Deborah; Niemans, Raymon; Bauwens, Matthias; Yaromina, Ala; van Kuijk, Simon J A; Lieuwes, Natasja G; Biemans, Rianne; Pooters, Ivo; Pellegrini, Paul A; Lengkeek, Nigel A; Greguric, Ivan; Tonissen, Kathryn F; Supuran, Claudiu T; Lambin, Philippe; Dubois, Ludwig; Poulsen, Sally-Ann

    2016-07-14

    Tumor hypoxia contributes resistance to chemo- and radiotherapy, while oxygenated tumors are sensitive to these treatments. The indirect detection of hypoxic tumors is possible by targeting carbonic anhydrase IX (CA IX), an enzyme overexpressed in hypoxic tumors, with sulfonamide-based imaging agents. In this study, we present the design and synthesis of novel gallium-radiolabeled small-molecule sulfonamides targeting CA IX. The compounds display favorable in vivo pharmacokinetics and stability. We demonstrate that our lead compound, [(68)Ga]-2, discriminates CA IX-expressing tumors in vivo in a mouse xenograft model using positron emission tomography (PET). This compound shows specific tumor accumulation and low uptake in blood and clears intact to the urine. These findings were reproduced in a second study using PET/computed tomography. Small molecules investigated to date utilizing (68)Ga for preclinical CA IX imaging are scarce, and this is one of the first effective (68)Ga compounds reported for PET imaging of CA IX.

  16. Bond lengths at buried InAsP/InP interfaces in InP/InGaAs multi quantum wells

    NASA Astrophysics Data System (ADS)

    Boscherini, F.; Pascarelli, S.; Lamberti, C.; Bordiga, S.; Schiavini, G. M.

    1995-05-01

    As K-edge EXAFS has been carried out on InAsxP1-x/InP buried, epitaxial interfaces in strained layer InAsxP1-x/InP superlattices. Very little is known on the local structure of thin semiconductor layers in strained (multi) quantum wells. In particular the question which is still open is to what extent tetragonal distorsion and/or interface strain can alter the known "rigidity" of semiconductor bonds. The EXAFS analysis shows that the first shell environment of As at these interfaces is similar to that found in bulk InAsxP1-x alloys of similar composition, as determined experimentally and by comparison with recent theories of bond lengths in semiconductor alloys. In particular we measure an Assbnd In bond length which varies at most 0.02Åwith As concentration at the interface; this implies that epitaxy with InP is accompanied by local structural distortions, such as bond angle variations, which accommodate the nearly constant Assbnd In bond length. For completeness we also report results from high resolution X-ray diffraction and high resolution transmission electron microscopy which confirm the high crystalline perfection of the investigated samples.

  17. Combined electrical and resonant optical excitation characterization of multi-quantum well InGaN-based light-emitting diodes

    SciTech Connect

    Presa, S.; Maaskant, P. P.; Corbett, B.; Kappers, M. J.; Humphreys, C. J.

    2016-07-15

    We present a comprehensive study of the emission spectra and electrical characteristics of InGaN/GaN multi-quantum well light-emitting diode (LED) structures under resonant optical pumping and varying electrical bias. A 5 quantum well LED with a thin well (1.5 nm) and a relatively thick barrier (6.6 nm) shows strong bias-dependent properties in the emission spectra, poor photovoltaic carrier escape under forward bias and an increase in effective resistance when compared with a 10 quantum well LED with a thin (4 nm) barrier. These properties are due to a strong piezoelectric field in the well and associated reduced field in the thicker barrier. We compare the voltage ideality factors for the LEDs under electrical injection, light emission with current, photovoltaic mode (PV) and photoluminescence (PL) emission. The PV and PL methods provide similar values for the ideality which are lower than for the resistance-limited electrical method. Under optical pumping the presence of an n-type InGaN underlayer in a commercial LED sample is shown to act as a second photovoltaic source reducing the photovoltage and the extracted ideality factor to less than 1. The use of photovoltaic measurements together with bias-dependent spectrally resolved luminescence is a powerful method to provide valuable insights into the dynamics of GaN LEDs.

  18. Strong quantum-confined Stark effect in a lattice-matched GeSiSn/GeSn multi-quantum-well structure

    NASA Astrophysics Data System (ADS)

    Peng, Ruizhi; Chunfuzhang; Han, Genquan; Hao, Yue

    2017-06-01

    This paper presents modeling and simulation of a multiple quantum well structure formed with Ge0.95Sn0.05 quantum wells separated by Ge0.51Si0.35Sn0.14 barriers for the applications. These alloy compositions are chosen to satisfy two conditions simultaneously: type-I band alignment between Ge0.95Sn0.05/Ge0.51Si0.35Sn0.14 and a lattice match between wells and barriers. This lattice match ensures that the strain-free structure can be grown upon a relaxed Ge0.51Si0.35Sn0.14 buffer on a silicon substrate - a CMOS compatible process. A electro-absorption modulator with the Ge0.95Sn0.05/Ge0.51Si0.35Sn0.14 multiple quantum well structure based on quantum-confined Stark effect(QCSE) is demonstrated in theory. The energy band diagrams of the GeSiSn/GeSn multi-quantum-well structure at 0 and 0.5V bias are calculated, respectively. And the corresponding absorption coefficients as a function of cut-off energy for this multiple quantum well structure at 0 and 0.5Vbias are also obtained, respectively. The reduction of cut-off energy is observed with the applying of the external electric field, indicating a strong QCSE in the structure.

  19. Improved light extraction efficiency of InGaN-based multi-quantum well light emitting diodes by using a single die growth.

    PubMed

    Park, Min Joo; Kwon, K W; Kim, Y H; Park, S H; Kwak, Joon Seop

    2011-05-01

    We have demonstrated that the light extraction efficiency of the InGaN based multi-quantum well light-emitting diodes (LEDs) can be improved by using a single die growth (SDG) method. The SDG was performed by patterning the n-GaN and sapphire substrate with a size of single chip (600 x 250 microm2) by using a laser scriber, followed by the regrowth of the n-GaN and LED structures on the laser patterned n-GaN. We fabricated lateral LED chips having the SDG structures (SDG-LEDs), in which the thickness of the regrown n-GaN was varied from 2 to 6 microm. For comparison, we also fabricated conventional LED chips without the SDG structures. The SDG-LEDs showed lower operating voltage when compared to the conventional LEDs. In addition, the output power of the SDG-LEDs was significantly higher than that of the conventional LEDs. From optical ray tracing simulations, the increase in the thickness and sidewall angle of the regrown n-GaN and LED structures may enhance photon escapes from the tilted facets of the regrown n-GaN, followed by the increase in light output power and extraction efficiency of the SDG-LEDs.

  20. Combined electrical and resonant optical excitation characterization of multi-quantum well InGaN-based light-emitting diodes

    NASA Astrophysics Data System (ADS)

    Presa, S.; Maaskant, P. P.; Kappers, M. J.; Humphreys, C. J.; Corbett, B.

    2016-07-01

    We present a comprehensive study of the emission spectra and electrical characteristics of InGaN/GaN multi-quantum well light-emitting diode (LED) structures under resonant optical pumping and varying electrical bias. A 5 quantum well LED with a thin well (1.5 nm) and a relatively thick barrier (6.6 nm) shows strong bias-dependent properties in the emission spectra, poor photovoltaic carrier escape under forward bias and an increase in effective resistance when compared with a 10 quantum well LED with a thin (4 nm) barrier. These properties are due to a strong piezoelectric field in the well and associated reduced field in the thicker barrier. We compare the voltage ideality factors for the LEDs under electrical injection, light emission with current, photovoltaic mode (PV) and photoluminescence (PL) emission. The PV and PL methods provide similar values for the ideality which are lower than for the resistance-limited electrical method. Under optical pumping the presence of an n-type InGaN underlayer in a commercial LED sample is shown to act as a second photovoltaic source reducing the photovoltage and the extracted ideality factor to less than 1. The use of photovoltaic measurements together with bias-dependent spectrally resolved luminescence is a powerful method to provide valuable insights into the dynamics of GaN LEDs.

  1. Effect of Sapphire Substrate Thickness on the Characteristics of 450 nm InGaN/GaN Multi-Quantum Well Light-Emitting Diodes.

    PubMed

    Tawfik, Wael Z; Bea, Seo-Jung; Yang, Seung Bea; Ryu, Sang-Wan; Lee, June Key

    2015-07-01

    450 nm InGaN/GaN multi-quantum well (MQW) ligth-emitting diodes (LEDs) prepared on sapphire substrate with different thicknesses were fabricated and characterized. By thinning the sapphire substrate to 50 µm, it was found that the LED exhibited the highest light output power of ~48 mW under high injection current of 50 mA, improved by about 35% compared to that with 200 µm-thick sapphire without increasing the operating voltage. The electroluminescence intensity was increased and the spectral peak wavelength was blue-shifted, because the wafer bowing-induced mechanical stress alters the piezoelectric field in the InGaN/GaN MQW active region of the LED. The internal quantum efficiency was also improved by about 10% at an injection current of 50 mA. Moreover, the external quantum efficiency and light extraction efficiency were optimized because of enhanced light output intensity. The results confirmed that sapphire substrate thinning effectively alters the piezoelectric field in the InGaN/GaN active region, and hence increases both of the effective band gap and the probability of radiative recombination.

  2. 1550-nm InGaAsP multi-quantum-well structures selectively grown on v-groove-patterned SOI substrates

    NASA Astrophysics Data System (ADS)

    Megalini, Ludovico; Bonef, Bastien; Cabinian, Brian C.; Zhao, Hongwei; Taylor, Aidan; Speck, James S.; Bowers, John E.; Klamkin, Jonathan

    2017-07-01

    We report direct growth of 1550-nm InGaAsP multi-quantum-well (MQW) structures in densely packed, smooth, highly crystalline, and millimeter-long InP nanoridges grown by metalorganic chemical vapor deposition on silicon-on-insulator (SOI) substrates. Aspect-ratio-trapping and selective area growth techniques were combined with a two-step growth process to obtain good material quality as revealed by photoluminescence, scanning electronic microscopy, and high-resolution X-ray diffraction characterization. Transmission electron microscopy images revealed sharp MQW/InP interfaces as well as thickness variation of the MQW layer. This was confirmed by atom probe tomography analysis, which also suggests homogenous incorporation of the various III-V elements of the MQW structure. This approach is suitable for the integration of InP-based nanoridges in the SOI platform for new classes of ultra-compact, low-power, nano-electronic, and photonic devices for future tele- and data-communications applications.

  3. High resolution UV resonance enhanced two-photon ionization spectroscopy with mass selection of biologically relevant molecules in the gas phase

    NASA Astrophysics Data System (ADS)

    Chervenkov, S.; Wang, P. Q.; Karaminkov, R.; Chakraborty, T.; Braun, Juergen E.; Neusser, Hans J.

    2005-04-01

    The high resolution Doppler-free resonance-enhanced two-photon ionization (R2PI) spectroscopy with mass selection of jet-cooled (2-12 K) molecular species is a powerful experimental method providing comprehensive information on both isolated molecules and molecular clusters. We have demonstrated for the first time that this technique can be applied to large molecules and provides detailed information on their conformational structure. It allows rotationally resolved (FWHM = 70 MHz) spectra of the vibronic bands of the S1<--S0 electronic transition of the studied molecular systems to be measured. A specially designed computer-assisted fitting routine based on genetic algorithms is used to determine their rotational constants in the ground and excited electronic states, respectively, and the transition moment ratio. To interpret the experimental information and to discriminate and unambiguously assign the observed approach to the study of the neurotransmitter molecule, ephedrine. The results elucidate the role of the intramolecular hydrogen bonds stabilizing the respective conformations and affecting their intrinsic properties.

  4. Microbial Mats in the Tswaing Impact Crater: Results of a South African Exobiology Expedition and Implications for the Search for Biological Molecules on Mars

    NASA Technical Reports Server (NTRS)

    Cockell, C. S.; Brandt, D.; Hand, K.; Lee, P. C.

    2001-01-01

    We describe microbial mats from the Tswaing impact crater in South Africa. The mats provide insights into the unique biological characteristics of impact craters and can help strategies for the search for biomolecules on Mars. Additional information is contained in the original extended abstract.

  5. Microbial Mats in the Tswaing Impact Crater: Results of a South African Exobiology Expedition and Implications for the Search for Biological Molecules on Mars

    NASA Technical Reports Server (NTRS)

    Cockell, C. S.; Brandt, D.; Hand, K.; Lee, P. C.

    2001-01-01

    We describe microbial mats from the Tswaing impact crater in South Africa. The mats provide insights into the unique biological characteristics of impact craters and can help strategies for the search for biomolecules on Mars. Additional information is contained in the original extended abstract.

  6. Biomimetic polymers responsive to a biological signaling molecule: nitric oxide triggered reversible self-assembly of single macromolecular chains into nanoparticles.

    PubMed

    Hu, Jinming; Whittaker, Michael R; Duong, Hien; Li, Yang; Boyer, Cyrille; Davis, Thomas P

    2014-07-21

    Novel nitric oxide (NO) responsive monomers (NAPMA and APUEMA) containing o-phenylenediamine functional groups have been polymerized to form NO-responsive macromolecular chains as truly biomimetic polymers. Upon exposure to NO--a ubiquitous cellular signaling molecule--the NAPMA- and APUEMA-labeled thermoresponsive copolymers exhibited substantial changes in solubility, clearly characterized by tuneable LCST behavior, thereby inducing self-assembly into nanoparticulate structures. Moreover, the NO-triggered self-assembly process in combination with environmentally sensitive fluorescence dyes could be employed to detect and image endogenous NO.

  7. System in biology leading to cell pathology: stable protein-protein interactions after covalent modifications by small molecules or in transgenic cells.

    PubMed

    Malina, Halina Z

    2011-01-19

    The physiological processes in the cell are regulated by reversible, electrostatic protein-protein interactions. Apoptosis is such a regulated process, which is critically important in tissue homeostasis and development and leads to complete disintegration of the cell. Pathological apoptosis, a process similar to apoptosis, is associated with aging and infection. The current study shows that pathological apoptosis is a process caused by the covalent interactions between the signaling proteins, and a characteristic of this pathological network is the covalent binding of calmodulin to regulatory sequences. Small molecules able to bind covalently to the amino group of lysine, histidine, arginine, or glutamine modify the regulatory sequences of the proteins. The present study analyzed the interaction of calmodulin with the BH3 sequence of Bax, and the calmodulin-binding sequence of myristoylated alanine-rich C-kinase substrate in the presence of xanthurenic acid in primary retinal epithelium cell cultures and murine epithelial fibroblast cell lines transformed with SV40 (wild type [WT], Bid knockout [Bid-/-], and Bax-/-/Bak-/- double knockout [DKO]). Cell death was observed to be associated with the covalent binding of calmodulin, in parallel, to the regulatory sequences of proteins. Xanthurenic acid is known to activate caspase-3 in primary cell cultures, and the results showed that this activation is also observed in WT and Bid-/- cells, but not in DKO cells. However, DKO cells were not protected against death, but high rates of cell death occurred by detachment. The results showed that small molecules modify the basic amino acids in the regulatory sequences of proteins leading to covalent interactions between the modified sequences (e.g., calmodulin to calmodulin-binding sites). The formation of these polymers (aggregates) leads to an unregulated and, consequently, pathological protein network. The results suggest a mechanism for the involvement of small molecules

  8. Influence of chloramine T iodination on the biological and immunological activity or the molecular radius of the human growth hormone molecule

    SciTech Connect

    Bartolini, P.; Ribela, M.T.

    1986-01-01

    Potential alterations of the somatotropic activity of human growth hormone (hGH) resulting from Chloramine T labelling reaction, iodination up to 2.7 atoms/molecule and indirect radiation effects, have been studied. Three 2X2 factorial assays, performed in hypophysectomized rats, failed to reveal any significant difference (P greater than 0.05) in true growth promoting activity between hGH and (127-I)hGH, even after storing the latter with 125-I. Similar results were obtained applying a sensitive and precise gel filtration technique for Stokes Radius determination and radioimmunoassay.

  9. Mobius Molecules

    ERIC Educational Resources Information Center

    Eckert, J. M.

    1973-01-01

    Discusses formation of chemical molecules via Mobius strip intermediates, and concludes that many special physics-chemical properties of the fully closed circular form (1) of polyoma DNA are explainable by this topological feature. (CC)

  10. Interstellar Molecules

    ERIC Educational Resources Information Center

    Solomon, Philip M.

    1973-01-01

    Radioastronomy reveals that clouds between the stars, once believed to consist of simple atoms, contain molecules as complex as seven atoms and may be the most massive objects in our Galaxy. (Author/DF)

  11. Modeling Molecules

    NASA Technical Reports Server (NTRS)

    2000-01-01

    The molecule modeling method known as Multibody Order (N) Dynamics, or MBO(N)D, was developed by Moldyn, Inc. at Goddard Space Flight Center through funding provided by the SBIR program. The software can model the dynamics of molecules through technology which stimulates low-frequency molecular motions and properties, such as movements among a molecule's constituent parts. With MBO(N)D, a molecule is substructured into a set of interconnected rigid and flexible bodies. These bodies replace the computation burden of mapping individual atoms. Moldyn's technology cuts computation time while increasing accuracy. The MBO(N)D technology is available as Insight II 97.0 from Molecular Simulations, Inc. Currently the technology is used to account for forces on spacecraft parts and to perform molecular analyses for pharmaceutical purposes. It permits the solution of molecular dynamics problems on a moderate workstation, as opposed to on a supercomputer.

  12. Interstellar Molecules

    ERIC Educational Resources Information Center

    Solomon, Philip M.

    1973-01-01

    Radioastronomy reveals that clouds between the stars, once believed to consist of simple atoms, contain molecules as complex as seven atoms and may be the most massive objects in our Galaxy. (Author/DF)

  13. Mobius Molecules

    ERIC Educational Resources Information Center

    Eckert, J. M.

    1973-01-01

    Discusses formation of chemical molecules via Mobius strip intermediates, and concludes that many special physics-chemical properties of the fully closed circular form (1) of polyoma DNA are explainable by this topological feature. (CC)

  14. Integrating computational and chemical biology tools in the discovery of antiangiogenic small molecule ligands of FGF2 derived from endogenous inhibitors

    PubMed Central

    Foglieni, Chiara; Pagano, Katiuscia; Lessi, Marco; Bugatti, Antonella; Moroni, Elisabetta; Pinessi, Denise; Resovi, Andrea; Ribatti, Domenico; Bertini, Sabrina; Ragona, Laura; Bellina, Fabio; Rusnati, Marco; Colombo, Giorgio; Taraboletti, Giulia

    2016-01-01

    The FGFs/FGFRs system is a recognized actionable target for therapeutic approaches aimed at inhibiting tumor growth, angiogenesis, metastasis, and resistance to therapy. We previously identified a non-peptidic compound (SM27) that retains the structural and functional properties of the FGF2-binding sequence of thrombospondin-1 (TSP-1), a major endogenous inhibitor of angiogenesis. Here we identified new small molecule inhibitors of FGF2 based on the initial lead. A similarity-based screening of small molecule libraries, followed by docking calculations and experimental studies, allowed selecting 7 bi-naphthalenic compounds that bound FGF2 inhibiting its binding to both heparan sulfate proteoglycans and FGFR-1. The compounds inhibit FGF2 activity in in vitro and ex vivo models of angiogenesis, with improved potency over SM27. Comparative analysis of the selected hits, complemented by NMR and biochemical analysis of 4 newly synthesized functionalized phenylamino-substituted naphthalenes, allowed identifying the minimal stereochemical requirements to improve the design of naphthalene sulfonates as FGF2 inhibitors. PMID:27000667

  15. Enumerating molecules.

    SciTech Connect

    Visco, Donald Patrick, Jr.; Faulon, Jean-Loup Michel; Roe, Diana C.

    2004-04-01

    This report is a comprehensive review of the field of molecular enumeration from early isomer counting theories to evolutionary algorithms that design molecules in silico. The core of the review is a detail account on how molecules are counted, enumerated, and sampled. The practical applications of molecular enumeration are also reviewed for chemical information, structure elucidation, molecular design, and combinatorial library design purposes. This review is to appear as a chapter in Reviews in Computational Chemistry volume 21 edited by Kenny B. Lipkowitz.

  16. DNA: An Extensible Molecule

    NASA Astrophysics Data System (ADS)

    Cluzel, Philippe; Lebrun, Anne; Heller, Christoph; Lavery, Richard; Viovy, Jean-Louis; Chatenay, Didier; Caron, Francois

    1996-02-01

    The force-displacement response of a single duplex DNA molecule was measured. The force saturates at a plateau around 70 piconewtons, which ends when the DNA has been stretched about 1.7 times its contour length. This behavior reveals a highly cooperative transition to a state here termed S-DNA. Addition of an intercalator suppresses this transition. Molecular modeling of the process also yields a force plateau and suggests a structure for the extended form. These results may shed light on biological processes involving DNA extension and open the route for mechanical studies on individual molecules in a previously unexplored range.

  17. InGaAs/GaAsP strain balanced multi-quantum wires grown on misoriented GaAs substrates for high efficiency solar cells

    NASA Astrophysics Data System (ADS)

    Alonso-Álvarez, D.; Thomas, T.; Führer, M.; Hylton, N. P.; Ekins-Daukes, N. J.; Lackner, D.; Philipps, S. P.; Bett, A. W.; Sodabanlu, H.; Fujii, H.; Watanabe, K.; Sugiyama, M.; Nasi, L.; Campanini, M.

    2014-08-01

    Quantum wires (QWRs) form naturally when growing strain balanced InGaAs/GaAsP multi-quantum wells (MQW) on GaAs [100] 6° misoriented substrates under the usual growth conditions. The presence of wires instead of wells could have several unexpected consequences for the performance of the MQW solar cells, both positive and negative, that need to be assessed to achieve high conversion efficiencies. In this letter, we study QWR properties from the point of view of their performance as solar cells by means of transmission electron microscopy, time resolved photoluminescence and external quantum efficiency (EQE) using polarised light. We find that these QWRs have longer lifetimes than nominally identical QWs grown on exact [100] GaAs substrates, of up to 1 μs, at any level of illumination. We attribute this effect to an asymmetric carrier escape from the nanostructures leading to a strong 1D-photo-charging, keeping electrons confined along the wire and holes in the barriers. In principle, these extended lifetimes could be exploited to enhance carrier collection and reduce dark current losses. Light absorption by these QWRs is 1.6 times weaker than QWs, as revealed by EQE measurements, which emphasises the need for more layers of nanostructures or the use light trapping techniques. Contrary to what we expected, QWR show very low absorption anisotropy, only 3.5%, which was the main drawback a priori of this nanostructure. We attribute this to a reduced lateral confinement inside the wires. These results encourage further study and optimization of QWRs for high efficiency solar cells.

  18. High pressure and time resolved studies of optical properties of n-type doped GaN/AlN multi-quantum wells: Experimental and theoretical analysis

    SciTech Connect

    Kaminska, A.; Jankowski, D.; Sobczak, K.; Beeler, M.; Monroy, E.; Borysiuk, J.

    2016-09-07

    High-pressure and time-resolved studies of the optical emission from n-type doped GaN/AlN multi-quantum-wells (MQWs) with various well thicknesses are analysed in comparison with ab initio calculations of the electronic (band structure, density of states) and optical (emission energies and their pressure derivatives, oscillator strength) properties. The optical properties of GaN/AlN MQWs are strongly affected by quantum confinement and polarization-induced electric fields. Thus, the photoluminescence (PL) peak energy decreases by over 1 eV with quantum well (QW) thicknesses increasing from 1 to 6 nm. Furthermore, the respective PL decay times increased from about 1 ns up to 10 μs, due to the strong built-in electric field. It was also shown that the band gap pressure coefficients are significantly reduced in MQWs as compared to bulk AlN and GaN crystals. Such coefficients are strongly dependent on the geometric factors such as the thickness of the wells and barriers. The transition energies, their oscillator strength, and pressure dependence are modeled for tetragonally strained structures of the same geometry using a full tensorial representation of the strain in the MQWs under external pressure. These MQWs were simulated directly using density functional theory calculations, taking into account two different systems: the semi-insulating QWs and the n-doped QWs with the same charge density as in the experimental samples. Such an approach allowed an assessment of the impact of n-type doping on optical properties of GaN/AlN MQWs. We find a good agreement between these two approaches and between theory and experimental results. We can therefore confirm that the nonlinear effects induced by the tetragonal strain related to the lattice mismatch between the substrates and the polar MQWs are responsible for the drastic decrease of the pressure coefficients observed experimentally.

  19. Correlation of optical and structural properties of GaN/AlN multi-quantum wells—Ab initio and experimental study

    SciTech Connect

    Kaminska, A.; Strak, P.; Sakowski, K.; Sobczak, K.; Domagala, J. Z.; Grzanka, E.

    2016-01-07

    The results of comprehensive theoretical and experimental study of binary GaN/AlN multi-quantum well (MQW) systems oriented along polar c-direction of their wurtzite structure are presented. A series of structures with quantum wells and barriers of various thicknesses were grown by plasma-assisted molecular-beam epitaxy and characterized by x-ray diffraction and transmission electron microscopy. It was shown that in general the structures of good quality were obtained, with the defect density decreasing with increasing quantum well thickness. The optical transition energies in these structures were investigated comparing experimental measurements with ab initio calculations of the entire GaN/AlN MQW structure depending on the QW widths and strains, allowing for direct determination of the energies of optical transitions and the electric fields in wells/barriers by electric potential double averaging procedure. Photoluminescence (PL) measurements revealed that the emission efficiency as well as the shape of luminescence spectra correlated well with their structural quality. Additionally, due to the Quantum-Confined Stark Effect, the emission energy decreased by over 1 eV for quantum well thicknesses increasing from 1 nm up to 6 nm, and this effect was accompanied by the drastic drop of the PL efficiency. The experimental results are consistent with theoretical models. Comparison of experimental data obtained by a number of different characterization techniques with the density functional theory results received on the same geometry structure allowed to prove directly the theoretical models and to determine the polarization and the oscillator strengths in the AlN/GaN nitride systems for the first time.

  20. Molecules as Automata

    NASA Astrophysics Data System (ADS)

    Cardelli, Luca

    Molecular biology investigates the structure and function of biochemical systems starting from their basic building blocks: macromolecules. A macromolecule is a large, complex molecule (a protein or a nucleic acid) that usually has inner mutable state and external activity. Informal explanations of biochemical events trace individual macromolecules through their state changes and their interaction histories: a macromolecule is endowed with an identity that is retained through its transformations, even through changes in molecular energy and mass. A macromolecule, therefore, is qualitatively different from the small molecules of inorganic chemistry. Such molecules are stateless: in the standard notation for chemical reactions they are seemingly created and destroyed, and their atomic structure is used mainly for the bookkeeping required by the conservation of mass.

  1. JAK/STAT signalling--an executable model assembled from molecule-centred modules demonstrating a module-oriented database concept for systems and synthetic biology.

    PubMed

    Blätke, Mary Ann; Dittrich, Anna; Rohr, Christian; Heiner, Monika; Schaper, Fred; Marwan, Wolfgang

    2013-06-01

    Mathematical models of molecular networks regulating biological processes in cells or organisms are most frequently designed as sets of ordinary differential equations. Various modularisation methods have been applied to reduce the complexity of models, to analyse their structural properties, to separate biological processes, or to reuse model parts. Taking the JAK/STAT signalling pathway with the extensive combinatorial cross-talk of its components as a case study, we make a natural approach to modularisation by creating one module for each biomolecule. Each module consists of a Petri net and associated metadata and is organised in a database publically accessible through a web interface (). The Petri net describes the reaction mechanism of a given biomolecule and its functional interactions with other components including relevant conformational states. The database is designed to support the curation, documentation, version control, and update of individual modules, and to assist the user in automatically composing complex models from modules. Biomolecule centred modules, associated metadata, and database support together allow the automatic creation of models by considering differential gene expression in given cell types or under certain physiological conditions or states of disease. Modularity also facilitates exploring the consequences of alternative molecular mechanisms by comparative simulation of automatically created models even for users without mathematical skills. Models may be selectively executed as an ODE system, stochastic, or qualitative models or hybrid and exported in the SBML format. The fully automated generation of models of redesigned networks by metadata-guided modification of modules representing biomolecules with mutated function or specificity is proposed.

  2. The IgG molecule as a biological immune response modifier: mechanisms of action of intravenous immune serum globulin in autoimmune and inflammatory disorders.

    PubMed

    Ballow, Mark

    2011-02-01

    Intravenous immune globulin (IVIG) is an important treatment modality in patients with humoral or B-cell immune deficiency as replacement therapy. Soon after its introduction in the early 1980s for the treatment of patients with immune deficiency, IVIG was used in the treatment of children with idiopathic thrombocytopenia purpura. Presently, more commercial IVIG is used for the treatment of autoimmune and inflammatory disorders than as replacement therapy in patients with immune deficiency. Understanding the mechanisms of action of IVIG in these autoimmune and inflammatory disorders has occupied investigators over the past 3 decades. A number of mechanisms for the immune modulation and anti-inflammatory actions of IVIG have been described, including Fc receptor blockade, inhibition of complement deposition, enhancement of regulatory T cells, inhibition or neutralization of cytokines and growth factors, accelerated clearance of autoantibodies, modulation of adhesion molecules and cell receptors, and activation of regulatory macrophages through the FcγRIIb receptor. It can now be appreciated that IVIG affects many different pathways to modulate the immune and inflammatory response. Further delineation of these pathways might lead to new treatment strategies.

  3. Drug Delivery Through the Skin: Molecular Simulations of Barrier Lipids to Design more Effective Noninvasive Dermal and Transdermal Delivery Systems for Small Molecules Biologics and Cosmetics

    SciTech Connect

    J Torin Huzil; S Sivaloganathan; M Kohandel; M Foldvari

    2011-12-31

    The delivery of drugs through the skin provides a convenient route of administration that is often preferable to injection because it is noninvasive and can typically be self-administered. These two factors alone result in a significant reduction of medical complications and improvement in patient compliance. Unfortunately, a significant obstacle to dermal and transdermal drug delivery alike is the resilient barrier that the epidermal layers of the skin, primarily the stratum corneum, presents for the diffusion of exogenous chemical agents. Further advancement of transdermal drug delivery requires the development of novel delivery systems that are suitable for modern, macromolecular protein and nucleotide therapeutic agents. Significant effort has already been devoted to obtain a functional understanding of the physical barrier properties imparted by the epidermis, specifically the membrane structures of the stratum corneum. However, structural observations of membrane systems are often hindered by low resolutions, making it difficult to resolve the molecular mechanisms related to interactions between lipids found within the stratum corneum. Several models describing the molecular diffusion of drug molecules through the stratum corneum have now been postulated, where chemical permeation enhancers are thought to disrupt the underlying lipid structure, resulting in enhanced permeability. Recent investigations using biphasic vesicles also suggested a possibility for novel mechanisms involving the formation of complex polymorphic lipid phases. In this review, we discuss the advantages and limitations of permeation-enhancing strategies and how computational simulations, at the atomic scale, coupled with physical observations can provide insight into the mechanisms of diffusion through the stratum corneum.

  4. Systems Chemical Biology

    PubMed Central

    Oprea, Tudor I.; Tropsha, Alexander; Faulon, Jean-Loup; Rintoul, Mark D.

    2009-01-01

    The increasing availability of data related to genes, proteins and their modulation by small molecules, paralleled by the emergence of simulation tools in systems biology, has provided a vast amount of biological information. However, there is a critical need to develop cheminformatics tools that can integrate chemical knowledge with these biological databases, with the goal of creating systems chemical biology. PMID:17637771

  5. Discovery of RNA Binding Small Molecules Using Small Molecule Microarrays.

    PubMed

    Connelly, Colleen M; Abulwerdi, Fardokht A; Schneekloth, John S

    2017-01-01

    New methods to identify RNA-binding small molecules open yet unexplored opportunities for the pharmacological modulation of RNA-driven biology and disease states. One such approach is the use of small molecule microarrays (SMMs). Typically, SMMs are generated by spatially arraying and covalently linking a library of small molecules to a glass surface. Next, incubation of the arrays with a fluorescently labeled RNA reveals binding interactions that are detected upon slide imaging. The relative ease with which SMMs are manufactured enables the screening of multiple oligonucleotides in parallel against tens of thousands of small molecules, providing information about both binding and selectivity of identified RNA-small molecule interactions. This approach is useful for screening a broad variety of structurally and functionally diverse RNAs. Here, we present a general method for the preparation and use of SMMs to rapidly identify small molecules that selectively bind to an RNA of interest.

  6. Ultrathin (1 nm) vertically shadowed platinum-carbon replicas for imaging individual molecules in freeze-etched biological DNA and material science metal and plastic specimens.

    PubMed

    Ruben, G C

    1989-12-01

    Single molecule resolution in beam-sensitive, uncoated, noncrystalline materials has heretofore not been possible except in thin (less than or equal to 150 A) platinum-carbon (Pt-C) replicas, which are resistant to electron beam destruction. Previously, the granularity of metal film replicas limited their resolution to greater than or equal to 20 A. This paper demonstrates that Pt-C film granularity and resolution are a function of the method of replication and other controllable factors. Low-angle 20 degrees rotary, 45 degrees unidirectional, and vertical 9.7 +/- 1 A Pt-C films deposited on mica under the same conditions were compared. Vertical replication had a 5 A granularity, the highest resolution, and evenly coated the whole surface. A 45 degrees replication had a 9.5 A granularity, a slightly poorer resolution, and a discontinuous surface coating. The use of 20 degrees rotary replication proved to be unsuitable for high-resolution imaging, with 20-25 A granularity and resolution two to three times poorer. Vertical and 45 degrees Pt-C replicas can visualize the deep-etched DNA helix and the 13.3 A 3(2) helix of pectin in a gel. The DNA double helix, the complex structures of sol-gel glasses, Immobilon filters (polyvinylidene fluoride), a polymethacrylate plastic, the metal oxide surfaces of 440c stainless steel, and aluminum are illustrated. This high-resolution vertical Pt-C replica technique can image in the context of solutions, gels, or solids, single molecular chains 3-7 A wide, their associations, and their conformation. Included in the present article are first time descriptions for removing replicas from metals and plastics and for making high-magnification photographic prints of normal contrast using a reversal rephotographic process.

  7. Reduction of graphene oxide by resveratrol: a novel and simple biological method for the synthesis of an effective anticancer nanotherapeutic molecule

    PubMed Central

    Gurunathan, Sangiliyandi; Han, Jae Woong; Kim, Eun Su; Park, Jung Hyun; Kim, Jin-Hoi

    2015-01-01

    Objective Graphene represents a monolayer or a few layers of sp2-bonded carbon atoms with a honeycomb lattice structure. Unique physical, chemical, and biological properties of graphene have attracted great interest in various fields including electronics, energy, material industry, and medicine, where it is used for tissue engineering and scaffolding, drug delivery, and as an antibacterial and anticancer agent. However, graphene cytotoxicity for ovarian cancer cells is still not fully investigated. The objective of this study was to synthesize graphene using a natural polyphenol compound resveratrol and to investigate its toxicity for ovarian cancer cells. Methods The successful reduction of graphene oxide (GO) to graphene was confirmed by UV-vis and Fourier transform infrared spectroscopy. Dynamic light scattering and scanning electron microscopy were employed to evaluate particle size and surface morphology of GO and resveratrol-reduced GO (RES-rGO). Raman spectroscopy was used to determine the removal of oxygen-containing functional groups from GO surface and to ensure the formation of graphene. We also performed a comprehensive analysis of GO and RES-rGO cytotoxicity by examining the morphology, viability, membrane integrity, activation of caspase-3, apoptosis, and alkaline phosphatase activity of ovarian cancer cells. Results The results also show that resveratrol effectively reduced GO to graphene and the properties of RES-rGO nanosheets were comparable to those of chemically reduced graphene. Biological experiments showed that GO and RES-rGO caused a dose-dependent membrane leakage and oxidative stress in cancer cells, and reduced their viability via apoptosis confirmed by the upregulation of apoptosis executioner caspase-3. Conclusion Our data demonstrate a single, simple green approach for the synthesis of highly water-dispersible functionalized graphene nanosheets, suggesting a possibility of replacing toxic hydrazine by a natural and safe phenolic

  8. Reduction of graphene oxide by resveratrol: a novel and simple biological method for the synthesis of an effective anticancer nanotherapeutic molecule.

    PubMed

    Gurunathan, Sangiliyandi; Han, Jae Woong; Kim, Eun Su; Park, Jung Hyun; Kim, Jin-Hoi

    2015-01-01

    Graphene represents a monolayer or a few layers of sp2-bonded carbon atoms with a honeycomb lattice structure. Unique physical, chemical, and biological properties of graphene have attracted great interest in various fields including electronics, energy, material industry, and medicine, where it is used for tissue engineering and scaffolding, drug delivery, and as an antibacterial and anticancer agent. However, graphene cytotoxicity for ovarian cancer cells is still not fully investigated. The objective of this study was to synthesize graphene using a natural polyphenol compound resveratrol and to investigate its toxicity for ovarian cancer cells. The successful reduction of graphene oxide (GO) to graphene was confirmed by UV-vis and Fourier transform infrared spectroscopy. Dynamic light scattering and scanning electron microscopy were employed to evaluate particle size and surface morphology of GO and resveratrol-reduced GO (RES-rGO). Raman spectroscopy was used to determine the removal of oxygen-containing functional groups from GO surface and to ensure the formation of graphene. We also performed a comprehensive analysis of GO and RES-rGO cytotoxicity by examining the morphology, viability, membrane integrity, activation of caspase-3, apoptosis, and alkaline phosphatase activity of ovarian cancer cells. The results also show that resveratrol effectively reduced GO to graphene and the properties of RES-rGO nanosheets were comparable to those of chemically reduced graphene. Biological experiments showed that GO and RES-rGO caused a dose-dependent membrane leakage and oxidative stress in cancer cells, and reduced their viability via apoptosis confirmed by the upregulation of apoptosis executioner caspase-3. Our data demonstrate a single, simple green approach for the synthesis of highly water-dispersible functionalized graphene nanosheets, suggesting a possibility of replacing toxic hydrazine by a natural and safe phenolic compound resveratrol, which has similar

  9. Spacer conformation in biologically active molecules. Part 2. Structure and conformation of 4-[2-(diphenylmethylamino)ethyl]-1-(2-methoxyphenyl) piperazine and its diphenylmethoxy analog—potential 5-HT 1A receptor ligands

    NASA Astrophysics Data System (ADS)

    Karolak-Wojciechowska, J.; Fruziński, A.; Czylkowski, R.; Paluchowska, M. H.; Mokrosz, M. J.

    2003-09-01

    As a part of studies on biologically active molecule structures with aliphatic linking chain, the structures of 4-[2-diphenylmethylamino)ethyl]-1-(2-methoxyphenyl)piperazine dihydrochloride ( 1) and 4-[2-diphenylmethoxy)ethyl]-1-(2-methoxyphenyl)piperazine fumarate ( 2) have been reported. In both compounds, four atomic non-all-carbons linking chains (N)C-C-X-C are present. The conformation of that linking spacer depends on the nature of the X-atom. The preferred conformation for chain with XNH has been found to be fully extended while for that with XO—the bend one. It was confirmed by conformational calculations (strain energy distribution and random search) and crystallographic data, including statistics from CCDC.

  10. Feasibility study for the rapid screening of target molecules using translational diffusion coefficients: diffusion-ordered NMR spectroscopy of biological toxins.

    PubMed

    Henderson, Terry J

    2010-02-01

    A panel of 15 biological toxins ranging between approximately 60-28,000 g/mol was used to evaluate the feasibility of screening aqueous samples for toxin analytes based on their translational diffusion coefficients, D(t). Toxin D(t) values were measured by pulsed-field gradient (1)H NMR spectroscopy using a bipolar pulse pair, longitudinal eddy current delay pulse sequence incorporating water suppression to achieve the maximum dynamic range for toxin signals. To collect data for an effective screening protocol, reference D(t) values were determined from five independent measurements at both 25 and 37 degrees C for all toxins in the panel. In the protocol, D(t) values are measured at both temperatures for a suspected toxin target in a sample, and for assignment as a potential toxin analyte, the measurements are required to fall within +/-0.25 x 10(-6) cm(2)/s of both reference D(t) values for at least one toxin in the panel. Only solution viscosity was found to influence sample D(t) measurements appreciably; however, the measurements are easily corrected for viscosity effects by calculating the D(t) value of the suspected toxin at infinite dilution. In conclusion, the protocol provides a rapid and effective means for screening aqueous samples for all toxins in the panel, narrowing toxin identification to < or = 2 possibilities in virtually all cases.

  11. Synthesis and biological evaluation of new 3-(6-hydroxyindol-2-yl)-5-(Phenyl) pyridine or pyrazine V-Shaped molecules as kinase inhibitors and cytotoxic agents.

    PubMed

    Kassis, Pamela; Brzeszcz, Joanna; Bénéteau, Valérie; Lozach, Olivier; Meijer, Laurent; Le Guével, Rémi; Guillouzo, Christiane; Lewiński, Krzysztof; Bourg, Stéphane; Colliandre, Lionel; Routier, Sylvain; Mérour, Jean-Yves

    2011-11-01

    We here report the synthesis and biological evaluation of new 3-[(2-indolyl)]-5-phenyl-3,5-pyridine, 3-[(2-indolyl)]-5-phenyl-2,4-pyridine and 3-[(2-indolyl)]-5-phenyl-2,6-pyrazine derivatives designed as potential CDK inhibitors. Indoles and phenyls were used to generate several substitutions of the pyridine and pyrazine rings. The synthesis included Stille or Suzuki type reactions, which were carried out on the 3,5-dibromopyridine, 2,4-dichloropyridine and 2,6-dichloro-1-4-pyrazine moieties. Cell effects of the V-shaped family were in the micromolar range. Kinase assays were conducted and showed that compound 11 inhibited CDK5 with an inhibitory concentration of 160 nM with a moderate selectivity over GSK3 compared to the reference C which exhibited a slightly lower activity on CDK5 (1.5 μM). Compound 11 was also found to be the most potent compound in the series and was identified as a new lead for DYRK1A inhibitor discovery (IC(50) = 60 nM). Docking studies were carried out in order to investigate the inhibition of DYRK1A.

  12. Growth and characterization of strained Si 1- xGe x multi-quantum-well waveguide photodetectors on (1 1 0) Si for 1.3 and 1.55 μm

    NASA Astrophysics Data System (ADS)

    Bernhard-Höfer, K.; Zrenner, A.; Brunner, J.; Abstreiter, G.; Wittmann, F.; Eisele, I.

    1998-07-01

    Pseudomorphic Si 1- xGe x/Si multi-quantum well p-i-n photodiodes have been grown on (1 1 0) Si by molecular beam epitaxy. Using waveguide geometry we have obtained an external quantum efficiency of 17% at 1.32 μm (TE-polarisation) with a Ge mole fraction of x=0.5. At λ=1.52 μm (TE-polarisation) an external quantum efficiency of 7% has been achieved. From the dependence of photocurrent on device length effective interband absorption coefficients for x=0.5 and 0.37 have been determined quantitatively.

  13. Single-molecule nanopore enzymology

    PubMed Central

    Wloka, Carsten; Maglia, Giovanni

    2017-01-01

    Biological nanopores are a class of membrane proteins that open nanoscale water-conduits in biological membranes. When they are reconstituted in artificial membranes and a bias voltage is applied across the membrane, the ionic current passing through individual nanopores can be used to monitor chemical reactions, to recognize individual molecules and, of most interest, to sequence DNA. More recently, proteins and enzymes have started being analysed with nanopores. Monitoring enzymatic reactions with nanopores, i.e. nanopore enzymology, has the unique advantage that it allows long-timescale observations of native proteins at the single-molecule level. Here we describe the approaches and challenges in nanopore enzymology. PMID:28630164

  14. Single-molecule electrometry

    NASA Astrophysics Data System (ADS)

    Ruggeri, Francesca; Zosel, Franziska; Mutter, Natalie; Różycka, Mirosława; Wojtas, Magdalena; Ożyhar, Andrzej; Schuler, Benjamin; Krishnan, Madhavi

    2017-05-01

    Mass and electrical charge are fundamental properties of biological macromolecules. Although molecular mass has long been determined with atomic precision, a direct and precise determination of molecular charge remains an outstanding challenge. Here we report high-precision (<1e) measurements of the electrical charge of molecules such as nucleic acids, and globular and disordered proteins in solution. The measurement is based on parallel external field-free trapping of single macromolecules, permits the estimation of a dielectric coefficient of the molecular interior and can be performed in real time. Further, we demonstrate the direct detection of single amino acid substitution and chemical modifications in proteins. As the electrical charge of a macromolecule strongly depends on its three-dimensional conformation, this kind of high-precision electrometry offers an approach to probe the structure, fluctuations and interactions of a single molecule in solution.

  15. An optical conveyor for molecules.

    PubMed

    Weinert, Franz M; Braun, Dieter

    2009-12-01

    Trapping single ions under vacuum allows for precise spectroscopy in atomic physics. The confinement of biological molecules in bulk water is hindered by the lack of comparably strong forces. Molecules have been immobilized to surfaces, however often with detrimental effects on their function. Here, we optically trap molecules by creating the microscale analogue of a conveyor belt: a bidirectional flow is combined with a perpendicular thermophoretic molecule drift. Arranged in a toroidal geometry, the conveyor accumulates a hundredfold excess of 5-base DNA within seconds. The concentrations of the trapped DNA scale exponentially with length, reaching trapping potential depths of 14 kT for 50 bases. The mechanism does not require microfluidics, electrodes, or surface modifications. As a result, the trap can be dynamically relocated. The optical conveyor can be used to enhance diffusion-limited surface reactions, redirect cellular signaling, observe individual biomolecules over a prolonged time, or approach single-molecule chemistry in bulk water.

  16. Foldit Biology

    DTIC Science & Technology

    2015-07-31

    and widely used talking points in the biology curriculum: Hemoglobin, Lysozyme and Lactase . Hemoglobin is our first example and is currently used to...its ability to succinctly capture into one package all of the important aspects of a protein interacting with other molecules. Lactase is the...third example, in which we introduce interactive gameplay to show how enzymes work. Like the Lysozyme example, the Lactase example is a multi-state

  17. Enhanced Raman scattering of biological molecules

    NASA Astrophysics Data System (ADS)

    Montoya, Joseph R.

    The results presented in this thesis, originate from the aspiration to develop an identification algorithm for Salmonella enterica Serovar Enteritidis (S. enterica), Escherichia coli (E. coli), Bacillus globigii ( B. globigii), and Bacillus megaterium ( B. megaterium) using "enhanced" Raman scattering. We realized our goal, with a method utilizing an immunoassay process in a spectroscopic technique, and the direct use of the enhanced spectral response due to bacterial surface elements. The enhanced Raman signal originates from Surface Enhanced Raman Scattering (SERS) and/or Morphological Dependent Resonances (MDR's). We utilized a modified Lee-Meisel colloidal production method to produce a SERS active substrate, which was applied to a SERS application for the amino acid Glycine. The comparison indicates that the SERS/FRACTAL/MDR process can produce an increase of 107 times more signal than the bulk Raman signal from Glycine. In the extension of the Glycine results, we studied the use of SERS related to S. enterica, where we have shown that the aromatic amino acid contribution from Phenylalanine, Tyrosine, and Tryptophan produces a SERS response that can be used to identify the associated SERS vibrational modes of a S. enterica one or two antibody complexes. The "fingerprint" associated with the spectral signature in conjunction with an enhanced Raman signal allows conclusions to be made: (1) about the orientation of the secondary structure on the metal; (2) whether bound/unbound antibody can be neglected; (3) whether we can lower the detection limit. We have lowered the detection limit of S. enterica to 106 bacteria/ml. We also show a profound difference between S. enterica and E. coli SERS spectra even when there exists non-specific binding on E. coli indicating a protein conformation change induced by the addition of the antigen S. enterica. We confirm TEM imagery data, indicating that the source of the aromatic amino acid SERS response is originating from fractal structures on the surface of the bacteria with appropriate associated absorption spectra. In addition, we show that SERS may be used by directly detecting cell surface chemistry, with a report of a SERS response from gram-positive bacteria, B. globigii and B. megaterium combined, with silver fractal aggregates.

  18. The Biological Revolution: Commercialization of the Molecule.

    ERIC Educational Resources Information Center

    Lasagna, Louis

    1987-01-01

    Academia and industry both have an interest in the economic aspects of drug development, including the rising cost of new drug discovery, the decrease in the effective patent life of new drugs as the drug improvement process lengthens, and the impact of drug-related litigation. (MLW)

  19. Review: Nectar biology: From molecules to ecosystems.

    PubMed

    Roy, Rahul; Schmitt, Anthony J; Thomas, Jason B; Carter, Clay J

    2017-09-01

    Plants attract mutualistic animals by offering a reward of nectar. Specifically, floral nectar (FN) is produced to attract pollinators, whereas extrafloral nectar (EFN) mediates indirect defenses through the attraction of mutualist predatory insects to limit herbivory. Nearly 90% of all plant species, including 75% of domesticated crops, benefit from animal-mediated pollination, which is largely facilitated by FN. Moreover, EFN represents one of the few defense mechanisms for which stable effects on plant health and fitness have been demonstrated in multiple systems, and thus plays a crucial role in the resistance phenotype of plants producing it. In spite of its central role in plant-animal interactions, the molecular events involved in the development of both floral and extrafloral nectaries (the glands that produce nectar), as well as the synthesis and secretion of the nectar itself, have been poorly understood until recently. This review will cover major recent developments in the understanding of (1) nectar chemistry and its role in plant-mutualist interactions, (2) the structure and development of nectaries, (3) nectar production, and (4) its regulation by phytohormones. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Interaction of Phenyldichloroarsine with Biological Molecules

    DTIC Science & Technology

    1986-08-01

    study the binding of PDA to glutathione, meso-2,3-dimercapto- succinic acid ( DMSA ), and British anti-Lewisite (BAL). The results clearly show that PDA...spectroscopy ( C-NMR) was used to study the binding of PDA to glutathione, meso-2,3-dimercapto- succinic acid ( DMSA ), and British anti-Lewisite (BAL). The...PDAandBAL. . . . * . . . . . . . 5 PDA and BAL .a.io . . . . . . . . . 5PDA and Glutathione .. .. .. . .. 7 PDA and DMSA . . . .. ......... 10 CONCLUSIONS

  1. Mind Molecules

    PubMed Central

    Snyder, Solomon H.

    2011-01-01

    Scientific styles vary tremendously. For me, research is largely about the unfettered pursuit of novel ideas and experiments that can test multiple ideas in a day, not a year, an approach that I learned from my mentor Julius “Julie” Axelrod. This focus on creative conceptualizations has been my métier since working in the summers during medical school at the National Institutes of Health, during my two years in the Axelrod laboratory, and throughout my forty-five years at Johns Hopkins University School of Medicine. Equally important has been the “high” that emerges from brainstorming with my students. Nothing can compare with the eureka moments when, together, we sense new insights and, better yet, when high-risk, high-payoff experiments succeed. Although I have studied many different questions over the years, a common theme emerges: simple biochemical approaches to understanding molecular messengers, usually small molecules. Equally important has been identifying, purifying, and cloning the messengers' relevant biosynthetic, degradative, or target proteins, at all times seeking potential therapeutic relevance in the form of drugs. In the interests of brevity, this Reflections article is highly selective, and, with a few exceptions, literature citations are only of findings of our laboratory that illustrate notable themes. PMID:21543333

  2. Computational Systems Chemical Biology

    PubMed Central

    Oprea, Tudor I.; May, Elebeoba E.; Leitão, Andrei; Tropsha, Alexander

    2013-01-01

    There is a critical need for improving the level of chemistry awareness in systems biology. The data and information related to modulation of genes and proteins by small molecules continue to accumulate at the same time as simulation tools in systems biology and whole body physiologically-based pharmacokinetics (PBPK) continue to evolve. We called this emerging area at the interface between chemical biology and systems biology systems chemical biology, SCB (Oprea et al., 2007). The overarching goal of computational SCB is to develop tools for integrated chemical-biological data acquisition, filtering and processing, by taking into account relevant information related to interactions between proteins and small molecules, possible metabolic transformations of small molecules, as well as associated information related to genes, networks, small molecules and, where applicable, mutants and variants of those proteins. There is yet an unmet need to develop an integrated in silico pharmacology / systems biology continuum that embeds drug-target-clinical outcome (DTCO) triplets, a capability that is vital to the future of chemical biology, pharmacology and systems biology. Through the development of the SCB approach, scientists will be able to start addressing, in an integrated simulation environment, questions that make the best use of our ever-growing chemical and biological data repositories at the system-wide level. This chapter reviews some of the major research concepts and describes key components that constitute the emerging area of computational systems chemical biology. PMID:20838980

  3. Computational systems chemical biology.

    PubMed

    Oprea, Tudor I; May, Elebeoba E; Leitão, Andrei; Tropsha, Alexander

    2011-01-01

    There is a critical need for improving the level of chemistry awareness in systems biology. The data and information related to modulation of genes and proteins by small molecules continue to accumulate at the same time as simulation tools in systems biology and whole body physiologically based pharmacokinetics (PBPK) continue to evolve. We called this emerging area at the interface between chemical biology and systems biology systems chemical biology (SCB) (Nat Chem Biol 3: 447-450, 2007).The overarching goal of computational SCB is to develop tools for integrated chemical-biological data acquisition, filtering and processing, by taking into account relevant information related to interactions between proteins and small molecules, possible metabolic transformations of small molecules, as well as associated information related to genes, networks, small molecules, and, where applicable, mutants and variants of those proteins. There is yet an unmet need to develop an integrated in silico pharmacology/systems biology continuum that embeds drug-target-clinical outcome (DTCO) triplets, a capability that is vital to the future of chemical biology, pharmacology, and systems biology. Through the development of the SCB approach, scientists will be able to start addressing, in an integrated simulation environment, questions that make the best use of our ever-growing chemical and biological data repositories at the system-wide level. This chapter reviews some of the major research concepts and describes key components that constitute the emerging area of computational systems chemical biology.

  4. Nucleic Acids as Information Molecules.

    ERIC Educational Resources Information Center

    McInerney, Joseph D.

    1996-01-01

    Presents an activity that aims at enabling students to recognize that DNA and RNA are information molecules whose function is to store, copy, and make available the information in biological systems, without feeling overwhelmed by the specialized vocabulary and the minutia of the central dogma. (JRH)

  5. Nanodevices for Single Molecule Studies

    NASA Astrophysics Data System (ADS)

    Craighead, H. G.; Stavis, S. M.; Samiee, K. T.

    During the last two decades, biotechnology research has resulted in progress in fields as diverse as the life sciences, agriculture and healthcare. While existing technology enables the analysis of a variety of biological systems, new tools are needed for increasing the efficiency of current methods, and for developing new ones altogether. Interest has grown in single molecule analysis for these reasons.

  6. Nucleic Acids as Information Molecules.

    ERIC Educational Resources Information Center

    McInerney, Joseph D.

    1996-01-01

    Presents an activity that aims at enabling students to recognize that DNA and RNA are information molecules whose function is to store, copy, and make available the information in biological systems, without feeling overwhelmed by the specialized vocabulary and the minutia of the central dogma. (JRH)

  7. [Application of small molecule compounds inducing differentiation of stem cells].

    PubMed

    Li, Xia; Shan, Lei; Li, Wen-lin; Zhang, Shou-de; Zhang, Wei-dong

    2011-02-01

    With the development of stem cells and regenerative medicine (treatment of various diseases using stem cells) research, the induction of differentiation of human stem cell technology has also made significant progress. The development of chemical biology offers a variety of small biological molecules for stem cell biology. This review focuses on how small molecule compounds (natural and synthetic) induce differentiation of stem cells.

  8. Excitonic localization in AlN-rich Al{sub x}Ga{sub 1−x}N/Al{sub y}Ga{sub 1−y}N multi-quantum-well grain boundaries

    SciTech Connect

    Ajia, Idris A.; Roqan, I. S.; Edwards, P. R.; Martin, R. W.; Liu, Z.; Yan, J. C.

    2014-09-22

    AlGaN/AlGaN multi-quantum-wells (MQW) with AlN-rich grains have been grown by metal organic chemical vapor deposition. The grains are observed to have strong excitonic localization characteristics that are affected by their sizes. The tendency to confine excitons progressively intensifies with increasing grain boundary area. Photoluminescence results indicate that the MQW have a dominant effect on the peak energy of the near-bandedge emission at temperatures below 150 K, with the localization properties of the grains becoming evident beyond 150 K. Cathodoluminescence maps reveal that the grain boundary has no effect on the peak intensities of the AlGaN/AlGaN samples.

  9. Characterization of the interface abruptness of In 0.53Ga 0.47As/InP multi quantum wells by Raman spectroscopy, X-ray diffractometry and photoluminescence

    NASA Astrophysics Data System (ADS)

    Geurts, J.; Finders, J.; Woitok, J.; Gnoth, D.; Kohl, A.; Heime, K.

    1994-12-01

    For lattice-matched InGaAs/InP multi quantum well structures, the interface abruptness was investigated by a combination of X-ray diffractometry, Raman spectroscopy and photoluminescence. The focus was on the effects of the gas switching parameters at the InGaAs-to-InP interface, especially the PH 3 and H 2 purging times. Ternary InAsP and quaternary InGaAsP interface layers due to carry-over and exchange effects were directly identified. Their thicknesses drastically depend on the PH 3 purging time. H 2 purging affects the interface quality to some degree, but it has only minor effects on the chemical composition at the interfaces.

  10. Single-molecule studies of DNA mechanics.

    PubMed

    Bustamante, C; Smith, S B; Liphardt, J; Smith, D

    2000-06-01

    During the past decade, physical techniques such as optical tweezers and atomic force microscopy were used to study the mechanical properties of DNA at the single-molecule level. Knowledge of DNA's stretching and twisting properties now permits these single-molecule techniques to be used in the study of biological processes such as DNA replication and transcription.

  11. Correction: El Azab, I.H., et al. Microwave-Assisted Synthesis of Novel 2H-Chromene Derivatives Bearing Phenylthiazolidinones and Their Biological Activity Assessment. Molecules 2014, 19, 19648-19664.

    PubMed

    El Azab, Islam H; Youssef, Mohamed M; Amin, Amin M

    2015-02-09

    The authors wish to revise the Author Affiliation section of the title paper, published in Molecules [1], (doi:10.3390/molecules191219648, website: http://www.mdpi.com/1420-3049/19/12/19648). To recognize the fact that the research described was performed in part at the facilities of Taif University and to acknowledge that institution's generous financial support[...].

  12. Models for synthetic biology

    PubMed Central

    Kaznessis, Yiannis N

    2007-01-01

    Synthetic biological engineering is emerging from biology as a distinct discipline based on quantification. The technologies propelling synthetic biology are not new, nor is the concept of designing novel biological molecules. What is new is the emphasis on system behavior. The objective is the design and construction of new biological devices and systems to deliver useful applications. Numerous synthetic gene circuits have been created in the past decade, including bistable switches, oscillators, and logic gates, and possible applications abound, including biofuels, detectors for biochemical and chemical weapons, disease diagnosis, and gene therapies. More than fifty years after the discovery of the molecular structure of DNA, molecular biology is mature enough for real quantification that is useful for biological engineering applications, similar to the revolution in modeling in chemistry in the 1950s. With the excitement that synthetic biology is generating, the engineering and biological science communities appear remarkably willing to cross disciplinary boundaries toward a common goal. PMID:17986347

  13. Single-Molecule Studies in Live Cells.

    PubMed

    Yu, Ji

    2016-05-27

    Live-cell single-molecule experiments are now widely used to study complex biological processes such as signal transduction, self-assembly, active trafficking, and gene regulation. These experiments' increased popularity results in part from rapid methodological developments that have significantly lowered the technical barriers to performing them. Another important advance is the development of novel statistical algorithms, which, by modeling the stochastic behaviors of single molecules, can be used to extract systemic parameters describing the in vivo biochemistry or super-resolution localization of biological molecules within their physiological environment. This review discusses recent advances in experimental and computational strategies for live-cell single-molecule studies, as well as a selected subset of biological studies that have utilized these new technologies.

  14. Small Molecule CXCR3 Antagonists.

    PubMed

    Andrews, Stephen P; Cox, Rhona J

    2016-04-14

    Chemokines and their receptors are known to play important roles in disease. More than 40 chemokine ligands and 20 chemokine receptors have been identified, but, to date, only two small molecule chemokine receptor antagonists have been approved by the FDA. The chemokine receptor CXCR3 was identified in 1996, and nearly 20 years later, new areas of CXCR3 disease biology continue to emerge. Several classes of small molecule CXCR3 antagonists have been developed, and two have shown efficacy in preclinical models of inflammatory disease. However, only one CXCR3 antagonist has been evaluated in clinical trials, and there remain many opportunities to further investigate known classes of CXCR3 antagonists and to identify new chemotypes. This Perspective reviews the known CXCR3 antagonists and considers future opportunities for the development of small molecules for clinical evaluation.

  15. Spectroscopic (FT-IR, FT-Raman, UV, 1H and 13C NMR) profiling and computational studies on methyl 5-methoxy-1H-indole-2-carboxylate: A potential precursor to biologically active molecules

    NASA Astrophysics Data System (ADS)

    Almutairi, Maha S.; Xavier, S.; Sathish, M.; Ghabbour, Hazem A.; Sebastian, S.; Periandy, S.; Al-Wabli, Reem I.; Attia, Mohamed I.

    2017-04-01

    Methyl 5-methoxy-1H-indole-2-carboxylate (MMIC) was prepared via esterification of commercially available 5-methoxyindole-2-carboxylic acid. The title molecule MMIC was characterised using FT-IR and FT-Raman in the ranges of 4000-500 and 4000-50 cm-1, respectively. The fundamental modes of the vibrations were assigned and the UV-visible spectrum of the MMIC molecule was recorded in the range of 200-400 nm to explore its electronic nature. The HOMO-LUMO energy distribution was calculated and the bonding and anti-bonding structures of the title molecule were studied and analysed using the natural bond orbital (NBO) approach. The reactivity of the MMIC molecule was also investigated and both the positive and negative centres of the molecule were identified using chemical descriptors and molecular electrostatic potential (MEP) analysis. The chemical shifts of the 1H and 13C NMR spectra were noted and the magnetic field environment of the MMIC molecule are discussed. The non-linear optical (NLO) properties of the title molecule were studied based on its calculated values of polarisability and hyperpolarisability. All computations were obtained by DFT methods using the 6-311++G (d,p) basis set.

  16. Superresolution Imaging using Single-Molecule Localization

    PubMed Central

    Patterson, George; Davidson, Michael; Manley, Suliana; Lippincott-Schwartz, Jennifer

    2013-01-01

    Superresolution imaging is a rapidly emerging new field of microscopy that dramatically improves the spatial resolution of light microscopy by over an order of magnitude (∼10–20-nm resolution), allowing biological processes to be described at the molecular scale. Here, we discuss a form of superresolution microscopy based on the controlled activation and sampling of sparse subsets of photoconvertible fluorescent molecules. In this single-molecule based imaging approach, a wide variety of probes have proved valuable, ranging from genetically encodable photoactivatable fluorescent proteins to photoswitchable cyanine dyes. These have been used in diverse applications of superresolution imaging: from three-dimensional, multicolor molecule localization to tracking of nanometric structures and molecules in living cells. Single-molecule-based superresolution imaging thus offers exciting possibilities for obtaining molecular-scale information on biological events occurring at variable timescales. PMID:20055680

  17. Molecule by molecule, the physics and chemistry of life: SMB 2007.

    PubMed

    Block, Steven M; Larson, Matthew H; Greenleaf, William J; Herbert, Kristina M; Guydosh, Nicholas R; Anthony, Peter C

    2007-04-01

    Interdisciplinary work in the life sciences at the boundaries of biology, chemistry and physics is making enormous strides. This progress was showcased at the recent Single Molecule Biophysics conference.

  18. Molecule by molecule, the physics and chemistry of life: SMB 2007

    PubMed Central

    Block, Steven M; Larson, Matthew H; Greenleaf, William J; Herbert, Kristina M; Guydosh, Nicholas R; Anthony, Peter C

    2007-01-01

    Interdisciplinary work in the life sciences at the boundaries of biology, chemistry and physics is making enormous strides. This progress was showcased at the recent Single Molecule Biophysics conference. PMID:17372599

  19. Physics of Molecules

    NASA Astrophysics Data System (ADS)

    Williams, D.; Murdin, P.

    2000-11-01

    Many varieties of molecule have been detected in the Milky Way and in other galaxies. The processes by which these molecules are formed and destroyed are now broadly understood (see INTERSTELLAR CHEMISTRY). These molecules are important components of galaxies in two ways. Firstly, radiation emitted by molecules enables us to trace the presence of diffuse gas, to infer its physical properties and ...

  20. Analyzing single-molecule manipulation experiments.

    PubMed

    Calderon, Christopher P; Harris, Nolan C; Kiang, Ching-Hwa; Cox, Dennis D

    2009-01-01

    Single-molecule manipulation studies can provide quantitative information about the physical properties of complex biological molecules without ensemble artifacts obscuring the measurements. We demonstrate computational techniques which aim at more fully utilizing the wealth of information contained in noisy experimental time series. The "noise" comes from multiple sources e.g., inherent thermal motion, instrument measurement error, etc. The primary focus of this paper is a methodology that uses time domain based methods to extract the effective molecular friction from single-molecule pulling data. We studied molecules composed of eight tandem repeat titin I27 domains, but the modeling approaches have applicability to other single-molecule mechanical studies. The merits and challenges associated with applying such a computational approach to existing single-molecule manipulation data are also discussed. Copyright (c) 2009 John Wiley & Sons, Ltd.

  1. Aggregated Gas Molecules: Toxic to Protein?

    PubMed Central

    Zhang, Meng; Zuo, Guanghong; Chen, Jixiu; Gao, Yi; Fang, Haiping

    2013-01-01

    The biological toxicity of high levels of breathing gases has been known for centuries, but the mechanism remains elusive. Earlier work mainly focused on the influences of dispersed gas molecules dissolved in water on biomolecules. However, recent studies confirmed the existence of aggregated gas molecules at the water-solid interface. In this paper, we have investigated the binding preference of aggregated gas molecules on proteins with molecular dynamics simulations, using nitrogen (N2) gas and the Src-homology 3 (SH3) domain as the model system. Aggregated N2 molecules were strongly bound by the active sites of the SH3 domain, which could impair the activity of the protein. In contrast, dispersed N2 molecules did not specifically interact with the SH3 domain. These observations extend our understanding of the possible toxicity of aggregates of gas molecules in the function of proteins. PMID:23588597

  2. Chemical biology at the crossroads of molecular structure and mechanism.

    PubMed

    Doudna, Jennifer A

    2005-11-01

    Chemical insight into biological function is the holy grail of structural biology. Small molecules are central players as building blocks, effectors and probes of macromolecular structure and function.

  3. Formation properties of an InGaN active layer for high-efficiency InGaN/GaN multi-quantum-well-nanowire light-emitting diodes

    NASA Astrophysics Data System (ADS)

    Hwang, Sung Won; Lee, Bongsoo; Choi, Suk-Ho

    2016-09-01

    Nitride-based nanowires (NWs) have several advantages, such as flexibility in choosing a substrate, easy fabrication, large light-emitting area, no internal electric field, enhanced light extraction, and reduced defects by strain relief, that are useful for enhancing the efficiency of light-emitting diodes (LEDs). Here, we report how crucial the formation properties of the InGaN active layer are for enhancing the efficiency of core-shell InGaN/GaN multi-quantum-well (MQW)-NW LEDs that are selectively grown on oxide templates with perfectly-circular hole patterns. The nanostructures are analyzed for two types of LEDs, one containing defect-free MQW active layer and the other containing MQW layer with defects by using high-resolution transmission electron microscopy. The I-V curve of the defect-free LED shows a rectifying behavior with an on/off ratio of ~109, typical of a diode, and the off-state leakage current of the LED with defects is much larger than that of the defect-free LED, resulting in brighter electroluminescence from the latter device. These results suggest that well-defined nonpolar InGaN/GaN MQW-NWs can be utilized for the realization of high-performance LEDs.

  4. CROSS-DISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY: Wavelength Red-Shift of Long Wavelength InGaN/GaN Multi-Quantum Well by Using an InGaN Underlying Layer

    NASA Astrophysics Data System (ADS)

    Huang, Li-Rong; Wen, Feng; Tong, Liang-Zhu; Huang, De-Xiu

    2009-07-01

    Long-wavelength GaN based light-emitting diodes are of importance in full color displays, monolithic white light- emitting diodes and solid-state lighting, etc. However, their epitaxial growth faces great challenges because high indium (In) compositions of InGaN are difficult to grow. In order to enhance In incorporation and lengthen the emission wavelength of a InGaN/GaN multi-quantum well (MQW), we insert an InGaN underlying layer underneath the MQW. InGaN/GaN MQWs with various InGaN underlying layers, such as graded InyGa1-yN material with linearly increasing In content, or InyGa1-yN with fixed In content but different thicknesses, are grown by metal-organic chemical vapor deposition. Experimental results demonstrate the enhancement of In incorporation and the emission wavelength redshift by the insertion of an InGaN underlying layer.

  5. Nanoscale imaging of InN segregation and polymorphism in single vertically aligned InGaN/GaN multi quantum well nanorods by tip-enhanced Raman scattering.

    PubMed

    Poliani, E; Wagner, M R; Reparaz, J S; Mandl, M; Strassburg, M; Kong, X; Trampert, A; Sotomayor Torres, C M; Hoffmann, A; Maultzsch, J

    2013-07-10

    Vertically aligned GaN nanorod arrays with nonpolar InGaN/GaN multi quantum wells (MQW) were grown by MOVPE on c-plane GaN-on-sapphire templates. The chemical and structural properties of single nanorods are optically investigated with a spatial resolution beyond the diffraction limit using tip-enhanced Raman spectroscopy (TERS). This enables the local mapping of variations in the chemical composition, charge distribution, and strain in the MQW region of the nanorods. Nanoscale fluctuations of the In content in the InGaN layer of a few percent can be identified and visualized with a lateral resolution below 35 nm. We obtain evidence for the presence of indium clustering and the formation of cubic inclusions in the wurtzite matrix near the QW layers. These results are directly confirmed by high-resolution TEM images, revealing the presence of stacking faults and different polymorphs close to the surface near the MQW region. The combination of TERS and HRTEM demonstrates the potential of this nanoscale near-field imaging technique, establishing TERS as a very potent, comprehensive, and nondestructive tool for the characterization and optimization of technologically relevant semiconductor nanostructures.

  6. Targeting the undruggable proteome: the small molecules of my dreams.

    PubMed

    Crews, Craig M

    2010-06-25

    Biologically active small molecules have long proven useful in the exploration of cell biology. Although many early compounds were by-products of drug development efforts, recent increased small molecule screening efforts in academia have expanded the repertoire of biological processes investigated to include areas of biology that are not of immediate pharmaceutical interest. Many of these new bioassays score for small molecule-induced phenotypic changes at the cellular or even organismal level and thus have been described as "chemical genetic" screens. However, this analogy with traditional genetic screens is misleading; although each gene has roughly an equivalent chance of being mutated in a traditional genetic screen, the amount of "proteomic space" that a chemical genetics approach can reach using current small molecule libraries is considerably smaller. Thus, new chemical biology methodologies are needed to target the remaining "undruggable proteome" with small druglike molecules.

  7. The Molecule Cloud - compact visualization of large collections of molecules.

    PubMed

    Ertl, Peter; Rohde, Bernhard

    2012-07-06

    Analysis and visualization of large collections of molecules is one of the most frequent challenges cheminformatics experts in pharmaceutical industry are facing. Various sophisticated methods are available to perform this task, including clustering, dimensionality reduction or scaffold frequency analysis. In any case, however, viewing and analyzing large tables with molecular structures is necessary. We present a new visualization technique, providing basic information about the composition of molecular data sets at a single glance. A method is presented here allowing visual representation of the most common structural features of chemical databases in a form of a cloud diagram. The frequency of molecules containing particular substructure is indicated by the size of respective structural image. The method is useful to quickly perceive the most prominent structural features present in the data set. This approach was inspired by popular word cloud diagrams that are used to visualize textual information in a compact form. Therefore we call this approach "Molecule Cloud". The method also supports visualization of additional information, for example biological activity of molecules containing this scaffold or the protein target class typical for particular scaffolds, by color coding. Detailed description of the algorithm is provided, allowing easy implementation of the method by any cheminformatics toolkit. The layout algorithm is available as open source Java code. Visualization of large molecular data sets using the Molecule Cloud approach allows scientists to get information about the composition of molecular databases and their most frequent structural features easily. The method may be used in the areas where analysis of large molecular collections is needed, for example processing of high throughput screening results, virtual screening or compound purchasing. Several example visualizations of large data sets, including PubChem, ChEMBL and ZINC databases using

  8. Target molecules detection by waveguiding in a photonic silicon membrane

    DOEpatents

    Letant, Sonia; Van Buuren, Anthony; Terminello, Louis

    2004-08-31

    Disclosed herein is a photonic silicon filter capable of binding and detecting biological and chemical target molecules in liquid or gas samples. A photonic waveguiding silicon filter with chemical and/or biological anchors covalently attached to the pore walls selectively bind target molecules. The system uses transmission curve engineering principles to allow measurements to be made in situ and in real time to detect the presence of various target molecules and determine the concentration of bound target.

  9. Target molecules detection by waveguiding in a photonic silicon membrane

    DOEpatents

    Letant, Sonia E.; Van Buuren, Anthony; Terminello, Louis; Hart, Bradley R.

    2006-12-26

    Disclosed herein is a porous silicon filter capable of binding and detecting biological and chemical target molecules in liquid or gas samples. A photonic waveguiding silicon filter with chemical and/or biological anchors covalently attached to the pore walls bind target molecules. The system uses transmission curve engineering principles to allow measurements to be made in situ and in real time to detect the presence of various target molecules and calculate the concentration of bound target.

  10. Torque Measurement at the Single Molecule Level

    PubMed Central

    Forth, Scott; Sheinin, Maxim Y.; Inman, James; Wang, Michelle D.

    2017-01-01

    Methods for exerting and measuring forces on single molecules have revolutionized the study of the physics of biology. However, it is often the case that biological processes involve rotation or torque generation, and these parameters have been more difficult to access experimentally. Recent advances in the single molecule field have led to the development of techniques which add the capability of torque measurement. By combining force, displacement, torque, and rotational data, a more comprehensive description of the mechanics of a biomolecule can be achieved. In this review, we highlight a number of biological processes for which torque plays a key mechanical role. We describe the various techniques that have been developed to directly probe the torque experienced by a single molecule, and detail a variety of measurements made to date using these new technologies. We conclude by discussing a number of open questions and propose systems of study which would be well suited for analysis with torsional measurement techniques. PMID:23541162

  11. Biological spectra analysis: Linking biological activity profiles to molecular structure

    PubMed Central

    Fliri, Anton F.; Loging, William T.; Thadeio, Peter F.; Volkmann, Robert A.

    2005-01-01

    Establishing quantitative relationships between molecular structure and broad biological effects has been a longstanding challenge in science. Currently, no method exists for forecasting broad biological activity profiles of medicinal agents even within narrow boundaries of structurally similar molecules. Starting from the premise that biological activity results from the capacity of small organic molecules to modulate the activity of the proteome, we set out to investigate whether descriptor sets could be developed for measuring and quantifying this molecular property. Using a 1,567-compound database, we show that percent inhibition values, determined at single high drug concentration in a battery of in vitro assays representing a cross section of the proteome, provide precise molecular property descriptors that identify the structure of molecules. When broad biological activity of molecules is represented in spectra form, organic molecules can be sorted by quantifying differences between biological spectra. Unlike traditional structure–activity relationship methods, sorting of molecules by using biospectra comparisons does not require knowledge of a molecule's putative drug targets. To illustrate this finding, we selected as starting point the biological activity spectra of clotrimazole and tioconazole because their putative target, lanosterol demethylase (CYP51), was not included in the bioassay array. Spectra similarity obtained through profile similarity measurements and hierarchical clustering provided an unbiased means for establishing quantitative relationships between chemical structures and biological activity spectra. This methodology, which we have termed biological spectra analysis, provides the capability not only of sorting molecules on the basis of biospectra similarity but also of predicting simultaneous interactions of new molecules with multiple proteins. PMID:15625110

  12. Systems biology, adverse outcome pathways, and ecotoxicology in the 21st century

    EPA Science Inventory

    While many definitions of systems biology exist, the majority of these contain most (if not all) of the following elements: global measurements of biological molecules to the extent technically feasible, dynamic measurements of key biological molecules to establish quantitative r...

  13. Systems biology, adverse outcome pathways, and ecotoxicology in the 21st century

    EPA Science Inventory

    While many definitions of systems biology exist, the majority of these contain most (if not all) of the following elements: global measurements of biological molecules to the extent technically feasible, dynamic measurements of key biological molecules to establish quantitative r...

  14. Ultrafast dynamics of single molecules.

    PubMed

    Brinks, Daan; Hildner, Richard; van Dijk, Erik M H P; Stefani, Fernando D; Nieder, Jana B; Hernando, Jordi; van Hulst, Niek F

    2014-04-21

    The detection of individual molecules has found widespread application in molecular biology, photochemistry, polymer chemistry, quantum optics and super-resolution microscopy. Tracking of an individual molecule in time has allowed identifying discrete molecular photodynamic steps, action of molecular motors, protein folding, diffusion, etc. down to the picosecond level. However, methods to study the ultrafast electronic and vibrational molecular dynamics at the level of individual molecules have emerged only recently. In this review we present several examples of femtosecond single molecule spectroscopy. Starting with basic pump-probe spectroscopy in a confocal detection scheme, we move towards deterministic coherent control approaches using pulse shapers and ultra-broad band laser systems. We present the detection of both electronic and vibrational femtosecond dynamics of individual fluorophores at room temperature, showing electronic (de)coherence, vibrational wavepacket interference and quantum control. Finally, two colour phase shaping applied to photosynthetic light-harvesting complexes is presented, which allows investigation of the persistent coherence in photosynthetic complexes under physiological conditions at the level of individual complexes.

  15. Small molecule inhibitors of ebola virus infection.

    PubMed

    Picazo, Edwige; Giordanetto, Fabrizio

    2015-02-01

    Ebola viruses are extremely virulent and highly transmissible. They are responsible for sporadic outbreaks of severe hemorrhagic fevers with human mortality rates of up to 90%. No prophylactic or therapeutic treatments in the form of vaccine, biologicals or small molecule, currently exist. Yet, a wealth of antiviral research on ebola virus is being generated and potential inhibitors have been identified in biological screening and medicinal chemistry programs. Here, we detail the state-of-the-art in small molecule inhibitors of ebola virus infection, with >60 examples, including approved drugs, compounds currently in clinical trials, and more exploratory leads, and summarize the associated in vitro and in vivo evidence for their effectiveness.

  16. The origin of life. [genetically important molecules

    NASA Technical Reports Server (NTRS)

    Horowitz, N. H.; Hubbard, J. S.

    1974-01-01

    Research in the areas of precambrian paleontology, chemical evolution of genetically important monomers, prebiotic dehydration-condensation reactions, organic compounds in meteorites and interstellar space, and biological exploration of the planets is summarized. Fossils in precambrian cherts and findings of eukaryotic cells are described, and recent investigations of prebiotic conditions, energy sources, and starting materials for genetic molecules are outlined. Studies of homogeneous and heterogeneous dehydrations and of nonaqueous thermal dehydrations are described. The detection of amino acids, purines, and pyrimidines in meteorites and of biologically significant molecules in interstellar clouds is discussed, as well as the possibilities of life on Jupiter, Mars, and Titan.

  17. The origin of life. [genetically important molecules

    NASA Technical Reports Server (NTRS)

    Horowitz, N. H.; Hubbard, J. S.

    1974-01-01

    Research in the areas of precambrian paleontology, chemical evolution of genetically important monomers, prebiotic dehydration-condensation reactions, organic compounds in meteorites and interstellar space, and biological exploration of the planets is summarized. Fossils in precambrian cherts and findings of eukaryotic cells are described, and recent investigations of prebiotic conditions, energy sources, and starting materials for genetic molecules are outlined. Studies of homogeneous and heterogeneous dehydrations and of nonaqueous thermal dehydrations are described. The detection of amino acids, purines, and pyrimidines in meteorites and of biologically significant molecules in interstellar clouds is discussed, as well as the possibilities of life on Jupiter, Mars, and Titan.

  18. Single Molecule Studies on Dynamics in Liquid Crystals

    PubMed Central

    Täuber, Daniela; von Borczyskowski, Christian

    2013-01-01

    Single molecule (SM) methods are able to resolve structure related dynamics of guest molecules in liquid crystals (LC). Highly diluted small dye molecules on the one hand explore structure formation and LC dynamics, on the other hand they report about a distortion caused by the guest molecules. The anisotropic structure of LC materials is used to retrieve specific conformation related properties of larger guest molecules like conjugated polymers. This in particular sheds light on organization mechanisms within biological cells, where large molecules are found in nematic LC surroundings. This review gives a short overview related to the application of highly sensitive SM detection schemes in LC. PMID:24077123

  19. Single-molecule detection: applications to ultrasensitive biochemical analysis

    NASA Astrophysics Data System (ADS)

    Castro, Alonso; Shera, E. Brooks

    1995-06-01

    Recent developments in laser-based detection of fluorescent molecules have made possible the implementation of very sensitive techniques for biochemical analysis. We present and discuss our experiments on the applications of our recently developed technique of single-molecule detection to the analysis of molecules of biological interest. These newly developed methods are capable of detecting and identifying biomolecules at the single-molecule level of sensitivity. In one case, identification is based on measuring fluorescence brightness from single molecules. In another, molecules are classified by determining their electrophoretic velocities.

  20. Life at the Single Molecule Level

    SciTech Connect

    Xie, Xiaoliang Sunny

    2011-03-04

    In a living cell, gene expression—the transcription of DNA to messenger RNA followed by translation to protein—occurs stochastically, as a consequence of the low copy number of DNA and mRNA molecules involved. Can one monitor these processes in a living cell in real time? How do cells with identical genes exhibit different phenotypes? Recent advances in single-molecule imaging in living bacterial cells allow these questions to be answered at the molecular level in a quantitative manner. It was found that rare events of single molecules can have important biological consequences.

  1. Performance enhancement of blue light-emitting diodes with InGaN/GaN multi-quantum wells grown on Si substrates by inserting thin AlGaN interlayers

    NASA Astrophysics Data System (ADS)

    Kimura, Shigeya; Yoshida, Hisashi; Uesugi, Kenjiro; Ito, Toshihide; Okada, Aoi; Nunoue, Shinya

    2016-09-01

    We have grown blue light-emitting diodes (LEDs) having InGaN/GaN multi-quantum wells (MQWs) with thin AlyGa1-yN (0 < y < 0.3) interlayers on Si(111) substrates. It was found by high-resolution transmission electron microscopy observations and three-dimensional atom probe analysis that 1-nm-thick interlayers with an AlN mole fraction of less than y = 0.3 were continuously formed between GaN barriers and InGaN wells, and that the AlN mole fraction up to y = 0.15 could be consistently controlled. The external quantum efficiency of the blue LED was enhanced in the low-current-density region (≤45 A/cm2) but reduced in the high-current-density region by the insertion of the thin Al0.15Ga0.85N interlayers in the MQWs. We also found that reductions in both forward voltage and wavelength shift with current were achieved by inserting the interlayers even though the inserted AlGaN layers had potential higher than that of the GaN barriers. The obtained peak wall-plug efficiency was 83% at room temperature. We suggest that the enhanced electroluminescence (EL) performance was caused by the introduction of polarization-induced hole carriers in the InGaN wells on the side adjacent to the thin AlGaN/InGaN interface and efficient electron carrier transport through multiple wells. This model is supported by temperature-dependent EL properties and band-diagram simulations. We also found that inserting the interlayers brought about a reduction in the Shockley-Read-Hall nonradiative recombination component, corresponding to the shrinkage of V-defects. This is another conceivable reason for the observed performance enhancement.

  2. InGaN/GaN multi-quantum well and LED growth on wafer-bonded sapphire-on-polycrystalline AlN substrates by metalorganic chemical vapor deposition.

    SciTech Connect

    Crawford, Mary Hagerott; Olson, S. M.; Banas, M.; Park, Y. -B.; Ladous, C.; Russell, Michael J.; Thaler, Gerald; Zahler, J. M.; Pinnington, T.; Koleske, Daniel David; Atwater, Harry A.

    2008-06-01

    We report growth of InGaN/GaN multi-quantum well (MQW) and LED structures on a novel composite substrate designed to eliminate the coefficient of thermal expansion (CTE) mismatch problems which impact GaN growth on bulk sapphire. To form the composite substrate, a thin sapphire layer is wafer-bonded to a polycrystalline aluminum nitride (P-AlN) support substrate. The sapphire layer provides the epitaxial template for the growth; however, the thermo-mechanical properties of the composite substrate are determined by the P-AlN. Using these substrates, thermal stresses associated with temperature changes during growth should be reduced an order of magnitude compared to films grown on bulk sapphire, based on published CTE data. In order to test the suitability of the substrates for GaN LED growth, test structures were grown by metalorganic chemical vapor deposition (MOCVD) using standard process conditions for GaN growth on sapphire. Bulk sapphire substrates were included as control samples in all growth runs. In situ reflectance monitoring was used to compare the growth dynamics for the different substrates. The material quality of the films as judged by X-ray diffraction (XRD), photoluminescence and transmission electron microscopy (TEM) was similar for the composite substrate and the sapphire control samples. Electroluminescence was obtained from the LED structure grown on a P-AlN composite substrate, with a similar peak wavelength and peak width to the control samples. XRD and Raman spectroscopy results confirm that the residual strain in GaN films grown on the composite substrates is dramatically reduced compared to growth on bulk sapphire substrates.

  3. Wafer-scale controlled exfoliation of metal organic vapor phase epitaxy grown InGaN/GaN multi quantum well structures using low-tack two-dimensional layered h-BN

    NASA Astrophysics Data System (ADS)

    Ayari, Taha; Sundaram, Suresh; Li, Xin; El Gmili, Youssef; Voss, Paul L.; Salvestrini, Jean Paul; Ougazzaden, Abdallah

    2016-04-01

    Recent advances in epitaxial growth have led to the growth of III-nitride devices on 2D layered h-BN. This advance has the potential for wafer-scale transfer to arbitrary substrates, which could improve the thermal management and would allow III-N devices to be used more flexibly in a broader range of applications. We report wafer scale exfoliation of a metal organic vapor phase epitaxy grown InGaN/GaN Multi Quantum Well (MQW) structure from a 5 nm thick h-BN layer that was grown on a 2-inch sapphire substrate. The weak van der Waals bonds between h-BN atomic layers break easily, allowing the MQW structure to be mechanically lifted off from the sapphire substrate using a commercial adhesive tape. This results in the surface roughness of only 1.14 nm on the separated surface. Structural characterizations performed before and after the lift-off confirm the conservation of structural properties after lift-off. Cathodoluminescence at 454 nm was present before lift-off and 458 nm was present after. Electroluminescence near 450 nm from the lifted-off structure has also been observed. These results show that the high crystalline quality ultrathin h-BN serves as an effective sacrificial layer—it maintains performance, while also reducing the GaN buffer thickness and temperature ramps as compared to a conventional two-step growth method. These results support the use of h-BN as a low-tack sacrificial underlying layer for GaN-based device structures and demonstrate the feasibility of large area lift-off and transfer to any template, which is important for industrial scale production.

  4. Wafer-scale controlled exfoliation of metal organic vapor phase epitaxy grown InGaN/GaN multi quantum well structures using low-tack two-dimensional layered h-BN

    SciTech Connect

    Ayari, Taha; Li, Xin; Voss, Paul L.; Ougazzaden, Abdallah; Sundaram, Suresh; El Gmili, Youssef; Salvestrini, Jean Paul

    2016-04-25

    Recent advances in epitaxial growth have led to the growth of III-nitride devices on 2D layered h-BN. This advance has the potential for wafer-scale transfer to arbitrary substrates, which could improve the thermal management and would allow III-N devices to be used more flexibly in a broader range of applications. We report wafer scale exfoliation of a metal organic vapor phase epitaxy grown InGaN/GaN Multi Quantum Well (MQW) structure from a 5 nm thick h-BN layer that was grown on a 2-inch sapphire substrate. The weak van der Waals bonds between h-BN atomic layers break easily, allowing the MQW structure to be mechanically lifted off from the sapphire substrate using a commercial adhesive tape. This results in the surface roughness of only 1.14 nm on the separated surface. Structural characterizations performed before and after the lift-off confirm the conservation of structural properties after lift-off. Cathodoluminescence at 454 nm was present before lift-off and 458 nm was present after. Electroluminescence near 450 nm from the lifted-off structure has also been observed. These results show that the high crystalline quality ultrathin h-BN serves as an effective sacrificial layer—it maintains performance, while also reducing the GaN buffer thickness and temperature ramps as compared to a conventional two-step growth method. These results support the use of h-BN as a low-tack sacrificial underlying layer for GaN-based device structures and demonstrate the feasibility of large area lift-off and transfer to any template, which is important for industrial scale production.

  5. 7th Annual Systems Biology Symposium: Systems Biology and Engineering

    SciTech Connect

    Galitski, Timothy P.

    2008-04-01

    Systems biology recognizes the complex multi-scale organization of biological systems, from molecules to ecosystems. The International Symposium on Systems Biology has been hosted by the Institute for Systems Biology in Seattle, Washington, since 2002. The annual two-day event gathers the most influential researchers transforming biology into an integrative discipline investingating complex systems. Engineering and application of new technology is a central element of systems biology. Genome-scale, or very small-scale, biological questions drive the enigneering of new technologies, which enable new modes of experimentation and computational analysis, leading to new biological insights and questions. Concepts and analytical methods in engineering are now finding direct applications in biology. Therefore, the 2008 Symposium, funded in partnership with the Department of Energy, featured global leaders in "Systems Biology and Engineering."

  6. Synthetic biology: insights into biological computation.

    PubMed

    Manzoni, Romilde; Urrios, Arturo; Velazquez-Garcia, Silvia; de Nadal, Eulàlia; Posas, Francesc

    2016-04-18

    Organisms have evolved a broad array of complex signaling mechanisms that allow them to survive in a wide range of environmental conditions. They are able to sense external inputs and produce an output response by computing the information. Synthetic biology attempts to rationally engineer biological systems in order to perform desired functions. Our increasing understanding of biological systems guides this rational design, while the huge background in electronics for building circuits defines the methodology. In this context, biocomputation is the branch of synthetic biology aimed at implementing artificial computational devices using engineered biological motifs as building blocks. Biocomputational devices are defined as biological systems that are able to integrate inputs and return outputs following pre-determined rules. Over the last decade the number of available synthetic engineered devices has increased exponentially; simple and complex circuits have been built in bacteria, yeast and mammalian cells. These devices can manage and store information, take decisions based on past and present inputs, and even convert a transient signal into a sustained response. The field is experiencing a fast growth and every day it is easier to implement more complex biological functions. This is mainly due to advances in in vitro DNA synthesis, new genome editing tools, novel molecular cloning techniques, continuously growing part libraries as well as other technological advances. This allows that digital computation can now be engineered and implemented in biological systems. Simple logic gates can be implemented and connected to perform novel desired functions or to better understand and redesign biological processes. Synthetic biological digital circuits could lead to new therapeutic approaches, as well as new and efficient ways to produce complex molecules such as antibiotics, bioplastics or biofuels. Biological computation not only provides possible biomedical and

  7. Formation of Ultracold Molecules

    SciTech Connect

    Cote, Robin

    2016-01-28

    Advances in our ability to slow down and cool atoms and molecules to ultracold temperatures have paved the way to a revolution in basic research on molecules. Ultracold molecules are sensitive of very weak interactions, even when separated by large distances, which allow studies of the effect of those interactions on the behavior of molecules. In this program, we have explored ways to form ultracold molecules starting from pairs of atoms that have already reached the ultracold regime. We devised methods that enhance the efficiency of ultracold molecule production, for example by tuning external magnetic fields and using appropriate laser excitations. We also investigates the properties of those ultracold molecules, especially their de-excitation into stable molecules. We studied the possibility of creating new classes of ultra-long range molecules, named macrodimers, thousand times more extended than regular molecules. Again, such objects are possible because ultra low temperatures prevent their breakup by collision. Finally, we carried out calculations on how chemical reactions are affected and modified at ultracold temperatures. Normally, reactions become less effective as the temperature decreases, but at ultracold temperatures, they can become very effective. We studied this counter-intuitive behavior for benchmark chemical reactions involving molecular hydrogen.

  8. Surface-assisted laser desorption/ionization time-of-flight mass spectrometry of small drug molecules and high molecular weight synthetic/biological polymers using electrospun composite nanofibers.

    PubMed

    Bian, Juan; Olesik, Susan V

    2017-03-27

    Polyacrylonitrile/Nafion®/carbon nanotube (PAN/Nafion®/CNT) composite nanofibers were prepared using electrospinning. These electrospun nanofibers were studied as possible substrates for surface-assisted laser desorption/ionization (SALDI) and matrix-enhanced surface-assisted laser desorption/ionization time-of-flight mass spectrometry (ME-SALDI/TOF-MS) for the first time in this paper. Electrospinning provides this novel substrate with a uniform morphology and a narrow size distribution, where CNTs were evenly and firmly immobilized on polymeric nanofibers. The results show that PAN/Nafion®/CNT nanofibrous mats are good substrates for the analysis of both small drug molecules and high molecular weight polymers with high sensitivity. Markedly improved reproducibility was observed relative to MALDI. Due to the composite formation between the polymers and the CNTs, no contamination of the carbon nanotubes to the mass spectrometer was observed. Furthermore, electrospun nanofibers used as SALDI substrates greatly extended the duration of ion signals of target analytes compared to the MALDI matrix. The proposed SALDI approach was successfully used to quantify small drug molecules with no interference in the low mass range. The results show that verapamil could be detected with a surface concentration of 220 femtomoles, indicating the high detection sensitivity of this method. Analysis of peptides and proteins with the electrospun composite substrate using matrix assisted-SALDI was improved and a low limit of detection of approximately 6 femtomoles was obtained for IgG. Both SALDI and ME-SALDI analyses displayed high reproducibility with %RSD ≤ 9% for small drug molecules and %RSD ≤ 14% for synthetic polymers and proteins.

  9. New platinum(II) complexes conjugated at position 7α of 17β-acetyl-testosterone as new combi-molecules against prostate cancer: design, synthesis, structure-activity relationships and biological evaluation.

    PubMed

    Fortin, Sébastien; Brasseur, Kevin; Morin, Nathalie; Asselin, Éric; Bérubé, Gervais

    2013-10-01

    Prostate cancer is a major public health problem worldwide and, more specifically, new treatments for hormone-refractory cancers are highly sought by several research groups. Although platinum(II)-based chemotherapy and other strategies grow in interest to treat castration-resistant prostate cancer (CRPC), they still exhibit modest activity on CRPC and overall patient survival. In this study, we designed and prepared new combi-molecules using 17β-acetyl-testosterone and amino acid platinum(II) complexes linked at the position 7α to target and to improve the antiproliferative activity of platinum(II)-based chemotherapy on prostate cancer cells. Twelve chemical intermediates and six new combi-molecules were prepared and characterized. Structure-activity relationships studies show that the platinum complex moiety is essential for an optimal cytocidal activity. Moreover, stereochemistry of the amino acid involved in the platinum complexes had only minor effects on the antiproliferative activity whereas pyridinyl (10a and b) and thiazolyl (10f) complexes exhibited the highest cytocidal activities that are significantly superior to that of cisplatin used as control on human prostate adenocarcinoma LNCaP (AR+), PC3 (AR-) and DU145 (AR-). Compounds 10a, b and f arrested the cell cycle progression in S-phase and induced double strand breaks as confirmed by the phosphorylation of histone H2AX into γH2AX. Compounds 10a and f showed 33 and 30% inhibition, respectively of the growth of HT-1080 tumors grafted onto chick chorioallantoic membranes. Finally, compounds 10a and 10f exhibited low toxicity on the chick embryos (18 and 21% of death, respectively), indicating that these new combi-molecules might be a promising new class of anticancer agents for prostate cancer.

  10. The status of molecules

    SciTech Connect

    Barnes, T. :

    1994-10-01

    This report summarizes the experimental and theoretical status of hadronic molecules, which are weakly-bound states of two or more hadrons. We begin with a brief history of the subject and discuss a few good candidates, and then abstract some signatures for molecules which may be of interest in the classification of possible molecule states. Next we argue that a more general understanding of 2 {yields} 2 hadron-hadron scattering amplitudes will be crucial for molecule searches, and discuss some of our recent work in this area. We conclude with a discussion of a few more recent molecule candidates (notably the f{sub o}(1710)) which are not well established as molecules but satisfy some of the expected signatures.

  11. How organic molecules can control electronic devices.

    PubMed

    Vilan, Ayelet; Cahen, David

    2002-01-01

    This article examines a somewhat counter-intuitive approach to molecular-based electronic devices. Control over the electronic energy levels at the surfaces of conventional semiconductors and metals is achieved by assembling on the solid surfaces, poorly organized, partial monolayers (MLs) of molecules instead of the more commonly used ideal ones. Once those surfaces become interfaces, these layers exert electrostatic rather than electrodynamic control over the resulting devices, based on both electrical monopole and dipole effects of the molecules. Thus electronic transport devices, incorporating molecules, can be constructed without current flow through the molecules. This is illustrated for a gallium arsenide (GaAs) sensor as well as for gold-silicon (Au-Si) and Au-GaAs diodes. Incorporating molecules into solid interfaces becomes possible, using a 'soft' electrical contacting procedure, so as not to damage the molecules. Because there are only a few molecular restrictions, this approach opens up possibilities for the use of more complex (including biologically active) molecules as it circumvents requirements for ideal MLs and for molecules that can tolerate actual electron transport through them.

  12. Biological Molecular Machines

    NASA Astrophysics Data System (ADS)

    Kurzyński, Michał

    2007-11-01

    Like small molecules taking part in usual chemical reactions, biological molecular machines perform their functions owing to thermal fluctuations and the only difference consists in more complex and specially organized internal dynamics. It is this dynamics that determines processes of free energy transduction in molecular machines. The case of the actomyosin motor is considered in some detail.

  13. Evidence of water molecules--a statistical evaluation of water molecules based on electron density.

    PubMed

    Nittinger, Eva; Schneider, Nadine; Lange, Gudrun; Rarey, Matthias

    2015-04-27

    Water molecules play important roles in many biological processes, especially when mediating protein-ligand interactions. Dehydration and the hydrophobic effect are of central importance for estimating binding affinities. Due to the specific geometric characteristics of hydrogen bond functions of water molecules, meaning two acceptor and two donor functions in a tetrahedral arrangement, they have to be modeled accurately. Despite many attempts in the past years, accurate prediction of water molecules-structurally as well as energetically-remains a grand challenge. One reason is certainly the lack of experimental data, since energetic contributions of water molecules can only be measured indirectly. However, on the structural side, the electron density clearly shows the positions of stable water molecules. This information has the potential to improve models on water structure and energy in proteins and protein interfaces. On the basis of a high-resolution subset of the Protein Data Bank, we have conducted an extensive statistical analysis of 2.3 million water molecules, discriminating those water molecules that are well resolved and those without much evidence of electron density. In order to perform this classification, we introduce a new measurement of electron density around an individual atom enabling the automatic quantification of experimental support. On the basis of this measurement, we present an analysis of water molecules with a detailed profile of geometric and structural features. This data, which is freely available, can be applied to not only modeling and validation of new water models in structural biology but also in molecular design.

  14. [Endothelial cell adhesion molecules].

    PubMed

    Ivanov, A N; Norkin, I A; Puchin'ian, D M; Shirokov, V Iu; Zhdanova, O Iu

    2014-01-01

    The review presents current data concerning the functional role of endothelial cell adhesion molecules belonging to different structural families: integrins, selectins, cadherins, and the immunoglobulin super-family. In this manuscript the regulatory mechanisms and factors of adhesion molecules expression and distribution on the surface of endothelial cells are discussed. The data presented reveal the importance of adhesion molecules in the regulation of structural and functional state of endothelial cells in normal conditions and in pathology. Particular attention is paid to the importance of these molecules in the processes of physiological and pathological angiogenesis, regulation of permeability of the endothelial barrier and cell transmigration.

  15. Chapter 3: Small Molecules and Disease

    PubMed Central

    Wishart, David S.

    2012-01-01

    “Big” molecules such as proteins and genes still continue to capture the imagination of most biologists, biochemists and bioinformaticians. “Small” molecules, on the other hand, are the molecules that most biologists, biochemists and bioinformaticians prefer to ignore. However, it is becoming increasingly apparent that small molecules such as amino acids, lipids and sugars play a far more important role in all aspects of disease etiology and disease treatment than we realized. This particular chapter focuses on an emerging field of bioinformatics called “chemical bioinformatics” – a discipline that has evolved to help address the blended chemical and molecular biological needs of toxicogenomics, pharmacogenomics, metabolomics and systems biology. In the following pages we will cover several topics related to chemical bioinformatics. First, a brief overview of some of the most important or useful chemical bioinformatic resources will be given. Second, a more detailed overview will be given on those particular resources that allow researchers to connect small molecules to diseases. This section will focus on describing a number of recently developed databases or knowledgebases that explicitly relate small molecules – either as the treatment, symptom or cause – to disease. Finally a short discussion will be provided on newly emerging software tools that exploit these databases as a means to discover new biomarkers or even new treatments for disease. PMID:23300405

  16. Mechanics of Biological Nanotechnology

    NASA Astrophysics Data System (ADS)

    Phillips, Rob; Purohit, Prashant K.; Kondev, Jané

    One of the most compelling areas to be touched by nanotechnology is biological science. Indeed, we will argue that there is a fascinating interplay between these two subjects, with biology as a key beneficiary of advances in nanotechnology as a result of a new generation of single molecule experiments that complement traditional assays involving statistical assemblages of molecules. This interplay runs in both directions, with nanotechnology continually receiving inspiration from biology itself. The goal of this chapter is to highlight some representative examples of the exchange between biology and nanotechnology and to illustrate the role of nanomechanics in this field and how mechanical models have arisen in response to the emergence of this new field. Primary attention will be given to the particular example of the processes that attend the life cycle of bacterial viruses. Viruses feature many of the key lessons of biological nanotechnology, including self assembly, as evidenced in the spontaneous formation of the protein shell (capsid) within which the viral genome is packaged, and a motor-mediated biological process, namely, the packaging of DNA in this capsid by a molecular motor that pushes the DNA into the capsid. We argue that these processes in viruses are a compelling real-world example of nature's nanotechnology and reveal the nanomechanical challenges that will continue to be confronted at the nanotechnology-biology interface.

  17. Mechanics of Biological Nanotechnology

    NASA Astrophysics Data System (ADS)

    Phillips, Rob; Purohit, Prashant; Kondev, Jané

    One of the most compelling areas to be touched by nanotechnology is biological science. Indeed, we will argue that there is a fascinating interplay between these two subjects, with biology as a key beneficiary of advances in nanotechnology as a result of a new generation of single-molecule experiments that complement traditional assays involving statistical assemblages of molecules. This interplay runs in both directions, with nanotechnology continually receiving inspiration from biology itself. The goal of this chapter is to highlight some representative examples of the exchange between biology and nanotechnology and to illustrate the role of nanomechanics in this field and how mechanical models have arisen in response to the emergence of this new field. Primary attention will be given to the particular example of the processes that attend the life cycle of bacterial viruses. Viruses feature many of the key lessons of biological nanotechnology, including self assembly, as evidenced in the spontaneous formation of the protein shell (capsid) within which the viral genome is packaged, and a motor-mediated biological process, namely the packaging of DNA in this capsid by a molecular motor that pushes the DNA into the capsid. We argue that these processes in viruses are a compelling real-world example of nature's nanotechnology, and they reveal the nanomechanical challenges that will continue to be confronted at the nanotechnology-biology interface.

  18. Enzymatic DNA molecules

    NASA Technical Reports Server (NTRS)

    Joyce, Gerald F. (Inventor); Breaker, Ronald R. (Inventor)

    1998-01-01

    The present invention discloses deoxyribonucleic acid enzymes--catalytic or enzymatic DNA molecules--capable of cleaving nucleic acid sequences or molecules, particularly RNA, in a site-specific manner, as well as compositions including same. Methods of making and using the disclosed enzymes and compositions are also disclosed.

  19. Molecules between the Stars.

    ERIC Educational Resources Information Center

    Verschuur, Gerrit L.

    1987-01-01

    Provides a listing of molecules discovered to date in the vast interstellar clouds of dust and gas. Emphasizes the recent discoveries of organic molecules. Discusses molecular spectral lines, MASERs (microwave amplification by stimulated emission of radiation), molecular clouds, and star birth. (TW)

  20. Molecules between the Stars.

    ERIC Educational Resources Information Center

    Verschuur, Gerrit L.

    1987-01-01

    Provides a listing of molecules discovered to date in the vast interstellar clouds of dust and gas. Emphasizes the recent discoveries of organic molecules. Discusses molecular spectral lines, MASERs (microwave amplification by stimulated emission of radiation), molecular clouds, and star birth. (TW)