Vibrational spectroscopic and molecular docking study of (2E)-N-(4-chloro-2-oxo-1,2-dihydroquinolin-3-yl)-3-phenylprop-2-enamide.

PubMed

Ulahannan, Rajeev T; Panicker, C Yohannan; Varghese, Hema Tresa; Musiol, Robert; Jampilek, Josef; Van Alsenoy, Christian; War, Javeed Ahmad; Al-Saadi, Abdulaziz A

2015-01-01

FT-IR and FT-Raman spectra of (2E)-N-(4-chloro-2-oxo-1,2-dihydroquinolin-3-yl)-3-phenylprop-2-enamide were recorded and analyzed experimentally and theoretically. The synthesis, (1)H NMR and PES scan results are also discussed. Nonlinear optical behavior of the examined molecule was investigated by the determination of first hyperpolarizability. The calculated HOMO and LUMO energies show the chemical activity of the molecule. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. From the MEP it is evident that the negative charge covers the carbonyl group and the positive region is over the NH group. The calculated geometrical parameters (SDD) are in agreement with that of similar derivatives. Molecular docking simulations against targets from Mycobacterium tuberculosis are reported and the results suggest that the compound might exhibit inhibitory activity against PknB. Copyright © 2015 Elsevier B.V. All rights reserved.

Synthesis, spectral characterization and density functional theory exploration of 1-(quinolin-3-yl)piperidin-2-ol

NASA Astrophysics Data System (ADS)

Suresh, M.; Syed Ali Padusha, M.; Bharanidharan, S.; Saleem, H.; Dhandapani, A.; Manivarman, S.

2015-06-01

The experimental and theoretical vibrational frequencies of a newly synthesized compound, namely 1-(quinolin-3-yl)piperidin-2-ol (QPPO) are analyzed. The experimental FT-IR (4000-400 cm-1) and FT-Raman (4000-100 cm-1) of the molecule in solid phase have been recorded. The optimized molecular structure, vibrational assignments of QPPO have been investigated experimentally and theoretically using Gaussian03W software package. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. The first order hyperpolarizability (β0) is calculated to find its character in non-linear optics. Gauge including atomic orbital (GIAO) method is used to calculate 1H NMR chemical shift calculations were carried out and compared with experimental data. The electronic properties like UV-Visible spectral analysis and HOMO-LUMO energies were reported. The energy gap shows that the charge transfer occurs within the molecule. Thermodynamic parameters of the title compound were calculated at various temperatures.

Studies on molecular structure, vibrational spectra and molecular docking analysis of 3-Methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl 4-aminobenzoate.

PubMed

Suresh, D M; Amalanathan, M; Joe, I Hubert; Jothy, V Bena; Diao, Yun-Peng

2014-09-15

The molecular structure, vibrational analysis and molecular docking analysis of the 3-Methyl-1,4-dioxo-1,4-dihydronaphthalen-2-yl 4-aminobenzoate (MDDNAB) molecule have been carried out using FT-IR and FT-Raman spectroscopic techniques and DFT method. The equilibrium geometry, harmonic vibrational wave numbers, various bonding features have been computed using density functional method. The calculated molecular geometry has been compared with experimental data. The detailed interpretation of the vibrational spectra has been carried out by using VEDA program. The hyper-conjugative interactions and charge delocalization have been analyzed using natural bond orbital (NBO) analysis. The simulated FT-IR and FT-Raman spectra satisfactorily coincide with the experimental spectra. The PES and charge analysis have been made. The molecular docking was done to identify the binding energy and the Hydrogen bonding with the cancer protein molecule. Copyright © 2014 Elsevier B.V. All rights reserved.

Theoretical study on the molecular structure and vibrational properties, NBO and HOMO-LUMO analysis of the POX3 (X = F, Cl, Br, I) series of molecules

NASA Astrophysics Data System (ADS)

Galván, Jorge E.; Gil, Diego M.; Lanús, Hernán E.; Altabef, Aida Ben

2015-02-01

The fourth member of the series of compounds of the type POX3 with X = I was synthesized and characterized by infrared spectroscopy. The geometrical parameters and vibrational properties of POX3 (X = F, Cl, Br, I) molecules were investigated theoretically by means DFT and ab initio methods. Available geometrical and vibrational data were used together with theoretical calculations in order to obtain a set of scaled force constants. The observed trends in geometrical parameters are analyzed and compared with those obtained in a previous work for the VOX3 (X = F, Cl, Br, I) series of compounds. NBO analysis was performed in order to know the hyper-conjugative interactions that favor one structure over another. The molecular properties such as ionization potential, electron affinity, electronegativity, chemical potential, chemical hardness, softness and global electrophilicity index have been deduced from HOMO-LUMO analysis.

Sorption of adamantane phenylamide derivatives on hyper-cross-linked polystyrene from water-acetonitrile eluents

NASA Astrophysics Data System (ADS)

Shafigulin, R. V.; Konstantinov, A. V.; Bulanova, A. V.; Il'in, M. M.; Davankov, V. A.

2016-11-01

Study of the main physicochemical features of the sorption of phenylamide adamantane derivatives on hyper-cross-linked polystyrene from water-acetonitrile solutions shows that both hydrophobic and electronic interactions make a large contribution to retention, especially for a chlorine-containing derivative in which there are π- p and π- d interactions between the outer-shell electrons of the chlorine atom in addition to π- π interactions between aromatic fragments of the sorbate and sorbent.

Quantum chemical and experimental studies on the structure and vibrational spectra of an alkaloid-Corlumine

NASA Astrophysics Data System (ADS)

Mishra, Rashmi; Joshi, Bhawani Datt; Srivastava, Anubha; Tandon, Poonam; Jain, Sudha

2014-01-01

The study concentrates on an important natural product, phthalide isoquinoline alkaloid Corlumine (COR) [(6R)-6-[(1S)-1,2,3,4-Tetrahydro-6,7-dimethoxy-2-methylisoquinolin-1-yl] furo [3,4-e]-1,3-benzodioxol-8(6H)-one] well known to exhibit spasmolytic and GABA antagonist activity. It was fully characterized by a variety of experimental methods including vibrational spectroscopy (IR and Raman), thermal analysis (DSC), UV and SEM. For a better interpretation and analysis of the results quantum chemical calculations employing DFT were also performed. TD-DFT was employed to elucidate electronic properties for both gaseous and solvent environment using IEF-PCM model. Graphical representation of HOMO and LUMO would provide a valuable insight into the nature of reactivity and some of the structural and physical properties of the title molecule. The structure-activity relationship have been interpreted by mapping electrostatic potential surface (MEP), which is valuable information for the quality control of medicines and drug-receptor interactions. Stability of the molecule arising from hyper conjugative interactions, charge delocalisation has been analyzed using natural bond orbital (NBO) analysis. Computation of thermodynamical properties would help to have a deep insight into the molecule for further applications.

Enhancement of atom transfer in different surface chemistry of hydrogenated vs. fluorinated tribromobenzene on Ag(111) and Cu(111)

NASA Astrophysics Data System (ADS)

Cecily mary glory, D.; Sambathkumar, K.; Madivanane, R.; Rajkamal, N.; Venkatachalapathy, M.

2017-12-01

Systematic interactions of hydrogenated & fluorinated tribromobenzene on Ag and Cu surfaces. First bromine dehalogenation takes place right upon adsorption due to catalytic properties of Ag. Different adsorption geometries of monomers and dimmers of 1,3,5-tribromo-2,4,6-trifluoro-benzene(TBFB) and 1,3,5-tribromobenzene(TBB). DFT calculations of the Csbnd Br binding energy dependent on the amount of remaining bromine atoms for both TBFB and TBB were performed. The experiments were performed at low temperature of 80 K.STM measurements where performed for of TBFB and TBB. STM show adsorbed molecules in a loose arrangement of molecules. NBO analysis the stability of the molecule arising within hyper-conjugative interactions. The HOMO and LUMO energies and electronic charge transfer (ECT) confirms that electronic transition. High field indicates that this molecule exhibit considerable electrical conductivity in atomic charges. The ESP map is found to be positive within the molecule. The negative charges have a tendency to drift from left to right. The computed thermodynamic parameters like heat capacities (Cºp,m), entropies (Sºm) and enthalpies changes (Hºm) are used for various electrical field.

Hyper-Assembly of Self-Assembled Glycoclusters Mediated by Specific Carbohydrate-Carbohydrate Interactions.

PubMed

Yan, Gengwei; Yamaguchi, Takumi; Suzuki, Tatsuya; Yanaka, Saeko; Sato, Sota; Fujita, Makoto; Kato, Koichi

2017-05-04

Hybridization of a self-assembled, spherical complex with oligosaccharides containing Lewis X, a functional trisaccharide displayed on various cell surfaces, yielded well-defined glycoclusters. The self-assembled glycoclusters exhibited homophilic hyper-assembly in aqueous solution in a Ca 2+ -dependent manner through specific carbohydrate-carbohydrate interactions, offering a structural scaffold for functional biomimetic systems. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hyperunified field theory and gravitational gauge-geometry duality

NASA Astrophysics Data System (ADS)

Wu, Yue-Liang

2018-01-01

A hyperunified field theory is built in detail based on the postulates of gauge invariance and coordinate independence along with the conformal scaling symmetry. All elementary particles are merged into a single hyper-spinor field and all basic forces are unified into a fundamental interaction governed by the hyper-spin gauge symmetry SP(1, D_h-1). The dimension D_h of hyper-spacetime is conjectured to have a physical origin in correlation with the hyper-spin charge of elementary particles. The hyper-gravifield fiber bundle structure of biframe hyper-spacetime appears naturally with the globally flat Minkowski hyper-spacetime as a base spacetime and the locally flat hyper-gravifield spacetime as a fiber that is viewed as a dynamically emerged hyper-spacetime characterized by a non-commutative geometry. The gravitational origin of gauge symmetry is revealed with the hyper-gravifield that plays an essential role as a Goldstone-like field. The gauge-gravity and gravity-geometry correspondences bring about the gravitational gauge-geometry duality. The basic properties of hyperunified field theory and the issue on the fundamental scale are analyzed within the framework of quantum field theory, which allows us to describe the laws of nature in deriving the gauge gravitational equation with the conserved current and the geometric gravitational equations of Einstein-like type and beyond.

Nonspecific Interaction of Streptavidin with Urease-Conjugated Antibodies

DTIC Science & Technology

1991-11-01

11l1llilll li ii________ l__ :’SUFFIELD MEMORANDUM= NO. 1358 NONSPECIFIC INTERACTION OF STREPTAVIDIN WITH UREASE -CONJUGATED ANTIBODIES E LECT- by 92-01626...ESTABLISHMENT SUFFIELD RALSTON ALBERTA Suffield Memorandum No. 1358 Nonspecific Interaction of Streptavidin with Urease -Conjugated Antibodies by H. Gail...mixture, a urease -conjugated antibody. The variations could be diminished by allowing the reagents to stand at room temperature for two to three hours

On Developing HyperCard Stacks for the Study of Chinese Characters: KanjiCard.

ERIC Educational Resources Information Center

Nakajima, Kazuko

1988-01-01

Describes "KanjiCard," an interactive self-tutorial program for beginning students of Japanese to learn Kanji, Chinese characters used in the Japanese language. The Macintosh-developed approach uses "HyperCard" technology, computer-assisted animation, and voice digitizing to achieve enhanced graphic presentation. (Author/CB)

HyperGLOB/Freedom: Preparing Student Designers for a New Media.

ERIC Educational Resources Information Center

Slawson, Brian

The HyperGLOB project introduced university-level graphic design students to interactive multimedia. This technology involves using the personal computer to display and manipulate a variety of electronic media simultaneously (combining elements of text and speech, music and sound, still images, motion video, and animated graphics) and allows…

Synthesis and evaluation of NLO properties of π-conjugated donor-acceptor systems bearing pyrrole and thiophene heterocycles

NASA Astrophysics Data System (ADS)

Castro, M. Cidália R.; Fonseca, A. Maurício C.; Belsley, M.; Raposo, M. Manuela M.

2011-05-01

Two series of novel push-pull heterocyclic azo dyes have been synthesized and characterized. The two series of compounds were based on different combinations of π-conjugated bridges (bithiophene and thienylpyrrole) which also act simultaneously as donor groups, together with diazo(benzo)thiazolyl as acceptor moieties. Their thermal stability and electrochemical behavior were characterized, while hyper-Rayleigh scattering (HRS) was employed to evaluate their second-order nonlinear optical properties. The results of these studies have been critically analyzed together with several thienylpyrrole azo dyes reported earlier from our laboratories in which the thienylpyrrole system was used as the donor group functionalized with aryl and (benzo)thiazolyldiazene as acceptor moiety. The measured molecular first hyperpolarizabilities and the observed linear optical and redox behavior showed strong variations in function of the heterocyclic spacers used (bithiophene or thienylpyrrole) and were also sensitive to the acceptor strength of the diazenehetero(aryl) moiety.

Design, Synthesis, and Evaluation of N- and C-Terminal Protein Bioconjugates as G Protein-Coupled Receptor Agonists.

PubMed

Healey, Robert D; Wojciechowski, Jonathan P; Monserrat-Martinez, Ana; Tan, Susan L; Marquis, Christopher P; Sierecki, Emma; Gambin, Yann; Finch, Angela M; Thordarson, Pall

2018-02-21

A G protein-coupled receptor (GPCR) agonist protein, thaumatin, was site-specifically conjugated at the N- or C-terminus with a fluorophore for visualization of GPCR:agonist interactions. The N-terminus was specifically conjugated using a synthetic 2-pyridinecarboxyaldehyde reagent. The interaction profiles observed for N- and C-terminal conjugates were varied; N-terminal conjugates interacted very weakly with the GPCR of interest, whereas C-terminal conjugates bound to the receptor. These chemical biology tools allow interactions of therapeutic proteins:GPCR to be monitored and visualized. The methodology used for site-specific bioconjugation represents an advance in application of 2-pyridinecarboxyaldehydes for N-terminal specific bioconjugations.

Spectroscopic and quantum chemical analysis of a natural product - Hayatin hydrochloride

NASA Astrophysics Data System (ADS)

Mishra, Rashmi; Srivastava, Anubha; Tandon, Poonam; Jain, Sudha

2015-08-01

Majority of drugs in use today are natural products, natural product mimics or semi synthetic derivatives. Therefore in recent times, focus on plant research has increased all over the world and large body of evidence has been collected to show immense potential of medicinal plants used in various traditional systems. Therefore, in the present communication to aid that research, structural and spectroscopic analysis of a natural product, an alkaloid Hayatin hydrochloride was performed. Both ab initio Hartree-Fock and density functional theory employing B3LYP with complete relaxation in the potential energy surface using 6-311G (d,p) basis set were used for the calculations. The vibrational frequencies were calculated and scaled values were compared with experimental FT-IR and micro-Raman spectra. The complete assignments were performed on the basis of potential energy distribution. The structure-activity relationship has also been interpreted by mapping electrostatic potential surface, which are valuable information for the quality control of medicines and drug-receptor interactions. Electronic properties have been analysed employing TD-DFT for both gaseous and solvent phase. The calculated HOMO and LUMO energies show that charge transfer occurs within the molecule. Stability of the molecule arising from hyper conjugative interactions, charge delocalization has been analyzed using natural bond orbital (NBO) analysis.

HYPERCLIPS

NASA Technical Reports Server (NTRS)

Hill, R. W.

1994-01-01

The integration of CLIPS into HyperCard combines the intuitive, interactive user interface of the Macintosh with the powerful symbolic computation of an expert system interpreter. HyperCard is an excellent environment for quickly developing the front end of an application with buttons, dialogs, and pictures, while the CLIPS interpreter provides a powerful inference engine for complex problem solving and analysis. In order to understand the benefit of integrating HyperCard and CLIPS, consider the following: HyperCard is an information storage and retrieval system which exploits the use of the graphics and user interface capabilities of the Apple Macintosh computer. The user can easily define buttons, dialog boxes, information templates, pictures, and graphic displays through the use of the HyperCard tools and scripting language. What is generally lacking in this environment is a powerful reasoning engine for complex problem solving, and this is where CLIPS plays a role. CLIPS 5.0 (C Language Integrated Production System, v5.0) was developed at the Johnson Space Center Software Technology Branch to allow artificial intelligence research, development, and delivery on conventional computers. CLIPS 5.0 supports forward chaining rule systems, object-oriented language, and procedural programming for the construction of expert systems. It features incremental reset, seven conflict resolution stategies, truth maintenance, and user-defined external functions. Since CLIPS is implemented in the C language it is highly portable; in addition, it is embeddable as a callable routine from a program written in another language such as Ada or Fortran. By integrating HyperCard and CLIPS the advantages and uses of both packages are made available for a wide range of applications: rapid prototyping of knowledge-based expert systems, interactive simulations of physical systems and intelligent control of hypertext processes, to name a few. HyperCLIPS 2.0 is written in C-Language (54%) and Pascal (46%) for Apple Macintosh computers running Macintosh System 6.0.2 or greater. HyperCLIPS requires HyperCard 1.2 or higher and at least 2Mb of RAM are recommended to run. An executable is provided. To compile the source code, the Macintosh Programmer's Workshop (MPW) version 3.0, CLIPS 5.0 (MSC-21927), and the MPW C-Language compiler are also required. NOTE: Installing this program under Macintosh System 7 requires HyperCard v2.1. This program is distributed on a 3.5 inch Macintosh format diskette. A copy of the program documentation is included on the diskette, but may be purchased separately. HyperCLIPS was developed in 1990 and version 2.0 was released in 1991. HyperCLIPS is a copyrighted work with all copyright vested in NASA. Apple, Macintosh, MPW, and HyperCard are registered trademarks of Apple Computer, Inc.

Trapping of muscle relaxant methocarbamol degradation product by complexation with copper(II) ion: Spectroscopic and quantum chemical studies

NASA Astrophysics Data System (ADS)

Mansour, Ahmed M.; Shehab, Ola R.

2014-07-01

Structural properties of methocarbamol (Mcm) were extensively studied both experimentally and theoretically using FT IR, 1H NMR, UV-Vis., geometry optimization, Mulliken charge, and molecular electrostatic potential. Stability arises from hyper-conjugative interactions, charge delocalization and H-bonding was analyzed using natural bond orbital (NBO) analysis. Mcm was decomposed in ethanol/water mixture at 80 °C to guaifenesin [(RS)-3-(2-methoxyphenoxy)propane-1,2-diol] and carbamate ion [NH2COO-], where the degradation mechanism was explained by trapping the carbamate ion via the complexation with copper(II) ion. The structure of the isolated complex ([Cu(NH2COO)2(H2O)]ṡ4H2O) was elucidated by spectral, thermal, and magnetic tools. Electronic spectra were discussed by TD-DFT and the descriptions of frontier molecular orbitals and the relocations of the electron density were determined. Calculated g-tensor values showed best agreement with experimental values from EPR when carried out using both the B3LYP and B3PW91 functional.

QM/MM methodology, docking and spectroscopic (FT-IR/FT-Raman, NMR, UV) and Fukui function analysis on adrenergic agonist

NASA Astrophysics Data System (ADS)

Uma Maheswari, J.; Muthu, S.; Sundius, Tom

2015-02-01

The Fourier transform infrared, FT-Raman, UV and NMR spectra of Ternelin have been recorded and analyzed. Harmonic vibrational frequencies have been investigated with the help of HF with 6-31G (d,p) and B3LYP with 6-31G (d,p) and LANL2DZ basis sets. The 1H and 13C nuclear magnetic resonance (NMR) chemical shifts of the molecule were calculated by GIAO method. The polarizability (α) and the first hyperpolarizability (β) values of the investigated molecule have been computed using DFT quantum mechanical calculations. Stability of the molecule arising from hyper conjugative interactions, and charge delocalization has been analyzed using natural bond orbital (NBO) analysis. The electron density-based local reactivity descriptors such as Fukui functions were calculated to explain the chemical selectivity or reactivity site in Ternelin. Finally the calculated results were compared to simulated infrared and Raman spectra of the title compound which show good agreement with observed spectra. Molecular docking studies have been carried out in the active site of Ternelin and reactivity with ONIOM was also investigated.

Calculated hyperfine coupling constants for 5,5-dimethyl-1-pyrroline N-oxide radical products in water and benzene

NASA Astrophysics Data System (ADS)

Nardali, Ş.; Ucun, F.; Karakaya, M.

2017-11-01

The optimized structures of some radical adducts of 5,5-dimethyl-1-pyrroline N-oxide were computed by different methods on ESR spectra. As trapped radicals, H, N3, NH2, CH3, CCl3, OOH in water and F, OH, CF3, CH2OH, OC2H5 in benzene solutions were used. The calculated isotropic hyperfine coupling constants of all the trapped radicals were compared with the corresponding experimental data. The hyperfine coupling constant due to the β proton of the nitroxide radical was seen to be consist with the McConnel's relation αβ = B 0 + B 1cos2θ and, to be effected with the opposite spin density of oxygen nucleus bonded to the nitrogen. It was concluded that in hyperfine calculations the DFT(B3PW91)/LanL2DZ level is superior computational quantum model relative to the used other level. Also, the study has been enriched by the computational of the optimized geometrical parameters, the hyper conjugative interaction energies, the atomic charges and spin densities for all the radical adducts.

Acid-base properties, FT-IR, FT-Raman spectroscopy and computational study of 1-(pyrid-4-yl)piperazine.

PubMed

Mary, Y Sheena; Panicker, C Yohannan; Varghese, Hema Tresa; Van Alsenoy, Christian; Procházková, Markéta; Sevčík, Richard; Pazdera, Pavel

2014-01-01

We report the vibrational spectral analysis was carried out using FT-IR and FT-Raman spectroscopy for 1-(pyrid-4-yl)piperazine (PyPi). Single crystals of PyPi suitable for X-ray structural analysis were obtained. The acid-base properties are also reported. PyPi supported on a weak acid cation-exchanger in the single protonated form and this system can be used efficiently as the solid supported analogue of 4-N,N-dimethyl-aminopyridine. The complete vibrational assignments of wavenumbers were made on the basis of potential energy distribution. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule and with the molecular electrostatic potential map was applied for the reactivity assessment of PyPi molecule toward proton, electrophiles and nucleopholes as well. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. The calculated first hyperpolarizability of PyPi is 17.46 times that of urea. Copyright © 2013 Elsevier B.V. All rights reserved.

Quality Matters: Extension of Clusters of Residues with Good Hydrophobic Contacts Stabilize (Hyper)Thermophilic Proteins

PubMed Central

2015-01-01

Identifying determinant(s) of protein thermostability is key for rational and data-driven protein engineering. By analyzing more than 130 pairs of mesophilic/(hyper)thermophilic proteins, we identified the quality (residue-wise energy) of hydrophobic interactions as a key factor for protein thermostability. This distinguishes our study from previous ones that investigated predominantly structural determinants. Considering this key factor, we successfully discriminated between pairs of mesophilic/(hyper)thermophilic proteins (discrimination accuracy: ∼80%) and searched for structural weak spots in E. coli dihydrofolate reductase (classification accuracy: 70%). PMID:24437522

Intra- and inter-brain synchronization during musical improvisation on the guitar.

PubMed

Müller, Viktor; Sänger, Johanna; Lindenberger, Ulman

2013-01-01

Humans interact with the environment through sensory and motor acts. Some of these interactions require synchronization among two or more individuals. Multiple-trial designs, which we have used in past work to study interbrain synchronization in the course of joint action, constrain the range of observable interactions. To overcome the limitations of multiple-trial designs, we conducted single-trial analyses of electroencephalography (EEG) signals recorded from eight pairs of guitarists engaged in musical improvisation. We identified hyper-brain networks based on a complex interplay of different frequencies. The intra-brain connections primarily involved higher frequencies (e.g., beta), whereas inter-brain connections primarily operated at lower frequencies (e.g., delta and theta). The topology of hyper-brain networks was frequency-dependent, with a tendency to become more regular at higher frequencies. We also found hyper-brain modules that included nodes (i.e., EEG electrodes) from both brains. Some of the observed network properties were related to musical roles during improvisation. Our findings replicate and extend earlier work and point to mechanisms that enable individuals to engage in temporally coordinated joint action.

Intra- and Inter-Brain Synchronization during Musical Improvisation on the Guitar

PubMed Central

Müller, Viktor; Sänger, Johanna; Lindenberger, Ulman

2013-01-01

Humans interact with the environment through sensory and motor acts. Some of these interactions require synchronization among two or more individuals. Multiple-trial designs, which we have used in past work to study interbrain synchronization in the course of joint action, constrain the range of observable interactions. To overcome the limitations of multiple-trial designs, we conducted single-trial analyses of electroencephalography (EEG) signals recorded from eight pairs of guitarists engaged in musical improvisation. We identified hyper-brain networks based on a complex interplay of different frequencies. The intra-brain connections primarily involved higher frequencies (e.g., beta), whereas inter-brain connections primarily operated at lower frequencies (e.g., delta and theta). The topology of hyper-brain networks was frequency-dependent, with a tendency to become more regular at higher frequencies. We also found hyper-brain modules that included nodes (i.e., EEG electrodes) from both brains. Some of the observed network properties were related to musical roles during improvisation. Our findings replicate and extend earlier work and point to mechanisms that enable individuals to engage in temporally coordinated joint action. PMID:24040094

Molecular docking, vibrational, structural, electronic and optical studies of {4 - (2, 6) dichlorophenyl amino 2 - methylidene 4 - oxobutanoic acid and 4- (2, 5)} dichlorophenyl amino 2 - methylidene 4 - oxobutanoic acid - A comparative study

NASA Astrophysics Data System (ADS)

Vanasundari, K.; Balachandran, V.; Kavimani, M.; Narayana, B.

2018-03-01

Spectroscopic and structural investigations of 4 - [(2, 6 - dichlorophenyl) amino] 2 -methylidene 4 - oxobutanoic acid (6DAMB) and 4-[(2, 5- dichlorophenyl) amino] 2 - methylidene 4 - oxobutanoic acid (5DAMB) are presented by using experimental (FT-IR and FT-Raman) spectra and theoretical (DFT approach) calculations. Seventy-two characteristic vibrational bands of the title compounds were assigned and compared with available experimental data. Stability of the molecule arising from hyper-conjugative interactions and charge delocalization was analyzed using natural bond orbital (NBO) analysis. Several descriptors determined from the energies of frontier molecular orbital (HOMO and LUMO) were applied to describe the reactivity of the title compound. The dipole moment and first hyperpolarizabilities of the studied compounds indicate that the compound is a good candidate of nonlinear optical materials. Theoretical Ultraviolet-Visible spectra of title compounds have been analyzed using the TD-DFT method. The noncovalent interactions like hydrogen bonding and Van der Waals interaction were identified from the molecular geometry and electron localization function. These interactions in molecules have been studied by using reduced density gradient (RDG) and graphed by Multiwfn. Auto-dock studies reveal that butanoic acid derivatives play a vital role in bonding and results draw us to the concluded that both compounds inhibit Placenta growth factor (PIGF-1) and that have good biological activities. This study may also provide further investigation on butanoic acid derivatives for pharmacological importance.

HyperCard to SPSS: improving data integrity.

PubMed

Gostel, R

1993-01-01

This article describes a database design that captures responses in a HyperCard stack and moves the data to SPSS for the Macintosh without the need to rekey data. Pregnant women used an interactive computer application with a touch screen to answer questions and receive educational information about fetal alcohol syndrome. A database design was created to capture survey responses through interaction with a computer by a sample of prenatal women during formative evaluation trials. The author does not compare this method of data collection to other methods. This article simply describes the method of data collection as a useful research tool.

Arabidopsis TCP Transcription Factors Interact with the SUMO Conjugating Machinery in Nuclear Foci

PubMed Central

Mazur, Magdalena J.; Spears, Benjamin J.; Djajasaputra, André; van der Gragt, Michelle; Vlachakis, Georgios; Beerens, Bas; Gassmann, Walter; van den Burg, Harrold A.

2017-01-01

In Arabidopsis more than 400 proteins have been identified as SUMO targets, both in vivo and in vitro. Among others, transcription factors (TFs) are common targets for SUMO conjugation. Here we aimed to exhaustively screen for TFs that interact with the SUMO machinery using an arrayed yeast two-hybrid library containing more than 1,100 TFs. We identified 76 interactors that foremost interact with the SUMO conjugation enzyme SCE1 and/or the SUMO E3 ligase SIZ1. These interactors belong to various TF families, which control a wide range of processes in plant development and stress signaling. Amongst these interactors, the TCP family was overrepresented with several TCPs interacting with different proteins of the SUMO conjugation cycle. For a subset of these TCPs we confirmed that the catalytic site of SCE1 is essential for this interaction. In agreement, TCP1, TCP3, TCP8, TCP14, and TCP15 were readily SUMO modified in an E. coli sumoylation assay. Strikingly, these TCP-SCE1 interactions were found to redistribute these TCPs into nuclear foci/speckles, suggesting that these TCP foci represent sites for SUMO (conjugation) activity. PMID:29250092

Experimental and computational approaches to the analysis of the molecular structure of (E)-3-(3-(4-nitrophenyl)triaz-1-en-1-yl)-1H-pyrazole-4-carbonitrile

NASA Astrophysics Data System (ADS)

Al-Azmi, Amal; Shalaby, Mona Abbas

2018-03-01

A green, fast and straightforward procedure for the synthesis of (E)-3-(3-(4-nitrophenyl)triaz-1-en-1-yl)-1H-pyrazole-4-carbonitrile is described in this paper. The method uses a coupling reaction between 4- nitrophenyl diazonium chloride and 5-aminopyrazole-4-carbonitrile. The structure is confirmed by different spectroscopic studies such as IR, NMR, HRMS and UV-vis spectroscopy in addition to X-ray single-crystal determination. The molecular geometry, vibrational frequencies and gauge-invariant atomic orbital (GIAO) 1H and 13C NMR chemical shift values of (E)-3-(3-(4-nitrophenyl)triaz-1-en-1-yl)-1H-pyrazole-4-carbonitrile are calculated in the ground state using the Hartree-Fock (HF) method and density functional theory (DFT) with the 6-31G(d) basis set, and are compared with the experimental data. The natural bond orbital (NBO) analysis is performed so as to discuss the stability of the molecule that arises from hyper conjugative interactions and charge delocalization. The electronic properties, such as HOMO and LUMO energies, were calculated using time dependent density functional theory (TD-DFT) approach.

Molecular conformational analysis, vibrational spectra, NBO analysis and first hyperpolarizability of (2E)-3-phenylprop-2-enoic anhydride based on density functional theory calculations.

PubMed

Sheena Mary, Y; Raju, K; Panicker, C Yohannan; Al-Saadi, Abdulaziz A; Thiemann, Thies; Van Alsenoy, Christian

2014-07-15

The conformational behavior and structural stability of (2E)-3-phenylprop-2-enoic anhydride were investigated by using density functional theory. Seventeen possible stable conformations of the title compound were determined and verified with their calculated vibrational frequencies being all positive. The optimized molecular structure, vibrational wavenumbers, corresponding vibrational assignments of (2E)-3-phenylprop-2-enoic anhydride have been investigated experimentally and theoretically using Gaussian09 software package. Potential energy distribution of normal modes vibrations was done using GAR2PED program. The HOMO and LUMO analysis are used to determine the charge transfer within the molecule. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. The calculated first hyperpolarizability of the title compound is 12×10(-30) esu and is 92.31 times that of the standard NLO material urea and the title compound is an attractive object for future studies of nonlinear optical properties. MEP was performed by the DFT method and the predicted infrared intensities and Raman activities have also been reported. Copyright © 2014 Elsevier B.V. All rights reserved.

Molecular structure, FT-IR, FT-Raman, NBO, HOMO and LUMO, MEP, NLO and molecular docking study of 2-[(E)-2-(2-bromophenyl)ethenyl]quinoline-6-carboxylic acid.

PubMed

Ulahannan, Rajeev T; Panicker, C Yohannan; Varghese, Hema Tresa; Musiol, Robert; Jampilek, Josef; Van Alsenoy, Christian; War, Javeed Ahmad; Srivastava, S K

2015-01-01

The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of 2-[(E)-2-(2-bromophenyl)ethenyl]quinoline-6-carboxylic acid have been investigated experimentally and theoretically using Gaussian09 software package. Potential energy distribution of the normal modes of vibrations was done using GAR2PED program. (1)H NMR chemical shifts calculations were carried out by using B3LYP functional with SDD basis set. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. MEP was performed by the DFT method and the predicted infrared intensities and Raman activities have also been reported. The calculated geometrical parameters are in agreement with that of similar derivatives. The title compound forms a stable complex with PknB as is evident from the binding affinity values and the molecular docking results suggest that the compound might exhibit inhibitory activity against PknB and this may result in development of new anti-tuberculostic agents. Copyright © 2015 Elsevier B.V. All rights reserved.

Theoretical investigations on molecular structure, vibrational spectra, HOMO, LUMO, NBO analysis and hyperpolarizability calculations of thiophene-2-carbohydrazide.

PubMed

Balachandran, V; Janaki, A; Nataraj, A

2014-01-24

The Fourier-Transform infrared and Fourier-Transform Raman spectra of thiophene-2-carbohydrazide (TCH) was recorded in the region 4000-400 cm(-1) and 3500-100 cm(-1). Quantum chemical calculations of energies, geometrical structure and vibrational wavenumbers of TCH were carried out by DFT (B3LYP) method with 6-311++G(d,p) as basis set. The difference between the observed and scaled wavenumber values of most of the fundamentals is very small. Stability of the molecule arising from hyper conjugative interaction and charge delocalization has been analyzed using natural bond orbital (NBO) analysis. UV spectrum was measured in different solvent. The energy and oscillator strength are calculated by Time Dependant Density Functional Theory (TD-DFT) results. The calculated HOMO and LUMO energies also confirm that charge transfer occurs within the molecule. The complete assignments were performed on the basis of the potential energy distribution (PED) of vibrational modes, calculated with scaled quantum mechanics (SQM) method. Finally the theoretical FT-IR, FT-Raman, and UV spectra of the title molecule have also been constructed. Copyright © 2013 Elsevier B.V. All rights reserved.

Hyper-Ramsey spectroscopy with probe-laser-intensity fluctuations

NASA Astrophysics Data System (ADS)

Beloy, K.

2018-03-01

We examine the influence of probe-laser-intensity fluctuations on hyper-Ramsey spectroscopy. We assume, as is appropriate for relevant cases of interest, that the probe-laser intensity I determines both the Rabi frequency (∝√{I } ) and the frequency shift to the atomic transition (∝I ) during probe-laser interactions with the atom. The spectroscopic signal depends on these two quantities that covary with fluctuations in the probe-laser intensity. Introducing a simple model for the fluctuations, we find that the signature robustness of the hyper-Ramsey method can be compromised. Taking the Yb+ electric octupole clock transition as an example, we quantify the clock error under different levels of probe-laser-intensity fluctuations.

Striatal hyper-sensitivity during stress in remitted individuals with recurrent depression

PubMed Central

Admon, Roee; Holsen, Laura M.; Aizley, Harlyn; Remington, Anne; Whitfield-Gabrieli, Susan; Goldstein, Jill M.; Pizzagalli, Diego A.

2014-01-01

Background Increased sensitivity to stress and dysfunctional reward processing are two primary characteristics of Major Depressive Disorder (MDD) that may persist following remission. Preclinical work has established the pivotal role of the striatum in mediating both stress and reward responses. Human neuroimaging studies have corroborated these preclinical findings and highlighted striatal dysfunction in MDD in response to reward, but have yet to investigate striatal function during stress, in particular in individuals with recurrent depression. Methods Thirty three remitted individuals with a history of recurrent MDD (rMDD) and 35 matched healthy controls underwent a validated mild psychological stress task involving viewing of negative stimuli during fMRI. Cortisol and anxiety levels were assessed throughout scanning. Stress-related activation was investigated in three striatal regions: caudate, nucleus accumbens (Nacc), and putamen. Psychophysiological interaction (PPI) analyses probed connectivity of those regions with central structures of the neural stress circuitry, the amygdala and hippocampus. Results The task increased cortisol and anxiety levels, although to a greater extent in rMDD than healthy controls. In response to the negative stimuli, rMDD individuals, but not controls, also exhibited significantly potentiated caudate, Nacc, and putamen activations, as well as increased caudate-amygdala and caudate-hippocampus connectivity. Conclusions Findings highlight striatal hyper-sensitivity in response to a mild psychological stress in rMDD, as manifested by hyper-activation and hyper-connectivity with the amygdala and hippocampus. Striatal hyper-sensitivity during stress might thus constitute a trait mark of depression, providing a potential neural substrate for the interaction between stress and reward dysfunction in MDD. PMID:25483401

Synthesis, XRD single crystal structure analysis, vibrational spectral analysis, molecular dynamics and molecular docking studies of 2-(3-methoxy-4-hydroxyphenyl) benzothiazole

NASA Astrophysics Data System (ADS)

Sarau Devi, A.; Aswathy, V. V.; Sheena Mary, Y.; Yohannan Panicker, C.; Armaković, Stevan; Armaković, Sanja J.; Ravindran, Reena; Van Alsenoy, C.

2017-11-01

The vibrational spectra and corresponding vibrational assignments of 2-(3-methoxy-4-hydroxyphenyl)benzothiazole is reported. Single crystal XRD data of the title compound is reported and the orientation of methoxy group is cis to nitrogen atom of the thiazole ring. The phenyl ring breathing modes of the title compound are assigned at 1042 and 731 cm-1 theoretically. The charge transfer within the molecule is studied using frontier molecular orbital analysis. The chemical reactivity descriptors are calculated theoretically. The NMR spectral data predicted theoretically are in good agreement with the experimental data. The strong negative region spread over the phenyl rings, nitrogen atom and oxygen atom of the hydroxyl group in the MEP plot is due to the immense conjugative and hyper conjugative resonance charge delocalization of π-electrons. Molecule sites prone to electrophilic attacks have been determined by analysis of ALIE surfaces, while Fukui functions provided further insight into the local reactivity properties of title molecule. Autoxidation properties have been investigated by calculation of bond dissociation energies (BDEs) of hydrogen abstraction, while BDEs of the rest of the single acyclic bonds were valuable for the further investigation of degradation properties. Calculation of radial distribution functions was performed in order to determine which atoms of the title molecule have pronounced interactions with water molecules. The title compound forms a stable complex with aryl hydrocarbon receptor and can be a lead compound for developing new anti-tumor drug. Antimicrobial properties of the title compound was screened against one bacterial culture Escherchia coli and four fungal cultures viz., Aspergillus niger, Pencillum chrysogenum, Saccharomyces cerevisiae and Rhyzopus stolonifer.

Spectroscopic studies (FTIR, FT-Raman and UV-Visible), normal coordinate analysis, NBO analysis, first order hyper polarizability, HOMO and LUMO analysis of (1R)-N-(Prop-2-yn-1-yl)-2,3-dihydro-1H-inden-1-amine molecule by ab initio HF and density functional methods.

PubMed

Muthu, S; Ramachandran, G

2014-01-01

The Fourier transform infrared (FT-IR) and FT-Raman of (1R)-N-(Prop-2-yn-1-yl)-2,3-dihydro-1H-inden-1-amine (1RNPDA) were recorded in the regions 4000-400 cm(-1) and 4000-100 cm(-1) respectively. A complete assignment and analysis of the fundamental vibrational modes of the molecule were carried out. The observed fundamental modes have been compared with the harmonic vibrational frequencies computed using HF method by employing 6-31G(d,p) basis set and DFT(B3LYP) method by employing 6-31G(d,p) basis set. The vibrational studies were interpreted in terms of Potential Energy Distribution (PED). The complete vibrational frequency assignments were made by Normal Co-ordinate Analysis (NCA) following the scaled quantum mechanical force field methodology (SQMFF). The first order hyper polarizability (β0) of this molecular system and related properties (α, μ, and Δα) are calculated using B3LYP/6-31G(d,p) method based on the finite-field approach. The thermodynamic functions of the title compound were also performed at the above methods and basis set. A detailed interpretation of the infrared and Raman spectra of 1RNPDA is reported. The (1)H and (13)C nuclear magnetic resonance (NMR) chemical shifts of the molecule were calculated using the GIAO method confirms with the experimental values. Stability of the molecule arising from hyper-conjugative interactions and charge delocalization has been analyzed using Natural Bond Orbital (NBO) analysis. UV-vis spectrum of the compound was recorded and electronic properties such as excitation energies, oscillator strength and wavelength were performed by TD-DFT/B3LYP using 6-31G(d,p) basis set. The HOMO and LUMO energy gap reveals that the energy gap reflects the chemical activity of the molecule. The observed and calculated wave numbers are formed to be in good agreement. The experimental spectra also coincide satisfactorily with those of theoretically constructed spectra. Copyright © 2013 Elsevier B.V. All rights reserved.

Time-resolved energy transfer in DNA sequence detection using water-soluble conjugated polymers: the role of electrostatic and hydrophobic interactions.

PubMed

Xu, Qing-Hua; Gaylord, Brent S; Wang, Shu; Bazan, Guillermo C; Moses, Daniel; Heeger, Alan J

2004-08-10

We have investigated the energy transfer processes in DNA sequence detection by using cationic conjugated polymers and peptide nucleic acid (PNA) probes with ultrafast pump-dump-emission spectroscopy. Pump-dump-emission spectroscopy provides femtosecond temporal resolution and high sensitivity and avoids interference from the solvent response. The energy transfer from donor (the conjugated polymer) to acceptor (a fluorescent molecule attached to a PNA terminus) has been time resolved. The results indicate that both electrostatic and hydrophobic interactions contribute to the formation of cationic conjugated polymers/PNA-C/DNA complexes. The two interactions result in two different binding conformations. This picture is supported by the average donor-acceptor separations as estimated from time-resolved and steady-state measurements. Electrostatic interactions dominate at low concentrations and in mixed solvents.

Time-resolved energy transfer in DNA sequence detection using water-soluble conjugated polymers: The role of electrostatic and hydrophobic interactions

PubMed Central

Xu, Qing-Hua; Gaylord, Brent S.; Wang, Shu; Bazan, Guillermo C.; Moses, Daniel; Heeger, Alan J.

2004-01-01

We have investigated the energy transfer processes in DNA sequence detection by using cationic conjugated polymers and peptide nucleic acid (PNA) probes with ultrafast pump-dump-emission spectroscopy. Pump-dump-emission spectroscopy provides femtosecond temporal resolution and high sensitivity and avoids interference from the solvent response. The energy transfer from donor (the conjugated polymer) to acceptor (a fluorescent molecule attached to a PNA terminus) has been time resolved. The results indicate that both electrostatic and hydrophobic interactions contribute to the formation of cationic conjugated polymers/PNA-C/DNA complexes. The two interactions result in two different binding conformations. This picture is supported by the average donor–acceptor separations as estimated from time-resolved and steady-state measurements. Electrostatic interactions dominate at low concentrations and in mixed solvents. PMID:15282375

Photoresponsive peptide azobenzene conjugates that specifically interact with platinum surfaces

NASA Astrophysics Data System (ADS)

Dinçer, S.; Tamerler, C.; Sarıkaya, M.; Pişkin, E.

2008-05-01

The aim of this study is to prepare photoresponsive peptide-azobenzene compounds which interacts with platinum surfaces specifically, in order to create smart surfaces for further novel applications in design of smart biosensors and array platforms. Here, a water-soluble azobenzene molecule, 4-hydroxyazo benzene,4-sulfonic acid was synthesized by diazo coupling reaction. A platinum-specific peptide, originally selected by a phage display technique was chemically synthesized/purchased, and conjugated with the azobenzene compound activated with carbonyldiimidazole. Both azobenzene and its conjugate were characterized (including photoresponsive properties) by FTIR, NMR, and UV-spectrophotometer. The yield of conjugation reaction estimated by ninhydrin assay was about 65%. Peptide incorporation did not restrict the light-sensitivity of azobenzene. Adsorption of both the peptide and its azobenzene conjugate was followed by Quartz Crystal Microbalance (QCM) system. The kinetic evaluations exhibited that both molecules interact platinum surfaces, quite rapidly and strongly.

Design, synthesis and characterization of peptidomimetic conjugate of BODIPY targeting HER2 protein extracellular domain

PubMed Central

Banappagari, Sashikanth; McCall, Alecia; Fontenot, Krystal; Vicente, M. Graca H.; Gujar, Amit; Satyanarayanajois, Seetharama

2013-01-01

Among the EGFRs, HER2 is a major heterodimer partner and also has important implications in the formation of particular tumors. Interaction of HER2 protein with other EGFR proteins can be modulated by small molecule ligands and, hence, these protein-protein interactions play a key role in biochemical reactions related to control of cell growth. A peptidomimetic (compound 5-1) that binds to HER2 protein extracellular domain and inhibits protein-protein interactions of EGFRs was conjugated with BODIPY (4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene). Conjugation of BODIPY to the peptidomimetic was investigated by different approaches. The conjugate was characterized for its ability to bind to HER2 overexpressing SKBR-3 and BT-474 cells. Furthermore, cellular uptake of conjugate of BODIPY was studied in the presence of membrane tracker and Lyso tracker using confocal microscopy. Our results suggested that fluorescently labeled compound 5-7 binds to the extracellular domain and stays in the membrane for nearly 24 h. After 24 h there is an indication of internalization of the conjugate. Inhibition of protein-protein interaction and downstream signaling effect of compound 5-1 was also studied by proximity ligation assay and western blot analysis. Results suggested that compound 5-1 inhibits protein-protein interactions of HER2-HER3 and phosphorylation of HER2 in a time-dependent manner. PMID:23688700

Synthesis and interaction of sterol-uridine conjugate with DMPC liposomes studied by differential scanning calorimetry.

PubMed

Escobar, Jhon Fernando Berrío; Restrepo, Manuel Humberto Pastrana; Fernández, Diana Margarita Márquez; Martínez, Alejandro Martínez; Giordani, Cristiano; Castelli, Francesco; Sarpietro, Maria Grazia

2018-06-01

Differential scanning calorimetry (DSC) is a thermoanalytical technique which provides information on the interaction between drugs and models of cell membranes. Studies on the calorimetric behavior of hydrated phospholipids within liposomes are employed to shed light on the changes in the physico-chemical properties when interacting with drugs. In this report, new potential anti-cancer drugs such as uridine and uridine derivatives (acetonide and its succinate), 3β-5α,8α-endoperoxide-cholestan-6-en-3-ol (5,8-epidioxicholesterol) and conjugate (uridine acetonide-epidioxicholesterol succinate) have been synthesized. Steglich esterification method using coupling agents allowed to obtain the uridine acetonide-sterol conjugate. The study on the interaction between the drugs and dimiristoyl-phophatidilcholine (DMPC) liposomes has been conducted by the use of DSC. The analysis of the DSC curves indicated that the uridine and derivatives (acetonide and its succinate) present a very soft interaction with the DMPC liposomes, whereas the 5,8-epidioxicholesterol and the conjugate showed a strong effect on the thermotropic behavior. Our results suggested that the lipophilic character of uridine acetonide-sterol conjugate improves the affinity with the DMPC liposomes. Copyright © 2018 Elsevier B.V. All rights reserved.

Model fitting for small skin permeability data sets: hyperparameter optimisation in Gaussian Process Regression.

PubMed

Ashrafi, Parivash; Sun, Yi; Davey, Neil; Adams, Roderick G; Wilkinson, Simon C; Moss, Gary Patrick

2018-03-01

The aim of this study was to investigate how to improve predictions from Gaussian Process models by optimising the model hyperparameters. Optimisation methods, including Grid Search, Conjugate Gradient, Random Search, Evolutionary Algorithm and Hyper-prior, were evaluated and applied to previously published data. Data sets were also altered in a structured manner to reduce their size, which retained the range, or 'chemical space' of the key descriptors to assess the effect of the data range on model quality. The Hyper-prior Smoothbox kernel results in the best models for the majority of data sets, and they exhibited significantly better performance than benchmark quantitative structure-permeability relationship (QSPR) models. When the data sets were systematically reduced in size, the different optimisation methods generally retained their statistical quality, whereas benchmark QSPR models performed poorly. The design of the data set, and possibly also the approach to validation of the model, is critical in the development of improved models. The size of the data set, if carefully controlled, was not generally a significant factor for these models and that models of excellent statistical quality could be produced from substantially smaller data sets. © 2018 Royal Pharmaceutical Society.

Hyper-Systolic Processing on APE100/QUADRICS:. n2-LOOP Computations

NASA Astrophysics Data System (ADS)

Lippert, Thomas; Ritzenhöfer, Gero; Glaessner, Uwe; Hoeber, Henning; Seyfried, Armin; Schilling, Klaus

We investigate the performance gains from hyper-systolic implementations of n2-loop problems on the massively parallel computer Quadrics, exploiting its three-dimensional interprocessor connectivity. For illustration we study the communication aspects of an exact molecular dynamics simulation of n particles with Coulomb (or gravitational) interactions. We compare the interprocessor communication costs of the standard-systolic and the hyper-systolic approaches for various granularities. We predict gain factors as large as three on the Q4 and eight on the QH4 and measure actual performances on these machine configurations. We conclude that it appears feasible to investigate the thermodynamics of a full gravitating n-body problem with O(16.000) particles using the new method on a QH4 system.

A multi-scale model for hair follicles reveals heterogeneous domains driving rapid spatiotemporal hair growth patterning.

PubMed

Wang, Qixuan; Oh, Ji Won; Lee, Hye-Lim; Dhar, Anukriti; Peng, Tao; Ramos, Raul; Guerrero-Juarez, Christian Fernando; Wang, Xiaojie; Zhao, Ran; Cao, Xiaoling; Le, Jonathan; Fuentes, Melisa A; Jocoy, Shelby C; Rossi, Antoni R; Vu, Brian; Pham, Kim; Wang, Xiaoyang; Mali, Nanda Maya; Park, Jung Min; Choi, June-Hyug; Lee, Hyunsu; Legrand, Julien M D; Kandyba, Eve; Kim, Jung Chul; Kim, Moonkyu; Foley, John; Yu, Zhengquan; Kobielak, Krzysztof; Andersen, Bogi; Khosrotehrani, Kiarash; Nie, Qing; Plikus, Maksim V

2017-07-11

The control principles behind robust cyclic regeneration of hair follicles (HFs) remain unclear. Using multi-scale modeling, we show that coupling inhibitors and activators with physical growth of HFs is sufficient to drive periodicity and excitability of hair regeneration. Model simulations and experimental data reveal that mouse skin behaves as a heterogeneous regenerative field, composed of anatomical domains where HFs have distinct cycling dynamics. Interactions between fast-cycling chin and ventral HFs and slow-cycling dorsal HFs produce bilaterally symmetric patterns. Ear skin behaves as a hyper-refractory domain with HFs in extended rest phase. Such hyper-refractivity relates to high levels of BMP ligands and WNT antagonists, in part expressed by ear-specific cartilage and muscle. Hair growth stops at the boundaries with hyper-refractory ears and anatomically discontinuous eyelids, generating wave-breaking effects. We posit that similar mechanisms for coupled regeneration with dominant activator, hyper-refractory, and wave-breaker regions can operate in other actively renewing organs.

Synthesis of 4-((1E, 6E)-7-(4-hydroxy-3-methoxyphenyl)-3, 5-dioxohepta-1, 6-dienyl)-2-methoxyphenyl 4-fluorobenzoate, a novel monoester derivative of curcumin, its experimental and theoretical (DFT) studies

NASA Astrophysics Data System (ADS)

Srivastava, Sangeeta; Gupta, Preeti; Amandeep; Singh, Ranvijay Pratap

2016-04-01

Curcumin (1), isolated as a major component from the chloroform extract of Curcuma longa was converted to its ester derivative 4-((1E, 6E)-7-(4-hydroxy-3-methoxyphenyl)-3,5-dioxohepta-1,6-dienyl)-2-methoxyphenyl 4-fluorobenzoate (2). The compound has been characterized with the help of 1H, 13C NMR, UV, IR and mass spectrometry. The molecular geometry of synthesized compound was calculated in ground state by Density functional theory (DFT/B3LYP) using 6-31G (d,p) basis set. 1H and 13C NMR chemical shifts were calculated in ground state by using Gauge-Including Atomic Orbital (GIAO) approach and these values were correlated with experimental observations. The electronic properties such as HOMO and LUMO energies were calculated using time dependent Density Functional Theory (TD-DFT). Stability of the molecule as a result of hyper conjugative interactions and electron delocalization were analysed using Natural bond orbital (NBO) analysis. Intramolecular interactions were analysed by AIM (Atom in molecule) approach. Global reactivity descriptors were calculated to study the reactive site within molecule. The vibrational wavenumbers were calculated using DFT method and assigned with the help of potential energy distribution (PED). First hyperpolarizability values have been calculated to describe the nonlinear optical (NLO) property of the synthesized compounds. Molecular electrostatic potential (MEP) analysis has also been carried out.

Interactions of Nitroxide-Conjugated and Non-Conjugated Glycodendrimers with Normal and Cancer Cells and Biocompatibility Studies.

PubMed

Andreozzi, Elisa; Antonelli, Antonella; Cangiotti, Michela; Canonico, Barbara; Sfara, Carla; Pianetti, Anna; Bruscolini, Francesca; Sahre, Karin; Appelhans, Dietmar; Papa, Stefano; Ottaviani, Maria Francesca

2017-02-15

Poly(propyleneimine) glycodendrimers fully modified with maltose units were administered to different cancer cell lines and their effect on cell viability was evaluated by using MTS assay and flow cytometry. The mechanism of dendrimer-cell interactions was investigated by the electron paramagnetic resonance (EPR) technique by using a new nitroxide-conjugated glycodendrimer. The nitroxide groups did not modify both the biological properties (cell viability and apoptosis degree) of the dendrimers in the presence of the cells and the dendrimer-cell interactions. Since this class of dendrimers is already known to be biocompatible for human healthy cells, noncancer cells such as human peripheral blood mononuclear cells (PBMCs) and macrophages were also treated with the glycodendrimer, and EPR spectra of the nitroxide-conjugated glycodendrimer were compared for cancer and noncancer cells. It was found that this dendrimer selectively affects the cell viability of tumor cells, while, surprisingly, PBMC proliferation is induced. Moreover, H-bond-active glycodendrimer-cell interactions were different for the different cancer cell lines and noncancer cells. The nitroxide-conjugated glycodendrimer was able to interact with the cell membrane and eventually cross it, getting in contact with cytosol antioxidants. This study helps to clarify the potential anticancer effect of this class of dendrimers opening to future applications of these macromolecules as new antitumor agents.

Self-assembling peptide-based building blocks in medical applications

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

Acar, Handan; Srivastava, Samanvaya; Chung, Eun Ji

Peptides and peptide-conjugates, comprising natural and synthetic building blocks, are an increasingly popular class of biomaterials. Self-assembled nanostructures based on peptides and peptide-conjugates offer advantages such as precise selectivity and multifunctionality that can address challenges and limitations in the clinic. In this review article, we discuss recent developments in the design and self-assembly of various nanomaterials based on peptides and peptide-conjugates for medical applications, and categorize them into two themes based on the driving forces of molecular self-assembly. First, we present the self-assembled nanostructures driven by the supramolecular interactions between the peptides, with or without the presence of conjugates. Themore » studies where nanoassembly is driven by the interactions between the conjugates of peptide-conjugates are then presented. Particular emphasis is given to in vivo studies focusing on therapeutics, diagnostics, immune modulation and regenerative medicine. Finally, challenges and future perspectives are presented.« less

The sensitive and selective adsorption of aromatic compounds with highly crosslinked polymer nanoparticles

NASA Astrophysics Data System (ADS)

Liu, Shuqin; Chen, Darui; Zheng, Juan; Zeng, Lewei; Jiang, Jijun; Jiang, Ruifeng; Zhu, Fang; Shen, Yong; Wu, Dingcai; Ouyang, Gangfeng

2015-10-01

This study presents the preparation and characterization of a nanoscale Davankov-type hyper-crosslinked-polymer (HCP) as an adsorbent of benzene-ring-containing dyes and organic pollutants. HCP nanoparticles post-crosslinked from a poly(DVB-co-VBC) precursor were synthesized in this study, possessing ultrahigh surface area, hydrophobicity and stability. The as-synthesized Davankov-type HCP exhibited a rapid and selective adsorption ability towards the benzene-ring-containing dyes due to its highly conjugated structure. Besides, for the first time, the prepared HCP nanoparticles were adopted for the adsorption of nonpolar organic pollutants by means of solid-phase microextraction (SPME). Owing to its high hydrophobicity, diverse pore size distribution and highly conjugated structure, a 10 μm HCP coating exhibited excellent adsorption abilities towards benzene-ring-containing polycyclic aromatic hydrocarbons (PAHs) and benzene series compounds (benzene, toluene, ethylbenzene and o-xylene; abbreviated to BTEX) and to highly hydrophobic long-chain n-alkanes. Finally, the HCP-nanoparticles-coated SPME fiber was applied to the simultaneous analysis of five PAHs in environmental water samples and satisfactory recoveries were achieved. The findings could provide a new benchmark for the exploitation of superb HCPs as effective adsorbents for SPME or other adsorption applications.This study presents the preparation and characterization of a nanoscale Davankov-type hyper-crosslinked-polymer (HCP) as an adsorbent of benzene-ring-containing dyes and organic pollutants. HCP nanoparticles post-crosslinked from a poly(DVB-co-VBC) precursor were synthesized in this study, possessing ultrahigh surface area, hydrophobicity and stability. The as-synthesized Davankov-type HCP exhibited a rapid and selective adsorption ability towards the benzene-ring-containing dyes due to its highly conjugated structure. Besides, for the first time, the prepared HCP nanoparticles were adopted for the adsorption of nonpolar organic pollutants by means of solid-phase microextraction (SPME). Owing to its high hydrophobicity, diverse pore size distribution and highly conjugated structure, a 10 μm HCP coating exhibited excellent adsorption abilities towards benzene-ring-containing polycyclic aromatic hydrocarbons (PAHs) and benzene series compounds (benzene, toluene, ethylbenzene and o-xylene; abbreviated to BTEX) and to highly hydrophobic long-chain n-alkanes. Finally, the HCP-nanoparticles-coated SPME fiber was applied to the simultaneous analysis of five PAHs in environmental water samples and satisfactory recoveries were achieved. The findings could provide a new benchmark for the exploitation of superb HCPs as effective adsorbents for SPME or other adsorption applications. Electronic supplementary information (ESI) available: Fig. S1-S8, details of optimization of the SPME condition, Tables S1-S5. See DOI: 10.1039/c5nr04624f

BSA modification to reduce CTAB induced nonspecificity and cytotoxicity of aptamer-conjugated gold nanorods

NASA Astrophysics Data System (ADS)

Yasun, Emir; Li, Chunmei; Barut, Inci; Janvier, Denisse; Qiu, Liping; Cui, Cheng; Tan, Weihong

2015-05-01

Aptamer-conjugated gold nanorods (AuNRs) are excellent candidates for targeted hyperthermia therapy of cancer cells. However, in high concentrations of AuNRs, aptamer conjugation alone fails to result in highly cell-specific AuNRs due to the presence of positively charged cetyltrimethylammonium bromide (CTAB) as a templating surfactant. Besides causing nonspecific electrostatic interactions with the cell surfaces, CTAB can also be cytotoxic, leading to uncontrolled cell death. To avoid the nonspecific interactions and cytotoxicity triggered by CTAB, we report the further biologically inspired modification of aptamer-conjugated AuNRs with bovine serum albumin (BSA) protein. Following this modification, interaction between CTAB and the cell surface was efficiently blocked, thereby dramatically reducing the side effects of CTAB. This approach may provide a general and simple method to avoid one of the most serious issues in biomedical applications of nanomaterials: nonspecific binding of the nanomaterials with biological cells.Aptamer-conjugated gold nanorods (AuNRs) are excellent candidates for targeted hyperthermia therapy of cancer cells. However, in high concentrations of AuNRs, aptamer conjugation alone fails to result in highly cell-specific AuNRs due to the presence of positively charged cetyltrimethylammonium bromide (CTAB) as a templating surfactant. Besides causing nonspecific electrostatic interactions with the cell surfaces, CTAB can also be cytotoxic, leading to uncontrolled cell death. To avoid the nonspecific interactions and cytotoxicity triggered by CTAB, we report the further biologically inspired modification of aptamer-conjugated AuNRs with bovine serum albumin (BSA) protein. Following this modification, interaction between CTAB and the cell surface was efficiently blocked, thereby dramatically reducing the side effects of CTAB. This approach may provide a general and simple method to avoid one of the most serious issues in biomedical applications of nanomaterials: nonspecific binding of the nanomaterials with biological cells. Electronic supplementary information (ESI) available: Fig. S-1 to S-6 are included. See DOI: 10.1039/c5nr01704a

Hyper-Resolution Groundwater Modeling using MODFLOW 6

NASA Astrophysics Data System (ADS)

Hughes, J. D.; Langevin, C.

2017-12-01

MODFLOW 6 is the latest version of the U.S. Geological Survey's modular hydrologic model. MODFLOW 6 was developed to synthesize many of the recent versions of MODFLOW into a single program, improve the way different process models are coupled, and to provide an object-oriented framework for adding new types of models and packages. The object-oriented framework and underlying numerical solver make it possible to tightly couple any number of hyper-resolution models within coarser regional models. The hyper-resolution models can be used to evaluate local-scale groundwater issues that may be affected by regional-scale forcings. In MODFLOW 6, hyper-resolution meshes can be maintained as separate model datasets, similar to MODFLOW-LGR, which simplifies the development of a coarse regional model with imbedded hyper-resolution models from a coarse regional model. For example, the South Atlantic Coastal Plain regional water availability model was converted from a MODFLOW-2000 model to a MODFLOW 6 model. The horizontal discretization of the original model is approximately 3,218 m x 3,218 m. Hyper-resolution models of the Aiken and Sumter County water budget areas in South Carolina with a horizontal discretization of approximately 322 m x 322 m were developed and were tightly coupled to a modified version of the original coarse regional model that excluded these areas. Hydraulic property and aquifer geometry data from the coarse model were mapped to the hyper-resolution models. The discretization of the hyper-resolution models is fine enough to make detailed analyses of the effect that changes in groundwater withdrawals in the production aquifers have on the water table and surface-water/groundwater interactions. The approach used in this analysis could be applied to other regional water availability models that have been developed by the U.S. Geological Survey to evaluate local scale groundwater issues.

Layered crystal structure, conformational and vibrational properties of 2,2,2-trichloroethoxysulfonamide: An experimental and theoretical study

NASA Astrophysics Data System (ADS)

Gil, Diego M.; Piro, Oscar E.; Echeverría, Gustavo A.; Tuttolomondo, María E.; Altabef, Aída Ben

2013-12-01

The molecular structure of 2,2,2-trichloroethoxysulfonamide, CCl3CH2OSO2NH2, has been determined in the solid state by X-ray diffraction data and in the gas phase by ab initio (MP2) and DFT calculations. The substance crystallizes in the monoclinic P21/c space group with a = 9.969(3) Å, b = 22.914(6) Å, c = 7.349(2) Å, β = 91.06(3)°, and Z = 8 molecules per unit cell. There are two independent, but closely related molecular conformers in the crystal asymmetric unit. They only differ in the angular orientation of the sulfonamide (sbnd SO2NH2) group. The conformers are arranged in the lattice as center-symmetric Nsbnd H⋯O(sulf)-bonded dimers. Neighboring dimers are linked through further Nsbnd H⋯O(sulf) bonds giving rise to a crystal layered structure. The solid state infrared and Raman spectra have been recorded and the observed bands assigned to the molecular vibration modes. Also, the thermal behavior of the substance was investigated by TG-DT analysis. The stability of the molecule arising from hyper-conjugative interactions and charge delocalization has been analyzed using natural bond (NBO) analysis.

Spectroscopic (FT-IR, FT-Raman, and UV-visible) and quantum chemical studies on molecular geometry, Frontier molecular orbitals, NBO, NLO and thermodynamic properties of 1-acetylindole.

PubMed

Shukla, Vikas K; Al-Abdullah, Ebtehal S; El-Emam, Ali A; Sachan, Alok K; Pathak, Shilendra K; Kumar, Amarendra; Prasad, Onkar; Bishnoi, Abha; Sinha, Leena

2014-12-10

Quantum chemical calculations of ground state energy, geometrical structure and vibrational wavenumbers of 1-acetylindole were carried out using density functional (DFT/B3LYP) method with 6-311++G(d,p) basis set. The FT-IR and FT-Raman spectra were recorded in the condensed state. The fundamental vibrational wavenumbers were calculated and a good correlation between experimental and scaled calculated wavenumbers has been accomplished. Electric dipole moment, polarizability and first static hyperpolarizability values of 1-acetylindole have been calculated at the same level of theory and basis set. The results show that the 1-acetylindole molecule possesses nonlinear optical (NLO) behavior with non-zero values. Stability of the molecule arising from hyper-conjugative interactions and charge delocalization has been analyzed using natural bond orbital (NBO) analysis. UV-Visible spectrum of the molecule was recorded in the region 200-500nm and the electronic properties like HOMO and LUMO energies and composition were obtained using TD-DFT method. The calculated energies and oscillator strengths are in good correspondence with the experimental data. The thermodynamic properties of the compound under investigation were calculated at different temperatures. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparative studies on molecular structure, vibrational spectra and hyperpolarizabilies of NLO chromophore Ethyl 4-Dimethylaminobenzoate

NASA Astrophysics Data System (ADS)

Amalanathan, M.; Jasmine, G. Femina; Roy, S. Dawn Dharma

2017-08-01

The molecular structure, vibrational spectra and polarizabilities of Ethyl 4-Dimethylaminobenzoate (EDAB) was investigated by density functional theory employing Becke's three parameter hybrid exchange functional with Lee-Yang-Parr (B3LYP) co-relational functional involving 6-311++G(d,p) basis set and compared with some other levels. A detailed interpretation of the IR and Raman spectra of EDBA have been reported and analyzed. Complete vibrational assignments of the vibrational modes have been done on the basis of the potential energy distribution (TED) using VEDA software. The molecular electrostatic potential mapped onto total density surface has been obtained. A study on the electronic properties, such as absorption wavelength, and frontier molecular orbitals energy, was performed using DFT approach. The stability of the molecule arising from hyper conjugative interactions and accompanying charge delocalization has been analyzed using natural bond orbital (NBO) analysis. The natural and Mulliken charge also calculated and compared with different level of calculation. The dipole moment, polarizability and first, second order hyperpolarizabilities of the title molecule were calculated and compared with the experimental values. The energy gap between frontier orbitals has been used along with electric moments and first order hyperpolarizability, to understand the non linear optical (NLO) activity of the molecule. The NLO activity of molecule was confirmed by SHG analysis.

Theoretical investigations on the structure and properties of p-n-alkoxy benzoic acid based liquid crystals

NASA Astrophysics Data System (ADS)

Subhapriya, P.; Dhanapal, V.; Sadasivam, K.; Vijayanand, P. S.

2016-05-01

The present study focused on the structural conformations, alkoxy chain lengths and mesogenic properties of two mole of alkoxy benzoic acid(nOBA) and one mole of suberic acid (SA) hydrogen bonded (nOBASA) complexes (n=8 to 10) by density functional theory (DFT) calculations and the Fourier Transform Infrared (FT-IR) spectrum. The intermolecular hydrogen bond formation was confirmed by the optimized geometric bond lengths and bond angles obtained by computation. Using the natural bond orbital (NBO) analysis, the stability of the molecule arising from hyper conjugative interactions and charge delocalization has been analyzed. Results obtained shows that the charge in electron density (ED) in σ*and π* antibonding orbital and second order delocalization energies E(2) authorizes the occurrence of intermolecular charge transfer. The molecular electrostatic potential (MEP) surface map is plotted over the optimized geometry of the molecule to obtain the chemical reactivity of the molecule. From the local charge distributions, the mesomorphic behavior and the nematic phase stabilities for each of the molecule have been predicted. Finally the calculated result is applied to simulated infrared spectra of 8OBASA mesogens which shows good agreement with the observed spectra. The comparison of the theoretical results obtained with the experimental ones shows the reliability of this DFT method.

Spectroscopic investigations and molecular docking study of 3-(1H-imidazol-1-yl)-1-phenylpropan-1-one, a potential precursor to bioactive agents

NASA Astrophysics Data System (ADS)

Al-Alshaikh, Monirah A.; Mary Y, Sheena; Panicker, C. Yohannan; Attia, Mohamed I.; El-Emam, Ali A.; Alsenoy, C. Van

2016-04-01

The optimized molecular structure, vibrational wavenumbers, corresponding vibrational assignments of 3-(1H-imidazol-1-yl)-1-phenylpropan-1-one have been investigated theoretically and experimentally. The calculated geometrical parameters of the title compound are in agreement with the reported XRD data. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. Molecular electrostatic potential was performed by the DFT method and from the MEP plot, it is evident that the negative charge covers the carbonyl group and the nitrogen atom N3 of the imidazole ring and the positive region is over the remaining portions of the molecule. The first and second hyperpolarizabilities are calculated and the first hyperpolarizability of the title compound is 16.99 times that of standard NLO material urea and the title compound and its derivatives are good object for further studies in nonlinear optics. The docked ligand title compound forms a stable complex with plasmodium falciparum and gives a binding affinity value of -5.5 kcal/mol and the preliminary results suggest that the compound might exhibit antimalarial activity against plasmodium falciparum.

Vibrational, UV spectra, NBO, first order hyperpolarizability and HOMO-LUMO analysis of carvedilol

NASA Astrophysics Data System (ADS)

Swarnalatha, N.; Gunasekaran, S.; Nagarajan, M.; Srinivasan, S.; Sankari, G.; Ramkumaar, G. R.

2015-02-01

In this work, we have investigated experimentally and theoretically on the molecular structure, vibrational spectra, UV spectral analysis and NBO studies of cardio-protective drug carvedilol. The FT-Raman and FT-IR spectra for carvedilol in the solid phase have been recorded in the region 4000-100 cm-1 and 4000-400 cm-1 respectively. Theoretical calculations were performed by using density functional theory (DFT) method at B3LYP/6-31G(d,p) and B3LYP/6-31++G(d,p) basis set levels. The harmonic vibrational frequencies, the optimized geometric parameters have been interpreted and compared with the reported experimental values. The complete vibrational assignments were performed on the basis of potential energy distribution (PED) of the vibrational modes. The thermodynamic properties and molecular electrostatic potential surfaces of the molecule were constructed. The electronic absorption spectrum was recorded in the region 400-200 nm and electronic properties such as HOMO and LUMO energies were calculated. The stability of the molecule arising from hyper conjugative interactions and charge delocalization have been analyzed from natural bond orbital (NBO) analysis. The first order hyperpolarizability of the title molecule was also calculated. The photo stability of carvedilol under different storage conditions were analyzed using UV-Vis spectral technique.

Repulsive four-body interactions of α particles and quasistable nuclear α -particle condensates in heavy self-conjugate nuclei

NASA Astrophysics Data System (ADS)

Bai, Dong; Ren, Zhongzhou

2018-05-01

We study the effects of repulsive four-body interactions of α particles on nuclear α -particle condensates in heavy self-conjugate nuclei using a semianalytic approach, and find that the repulsive four-body interactions could decrease the critical number of α particles, beyond which quasistable α -particle condensate states can no longer exist, even if these four-body interactions make only tiny contributions to the total energy of the Hoyle-like state of 16O. Explicitly, we study eight benchmark parameter sets, and find that the critical number Ncr decreases by |Δ Ncr|˜1 -4 from Ncr˜11 with vanishing four-body interactions. We also discuss the effects of four-body interactions on energies and radii of α -particle condensates. Our study can be useful for future experiments to study α -particle condensates in heavy self-conjugate nuclei. Also, the experimental determination of Ncr will eventually help establish a better understanding on the α -particle interactions, especially the four-body interactions.

A multi-scale model for hair follicles reveals heterogeneous domains driving rapid spatiotemporal hair growth patterning

PubMed Central

Wang, Qixuan; Oh, Ji Won; Lee, Hye-Lim; Dhar, Anukriti; Peng, Tao; Ramos, Raul; Guerrero-Juarez, Christian Fernando; Wang, Xiaojie; Zhao, Ran; Cao, Xiaoling; Le, Jonathan; Fuentes, Melisa A; Jocoy, Shelby C; Rossi, Antoni R; Vu, Brian; Pham, Kim; Wang, Xiaoyang; Mali, Nanda Maya; Park, Jung Min; Choi, June-Hyug; Lee, Hyunsu; Legrand, Julien M D; Kandyba, Eve; Kim, Jung Chul; Kim, Moonkyu; Foley, John; Yu, Zhengquan; Kobielak, Krzysztof; Andersen, Bogi; Khosrotehrani, Kiarash; Nie, Qing; Plikus, Maksim V

2017-01-01

The control principles behind robust cyclic regeneration of hair follicles (HFs) remain unclear. Using multi-scale modeling, we show that coupling inhibitors and activators with physical growth of HFs is sufficient to drive periodicity and excitability of hair regeneration. Model simulations and experimental data reveal that mouse skin behaves as a heterogeneous regenerative field, composed of anatomical domains where HFs have distinct cycling dynamics. Interactions between fast-cycling chin and ventral HFs and slow-cycling dorsal HFs produce bilaterally symmetric patterns. Ear skin behaves as a hyper-refractory domain with HFs in extended rest phase. Such hyper-refractivity relates to high levels of BMP ligands and WNT antagonists, in part expressed by ear-specific cartilage and muscle. Hair growth stops at the boundaries with hyper-refractory ears and anatomically discontinuous eyelids, generating wave-breaking effects. We posit that similar mechanisms for coupled regeneration with dominant activator, hyper-refractory, and wave-breaker regions can operate in other actively renewing organs. DOI: http://dx.doi.org/10.7554/eLife.22772.001 PMID:28695824

Prescreening of Nicotine Hapten Linkers in Vitro To Select Hapten-Conjugate Vaccine Candidates for Pharmacokinetic Evaluation in Vivo.

PubMed

Arutla, Viswanath; Leal, Joseph; Liu, Xiaowei; Sokalingam, Sriram; Raleigh, Michael; Adaralegbe, Adejimi; Liu, Li; Pentel, Paul R; Hecht, Sidney M; Chang, Yung

2017-05-08

Since the demonstration of nicotine vaccines as a possible therapeutic intervention for the effects of tobacco smoke, extensive effort has been made to enhance nicotine specific immunity. Linker modifications of nicotine haptens have been a focal point for improving the immunogenicity of nicotine, in which the evaluation of these modifications usually relies on in vivo animal models, such as mice, rats or nonhuman primates. Here, we present two in vitro screening strategies to estimate and predict the immunogenic potential of our newly designed nicotine haptens. One utilizes a competition enzyme-linked immunoabsorbent assay (ELISA) to profile the interactions of nicotine haptens or hapten-protein conjugates with nicotine specific antibodies, both polyclonal and monoclonal. Another relies on computational modeling of the interactions between haptens and amino acid residues near the conjugation site of the carrier protein to infer linker-carrier protein conjugation effect on antinicotine antibody response. Using these two in vitro methods, we ranked the haptens with different linkers for their potential as viable vaccine candidates. The ELISA-based hapten ranking was in an agreement with the results obtained by in vivo nicotine pharmacokinetic analysis. A correlation was found between the average binding affinity (IC 50 ) of the haptens to an anti-Nic monoclonal antibody and the average brain nicotine concentration in the immunized mice. The computational modeling of hapten and carrier protein interactions helps exclude conjugates with strong linker-carrier conjugation effects and low in vivo efficacy. The simplicity of these in vitro screening strategies should facilitate the selection and development of more effective nicotine conjugate vaccines. In addition, these data highlight a previously under-appreciated contribution of linkers and hapten-protein conjugations to conjugate vaccine immunogenicity by virtue of their inclusion in the epitope that binds and activates B cells.

PEG-coumarin nanoaggregates as π-π stacking derived small molecule lipophile containing self-assemblies for anti-tumour drug delivery.

PubMed

Behl, Gautam; Kumar, Parveen; Sikka, Manisha; Fitzhenry, Laurence; Chhikara, Aruna

2018-03-01

Polymeric self-assemblies formed by non-covalent interactions such as hydrophobic interactions, hydrogen bonding, π-π stacking, host-guest and electrostatic interactions have been utilised widely and exhibit controlled release of encapsulated drug. Beside carrier-carrier interactions, small molecule amphiphiles exhibiting carrier-drug interactions have recently been an area of interest for cancer drug delivery, as most of the hydrophobic anti-tumour drugs are aromatic and exhibit π-π conjugated structure. In the present study PEG-coumarin (PC) conjugates forming self-assembled nanoaggregates were synthesised with PEG (polyethylene glycol) as hydrophilic block and coumarin as small molecule lipophilic segment. Curcumin (CUR) as model conjugated aromatic drug was loaded in to the nanoaggregates via dual hydrophobic and π-π stacking interactions. The interactions between the conjugates and CUR, drug release profile and in vitro anti-tumour efficacy were investigated in detail. CUR-loaded nanoaggregate self-assembly was driven by π-π interactions and a maximum loading level of about 18 wt.% (~60 % encapsulation efficiency) was achieved. The average hydrodynamic diameter (D av ) was in the range of 120-160 nm and a spherical morphology was observed by transmission electron microscopy (TEM). A sustained release of CUR was observed for 90 h. Cytotoxicity evaluation of CUR-loaded nanoaggregates on pancreatic cancer cell lines indicated higher efficacy, IC 50 ~11 and ~15 μM as compared to free CUR, IC 50 ~14 and ~20 μM on human pancreatic carcinoma (MIA PaCa-2) and human pancreatic duct epithelioid carcinoma (PANC-1) cell lines respectively. PC conjugates provided a new strategy of fabricating nanoparticles for drug delivery and may form the basis for the development of advanced biomaterials in near future.

Controlling Molecular Ordering in Solution-State Conjugated Polymers

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

Zhu, Jiahua; Han, Youngkyu; Kumar, Rajeev

Rationally encoding molecular interactions that can control the assembly structure and functional expression in solution of conjugated polymers holds great potential for enabling optimal organic optoelectronic and sensory materials. In this work, we show that thermally-controlled and surfactant-guided assembly of water-soluble conjugated polymers in aqueous solution is a simple and effective strategy to generate optoelectronic materials with desired molecular ordering. We have studied a conjugated polymer consisting of a hydrophobic thiophene backbone and hydrophilic, thermo-responsive ethylene oxide side groups, which shows a step-wise, multi-dimensional assembly in water. By incorporating the polymer into phase-segregated domains of an amphiphilic surfactant in solution,more » we demonstrate that both chain conformation and degree of molecular ordering of the conjugated polymer can be tuned in hexagonal, micellar and lamellar phases of the surfactant solution. The controlled molecular ordering in conjugated polymer assembly is demonstrated as a key factor determining the electronic interaction and optical function.« less

Controlling Molecular Ordering in Solution-State Conjugated Polymers

DOE PAGES

Zhu, Jiahua; Han, Youngkyu; Kumar, Rajeev; ...

2015-07-17

Rationally encoding molecular interactions that can control the assembly structure and functional expression in solution of conjugated polymers holds great potential for enabling optimal organic optoelectronic and sensory materials. In this work, we show that thermally-controlled and surfactant-guided assembly of water-soluble conjugated polymers in aqueous solution is a simple and effective strategy to generate optoelectronic materials with desired molecular ordering. We have studied a conjugated polymer consisting of a hydrophobic thiophene backbone and hydrophilic, thermo-responsive ethylene oxide side groups, which shows a step-wise, multi-dimensional assembly in water. By incorporating the polymer into phase-segregated domains of an amphiphilic surfactant in solution,more » we demonstrate that both chain conformation and degree of molecular ordering of the conjugated polymer can be tuned in hexagonal, micellar and lamellar phases of the surfactant solution. The controlled molecular ordering in conjugated polymer assembly is demonstrated as a key factor determining the electronic interaction and optical function.« less

Hypermedia = hypercommunication

NASA Technical Reports Server (NTRS)

Laff, Mark R.

1990-01-01

New hardware and software technology gave application designers the freedom to use new realism in human computer interaction. High-quality images, motion video, stereo sound and music, speech, touch, gesture provide richer data channels between the person and the machine. Ultimately, this will lead to richer communication between people with the computer as an intermediary. The whole point of hyper-books, hyper-newspapers, virtual worlds, is to transfer the concept and relationships, the 'data structure', from the mind of creator to that of user. Some of the characteristics of this rich information channel are discussed, and some examples are presented.

Interactive Video and Informal Learning Environments.

ERIC Educational Resources Information Center

Morrissey, Kristine A.

The Michigan State University Museum used an interactive videodisc (IVD) as an introduction to a special exhibit, "Birds in Trouble in Michigan." The hardware components included a videodisc player, a microcomputer, a video monitor, and a mouse. Software included a HyperCard program and the videodisc "Audubon Society's VideoGuide to…

Russian HyperTutor: Designing Interactive Multimedia for the Macintosh.

ERIC Educational Resources Information Center

Mitrevski, George

1995-01-01

Describes an interactive, multimedia computer program designed to teach Russian grammar, and accompany a commercial textbook. Each of the 35 lessons integrates graphics, sound, and animation. A dictionary and extensive vocabulary exercises are also included. Tutorials provide simple but concise grammar explanations that the teacher can edit or…

On the interpretation of synchronization in EEG hyperscanning studies: a cautionary note.

PubMed

Burgess, Adrian P

2013-01-01

EEG Hyperscanning is a method for studying two or more individuals simultaneously with the objective of elucidating how co-variations in their neural activity (i.e., hyperconnectivity) are influenced by their behavioral and social interactions. The aim of this study was to compare the performance of different hyper-connectivity measures using (i) simulated data, where the degree of coupling could be systematically manipulated, and (ii) individually recorded human EEG combined into pseudo-pairs of participants where no hyper-connections could exist. With simulated data we found that each of the most widely used measures of hyperconnectivity were biased and detected hyper-connections where none existed. With pseudo-pairs of human data we found spurious hyper-connections that arose because there were genuine similarities between the EEG recorded from different people independently but under the same experimental conditions. Specifically, there were systematic differences between experimental conditions in terms of the rhythmicity of the EEG that were common across participants. As any imbalance between experimental conditions in terms of stimulus presentation or movement may affect the rhythmicity of the EEG, this problem could apply in many hyperscanning contexts. Furthermore, as these spurious hyper-connections reflected real similarities between the EEGs, they were not Type-1 errors that could be overcome by some appropriate statistical control. However, some measures that have not previously been used in hyperconnectivity studies, notably the circular correlation co-efficient (CCorr), were less susceptible to detecting spurious hyper-connections of this type. The reason for this advantage in performance is discussed and the use of the CCorr as an alternative measure of hyperconnectivity is advocated.

Quantitative computed tomography determined regional lung mechanics in normal nonsmokers, normal smokers and metastatic sarcoma subjects.

PubMed

Choi, Jiwoong; Hoffman, Eric A; Lin, Ching-Long; Milhem, Mohammed M; Tessier, Jean; Newell, John D

2017-01-01

Extra-thoracic tumors send out pilot cells that attach to the pulmonary endothelium. We hypothesized that this could alter regional lung mechanics (tissue stiffening or accumulation of fluid and inflammatory cells) through interactions with host cells. We explored this with serial inspiratory computed tomography (CT) and image matching to assess regional changes in lung expansion. We retrospectively assessed 44 pairs of two serial CT scans on 21 sarcoma patients: 12 without lung metastases and 9 with lung metastases. For each subject, two or more serial inspiratory clinically-derived CT scans were retrospectively collected. Two research-derived control groups were included: 7 normal nonsmokers and 12 asymptomatic smokers with two inspiratory scans taken the same day or one year apart respectively. We performed image registration for local-to-local matching scans to baseline, and derived local expansion and density changes at an acinar scale. Welch two sample t test was used for comparison between groups. Statistical significance was determined with a p value < 0.05. Lung regions of metastatic sarcoma patients (but not the normal control group) demonstrated an increased proportion of normalized lung expansion between the first and second CT. These hyper-expanded regions were associated with, but not limited to, visible metastatic lung lesions. Compared with the normal control group, the percent of increased normalized hyper-expanded lung in sarcoma subjects was significantly increased (p < 0.05). There was also evidence of increased lung "tissue" volume (non-air components) in the hyper-expanded regions of the cancer subjects relative to non-hyper-expanded regions. "Tissue" volume increase was present in the hyper-expanded regions of metastatic and non-metastatic sarcoma subjects. This putatively could represent regional inflammation related to the presence of tumor pilot cell-host related interactions. This new quantitative CT (QCT) method for linking serial acquired inspiratory CT images may provide a diagnostic and prognostic means to objectively characterize regional responses in the lung following oncological treatment and monitoring for lung metastases.

A Scheme for the Evaluation of Electron Delocalization and Conjugation Efficiency in Linearly π-Conjugated Systems.

PubMed

Bruschi, Maurizio; Limacher, Peter A; Hutter, Jürg; Lüthi, Hans Peter

2009-03-10

In this study, we present a scheme for the evaluation of electron delocalization and conjugation efficiency in lineraly π-conjugated systems. The scheme, based on the natural bond orbital theory, allows monitoring the evolution of electron delocalization along an extended conjugation path as well as its response to chemical modification. The scheme presented is evaluated and illustrated by means of a computational investigation of π-conjugation in all-trans polyacetylene [PA; H(-CH═CH)n-H], polydiacetylene [PDA, H(-C≡C-CH═CH)n-H], and polytriacetylene [PTA, H(-C≡C-CH═CH-C≡C)n-H] with up to 180 carbon atoms, all related by the number of ethynyl units incorporated in the chain. We are able to show that for short oligomers the incorporation of ethynyl spacers into the PA chain increases the π-delocalization energy, but, on the other hand, reduces the efficiency with which π-electron delocalization is promoted along the backbone. This explains the generally shorter effective conjugation lengths observed for the properties of the polyeneynes (PDA and PTA) relative to the polyenes (PA). It will also be shown that the reduced conjugation efficiency, within the NBO-based model presented in this work, can be related to the orbital interaction pattern along the π-conjugated chain. We will show that the orbital interaction energy pattern is characteristic for the type and the length of the backbone and may therefore serve as a descriptor for linearly π-conjugated chains.

Maternal hyperthyroidism alters the pattern of expression of cardiac renin-angiotensin system components in rat offspring.

PubMed

Lino, Caroline A; Shibata, Caroline E R; Barreto-Chaves, Maria Luiza M

2014-03-01

Changes in perinatal environment can lead to physiological, morphological, or metabolic alterations in adult life. It is well known that thyroid hormones (TH) are critical for the development, growth, and maturation of organs and systems. In addition, TH interact with the renin-angiotensin system (RAS), and both play a critical role in adult cardiovascular function. The objective of this study was to evaluate the effect of maternal hyperthyroidism on cardiac RAS components in pups during development. From gestational day nine (GD9), pregnant Wistar rats received thyroxine (T4, 12 mg/l in tap water; Hyper group) or vehicle (control group). Dams and pups were killed on GD18 and GD20. Serum concentrations of triiodothyronine (T3) and T4 were higher in the Hyper group than in the control group dams. Cardiac hypertrophy was observed in Hyper pups on GD20. Cardiac angiotensin-converting enzyme (ACE) activity was significantly lower in Hyper pups on both GD18 and GD20, but there was no difference in Ang I/Ang II levels. Ang II receptors expression was higher in the Hyper pup heart on GD18. Maternal hyperthyroidism is associated with alterations in fetal development and altered pattern of expression in RAS components, which in addition to cardiac hypertrophy observed on GD20 may represent an important predisposing factor to cardiovascular diseases in adult life.

Hyper-branched CdTe nanostructures based on the self-assembling of quantum dots and their optical properties.

PubMed

Pan, Ling-Yun; Pan, Gen-Cai; Zhang, Yong-Lai; Gao, Bing-Rong; Dai, Zhen-Wen

2013-02-01

As the priority of interconnects and active components in nanoscale optical and electronic devices, three-dimensional hyper-branched nanostructures came into focus of research. Recently, a novel crystallization route, named as "nonclassical crystallization," has been reported for three-dimensional nanostructuring. In this process, Quantum dots are used as building blocks for the construction of the whole hyper-branched structures instead of ions or single-molecules in conventional crystallization. The specialty of these nanostructures is the inheritability of pristine quantum dots' physical integrity because of their polycrystalline structures, such as quantum confinement effect and thus the luminescence. Moreover, since a longer diffusion length could exist in polycrystalline nanostructures due to the dramatically decreased distance between pristine quantum dots, the exciton-exciton interaction would be different with well dispersed quantum dots and single crystal nanostructures. This may be a benefit for electron transport in solar cell application. Therefore, it is very necessary to investigate the exciton-exciton interaction in such kind of polycrystalline nanostructures and their optical properites for solar cell application. In this research, we report a novel CdTe hyper-branched nanostructures based on self-assembly of CdTe quantum dots. Each branch shows polycrystalline with pristine quantum dots as the building units. Both steady state and time-resolved spectroscopy were performed to investigate the properties of carrier transport. Steady state optical properties of pristine quantum dots are well inherited by formed structures. While a suppressed multi-exciton recombination rate was observed. This result supports the percolation of carriers through the branches' network.

Machine Learning Classification Combining Multiple Features of A Hyper-Network of fMRI Data in Alzheimer's Disease

PubMed Central

Guo, Hao; Zhang, Fan; Chen, Junjie; Xu, Yong; Xiang, Jie

2017-01-01

Exploring functional interactions among various brain regions is helpful for understanding the pathological underpinnings of neurological disorders. Brain networks provide an important representation of those functional interactions, and thus are widely applied in the diagnosis and classification of neurodegenerative diseases. Many mental disorders involve a sharp decline in cognitive ability as a major symptom, which can be caused by abnormal connectivity patterns among several brain regions. However, conventional functional connectivity networks are usually constructed based on pairwise correlations among different brain regions. This approach ignores higher-order relationships, and cannot effectively characterize the high-order interactions of many brain regions working together. Recent neuroscience research suggests that higher-order relationships between brain regions are important for brain network analysis. Hyper-networks have been proposed that can effectively represent the interactions among brain regions. However, this method extracts the local properties of brain regions as features, but ignores the global topology information, which affects the evaluation of network topology and reduces the performance of the classifier. This problem can be compensated by a subgraph feature-based method, but it is not sensitive to change in a single brain region. Considering that both of these feature extraction methods result in the loss of information, we propose a novel machine learning classification method that combines multiple features of a hyper-network based on functional magnetic resonance imaging in Alzheimer's disease. The method combines the brain region features and subgraph features, and then uses a multi-kernel SVM for classification. This retains not only the global topological information, but also the sensitivity to change in a single brain region. To certify the proposed method, 28 normal control subjects and 38 Alzheimer's disease patients were selected to participate in an experiment. The proposed method achieved satisfactory classification accuracy, with an average of 91.60%. The abnormal brain regions included the bilateral precuneus, right parahippocampal gyrus\\hippocampus, right posterior cingulate gyrus, and other regions that are known to be important in Alzheimer's disease. Machine learning classification combining multiple features of a hyper-network of functional magnetic resonance imaging data in Alzheimer's disease obtains better classification performance. PMID:29209156

A versatile targeting system with lentiviral vectors bearing the biotin-adaptor peptide

PubMed Central

Morizono, Kouki; Xie, Yiming; Helguera, Gustavo; Daniels, Tracy R.; Lane, Timothy F.; Penichet, Manuel L.; Chen, Irvin S. Y.

2010-01-01

Background Targeted gene transduction in vivo is the ultimate preferred method for gene delivery. We previously developed targeting lentiviral vectors that specifically recognize cell surface molecules with conjugated antibodies and mediate targeted gene transduction both in vitro and in vivo. Although effective in some experimental settings, the conjugation of virus with antibodies is mediated by the interaction between protein A and the Fc region of antibodies, which is not as stable as covalent conjugation. We have now developed a more stable conjugation strategy utilizing the interaction between avidin and biotin. Methods We inserted the biotin-adaptor-peptide, which was biotinylated by secretory biotin ligase at specific sites, into our targeting envelope proteins, enabling conjugation of the pseudotyped virus with avidin, streptavidin or neutravidin. Results When conjugated with avidin-antibody fusion proteins or the complex of avidin and biotinylated targeting molecules, the vectors could mediate specific transduction to targeted cells recognized by the targeting molecules. When conjugated with streptavidin-coated magnetic beads, transduction by the vectors was targeted to the locations of magnets. Conclusions This targeting vector system can be used for broad applications of targeted gene transduction using biotinylated targeting molecules or targeting molecules fused with avidin. PMID:19455593

Incorporating human-water dynamics in a hyper-resolution land surface model

NASA Astrophysics Data System (ADS)

Vergopolan, N.; Chaney, N.; Wanders, N.; Sheffield, J.; Wood, E. F.

2017-12-01

The increasing demand for water, energy, and food is leading to unsustainable groundwater and surface water exploitation. As a result, the human interactions with the environment, through alteration of land and water resources dynamics, need to be reflected in hydrologic and land surface models (LSMs). Advancements in representing human-water dynamics still leave challenges related to the lack of water use data, water allocation algorithms, and modeling scales. This leads to an over-simplistic representation of human water use in large-scale models; this is in turn leads to an inability to capture extreme events signatures and to provide reliable information at stakeholder-level spatial scales. The emergence of hyper-resolution models allows one to address these challenges by simulating the hydrological processes and interactions with the human impacts at field scales. We integrated human-water dynamics into HydroBlocks - a hyper-resolution, field-scale resolving LSM. HydroBlocks explicitly solves the field-scale spatial heterogeneity of land surface processes through interacting hydrologic response units (HRUs); and its HRU-based model parallelization allows computationally efficient long-term simulations as well as ensemble predictions. The implemented human-water dynamics include groundwater and surface water abstraction to meet agricultural, domestic and industrial water demands. Furthermore, a supply-demand water allocation scheme based on relative costs helps to determine sectoral water use requirements and tradeoffs. A set of HydroBlocks simulations over the Midwest United States (daily, at 30-m spatial resolution for 30 years) are used to quantify the irrigation impacts on water availability. The model captures large reductions in total soil moisture and water table levels, as well as spatiotemporal changes in evapotranspiration and runoff peaks, with their intensity related to the adopted water management strategy. By incorporating human-water dynamics in a hyper-resolution LSM this work allows for progress on hydrological monitoring and predictions, as well as drought preparedness and water impact assessments at relevant decision-making scales.

Refined hyperentanglement purification of two-photon systems for high-capacity quantum communication with cavity-assisted interaction

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

Du, Fang-Fang; Li, Tao; Long, Gui-Lu, E-mail: gllong@tsinghua.edu.cn

Hyperentanglement, defined as the entanglement in multiple degrees of freedom (DOFs) of a photonic quantum system, has attracted much attention recently as it can improve the channel capacity of quantum communication largely. Here we present a refined hyperentanglement purification protocol (hyper-EPP) for two-photon systems in mixed hyperentangled states in both the spatial-mode and polarization DOFs, assisted by cavity quantum electrodynamics. By means of the spatial (polarization) quantum state transfer process, the quantum states that are discarded in the previous hyper-EPPs can be preserved. That is, the spatial (polarization) state of a four-photon system with high fidelity can be transformed intomore » another four-photon system with low fidelity, not disturbing its polarization (spatial) state, which makes this hyper-EPP take the advantage of possessing a higher efficiency.« less

Using Animation and Interactivity To Enrich Reading and Writing Activities.

ERIC Educational Resources Information Center

Gladhart, Marsha A.

In the hands of inspired teachers, computers can provide opportunities for creativity and interaction that add new excitement to learning. PowerPoint and HyperStudio are just two examples of computer software that are frequently used by students to share knowledge and develop communication skills using multimedia. Publishing their work with the…

Galaxy Interactions and AGN-triggering to z~1: an unprecedented new view from the Hyper Suprime-Cam Survey

NASA Astrophysics Data System (ADS)

Goulding, Andy D.; Greene, Jenny E.; Bezanson, Rachel; Greco, Johnny; Johnson, Sean; Medezinski, Elinor; Strauss, Michael A.; HSC Collaboration

2017-01-01

Collisions and interactions between galaxies are thought to be pivotal stages in their formation and evolution, causing the rapid production of new stars, and may also serve as a mechanism for fueling supermassive black holes (BH). Harnessing the exquisite spatial resolution (0.3—0.7 arcsec) afforded by the new 1400 deg2 Hyper Suprime-Cam (HSC) Survey, we present our new constraints on the importance of major and minor mergers in growing BHs throughout the last ~7 Gyrs. Utilizing the first ~170 deg2 of the HSC Survey, and mid-infrared observations in the WISE All-Sky survey, we have robustly selected active galactic nuclei (AGN), starburst, and mass-matched control galaxy samples, totaling ~120,000 spectroscopically confirmed systems at i<22 mag. We identify galaxy interactions using a novel machine-learning technique, and use these data to map the growth of BHs as a function of interaction-stage, redshift and AGN luminosity, ultimately providing the necessary large-number statistics required to investigate merger—AGN triggering in the context of galaxy evolution out to z~1.

3D Hybrid Simulations of Interactions of High-Velocity Plasmoids with Obstacles

NASA Astrophysics Data System (ADS)

Omelchenko, Y. A.; Weber, T. E.; Smith, R. J.

2015-11-01

Interactions of fast plasma streams and objects with magnetic obstacles (dipoles, mirrors, etc) lie at the core of many space and laboratory plasma phenomena ranging from magnetoshells and solar wind interactions with planetary magnetospheres to compact fusion plasmas (spheromaks and FRCs) to astrophysics-in-lab experiments. Properly modeling ion kinetic, finite-Larmor radius and Hall effects is essential for describing large-scale plasma dynamics, turbulence and heating in complex magnetic field geometries. Using an asynchronous parallel hybrid code, HYPERS, we conduct 3D hybrid (particle-in-cell ion, fluid electron) simulations of such interactions under realistic conditions that include magnetic flux coils, ion-ion collisions and the Chodura resistivity. HYPERS does not step simulation variables synchronously in time but instead performs time integration by executing asynchronous discrete events: updates of particles and fields carried out as frequently as dictated by local physical time scales. Simulations are compared with data from the MSX experiment which studies the physics of magnetized collisionless shocks through the acceleration and subsequent stagnation of FRC plasmoids against a strong magnetic mirror and flux-conserving boundary.

Study on the structure, vibrational analysis and molecular docking of fluorophenyl derivatives using FT-IR and density functional theory computations

NASA Astrophysics Data System (ADS)

Al-Tamimi, Abdul-Malek S.; Mary, Y. Sheena; Hassan, Hanan M.; Resmi, K. S.; El-Emam, Ali A.; Narayana, B.; Sarojini, B. K.

2018-07-01

The density functional calculations were performed at the B3LYP/6-311++G (5D, 7F) level to find the geometrical parameters, vibrational wavenumbers and various molecular properties of three fluorophenyl derivatives, methyl 4,4″-difluoro-5‧-methoxy-1,1':3‧,1″-terphenyl-4‧-carboxylate (MDFMTPC), 2,2'-(disulfanediyl)bis[4,6-(4-fluorophenyl)pyrimidine] (DFFPPY) and (6Z)-3,5‧-bis(4-fluorophenyl)-6-(1-hydroxyethylidene)cyclohex-2-en-1-one (FPHYCY). The phenyl ring Csbnd C, Cdbnd O and Csbnd H stretching modes produces VCD spectrum and these modes are efficient configuration markers. Using natural bond orbital analysis the stability of the molecules due to hyper-conjugative interactions were discussed. From the HOMO and LUMO energies, the chemical descriptors are compared for the title compounds. The first hyperpolarizabilities of MDFMTPC, DFFPPY and FPHYCY are respectively, 41.08, 69.27 and 38.38 times that of urea. Molar refractivity values are increasing in the order, FPHYCY > MDFMTPC > DFFPPY and this is responsible for the binding nature of the molecular assembly and can be used for the cure of different diseases. PASS analysis of the title compounds predicts chlordecone reductase inhibitor activity for MDFMTPC, thioredoxin inhibitor activity for DFFPPY and testosterone 17beta-dehydrogenase (NADP+) inhibitor activity for FPHYCY. Docking studies reveal that MDFMTPC, DFFPPY and FPHYCY can be lead compounds for developing new anti-cancerous, anti-tumor, prostate cancer drugs. Using Hirshfeld surface and 2D-finger print plots, the type and nature of intermolecular interactions were reported.

Spectroscopic investigation (FTIR spectrum), NBO, HOMO-LUMO energies, NLO and thermodynamic properties of 8-Methyl-N-vanillyl-6-nonenamideby DFT methods

NASA Astrophysics Data System (ADS)

Sherin Percy Prema Leela, J.; Hemamalini, R.; Muthu, S.; Al-Saadi, Abdulaziz A.

2015-07-01

Capsicum a hill grown vegetable is also known as red pepper or chili pepper. Capsaicin(8-Methyl-N-vanillyl-6-nonenamide) is the active component in chili peppers, which is currently used in the treatment of osteoarthritis, psoriasis and cancer. Fourier transform infrared (FT-IR) spectrum of Capsaicin in the solid phase were recorded in the region 4000-400 cm-1 and analyzed. The vibrational frequencies of the title compound were obtained theoretically by DFT/B3LYP calculations employing the standard 6-311++G(d,p) basis set and were compared with Fourier transform infrared spectrum. Complete vibrational assignment analysis and correlation of the fundamental modes for the title compound were carried out. The vibrational harmonic frequencies were scaled using scale factor, yielding a good agreement between the experimentally recorded and the theoretically calculated values. Stability of the molecule arising from hyper conjugative interactions, charge delocalization and intra molecular hydrogen bond-like weak interaction has been analyzed using Natural bond orbital (NBO) analysis by using B3LYP/6-311++G(d,p) method. The results show that electron density (ED) in the σ∗ and π∗ antibonding orbitals and second-order delocalization energies E (2) confirm the occurrence of intra molecular charge transfer (ICT) within the molecule. The dipole moment (μ), polarizability (α) and the hyperpolarizability (β) values of the molecule has been computed. Thermodynamic properties (heat capacity, entropy and enthalpy) of the title compound at different temperatures were calculated.

The effect of controlled release of PDGF-BB from heparin-conjugated electrospun PCL/gelatin scaffolds on cellular bioactivity and infiltration

PubMed Central

Lee, Jongman; Yoo, James J.; Atala, Anthony; Lee, Sang Jin

2013-01-01

Heparin-conjugated electrospun poly(ε-caprolactone) (PCL)/gelatin scaffolds were developed to provide controlled release of platelet-derived growth factor-BB (PDGF-BB) and allow prolonged bioactivity of this molecule. A mixture of PCL and gelatin was electrospun into three different morphologies. Next, heparin molecules were conjugated to the reactive surface of the scaffolds. This heparin-conjugated scaffold allowed the immobilization of PDGF-BB via electrostatic interaction. In vitro PDGF-BB release profiles indicated that passive physical adsorption of PDGF-BB to non-heparinized scaffolds resulted in an initial burst release of PDGF-BB within 5 days, which then leveled off. However, electrostatic interaction between PDGF-BB and the heparin-conjugated scaffolds gave rise to a sustained release of PDGF-BB over the course of 20 days without an initial burst. Moreover, PDGF-BB that was strongly bound to the heparin-conjugated scaffolds enhanced smooth muscle cell (SMC) proliferation. In addition, scaffolds composed of 3.0 µm diameter fibers that were immobilized with PDGF-BB accelerated SMC infiltration into the scaffold when compared to scaffolds composed of smaller diameter fibers or scaffolds that did not release PDGF-BB. We concluded that the combination of the large pore structure in the scaffolds and the heparin-mediated delivery of PDGF-BB provided the most effective cellular interactions through synergistic physical and chemical cues. PMID:22770570

Surface-Enhanced Hyper-Raman Spectra of Adenine, Guanine, Cytosine, Thymine, and Uracil

PubMed Central

2016-01-01

Using picosecond excitation at 1064 nm, surface-enhanced hyper-Raman scattering (SEHRS) spectra of the nucleobases adenine, guanine, cytosine, thymine, and uracil with two different types of silver nanoparticles were obtained. Comparing the SEHRS spectra with SERS data from the identical samples excited at 532 nm and with known infrared spectra, the major bands in the spectra are assigned. Due to the different selection rules for the one- and two-photon excited Raman scattering, we observe strong variation in relative signal strengths of many molecular vibrations obtained in SEHRS and SERS spectra. The two-photon excited spectra of the nucleobases are found to be very sensitive with respect to molecule–nanoparticle interactions. Using both the SEHRS and SERS data, a comprehensive vibrational characterization of the interaction of nucleobases with silver nanostructures can be achieved. PMID:28077982

Teaching earth science

USGS Publications Warehouse

Alpha, Tau Rho; Diggles, Michael F.

1998-01-01

This CD-ROM contains 17 teaching tools: 16 interactive HyperCard 'stacks' and a printable model. They are separated into the following categories: Geologic Processes, Earthquakes and Faulting, and Map Projections and Globes. A 'navigation' stack, Earth Science, is provided as a 'launching' place from which to access all of the other stacks. You can also open the HyperCard Stacks folder and launch any of the 16 stacks yourself. In addition, a 17th tool, Earth and Tectonic Globes, is provided as a printable document. Each of the tools can be copied onto a 1.4-MB floppy disk and distributed freely.

On the interpretation of synchronization in EEG hyperscanning studies: a cautionary note

PubMed Central

Burgess, Adrian P.

2013-01-01

EEG Hyperscanning is a method for studying two or more individuals simultaneously with the objective of elucidating how co-variations in their neural activity (i.e., hyperconnectivity) are influenced by their behavioral and social interactions. The aim of this study was to compare the performance of different hyper-connectivity measures using (i) simulated data, where the degree of coupling could be systematically manipulated, and (ii) individually recorded human EEG combined into pseudo-pairs of participants where no hyper-connections could exist. With simulated data we found that each of the most widely used measures of hyperconnectivity were biased and detected hyper-connections where none existed. With pseudo-pairs of human data we found spurious hyper-connections that arose because there were genuine similarities between the EEG recorded from different people independently but under the same experimental conditions. Specifically, there were systematic differences between experimental conditions in terms of the rhythmicity of the EEG that were common across participants. As any imbalance between experimental conditions in terms of stimulus presentation or movement may affect the rhythmicity of the EEG, this problem could apply in many hyperscanning contexts. Furthermore, as these spurious hyper-connections reflected real similarities between the EEGs, they were not Type-1 errors that could be overcome by some appropriate statistical control. However, some measures that have not previously been used in hyperconnectivity studies, notably the circular correlation co-efficient (CCorr), were less susceptible to detecting spurious hyper-connections of this type. The reason for this advantage in performance is discussed and the use of the CCorr as an alternative measure of hyperconnectivity is advocated. PMID:24399948

Controlled Interactions between Two Dimensional Layered Inorganic Nanosheets and Polymers

DTIC Science & Technology

2016-06-15

with end-functionalized polymers . First, an end-functionalized polymer with conjugated end-molecule, pyrene, is successfully employed to boron... polymers . First, an end-functionalized polymer with conjugated end-molecule, pyrenes, is successfully employed to boron nitride nanosheets (BNNS), and...AFRL-AFOSR-JP-TR-2016-0071 Controlled Interactions between Two Dimensional Layered Inorganic Nanosheets and Polymers Cheolmin Park YONSEI UNIVERSITY

Sensitivity and specificity of PS/AA-modified nanoparticles used in malaria detection

PubMed Central

Thiramanas, Raweewan; Jangpatarapongsa, Kulachart; Asawapirom, Udom; Tangboriboonrat, Pramuan; Polpanich, Duangporn

2013-01-01

Summary Polystyrene (PS) nanoparticle (NP) copolymerized with acrylic acid (AA) and coloured monomer, i.e. 2,3,6,7-tetra(2,2′-bithiophene)-1,4,5,8-naphthalenetetracarboxylic-N,N′-di(2-methylallyl)-bisimide (ALN8T), was synthesized via the miniemulsion polymerization. Before applying for malaria antigen detection, the blue NP was conjugated with human polyclonal malaria IgG antibody (Ab) specific to Plasmodium falciparum. For the conjugation, three methods, i.e. physical adsorption, covalent coupling and affinity binding via streptavidin (SA) and biotin interaction, were employed. The optimum ratio of Ab to NPs used in each immobilization procedure and the latex agglutination test based on the reaction between Ab conjugated NPs and malaria patient plasma were investigated. All Ab–latex conjugates provided the high sensitivity for the detection of P. falciparum malaria plasma. The highest specificity to P. falciparum was obtained from using Ab–NPs conjugated via the SA–biotin interaction. PMID:23298152

Interactions between inner membrane proteins in donor and recipient cells limit conjugal DNA transfer.

PubMed

Marrero, Joeli; Waldor, Matthew K

2005-06-01

Conjugation enables horizontal transmission of DNA among bacteria, thereby facilitating the rapid spread of genes such as those conferring resistance to antibiotics. Cell-cell contact is required for conjugative DNA transfer but does not ensure its success. The presence of certain plasmids in potential recipient cells inhibits redundant transfer of these plasmids from competent donors despite contact between donor and recipient cells. Here, we used two closely related integrating conjugative elements (ICEs), SXT and R391, to identify genes that inhibit redundant conjugative transfer. Cells containing SXT exclude transfer of a second copy of SXT but not R391 and vice versa. The specific exclusion of SXT and R391 is dependent upon variants of TraG and Eex, ICE-encoded inner membrane proteins in donor and recipient cells, respectively. We identified short sequences within each variant that determine the exquisite specificity of self-recognition; these data suggest that direct interactions between TraG and Eex mediate exclusion.

Synthesis, spectroscopic, and photophysical characterization and photosensitizing activity toward prokaryotic and eukaryotic cells of porphyrin-magainin and -buforin conjugates.

PubMed

Dosselli, Ryan; Ruiz-González, Rubén; Moret, Francesca; Agnolon, Valentina; Compagnin, Chiara; Mognato, Maddalena; Sella, Valentina; Agut, Montserrat; Nonell, Santi; Gobbo, Marina; Reddi, Elena

2014-02-27

Cationic antimicrobial peptides (CAMPs) and photodynamic therapy (PDT) are attractive tools to combat infectious diseases and to stem further development of antibiotic resistance. In an attempt to increase the efficiency of bacteria inactivation, we conjugated a PDT photosensitizer, cationic or neutral porphyrin, to a CAMP, buforin or magainin. The neutral and hydrophobic porphyrin, which is not photoactive per se against Gram-negative bacteria, efficiently photoinactivated Escherichia coli after conjugation to either buforin or magainin. Conjugation to magainin resulted in the considerable strengthening of the cationic and hydrophilic porphyrin's interaction with the bacterial cells, as shown by the higher bacteria photoinactivation activity retained after washing the bacterial suspension. The porphyrin-peptide conjugates also exhibited strong interaction capability as well as photoactivity toward eukaryotic cells, namely, human fibroblasts. These findings suggest that these CAMPs have the potential to carry drugs and other types of cargo inside mammalian cells similar to cell-penetrating peptides.

Lymphatic transport and lymph node targeting of methotrexate-conjugated PEGylated dendrimers are enhanced by reducing the length of the drug linker or masking interactions with the injection site.

PubMed

Ryan, Gemma M; McLeod, Victoria M; Mehta, Dharmini; Kelly, Brian D; Stanislawski, Pauline C; Owen, David J; Kaminskas, Lisa M; Porter, Christopher J H

2017-11-01

Drug conjugation to dendrimer-based delivery systems has been shown to enhance delivery to the lymphatic system after subcutaneous administration. Dendrimer interaction with components of the interstitium at the injection site, however, may prevent drainage from the injection site. The current study sought to vary the length of a linker employed to conjugate methotrexate (MTX) to a PEGylated dendrimer, in an attempt to reduce MTX interaction with interstitial binding sites and enhance lymphatic drainage. Dendrimers with shorter linkers resulted in higher lymphatic drainage, presumably via shielding of interaction sites by the PEG mantle, but were not retained in lymph nodes. Improved drainage of dendrimers with longer linkers was achieved through coadministration with dextran to mask interactions at the injection site while maintaining retention within the node. Enhanced drug exposure to the lymph node has the potential to enhance the treatment of lymph-node resident cancer metastases. Copyright © 2017 Elsevier Inc. All rights reserved.

Responsive Guest Encapsulation of Dynamic Conjugated Microporous Polymers.

PubMed

Xu, Lai; Li, Youyong

2016-06-30

The host-guest complexes of conjugated microporous polymers encapsulating C60 and dye molecules have been investigated systematically. The orientation of guest molecules inside the cavities, have different terms: inside the open cavities of the polymer, or inside the cavities formed by packing different polymers. The host backbone shows responsive dynamic behavior in order to accommodate the size and shape of incoming guest molecule or guest aggregates. Simulations show that the host-guest binding of conjugated polymers is stronger than that of non-conjugated polymers. This detailed study could provide a clear picture for the host-guest interaction for dynamic conjugated microporous polymers. The mechanism obtained could guide designing new conjugated microporous polymers.

Dynamical and structural transitions in periodically-driven emulsions: Reversibility loss and random hyper-unifom organization

NASA Astrophysics Data System (ADS)

Weijs, Joost H.; Jeanneret, Raphaël; Dreyfus, Rémi; Bartolo, Denis

2015-03-01

We present experiments and numerical simulations of a microfluidic echo process, in which a large number of droplets interact in a periodically driven viscous fluid [Jeanneret & Bartolo, Nature Comm. 5, 3474 (2013)]. Upon increasing the driving amplitude we demonstrate the collective reversibility loss of the droplet dynamics. In addition we show that this genuine dynamical phase transition is associated with a structural one: at the onset of irreversibility the droplet ensemble self-organises into a random hyperuniform state. Numerical simulations evidence that the purely reversible hydrodynamic interactions together with hard-core repulsion account for most of our experimental findings. Hyperuniformity is relevant for the production of large-band-gap materials, but are difficult to construct both numerically and experimentally. The hydrodynamic echo-process may provide a robust, fast, and simple way to produce hyper uniform structures over a wide range of packing fractions.

Oxazine dye-conjugated dna oligonucleotides: Förster resonance energy transfer in view of molecular dye-DNA interactions.

PubMed

Kupstat, Annette; Ritschel, Thomas; Kumke, Michael U

2011-12-21

In this work, the photophysical properties of two oxazine dyes (ATTO 610 and ATTO 680) covalently attached via a C6-amino linker to the 5'-end of short single-stranded as well as double-stranded DNA (ssDNA and dsDNA, respectively) of different lengths were investigated. The two oxazine dyes were chosen because of the excellent spectral overlap, the high extinction coefficients, and the high fluorescence quantum yield of ATTO 610, making them an attractive Förster resonance energy transfer (FRET) pair for bioanalytical applications in the far-red spectral range. To identify possible molecular dye-DNA interactions that cause photophysical alterations, we performed a detailed spectroscopic study, including time-resolved fluorescence anisotropy and fluorescence correlation spectroscopy measurements. As an effect of the DNA conjugation, the absorption and fluorescence maxima of both dyes were bathochromically shifted and the fluorescence decay times were increased. Moreover, the absorption of conjugated ATTO 610 was spectrally broadened, and a dual fluorescence emission was observed. Steric interactions with ssDNA as well as dsDNA were found for both dyes. The dye-DNA interactions were strengthened from ssDNA to dsDNA conjugates, pointing toward interactions with specific dsDNA domains (such as the top of the double helix). Although these interactions partially blocked the dye-linker rotation, a free (unhindered) rotational mobility of at least one dye facilitated the appropriate alignment of the transition dipole moments in doubly labeled ATTO 610/ATTO 680-dsDNA conjugates for the performance of successful FRET. Considering the high linker flexibility for the determination of the donor-acceptor distances, good accordance between theoretical and experimental FRET parameters was obtained. The considerably large Förster distance of ~7 nm recommends the application of this FRET pair not only for the detection of binding reactions between nucleic acids in living cells but also for monitoring interactions of larger biomolecules such as proteins.

Vibrational spectroscopic (FT-IR and FT-Raman) studies, HOMO-LUMO, NBO analysis and MEP of 6-methyl-1-({[(2E)-2-methyl-3-phenyl-prop-2-en-1-yl]oxy}methyl)-1,2,3,4-tetra-hydroquinazoline-2,4-dione, a potential chemotherapeutic agent, using density functional methods.

PubMed

Sebastian, Sr S H Roseline; Al-Tamimi, Abdul-Malek S; El-Brollosy, Nasser R; El-Emam, Ali A; Yohannan Panicker, C; Van Alsenoy, Christian

2015-01-05

6-Methyl-1-({[(2E)-2-methyl-3-phenyl-prop-2-en-1-yl]oxy}methyl)-1,2,3,4-tetra-hydro quinazoline-2,4-dione was prepared via treatment of silylated 6-methylquinazoline-2,4-dione with bis-[(E)-2-methyl-3-phenylallyloxy]methane. FT-IR and FT-Raman spectra were recorded and analyzed. The vibrational wavenumbers were computed using DFT methods and are assigned with the help of potential energy distribution method. The first hyperpolarizability, infrared intensities and Raman activities also reported. The geometrical parameters of the title compound obtained from XRD studies are in agreement with the calculated (B3LYP) values. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. The HOMO and LUMO analysis are used to determine the charge transfer within the molecule. MEP was performed by the B3LYP method and from the MEP it is evident that the negative charge covers the CO group and the positive region is over the phenyl ring and NH group. Copyright © 2014 Elsevier B.V. All rights reserved.

Vibrational spectra and normal coordinate analysis of 2-hydroxy-3-(2-methoxyphenoxy) propyl carbamate

NASA Astrophysics Data System (ADS)

Muthu, S.; Renuga, S.

2014-11-01

In this work, the vibrational spectral analysis was carried out by using FT-Raman and FTIR spectroscopy in the range 50-4000 cm-1 and 450-4000 cm-1 respectively, for 2-hydroxy-3-(2-methoxyphenoxy) propyl carbamate (2H3MPPLC) molecule. The molecular structure, fundamental vibrational frequencies and intensities of the vibrational bands were interpreted with the aid of structure optimizations and normal coordinate force field calculations based on density functional theory (DFT) and ab initio HF methods with 6-31G(d,p) basis set. The complete vibrational assignments of wave numbers were made on the basis of potential energy distribution (PED). The results of the calculations were applied to simulated spectra of the title compound, which show excellent agreement with observed spectra. The scaled B3LYP/6-31G(d,p) results show the best agreement with the experimental values over the other method. Stability of the molecule arising from hyper conjugative interactions, charge delocalization has been analyzed using natural bond orbital (NBO) analysis. The results confirm the occurrence of intramolecular charge-transfer (ICT) within the molecule. The dipole moment (μ), polarizability (α) and hyperpolarizability (β) of the investigated molecule has been computed using B3LYP/6-31G(d,p) method. Mulliken population analysis on atomic charges was also calculated. Besides, frontier molecular orbitals, molecular electrostatic potential (MEP) and thermodynamic properties were performed.

Synthesis, spectral characterization and computed optical analysis of potent triazole based compounds

NASA Astrophysics Data System (ADS)

Sumrra, Sajjad H.; Mushtaq, Fazila; Khalid, Muhammad; Raza, Muhammad Asam; Nazar, Muhammad Faizan; Ali, Bakhat; Braga, Ataualpa A. C.

2018-02-01

Biologically active triazole Schiff base ligand (L) and metal complexes [Fe(II), Co(II), Ni(II), Cu(II) and Zn(II)] are reported herein. The ligand acted as tridentate and coordinated towards metallic ions via azomethine-N, triazolic-N moiety and deprotonated-O of phenyl substituents in an octahedral manner. These compounds were characterized by physical, spectral and analytical analysis. The synthesized ligand and metal complexes were screened for antibacterial pathogens against Chromohalobacter salexigens, Chromohalobacter israelensi, Halomonas halofila and Halomonas salina, antifungal bioassay against Aspergillus niger and Aspergellus flavin, antioxidant (DPPH, phosphomolybdate) and also for enzyme inhibition [butyrylcholinesterase (BChE) and acetylcholinesterase (AChE)] studies. The results of these activities indicated the ligand to possess potential activity which significantly increased upon chelation. Moreover, vibrational bands, frontier molecular orbitals (FMOs) and natural bond analysis (NBO) of ligand (1) were carried out through density functional theory (DFT) with B3lYP/6-311 ++G (d,p) approach. While, UV-Vis analysis was performed by time dependent TD-DFT with B3lYP/6-311 ++G (d,p) method. NBO analysis revealed that investigated compound (L) contains enormous molecular stability owing to hyper conjugative interactions. Theoretical spectroscopic findings showed good agreement to experimental spectroscopic data. Global reactivity descriptors were calculated using the energies of FMOs which indicated compound (L) might be bioactive. These parameters confirmed the charge transfer phenomenon and reasonable correspondence with experimental bioactivity results.

Molecular structure, vibrational, electronic and thermal properties of 4-vinylcyclohexene by quantum chemical calculations

NASA Astrophysics Data System (ADS)

Nagabalasubramanian, P. B.; Periandy, S.; Karabacak, Mehmet; Govindarajan, M.

2015-06-01

The solid phase FT-IR and FT-Raman spectra of 4-vinylcyclohexene (abbreviated as 4-VCH) have been recorded in the region 4000-100 cm-1. The optimized molecular geometry and vibrational frequencies of the fundamental modes of 4-VCH have been precisely assigned and analyzed with the aid of structure optimizations and normal coordinate force field calculations based on density functional theory (DFT) method at 6-311++G(d,p) level basis set. The theoretical frequencies were properly scaled and compared with experimentally obtained FT-IR and FT-Raman spectra. Also, the effect due the substitution of vinyl group on the ring vibrational frequencies was analyzed and a detailed interpretation of the vibrational spectra of this compound has been made on the basis of the calculated total energy distribution (TED). The time dependent DFT (TD-DFT) method was employed to predict its electronic properties, such as electronic transitions by UV-Visible analysis, HOMO and LUMO energies, molecular electrostatic potential (MEP) and various global reactivity and selectivity descriptors (chemical hardness, chemical potential, softness, electrophilicity index). Stability of the molecule arising from hyper conjugative interaction, charge delocalization has been analyzed using natural bond orbital (NBO) analysis. Atomic charges obtained by Mulliken population analysis and NBO analysis are compared. Thermodynamic properties (heat capacity, entropy and enthalpy) of the title compound at different temperatures are also calculated.

Vibrational and spectroscopic investigation on the structure of 5H-dibenzo[b,f]azipine-5-carboxamide

NASA Astrophysics Data System (ADS)

Muthu, S.; Renuga, S.

2013-10-01

Fourier transform Raman and Fourier transform infrared spectra of 5H-dibenzo[b,f]azepine-5-carboxamide were recorded in the regions 4000-100 cm-1 and 4000-400 cm-1 respectively in the solid phase. 5H-dibenzo[b,f]azepine-5-carboxamide is typically used for the treatment of seizure disorders and neuropathic pain. The equilibrium geometry harmonic vibrational frequencies, infrared intensities and Raman scattering activities were calculated by density functional B3LYP/6-31G(d,p) method. A detailed interpretation of the vibrational spectra of this compound has been made on the basis of the calculated Potential energy distribution (PED). The thermodynamic functions of the title compound were also performed at the above methods and basis set. A detailed interpretation of the infrared and Raman spectra of 5H-dibenzo[b,f]azepine-5-carboxamide is reported. Stability of the molecule arising from hyper conjugative interactions, charge delocalization has been analyzed using natural bond orbital (NBO) analysis. The linear polarizability (α) and the first order hyperpolarizability (β) values of the investigated molecule have been computed using DFT quantum mechanical calculations. The calculated HOMO and LUMO energies show that charge transfer occurs within the molecule. The observed and calculated wave numbers are found to be in good agreement. The experimental spectra also coincide satisfactorily with those of theoretically constructed spectra.

Mannose glycoconjugates functionalized at positions 1 and 6. Binding analysis to DC-SIGN using biosensors.

PubMed

Reina, José J; Maldonado, Olivia S; Tabarani, Georges; Fieschi, Franck; Rojo, Javier

2007-01-01

The design of glycoconjugates to allow the generation of multivalent ligands capable of interacting with the receptor DC-SIGN is a topic of high interest due to the role played by this lectin in pathogen infections. Mannose, a ligand of this lectin, could be conjugated at two different positions, 1 and 6, not implicated in the binding process. We have prepared mannose conjugates at these two positions with a long spacer to allow their attachment to a biosensor chip surface. Analysis of the interaction between these surfaces and the tetravalent extracellular domain (ECD) of DC-SIGN by SPR biosensor has demonstrated that both positions are available for this conjugation without affecting the protein binding process. These results emphasize the possibility to conjugate mannose at position 6, allowing the incorporation of hydrophobic groups at the anomeric position to interact with hydrophobic residues in the carbohydrate recognition domain of DC-SIGN, increasing binding affinities. This fact is relevant for the future design of new ligands and the corresponding multivalent systems for DC-SIGN.

The Adoption of Mobile Learning in a Traditional Training Environment: The C95-Challenge Project Experience

ERIC Educational Resources Information Center

Catenazzi, Nadia; Sommaruga, Lorenzo; De Angelis, Kylene; Gabbianelli, Giulio

2016-01-01

Within the C95-Challenge Erasmus+ project, mobile learning technologies are adopted and tested for bus and truck drivers training according to the EU 2003/59/EC Directive. Different kinds of training contents are developed in the form of interactive slides, hyper-videos, interactive quizzes and delivered on mobile devices. Existing apps and games…

PML IV/ARF interaction enhances p53 SUMO-1 conjugation, activation, and senescence

PubMed Central

Ivanschitz, Lisa; Takahashi, Yuki; Jollivet, Florence; Ayrault, Olivier; Le Bras, Morgane; de Thé, Hugues

2015-01-01

Promyelocytic leukemia protein (PML) nuclear bodies (NBs) recruit multiple partners, including p53 and many of its regulators. NBs are believed to facilitate several posttranslational modifications and are key regulators of senescence. PML, the organizer of NBs, is expressed as a number of splice variants that all efficiently recruit p53 partners. However, overexpression of only one of them, PML IV, triggers p53-driven senescence. Here, we show that PML IV specifically binds ARF, a key p53 regulator. Similar to ARF, PML IV enhances global SUMO-1 conjugation, particularly that of p53, resulting in p53 stabilization and activation. ARF interacts with and stabilizes the NB-associated UBC9 SUMO-conjugating enzyme, possibly explaining PML IV-enhanced SUMOylation. These results unexpectedly link two key tumor suppressors, highlighting their convergence for global control of SUMO conjugation, p53 activation, and senescence induction. PMID:26578773

PML IV/ARF interaction enhances p53 SUMO-1 conjugation, activation, and senescence.

PubMed

Ivanschitz, Lisa; Takahashi, Yuki; Jollivet, Florence; Ayrault, Olivier; Le Bras, Morgane; de Thé, Hugues

2015-11-17

Promyelocytic leukemia protein (PML) nuclear bodies (NBs) recruit multiple partners, including p53 and many of its regulators. NBs are believed to facilitate several posttranslational modifications and are key regulators of senescence. PML, the organizer of NBs, is expressed as a number of splice variants that all efficiently recruit p53 partners. However, overexpression of only one of them, PML IV, triggers p53-driven senescence. Here, we show that PML IV specifically binds ARF, a key p53 regulator. Similar to ARF, PML IV enhances global SUMO-1 conjugation, particularly that of p53, resulting in p53 stabilization and activation. ARF interacts with and stabilizes the NB-associated UBC9 SUMO-conjugating enzyme, possibly explaining PML IV-enhanced SUMOylation. These results unexpectedly link two key tumor suppressors, highlighting their convergence for global control of SUMO conjugation, p53 activation, and senescence induction.

A Systems Model for Ursodeoxycholic Acid Metabolism in Healthy and Patients With Primary Biliary Cirrhosis

PubMed Central

Dobbins, RL; O'Connor‐Semmes, RL; Young, MA

2016-01-01

A systems model was developed to describe the metabolism and disposition of ursodeoxycholic acid (UDCA) and its conjugates in healthy subjects based on pharmacokinetic (PK) data from published studies in order to study the distribution of oral UDCA and potential interactions influencing therapeutic effects upon interruption of its enterohepatic recirculation. The base model was empirically adapted to patients with primary biliary cirrhosis (PBC) based on current understanding of disease pathophysiology and clinical measurements. Simulations were performed for patients with PBC under two competing hypotheses: one for inhibition of ileal absorption of both UDCA and conjugates and the other only of conjugates. The simulations predicted distinctly different bile acid distribution patterns in plasma and bile. The UDCA model adapted to patients with PBC provides a platform to investigate a complex therapeutic drug interaction among UDCA, UDCA conjugates, and inhibition of ileal bile acid transport in this rare disease population. PMID:27537780

Multiple Syntrophic Interactions in a Terephthalate-Degrading Methanogenic Consortium

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

Lykidis, Athanasios; Chen, Chia-Lung; Tringe, Susannah G.

2010-08-05

Terephthalate (TA) is one of the top 50 chemicals produced worldwide. Its production results in a TA-containing wastewater that is treated by anaerobic processes through a poorly understood methanogenic syntrophy. Using metagenomics, we characterized the methanogenic consortium tinside a hyper-mesophilic (i.e., between mesophilic and thermophilic), TA-degrading bioreactor. We identified genes belonging to dominant Pelotomaculum species presumably involved in TA degradation through decarboxylation, dearomatization, and modified ?-oxidation to H{sub 2}/CO{sub 2} and acetate. These intermediates are converted to CH{sub 4}/CO{sub 2} by three novel hyper-mesophilic methanogens. Additional secondary syntrophic interactions were predicted in Thermotogae, Syntrophus and candidate phyla OP5 and WWE1more » populations. The OP5 encodes genes capable of anaerobic autotrophic butyrate production and Thermotogae, Syntrophus and WWE1 have the genetic potential to oxidize butyrate to COsub 2}/H{sub 2} and acetate. These observations suggest that the TA-degrading consortium consists of additional syntrophic interactions beyond the standard H{sub 2}-producing syntroph ? methanogen partnership that may serve to improve community stability.« less

Modeling human perception of orientation in altered gravity

PubMed Central

Clark, Torin K.; Newman, Michael C.; Oman, Charles M.; Merfeld, Daniel M.; Young, Laurence R.

2015-01-01

Altered gravity environments, such as those experienced by astronauts, impact spatial orientation perception, and can lead to spatial disorientation and sensorimotor impairment. To more fully understand and quantify the impact of altered gravity on orientation perception, several mathematical models have been proposed. The utricular shear, tangent, and the idiotropic vector models aim to predict static perception of tilt in hyper-gravity. Predictions from these prior models are compared to the available data, but are found to systematically err from the perceptions experimentally observed. Alternatively, we propose a modified utricular shear model for static tilt perception in hyper-gravity. Previous dynamic models of vestibular function and orientation perception are limited to 1 G. Specifically, they fail to predict the characteristic overestimation of roll tilt observed in hyper-gravity environments. To address this, we have proposed a modification to a previous observer-type canal-otolith interaction model based upon the hypothesis that the central nervous system (CNS) treats otolith stimulation in the utricular plane differently than stimulation out of the utricular plane. Here we evaluate our modified utricular shear and modified observer models in four altered gravity motion paradigms: (a) static roll tilt in hyper-gravity, (b) static pitch tilt in hyper-gravity, (c) static roll tilt in hypo-gravity, and (d) static pitch tilt in hypo-gravity. The modified models match available data in each of the conditions considered. Our static modified utricular shear model and dynamic modified observer model may be used to help quantitatively predict astronaut perception of orientation in altered gravity environments. PMID:25999822

Conjugative DNA Transfer Is Enhanced by Plasmid R1 Partitioning Proteins

PubMed Central

Gruber, Christian J.; Lang, Silvia; Rajendra, Vinod K. H.; Nuk, Monika; Raffl, Sandra; Schildbach, Joel F.; Zechner, Ellen L.

2016-01-01

Bacterial conjugation is a form of type IV secretion used to transport protein and DNA directly to recipient bacteria. The process is cell contact-dependent, yet the mechanisms enabling extracellular events to trigger plasmid transfer to begin inside the cell remain obscure. In this study of plasmid R1 we investigated the role of plasmid proteins in the initiation of gene transfer. We find that TraI, the central regulator of conjugative DNA processing, interacts physically, and functionally with the plasmid partitioning proteins ParM and ParR. These interactions stimulate TraI catalyzed relaxation of plasmid DNA in vivo and in vitro and increase ParM ATPase activity. ParM also binds the coupling protein TraD and VirB4-like channel ATPase TraC. Together, these protein-protein interactions probably act to co-localize the transfer components intracellularly and promote assembly of the conjugation machinery. Importantly these data also indicate that the continued association of ParM and ParR at the conjugative pore is necessary for plasmid transfer to start efficiently. Moreover, the conjugative pilus and underlying secretion machinery assembled in the absence of Par proteins mediate poor biofilm formation and are completely dysfunctional for pilus specific R17 bacteriophage uptake. Thus, functional integration of Par components at the interface of relaxosome, coupling protein, and channel ATPases appears important for an optimal conformation and effective activation of the transfer machinery. We conclude that low copy plasmid R1 has evolved an active segregation system that optimizes both its vertical and lateral modes of dissemination. PMID:27486582

Design of Stomach Acid-Stable and Mucin-Binding Enzyme Polymer Conjugates.

PubMed

Cummings, Chad S; Campbell, Alan S; Baker, Stefanie L; Carmali, Sheiliza; Murata, Hironobu; Russell, Alan J

2017-02-13

The reduced immunogenicity and increased stability of protein-polymer conjugates has made their use in therapeutic applications particularly attractive. However, the physicochemical interactions between polymer and protein, as well as the effect of this interaction on protein activity and stability, are still not fully understood. In this work, polymer-based protein engineering was used to examine the role of polymer physicochemical properties on the activity and stability of the chymotrypsin-polymer conjugates and their degree of binding to intestinal mucin. Four different chymotrypsin-polymer conjugates, each with the same polymer density, were synthesized using "grafting-from" atom transfer radical polymerization. The influence of polymer charge on chymotrypsin-polymer conjugate mucin binding, bioactivity, and stability in stomach acid was determined. Cationic polymers covalently attached to chymotrypsin showed high mucin binding, while zwitterionic, uncharged, and anionic polymers showed no mucin binding. Cationic polymers also increased chymotrypsin activity from pH 6-8, while zwitterionic polymers had no effect, and uncharged and anionic polymers decreased enzyme activity. Lastly, cationic polymers decreased the tendency of chymotrypsin to structurally unfold at extremely low pH, while uncharged and anionic polymers induced unfolding more quickly. We hypothesized that when polymers are covalently attached to the surface of a protein, the degree to which those polymers interact with the protein surface is the predominant determinant of whether the polymer will stabilize or inactivate the protein. Preferential interactions between the polymer and the protein lead to removal of water from the surface of the protein, and this, we believe, inactivates the enzyme.

Functional Hybrid Biomaterials based on Peptide-Polymer Conjugates for Nanomedicine

NASA Astrophysics Data System (ADS)

Shu, Jessica Yo

The focus of this dissertation is the design, synthesis and characterization of hybrid functional biomaterials based on peptide-polymer conjugates for nanomedicine. Generating synthetic materials with properties comparable to or superior than those found in nature has been a "holy grail" for the materials community. Man-made materials are still rather simplistic when compared to the chemical and structural complexity of a cell. Peptide-polymer conjugates have the potential to combine the advantages of the biological and synthetic worlds---that is they can combine the precise chemical structure and diverse functionality of biomolecules with the stability and processibility of synthetic polymers. As a new family of soft matter, they may lead to materials with novel properties that have yet to be realized with either of the components alone. In order for peptide-polymer conjugates to reach their full potential as useful materials, the structure and function of the peptide should be maintained upon polymer conjugation. The success in achieving desirable, functional assemblies relies on fundamentally understanding the interactions between each building block and delicately balancing and manipulating these interactions to achieve targeted assemblies without interfering with designed structures and functionalities. Such fundamental studies of peptide-polymer interactions were investigated as the nature of the polymer (hydrophilic vs. hydrophobic) and the site of its conjugation (end-conjugation vs. side-conjugation) were varied. The fundamental knowledge gained was then applied to the design of amphiphiles that self-assemble to form stable functional micelles. The micelles exhibited exceptional monodispersity and long-term stability, which is atypical of self-assembled systems. Thus such micelles based on amphiphilic peptide-polymer conjugates may meet many current demands in nanomedicine, in particular for drug delivery of hydrophobic anti-cancer therapeutics. Lastly, biological evaluations were performed to investigate the potential of micelles as drug delivery vehicles. In vitro cell studies demonstrated that the micelles can be used as a delivery vehicle to tailor the cellular uptake, time release, and intracellular trafficking of drugs. In vivo biodistribution and pharmacokinetic experiments showed long blood circulation. This work demonstrates that peptide-polymer conjugates can be used as building blocks to generate hierarchical functional nanostructures with a wide range of applications, only one of which is drug delivery.

A correlative and quantitative imaging approach enabling characterization of primary cell-cell communication: Case of human CD4+ T cell-macrophage immunological synapses.

PubMed

Kasprowicz, Richard; Rand, Emma; O'Toole, Peter J; Signoret, Nathalie

2018-05-22

Cell-to-cell communication engages signaling and spatiotemporal reorganization events driven by highly context-dependent and dynamic intercellular interactions, which are difficult to capture within heterogeneous primary cell cultures. Here, we present a straightforward correlative imaging approach utilizing commonly available instrumentation to sample large numbers of cell-cell interaction events, allowing qualitative and quantitative characterization of rare functioning cell-conjugates based on calcium signals. We applied this approach to examine a previously uncharacterized immunological synapse, investigating autologous human blood CD4 + T cells and monocyte-derived macrophages (MDMs) forming functional conjugates in vitro. Populations of signaling conjugates were visualized, tracked and analyzed by combining live imaging, calcium recording and multivariate statistical analysis. Correlative immunofluorescence was added to quantify endogenous molecular recruitments at the cell-cell junction. By analyzing a large number of rare conjugates, we were able to define calcium signatures associated with different states of CD4 + T cell-MDM interactions. Quantitative image analysis of immunostained conjugates detected the propensity of endogenous T cell surface markers and intracellular organelles to polarize towards cell-cell junctions with high and sustained calcium signaling profiles, hence defining immunological synapses. Overall, we developed a broadly applicable approach enabling detailed single cell- and population-based investigations of rare cell-cell communication events with primary cells.

Synthetic, XRD, non-covalent interactions and solvent dependent nonlinear optical studies of Sulfadiazine-Ortho-Vanillin Schiff base: (E)-4-((2-hydroxy-3-methoxy- benzylidene) amino)-N-(pyrimidin-2-yl)benzene-sulfonamide

NASA Astrophysics Data System (ADS)

Shahid, Muhammad; Salim, Muhammad; Khalid, Muhammad; Tahir, Muhammad Nawaz; Khan, Muhammad Usman; Braga, Ataualpa Albert Carmo

2018-06-01

In this study, Sulfadiazine-Ortho-Vanillin Schiff base namely (E)-4-((2-hydroxy-3-methoxybenzylidene)amino)sbnd N-(pyrimidin-2-yl)benzene-sulfonamide (BS) was synthesized. Chemical characterization and computational studies using different techniques like XRD, FT-IR, UV-Vis, NBO, FMO, and MEP have been employed. Density functional theory (DFT) calculations have been performed at M06-2X/6-311 + G(d,p) level of theory to obtain optimized geometry and vibrational wave numbers for (E)-4-((2-hydroxy-3-methoxybenzylidene)amino)sbnd N-(pyrimidin-2-yl)benzene-sulfonamide (BS). The DFT optimized geometry supports the experimental XRD parameters. Frontier molecular orbital (FMO) energies and molecular electrostatic potential (MEP) surfaces have been executed at M06-2X/6-311 + G(d,p) level of theory. NBO analysis has been carried out at M06-2X/6-311 + G(d,p) level which not only discovered the hyper conjugative interactions and stability in title molecule but also reconfirmed the existence of Nsbnd H⋯N hydrogen bonds between the dimer. The findings of small EHOMO-ELUMO gap shows less hardness and larger softness values which suggested the bioactiveness of the title molecule. Finally, the effect of solvent on nonlinear optical (NLO) properties has been executed using M06-2X level of theory and 6-311 + G (d,p) basis set. The solvent polarity enhanced the NLO response from 3.62 × 10-30 esu to 4.66 × 10-30 esu indicating the considerable NLO character hence in general may have potential applications in the development of non-linear optical materials.

Solution structure of a highly stable DNA duplex conjugated to a minor groove binder.

PubMed Central

Kumar, S; Reed, M W; Gamper, H B; Gorn, V V; Lukhtanov, E A; Foti, M; West, J; Meyer, R B; Schweitzer, B I

1998-01-01

The tripeptide 1,2-dihydro-(3 H )-pyrrolo[3,2- e ]indole-7-carboxylate (CDPI3) binds to the minor groove of DNA with high affinity. When this minor groove binder is conjugated to the 5'-end of short oligonucleotides the conjugates form unusually stable hybrids with complementary DNA and thus may have useful diagnostic and/or therapeutic applications. In order to gain an understanding of the structural interactions between the CDPI3minor groove binding moiety and the DNA, we have determined and compared the solution structure of a duplex consisting of oligodeoxyribonucleotide 5'-TGATTATCTG-3' conjugated at the 5'-end to CDPI3 and its complementary strand to an unmodified control duplex of the same sequence using nuclear magnetic resonance techniques. Thermal denaturation studies indicated that the hybrid of this conjugate with its complementary strand had a melting temperature that was 30 degrees C higher compared with the unmodified control duplex. Following restrained molecular dynamics and relaxation matrix refinement, the solution structure of the CDPI3-conjugated DNA duplex demonstrated that the overall shape of the duplex was that of a straight B-type helix and that the CDPI3moiety was bound snugly in the minor groove, where it was stabilized by extensive van der Waal's interactions. PMID:9443977

Solution structure of a highly stable DNA duplex conjugated to a minor groove binder.

PubMed

Kumar, S; Reed, M W; Gamper, H B; Gorn, V V; Lukhtanov, E A; Foti, M; West, J; Meyer, R B; Schweitzer, B I

1998-02-01

The tripeptide 1,2-dihydro-(3 H )-pyrrolo[3,2- e ]indole-7-carboxylate (CDPI3) binds to the minor groove of DNA with high affinity. When this minor groove binder is conjugated to the 5'-end of short oligonucleotides the conjugates form unusually stable hybrids with complementary DNA and thus may have useful diagnostic and/or therapeutic applications. In order to gain an understanding of the structural interactions between the CDPI3minor groove binding moiety and the DNA, we have determined and compared the solution structure of a duplex consisting of oligodeoxyribonucleotide 5'-TGATTATCTG-3' conjugated at the 5'-end to CDPI3 and its complementary strand to an unmodified control duplex of the same sequence using nuclear magnetic resonance techniques. Thermal denaturation studies indicated that the hybrid of this conjugate with its complementary strand had a melting temperature that was 30 degrees C higher compared with the unmodified control duplex. Following restrained molecular dynamics and relaxation matrix refinement, the solution structure of the CDPI3-conjugated DNA duplex demonstrated that the overall shape of the duplex was that of a straight B-type helix and that the CDPI3moiety was bound snugly in the minor groove, where it was stabilized by extensive van der Waal's interactions.

Systemic aspects of conjugal resilience in couples with a child facing cancer and marrow transplantation.

PubMed

Martin, Julie; Péloquin, Katherine; Vachon, Marie-France; Duval, Michel; Sultan, Serge

The negative impact of paediatric cancer on parents is well known and is even greater when intensive treatments are used. This study aimed to describe how couples whose child has received a transplant for the treatment of leukaemia view conjugal resilience and to evaluate the role of we-ness as a precursor of conjugal adjustment. Four parental couples were interviewed. Interviews were analysed in two ways: inductive thematic analysis and rating of verbal content with the We-ness Coding Scale . Participants report that conjugal resilience involves the identification of the couple as a team and cohesion in the couple. Being a team generates certain collaborative interactions that lead to conjugal resilience. A sense of we-ness in parents is associated with fluctuation in the frequency of themes. Participants' vision of conjugal resilience introduced novel themes. The sense of we-ness facilitates cohesion and the process of conjugal resilience.

Carbohydrates in Supramolecular Chemistry.

PubMed

Delbianco, Martina; Bharate, Priya; Varela-Aramburu, Silvia; Seeberger, Peter H

2016-02-24

Carbohydrates are involved in a variety of biological processes. The ability of sugars to form a large number of hydrogen bonds has made them important components for supramolecular chemistry. We discuss recent advances in the use of carbohydrates in supramolecular chemistry and reveal that carbohydrates are useful building blocks for the stabilization of complex architectures. Systems are presented according to the scaffold that supports the glyco-conjugate: organic macrocycles, dendrimers, nanomaterials, and polymers are considered. Glyco-conjugates can form host-guest complexes, and can self-assemble by using carbohydrate-carbohydrate interactions and other weak interactions such as π-π interactions. Finally, complex supramolecular architectures based on carbohydrate-protein interactions are discussed.

Conjugation of antibodies to gold nanorods through Fc portion: synthesis and molecular specific imaging

PubMed Central

Joshi, Pratixa P.; Yoon, Soon Joon; Hardin, William G.; Emelianov, Stanislav; Sokolov, Konstantin V.

2013-01-01

Anisotropic gold nanorods provide a convenient combination of properties, such as tunability of plasmon resonances and strong extinction cross-sections in the near-infrared to red spectral region. These properties have created significant interest in the development of antibody conjugation methods for synthesis of targeted nanorods for a number of biomedical applications, including molecular specific imaging and therapy. Previously published conjugation approaches have achieved molecular specificity. However, the current conjugation methods have several downsides including low stability and potential cytotoxicity of bioconjugates that are produced by electrostatic interactions as well as lack of control over antibody orientation during covalent conjugation. Here we addressed these shortcomings by introducing directional antibody conjugation to the gold nanorod surface. The directional conjugation is achieved through the carbohydrate moiety, which is located on one of the heavy chains of the Fc portion of most antibodies. The carbohydrate is oxidized under mild conditions to a hydrazide reactive aldehyde group. Then, a heterofunctional linker with hydrazide and dithiol groups is used to attach antibodies to gold nanorods. The directional conjugation approach was characterized using electron microscopy, zeta potential and extinction spectra. We also determined spectral changes associated with nanorod aggregation; these spectral changes can be used as a convenient quality control of nanorod bioconjugates. Molecular specificity of the synthesized antibody targeted nanorods was demonstrated using hyperspectral optical and photoacoustic imaging of cancer cell culture models. Additionally, we observed characteristic changes in optical spectra of molecular specific nanorods after their interactions with cancer cells; the observed spectral signatures can be explored for sensitive cancer detection. PMID:23631707

Transient Intervals of Hyper-Gravity Enhance Endothelial Barrier Integrity: Impact of Mechanical and Gravitational Forces Measured Electrically

PubMed Central

Szulcek, Robert; van Bezu, Jan; Boonstra, Johannes; van Loon, Jack J. W. A.; van Nieuw Amerongen, Geerten P.

2015-01-01

Background Endothelial cells (EC) guard vascular functions by forming a dynamic barrier throughout the vascular system that sensitively adapts to ‘classical’ biomechanical forces, such as fluid shear stress and hydrostatic pressure. Alterations in gravitational forces might similarly affect EC integrity, but remain insufficiently studied. Methods In an unique approach, we utilized Electric Cell-substrate Impedance Sensing (ECIS) in the gravity-simulators at the European Space Agency (ESA) to study dynamic responses of human EC to simulated micro- and hyper-gravity as well as to classical forces. Results Short intervals of micro- or hyper-gravity evoked distinct endothelial responses. Stimulated micro-gravity led to decreased endothelial barrier integrity, whereas hyper-gravity caused sustained barrier enhancement by rapid improvement of cell-cell integrity, evidenced by a significant junctional accumulation of VE-cadherin (p = 0.011), significant enforcement of peripheral F-actin (p = 0.008) and accompanied by a slower enhancement of cell-matrix interactions. The hyper-gravity triggered EC responses were force dependent and nitric-oxide (NO) mediated showing a maximal resistance increase of 29.2±4.8 ohms at 2g and 60.9±6.2 ohms at 4g vs. baseline values that was significantly suppressed by NO blockage (p = 0.011). Conclusion In conclusion, short-term application of hyper-gravity caused a sustained improvement of endothelial barrier integrity, whereas simulated micro-gravity weakened the endothelium. In clear contrast, classical forces of shear stress and hydrostatic pressure induced either short-lived or no changes to the EC barrier. Here, ECIS has proven a powerful tool to characterize subtle and distinct EC gravity-responses due to its high temporal resolution, wherefore ECIS has a great potential for the study of gravity-responses such as in real space flights providing quantitative assessment of a variety of cell biological characteristics of any adherent growing cell type in an automated and continuous fashion. PMID:26637177

A molecular design principle of lyotropic liquid-crystalline conjugated polymers with directed alignment capability for plastic electronics

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

Kim, Bong-Gi; Jeong, Eun Jeong; Chung, Jong Won

Conjugated polymers with a one-dimensional p-orbital overlap exhibit optoelectronic anisotropy. Their unique anisotropic properties can be fully realized in device applications only when the conjugated chains are aligned. Here, we report a molecular design principle of conjugated polymers to achieve concentration-regulated chain planarization, self-assembly, liquid-crystal-like good mobility and non-interdigitated side chains. As a consequence of these intra- and intermolecular attributes, chain alignment along an applied flow field occurs. This liquid-crystalline conjugated polymer was realized by incorporating intramolecular sulphur–fluorine interactions and bulky side chains linked to a tetrahedral carbon having a large form factor. By optimizing the polymer concentration and themore » flow field, we could achieve a high dichroic ratio of 16.67 in emission from conducting conjugated polymer films. Two-dimensional grazing-incidence X-ray diffraction was performed to analyse a well-defined conjugated polymer alignment. Thin-film transistors built on highly aligned conjugated polymer films showed more than three orders of magnitude faster carrier mobility along the conjugated polymer alignment direction than the perpendicular direction.« less

Substituent effects that control conjugated oligomer conformation through non-covalent interactions

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

Sharber, Seth A.; Baral, Rom Nath; Frausto, Fanny

Although understanding the conformations and arrangements of conjugated materials as solids is key to their prospective applications, predictive power over these structural factors remains elusive. In this work, substituent effects tune non-covalent interactions between side-chain fluorinated benzyl esters and main-chain terminal arenes, in turn controlling the conformations and interchromophore aggregation of three-ring phenylene-ethynylenes (PEs). Cofacial fluoroarene–arene (ArF–ArH) interactions cause twisting in the PE backbone, interrupting intramolecular conjugation as well as blocking chromophore aggregation, both of which prevent the typically observed bathochromic shift observed upon transitioning PEs from solution to solid. This work highlights two structural factors that determine whether themore » ArF–ArH interactions, and the resulting twisted, unaggregated chromophores, occur in these solids: (i) the electron-releasing characteristic of substituents on ArH, with more electron-releasing character favoring ArF–ArH interactions, and (ii) the fluorination pattern of the ArF ring, with 2,3,4,5,6-pentafluorophenyl favoring ArF–ArH interactions over 2,4,6-trifluorophenyl. Furthermore, these trends indicate that considerations of electrostatic complementarity, whether through a polar-π or substituent–substituent mechanism, can serve as an effective design principle in controlling the interaction strengths, and therefore the optoelectronic properties, of these molecules as solids.« less

Substituent effects that control conjugated oligomer conformation through non-covalent interactions

DOE PAGES

Sharber, Seth A.; Baral, Rom Nath; Frausto, Fanny; ...

2017-03-31

Although understanding the conformations and arrangements of conjugated materials as solids is key to their prospective applications, predictive power over these structural factors remains elusive. In this work, substituent effects tune non-covalent interactions between side-chain fluorinated benzyl esters and main-chain terminal arenes, in turn controlling the conformations and interchromophore aggregation of three-ring phenylene-ethynylenes (PEs). Cofacial fluoroarene–arene (ArF–ArH) interactions cause twisting in the PE backbone, interrupting intramolecular conjugation as well as blocking chromophore aggregation, both of which prevent the typically observed bathochromic shift observed upon transitioning PEs from solution to solid. This work highlights two structural factors that determine whether themore » ArF–ArH interactions, and the resulting twisted, unaggregated chromophores, occur in these solids: (i) the electron-releasing characteristic of substituents on ArH, with more electron-releasing character favoring ArF–ArH interactions, and (ii) the fluorination pattern of the ArF ring, with 2,3,4,5,6-pentafluorophenyl favoring ArF–ArH interactions over 2,4,6-trifluorophenyl. Furthermore, these trends indicate that considerations of electrostatic complementarity, whether through a polar-π or substituent–substituent mechanism, can serve as an effective design principle in controlling the interaction strengths, and therefore the optoelectronic properties, of these molecules as solids.« less

Synthesis, characterization and target protein binding of drug-conjugated quantum dots in vitro and in living cells

NASA Astrophysics Data System (ADS)

Choi, Youngseon; Kim, Minjung; Cho, Yoojin; Yun, Eunsuk; Song, Rita

2013-02-01

Elucidation of unknown target proteins of a drug is of great importance in understanding cell biology and drug discovery. There have been extensive studies to discover and identify target proteins in the cell. Visualization of targets using drug-conjugated probes has been an important approach to gathering mechanistic information of drug action at the cellular level. As quantum dot (QD) nanocrystals have attracted much attention as a fluorescent probe in the bioimaging area, we prepared drug-conjugated QD to explore the potential of target discovery. As a model drug, we selected a well-known anticancer drug, methotrexate (MTX), which has been known to target dihydrofolate reductase (DHFR) with high affinity binding (Kd = 0.54 nM). MTX molecules were covalently attached to amino-PEG-polymer-coated QDs. Specific interactions of MTX-conjugated QDs with DHFR were identified using agarose gel electrophoresis and fluorescence microscopy. Cellular uptake of the MTX-conjugated QDs in living CHO cells was investigated with regard to their localization and distribution pattern. MTX-QD was found to be internalized into the cells via caveolae-medicated endocytosis without significant sequestration in endosomes. A colocalization experiment of the MTX-QD conjugate with antiDHFR-TAT-QD also confirmed that MTX-QD binds to the target DHFR. This study showed the potential of the drug-QD conjugate to identify or visualize drug-target interactions in the cell, which is currently of great importance in the area of drug discovery and chemical biology.

Effects of Polymer Conjugation on Hybridization Thermodynamics of Oligonucleic Acids.

PubMed

Ghobadi, Ahmadreza F; Jayaraman, Arthi

2016-09-15

In this work, we perform coarse-grained (CG) and atomistic simulations to study the effects of polymer conjugation on hybridization/melting thermodynamics of oligonucleic acids (ONAs). We present coarse-grained Langevin molecular dynamics simulations (CG-NVT) to assess the effects of the polymer flexibility, length, and architecture on hybridization/melting of ONAs with different ONA duplex sequences, backbone chemistry, and duplex concentration. In these CG-NVT simulations, we use our recently developed CG model of ONAs in implicit solvent, and treat the conjugated polymer as a CG chain with purely repulsive Weeks-Chandler-Andersen interactions with all other species in the system. We find that 8-100-mer linear polymer conjugation destabilizes 8-mer ONA duplexes with weaker Watson-Crick hydrogen bonding (WC H-bonding) interactions at low duplex concentrations, while the same polymer conjugation has an insignificant impact on 8-mer ONA duplexes with stronger WC H-bonding. To ensure the configurational space is sampled properly in the CG-NVT simulations, we also perform CG well-tempered metadynamics simulations (CG-NVT-MetaD) and analyze the free energy landscape of ONA hybridization for a select few systems. We demonstrate that CG-NVT-MetaD simulation results are consistent with the CG-NVT simulations for the studied systems. To examine the limitations of coarse-graining in capturing ONA-polymer interactions, we perform atomistic parallel tempering metadynamics simulations at well-tempered ensemble (AA-MetaD) for a 4-mer DNA in explicit water with and without conjugation to 8-mer poly(ethylene glycol) (PEG). AA-MetaD simulations also show that, for a short DNA duplex at T = 300 K, a condition where the DNA duplex is unstable, conjugation with PEG further destabilizes DNA duplex. We conclude with a comparison of results from these three different types of simulations and discuss their limitations and strengths.

Counter anion effect on structural, opto-electronic and charge transport properties of fused π-conjugated imidazolium compound

NASA Astrophysics Data System (ADS)

Vinodha, M.; Senthilkumar, K.

2018-05-01

The structure-activity relationship of fused π-conjugated imidazolium cation with three counter anion molecules, BF4-, CF3SO3- and (CF3SO2)2N-, was studied using electronic structure calculations. The structural, opto-electronic and charge transport properties of these complexes were studied. The charge transfer from π-conjugated imidazolium(I) to counter anion was confirmed in all the studied complexes. Interaction energy varies significantly depending on the counter anion and the stability was found higher for I-BF4 complex than both I-CF3SO3 and I-(CF3SO2)2N complexes. The strong (C-H)+...F- hydrogen bond of length 1.95 Å between fused π-conjugated imidazolium and BF-4 anion is the driving force for the strongest interaction energy in I-BF4 complex. The energy decomposition analysis confirms that the interaction between imidazolium and counter anion is mainly driven by electrostatic and orbital interaction. It has been observed that the absorption spectra of the complex are independent of anion nature but the influence of anion character is observed on frontier molecular orbital pattern. The charge transport property of I-BF4 complex was studied by using tight-binding Hamiltonian approach and found that the hole mobility in I-BF4 is 1.13 × 10-4 cm2 V-1 s-1.

PEG-coumarin based biocompatible self-assembled fluorescent nanoaggregates synthesized via click reactions and studies of aggregation behavior.

PubMed

Behl, Gautam; Sikka, Manisha; Chhikara, Aruna; Chopra, Madhu

2014-02-15

Click chemistry has found wide application in drug discovery, bioconjugation reactions, polymer chemistry and synthesis of amphiphilic materials with pharmaceutical and biomedical applications. Triazole substitution via a click reaction alters photophysical properties of coumarin. Both coumarin and triazole moieties participate in π-π stacking interactions. Hence it should be possible to prepare fluorescent self-assembly systems by conjugation of coumarin to poly (ethylene glycol) (PEG) via click reactions exhibiting hydrophilic, hydrophobic and π-π stacking interactions. Moreover, the materials can be suitable platforms to assess fluorescence modulation effect of triazole substitution on coumarins. PEG supported coumarin conjugates were synthesized and the fluorescence modulation effect of the formation of triazole on coumarin was assessed. Their aggregation properties were studied by surface tension measurements, dynamic light scattering (DLS), transmission electron microscopy (TEM), fluorescence and (1)H NMR spectroscopy. The conjugates were found to form nanoaggregates in the size range of 100-120 nm with a negative free energy of micellization (~-27 kJ mol(-1)) confirming aggregation and self-assembly. The Quantum yield of 4-methyl-7-propargylcoumarin (7P4MC) was enhanced after triazole formation with azide functionalized PEG (methoxy-PEG350 azide). The conjugates were found to exhibit π-π stacking interactions in addition to hydrophilic and hydrophobic interactions. They were found to be biocompatible with human pancreatic cancer cells. Copyright © 2013 Elsevier Inc. All rights reserved.

Inception of self-interacting dark matter with dark charge conjugation symmetry

DOE PAGES

Ma, Ernest

2017-07-04

A new understanding of the stability of self-interacting dark matter is pointed out, based on the simplest spontaneously broken Abelian gauge model with one complex scalar and one Dirac fermion. The key is the imposition of dark charge conjugation symmetry. It allows the possible existence of two stable particles: the Dirac fermion and the vector gauge boson which acts as a light mediator for the former's self-interaction. Since this light mediator does not decay, it avoids the strong cosmological constraints recently obtained for all such models where the light mediator decays into standard-model particles.

Hypersonic Aeroelastic Analysis

DTIC Science & Technology

1975-09-30

Interaction", WADC TR-58-95. July 1960. 6 Blessing, A. H., and Honawalt, A. J., "Thermal Effects on Static Aero- elastlc Stability and Control, Part I...Problems in Multilayer Plato Cylinders and Spheres Subject to Arbitrary Aerodynamic Heat Transfer". TN 4061-124, N.W.C. China Lake, July ...547-553. 64 Orlik-Rlickemann, K. J., "Dynamic Viscous Pressure-Interaction in Hyper- Flow", Aeronautical Report LR-525, July 1970, National Research

Role of Polyamines in Asthma Pathophysiology

PubMed Central

2018-01-01

Asthma is a complex disease of airways, where the interactions of immune and structural cells result in disease outcomes with airway remodeling and airway hyper-responsiveness. Polyamines, which are small-sized, natural super-cations, interact with negatively charged intracellular macromolecules, and altered levels of polyamines and their interactions have been associated with different pathological conditions including asthma. Elevated levels of polyamines have been reported in the circulation of asthmatic patients as well as in the lungs of a murine model of asthma. In various studies, polyamines were found to potentiate the pathogenic potential of inflammatory cells, such as mast cells and granulocytes (eosinophils and neutrophils), by either inducing the release of their pro-inflammatory mediators or prolonging their life span. Additionally, polyamines were crucial in the differentiation and alternative activation of macrophages, which play an important role in asthma pathology. Importantly, polyamines cause airway smooth muscle contraction and thus airway hyper-responsiveness, which is the key feature in asthma pathophysiology. High levels of polyamines in asthma and their active cellular and macromolecular interactions indicate the importance of the polyamine pathway in asthma pathogenesis; therefore, modulation of polyamine levels could be a suitable approach in acute and severe asthma management. This review summarizes the possible roles of polyamines in different pathophysiological features of asthma. PMID:29316647

Surface-Enhanced Raman and Surface-Enhanced Hyper-Raman Scattering of Thiol-Functionalized Carotene

PubMed Central

2016-01-01

A thiol-modified carotene, 7′-apo-7′-(4-mercaptomethylphenyl)-β-carotene, was used to obtain nonresonant surface-enhanced Raman scattering (SERS) spectra of carotene at an excitation wavelength of 1064 nm, which were compared with resonant SERS spectra at an excitation wavelength of 532 nm. These spectra and surface-enhanced hyper-Raman scattering (SEHRS) spectra of the functionalized carotene were compared with the spectra of nonmodified β-carotene. Using SERS, normal Raman, and SEHRS spectra, all obtained for the resonant case, the interaction of the carotene molecules with silver nanoparticles, as well as the influence of the resonance enhancement and the SERS enhancement on the spectra, were investigated. The interaction with the silver surface occurs for both functionalized and nonfunctionalized β-carotene, but only the stronger functionalization-induced interaction enables the acquisition of nonresonant SERS spectra of β-carotene at low concentrations. The resonant SEHRS and SERS spectra are very similar. Nevertheless, the SEHRS spectra contain additional bands of infrared-active modes of carotene. Increased contributions from bands that experience low resonance enhancement point to a strong interaction between silver nanoparticles and electronic levels of the molecules, thereby giving rise to a decrease in the resonance enhancement in SERS and SEHRS. PMID:28077983

Conjugal violence in the perspective of "Family Health Strategy" professionals: a public health problem and the need to provide care for the women

PubMed Central

Gomes, Nadirlene Pereira; Erdmann, Alacoque Lorenzini

2014-01-01

Objective to construct a theoretical matrix based on the meanings of the interactions and actions experienced by the professionals regarding the nursing care practices and the health of women in situations of conjugal violence in the ambit of the Family Health Strategy. Methods research based in Grounded Theory. Following approval by the Research Ethics Committee, 52 professionals were interviewed in Santa Catarina, Brazil. The analysis was based on open, axial and selective codifications. Results the theoretical model was delimited based on the phenomenon "Recognizing conjugal violence as a public health problem, and the need for management of the care for the woman", which reflects the experience of the professionals in relation to care for the woman, as well as the meanings attributed to this care. Conclusions the phenomenon allows one to understand the movement of action and interaction regarding the care for the woman in a situation of conjugal violence. PMID:24553706

Conjugal violence in the perspective of "Family Health Strategy" professionals: a public health problem and the need to provide care for the women.

PubMed

Gomes, Nadirlene Pereira; Erdmann, Alacoque Lorenzini

2014-01-01

to construct a theoretical matrix based on the meanings of the interactions and actions experienced by the professionals regarding the nursing care practices and the health of women in situations of conjugal violence in the ambit of the Family Health Strategy. research based in Grounded Theory. Following approval by the Research Ethics Committee, 52 professionals were interviewed in Santa Catarina, Brazil. The analysis was based on open, axial and selective codifications. the theoretical model was delimited based on the phenomenon "Recognizing conjugal violence as a public health problem, and the need for management of the care for the woman", which reflects the experience of the professionals in relation to care for the woman, as well as the meanings attributed to this care. the phenomenon allows one to understand the movement of action and interaction regarding the care for the woman in a situation of conjugal violence.

Controllable synthesis of protein-conjugated lead sulfide nanocubes by using bovine hemoglobin as a capping agent

NASA Astrophysics Data System (ADS)

Yang, Guangrui; Qin, Dezhi; Zhang, Li

2014-06-01

A simple, convenient, and controllable strategy was reported in this contribution for protein-assisted synthesis BHb-conjugated PbS nanocubes. Powder X-ray diffraction, energy disperse X-ray spectroscopy, transmission electron microscopy, high-resolution transmission electron microscopy, and selected-area electron diffraction characterizations were used to determine the structure and morphology of BHb-conjugated PbS nanocubes. The prepared PbS nanocrystals with cubic rock salt structure were uniform and monodispersed with homogeneous size around 12 nm. The results of Fourier transform infrared and circular dichroism assay proved that Pb2+/PbS had coordination interaction with functional groups of BHb besides physical-binding effect, and the secondary structure of protein significantly changed with this interaction. Thermogravimetric analysis results confirmed the existence of BHb in PbS nanocrystals and indicated that the conjugate bonds existed between PbS and BHb. A clear perspective was shown here that special nanostructure could be created by using proteins as a mediating template at the inorganic-organic interface.

Non-covalent conjugation of cutinase from Fusarium sp. ICT SAC1 with pectin for enhanced stability: Process minutiae, kinetics, thermodynamics and structural study.

PubMed

Muley, Abhijeet B; Chaudhari, Sandeep A; Singhal, Rekha S

2017-09-01

Cutinase, a member of α/β-fold hydrolase family possess potentially diverse applications in several industrial processes and products. The present work aims towards thermo-stabilization of cutinase from novel source Fusarium sp. ICT SAC1 via non-covalent interaction with polysaccharides. Although all six polysaccharides chosen for study enhanced the thermal stability, pectin was found to be most promising. The interaction protocol for cutinase with pectin was optimized sequentially with respect to the ratio of enzyme to pectin, solution pH, and buffer strength. Cutinase-pectin conjugate under optimized conditions (1:12, pH-6.5, 50mM) showed enhanced thermal stability as evident from lower inactivation rate constant, higher half-life and D-value within the 40-55°C. A slender rise in K m and V max values and enhanced thermodynamic parameters of cutinase-pectin conjugate were observed after non-covalent interaction. Entropy values were 1.5-fold higher for cutinase-pectin conjugate at each temperature suggesting an upsurge in number of protein molecules in a transition activated state. Positive values of entropy for both forms of cutinase suggested a rise in disordered conformation. Noticeable conformational changes in cutinase after conjugation with pectin were confirmed by FTIR as well as fluorescence emission spectra. An increment in helix to turn conversion was observed in complexed cutinase vis-à-vis free cutinase. Copyright © 2017 Elsevier B.V. All rights reserved.

Concentration-Driven Assembly and Sol–Gel Transition of π-Conjugated Oligopeptides

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

Zhou, Yuecheng; Li, Bo; Li, Songsong

Advances in supramolecular assembly have enabled the design and synthesis of functional materials with well-defined structures across multiple length scales. Biopolymer-synthetic hybrid materials can assemble into supramolecular structures with a broad range of structural and functional diversity through precisely controlled noncovalent interactions between subunits. Despite recent progress, there is a need to understand the mechanisms underlying the assembly of biohybrid/synthetic molecular building blocks, which ultimately control the emergent properties of hierarchical assemblies. Here in this work, we study the concentration-driven self-assembly and gelation of π-conjugated synthetic oligopeptides containing different π-conjugated cores (quaterthiophene and perylene diimide) using a combination of particlemore » tracking microrheology, confocal fluorescence microscopy, optical spectroscopy, and electron microscopy. Our results show that π-conjugated oligopeptides self-assemble into β-sheet-rich fiber-like structures at neutral pH, even in the absence of electrostatic screening of charged residues. A critical fiber formation concentration c fiber and a critical gel concentration c gel are determined for fiber-forming π-conjugated oligopeptides, and the linear viscoelastic moduli (storage modulus G' and loss modulus G") are determined across a wide range of peptide concentrations. These results suggest that the underlying chemical structure of the synthetic π-conjugated cores greatly influences the self-assembly process, such that oligopeptides appended to π-conjugated cores with greater torsional flexibility tend to form more robust fibers upon increasing peptide concentration compared to oligopeptides with sterically constrained cores. Overall, our work focuses on the molecular assembly of π-conjugated oligopeptides driven by concentration, which is controlled by a combination of enthalpic and entropic interactions between oligopeptide subunits.« less

Concentration-Driven Assembly and Sol–Gel Transition of π-Conjugated Oligopeptides

DOE PAGES

Zhou, Yuecheng; Li, Bo; Li, Songsong; ...

2017-08-17

Advances in supramolecular assembly have enabled the design and synthesis of functional materials with well-defined structures across multiple length scales. Biopolymer-synthetic hybrid materials can assemble into supramolecular structures with a broad range of structural and functional diversity through precisely controlled noncovalent interactions between subunits. Despite recent progress, there is a need to understand the mechanisms underlying the assembly of biohybrid/synthetic molecular building blocks, which ultimately control the emergent properties of hierarchical assemblies. Here in this work, we study the concentration-driven self-assembly and gelation of π-conjugated synthetic oligopeptides containing different π-conjugated cores (quaterthiophene and perylene diimide) using a combination of particlemore » tracking microrheology, confocal fluorescence microscopy, optical spectroscopy, and electron microscopy. Our results show that π-conjugated oligopeptides self-assemble into β-sheet-rich fiber-like structures at neutral pH, even in the absence of electrostatic screening of charged residues. A critical fiber formation concentration c fiber and a critical gel concentration c gel are determined for fiber-forming π-conjugated oligopeptides, and the linear viscoelastic moduli (storage modulus G' and loss modulus G") are determined across a wide range of peptide concentrations. These results suggest that the underlying chemical structure of the synthetic π-conjugated cores greatly influences the self-assembly process, such that oligopeptides appended to π-conjugated cores with greater torsional flexibility tend to form more robust fibers upon increasing peptide concentration compared to oligopeptides with sterically constrained cores. Overall, our work focuses on the molecular assembly of π-conjugated oligopeptides driven by concentration, which is controlled by a combination of enthalpic and entropic interactions between oligopeptide subunits.« less

A multimode vibronic treatment of absorption, resonance Raman, and hyper-Rayleigh scattering of excitonically coupled molecular dimers

NASA Astrophysics Data System (ADS)

Myers Kelley, Anne

2003-08-01

The linear absorption spectra, resonance Raman excitation profiles and depolarization dispersion curves, and hyper-Rayleigh scattering profiles are calculated for excitonically coupled homodimers of a model electron donor-acceptor "push-pull" conjugated chromophore as a function of dimer geometry. The vibronic eigenstates of the dimer are calculated by diagonalizing the matrix of transition dipole couplings among the vibronic transitions of the constituent monomers. The absorption spectra show the usual red- or blueshifted transitions for J-type or H-type dimers, respectively. When the electronic coupling is large compared with the vibronic width of the monomer spectrum, the dimer absorption spectra exhibit simple Franck-Condon progressions having reduced vibronic intensities compared with the monomer, and the resonance Raman excitation profiles are shifted but otherwise only weakly perturbed. When the coupling is comparable to the vibronic width, the H-dimer absorption spectra exhibit irregular vibronic frequency spacings and intensity patterns and the effects on the Raman excitation profiles are larger. There is strong dispersion in the Raman depolarization ratios for dimer geometries in which both transitions carry oscillator strength. The first hyperpolarizabilities are somewhat enhanced in J-dimers and considerably reduced in H-dimers. These effects on the molecular β will amplify the effects of dimerization on the ground-state dipole moment in electro-optic materials formed from chromophore-doped polymers that must be electric field poled to obtain the net alignment needed for a macroscopic χ(2).

Gold nanoparticles as a platform for creating a multivalent poly-SUMO chain inhibitor that also augments ionizing radiation.

PubMed

Li, Yi-Jia; Perkins, Angela L; Su, Yang; Ma, Yuelong; Colson, Loren; Horne, David A; Chen, Yuan

2012-03-13

Protein-protein interactions mediated by ubiquitin-like (Ubl) modifications occur as mono-Ubl or poly-Ubl chains. Proteins that regulate poly-SUMO (small ubiquitin-like modifier) chain conjugates play important roles in cellular response to DNA damage, such as those caused by cancer radiation therapy. Additionally, high atomic number metals, such as gold, preferentially absorb much more X-ray energy than soft tissues, and thus augment the effect of ionizing radiation when delivered to cells. In this study, we demonstrate that conjugation of a weak SUMO-2/3 ligand to gold nanoparticles facilitated selective multivalent interactions with poly-SUMO-2/3 chains leading to efficient inhibition of poly-SUMO-chain-mediated protein-protein interactions. The ligand-gold particle conjugate significantly sensitized cancer cells to radiation but was not toxic to normal cells. This study demonstrates a viable approach for selective targeting of poly-Ubl chains through multivalent interactions created by nanoparticles that can be chosen based on their properties, such as abilities to augment radiation effects.

Gold nanoparticles as a platform for creating a multivalent poly-SUMO chain inhibitor that also augments ionizing radiation

PubMed Central

Li, Yi-Jia; Perkins, Angela L.; Su, Yang; Ma, Yuelong; Colson, Loren; Horne, David A.; Chen, Yuan

2012-01-01

Protein-protein interactions mediated by ubiquitin-like (Ubl) modifications occur as mono-Ubl or poly-Ubl chains. Proteins that regulate poly-SUMO (small ubiquitin-like modifier) chain conjugates play important roles in cellular response to DNA damage, such as those caused by cancer radiation therapy. Additionally, high atomic number metals, such as gold, preferentially absorb much more X-ray energy than soft tissues, and thus augment the effect of ionizing radiation when delivered to cells. In this study, we demonstrate that conjugation of a weak SUMO-2/3 ligand to gold nanoparticles facilitated selective multivalent interactions with poly-SUMO-2/3 chains leading to efficient inhibition of poly-SUMO-chain-mediated protein-protein interactions. The ligand-gold particle conjugate significantly sensitized cancer cells to radiation but was not toxic to normal cells. This study demonstrates a viable approach for selective targeting of poly-Ubl chains through multivalent interactions created by nanoparticles that can be chosen based on their properties, such as abilities to augment radiation effects. PMID:22388745

Systemic aspects of conjugal resilience in couples with a child facing cancer and marrow transplantation

PubMed Central

Martin, Julie; Péloquin, Katherine; Vachon, Marie-France; Duval, Michel; Sultan, Serge

2016-01-01

Introduction The negative impact of paediatric cancer on parents is well known and is even greater when intensive treatments are used. This study aimed to describe how couples whose child has received a transplant for the treatment of leukaemia view conjugal resilience and to evaluate the role of we-ness as a precursor of conjugal adjustment. Methods Four parental couples were interviewed. Interviews were analysed in two ways: inductive thematic analysis and rating of verbal content with the We-ness Coding Scale. Results Participants report that conjugal resilience involves the identification of the couple as a team and cohesion in the couple. Being a team generates certain collaborative interactions that lead to conjugal resilience. A sense of we-ness in parents is associated with fluctuation in the frequency of themes. Discussion Participants’ vision of conjugal resilience introduced novel themes. The sense of we-ness facilitates cohesion and the process of conjugal resilience. PMID:27687510

Graphical Representations of Electronic Search Patterns.

ERIC Educational Resources Information Center

Lin, Xia; And Others

1991-01-01

Discussion of search behavior in electronic environments focuses on the development of GRIP (Graphic Representor of Interaction Patterns), a graphing tool based on HyperCard that produces graphic representations of search patterns. Search state spaces are explained, and forms of data available from electronic searches are described. (34…

Designing an eMap to Teach Multimedia Applications Online

ERIC Educational Resources Information Center

Ruffini, Michael F.

2004-01-01

Teachers and students use multimedia software to create interactive presentations and content projects. Popular multimedia programs include: Microsoft's PowerPoint[R], Knowledge Adventure's HyperStudio[R], and Macromedia's Director MX 2004[R]. Creating multimedia projects engage students in active learning and thinking as they complete projects…

Molecularly precise dendrimer-drug conjugates with tunable drug release for cancer therapy.

PubMed

Zhou, Zhuxian; Ma, Xinpeng; Murphy, Caitlin J; Jin, Erlei; Sun, Qihang; Shen, Youqing; Van Kirk, Edward A; Murdoch, William J

2014-10-06

The structural preciseness of dendrimers makes them perfect drug delivery carriers, particularly in the form of dendrimer-drug conjugates. Current dendrimer-drug conjugates are synthesized by anchoring drug and functional moieties onto the dendrimer peripheral surface. However, functional groups exhibiting the same reactivity make it impossible to precisely control the number and the position of the functional groups and drug molecules anchored to the dendrimer surface. This structural heterogeneity causes variable pharmacokinetics, preventing such conjugates to be translational. Furthermore, the highly hydrophobic drug molecules anchored on the dendrimer periphery can interact with blood components and alter the pharmacokinetic behavior. To address these problems, we herein report molecularly precise dendrimer-drug conjugates with drug moieties buried inside the dendrimers. Surprisingly, the drug release rates of these conjugates were tailorable by the dendrimer generation, surface chemistry, and acidity. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Influence of the Surfactant Structure on Photoluminescent π-Conjugated Polymer Nanoparticles: Interfacial Properties and Protein Binding.

PubMed

Urbano, Laura; Clifton, Luke; Ku, Hoi Ki; Kendall-Troughton, Hannah; Vandera, Kalliopi-Kelli A; Matarese, Bruno F E; Abelha, Thais; Li, Peixun; Desai, Tejal; Dreiss, Cécile A; Barker, Robert D; Green, Mark A; Dailey, Lea Ann; Harvey, Richard D

2018-05-17

π-Conjugated polymer nanoparticles (CPNs) are under investigation as photoluminescent agents for diagnostics and bioimaging. To determine whether the choice of surfactant can improve CPN properties and prevent protein adsorption, five nonionic polyethylene glycol alkyl ether surfactants were used to produce CPNs from three representative π-conjugated polymers. The surfactant structure did not influence size or yield, which was dependent on the nature of the conjugated polymer. Hydrophobic interaction chromatography, contact angle, quartz crystal microbalance, and neutron reflectivity studies were used to assess the affinity of the surfactant to the conjugated polymer surface and indicated that all surfactants were displaced by the addition of a model serum protein. In summary, CPN preparation methods which rely on surface coating of a conjugated polymer core with amphiphilic surfactants may produce systems with good yields and colloidal stability in vitro, but may be susceptible to significant surface alterations in physiological fluids.

Pneumococcal conjugate vaccines: proceedings from an interactive symposium at the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy.

PubMed

Pelton, Stephen I; Dagan, Ron; Gaines, Beverly M; Klugman, Keith P; Laufer, Dagna; O'Brien, Katherine; Schmitt, Heinz J

2003-04-02

Globally, Streptococcus pneumoniae is a leading cause of invasive and noninvasive disease in infants and young children. The emergence of antibiotic-resistant strains has increased interest in prevention through immunization. Currently, the only available conjugate pneumococcal vaccine is a seven-valent formulation, PNCRM7. This paper presents excerpts from a symposium that provided an update of ongoing surveillance data and clinical trials evaluating pneumococcal conjugate vaccines. The topics addressed included: (1) PNCRM7 postmarketing safety data; (2) the impact of PNCRM7 in premature infants; (3) the direct and indirect effect of pneumococcal conjugate vaccines on colonization; (4) the effect of pneumococcal conjugate vaccines on replacement disease and the rate of resistance among replacement serotypes; (5) the current recommendations for the use of PNCRM7; and (6) the potential impact of conjugate vaccines in Europe and the Asia-Pacific region.

Conjugated organic framework with three-dimensionally ordered stable structure and delocalized π clouds

NASA Astrophysics Data System (ADS)

Guo, Jia; Xu, Yanhong; Jin, Shangbin; Chen, Long; Kaji, Toshihiko; Honsho, Yoshihito; Addicoat, Matthew A.; Kim, Jangbae; Saeki, Akinori; Ihee, Hyotcherl; Seki, Shu; Irle, Stephan; Hiramoto, Masahiro; Gao, Jia; Jiang, Donglin

2013-11-01

Covalent organic frameworks are a class of crystalline organic porous materials that can utilize π-π-stacking interactions as a driving force for the crystallization of polygonal sheets to form layered frameworks and ordered pores. However, typical examples are chemically unstable and lack intrasheet π-conjugation, thereby significantly limiting their applications. Here we report a chemically stable, electronically conjugated organic framework with topologically designed wire frameworks and open nanochannels, in which the π conjugation-spans the two-dimensional sheets. Our framework permits inborn periodic ordering of conjugated chains in all three dimensions and exhibits a striking combination of properties: chemical stability, extended π-delocalization, ability to host guest molecules and hole mobility. We show that the π-conjugated organic framework is useful for high on-off ratio photoswitches and photovoltaic cells. Therefore, this strategy may constitute a step towards realizing ordered semiconducting porous materials for innovations based on two-dimensionally extended π systems.

Tectono-magmatic evolution at distal magma-poor rifted margins: insights of the lithospheric breakup at the Australia-Antarctica margins.

NASA Astrophysics Data System (ADS)

Gillard, Morgane; Autin, Julia; Manatschal, Gianreto

2015-04-01

The discovery of large domains of hyper-extended continental crust and exhumed mantle along many present-day magma-poor rifted margins questions the processes that play during the lithospheric breakup and the onset of seafloor spreading. In particular, the amount of magma and its relation to tectonic structures is yet little understood. Trying to find answers to these questions asks to work at the most distal parts of rifted margins where the transition from rifting to steady state seafloor spreading occurred. The Australian-Antarctic conjugated margins provide an excellent study area. Indeed, the central sector of the Great Australian Bight/Wilkes Land developed in a magma-poor probably ultra-slow setting and displays a complex and not yet well understood Ocean-Continent Transition (OCT). This distal area is well imaged by numerous high quality seismic lines covering the whole OCT and the steady-state oceanic crust. The deformation recorded in the sedimentary units along these margins highlights a migration of the deformation toward the ocean and a clear polyphase evolution. In particular, the observation that each tectono-sedimentary unit downlaps oceanwards onto the basement suggests that final rifting is associated with the creation of new depositional ground under conditions that are not yet those of a steady state oceanic crust. These observations lead to a model of evolution for these distal margins implying the development of multiple detachment systems organizing out-of-sequence, each new detachment fault developing into the previously exhumed basement. This spatial and temporal organization of fault systems leads to a final symmetry of exhumed domains at both conjugated margins. Magma appears to gradually increase during the margin development and is particularly present in the more distal domain where we can observe clear magma/fault interactions. We propose that the evolution of such rifted margins is linked to cycles of delocalisation/re-localisation of the deformation which could be mainly influenced by magma and by the decoupling between the upper brittle deformation and the asthenospheric uplift. In this context, the lithospheric breakup appears to be triggered by progressive syn-extensional thermal and magmatic weakening. However, the observation of continentward dipping reflectors interpreted as flip-flop detachment systems suggests that the localisation of the spreading centre and the onset of the steady state oceanic spreading will not be necessarily associated with a clear magmatic oceanic crust. In case of a low magmatic budget we can rather observe the onset of steady state amagmatic oceanic spreading, similar to what is expected at ultra-slow spreading ridges. This model of evolution (Gillard, 2014, PhD thesis) could well explain the fact that most magma-poor margins display symmetric exhumed domains on conjugate margins. However it raises the question of the nature of magnetic anomalies in ocean-continent transitions and their value for the interpretation of the kinematic evolution of conjugate rifted margins.

Molecular structure, FT-IR, NBO, HOMO and LUMO, MEP and first order hyperpolarizability of (2E)-1-(2,4-Dichlorophenyl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one by HF and density functional methods.

PubMed

Sheena Mary, Y; Yohannan Panicker, C; Anto, P L; Sapnakumari, M; Narayana, B; Sarojini, B K

2015-01-25

(2E)-1-(2,4-Dichlorophenyl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one is synthesized by using 2,4-dichloroacetophenone and 3,4,5-trimethoxybenzaldehyde in ethanol. The structure of the compound was confirmed by IR and single crystal X-ray diffraction studies. FT-IR spectrum of (2E)-1-(2,4-dichloro-phenyl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one was recorded and analyzed. The crystal structure is also described. The vibrational wavenumbers were computed using HF and DFT methods and are assigned with the help of potential energy distribution method. The first hyperpolarizability and infrared intensities are also reported. The geometrical parameters of the title compound obtained from XRD studies are in agreement with the calculated (DFT) values. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. The HOMO and LUMO analysis are used to determine the charge transfer within the molecule. MEP was performed by the DFT method. From the MEP map of the title molecule, negative region is mainly localized over the electronegative oxygen atoms, in the carbonyl group and the oxygen atom O4 of the methoxy group and the maximum positive region is localized on the phenyl rings. Copyright © 2014 Elsevier B.V. All rights reserved.

Infrared spectrum, structural and optical properties and molecular docking study of 3-(4-fluorophenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbaldehyde.

PubMed

Mary, Y Sheena; Panicker, C Yohannan; Sapnakumari, M; Narayana, B; Sarojini, B K; Al-Saadi, Abdulaziz A; Van Alsenoy, C; War, Javeed Ahmad; Fun, H K

2015-03-05

The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of 3-(4-fluorophenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbaldehyde have been investigated experimentally and theoretically. The title compound was optimized using at HF and DFT levels of calculations. The B3LYP/6-311++G(d,p) (5D,7F) results and in agreement with experimental infrared bands. The normal modes are assigned using potential energy distribution. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using natural bonding orbital analysis. The frontier molecular orbital analysis is used to determine the charge transfer within the molecule. From molecular electrostatic potential map, it is evident that the negative electrostatic potential regions are mainly localized over the carbonyl group and mono substituted phenyl ring and are possible sites for electrophilic attack and, positive regions are localized around all para substituted phenyl and pyrazole ring, indicating possible sites for nucleophilic attack. First hyperpolarizability is calculated in order to find its role in nonlinear optics. The geometrical parameters are in agreement with experimental data. From the molecular docking studies, it is evident that the fluorine atom attached to phenyl ring and the carbonyl group attached to pyrazole ring are crucial for binding and the results draw us to the conclusion that the compound might exhibit phosphodiesterase inhibitory activity. Copyright © 2014 Elsevier B.V. All rights reserved.

Facile synthesis, single crystal analysis, and computational studies of sulfanilamide derivatives

NASA Astrophysics Data System (ADS)

Tahir, Muhammad Nawaz; Khalid, Muhammad; Islam, Ayesha; Ali Mashhadi, Syed Muddassir; Braga, Ataualpa A. C.

2017-01-01

Antibacterial resistance is a worldwide problem. Sulfanilamide is widely used antibacterial. For the first time, we report here a simple method for the derivative synthesis of the title drugs, single crystal XRD and density functional theory (DFT) studies. The optimized molecular structure, natural bond orbital (NBO), frontier molecular orbitals (FMOs) molecular electrostatic potential studies (MEP) and Mulliken population analysis (MPA) have been performed using M06-2X/6-31G(d, p). The FT-IR spectra and thermodynamic parameters were calculated at M06-2X/6-311 + G(2d,p) and B3LYP/6-31G(d, p) levels respectively, while, the UV-Vis analysis was performed using TD-DFT/B3LYP/6-31G(d, p) method. The experimental FT-IR spectra of both compounds were also carried out to reconfirm sbnd H⋯Osbnd hydrogen bonds. The DFT optimized parameters exhibiting good agreement with the experimental data. NBO analysis explored the hyper conjugative interaction and stability of title crystals, especially, reconfirmed the existence of sbnd H⋯Osbnd hydrogen bonds between the dimers. The FT-IR, thermodynamic parameters, MEP and MPA also revealed the hydrogen bonding detail is harmonious to XRD data. As a matter of the fact, the hydrogen bonding is a significant parameter for the understanding and design of molecular crystals, subsequently; it can also play a vital role in the supramolecular chemistry. Moreover, the global reactivity descriptors suggest that title compounds might be bioactive.

Synthesis, crystal structure analysis, spectral investigations, DFT computations, Biological activities and molecular docking of methyl(2E)-2-{[N-(2-formylphenyl)(4-methylbenzene) sulfonamido]methyl}-3-(4-fluorophenyl)prop-2-enoate, a potential bioactive agent

NASA Astrophysics Data System (ADS)

Murugavel, S.; Vetri Velan, V.; Kannan, Damodharan; Bakthadoss, Manickam

2016-03-01

The title compound methyl(2E)-2-{[N-(2-formylphenyl) (4-methylbenzene)sulfonamido]methyl}-3-(4-fluorophenyl) prop-2-enoate (MFMSF) has been synthesized and single crystals were grown by slow evaporation solution growth technique at room temperature. The grown crystals were characterized by FTIR, 1H NMR, 13C NMR, and single crystal X-ray diffraction. In the crystal, molecules are linked by intermolecular C-H…O hydrogen bonds forming a two-dimensional supramolecular network along [110] direction. The molecular geometry was also optimized using density functional theory (DFT/B3LYP) method with the 6-311G (d,p) basis set in ground state and compared with the experimental data. The entire vibrational assignments of wave numbers were made on the basis of potential energy distribution (PED) by VEDA 4 programme. Stability of the molecule arising from hyper conjugative interactions, charge delocalization has been analyzed using natural bond orbital (NBO) analysis. In addition, NLO, MEP, Mulliken, thermodynamic properties, HOMO and LUMO energy gap were theoretically predicted. The global chemical reactivity descriptors are calculated for MFMSF and used to predict their relative stability and reactivity. The antibacterial activity of the compound was also tested against various pathogens. The molecular docking studies concede that title compound may exhibit PBP-2X inhibitor activity.

Study on structure, vibrational analysis and molecular characteristics of some halogen substituted azido-phenylethanones using FTIR spectra and DFT

NASA Astrophysics Data System (ADS)

Prashanth, J.; Reddy, Byru Venkatram

2018-03-01

The Fourier transform infrared (FTIR) spectra of organic compounds 4-fluoro-2-azido-1-phenylethanone (FAP), 4-chloro-2-azido-1-phenylethanone (CAP) and 4-bromo-2-azido-1-phenylethanone (BAP) have been recorded in the region 4000-400 cm-1. The optimized molecular structure for global minimum energy of the titled molecules is determined by evaluating torsional potentials as a function of rotation angle about free rotation bonds among the substituent groups subjecting them to DFT employing B3LYP functional with 6-311++G (d,p) basis set. The vibrational frequencies along with infrared intensities are computed by SQM procedure. The rms error between observed and calculated frequencies is found to be 9.27, 8.17 and 7.95 cm-1 for FAP, CAP and BAP, respectively which shows good agreement between experimental and scaled values of calculated frequencies obtained by DFT. The vibrational assignments of all the fundamental bands of each molecule are made unambiguously using PED and eigen vectors obtained in the computations. The computed values of dipole moment, polarizability and hyperpolarizability indicate that the titled molecules exhibit NLO behaviour and hence may be considered for potential applicants for the development of NLO materials. HOMO and LUMO energies evaluated in the study demonstrate chemical stability of the molecules. NBO analysis is made to study the stability of the molecules arising from hyper conjugative interactions and charge delocalization. The molecular electrostatic surface potential (MESP) and thermodynamic parameters are also evaluated.

Strain-induced three-photon effects

NASA Astrophysics Data System (ADS)

Jeong, Jae-Woo; Shin, Sung-Chul; Lyubchanskii, I. L.; Varyukhin, V. N.

2000-11-01

Strain-induced three-photon effects such as optical second-harmonic generation and hyper-Rayleigh light scattering, characterized by electromagnetic radiation at the double frequency of an incident light, are phenomenologically investigated by adopting a nonlinear photoelastic interaction. The relations between the strain and the nonlinear optical susceptibility for crystal surfaces with point symmetries of 4mm and 3m are described by a symmetry analysis of the nonlinear photoelastic tensor. We theoretically demonstrate a possibility of determining the strain components by measuring the rotational anisotropy of radiation at the second-harmonic frequency. Hyper-Rayleigh light scattering by dislocation strain is also described using a nonlinear photoelastic tensor. The angular dependencies of light scattered at the double frequency of an incident light for different scattering geometries are analyzed.

Cytochrome c conjugated to ZnO-MAA nanoparticles: the study of interaction and influence on protein structure.

PubMed

Simšíková, Michaela; Antalík, Marián; Kaňuchová, Mária; Skvarla, Jiří

2013-08-01

Nanoparticle-protein conjugates have potential for numerous applications due to the combination of the properties of both components. In this paper we studied the conjugation of horse heart cytochrome c with ZnO nanoparticles modified by mercaptoacetic acid (MAA) which may be a material with great potential in anticancer therapy as a consequence of synergic effect of both components. Cyt c adsorption to the ZnO-MAA NPs surface was studied by UV-vis spectroscopy and by a dynamic light scattering in various pH. The results indicate that the optimal pH for the association of protein with modified nanoparticles is in range 5.8-8.5 where 90-96% of cytochrome c was assembled on ZnO-MAA nanoparticles. The interaction of proteins with nanoparticles often results in denaturation or loss of protein function. Our observations from UV-vis spectroscopy and circular dichroism performed preserved protein structure after the interaction with modified nanoparticles. Copyright © 2013 Elsevier B.V. All rights reserved.

Beyond Atg8 binding: The role of AIM/LIR motifs in autophagy.

PubMed

Fracchiolla, Dorotea; Sawa-Makarska, Justyna; Martens, Sascha

2017-05-04

Selective macroautophagy/autophagy mediates the selective delivery of cytoplasmic cargo material via autophagosomes into the lytic compartment for degradation. This selectivity is mediated by cargo receptor molecules that link the cargo to the phagophore (the precursor of the autophagosome) membrane via their simultaneous interaction with the cargo and Atg8 proteins on the membrane. Atg8 proteins are attached to membrane in a conjugation reaction and the cargo receptors bind them via short peptide motifs called Atg8-interacting motifs/LC3-interacting regions (AIMs/LIRs). We have recently shown for the yeast Atg19 cargo receptor that the AIM/LIR motifs also serve to recruit the Atg12-Atg5-Atg16 complex, which stimulates Atg8 conjugation, to the cargo. We could further show in a reconstituted system that the recruitment of the Atg12-Atg5-Atg16 complex is sufficient for cargo-directed Atg8 conjugation. Our results suggest that AIM/LIR motifs could have more general roles in autophagy.

Stimulated Brillouin scattering continuous wave phase conjugation in step-index fiber optics.

PubMed

Massey, Steven M; Spring, Justin B; Russell, Timothy H

2008-07-21

Continuous wave (CW) stimulated Brillouin scattering (SBS) phase conjugation in step-index optical fibers was studied experimentally and modeled as a function of fiber length. A phase conjugate fidelity over 80% was measured from SBS in a 40 m fiber using a pinhole technique. Fidelity decreases with fiber length, and a fiber with a numerical aperture (NA) of 0.06 was found to generate good phase conjugation fidelity over longer lengths than a fiber with 0.13 NA. Modeling and experiment support previous work showing the maximum interaction length which yields a high fidelity phase conjugate beam is inversely proportional to the fiber NA(2), but find that fidelity remains high over much longer fiber lengths than previous models calculated. Conditions for SBS beam cleanup in step-index fibers are discussed.

Poly(zwitterionic)protein conjugates offer increased stability without sacrificing binding affinity or bioactivity

NASA Astrophysics Data System (ADS)

Keefe, Andrew J.; Jiang, Shaoyi

2012-01-01

Treatment with therapeutic proteins is an attractive approach to targeting a number of challenging diseases. Unfortunately, the native proteins themselves are often unstable in physiological conditions, reducing bioavailability and therefore increasing the dose that is required. Conjugation with poly(ethylene glycol) (PEG) is often used to increase stability, but this has a detrimental effect on bioactivity. Here, we introduce conjugation with zwitterionic polymers such as poly(carboxybetaine). We show that poly(carboxybetaine) conjugation improves stability in a manner similar to PEGylation, but that the new conjugates retain or even improve the binding affinity as a result of enhanced protein-substrate hydrophobic interactions. This chemistry opens a new avenue for the development of protein therapeutics by avoiding the need to compromise between stability and affinity.

One-pot production of 18F-biotin by conjugation with 18F-FDG for pre-targeted imaging: synthesis and radio-labelling of a PEGylated precursor.

PubMed

Simpson, Michael; Trembleau, Laurent; Cheyne, Richard W; Smith, Tim A D

2011-02-01

The biotin-avidin affinity system is exploited in pre-targeted imaging using avidin-conjugated antibodies. (18)F-FDG is available at all PET centres. (18)F-FDG forms oximes by reaction with oxyamine. Herein we describe the synthesis of oxyamine-funtionalised biotin, its (18)F-labelling by conjugation with (18)F-FDG and confirm its ability to interact with avidin. Copyright © 2010 Elsevier Ltd. All rights reserved.

Immunosensor development for rice tungro bacilliform virus (RTBV) detection using antibody nano-gold conjugate

NASA Astrophysics Data System (ADS)

Uda, M. N. A.; Hasfalina, C. M.; Samsuzana, A. A.; Hashim, U.; Ariffin, Shahrul A. B.; Zamri, I.; Nur Sabrina, W.; B. Siti Noraini, B.; Faridah, S.; Mazidah, M.; Gopinath, Subash C. B.

2017-03-01

Rice tungro disease (RTD) causes major losses to rice crop plantation. Hence, a highly sensitive tools need to be developed for the detection of RTD which can be employed in both laboratory and field. An electrochemical immunosensor system for the detection of RTD, based on immobilized specific antibodies conjugated with gold nanoparticle was developed for this purpose. However, this paper focus for RTBV interaction using the conjugated antibodies which is added with polymer and deposited on carbon screen printed working electrodes.

Organic-Inorganic Composites of Semiconductor Nanocrystals for Efficient Excitonics.

PubMed

Guzelturk, Burak; Demir, Hilmi Volkan

2015-06-18

Nanocomposites of colloidal semiconductor nanocrystals integrated into conjugated polymers are the key to soft-material hybrid optoelectronics, combining advantages of both plastics and particles. Synergic combination of the favorable properties in the hybrids of colloidal nanocrystals and conjugated polymers offers enhanced performance and new functionalities in light-generation and light-harvesting applications, where controlling and mastering the excitonic interactions at the nanoscale are essential. In this Perspective, we highlight and critically consider the excitonic interactions in the organic-inorganic nanocomposites to achieve highly efficient exciton transfer through rational design of the nanocomposites. The use of strong excitonic interactions in optoelectronic devices can trigger efficiency breakthroughs in hybrid optoelectronics.

Computer Applications in Balancing Chemical Equations.

ERIC Educational Resources Information Center

Kumar, David D.

2001-01-01

Discusses computer-based approaches to balancing chemical equations. Surveys 13 methods, 6 based on matrix, 2 interactive programs, 1 stand-alone system, 1 developed in algorithm in Basic, 1 based on design engineering, 1 written in HyperCard, and 1 prepared for the World Wide Web. (Contains 17 references.) (Author/YDS)

The GenTechnique Project: Developing an Open Environment for Learning Molecular Genetics.

ERIC Educational Resources Information Center

Calza, R. E.; Meade, J. T.

1998-01-01

The GenTechnique project at Washington State University uses a networked learning environment for molecular genetics learning. The project is developing courseware featuring animation, hyper-link controls, and interactive self-assessment exercises focusing on fundamental concepts. The first pilot course featured a Web-based module on DNA…

XML: A Publisher's Perspective.

ERIC Educational Resources Information Center

Andrews, Timothy M.

1999-01-01

Explains eXtensible Markup Language (XML) and describes how Dow Jones Interactive is using it to improve the news-gathering and dissemination process through intranets and the World Wide Web. Discusses benefits of using XML, the relationship to HyperText Markup Language (HTML), lack of available software tools and industry support, and future…

A nanodiamond-fluorescein conjugate for cell studies

NASA Astrophysics Data System (ADS)

Pedroso-Santana, Seidy; Fleitas-Salazar, Noralvis; Sarabia-Sainz, Andrei; Silva-Campa, Erika; Burgara-Estrella, Alexel; Angulo-Molina, Aracely; Melendrez, Rodrigo; Pedroza-Montero, Martin; Riera, Raul

2018-03-01

The use of nanodiamonds in studies with living systems generally involves the modification of their surfaces with functional groups. Fluorescent molecules can be attached to these groups, so that one can know the exact position of the particles in each moment of the interaction with the cells. Here we modify the surface of detonation nanodiamonds and nitrogen-vacancy center nanodiamonds using carboxylation and hydroxylation procedures. Subsequent reactions with silicates and cysteine, before addition of fluorescein allow to obtain fluorescent nano-conjugates. We used confocal microscopy to observe the position of nanodiamonds interacting with HeLa cells. At 3 h post-incubation the green fluorescence is localized in extracellular rounded like-vesicles assemblies while at 24 h the conjugates can be observed inside the cells. The measurement of the fluorescence emitted by both conjugates allowed to find an enhanced emission of fluorescein isothiocyanate (FITC) when the nitrogen-vacancy center is present. We propose the existence of a fluorescence enhancement by electron transference process. The procedure described in this work allows the functionalization of nanodiamonds with FITC and other molecules using functional surface groups and small size mediators. Also, as was proved in our work, the nanodiamond-fluorescein conjugates can be used to track nanoparticles position within the cell. Localization studies are particularly important for drug delivery applications of nanodiamonds.

Incorporating functionalized polyethylene glycol lipids into reprecipitated conjugated polymer nanoparticles for bioconjugation and targeted labeling of cells

NASA Astrophysics Data System (ADS)

Kandel, Prakash K.; Fernando, Lawrence P.; Ackroyd, P. Christine; Christensen, Kenneth A.

2011-03-01

We report a simple and rapid method to prepare extremely bright, functionalized, stable, and biocompatible conjugated polymer nanoparticles incorporating functionalized polyethylene glycol (PEG) lipids by reprecipitation. These nanoparticles retain the fundamental spectroscopic properties of conjugated polymer nanoparticles prepared without PEG lipid, but demonstrate greater hydrophilicity and quantum yield compared to unmodified conjugated polymer nanoparticles. The sizes of these nanoparticles, as determined by TEM, were 21-26 nm. Notably, these nanoparticles were prepared with several PEG lipid functional end groups, including biotin and carboxy moieties that can be easily conjugated to biomolecules. We have demonstrated the availability of these end groups for functionalization using the interaction of biotin PEG lipid conjugated polymer nanoparticles with streptavidin. Biotinylated PEG lipid conjugated polymer nanoparticles bound streptavidin-linked magnetic beads, while carboxy and methoxy PEG lipid modified nanoparticles did not. Similarly, biotinylated PEG lipid conjugated polymer nanoparticles bound streptavidin-coated glass slides and could be visualized as diffraction-limited spots, while nanoparticles without PEG lipid or with non-biotin PEG lipid end groups were not bound. To demonstrate that nanoparticle functionalization could be used for targeted labelling of specific cellular proteins, biotinylated PEG lipid conjugated polymer nanoparticles were bound to biotinylated anti-CD16/32 antibodies on J774A.1 cell surface receptors, using streptavidin as a linker. This work represents the first demonstration of targeted delivery of conjugated polymer nanoparticles and demonstrates the utility of these new nanoparticles for fluorescence based imaging and sensing.We report a simple and rapid method to prepare extremely bright, functionalized, stable, and biocompatible conjugated polymer nanoparticles incorporating functionalized polyethylene glycol (PEG) lipids by reprecipitation. These nanoparticles retain the fundamental spectroscopic properties of conjugated polymer nanoparticles prepared without PEG lipid, but demonstrate greater hydrophilicity and quantum yield compared to unmodified conjugated polymer nanoparticles. The sizes of these nanoparticles, as determined by TEM, were 21-26 nm. Notably, these nanoparticles were prepared with several PEG lipid functional end groups, including biotin and carboxy moieties that can be easily conjugated to biomolecules. We have demonstrated the availability of these end groups for functionalization using the interaction of biotin PEG lipid conjugated polymer nanoparticles with streptavidin. Biotinylated PEG lipid conjugated polymer nanoparticles bound streptavidin-linked magnetic beads, while carboxy and methoxy PEG lipid modified nanoparticles did not. Similarly, biotinylated PEG lipid conjugated polymer nanoparticles bound streptavidin-coated glass slides and could be visualized as diffraction-limited spots, while nanoparticles without PEG lipid or with non-biotin PEG lipid end groups were not bound. To demonstrate that nanoparticle functionalization could be used for targeted labelling of specific cellular proteins, biotinylated PEG lipid conjugated polymer nanoparticles were bound to biotinylated anti-CD16/32 antibodies on J774A.1 cell surface receptors, using streptavidin as a linker. This work represents the first demonstration of targeted delivery of conjugated polymer nanoparticles and demonstrates the utility of these new nanoparticles for fluorescence based imaging and sensing. Electronic supplementary information (ESI) available: Additional TEM data, supplemental light scattering measurements, absorbance and fluorescence emission spectra, and photostability measurements. See DOI: 10.1039/c0nr00746c

Photorefractive Nonlinear Optics

DTIC Science & Technology

1991-01-15

conjugate interferometer for the measurement of thin film thickness, refractive index and absorption coefficients. Also, we have investigated...conjugate interferometer for the measurement of thin film thickness, refractive index and absorption coefficients. Also, we have investigated...interaction by considering the refractive index grating as a linear superposition of the gratings from each of the frequency components of the

Interaction of immobilized avidin with an aequorin-biotin conjugate: an aequorin-linked assay for biotin.

PubMed

Feltus, A; Ramanathan, S; Daunert, S

1997-12-01

Biotinylated recombinant aequorin was used in the development of a heterogeneous bioluminescence binding assay for biotin. This assay is based on a competition between a biotinylated aequorin conjugate and biotin for the binding sites of avidin immobilized on solid particles. Dose-response curves were obtained that relate solid-phase aequorin activity to the concentration of biotin. Under certain experimental conditions these curves were biphasic; i.e., as the biotin concentration increased, the solid-phase aequorin activity first increased reaching a maximum and then decreased at higher biotin concentrations. This "hook" effect was observed with four different types of immobilization supports. The effect was more pronounced when low concentrations of aequorin-biotin conjugate were used, and diminished at a high conjugate concentration. This behavior indicates a possible positive cooperativity in the interaction between the immobilized avidin and biotin. Scatchard plot analysis was also consistent with a positive cooperativity mechanism. By using the ascending portion of the dose-response curve, the detection limit of the assay for biotin was 1 x 10(-15) M (100 zmol of biotin in the sample). Copyright 1997 Academic Press.

A Systems Model for Ursodeoxycholic Acid Metabolism in Healthy and Patients With Primary Biliary Cirrhosis.

PubMed

Zuo, P; Dobbins, R L; O'Connor-Semmes, R L; Young, M A

2016-08-01

A systems model was developed to describe the metabolism and disposition of ursodeoxycholic acid (UDCA) and its conjugates in healthy subjects based on pharmacokinetic (PK) data from published studies in order to study the distribution of oral UDCA and potential interactions influencing therapeutic effects upon interruption of its enterohepatic recirculation. The base model was empirically adapted to patients with primary biliary cirrhosis (PBC) based on current understanding of disease pathophysiology and clinical measurements. Simulations were performed for patients with PBC under two competing hypotheses: one for inhibition of ileal absorption of both UDCA and conjugates and the other only of conjugates. The simulations predicted distinctly different bile acid distribution patterns in plasma and bile. The UDCA model adapted to patients with PBC provides a platform to investigate a complex therapeutic drug interaction among UDCA, UDCA conjugates, and inhibition of ileal bile acid transport in this rare disease population. © 2016 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Guanidinylated polyethyleneimine-polyoxypropylene-polyoxyethylene conjugates as gene transfection agents.

PubMed

Bromberg, Lev; Raduyk, Svetlana; Hatton, T Alan; Concheiro, Angel; Rodriguez-Valencia, Cosme; Silva, Maite; Alvarez-Lorenzo, Carmen

2009-05-20

Conjugates of linear and branched polyethyleneimine (PEI) and monoamine polyether Jeffamine M-2070 (PO/EO mol ratio 10/31, 2000 Da) were synthesized through polyether activation by cyanuric chloride followed by attachment to PEI and guanidinylation by 1H-pyrazole-carboxamidine hydrochloride. The resulting guanidinylated PEI-polyether conjugates (termed gPEI-Jeffamine) efficiently complexed plasmid DNA, and their polyplexes possessed enhanced colloidal stability in the presence of serum proteins. In vitro studies with mammalian CHO-1, 3T3, and Cos-7 cell lines demonstrated improved transfection efficiency of the pCMVbeta-gal plasmid/gPEI-Jeffamine polyplexes. The guanidinylation of the amino groups of PEI and the conjugation of PEI with the Jeffamine polyether enhanced the conjugates' interaction with genetic material and reduced the cytotoxicity of the polyplexes in experiments with the L929 cell line.

Peptide- and saccharide-conjugated dendrimers for targeted drug delivery: a concise review

PubMed Central

Liu, Jie; Gray, Warren D.; Davis, Michael E.; Luo, Ying

2012-01-01

Dendrimers comprise a category of branched materials with diverse functions that can be constructed with defined architectural and chemical structures. When decorated with bioactive ligands made of peptides and saccharides through peripheral chemical groups, dendrimer conjugates are turned into nanomaterials possessing attractive binding properties with the cognate receptors. At the cellular level, bioactive dendrimer conjugates can interact with cells with avidity and selectivity, and this function has particularly stimulated interests in investigating the targeting potential of dendrimer materials for the design of drug delivery systems. In addition, bioactive dendrimer conjugates have so far been studied for their versatile capabilities to enhance stability, solubility and absorption of various types of therapeutics. This review presents a brief discussion on three aspects of the recent studies to use peptide- and saccharide-conjugated dendrimers for drug delivery: (i) synthesis methods, (ii) cell- and tissue-targeting properties and (iii) applications of conjugated dendrimers in drug delivery nanodevices. With more studies to elucidate the structure–function relationship of ligand–dendrimer conjugates in transporting drugs, the conjugated dendrimers hold promise to facilitate targeted delivery and improve drug efficacy for discovery and development of modern pharmaceutics. PMID:23741608

Inhibition of bacterial conjugation by phage M13 and its protein g3p: quantitative analysis and model.

PubMed

Lin, Abraham; Jimenez, Jose; Derr, Julien; Vera, Pedro; Manapat, Michael L; Esvelt, Kevin M; Villanueva, Laura; Liu, David R; Chen, Irene A

2011-01-01

Conjugation is the main mode of horizontal gene transfer that spreads antibiotic resistance among bacteria. Strategies for inhibiting conjugation may be useful for preserving the effectiveness of antibiotics and preventing the emergence of bacterial strains with multiple resistances. Filamentous bacteriophages were first observed to inhibit conjugation several decades ago. Here we investigate the mechanism of inhibition and find that the primary effect on conjugation is occlusion of the conjugative pilus by phage particles. This interaction is mediated primarily by phage coat protein g3p, and exogenous addition of the soluble fragment of g3p inhibited conjugation at low nanomolar concentrations. Our data are quantitatively consistent with a simple model in which association between the pili and phage particles or g3p prevents transmission of an F plasmid encoding tetracycline resistance. We also observe a decrease in the donor ability of infected cells, which is quantitatively consistent with a reduction in pili elaboration. Since many antibiotic-resistance factors confer susceptibility to phage infection through expression of conjugative pili (the receptor for filamentous phage), these results suggest that phage may be a source of soluble proteins that slow the spread of antibiotic resistance genes.

Inhibition of Bacterial Conjugation by Phage M13 and Its Protein g3p: Quantitative Analysis and Model

PubMed Central

Lin, Abraham; Jimenez, Jose; Derr, Julien; Vera, Pedro; Manapat, Michael L.; Esvelt, Kevin M.; Villanueva, Laura; Liu, David R.; Chen, Irene A.

2011-01-01

Conjugation is the main mode of horizontal gene transfer that spreads antibiotic resistance among bacteria. Strategies for inhibiting conjugation may be useful for preserving the effectiveness of antibiotics and preventing the emergence of bacterial strains with multiple resistances. Filamentous bacteriophages were first observed to inhibit conjugation several decades ago. Here we investigate the mechanism of inhibition and find that the primary effect on conjugation is occlusion of the conjugative pilus by phage particles. This interaction is mediated primarily by phage coat protein g3p, and exogenous addition of the soluble fragment of g3p inhibited conjugation at low nanomolar concentrations. Our data are quantitatively consistent with a simple model in which association between the pili and phage particles or g3p prevents transmission of an F plasmid encoding tetracycline resistance. We also observe a decrease in the donor ability of infected cells, which is quantitatively consistent with a reduction in pili elaboration. Since many antibiotic-resistance factors confer susceptibility to phage infection through expression of conjugative pili (the receptor for filamentous phage), these results suggest that phage may be a source of soluble proteins that slow the spread of antibiotic resistance genes. PMID:21637841

Do π-conjugative effects facilitate SN2 reactions?

PubMed

Wu, Chia-Hua; Galabov, Boris; Wu, Judy I-Chia; Ilieva, Sonia; Schleyer, Paul von R; Allen, Wesley D

2014-02-26

Rigorous quantum chemical investigations of the SN2 identity exchange reactions of methyl, ethyl, propyl, allyl, benzyl, propargyl, and acetonitrile halides (X = F(-), Cl(-)) refute the traditional view that the acceleration of SN2 reactions for substrates with a multiple bond at Cβ (carbon adjacent to the reacting Cα center) is primarily due to π-conjugation in the SN2 transition state (TS). Instead, substrate-nucleophile electrostatic interactions dictate SN2 reaction rate trends. Regardless of the presence or absence of a Cβ multiple bond in the SN2 reactant in a series of analogues, attractive Cβ(δ(+))···X(δ(-)) interactions in the SN2 TS lower net activation barriers (E(b)) and enhance reaction rates, whereas repulsive Cβ(δ(-))···X(δ(-)) interactions increase E(b) barriers and retard SN2 rates. Block-localized wave function (BLW) computations confirm that π-conjugation lowers the net activation barriers of SN2 allyl (1t, coplanar), benzyl, propargyl, and acetonitrile halide identity exchange reactions, but does so to nearly the same extent. Therefore, such orbital interactions cannot account for the large range of E(b) values in these systems.

Reinforced self-assembly of donor-acceptor π-conjugated molecules to DNA templates by dipole-dipole interactions together with complementary hydrogen bonding interactions for biomimetics.

PubMed

Yang, Wanggui; Chen, Yali; Wong, Man Shing; Lo, Pik Kwan

2012-10-08

One of the most important criteria for the successful DNA-templated polymerization to generate fully synthetic biomimetic polymers is to design the complementary structural monomers, which assemble to the templates strongly and precisely before carrying polymerization. In this study, water-soluble, laterally thymine-substituted donor-acceptor π-conjugated molecules were designed and synthesized to self-assemble with complementary oligoadenines templates, dA(20) and dA(40), into stable and tubular assemblies through noncovalent interactions including π-π stacking, dipole-dipole interactions, and the complementary adenine-thymine (A-T) hydrogen-bonding. UV-vis, fluorescence, circular dichroism (CD), atomic force microscopy (AFM), and transmission electron microscopy (TEM) techniques were used to investigate the formation of highly robust nanofibrous structures. Our results have demonstrated for the first time that the dipole-dipole interactions are stronger and useful to reinforce the assembly of donor-acceptor π-conjugated molecules to DNA templates and the formation of the stable and robust supramolecular nanofibrous complexes together with the complementary hydrogen bonding interactions. This provides an initial step toward DNA-templated polymerization to create fully synthetic DNA-mimetic polymers for biotechnological applications. This study also presents an opportunity to precisely position donor-acceptor type molecules in a controlled manner and tailor-make advanced materials for various biotechnological applications.

Patterns of binding of aluminum-containing adjuvants to Haemophilus influenzae type b and meningococcal group C conjugate vaccines and components

PubMed Central

Otto, Robert B.D.; Burkin, Karena; Amir, Saba Erum; Crane, Dennis T.; Bolgiano, Barbara

2015-01-01

The basis of Haemophilus influenzae type b (Hib) and Neisseria meningitidis serogroup C (MenC) glycoconjugates binding to aluminum-containing adjuvants was studied. By measuring the amount of polysaccharide and protein in the non-adsorbed supernatant, the adjuvant, aluminum phosphate, AlPO4, was found to be less efficient than aluminum hydroxide, Al(OH)3 at binding to the conjugates, at concentrations relevant to licensed vaccine formulations and when equimolar. At neutral pH, binding of TT conjugates to AlPO4 was facilitated through the carrier protein, with only weak binding of AlPO4 to CRM197 being observed. There was slightly higher binding of either adjuvant to tetanus toxoid conjugates, than to CRM197 conjugates. This was verified in AlPO4 formulations containing DTwP–Hib, where the adsorption of TT-conjugated Hib was higher than CRM197-conjugated Hib. At neutral pH, the anionic Hib and MenC polysaccharides did not appreciably bind to AlPO4, but did bind to Al(OH)3, due to electrostatic interactions. Phosphate ions reduced the binding of the conjugates to the adjuvants. These patterns of adjuvant adsorption can form the basis for future formulation studies with individual and combination vaccines containing saccharide-protein conjugates. PMID:26194164

The Obscure World of Integrative and Mobilizable Elements, Highly Widespread Elements that Pirate Bacterial Conjugative Systems

PubMed Central

Guédon, Gérard; Libante, Virginie; Coluzzi, Charles; Payot, Sophie

2017-01-01

Conjugation is a key mechanism of bacterial evolution that involves mobile genetic elements. Recent findings indicated that the main actors of conjugative transfer are not the well-known conjugative or mobilizable plasmids but are the integrated elements. This paper reviews current knowledge on “integrative and mobilizable elements” (IMEs) that have recently been shown to be highly diverse and highly widespread but are still rarely described. IMEs encode their own excision and integration and use the conjugation machinery of unrelated co-resident conjugative element for their own transfer. Recent studies revealed a much more complex and much more diverse lifecycle than initially thought. Besides their main transmission as integrated elements, IMEs probably use plasmid-like strategies to ensure their maintenance after excision. Their interaction with conjugative elements reveals not only harmless hitchhikers but also hunters that use conjugative elements as target for their integration or harmful parasites that subvert the conjugative apparatus of incoming elements to invade cells that harbor them. IMEs carry genes conferring various functions, such as resistance to antibiotics, that can enhance the fitness of their hosts and that contribute to their maintenance in bacterial populations. Taken as a whole, IMEs are probably major contributors to bacterial evolution. PMID:29165361

Galaxy interactions trigger rapid black hole growth: An unprecedented view from the Hyper Suprime-Cam survey

NASA Astrophysics Data System (ADS)

Goulding, Andy D.; Greene, Jenny E.; Bezanson, Rachel; Greco, Johnny; Johnson, Sean; Leauthaud, Alexie; Matsuoka, Yoshiki; Medezinski, Elinor; Price-Whelan, Adrian M.

2018-01-01

Collisions and interactions between gas-rich galaxies are thought to be pivotal stages in their formation and evolution, causing the rapid production of new stars, and possibly serving as a mechanism for fueling supermassive black holes (BHs). Harnessing the exquisite spatial resolution (˜0{^''.}5) afforded by the first ˜170 deg2 of the Hyper Suprime-Cam (HSC) survey, we present our new constraints on the importance of galaxy-galaxy major mergers (1 : 4) in growing BHs throughout the last ˜8 Gyr. Utilizing mid-infrared observations in the WISE all-sky survey, we robustly select active galactic nuclei (AGN) and mass-matched control galaxy samples, totaling ˜140000 spectroscopically confirmed systems at i < 22 mag. We identify galaxy interaction signatures using a novel machine-learning random forest decision tree technique allowing us to select statistically significant samples of major mergers, minor mergers / irregular systems, and non-interacting galaxies. We use these samples to show that galaxies undergoing mergers are a factor of ˜2-7 more likely to contain luminous obscured AGN than non-interacting galaxies, and this is independent of both stellar mass and redshift to z < 0.9. Furthermore, based on our comparison of AGN fractions in mass-matched samples, we determine that the most luminous AGN population (LAGN ≳ 1045 erg s-1) systematically reside in merging systems over non-interacting galaxies. Our findings show that galaxy-galaxy interactions do, on average, trigger luminous AGN activity substantially more often than in secularly evolving non-interacting galaxies, and we further suggest that the BH growth rate may be closely tied to the dynamical time of the merger system.

On the physical origins of interaction-induced vibrational (hyper)polarizabilities.

PubMed

Zaleśny, Robert; Garcia-Borràs, Marc; Góra, Robert W; Medved', Miroslav; Luis, Josep M

2016-08-10

This paper presents the results of a pioneering exploration of the physical origins of vibrational contributions to the interaction-induced electric properties of molecular complexes. In order to analyze the excess nuclear relaxation (hyper)polarizabilities, a new scheme was proposed which relies on the computationally efficient Bishop-Hasan-Kirtman method for determining the nuclear relaxation contributions to electric properties. The extension presented herein is general and can be used with any interaction-energy partitioning method. As an example, in this study we employed the variational-perturbational interaction-energy decomposition scheme (at the MP2/aug-cc-pVQZ level) and the extended transition state method by employing three exchange-correlation functionals (BLYP, LC-BLYP, and LC-BLYP-dDsC) to study the excess properties of the HCN dimer. It was observed that the first-order electrostatic contribution to the excess nuclear relaxation polarizability cancels with the negative exchange repulsion term out to a large extent, resulting in a positive value of Δα(nr) due to the contributions from the delocalization and the dispersion terms. In the case of the excess nuclear relaxation first hyperpolarizability, the pattern of interaction contributions is very similar to that for Δα(nr), both in terms of their sign as well as relative magnitude. Finally, our results show that the LC-BLYP and LC-BLYP-dDsC functionals, which yield smaller values of the orbital relaxation term than BLYP, are more successful in predicting excess properties.

AGT M235T genotype/anxiety interaction and gender in the HyperGEN study.

PubMed

Knox, Sarah S; Guo, Xinxin; Zhang, Yuqing; Weidner, G; Williams, Scott; Ellison, R Curtis

2010-10-13

Both anxiety and elevated heart rate (HR) have been implicated in the development of hypertension. The HyperGen cohort, consisting of siblings with severe and mild hypertension, an age-matched random sample of persons from the same base populations, and unmedicated adult offspring of the hypertensive siblings (N = 1,002 men and 987 women), was analyzed for an association of the angiotenisinogen AGTM235T genotype (TT, MT, MM) with an endophenotype, heart rate (HR) in high and low anxious groups. The interaction of AGTM genotype with anxiety, which has been independently associated with hypertension, was investigated adjusting for age, hypertension status, smoking, alcohol consumption, beta blocker medication, body mass index, physical activity and hours of television viewing (sedentary life style). Although there was no main effect of genotype on HR in men or women, high anxious men with the TT genotype had high HR, whereas high anxious men with the MM genotype had low HR. In women, HR was inversely associated with anxiety but there was no interaction with genotype. The results suggest that high anxiety in men with the TT genotype may increase risk for hypertension whereas the MM genotype may be protective in high anxious men. This type of gene x environment interaction may be one reason why genome wide association studies sometimes fail to replicate. The locus may be important only in combination with certain environmental factors.

Impact of linker and conjugation chemistry on antigen binding, Fc receptor binding and thermal stability of model antibody-drug conjugates

PubMed Central

Acchione, Mauro; Kwon, Hyewon; Jochheim, Claudia M.; Atkins, William M.

2012-01-01

Antibody-drug conjugates (ADCs) with biotin as a model cargo tethered to IgG1 mAbs via different linkers and conjugation methods were prepared and tested for thermostability and ability to bind target antigen and Fc receptor. Most conjugates demonstrated decreased thermostability relative to unconjugated antibody, based on DSC, with carbohydrate and amine coupled ADCs showing the least effect compared with thiol coupled conjugates. A strong correlation between biotin-load and loss of stability is observed with thiol conjugation to one IgG scaffold, but the stability of a second IgG scaffold is relatively insensitive to biotin load. The same correlation for amine coupling was less significant. Binding of antibody to antigen and Fc receptor was investigated using surface plasmon resonance. None of the conjugates exhibited altered antigen affinity. Fc receptor FcγIIb (CD32b) interactions were investigated using captured antibody conjugate. Protein G and Protein A, known inhibitors of Fc receptor (FcR) binding to IgG, were also used to extend the analysis of the impact of conjugation on Fc receptor binding. H10NPEG4 was the only conjugate to show significant negative impact to FcR binding, which is likely due to higher biotin-load compared with the other ADCs. The ADC aHISNLC and aHISTPEG8 demonstrated some loss in affinity for FcR, but to much lower extent. The general insensitivity of target binding and effector function of the IgG1 platform to conjugation highlight their utility. The observed changes in thermostability require consideration for the choice of conjugation chemistry, depending on the system being pursued and particular application of the conjugate. PMID:22531451

Conjugated organic framework with three-dimensionally ordered stable structure and delocalized π clouds

PubMed Central

Guo, Jia; Xu, Yanhong; Jin, Shangbin; Chen, Long; Kaji, Toshihiko; Honsho, Yoshihito; Addicoat, Matthew A.; Kim, Jangbae; Saeki, Akinori; Ihee, Hyotcherl; Seki, Shu; Irle, Stephan; Hiramoto, Masahiro; Gao, Jia; Jiang, Donglin

2013-01-01

Covalent organic frameworks are a class of crystalline organic porous materials that can utilize π–π-stacking interactions as a driving force for the crystallization of polygonal sheets to form layered frameworks and ordered pores. However, typical examples are chemically unstable and lack intrasheet π-conjugation, thereby significantly limiting their applications. Here we report a chemically stable, electronically conjugated organic framework with topologically designed wire frameworks and open nanochannels, in which the π conjugation-spans the two-dimensional sheets. Our framework permits inborn periodic ordering of conjugated chains in all three dimensions and exhibits a striking combination of properties: chemical stability, extended π-delocalization, ability to host guest molecules and hole mobility. We show that the π-conjugated organic framework is useful for high on-off ratio photoswitches and photovoltaic cells. Therefore, this strategy may constitute a step towards realizing ordered semiconducting porous materials for innovations based on two-dimensionally extended π systems. PMID:24220603

Conformation-driven quantum interference effects mediated by through-space conjugation in self-assembled monolayers

NASA Astrophysics Data System (ADS)

Carlotti, Marco; Kovalchuk, Andrii; Wächter, Tobias; Qiu, Xinkai; Zharnikov, Michael; Chiechi, Ryan C.

2016-12-01

Tunnelling currents through tunnelling junctions comprising molecules with cross-conjugation are markedly lower than for their linearly conjugated analogues. This effect has been shown experimentally and theoretically to arise from destructive quantum interference, which is understood to be an intrinsic, electronic property of molecules. Here we show experimental evidence of conformation-driven interference effects by examining through-space conjugation in which π-conjugated fragments are arranged face-on or edge-on in sufficiently close proximity to interact through space. Observing these effects in the latter requires trapping molecules in a non-equilibrium conformation closely resembling the X-ray crystal structure, which we accomplish using self-assembled monolayers to construct bottom-up, large-area tunnelling junctions. In contrast, interference effects are completely absent in zero-bias simulations on the equilibrium, gas-phase conformation, establishing through-space conjugation as both of fundamental interest and as a potential tool for tuning tunnelling charge-transport in large-area, solid-state molecular-electronic devices.

The influence of bio-conjugation on photoluminescence of CdSe/ZnS quantum dots

NASA Astrophysics Data System (ADS)

Torchynska, Tetyana V.; Vorobiev, Yuri V.; Makhniy, Victor P.; Horley, Paul P.

2014-11-01

We report a considerable blue shift in the luminescence spectra of CdSe/ZnS quantum dots conjugated to anti-interleukin-10 antibodies. This phenomenon can be explained theoretically by accounting for bio-conjugation as a process causing electrostatic interaction between a quantum dot and an antibody, which reduces effective volume of the dot core. To solve the Schrödinger equation for an exciton confined in the quantum dot, we use mirror boundary conditions that were successfully tested for different geometries of quantum wells.

Quantum corrections to non-Abelian SUSY theories on orbifolds

NASA Astrophysics Data System (ADS)

Groot Nibbelink, Stefan; Hillenbach, Mark

2006-07-01

We consider supersymmetric non-Abelian gauge theories coupled to hyper multiplets on five and six dimensional orbifolds, S/Z and T/Z, respectively. We compute the bulk and local fixed point renormalizations of the gauge couplings. To this end we extend supergraph techniques to these orbifolds by defining orbifold compatible delta functions. We develop their properties in detail. To cancel the bulk one-loop divergences the bulk gauge kinetic terms and dimension six higher derivative operators are required. The gauge couplings renormalize at the Z fixed points due to vector multiplet self interactions; the hyper multiplet renormalizes only non- Z fixed points. In 6D the Wess-Zumino-Witten term and a higher derivative analogue have to renormalize in the bulk as well to preserve 6D gauge invariance.

Digitizing the Past: A History Book on CD-ROM.

ERIC Educational Resources Information Center

Rosenzweig, Roy

1993-01-01

Describes the development of an American history book with interactive CD-ROM technology that includes text, pictures, graphs and charts, audio, and film. Topics discussed include the use of HyperCard software to link information; access to primary sources of information; greater student control over learning; and the concept of collaborative…

Parietal Hyper-Connectivity, Aberrant Brain Organization, and Circuit-Based Biomarkers in Children with Mathematical Disabilities

ERIC Educational Resources Information Center

Jolles, Dietsje; Ashkenazi, Sarit; Kochalka, John; Evans, Tanya; Richardson, Jennifer; Rosenberg-Lee, Miriam; Zhao, Hui; Supekar, Kaustubh; Chen, Tianwen; Menon, Vinod

2016-01-01

Mathematical disabilities (MD) have a negative life-long impact on professional success, employment, and health outcomes. Yet little is known about the intrinsic functional brain organization that contributes to poor math skills in affected children. It is now increasingly recognized that math cognition requires coordinated interaction within a…

Professional judgement and decision-making in adventure sports coaching: the role of interaction.

PubMed

Collins, Loel; Collins, Dave

2016-01-01

This qualitative study presents the view that coaching practice places demands on the coach's adaptability and flexibility. These requirements for being adaptive and flexible are met through a careful process of professional judgement and decision-making based on context-appropriate bodies of knowledge. Adventure sports coaches were selected for study on the basis that adventure sports create a hyper-dynamic environment in which these features can be examined. Thematic analysis revealed that coaches were generally well informed and practised with respect to the technical aspects of their sporting disciplines. Less positively, however, they often relied on ad hoc contextualisation of generalised theories of coaching practice to respond to the hyper-dynamic environments encountered in adventure sports. We propose that coaching practice reflects the demands of the environment, individual learning needs of the students and the task at hand. Together, these factors outwardly resemble a constraints-led approach but, we suggest, actually reflect manipulation of these parameters from a cognitive rather than an ecological perspective. This process is facilitated by a refined judgement and decision-making process, sophisticated epistemology and an explicit interaction of coaching components.

The Educator's Guide to HyperCard and HyperTalk. A Longwood Professional Book.

ERIC Educational Resources Information Center

Culp, George H.; Watkins, G. Morgan

This book and three accompanying floppy disks introduce HyperCard 2.1 for the Macintosh microcomputer and its programming component, HyperTalk, to educators. The first four chapters introduce the basics of HyperCard, including its structure, which is based on a hierarchy of units; the use of tools and graphics; and ways of linking information…

Probable alpha and 14C cluster emission from hyper Ac nuclei

NASA Astrophysics Data System (ADS)

Santhosh, K. P.

2013-10-01

A systematic study on the probability for the emission of 4He and 14C cluster from hyper {Λ/207-234}Ac and non-strange normal 207-234Ac nuclei are performed for the first time using our fission model, the Coulomb and proximity potential model (CPPM). The predicted half lives show that hyper {Λ/207-234}Ac nuclei are unstable against 4He emission and 14C emission from hyper {Λ/217-228}Ac are favorable for measurement. Our study also show that hyper {Λ/207-234}Ac are stable against hyper {Λ/4}He and {Λ/14}C emission. The role of neutron shell closure ( N = 126) in hyper {Λ/214}Fr daughter and role of proton/neutron shell closure ( Z ≈ 82, N = 126) in hyper {Λ/210}Bi daughter are also revealed. As hyper-nuclei decays to normal nuclei by mesonic/non-mesonic decay and since most of the predicted half lives for 4He and 14C emission from normal Ac nuclei are favourable for measurement, we presume that alpha and 14C cluster emission from hyper Ac nuclei can be detected in laboratory in a cascade (two-step) process.

Differential responses of targeted lung redox enzymes to rat exposure to 60 or 85% oxygen

PubMed Central

Gan, Zhuohui; Roerig, David L.; Clough, Anne V.

2011-01-01

Rat exposure to 60% O2 (hyper-60) or 85% O2 (hyper-85) for 7 days confers susceptibility or tolerance, respectively, of the otherwise lethal effects of exposure to 100% O2. The objective of this study was to determine whether activities of the antioxidant cytosolic enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) and mitochondrial complex III are differentially altered in hyper-60 and hyper-85 lungs. Duroquinone (DQ), an NQO1 substrate, or its hydroquinone (DQH2), a complex III substrate, was infused into the arterial inflow of isolated, perfused lungs, and the venous efflux rates of DQH2 and DQ were measured. Based on inhibitor effects and kinetic modeling, capacities of NQO1-mediated DQ reduction (Vmax1) and complex III-mediated DQH2 oxidation (Vmax2) increased by ∼140 and ∼180% in hyper-85 lungs, respectively, compared with rates in lungs of rats exposed to room air (normoxic). In hyper-60 lungs, Vmax1 increased by ∼80%, with no effect on Vmax2. Additional studies revealed that mitochondrial complex I activity in hyper-60 and hyper-85 lung tissue homogenates was ∼50% lower than in normoxic lung homogenates, whereas mitochondrial complex IV activity was ∼90% higher in only hyper-85 lung tissue homogenates. Thus NQO1 activity increased in both hyper-60 and hyper-85 lungs, whereas complex III activity increased in hyper-85 lungs only. This increase, along with the increase in complex IV activity, may counter the effects the depression in complex I activity might have on tissue mitochondrial function and/or reactive oxygen species production and may be important to the tolerance of 100% O2 observed in hyper-85 rats. PMID:21551015

Differential responses of targeted lung redox enzymes to rat exposure to 60 or 85% oxygen.

PubMed

Gan, Zhuohui; Roerig, David L; Clough, Anne V; Audi, Said H

2011-07-01

Rat exposure to 60% O(2) (hyper-60) or 85% O(2) (hyper-85) for 7 days confers susceptibility or tolerance, respectively, of the otherwise lethal effects of exposure to 100% O(2). The objective of this study was to determine whether activities of the antioxidant cytosolic enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) and mitochondrial complex III are differentially altered in hyper-60 and hyper-85 lungs. Duroquinone (DQ), an NQO1 substrate, or its hydroquinone (DQH(2)), a complex III substrate, was infused into the arterial inflow of isolated, perfused lungs, and the venous efflux rates of DQH(2) and DQ were measured. Based on inhibitor effects and kinetic modeling, capacities of NQO1-mediated DQ reduction (V(max1)) and complex III-mediated DQH(2) oxidation (V(max2)) increased by ∼140 and ∼180% in hyper-85 lungs, respectively, compared with rates in lungs of rats exposed to room air (normoxic). In hyper-60 lungs, V(max1) increased by ∼80%, with no effect on V(max2). Additional studies revealed that mitochondrial complex I activity in hyper-60 and hyper-85 lung tissue homogenates was ∼50% lower than in normoxic lung homogenates, whereas mitochondrial complex IV activity was ∼90% higher in only hyper-85 lung tissue homogenates. Thus NQO1 activity increased in both hyper-60 and hyper-85 lungs, whereas complex III activity increased in hyper-85 lungs only. This increase, along with the increase in complex IV activity, may counter the effects the depression in complex I activity might have on tissue mitochondrial function and/or reactive oxygen species production and may be important to the tolerance of 100% O(2) observed in hyper-85 rats.

Kilometer-Scale Transient Atmospheres for Kinetic Payload Deposition on Icy Bodies

NASA Astrophysics Data System (ADS)

Koch, James

Entry, descent, and landing technologies for space exploration missions to atmospheric bodies traditionally exploit the body's ambient atmosphere as a medium through which a spacecraft or probe can interact to transfer momentum and energy for a soft landing. For bodies with no appreciable atmosphere, a significant engineering challenge exists to overcome the lack of passive methods to decelerate a spacecraft or probe. Proposed is a novel means for the creation of a transient atmosphere for airless icy bodies through the use of a two stage payload-penetrator probe. The first stage is a hyper-velocity penetrator that impacts the icy body. The second stage is an aero-braking-capable probe directed to pass through the ejecta plume from the hyper-velocity impact. Both experimental and computational studies show that a controlled high-energy impact can direct and transfer energy and momentum to a probe via a collimated ejecta plume. In an effort to provide clarity to this unexplored class of missions, a modeling-based engineering approach is taken to provide a first-order estimation of some of the involved physical phenomena. Three sub-studies are presented: an examination and characterization of ice plumes, modeling plume-probe interaction, and the extension of plume modeling as the basis for conceptual mission design. The modeling efforts are centered about two modeling formulations: smoothed particle hydrodynamics (SPH) and the arbitrary Largrangian-Eulerian (ALE) set of techniques. A database of fully-developed hypervelocity impacts and their associated plumes is created and used as inputs to a 1-D mathematical model for the interaction of a continuum-based plume and probe. A parametric study based on the hyper-velocity impact and staging of the probe-penetrator system is presented and discussed. Shown is that a tuned penetrator-probe mission has the potential to increase spacecraft payload mass fraction over conventional soft landing schemes.

Helping Students Design HyperCard Stacks.

ERIC Educational Resources Information Center

Dunham, Ken

1995-01-01

Discusses how to teach students to design HyperCard stacks. Highlights include introducing HyperCard, developing storyboards, introducing design concepts and scripts, presenting stacks, evaluating storyboards, and continuing projects. A sidebar presents a HyperCard stack evaluation form. (AEF)

Thio-Linked UDP–Peptide Conjugates as O-GlcNAc Transferase Inhibitors

PubMed Central

2018-01-01

O-GlcNAc transferase (OGT) is an essential glycosyltransferase that installs the O-GlcNAc post-translational modification on the nucleocytoplasmic proteome. We report the development of S-linked UDP–peptide conjugates as potent bisubstrate OGT inhibitors. These compounds were assembled in a modular fashion by photoinitiated thiol–ene conjugation of allyl-UDP and optimal acceptor peptides in which the acceptor serine was replaced with cysteine. The conjugate VTPVC(S-propyl-UDP)TA (Ki = 1.3 μM) inhibits the OGT activity in HeLa cell lysates. Linear fusions of this conjugate with cell penetrating peptides were explored as prototypes of cell-penetrant OGT inhibitors. A crystal structure of human OGT with the inhibitor revealed mimicry of the interactions seen in the pseudo-Michaelis complex. Furthermore, a fluorophore-tagged derivative of the inhibitor works as a high affinity probe in a fluorescence polarimetry hOGT assay. PMID:29723473

Conjugated Polymers/DNA Hybrid Materials for Protein Inactivation.

PubMed

Zhao, Likun; Zhang, Jiangyan; Xu, Huiming; Geng, Hao; Cheng, Yongqiang

2016-09-07

Chromophore-assisted light inactivation (CALI) is a powerful tool for analyzing protein functions due to the high degree of spatial and temporal resolution. In this work, we demonstrate a CALI approach based on conjugated polymers (CPs)/DNA hybrid material for protein inactivation. The target protein is conjugated with single-stranded DNA in advance. Single-stranded DNA can form CPs/DNA hybrid material with cationic CPs via electrostatic and hydrophobic interactions. Through the formation of CPs/DNA hybrid material, the target protein that is conjugated with DNA is brought into close proximity to CPs. Under irradiation, CPs harvest light and generate reactive oxygen species (ROS), resulting in the inactivation of the adjacent target protein. This approach can efficiently inactivate any target protein which is conjugated with DNA and has good specificity and universality, providing a new strategy for studies of protein function and adjustment of protein activity.

In vitro evaluation of biodegradable microspheres with surface-bound ligands.

PubMed

Keegan, Mark E; Royce, Sara M; Fahmy, Tarek; Saltzman, W Mark

2006-02-21

Protein ligands were conjugated to the surface of biodegradable microspheres. These microsphere-ligand conjugates were then used in two in vitro model systems to evaluate the effect of conjugated ligands on microsphere behavior. Microsphere retention in agarose columns was increased by ligands on the microsphere surface specific for receptors on the agarose matrix. In another experiment, conjugating the lectin Ulex europaeus agglutinin 1 to the microsphere surface increased microsphere adhesion to Caco-2 monolayers compared to control microspheres. This increase in microsphere adhesion was negated by co-administration of l-fucose, indicating that the increase in adhesion is due to specific interaction of the ligand with carbohydrate receptors on the cell surface. These results demonstrate that the ligands conjugated to the microspheres maintain their receptor binding activity and are present on the microsphere surface at a density sufficient to target the microspheres to both monolayers and three-dimensional matrices bearing complementary receptors.

A septal chromosome segregator protein evolved into a conjugative DNA-translocator protein

PubMed Central

Sepulveda, Edgardo; Vogelmann, Jutta

2011-01-01

Streptomycetes, Gram-positive soil bacteria well known for the production of antibiotics feature a unique conjugative DNA transfer system. In contrast to classical conjugation which is characterized by the secretion of a pilot protein covalently linked to a single-stranded DNA molecule, in Streptomyces a double-stranded DNA molecule is translocated during conjugative transfer. This transfer involves a single plasmid encoded protein, TraB. A detailed biochemical and biophysical characterization of TraB, revealed a close relationship to FtsK, mediating chromosome segregation during bacterial cell division. TraB translocates plasmid DNA by recognizing 8-bp direct repeats located in a specific plasmid region clt. Similar sequences accidentally also occur on chromosomes and have been shown to be bound by TraB. We suggest that TraB mobilizes chromosomal genes by the interaction with these chromosomal clt-like sequences not relying on the integration of the conjugative plasmid into the chromosome. PMID:22479692

Amphiphilic naproxen prodrugs: differential scanning calorimetry study on their interaction with phospholipid bilayers.

PubMed

Giuffrida, Maria Chiara; Pignatello, Rosario; Castelli, Francesco; Sarpietro, Maria Grazia

2017-09-01

Naproxen, a nonsteroid anti-inflammatory drug studied for Alzheimer's disease, was conjugated with lipoamino acids (LAA) directly or through a diethylamine (EDA) spacer to improve the drug lipophilicity and the interaction with phospholipid bilayers. The interaction of naproxen and its prodrugs with biomembrane models consisting of dimyristoylphosphatidylcholine multilamellar vesicles was studied by differential scanning calorimetry. The transfer of prodrugs from a lipophilic carrier to a biomembrane model was also studied. Naproxen conjugation to lipoamino acids improves its interaction with biomembrane models and affects the transfer from a lipophilic carrier to biomembrane model. LAA portion may localize between the phospholipid chains; the entity of the interaction depends not only on the presence of the spacer but also on the LAA chain length. Variation of LAA portion can modulate the naproxen prodrugs affinity towards the biological membrane as well as towards the lipophilic carrier. © 2017 Royal Pharmaceutical Society.

Native mass spectrometry and ion mobility characterization of trastuzumab emtansine, a lysine-linked antibody drug conjugate.

PubMed

Marcoux, Julien; Champion, Thierry; Colas, Olivier; Wagner-Rousset, Elsa; Corvaïa, Nathalie; Van Dorsselaer, Alain; Beck, Alain; Cianférani, Sarah

2015-08-01

Antibody-drug conjugates (ADCs) are biochemotherapeutics consisting of a cytotoxic chemical drug linked covalently to a monoclonal antibody. Two main classes of ADCs, namely cysteine and lysine conjugates, are currently available on the market or involved in clinical trials. The complex structure and heterogeneity of ADCs makes their biophysical characterization challenging. For cysteine conjugates, hydrophobic interaction chromatography is the gold standard technique for studying drug distribution, the naked antibody content, and the average drug to antibody ratio (DAR). For lysine ADC conjugates on the other hand, which are not amenable to hydrophobic interaction chromatography because of their higher heterogeneity, denaturing mass spectrometry (MS) and UV/Vis spectroscopy are the most powerful approaches. We report here the use of native MS and ion mobility (IM-MS) for the characterization of trastuzumab emtansine (T-DM1, Kadcyla(®)). This lysine conjugate is currently being considered for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and combines the anti-HER2 antibody trastuzumab (Herceptin(®)), with the cytotoxic microtubule-inhibiting maytansine derivative, DM1. We show that native MS combined with high-resolution measurements and/or charge reduction is beneficial in terms of the accurate values it provides of the average DAR and the drug load profiles. The use of spectral deconvolution is discussed in detail. We report furthermore the use of native IM-MS to directly determine DAR distribution profiles and average DAR values, as well as a molecular modeling investigation of positional isomers in T-DM1. © 2015 The Protein Society.

Engineering software development with HyperCard

NASA Technical Reports Server (NTRS)

Darko, Robert J.

1990-01-01

The successful and unsuccessful techniques used in the development of software using HyperCard are described. The viability of the HyperCard for engineering is evaluated and the future use of HyperCard by this particular group of developers is discussed.

Genetics Home Reference: X-linked hyper IgM syndrome

MedlinePlus

... Home Health Conditions X-linked hyper IgM syndrome X-linked hyper IgM syndrome Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description X-linked hyper IgM syndrome is a condition that ...

Simulation Studies of LCST-like Phase Transitions in Elastin-like Polypeptides (ELPs) and Conjugates of ELP with Rigid Macromolecules

NASA Astrophysics Data System (ADS)

Condon, Joshua; Martin, Tyler; Jayaraman, Arthi

We use atomistic (AA) and coarse-grained (CG) molecular dynamics simulations to elucidate the thermodynamic driving forces governing lower critical solution temperature (LCST)-like phase transition exhibited by elastin-like peptides (ELPs) and conjugates of ELP with other macromolecules. In the AA simulations, we study ELP oligomers in explicit water, and mark the transition as the temperature at which they undergo a change in ``hydration'' state. While AA simulations are restricted to small systems of short ELPs and do not capture the chain aggregation observed in experiments of ELPs, they guide the phenomenological CG model development by highlighting the solvent induced polymer-polymer effective interactions with changing temperature. In the CG simulations, we capture the LCST polymer aggregation by increasing polymer-polymer effective attractive interactions in an implicit solvent. We examine the impact of conjugating a block of LCST polymer to another rigid unresponsive macromolecular block on the LCST-like transition. We find that when multiple LCST polymers are conjugated to a rigid polymer block, increased crowding of the LCST polymers shifts the onset of chain aggregation to smaller effective polymer-polymer attraction compared to the free LCST polymers. These simulation results provide guidance on the design of conjugated bio-mimetic thermoresponsive materials, and shape the fundamental understanding of the impact of polymer crowding on phase behavior in thermoresponsive LCST polymer systems.

Patterns of binding of aluminum-containing adjuvants to Haemophilus influenzae type b and meningococcal group C conjugate vaccines and components.

PubMed

Otto, Robert B D; Burkin, Karena; Amir, Saba Erum; Crane, Dennis T; Bolgiano, Barbara

2015-09-01

The basis of Haemophilus influenzae type b (Hib) and Neisseria meningitidis serogroup C (MenC) glycoconjugates binding to aluminum-containing adjuvants was studied. By measuring the amount of polysaccharide and protein in the non-adsorbed supernatant, the adjuvant, aluminum phosphate, AlPO4, was found to be less efficient than aluminum hydroxide, Al(OH)3 at binding to the conjugates, at concentrations relevant to licensed vaccine formulations and when equimolar. At neutral pH, binding of TT conjugates to AlPO4 was facilitated through the carrier protein, with only weak binding of AlPO4 to CRM197 being observed. There was slightly higher binding of either adjuvant to tetanus toxoid conjugates, than to CRM197 conjugates. This was verified in AlPO4 formulations containing DTwP-Hib, where the adsorption of TT-conjugated Hib was higher than CRM197-conjugated Hib. At neutral pH, the anionic Hib and MenC polysaccharides did not appreciably bind to AlPO4, but did bind to Al(OH)3, due to electrostatic interactions. Phosphate ions reduced the binding of the conjugates to the adjuvants. These patterns of adjuvant adsorption can form the basis for future formulation studies with individual and combination vaccines containing saccharide-protein conjugates. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

The influence of the nature of a substituent on the parameters of the intra- and intermolecular interactions in molecules of cross-conjugated ketones

NASA Astrophysics Data System (ADS)

Kompaneets, V. V.; Vasilieva, I. A.

2017-08-01

We have quantitatively analyzed the vibronic parameters of two cross-conjugated δ-dimethylaminoketones. The presence of the -N(CH3)2, C=O, and -NO2 groups in the benzene ring has been shown to affect the manifestation of the vibronic parameters of characteristic bands that describe the state (vibrations, types of deformation upon excitation) of polyene systems with aromatic rings. Data on the influence of the nature of the substituent on the parameters of intra- and intermolecular interactions in the examined compounds have been presented.

Energetic Analysis of Conjugated Hydrocarbons Using the Interacting Quantum Atoms Method.

PubMed

Jara-Cortés, Jesús; Hernández-Trujillo, Jesús

2018-07-05

A number of aromatic, antiaromatic, and nonaromatic organic molecules was analyzed in terms of the contributions to the electronic energy defined in the quantum theory of atoms in molecules and the interacting quantum atoms method. Regularities were found in the exchange and electrostatic interatomic energies showing trends that are closely related to those of the delocalization indices defined in the theory. In particular, the CC interaction energies between bonded atoms allow to rationalize the energetic stabilization associated with the bond length alternation in conjugated polyenes. This approach also provides support to Clar's sextet rules devised for aromatic systems. In addition, the H⋯H bonding found in some of the aromatic molecules studied was of an attractive nature, according to the stabilizing exchange interaction between the bonded H atoms. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Nanoparticle-allergen interactions mediate human allergic responses: protein corona characterization and cellular responses.

PubMed

Radauer-Preiml, Isabella; Andosch, Ancuela; Hawranek, Thomas; Luetz-Meindl, Ursula; Wiederstein, Markus; Horejs-Hoeck, Jutta; Himly, Martin; Boyles, Matthew; Duschl, Albert

2016-01-16

Engineered nanomaterials (ENMs) interact with different biomolecules as soon as they are in contact, resulting in the formation of a biomolecule 'corona'. Hence, the 'corona' defines the biological identity of the ENMs and could affect the response of the immune system to ENM exposure. With up to 40 % of the world population suffering from type I allergy, a possible modulation of allergen effects by binding to ENMs is highly relevant with respect to work place and consumer safety. Therefore, the aim of this present study was to gain an insight into the interactions of gold nanoparticles with different seasonally and perennially occurring outdoor and indoor allergens. Gold nanoparticles (AuNPs) were conjugated with the major allergens of birch pollen (Bet v 1), timothy grass pollen (Phl p 5) and house dust mite (Der p 1). The AuNP-allergen conjugates were characterized by means of TEM negative staining, dynamic light scattering (DLS), z-potential measurements and hyperspectral imaging. Furthermore, 3D models were constructed, based on the characterization data, to visualize the interaction between the allergens and the AuNPs surface. Differences in the activation of human basophil cells derived from birch/grass pollen- and house dust mite-allergic patients in response to free allergen and AuNP-allergen conjugates were determined using the basophil activation assay (BAT). Potential allergen corona replacement during BAT was controlled for using Western blotting. The protease activity of AuNP-Der p 1 conjugates compared to free Der p 1 was assessed, by an enzymatic activity assay and a cellular assay pertaining to lung type II alveolar epithelial cell tight junction integrity. The formation of a stable corona was found for all three allergens used. Our data suggest, that depending on the allergen, different effects are observed after binding to ENMs, including enhanced allergic responses against Der p 1 and also, for some patients, against Bet v 1. Moreover elevated protease activity of AuNP-Der p 1 conjugates compared to free Der p 1 was found. In summary, this study presents that conjugation of allergens to ENMs can modulate the human allergic response, and that protease activity can be increased. Graphical Abstract Cross-linking of IgE receptors and degranulation of human basophils due to epitope alignment of nanoparticle-coated allergens.

Online size-exclusion high-performance liquid chromatography light scattering and differential refractometry methods to determine degree of polymer conjugation to proteins and protein-protein or protein-ligand association states.

PubMed

Kendrick, B S; Kerwin, B A; Chang, B S; Philo, J S

2001-12-15

Characterizing the solution structure of protein-polymer conjugates and protein-ligand interactions is important in fields such as biotechnology and biochemistry. Size-exclusion high-performance liquid chromatography with online classical light scattering (LS), refractive index (RI), and UV detection offers a powerful tool in such characterization. Novel methods are presented utilizing LS, RI, and UV signals to rapidly determine the degree of conjugation and the molecular mass of the protein conjugate. Baseline resolution of the chromatographic peaks is not required; peaks need only be sufficiently separated to represent relatively pure fractions. An improved technique for determining the polypeptide-only mass of protein conjugates is also described. These techniques are applied to determining the degree of erythropoietin glycosylation, the degree of polyethylene glycol conjugation to RNase A and brain-derived neurotrophic factor, and the solution association states of these molecules. Calibration methods for the RI, UV, and LS detectors will also be addressed, as well as online methods to determine protein extinction coefficients and dn/dc values both unconjugated and conjugated protein molecules. (c)2001 Elsevier Science.

Design of polymer conjugated 3-helix micelles as nanocarriers with tunable shapes.

PubMed

Ma, Dan; DeBenedictis, Elizabeth P; Lund, Reidar; Keten, Sinan

2016-11-24

Amphiphilic peptide-polymer conjugates have the ability to form stable nanoscale micelles, which show great promise for drug delivery and other applications. A recent design has utilized the end-conjugation of alkyl chains to 3-helix coiled coils to achieve amphiphilicity, combined with the side-chain conjugation of polyethylene glycol (PEG) to tune micelle size through entropic confinement forces. Here we investigate this phenomenon in depth, using coarse-grained dissipative particle dynamics (DPD) simulations in an explicit solvent and micelle theory. We analyze the conformations of PEG chains conjugated to three different positions on 3-helix bundle peptides to ascertain the degree of confinement upon assembly, as well as the ordering of the subunits making up the micelle. We discover that the micelle size and stability is dictated by a competition between the entropy of PEG chain conformations in the assembled state, as well as intermolecular cross-interactions among PEG chains that promote cohesion between neighboring conjugates. Our analyses build on the role of PEG molecular weight and conjugation site and lead to computational phase diagrams that can be used to design 3-helix micelles. This work opens pathways for the design of multifunctional micelles with tunable size, shape and stability.

Covalent complexes of albumin with serotonin, ketanserin and lysergic acid antagonize the activity of serotonin in human platelets

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

VanderBerg, S.R.; Gonias, S.L.

1989-01-01

Covalent conjugates of bovine serum albumin (BSA) and 5-HT, ketanserin or d-lysergic acid were synthesized and characterized by polyacrylamide gel electrophoresis, whole blood clearance experiments in mice and aggregation studies with human platelets. Using the standard synthesis procedure, each mol of BSA bound 13.4 mol of (/sup 3/H)5-HT. Derivatization did not cause significant protein aggregation as determined by electrophoresis. All three conjugates antagonized the ability of 5-HT to amplify aggregation caused by low concentrations of ADP. The antagonist activity of each conjugate was concentration dependent; 2.6 ..mu..M 5-HT-BSA completely inhibited the aggregation caused by 13 ..mu..M 5-HT. None of themore » BSA drug conjugates, including 5-HT-BSA, amplified platelet aggregation caused by ADP in the absence of 5-HT. Aggregation by ristocetin, collagen, epinephrine or ADP alone was not significantly affected by the conjugates. Whole blood elimination experiments in mice demonstrated that the three conjugates and underivatized BSA are equally stable in the circulation. These prototypic 5-HT drug-protein conjugates may be useful for probing 5-HT/sub 2/ receptor-ligand interactions in human platelets.« less

Basis set and electron correlation effects on the polarizability and second hyperpolarizability of model open-shell π-conjugated systems

NASA Astrophysics Data System (ADS)

Champagne, Benoı̂t; Botek, Edith; Nakano, Masayoshi; Nitta, Tomoshige; Yamaguchi, Kizashi

2005-03-01

The basis set and electron correlation effects on the static polarizability (α) and second hyperpolarizability (γ) are investigated ab initio for two model open-shell π-conjugated systems, the C5H7 radical and the C6H8 radical cation in their doublet state. Basis set investigations evidence that the linear and nonlinear responses of the radical cation necessitate the use of a less extended basis set than its neutral analog. Indeed, double-zeta-type basis sets supplemented by a set of d polarization functions but no diffuse functions already provide accurate (hyper)polarizabilities for C6H8 whereas diffuse functions are compulsory for C5H7, in particular, p diffuse functions. In addition to the 6-31G*+pd basis set, basis sets resulting from removing not necessary diffuse functions from the augmented correlation consistent polarized valence double zeta basis set have been shown to provide (hyper)polarizability values of similar quality as more extended basis sets such as augmented correlation consistent polarized valence triple zeta and doubly augmented correlation consistent polarized valence double zeta. Using the selected atomic basis sets, the (hyper)polarizabilities of these two model compounds are calculated at different levels of approximation in order to assess the impact of including electron correlation. As a function of the method of calculation antiparallel and parallel variations have been demonstrated for α and γ of the two model compounds, respectively. For the polarizability, the unrestricted Hartree-Fock and unrestricted second-order Møller-Plesset methods bracket the reference value obtained at the unrestricted coupled cluster singles and doubles with a perturbative inclusion of the triples level whereas the projected unrestricted second-order Møller-Plesset results are in much closer agreement with the unrestricted coupled cluster singles and doubles with a perturbative inclusion of the triples values than the projected unrestricted Hartree-Fock results. Moreover, the differences between the restricted open-shell Hartree-Fock and restricted open-shell second-order Møller-Plesset methods are small. In what concerns the second hyperpolarizability, the unrestricted Hartree-Fock and unrestricted second-order Møller-Plesset values remain of similar quality while using spin-projected schemes fails for the charged system but performs nicely for the neutral one. The restricted open-shell schemes, and especially the restricted open-shell second-order Møller-Plesset method, provide for both compounds γ values close to the results obtained at the unrestricted coupled cluster level including singles and doubles with a perturbative inclusion of the triples. Thus, to obtain well-converged α and γ values at low-order electron correlation levels, the removal of spin contamination is a necessary but not a sufficient condition. Density-functional theory calculations of α and γ have also been carried out using several exchange-correlation functionals. Those employing hybrid exchange-correlation functionals have been shown to reproduce fairly well the reference coupled cluster polarizability and second hyperpolarizability values. In addition, inclusion of Hartree-Fock exchange is of major importance for determining accurate polarizability whereas for the second hyperpolarizability the gradient corrections are large.

Preclinical manufacture of anti-HER2 liposome-inserting, scFv-PEG-lipid conjugate. 2. Conjugate micelle identity, purity, stability, and potency analysis.

PubMed

Nellis, David F; Giardina, Steven L; Janini, George M; Shenoy, Shilpa R; Marks, James D; Tsai, Richard; Drummond, Daryl C; Hong, Keelung; Park, John W; Ouellette, Thomas F; Perkins, Shelley C; Kirpotin, Dmitri B

2005-01-01

Analytical methods optimized for micellar F5cys-MP-PEG(2000)-DPSE protein-lipopolymer conjugate are presented. The apparent micelle molecular weight, determined by size exclusion chromatography, ranged from 330 to 960 kDa. The F5cys antibody and conjugate melting points, determined by differential scanning calorimetry, were near 82 degrees C. Traditional methods for characterizing monodisperse protein species were inapplicable to conjugate analysis. The isoelectric point of F5cys (9.2) and the conjugate (8.9) were determined by capillary isoelectric focusing (cIEF) after addition of the zwitterionic detergent CHAPS to the buffer. Conjugate incubation with phospholipase B selectively removed DSPE lipid groups and dispersed the conjugate prior to separation by chromatographic methods. Alternatively, adding 2-propanol (29.4 vol %) and n-butanol (4.5 vol %) to buffers for salt-gradient cation exchange chromatography provided gentler, nonenzymatic dispersion, resulting in well-resolved peaks. This method was used to assess stability, identify contaminants, establish lot-to-lot comparability, and determine the average chromatographic purity (93%) for conjugate lots, described previously. The F5cys amino acid content was confirmed after conjugation. The expected conjugate avidity for immobilized HER-2/neu was measured by bimolecular interaction analysis (BIAcore). Mock therapeutic assemblies were made by conjugate insertion into preformed doxorubicin-encapsulating liposomes for antibody-directed uptake of doxorubicin by HER2-overexpressing cancer cells in vitro. Together these developed assays established that the manufacturing method as described in the first part of this study consistently produced F5cys-MP-PEG(2000)-DSPE having sufficient purity, stability, and functionality for use in preclinical toxicology investigations.

Somatostatin Analogues for Receptor Targeted Photodynamic Therapy

PubMed Central

Kaščáková, Slávka; Hofland, Leo J.; De Bruijn, Henriette S.; Ye, Yunpeng; Achilefu, Samuel; van der Wansem, Katy; van der Ploeg-van den Heuvel, Angelique; van Koetsveld, Peter M.; Brugts, Michael P.; van der Lelij, Aart-Jan; Sterenborg, Henricus J. C. M.; ten Hagen, Timo L. M.; Robinson, Dominic J.; van Hagen, Martin P.

2014-01-01

Photodynamic therapy (PDT) is an established treatment modality, used mainly for anticancer therapy that relies on the interaction of photosensitizer, light and oxygen. For the treatment of pathologies in certain anatomical sites, improved targeting of the photosensitizer is necessary to prevent damage to healthy tissue. We report on a novel dual approach of targeted PDT (vascular and cellular targeting) utilizing the expression of neuropeptide somatostatin receptor (sst2) on tumor and neovascular-endothelial cells. We synthesized two conjugates containing the somatostatin analogue [Tyr3]-octreotate and Chlorin e6 (Ce6): Ce6-K3-[Tyr3]-octreotate (1) and Ce6-[Tyr3]-octreotate-K3-[Tyr3]-octreotate (2). Investigation of the uptake and photodynamic activity of conjugates in-vitro in human erythroleukemic K562 cells showed that conjugation of [Tyr3]-octreotate with Ce6 in conjugate 1 enhances uptake (by a factor 2) in cells over-expressing sst2 compared to wild-type cells. Co-treatment with excess free Octreotide abrogated the phototoxicity of conjugate 1 indicative of a specific sst2-mediated effect. In contrast conjugate 2 showed no receptor-mediated effect due to its high hydrophobicity. When compared with un-conjugated Ce6, the PDT activity of conjugate 1 was lower. However, it showed higher photostability which may compensate for its lower phototoxicity. Intra-vital fluorescence pharmacokinetic studies of conjugate 1 in rat skin-fold observation chambers transplanted with sst2 + AR42J acinar pancreas tumors showed significantly different uptake profiles compared to free Ce6. Co-treatment with free Octreotide significantly reduced conjugate uptake in tumor tissue (by a factor 4) as well as in the chamber neo-vasculature. These results show that conjugate 1 might have potential as an in-vivo sst2 targeting photosensitizer conjugate. PMID:25111655

Ultrasensitive detection of nitroexplosive - picric acid via a conjugated polyelectrolyte in aqueous media and solid support.

PubMed

Hussain, Sameer; Malik, Akhtar Hussain; Afroz, Mohammad Adil; Iyer, Parameswar Krishnan

2015-04-28

Picric acid (PA) detection at parts per trillion (ppt) levels is achieved by a conjugated polyelectrolyte (PMI) in 100% aqueous media and on a solid platform using paper strips and chitosan (CS) films. The unprecedented selectivity is accomplished via combination of ground state charge transfer and resonance energy transfer (RET) facilitated by favorable electrostatic interactions.

HPLC analysis of functionalized poly(amidoamine) dendrimers and the interaction between a folate-dendrimer conjugate and folate binding protein.

PubMed

Shi, Xiangyang; Bi, Xiangdong; Ganser, T Rose; Hong, Seungpyo; Myc, Lukasz A; Desai, Ankur; Holl, Mark M Banaszak; Baker, James R

2006-07-01

Poly(amidoamine) (PAMAM) dendrimers of different generations with carboxyl, acetyl, and hydroxyl terminal groups and a folic acid (FA)-dendrimer conjugate were separated and analyzed using reverse-phase high performance liquid chromatography (HPLC). Analysis of both the individual PAMAM derivatives and the separation of mixed generations can be achieved using a linear gradient 0-50% acetonitrile (ACN) (balance water) within 40 min. We also show that PAMAMs with defined acetylation and carboxylation degrees can be analyzed using HPLC. Furthermore, a generation 5 dendrimer-FA conjugate (G5.75Ac-FA4; Ac denotes acetyl) was analyzed and its specific binding with a bovine folic acid binding protein (FBP) was monitored. The HPLC and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) results indicate the formation of three complexes after the binding of G5.75Ac-FA4 with FBP. Dendrimers with FA moieties show much higher specific binding capability with FBP than those without FA moieties. Findings from this study indicate that HPLC is an effective technique not only for characterization and separation of functionalized PAMAM dendrimers and conjugates but also for investigation of the interaction between dendrimers and biomolecules.

E2~Ub conjugates regulate the kinase activity of Shigella effector OspG during pathogenesis

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

Pruneda, Jonathan N.; Smith, F. Donelson; Daurie, Angela

Pathogenic bacteria introduce effector proteins directly into the cytosol of eukaryotic cells to promote invasion and colonization. OspG, a Shigella spp. effector kinase, plays a role in this process by helping to suppress the host inflammatory response. OspG has been reported to bind host E2 ubiquitin-conjugating enzymes activated with ubiquitin (E2~Ub), a key enzyme complex in ubiquitin transfer pathways. A cocrystal structure of the OspG/UbcH5c~Ub complex reveals that complex formation has important ramifications for the activity of both OspG and the UbcH5c~Ub conjugate. OspG is a minimal kinase domain containing only essential elements required for catalysis. UbcH5c~Ub binding stabilizes anmore » active conformation of the kinase, greatly enhancing OspG kinase activity. In contrast, interaction with OspG stabilizes an extended, less reactive form of UbcH5c~Ub. Recognizing conserved E2 features, OspG can interact with at least ten distinct human E2s~Ub. Mouse oral infection studies indicate that E2~Ub conjugates act as novel regulators of OspG effector kinase function in eukaryotic host cells.« less

Conformational Order in Aggregates of Conjugated Polymers

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

Jackson, Nicholas E.; Kohlstedt, Kevin L.; Savoie, Brett M.

With the abundant variety and increasing chemical complexity of conjugated poly-friers proliferating the field of organic semiconductors, it has become increasingly important to correlate the polymer molecular structure with its mesoscale conformational and morphological attributes. For instance, it is unknown which combinations of chemical moieties and periodicities predictably produce mesoscale ordering. Interestingly) not all ordered morphologies result in efficient devices. In this work we have parametrized accurate classical force-fields and used these to compute the conformational and aggregation characteristics of single strands of common conjugated polymers. Molecular dynamics trajectories are shown to reproduce experimentally observed polymeric ordering, concluding that efficientmore » organic photovoltaic devices span a range of polymer conformational classes, and suggesting that the solution-phase morphologies have far-reaching effects. Encouragingly, these simulations indicate that despite the wide-range of conformational classes present in successful devices, local molecular ordering, and not long-range crystallinity, appears to be the necessary requirement for efficient devices. Finally, we examine what makes a "good" solvent for conjugated polymers, concluding that dispersive pi-electron solvent-polymer interactions, and not the electrostatic potential of the backbone interacting with the solvent, are what primarily determine a polymer's solubility in a particular solvent, and consequently its morphological characteristics.« less

From 1D Polymers to 2D Polymers: Preparation of Free-Standing Single-Monomer-Thick Two-Dimensional Conjugated Polymers in Water.

PubMed

Zhang, Na; Wang, Taisheng; Wu, Xing; Jiang, Chen; Zhang, Taiming; Jin, Bangkun; Ji, Hengxing; Bai, Wei; Bai, Ruke

2017-07-25

Recently, investigation on two-dimensional (2D) organic polymers has made great progress, and conjugated 2D polymers already play a dynamic role in both academic and practical applications. However, a convenient, noninterfacial approach to obtain single-layer 2D polymers in solution, especially in aqueous media, remains challenging. Herein, we present a facile, highly efficient, and versatile "1D to 2D" strategy for preparation of free-standing single-monomer-thick conjugated 2D polymers in water without any aid. The 2D structure was achieved by taking advantage of the side-by-side self-assembly of a rigid amphiphilic 1D polymer and following topochemical photopolymerization in water. The spontaneous formation of single-layer polymer sheets was driven by synergetic association of the hydrophobic interactions, π-π stacking interactions, and electrostatic repulsion. Both the supramolecular sheets and the covalent sheets were confirmed by spectroscopic analyses and electron microscope techniques. Moreover, in comparison of the supramolecular 2D polymer, the covalent 2D polymer sheets exhibited not only higher mechanical strength but also higher conductivity, which can be ascribed to the conjugated network within the covalent 2D polymer sheets.

Multivalent interaction based carbohydrate biosensors for signal amplification

PubMed Central

Wang, Yanyan; Chalagalla, Srinivas; Li, Tiehai; Sun, Xue-long; Zhao, Wei; Wang, Peng; Zeng, Xiangqun

2010-01-01

Multivalent interaction between boronic acids immobilized on Quartz Crystal Microbalance (QCM) sensor surface and the carbohydrates modified Au - nanoparticle (AuNP) has been demonstrated for the development of a sensitive carbohydrate biosensor. Briefly, a boronic acid - containing polymer (boropolymer) as multivalent carbohydrate receptor was oriented immobilized on the cysteamine coated electrode through isourea bond formation. Carbohydrates were conjugated to AuNPs to generate a multivalent carbohydrates moiety to amplify the response signal. Thus, the binding of the carbohydrate conjugated AuNPs to the boropolymer surface are multivalent which could simultaneously increase the binding affinity and specificity. We systematically studied the binding between five carbohydrate conjugated AuNPs and the boropolymer. Our studies show that the associate constant (Ka) was in the order of fucose < glucose < mannose < galactose < maltose. A linear response in the range from 23 µM to 3.83 mM was observed for mannose conjugated AuNPs and the boropolymer recognition elements, with the lower detection limit of 1.5 µM for the carbohydrate analytes. Furthermore, the multivalent binding between carbohydrates and boronic acids are reversible and allow the regeneration of boropolymer surface by using 1M acetic acid so as to sequentially capture and release the carbohydrate analytes. PMID:20863680

Networked Multi-Sensory Experiences: Beyond Browsers on the Web and in the Museum.

ERIC Educational Resources Information Center

Wagmister, Fabian; Burke, Jeff

This paper presents a vision of digital technology for the museum as a dynamic connection-making tool that defines new genres and enables new experiences of existing works. The following media-rich interactive installations and performances developed at the HyperMedia Studio, a digital media research unit in the UCLA (University of California Los…

Why Were Polysaccharides Necessary?

NASA Astrophysics Data System (ADS)

Tolstoguzov, Vladimir

2004-12-01

The main idea of this paper is that the primordial soup may be modelled by food systems whose structure-property relationship is based on non-specific interactions between denatured biopolymers. According to the proposed hypothesis, polysaccharides were the first biopolymers that decreased concentration of salts in the primordial soup, `compatibilised' and drove the joint evolution of proto-biopolymers. Synthesis of macromolecules within the polysaccharide-rich medium could have resulted in phase separation of the primordial soup and concentration of the polypeptides and nucleic acids in the dispersed phase particles. The concentration of proto-biopolymer mixtures favoured their cross-linking in hybrid supermacromolecules of conjugates. The cross-linking of proto-biopolymers could occur by hydrophobic, electrostatic interactions, H-bonds due to freezing aqueous mixed biopolymer dispersions and/or by covalent bonds due to the Maillard reaction. Cross-linking could have increased the local concentration of chemically different proto-biopolymers, fixed their relative positions and made their interactions reproducible. Attractive-repulsive interactions between cross-linked proto-biopolymer chains could develop pairing of the monomer units, improved chemical stability (against hydrolysis) and led to their mutual catalytic activity and coding. Conjugates could probably evolve to the first self-reproduced entities and then to specialized cellular organelles. Phase separation of the primordial soup with concentration of conjugates in the dispersed particles has probably resulted in proto-cells.

Photo-excitation of carotenoids causes cytotoxicity via singlet oxygen production

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

Yoshii, Hiroshi, E-mail: yoshii@nirs.go.jp; Faculty of Medical Sciences, University of Fukui, Eiheiji, Fukui 910-1193; Yoshii, Yukie, E-mail: yukiey@nirs.go.jp

Highlights: Black-Right-Pointing-Pointer Some photo-excited carotenoids have photosensitizing ability. Black-Right-Pointing-Pointer They are able to produce ROS. Black-Right-Pointing-Pointer Photo-excited fucoxanthin can produce singlet oxygen through energy transfer. -- Abstract: Carotenoids, natural pigments widely distributed in algae and plants, have a conjugated double bond system. Their excitation energies are correlated with conjugation length. We hypothesized that carotenoids whose energy states are above the singlet excited state of oxygen (singlet oxygen) would possess photosensitizing properties. Here, we demonstrated that human skin melanoma (A375) cells are damaged through the photo-excitation of several carotenoids (neoxanthin, fucoxanthin and siphonaxanthin). In contrast, photo-excitation of carotenoids that possess energymore » states below that of singlet oxygen, such as {beta}-carotene, lutein, loroxanthin and violaxanthin, did not enhance cell death. Production of reactive oxygen species (ROS) by photo-excited fucoxanthin or neoxanthin was confirmed using a reporter assay for ROS production with HeLa Hyper cells, which express a fluorescent indicator protein for intracellular ROS. Fucoxanthin and neoxanthin also showed high cellular penetration and retention. Electron spin resonance spectra using 2,2,6,6-tetramethil-4-piperidone as a singlet oxygen trapping agent demonstrated that singlet oxygen was produced via energy transfer from photo-excited fucoxanthin to oxygen molecules. These results suggest that carotenoids such as fucoxanthin, which are capable of singlet oxygen production through photo-excitation and show good penetration and retention in target cells, are useful as photosensitizers in photodynamic therapy for skin disease.« less

Density functional theory and Ab initio studies of vibrational spectroscopic (FT-IR, FT-Raman and UV) first order hyperpolarizabilities, NBO, HOMO-LUMO and TD-DFT analysis of the 1,2-Dihydropyrazolo (4,3-E) Pyrimidin-4-one

NASA Astrophysics Data System (ADS)

Ramachandran, G.; Muthu, S.; Uma Maheswari, J.

2013-02-01

Fourier transform Raman and Fourier transform infrared spectra of 1,2-Dihydropyrazolo (4,3-E) Pyrimidin-4-one were recorded in the regions 3500-100 cm-1 and 4000-400 cm-1 respectively in the solid phase. 1,2-Dihydropyrazolo (4, 3-E) Pyrimidin-4-one is used to treat hyperuricemia and its complication including chronic gout. The equilibrium geometry harmonic vibrational frequencies, infrared intensities and Raman intensities were calculated by Hartee Fock and density functional B3LYP methods with 6-31G (d, p) basis set, using Gaussian 03W program package on a Pentium IV/1.6 GHz personal computer. The thermodynamic functions of the title compound were also performed at the above methods and basis set. A detailed interpretation of the infrared and Raman spectra of 1,2-Dihydropyrazolo (4,3-E) Pyrimidin-4-one is reported. Stability of the molecule arising from hyper conjugative interactions, charge delocalization has been analyzed using natural bond orbital (NBO) analysis. UV-vis of the compound was recorded. The calculated HOMO and LUMO energies show that chemical activity of the molecule. The first order hyperpolarizability (β) of this novel molecular system and related properties of 1,2-Dihydropyrazolo (4,3-E) Pyrimidin-4-one are calculated using HF/6-31G (d, p) method on the finite field approach. The experimental spectra also coincide satisfactorily with those of theoretically constructed spectra.

Molecular structure, electronic properties, NLO, NBO analysis and spectroscopic characterization of Gabapentin with experimental (FT-IR and FT-Raman) techniques and quantum chemical calculations

NASA Astrophysics Data System (ADS)

Sinha, Leena; Karabacak, Mehmet; Narayan, V.; Cinar, Mehmet; Prasad, Onkar

2013-05-01

Gabapentin (GP), structurally related to the neurotransmitter GABA (gamma-aminobutyric acid), mimics the activity of GABA and is also widely used in neurology for the treatment of peripheral neuropathic pain. It exists in zwitterionic form in solid state. The present communication deals with the quantum chemical calculations of energies, geometrical structure and vibrational wavenumbers of GP using density functional (DFT/B3LYP) method with 6-311++G(d,p) basis set. In view of the fact that amino acids exist as zwitterions as well as in the neutral form depending on the environment (solvent, pH, etc.), molecular properties of both the zwitterionic and neutral form of GP have been analyzed. The fundamental vibrational wavenumbers as well as their intensities were calculated and compared with experimental FT-IR and FT-Raman spectra. The fundamental assignments were done on the basis of the total energy distribution (TED) of the vibrational modes, calculated with scaled quantum mechanical (SQM) method. The electric dipole moment, polarizability and the first hyperpolarizability values of the GP have been calculated at the same level of theory and basis set. The nonlinear optical (NLO) behavior of zwitterionic and neutral form has been compared. Stability of the molecule arising from hyper-conjugative interactions and charge delocalization has been analyzed using natural bond orbital analysis. Ultraviolet-visible (UV-Vis) spectrum of the title molecule has also been calculated using TD-DFT method. The thermodynamic properties of both the zwitterionic and neutral form of GP at different temperatures have been calculated.

Conformational stability, spectroscopic (FT-IR, FT-Raman and UV-Vis) analysis, NLO, NBO, FMO and Fukui function analysis of 4-hexylacetophenone by density functional theory.

PubMed

Saravanan, S; Balachandran, V

2015-03-05

The experimental and theoretical study on the structures and vibrations of 4-hexylacetophenone (abbreviated as 4HAP) are presented. The FT-IR and FT-Raman spectra of the title compound have been recorded in the region 4000-400cm(-1) and 3500-100cm(-1) respectively. The molecular structures, vibrational wavenumbers, infrared intensities and Raman activities were calculated using DFT (B3LYP and LSDA) method with 6-311++G(d,p) basis set. The most stable conformer of 4HAP is identified from the computational results. The assignments of the vibrational spectra have been carried out with the aid of normal coordinate analysis (NCA) following the scaled quantum mechanical force field methodology (SQMEF). The linear polarizability (α) and the first hyperpolarizability (βtot) values of the investigated molecule have been computed using B3LYP and LSDA with 6-311++G(d,p) basis set. Stability of the molecule arising from hyper conjugative interaction and charge transfer delocalization has been analyzed using natural bond orbital (NBO) analysis. The molecule orbital contributions are studied by density of energy states (DOSs). UV-Vis spectrum and effects of solvents have been discussed effects of solvents have been discussed and the electronic properties such as HOMO and LUMO energies were determined by time-dependent TD-DFT approach. Fukui function and Mulliken analysis on atomic charges of the title compound have been calculated. Finally, electrophilic and nucleophilic descriptors of the title molecule have been calculated. Copyright © 2014 Elsevier B.V. All rights reserved.

The HyperLeda project en route to the astronomical virtual observatory

NASA Astrophysics Data System (ADS)

Golev, V.; Georgiev, V.; Prugniel, Ph.

2002-07-01

HyperLeda (Hyper-Linked Extragalactic Databases and Archives) is aimed to study the evolution of galaxies, their kinematics and stellar populations and the structure of Local Universe. HyperLeda is involved in catalogue and software production, data-mining and massive data processing. The products are serviced to the community through web mirrors. The development of HyperLeda is distributed between different sites and is based on the background experience of the LEDA and Hypercat databases. The HyperLeda project is focused both on the European iAstro colaboration and as a unique database for studies of the physics of the extragalactic objects.

Relevance of biophysical interactions of nanoparticles with a model membrane in predicting cellular uptake: study with TAT peptide-conjugated nanoparticles

PubMed Central

Peetla, Chiranjeevi; Rao, Kavitha S.; Labhasetwar, Vinod

2009-01-01

The aim of the study was to test the hypothesis that the biophysical interactions of the trans-activating transcriptor (TAT) peptide-conjugated nanoparticles (NPs) with a model cell membrane could predict the cellular uptake of the encapsulated therapeutic agent. To test the above hypothesis, the biophysical interactions of ritonavir-loaded poly (L-lactide) nanoparticles (RNPs), either conjugated to a TAT peptide (TAT-RNPs) or scrambled TAT peptide (sc-TAT-RNPs), were studied with an endothelial cell model membrane (EMM) using a Langmuir film balance, and the corresponding human vascular endothelial cells (HUVECs) were used to study the uptake of the encapsulated therapeutic. Biophysical interactions were determined from the changes in surface pressure (SP) of the EMM as a function of time following interaction with NPs, and the compression isotherm (π–A) of the EMM lipid mixture in the presence of NPs. In addition, the EMMs were transferred onto a silicon substrate following interactions with NPs using the Langmuir–Schaeffer (LS) technique. The transferred LS films were imaged by atomic force microscopy (AFM) to determine the changes in lipid morphology and to characterize the NP–membrane interactions. TAT-RNPs showed an increase in SP of the EMM, which was dependent upon the amount of the peptide bound to NPs and the concentration of NPs, whereas sc-TAT-RNPs and RNPs did not show any significant change in SP. The isotherm experiment showed a shift towards higher mean molecular area (mmA) in the presence of TAT-RNPs, indicating their interactions with the lipids of the EMM, whereas sc-TAT-RNPs and RNPs did not show any significant change. The AFM images showed condensation of the lipids following interaction with TAT-RNPs, indicating their penetration into the EMM, whereas RNPs did not cause any change. Surface analysis and 3-D AFM images of the EMM further confirmed penetration of TAT-RNPs into the EMM whereas RNPs were seen anchored loosely to the membrane, and were significantly less in number than TAT-RNPs. We speculate that hydrophobic tyrosine of the TAT that forms the NP–interface drives the initial interactions of TAT-RNPs with the EMM, followed by electrostatic interactions with the anionic phospholipids of the membrane. In case of sc-TAT-RNPs, hydrophilic arginine forms the NP–interface that does not interact with the EMM, despite having the similar cationic charge on these NPs as TAT-RNPs. TAT peptide alone did not show any change in SP, suggesting that the interaction occurs when the peptide is conjugated to a carrier system. HUVECs showed higher uptake of the drug with TAT-RNPs as compared to that with sc-TAT-RNPs or RNPs, suggesting that the biophysical interactions of NPs with cell membrane lipids play a role in cellular internalization of NPs. In conclusion, TAT peptide sequence and the amount of TAT conjugated to NPs significantly affect the biophysical interactions of NPs with the EMM, and these interactions correlate with the cellular delivery of the encapsulated drug. Biophysical interactions with a model membrane thus could be effectively used in developing efficient functionalized nanocarrier systems for drug delivery applications. PMID:19243206

Chromophores in phenylenevinylene-based conjugated polymers: role of conformational kinks and chemical defects.

PubMed

Hennebicq, Emmanuelle; Deleener, Caroline; Brédas, Jean-Luc; Scholes, Gregory D; Beljonne, David

2006-08-07

The influence of chemical defects and conformational kinks on the nature of the lowest electronic excitations in phenylenevinylene-based polymers is assessed at the semiempirical quantum-chemical level. The amount of excited-state localization and the amplitude of through-space (Coulomb-like) versus through-bond (charge-transfer-like) interactions have been quantified by comparing the results provided by excitonic and supermolecular models. While excitation delocalization among conjugated segments delineated by the defects occurs in the acceptor configuration, self-confinement on individual chromophores follows from geometric relaxation in the excited-state donor configuration. The extent of excited-state localization is found to be sensitive to both the nature of the defect and the length of the conjugated chains. Implications for resonant energy transfer along conjugated polymer chains are discussed.

AGT M235T Genotype/Anxiety Interaction and Gender in the HyperGEN Study

PubMed Central

Knox, Sarah S.; Guo, Xinxin; Zhang, Yuqing; Weidner, G.; Williams, Scott; Ellison, R. Curtis

2010-01-01

Background Both anxiety and elevated heart rate (HR) have been implicated in the development of hypertension. The HyperGen cohort, consisting of siblings with severe and mild hypertension, an age-matched random sample of persons from the same base populations, and unmedicated adult offspring of the hypertensive siblings (N = 1,002 men and 987 women), was analyzed for an association of the angiotenisinogen AGTM235T genotype (TT, MT, MM) with an endophenotype, heart rate (HR) in high and low anxious groups. Methodology The interaction of AGTM genotype with anxiety, which has been independently associated with hypertension, was investigated adjusting for age, hypertension status, smoking, alcohol consumption, beta blocker medication, body mass index, physical activity and hours of television viewing (sedentary life style). Principal Findings Although there was no main effect of genotype on HR in men or women, high anxious men with the TT genotype had high HR, whereas high anxious men with the MM genotype had low HR. In women, HR was inversely associated with anxiety but there was no interaction with genotype. Conclusion/Significance The results suggest that high anxiety in men with the TT genotype may increase risk for hypertension whereas the MM genotype may be protective in high anxious men. This type of gene x environment interaction may be one reason why genome wide association studies sometimes fail to replicate. The locus may be important only in combination with certain environmental factors. PMID:20967221

Impact of styrenic polymer one-step hyper-cross-linking on volatile organic compound adsorption and desorption performance.

PubMed

Ghafari, Mohsen; Atkinson, John D

2018-06-05

A novel one-step hyper-cross-linking method, using 1,2-dichloroethane (DCE) and 1,6-dichlorohexane (DCH) cross-linkers, expands the micropore volume of commercial styrenic polymers. Performance of virgin and modified polymers was evaluated by measuring hexane, toluene, and methyl-ethyl-ketone (MEK) adsorption capacity, adsorption/desorption kinetics, and desorption efficiency. Hyper-cross-linked polymers have up to 128% higher adsorption capacity than virgin polymers at P/P 0  = 0.05 due to micropore volume increases up to 330%. Improvements are most pronounced with the DCE cross-linker. Hyper-cross-linking has minimal impact on hexane adsorption kinetics, but adsorption rates for toluene and MEK decrease by 6-41%. Desorption rates decreased (3-36%) for all materials after hyper-cross-linking, with larger decreases for DCE hyper-cross-linked polymers due to smaller average pore widths. For room temperature desorption, 20-220% more adsorbate remains in hyper-cross-linked polymers after regeneration compared to virgin materials. DCE hyper-cross-linked polymers have 13-92% more residual adsorbate than DCH counterparts. Higher temperatures were required for DCE hyper-cross-linked polymers to completely desorb VOCs compared to the DCH hyper-cross-linked and virgin counterparts. Results show that the one-step hyper-cross-linking method for modifying styrenic polymers improves adsorption capacity because of added micropores, but decreases adsorption/desorption kinetics and desorption efficiency for large VOCs due to a decrease in average pore width. Copyright © 2018 Elsevier B.V. All rights reserved.

Daclatasvir inhibits hepatitis C virus NS5A motility and hyper-accumulation of phosphoinositides

PubMed Central

Chukkapalli, Vineela; Berger, Kristi L.; Kelly, Sean M.; Thomas, Meryl; Deiters, Alexander; Randall, Glenn

2014-01-01

Combinations of direct-acting antivirals (DAAs) against the hepatitis C virus (HCV) have the potential to revolutionize the HCV therapeutic regime. An integral component of DAA combination therapies are HCV NS5A inhibitors. It has previously been proposed that NS5A DAAs inhibit two functions of NS5A: RNA replication and virion assembly. In this study, we characterize the impact of a prototype NS5A DAA, daclatasvir (DCV), on HCV replication compartment formation. DCV impaired HCV replicase localization and NS5A motility. In order to characterize the mechanism behind altered HCV replicase localization, we examined the impact of DCV on the interaction of NS5A with its essential cellular cofactor, phosphatidylinositol-4-kinase III α (PI4KA). We observed that DCV does not inhibit PI4KA directly, nor does it impair early events of the NS5A-PI4KA interaction that can occur when NS5A is expressed alone. NS5A functions that are unaffected by DCV include PI4KA binding, as determined by co-immunoprecipitation, and a basal accumulation of the PI4KA product, PI4P. However, DCV impairs late steps in PI4KA activation that requires NS5A expressed in the context of the HCV polyprotein. These NS5A functions include hyper-stimulation of PI4P levels and appropriate replication compartment formation. The data are most consistent with a model wherein DCV inhibits conformational changes in the NS5A protein or protein complex formations that occur in the context of HCV polyprotein expression and stimulate PI4P hyper-accumulation and replication compartment formation. PMID:25546252

Synthesis, structural, DFT studies, docking and antibacterial activity of a xanthene based hydrazone ligand

NASA Astrophysics Data System (ADS)

Naseem, Saira; Khalid, Muhammad; Tahir, Muhammad Nawaz; Halim, Mohammad A.; Braga, Ataualpa A. C.; Naseer, Muhammad Moazzam; Shafiq, Zahid

2017-09-01

Herein, we present the synthesis of novel xanthene-based hydrazone (1). The chemical structure of 1 was resolved using spectroscopic techniques such as NMR, FT-IR, UV-VIS and X-ray crystallographic approaches. X-ray diffraction analysis shows that the compound (1) crystallizes in triclinic crystal lattice with the Pbar1 space group and diffused to form multi-layered structure due to non-covalent interactions such as intramolecular hydrogen bonding (H.B). In addition to experimental investigation, density functional theory (DFT) calculation with M06-2X/6-31G(d,p) and B3LYP/6-31G(d,p) level of theories was performed on compound (1) to obtain optimized geometry, spectroscopic and electronic properties. DFT optimized geometry shows good agreement with the experimental XRD structure. The hyper conjugative interactions and hydrogen bonding network are responsible for the stability of compound (1) as revealed by natural bond orbital (NBO) calculation. Moreover, hydrogen bonding network in the dimer is confirmed by FT-IR and thermodynamic studies showing excellent agreement with XRD and NBO findings. TD-DFT/UV-VIS analysis provides insight that maximum excitation is found in 1 which shows good agreement with experimental UV-VIS result. The global reactivity parameters are calculated using the energies of frontier molecular orbitals also disclosed that the compound is more stable might be due to hydrogen bonding network. Experimental and molecular docking studies indicated that this compound has anti-bacterial and anti-diabetic properties. The binding affinity of this compound against the multidrug efflux pump subunit AcrB OS=Escherichia coli (strain K12) and Human Pancreatic Alpha-Amylase is -9.2 and -10.00 kcal/mol which are higher than the control drugs. Pi-Pi, Pi-anaion, amide-pi and pi-alkyl bonds play key role in drug-protein complexes.

Adsorption of alanine with heteroatom substituted fullerene for solar cell application: A DFT study.

PubMed

Dheivamalar, S; Sugi, L; Ravichandran, K; Sriram, S

2018-09-05

C 20 is the most important fullerene cage and alanine is the simplest representation of a backbone unit of the protein. The absorption feasibility of alanine molecule in the Si-doped C 20 and B-doped C 20 fullerenes has been studied based on calculated electronic properties of fullerenes using density functional theory (DFT). In this work, we explore the ability of Si-doped C 20 , B-doped C 20 fullerene to interact with alanine at the DFT-B3LYP/6-31G, RHF level of theory. We find that noticeable structural change takes place in C 20 when one of its carbon is substituted with Si or B. The molecular geometry, electronic properties and vibrational analysis have also been performed on the title compounds. The NMR study reveals the aromaticity of the pure and doped fullerene compounds. Stability of the doped fullerene - alanine compound arises from hyper conjugative interactions. It leads to one of the major property of bioactivity, charge transfer and delocalization of charge and this properties has been analyzed using Natural Bond Orbital (NBO) analysis. The energy gap of the doped fullerene reveals that there is a decrease in the size of energy gap significantly, making them more reactive as compared to C 20 fullerene. Theoretical studies of the electronic spectra by using time - dependent density functional theory (TD-DFT) method were helpful to interpret the observed electronic transition state. We aim to optimize the performance of the solar cells by altering the frontier orbital energy gaps. Considering all studied properties, it may be inferred that the applicability of C 20 fullerene as the non-linear optical (NLO) material and its NLO property would increase on doping fullerene with Si and B atom. Specifically C 19 Si would be better among them. Copyright © 2018. Published by Elsevier B.V.

Synthesis, spectroscopic analyses (FT-IR and NMR), vibrational study, chemical reactivity and molecular docking study and anti-tubercular activity of condensed oxadiazole and pyrazine derivatives

NASA Astrophysics Data System (ADS)

El-Azab, Adel S.; Mary, Y. Sheena; Abdel-Aziz, Alaa A. M.; Miniyar, Pankaj B.; Armaković, Stevan; Armaković, Sanja J.

2018-03-01

The Fourier transform infrared spectra of the compounds 2-(5-phenyl-1,3,4-oxadiazol-2-yl)pyrazine (PHOXPY), 2-(5-styryl-1,3,4-oxadiazol-2-yl)pyrazine (STOXPY) and 2-(5-(furan-2-yl)-1,3,4-oxadiazol-2-yl)pyrazine (FUOXPY) have been recorded and the wavenumbers are computed at the density functional theory level. The assignments of all the fundamental bands of each molecule are made using potential energy distribution. The computed values of dipole moment, polarizability and hyperpolarizability values indicate that the title molecules exhibit NLO properties. The HOMO and LUMO energies demonstrate the chemical stability of the molecules and NBO analysis is made to study the stability of molecules arising from hyper conjugative interactions and charge delocalization. Detailed computational analysis and spectroscopic characterization has been performed for three newly synthesized oxadiazole derivatives. Obtained computational and experimental results have been mutually compared in order to understand the influence of structural parts specific for each derivative. From the MIC determination, MTb H37Rv was found to be sensitive to compounds, PHOXPY, STOXPY and FUOXPY. The results obtained from anti-TB activity are more promising as the compounds were found to be more potent than reference standards, streptomycin and pyrazinamide. Efforts were made in order to predict both global and local reactive properties of the title oxadiazole derivatives, including their sensitivity towards autoxidation mechanism and influence of water. The results obtained from anti-TB activity are more promising for the title compounds. Interaction with representative protein Pterindeaminase inhibitor asricin A was also investigated using the molecular docking procedure. The docked ligands form stable complexes with the receptor ricin A and the docking results suggest that these compounds can be developed as new anti-cancer drugs.

HyperCard--A Science Teaching Tool.

ERIC Educational Resources Information Center

Parker, Carol

1992-01-01

Discussion of new technological resources available for science instruction focuses on the use of the HyperCard software for the Macintosh to design customized materials. Topics addressed include general features of HyperCard, designing HyperCard stacks, graphics, and designing buttons (i.e., links for moving through the stacks). Several sample…

In-situ fabrication of diketopyrrolopyrrole-carbazole-based conjugated polymer/TiO2 heterojunction for enhanced visible light photocatalysis

NASA Astrophysics Data System (ADS)

Yang, Long; Yu, Yuyan; Zhang, Jianling; Chen, Fu; Meng, Xiao; Qiu, Yong; Dan, Yi; Jiang, Long

2018-03-01

Aiming at developing highly efficient photocatalysts by broadening the light-harvesting region and suppressing photo-generated electron-hole recombination simultaneously, this work reports rational design and fabrication of donor-acceptor (D-A) conjugated polymer/TiO2 heterojunction catalyst with strong interfacial interactions by a facile in-situ thermal treatment. To expand the light-harvesting window, soluable conjugated copolymers with D-A architecture are prepared by Pd-mediated polycondensation of diketopyrrolopyrrole (DPP) and t-butoxycarbonyl (t-Boc) modified carbazole (Car), and used as visible-light-harvesting antenna to couple with TiO2 nanocrystals. The DPP-Car/TiO2 composites show wide range absorption in 300-1000 nm. To improve the interfacial binding at the interface, a facile in-situ thermal treatment is carried out to cleave the pendant t-Boc groups in carbazole units and liberate the polar amino groups (-NH-) which strongly bind to the surface of TiO2 through dipole-dipole interactions, forming a heterojunction interface. This in-situ thermal treatment changes the surface elemental distribution of TiO2, reinforces the interface bonding at the boundary of conjugated polymers/TiO2 and finally improves the photocatalytic efficiency of DPP-Car/TiO2 under visible-light irradiation. The interface changes are characterized and verified through Fourier-transform infrared spectroscopy (FT-IR), photo images, UV/Vis (solution state and powder diffuse reflection spectroscopy), X-ray powder diffraction (XRD), X-ray photoelectron spectroscopy (XPS), fluorescence, scanning electron microscopy(SEM) and transmission electron microscopy (TEM) techniques. This study provides a new strategy to avoid the low solubility of D-A conjugated polymers and construct highly-efficient conjugated polymer/TiO2 heterojunction by enforcing the interface contact and facilitating charge or energy transfer for the applications in photocatalysis.

Synthesis, characterization, mucoadhesion and biocompatibility of thiolated carboxymethyl dextran-cysteine conjugate.

PubMed

Shahnaz, G; Perera, G; Sakloetsakun, D; Rahmat, D; Bernkop-Schnürch, A

2010-05-21

This study was aimed at improving the mucoadhesive properties of carboxymethyl dextran by the covalent attachment of cysteine. Mediated by a carbodiimide, l-cysteine was covalently attached to the polymer. The resulting CMD-cysteine conjugate (CMD-(273) conjugate) displayed 273+/-20 micromol thiol groups per gram of polymer (mean+/-S.D.; n=3). Within 2h the viscosity of an aqueous mucus/CMD-(273) conjugate mixture pH 7.4 increased at 37 degrees C by more than 85% compared to a mucus/carboxymethyl dextran mixture indicating enlarged interactions between the mucus and the thiolated polymer. Due to the immobilization of cysteine, the swelling velocity of the polymer was significantly accelerated (p<0.05). In aqueous solutions the CMD-(273) conjugate was capable of forming inter- and/or intramolecular disulfide bonds. Because of this crosslinking process within the polymeric network, the cohesive properties of the conjugate were also improved. Tablets comprising the unmodified polymer disintegrated within 15 min, whereas tablets of the CMD-(273) conjugate remained stable for 160 min (means+/-S.D.; n=3). Results from LDH and MTT assays on Caco-2 cells revealed 4.96+/-0.98% cytotoxicity and 94.1+/-0.9% cell viability for the CMD-(273) conjugate, respectively. Controlled release of model compound from CMD-(273) conjugate tablets was observed over 6h. These findings suggest that CMD-(273) conjugate is a promising novel polymer for drug delivery systems providing improved mucoadhesive and cohesive properties, greater stability and biocompatibility. Copyright 2010 Elsevier B.V. All rights reserved.

Brain tumor magnetic targeting and biodistribution of superparamagnetic iron oxide nanoparticles linked with 70-kDa heat shock protein study by nonlinear longitudinal response

NASA Astrophysics Data System (ADS)

Shevtsov, Maxim A.; Nikolaev, Boris P.; Ryzhov, Vyacheslav A.; Yakovleva, Ludmila Y.; Dobrodumov, Anatolii V.; Marchenko, Yaroslav Y.; Margulis, Boris A.; Pitkin, Emil; Guzhova, Irina V.

2015-08-01

Brain tumor targeting efficiency and biodistribution of the superparamagnetic nanoparticles conjugated with heat shock protein Hsp70 (SPION-Hsp70) were evaluated in experimental glioma model. Synthesized conjugates were characterized using the method of longitudinal nonlinear response of magnetic nanoparticles to a weak ac magnetic field with measurements of second harmonic of magnetization (NLR-M2). Cellular interaction of magnetic conjugates was analyzed in 9L glioma cell culture. The biodistribution of the nanoparticles and their accumulation in tumors was assessed by the latter approach as well. The efficacy of Hsp70-conjugates for contrast enhancement in the orthotopic model of 9L glioma was assessed by MR imaging (11 T). Magnetic nanoparticles conjugated with Hsp70 had the relaxivity properties of the MR-negative contrast agents. Morphological observation and cell viability test demonstrated good biocompatibility of Hsp70-conjugates. Analysis of the T2-weighted MR scans in tumor-bearing rats demonstrated the high efficacy of Hsp70-conjugates in contrast enhancement of the glioma in comparison to non-conjugated nanoparticles. High contrast enhancement of the glioma was provided by the accumulation of the SPION-Hsp70 particles in the glioma tissue (as shown by the histological assay). Biodistribution analysis by NLR-M2 measurements evidenced the many-fold increase (~40) in the tumor-to-normal brain uptake ratio in the Hsp70-conjugates treated animals. Biodistribution pattern of Hsp70-decorated nanoparticles differed from that of non-conjugated SPIONs. Coating of the magnetic nanoparticles with Hsp70 protein enhances the tumor-targeting ability of the conjugates that could be applied in the MR imaging of the malignant brain tumors.

NASA EOSDIS: Enabling Science by Improving User Knowledge

NASA Technical Reports Server (NTRS)

Lindsay, Francis; Brennan, Jennifer; Blumenfeld, Joshua

2016-01-01

Lessons learned and impacts of applying these newer methods are explained and include several examples from our current efforts such as the interactive, on-line webinars focusing on data discovery and access including tool usage, informal and informative data chats with data experts across our EOSDIS community, data user profile interviews with scientists actively using EOSDIS data in their research, and improved conference and meeting interactions via EOSDIS data interactively used during hyper-wall talks and Worldview application. The suite of internet-based, interactive capabilities and technologies has allowed our project to expand our user community by making the data and applications from numerous Earth science missions more engaging, approachable and meaningful.

Preparation, structural analysis and bioactivity of ribonuclease A-albumin conjugate: tetra-conjugation or PEG as the linker.

PubMed

Li, Chunju; Lin, Qixun; Wang, Jun; Shen, Lijuan; Ma, Guanghui; Su, Zhiguo; Hu, Tao

2012-12-31

Ribonuclease A (RNase A) is a therapeutic enzyme with cytotoxic action against tumor cells. Its clinical application is limited by the short half-life and insufficient stability. Conjugation of albumin can overcome the limitation, whereas dramatically decrease the enzymatic activity of RNase A. Here, three strategies were proposed to prepare the RNase A-bovine serum albumin (BSA) conjugates. R-SMCC-B (a conjugate of four RNase A attached with one BSA) and R-PEG-B (a mono-conjugate) were prepared using Sulfo-SMCC (a short bifunctional linker) and mal-PEG-NHS (a bifunctional PEG), respectively. Mal-PEG-NHS and hexadecylamine (HDA) were used to prepare the mono-conjugate, R-HDA-B, where HDA was adopted to bind BSA. The PEG linker can elongate the proximity between RNase A and BSA. In contrast, four RNase A were closely located on BSA in R-SMCC-B. R-SMCC-B showed the lowest K(m) and the highest relative enzymatic activity and k(cat)/K(m) in the three conjugates. Presumably, the tetravalent interaction of RNase A in R-SMCC-B can increase the binding affinity to its substrate. In addition, the slow release of BSA from R-HDA-B may increase the enzymatic activity of R-HDA-B. Our study is expected to provide strategies to develop protein-albumin conjugate with high therapeutic potential. Copyright © 2012 Elsevier B.V. All rights reserved.

Ubiquitin in Motion: Structural Studies of the Ubiquitin-Conjugating Enzyme~Ubiquitin Conjugate

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

Pruneda, Jonathan N.; Stoll, Kate E.; Bolton, Laura J.

2011-03-15

Ubiquitination of proteins provides a powerful and versatile post-translational signal in the eukaryotic cell. The formation of a thioester bond between ubiquitin (Ub) and the active site of a ubiquitin-conjugating enzyme (E2) is critical for the transfer of Ub to substrates. Assembly of a functional ubiquitin ligase (E3) complex poised for Ub transfer involves recognition and binding of an E2~Ub conjugate. Therefore, full characterization of the structure and dynamics of E2~Ub conjugates is required for further mechanistic understanding of Ub transfer reactions. Here we present characterization of the dynamic behavior of E2~Ub conjugates of two human enzymes, UbcH5c~Ub and Ubc13~Ub,more » in solution as determined by nuclear magnetic resonance and small-angle X-ray scattering. Within each conjugate, Ub retains great flexibility with respect to the E2, indicative of highly dynamic species that adopt manifold orientations. The population distribution of Ub conformations is dictated by the identity of the E2: the UbcH5c~Ub conjugate populates an array of extended conformations, and the population of Ubc13~Ub conjugates favors a closed conformation in which the hydrophobic surface of Ub faces helix 2 of Ubc13. Finally, we propose that the varied conformations adopted by Ub represent available binding modes of the E2~Ub species and thus provide insight into the diverse E2~Ub protein interactome, particularly with regard to interaction with Ub ligases.« less

Inhomogeneity in the excited-state torsional disorder of a conjugated macrocycle.

PubMed

Yang, Jaesung; Ham, Sujin; Kim, Tae-Woo; Park, Kyu Hyung; Nakao, Kazumi; Shimizu, Hideyuki; Iyoda, Masahiko; Kim, Dongho

2015-03-12

The photophysics of conjugated polymers has generally been explained based on the interactions between the component conjugated chromophores in a tangled chain. However, conjugated chromophores are entities with static and dynamic structural disorder, which directly affects the conjugated polymer photophysics. Here we demonstrate the impact of chain structure torsional disorder on the spectral characteristics for a macrocyclic oligothiophene 1, which is obscured in conventional linear conjugated chromophores by diverse structural disorders such as those in chromophore size and shape. We used simultaneous multiple fluorescence parameter measurement for a single molecule and quantum-mechanical calculations to show that within the fixed conjugation length across the entire ring an inhomogeneity from torsional disorder in the structure of 1 plays a crucial role in causing its energetic disorder, which affords the spectral broadening of ∼220 meV. The torsional disorder in 1 fluctuated on the time scale of hundreds of milliseconds, typically accompanied by spectral drifts on the order of ∼10 meV. The fluctuations could generate torsional defects and change the electronic structure of 1 associated with the ring symmetry. These findings disclose the fundamental nature of conjugated chromophore that is the most elementary spectroscopic unit in conjugated polymers and suggest the importance of engineering structural disorder to optimize polymer-based device photophysics. Additionally, we combined defocused wide-field fluorescence microscopy and linear dichroism obtained from the simultaneous measurements to show that 1 emits polarized light with a changing polarization direction based on the torsional disorder fluctuations.

HyperCard for Educators. An Introduction.

ERIC Educational Resources Information Center

Bull, Glen L.; Harris, Judi

This guide is designed to provide a quick introduction to the basic elements of HyperCard for teachers who are familiar with other computer applications but may not have worked with hypermedia applications; previous familiarity with HyperCard or with Macintosh computers is not necessary. It is noted that HyperCard is a software construction…

The HyperCard Launching Pad.

ERIC Educational Resources Information Center

Aufdenspring, Gary; Aufdenspring, Deborah

1992-01-01

Describes how HyperCard software can be used to direct students to databases, applications, and explanations in an online environment. The use of HyperCard with other software is discussed; using HyperCard to set up tutorials is explained; and limitations are addressed, including the amount of memory needed and the speed of the hardware. (LRW)

Interaction study on bovine serum albumin physically binding to silver nanoparticles: Evolution from discrete conjugates to protein coronas

NASA Astrophysics Data System (ADS)

Guo, Jun; Zhong, Ruibo; Li, Wanrong; Liu, Yushuang; Bai, Zhijun; Yin, Jun; Liu, Jingran; Gong, Pei; Zhao, Xinmin; Zhang, Feng

2015-12-01

The nanostructures formed by inorganic nanoparticles together with organic molecules especially biomolecules have attracted increasing attention from both industries and researching fields due to their unique hybrid properties. In this paper, we systemically studied the interactions between amphiphilic polymer coated silver nanoparticles and bovine serum albumins by employing the fluorescence quenching approach in combination with the Stern-Volmer and Hill equations. The binding affinity was determined to 1.30 × 107 M-1 and the interaction was spontaneously driven by mainly the van der Waals force and hydrogen-bond mediated interactions, and negatively cooperative from the point of view of thermodynamics. With the non-uniform coating of amphiphilic polymer, the silver nanoparticles can form protein coronas which can become discrete protein-nanoparticle conjugates when controlling their molar ratios of mixing. The protein's conformational changes upon binding nanoparticles was also studied by using the three-dimensional fluorescence spectroscopy.

Conjugation of squalene to gemcitabine as unique approach exploiting endogenous lipoproteins for drug delivery

NASA Astrophysics Data System (ADS)

Sobot, Dunja; Mura, Simona; Yesylevskyy, Semen O.; Dalbin, Laura; Cayre, Fanny; Bort, Guillaume; Mougin, Julie; Desmaële, Didier; Lepetre-Mouelhi, Sinda; Pieters, Grégory; Andreiuk, Bohdan; Klymchenko, Andrey S.; Paul, Jean-Louis; Ramseyer, Christophe; Couvreur, Patrick

2017-05-01

Once introduced in the organism, the interaction of nanoparticles with various biomolecules strongly impacts their fate. Here we show that nanoparticles made of the squalene derivative of gemcitabine (SQGem) interact with lipoproteins (LPs), indirectly enabling the targeting of cancer cells with high LP receptors expression. In vitro and in vivo experiments reveal preeminent affinity of the squalene-gemcitabine bioconjugates towards LP particles with the highest cholesterol content and in silico simulations further display their incorporation into the hydrophobic core of LPs. To the best of our knowledge, the use of squalene to induce drug insertion into LPs for indirect cancer cell targeting is a novel concept in drug delivery. Interestingly, not only SQGem but also other squalene derivatives interact similarly with lipoproteins while such interaction is not observed with liposomes. The conjugation to squalene represents a versatile platform that would enable efficient drug delivery by simply exploiting endogenous lipoproteins.

Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, Part II.

PubMed

Armstrong, Scott C; Cozza, Kelly L

2003-01-01

Pharmacokinetic drug-drug interactions with codeine, dihydrocodeine, hydrocodone, oxycodone, and buprenorphine are reviewed in this column. These compounds have a very similar chemical structure to morphine. Unlike morphine, which is metabolized chiefly through conjugation reactions with uridine diphosphate glucuronosyl transferase (UGT) enzymes, these five drugs are metabolized both through oxidative reactions by the cytochrome P450 (CYP450) enzyme and conjugation by UGT enzymes. There is controversy as to whether codeine, dihydrocodeine, and hydrocodone are actually prodrugs requiring activation by the CYP450 2D6 enzyme or UGT enzymes. Oxycodone and buprenorphine, however, are clearly not prodrugs and are metabolized by the CYP450 2D6 and 3A4 enzymes, respectively. Knowledge of this metabolism assists in the understanding for the potential of drug-drug interactions with these drugs. This understanding is important so that clinicians can choose the proper dosages for analgesia and anticipate potential drug-drug interactions.

Talent in autism: hyper-systemizing, hyper-attention to detail and sensory hypersensitivity

PubMed Central

Baron-Cohen, Simon; Ashwin, Emma; Ashwin, Chris; Tavassoli, Teresa; Chakrabarti, Bhismadev

2009-01-01

We argue that hyper-systemizing predisposes individuals to show talent, and review evidence that hyper-systemizing is part of the cognitive style of people with autism spectrum conditions (ASC). We then clarify the hyper-systemizing theory, contrasting it to the weak central coherence (WCC) and executive dysfunction (ED) theories. The ED theory has difficulty explaining the existence of talent in ASC. While both hyper-systemizing and WCC theories postulate excellent attention to detail, by itself excellent attention to detail will not produce talent. By contrast, the hyper-systemizing theory argues that the excellent attention to detail is directed towards detecting ‘if p, then q’ rules (or [input–operation–output] reasoning). Such law-based pattern recognition systems can produce talent in systemizable domains. Finally, we argue that the excellent attention to detail in ASC is itself a consequence of sensory hypersensitivity. We review an experiment from our laboratory demonstrating sensory hypersensitivity detection thresholds in vision. We conclude that the origins of the association between autism and talent begin at the sensory level, include excellent attention to detail and end with hyper-systemizing. PMID:19528020

Water-Soluble Conjugated Polymers: Self-Assembly and Biosensor Applications

NASA Astrophysics Data System (ADS)

Bazan, Guillermo

2005-03-01

Homogeneous assays can be designed which take advantage of the optical amplification of conjugated polymers and the self-assembly characteristic of aqueous polyelectrolytes. For example, a ssDNA sequence sensor comprises an aqueous solution containing a cationic water soluble conjugated polymer such as poly(9,9-bis(trimethylammonium)-hexyl)-fluorene phenylene) with a peptide nucleic acid (PNA) labeled with a dye (PNA-C*). Signal transduction is controlled by hybridization of the neutral PNA-C* probe and the negative ssDNA target, resulting in favorable electrostatic interactions between the hybrid complex and the cationic polymer. Distance requirements for Förster energy transfer are thus met only when ssDNA of complementary sequence to the PNA-C* probe is present. Signal amplification by the conjugated polymer provides fluorescein emission >25 times higher than that of the directly excited dye. Transduction by electrostatic interactions followed by energy transfer is a general strategy. Examples involving other biomolecular recognition events, such as DNA/DNA, RNA/protein and RNA/RNA, will also be provided. The mechanism of biosensing will be discussed, with special attention to the varying contributions of hydrophobic and electrostatic forces, polymer conformation, charge density, local concentration of C*s and tailored defect sites for aggregation-induced optical changes. Finally, the water solubility of these conjugated polymers opens possibilities for spin casting onto organic materials, without dissolving the underlying layers. This property is useful for fabricating multilayer organic optoelectronic devices by simple solution techniques.

Parametric phase conjugation for the second harmonic of a nonlinear ultrasonic beam

NASA Astrophysics Data System (ADS)

Brysev, A. P.; Bunkin, F. V.; Hamilton, M. F.; Klopotov, R. V.; Krutyanskii, L. M.; Yan, K.

2003-01-01

The effect of phase conjugation for the second harmonic of a focused ultrasonic beam was investigated experimentally and by numerical simulation. An ultrasonic pulse with the carrier frequency f=3 MHz was emitted into water and focused at a point between the source and the phase conjugating system. The phase conjugation for the second harmonic of the incident wave (2 f=6 MHz) was performed in a magnetostrictive ceramic as a result of the parametric interaction of the incident wave with the pumping magnetic field (the pumping frequency was f p=4 f=12 MHz). The axial and focal distributions of sound pressure in the incident and conjugated beams were measured using a broadband PVDF membrane hydrophone. The corresponding calculations were performed by solving numerically the Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation allowing for the nonlinearity, diffraction, and thermoviscous absorption. The results of measurements agreed well with the calculations and showed that the field of a conjugate wave adequately reproduces the field of the second harmonic of the incident wave. A certain advantage of focusing with the phase conjugation for the second harmonic was demonstrated in comparison with the operation at the doubled frequency of the incident wave. The results of this study can serve as a basis for the utilization of the phase conjugation of harmonics in ultrasonic tomography and nondestructive testing.

Evaluation of RGD-targeted albumin carriers for specific delivery of auristatin E to tumor blood vessels.

PubMed

Temming, Kai; Meyer, Damon L; Zabinski, Roger; Dijkers, Eli C F; Poelstra, Klaas; Molema, Grietje; Kok, Robbert J

2006-01-01

Induction of apoptosis in endothelial cells is considered an attractive strategy to therapeutically interfere with a solid tumor's blood supply. In the present paper, we constructed cytotoxic conjugates that specifically target angiogenic endothelial cells, thus preventing typical side effects of apoptosis-inducing drugs. For this purpose, we conjugated the potent antimitotic agent monomethyl-auristatin-E (MMAE) via a lysosomal cleavable linker to human serum albumin (HSA) and further equipped this drug-albumin conjugate with cyclic c(RGDfK) peptides for multivalent interaction with alphavbeta3-integrin. The RGD-peptides were conjugated via either an extended poly(ethylene glycol) linker or a short alkyl linker. The resulting drug-targeting conjugates RGDPEG-MMAE-HSA and RGD-MMAE-HSA demonstrated high binding affinity and specificity for alphavbeta3-integrin expressing human umbilical vein endothelial cells (HUVEC). Both types of conjugates were internalized by endothelial cells and killed the target cells at low nM concentrations. Furthermore, we observed RGD-dependent binding of the conjugates to C26 carcinoma. Upon i.v. administration to C26-tumor bearing mice, both drug-targeting conjugates displayed excellent tumor homing properties. Our results demonstrate that RGD-modified albumins are suitable carriers for cell selective intracellular delivery of cytotoxic compounds, and further studies will be conducted to assess the antivascular and tumor inhibitory potential of RGDPEG-MMAE-HSA and RGD-MMAE-HSA.

Interactions between clinically used drugs and oral contraceptives.

PubMed Central

Bolt, H M

1994-01-01

Metabolism of contraceptive compounds may be influenced by various drugs. Of clinical importance is induction by barbiturates, by diphenylhydantoin, and especially by rifampicin, of enzymes that are responsible for degradation of estrogens. The major target is the hepatic microsomal estrogen-2-hydroxylase (cytochrome P450 3A4). Another type of interaction of drugs with disposition and effectiveness of estrogens is impairment of their enterohepatic circulation. This may be due to absorption of biliary estrogen conjugates (e.g., by cholestyramine) or to insufficient cleavage of the conjugate by intestinal bacteria, the latter being observed after administration of antibiotics (e.g., ampicillin, neomycin). PMID:7698081

PEGylated Red-Emitting Calcium Probe with Improved Sensing Properties for Neuroscience.

PubMed

Ponsot, Flavien; Shen, Weida; Ashokkumar, Pichandi; Audinat, Etienne; Klymchenko, Andrey S; Collot, Mayeul

2017-11-22

Monitoring calcium concentration in the cytosol is of main importance as this ion drives many biological cascades within the cell. To this end, molecular calcium probes are widely used. Most of them, especially the red emitting probes, suffer from nonspecific interactions with inner membranes due to the hydrophobic nature of their fluorophore. To circumvent this issue, calcium probes conjugated to dextran can be used to enhance the hydrophilicity and reduce the nonspecific interaction and compartmentalization. However, dextran conjugates also feature important drawbacks including lower affinity, lower dynamic range, and slow diffusion. Herein, we combined the advantage of molecular probes and dextran conjugate without their drawbacks by designing a new red emitting turn-on calcium probe based on PET quenching, Rhod-PEG, in which the rhodamine fluorophore bears four PEG 4 units. This modification led to a high affinity calcium probe (K d = 748 nM) with reduced nonspecific interactions, enhanced photostability, two-photon absorbance, and brightness compared to the commercially available Rhod-2. After spectral characterizations, we showed that Rhod-PEG quickly and efficiently diffused through the dendrites of pyramidal neurons with an enhanced sensitivity (ΔF/F 0 ) at shorter time after patching compared to Rhod-2.

Bioassay using blocking temperature: Interparticle interactions between biofunctionalized magnetic nanoparticles conjugated with biotargets

NASA Astrophysics Data System (ADS)

Wang, C. Y.; Yang, T. W.; Shen, D.; Chen, K. L.; Chen, J. M.; Liao, S. H.; Chieh, J. J.; Yang, H. C.; Wang, L. M.

2017-03-01

This paper reports a bioassay of alpha-fetoprotein (AFP) concentration achieved via the measurement of blocking temperature (TB). Biofunctionalized magnetic nanoparticles (BMNs) consisting of anti-alpha-fetoprotein coated onto dextran-coated magnetic nanoparticles composed of Fe3O4 were prepared and then conjugated with AFP biotargets. It was found that both the saturation magnetization and value of TB increased with the concentration of the associated AFP. Furthermore, the dependence of TB of the samples on magnetic field agreed with the interparticle interaction model. Thus, this study demonstrated a platform to detect biomarkers by characterizing TB with a sensitivity limit of 20 ppb of AFP. The promising results obtained for this bioassay can be attributed to the interparticle interactions and Néel motions of magnetic moments in the BMNs.

Integrated circuits based on conjugated polymer monolayer

DOE PAGES

Li, Mengmeng; Mangalore, Deepthi Kamath; Zhao, Jingbo; ...

2018-01-31

It is still a great challenge to fabricate conjugated polymer monolayer field-effect transistors (PoM-FETs) due to intricate crystallization and film formation of conjugated polymers. Here we demonstrate PoM-FETs based on a single monolayer of a conjugated polymer. The resulting PoM-FETs are highly reproducible and exhibit charge carrier mobilities reaching 3 cm 2 V -1 s -1. The high performance is attributed to the strong interactions of the polymer chains present already in solution leading to pronounced edge-on packing and well-defined microstructure in the monolayer. The high reproducibility enables the integration of discrete unipolar PoM-FETs into inverters and ring oscillators. Realmore » logic functionality has been demonstrated by constructing a 15-bit code generator in which hundreds of self-assembled PoM-FETs are addressed simultaneously. Lastly, our results provide the state-of-the-art example of integrated circuits based on a conjugated polymer monolayer, opening prospective pathways for bottom-up organic electronics.« less

Integrated circuits based on conjugated polymer monolayer

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

Li, Mengmeng; Mangalore, Deepthi Kamath; Zhao, Jingbo

It is still a great challenge to fabricate conjugated polymer monolayer field-effect transistors (PoM-FETs) due to intricate crystallization and film formation of conjugated polymers. Here we demonstrate PoM-FETs based on a single monolayer of a conjugated polymer. The resulting PoM-FETs are highly reproducible and exhibit charge carrier mobilities reaching 3 cm 2 V -1 s -1. The high performance is attributed to the strong interactions of the polymer chains present already in solution leading to pronounced edge-on packing and well-defined microstructure in the monolayer. The high reproducibility enables the integration of discrete unipolar PoM-FETs into inverters and ring oscillators. Realmore » logic functionality has been demonstrated by constructing a 15-bit code generator in which hundreds of self-assembled PoM-FETs are addressed simultaneously. Lastly, our results provide the state-of-the-art example of integrated circuits based on a conjugated polymer monolayer, opening prospective pathways for bottom-up organic electronics.« less

Integrated circuits based on conjugated polymer monolayer.

PubMed

Li, Mengmeng; Mangalore, Deepthi Kamath; Zhao, Jingbo; Carpenter, Joshua H; Yan, Hongping; Ade, Harald; Yan, He; Müllen, Klaus; Blom, Paul W M; Pisula, Wojciech; de Leeuw, Dago M; Asadi, Kamal

2018-01-31

It is still a great challenge to fabricate conjugated polymer monolayer field-effect transistors (PoM-FETs) due to intricate crystallization and film formation of conjugated polymers. Here we demonstrate PoM-FETs based on a single monolayer of a conjugated polymer. The resulting PoM-FETs are highly reproducible and exhibit charge carrier mobilities reaching 3 cm 2  V -1  s -1 . The high performance is attributed to the strong interactions of the polymer chains present already in solution leading to pronounced edge-on packing and well-defined microstructure in the monolayer. The high reproducibility enables the integration of discrete unipolar PoM-FETs into inverters and ring oscillators. Real logic functionality has been demonstrated by constructing a 15-bit code generator in which hundreds of self-assembled PoM-FETs are addressed simultaneously. Our results provide the state-of-the-art example of integrated circuits based on a conjugated polymer monolayer, opening prospective pathways for bottom-up organic electronics.

Variability in Word Duration as a Function of Probability, Speech Style, and Prosody

PubMed Central

Baker, Rachel E.; Bradlow, Ann R.

2010-01-01

This article examines how probability (lexical frequency and previous mention), speech style, and prosody affect word duration, and how these factors interact. Participants read controlled materials in clear and plain speech styles. As expected, more probable words (higher frequencies and second mentions) were significantly shorter than less probable words, and words in plain speech were significantly shorter than those in clear speech. Interestingly, we found second mention reduction effects in both clear and plain speech, indicating that while clear speech is hyper-articulated, this hyper-articulation does not override probabilistic effects on duration. We also found an interaction between mention and frequency, but only in plain speech. High frequency words allowed more second mention reduction than low frequency words in plain speech, revealing a tendency to hypo-articulate as much as possible when all factors support it. Finally, we found that first mentions were more likely to be accented than second mentions. However, when these differences in accent likelihood were controlled, a significant second mention reduction effect remained. This supports the concept of a direct link between probability and duration, rather than a relationship solely mediated by prosodic prominence. PMID:20121039

Biosensors from conjugated polyelectrolyte complexes

PubMed Central

Wang, Deli; Gong, Xiong; Heeger, Peter S.; Rininsland, Frauke; Bazan, Guillermo C.; Heeger, Alan J.

2002-01-01

A charge neutral complex (CNC) was formed in aqueous solution by combining an orange light emitting anionic conjugated polyelectrolyte and a saturated cationic polyelectrolyte at a 1:1 ratio (per repeat unit). Photoluminescence (PL) from the CNC can be quenched by both the negatively charged dinitrophenol (DNP) derivative, (DNP-BS−), and positively charged methyl viologen (MV2+). Use of the CNC minimizes nonspecific interactions (which modify the PL) between conjugated polyelectrolytes and biopolymers. Quenching of the PL from the CNC by the DNP derivative and specific unquenching on addition of anti-DNP antibody (anti-DNP IgG) were observed. Thus, biosensing of the anti-DNP IgG was demonstrated. PMID:11756675

A smart bioconjugate of alginate and pectinase with unusual biological activity toward chitosan.

PubMed

Sardar, Meryam; Roy, Ipsita; Gupta, Munishwar N

2003-01-01

The commercial preparation of pectinase (Pectinex Ultra SP-L) was conjugated to alginate by noncovalent interactions by employing 1% alginate during the conjugation protocol. The optimum "immobilization efficiency" was 0.76. The pH optimum and the thermal stability of the enzyme remained unchanged upon conjugation with alginate. The soluble bioconjugate showed a 3-fold increase in V(max)/K(m) as compared to the free enzyme when the smart biocatalyst was used for chitosan hydrolysis. Time course hydrolysis of chitosan thus showed higher conversion of chitosan into reducing oligosaccharides/sugars. The smart bioconjugate could be reused five times without any detectable loss of chitosanase activity.

Isolated dorsal root ganglion neurones inhibit receptor-dependent adenylyl cyclase activity in associated glial cells

PubMed Central

Ng, KY; Yeung, BHS; Wong, YH; Wise, H

2013-01-01

Background and Purpose Hyper-nociceptive PGE2 EP4 receptors and prostacyclin (IP) receptors are present in adult rat dorsal root ganglion (DRG) neurones and glial cells in culture. The present study has investigated the cell-specific expression of two other Gs-protein coupled hyper-nociceptive receptor systems: β-adrenoceptors and calcitonin gene-related peptide (CGRP) receptors in isolated DRG cells and has examined the influence of neurone–glial cell interactions in regulating adenylyl cyclase (AC) activity. Experimental Approach Agonist-stimulated AC activity was determined in mixed DRG cell cultures from adult rats and compared with activity in DRG neurone-enriched cell cultures and pure DRG glial cell cultures. Key Results Pharmacological analysis showed the presence of Gs-coupled β2-adrenoceptors and CGRP receptors, but not β1-adrenoceptors, in all three DRG cell preparations. Agonist-stimulated AC activity was weakest in DRG neurone-enriched cell cultures. DRG neurones inhibited IP receptor-stimulated glial cell AC activity by a process dependent on both cell–cell contact and neurone-derived soluble factors, but this is unlikely to involve purine or glutamine receptor activation. Conclusions and Implications Gs-coupled hyper-nociceptive receptors are readily expressed on DRG glial cells in isolated cell cultures and the activity of CGRP, EP4 and IP receptors, but not β2-adrenoceptors, in glial cells is inhibited by DRG neurones. Studies using isolated DRG cells should be aware that hyper-nociceptive ligands may stimulate receptors on glial cells in addition to neurones, and that variable numbers of neurones and glial cells will influence absolute measures of AC activity and affect downstream functional responses. PMID:22924655

On the Representation of Subgrid Microtopography Effects in Process-based Hydrologic Models

NASA Astrophysics Data System (ADS)

Jan, A.; Painter, S. L.; Coon, E. T.

2017-12-01

Increased availability of high-resolution digital elevation are enabling process-based hydrologic modeling on finer and finer scales. However, spatial variability in surface elevation (microtopography) exists below the scale of a typical hyper-resolution grid cell and has the potential to play a significant role in water retention, runoff, and surface/subsurface interactions. Though the concept of microtopographic features (depressions, obstructions) and the associated implications on flow and discharge are well established, representing those effects in watershed-scale integrated surface/subsurface hydrology models remains a challenge. Using the complex and coupled hydrologic environment of the Arctic polygonal tundra as an example, we study the effects of submeter topography and present a subgrid model parameterized by small-scale spatial heterogeneities for use in hyper-resolution models with polygons at a scale of 15-20 meters forming the surface cells. The subgrid model alters the flow and storage terms in the diffusion wave equation for surface flow. We compare our results against sub-meter scale simulations (acts as a benchmark for our simulations) and hyper-resolution models without the subgrid representation. The initiation of runoff in the fine-scale simulations is delayed and the recession curve is slowed relative to simulated runoff using the hyper-resolution model with no subgrid representation. Our subgrid modeling approach improves the representation of runoff and water retention relative to models that ignore subgrid topography. We evaluate different strategies for parameterizing subgrid model and present a classification-based method to efficiently move forward to larger landscapes. This work was supported by the Interoperable Design of Extreme-scale Application Software (IDEAS) project and the Next-Generation Ecosystem Experiments-Arctic (NGEE Arctic) project. NGEE-Arctic is supported by the Office of Biological and Environmental Research in the DOE Office of Science.

Observing and preventing rubidium runaway in a direct-infusion xenon-spin hyperpolarizer optimized for high-resolution hyper-CEST (chemical exchange saturation transfer using hyperpolarized nuclei) NMR.

PubMed

Witte, C; Kunth, M; Rossella, F; Schröder, L

2014-02-28

Xenon is well known to undergo host-guest interactions with proteins and synthetic molecules. As xenon can also be hyperpolarized by spin exchange optical pumping, allowing the investigation of highly dilute systems, it makes an ideal nuclear magnetic resonance probe for such host molecules. The utility of xenon as a probe can be further improved using Chemical Exchange Saturation Transfer using hyperpolarized nuclei (Hyper-CEST), but for highly accurate experiments requires a polarizer and xenon infusion system optimized for such measurements. We present the design of a hyperpolarizer and xenon infusion system specifically designed to meet the requirements of Hyper-CEST measurements. One key element of this design is preventing rubidium runaway, a chain reaction induced by laser heating that prevents efficient utilization of high photon densities. Using thermocouples positioned along the pumping cell we identify the sources of heating and conditions for rubidium runaway to occur. We then demonstrate the effectiveness of actively cooling the optical cell to prevent rubidium runaway in a compact setup. This results in a 2-3-fold higher polarization than without cooling, allowing us to achieve a polarization of 25% at continuous flow rates of 9 ml/min of (129)Xe. The simplicity of this design also allows it to be retrofitted to many existing polarizers. Combined with a direction infusion system that reduces shot-to-shot noise down to 0.56% we have captured Hyper-CEST spectra in unprecedented detail, allowing us to completely resolve peaks separated by just 1.62 ppm. Due to its high polarization and excellent stability, our design allows the comparison of underlying theories of host-guest systems with experiment at low concentrations, something extremely difficult with previous polarizers.

Synthesis and study of antibacterial activities of antibacterial glycopeptide antibiotics conjugated with benzoxaboroles.

PubMed

Printsevskaya, S S; Reznikova, M I; Korolev, A M; Lapa, G B; Olsufyeva, E N; Preobrazhenskaya, M N; Plattner, J J; Zhang, Y K

2013-04-01

The ability of boron-containing compounds to undergo a number of novel binding interactions with drug target functional groups has recently been described. In an extension of this work, we have incorporated a boron-containing scaffold, the benzoxaborole, into several glycopeptides antibiotics. The aim of this work is to exploit the inherent reactivity of boron to gain additional interactions with the bacterial cell wall components to improve binding affinity and to thereby overcome resistance. Three antibacterial glycopeptides (vancomycin, eremomycin and teicoplanin aglycone) have been selected for the construction of a series of 12 new benzoxaborole-glycopeptide conjugates. The hybrid antibiotics, in which the benzoxaborole and glycopeptide moieties were separated by a linker, exhibited excellent antibacterial activity against Gram-positive bacteria, including those with intermediate susceptibility to glycopeptides. Some analogs also demonstrated activity against vancomycin-resistant enterococci. Conjugation of antibiotics with benzoxaborole derivatives provides antibiotics with new and useful properties. Teicoplanin aglycone-benzoxaborole derivatives overcome resistance of Gram-positive bacteria to vancomycin.

Characterization of biomolecular nanoconjugates by high-throughput delivery and spectroscopic difference

PubMed Central

DeLong, Robert K; Risor, Azure; Kanomata, Masaaki; Laymon, Amanda; Jones, Brooke; Zimmerman, Scott D; Williams, Joseph; Witkowski, Colette; Warner, Mathew; Ruff, Michael; Garrad, Richard; Fallon, John K; Hickey, Anthony J; Sedaghat-Herati, Reza

2013-01-01

Aims Nanoparticle conjugates have the potential for delivering siRNA, splice-shifting oligomers or nucleic acid vaccines, and can be applicable to anticancer therapeutics. This article compares tripartite conjugates with gold nanoparticles or synthetic methoxypoly(ethylene glycol)-block-polyamidoamine dendrimers. Materials & methods Interactions with model liposomes of a 1:1 molar ratio of tripalmitin:cholesterol or phospholipid:cholesterol were investigated by high-throughput absorbance, as well as fluorescence difference and cellular luminescence assays. Results Spectral differences and dynamic light-scattering spectroscopy shifts demonstrated the interaction of conjugates with liposomes. Biological activity was demonstrated by upregulation of gene expression via splice-shifting oligomers, delivery of anti-B-Raf siRNA in cultured human cancer cells or tuberculosis antigen 85B plasmid expression vector in a coculture model of antigen presentation. Conclusion The data suggests that gold nanoparticles and methoxypoly(ethylene glycol)-block-polyamidoamine dendrimer nanoconjugates may have potential for binding, stabilization and delivery of splice-shifting oligomers, siRNA and nucleic acid vaccines for preclinical trials. PMID:22943129

Modified kinetics of enzymes interacting with nanoparticles

NASA Astrophysics Data System (ADS)

Díaz, Sebastián. A.; Breger, Joyce C.; Malanoski, Anthony; Claussen, Jonathan C.; Walper, Scott A.; Ancona, Mario G.; Brown, Carl W.; Stewart, Michael H.; Oh, Eunkeu; Susumu, Kimihiro; Medintz, Igor L.

2015-08-01

Enzymes are important players in multiple applications, be it bioremediation, biosynthesis, or as reporters. The business of catalysis and inhibition of enzymes is a multibillion dollar industry and understanding the kinetics of commercial enzymes can have a large impact on how these systems are optimized. Recent advances in nanotechnology have opened up the field of nanoparticle (NP) and enzyme conjugates and two principal architectures for NP conjugate systems have been developed. In the first example the enzyme is bound to the NP in a persistent manner, here we find that key factors such as directed enzyme conjugation allow for enhanced kinetics. Through controlled comparative experiments we begin to tease out specific mechanisms that may account for the enhancement. The second system is based on dynamic interactions of the enzymes with the NP. The enzyme substrate is bound to the NP and the enzyme is free in solution. Here again we find that there are many variables , such as substrate positioning and NP selection, that modify the kinetics.

Controlling photophysical properties of ultrasmall conjugated polymer nanoparticles through polymer chain packing

PubMed Central

Piwoński, Hubert; Michinobu, Tsuyoshi; Habuchi, Satoshi

2017-01-01

Applications of conjugated polymer nanoparticles (Pdots) for imaging and sensing depend on their size, fluorescence brightness and intraparticle energy transfer. The molecular design of conjugated polymers (CPs) has been the main focus of the development of Pdots. Here we demonstrate that proper control of the physical interactions between the chains is as critical as the molecular design. The unique design of twisted CPs and fine-tuning of the reprecipitation conditions allow us to fabricate ultrasmall (3.0–4.5 nm) Pdots with excellent photostability. Extensive photophysical and structural characterization reveals the essential role played by the packing of the polymer chains in the particles in the intraparticle spatial alignment of the emitting sites, which regulate the fluorescence brightness and the intraparticle energy migration efficiency. Our findings enhance understanding of the relationship between chain interactions and the photophysical properties of CP nanomaterials, providing a framework for designing and fabricating functional Pdots for imaging applications. PMID:28508857

Probing the recognition surface of a DNA triplex: binding studies with intercalator-neomycin conjugates.

PubMed

Xue, Liang; Xi, Hongjuan; Kumar, Sunil; Gray, David; Davis, Erik; Hamilton, Paris; Skriba, Michael; Arya, Dev P

2010-07-06

Thermodynamic studies on the interactions between intercalator-neomycin conjugates and a DNA polynucleotide triplex [poly(dA).2poly(dT)] were conducted. To draw a complete picture of such interactions, naphthalene diimide-neomycin (3) and anthraquinone-neomycin (4) conjugates were synthesized and used together with two other analogues, previously synthesized pyrene-neomycin (1) and BQQ-neomycin (2) conjugates, in our investigations. A combination of experiments, including UV denaturation, circular dichroism (CD) titration, differential scanning calorimetry (DSC), and isothermal titration calorimetry (ITC), revealed that all four conjugates (1-4) stabilized poly(dA).2poly(dT) much more than its parent compound, neomycin. UV melting experiments clearly showed that the temperature (T(m3-->2)) at which poly(dA).2poly(dT) dissociated into poly(dA).poly(dT) and poly(dT) increased dramatically (>12 degrees C) in the presence of intercalator-neomycin conjugates (1-4) even at a very low concentration (2 muM). In contrast to intercalator-neomycin conjugates, the increment of T(m3-->2) of poly(dA).2poly(dT) induced by neomycin was negligible under the same conditions. The binding preference of intercalator-neomycin conjugates (1-4) to poly(dA).2poly(dT) was also confirmed by competition dialysis and a fluorescent intercalator displacement assay. Circular dichroism titration studies revealed that compounds 1-4 had slightly larger binding site size ( approximately 7-7.5) with poly(dA).2poly(dT) as compared to neomycin ( approximately 6.5). The thermodynamic parameters of these intercalator-neomycin conjugates with poly(dA).2poly(dT) were derived from an integrated van't Hoff equation using the T(m3-->2) values, the binding site size numbers, and other parameters obtained from DSC and ITC. The binding affinity of all tested ligands with poly(dA).2poly(dT) increased in the following order: neomycin < 1 < 3 < 4 < 2. Among them, the binding constant [(2.7 +/- 0.3) x 10(8) M(-1)] of 2 with poly(dA).2poly(dT) was the highest, almost 1000-fold greater than that of neomycin. The binding of compounds 1-4 with poly(dA).2poly(dT) was mostly enthalpy-driven and gave negative DeltaC(p) values. The results described here suggest that the binding affinity of intercalator-neomycin conjugates for poly(dA).2poly(dT) increases as a function of the surface area of the intercalator moiety.

Infrared length scale and extrapolations for the no-core shell model

DOE PAGES

Wendt, K. A.; Forssén, C.; Papenbrock, T.; ...

2015-06-03

In this paper, we precisely determine the infrared (IR) length scale of the no-core shell model (NCSM). In the NCSM, the A-body Hilbert space is truncated by the total energy, and the IR length can be determined by equating the intrinsic kinetic energy of A nucleons in the NCSM space to that of A nucleons in a 3(A-1)-dimensional hyper-radial well with a Dirichlet boundary condition for the hyper radius. We demonstrate that this procedure indeed yields a very precise IR length by performing large-scale NCSM calculations for 6Li. We apply our result and perform accurate IR extrapolations for bound statesmore » of 4He, 6He, 6Li, and 7Li. Finally, we also attempt to extrapolate NCSM results for 10B and 16O with bare interactions from chiral effective field theory over tens of MeV.« less

The on-site quality-assurance system for Hyper Suprime-Cam: OSQAH

NASA Astrophysics Data System (ADS)

Furusawa, Hisanori; Koike, Michitaro; Takata, Tadafumi; Okura, Yuki; Miyatake, Hironao; Lupton, Robert H.; Bickerton, Steven; Price, Paul A.; Bosch, James; Yasuda, Naoki; Mineo, Sogo; Yamada, Yoshihiko; Miyazaki, Satoshi; Nakata, Fumiaki; Koshida, Shintaro; Komiyama, Yutaka; Utsumi, Yousuke; Kawanomoto, Satoshi; Jeschke, Eric; Noumaru, Junichi; Schubert, Kiaina; Iwata, Ikuru; Finet, Francois; Fujiyoshi, Takuya; Tajitsu, Akito; Terai, Tsuyoshi; Lee, Chien-Hsiu

2018-01-01

We have developed an automated quick data analysis system for data quality assurance (QA) for Hyper Suprime-Cam (HSC). The system was commissioned in 2012-2014, and has been offered for general observations, including the HSC Subaru Strategic Program, since 2014 March. The system provides observers with data quality information, such as seeing, sky background level, and sky transparency, based on quick analysis as data are acquired. Quick-look images and validation of image focus are also provided through an interactive web application. The system is responsible for the automatic extraction of QA information from acquired raw data into a database, to assist with observation planning, assess progress of all observing programs, and monitor long-term efficiency variations of the instrument and telescope. Enhancements of the system are being planned to facilitate final data analysis, to improve the HSC archive, and to provide legacy products for astronomical communities.

Enhanced emotion-induced amnesia in borderline personality disorder

PubMed Central

HURLEMANN, RENÉ; HAWELLEK, BARBARA; MAIER, WOLFGANG; DOLAN, RAYMOND J.

2009-01-01

Background Current biological concepts of borderline personality disorder (BPD) emphasize the interference of emotional hyperarousal and cognitive functions. A prototypical example is episodic memory. Pre-clinical investigations of emotion–episodic memory interactions have shown specific retrograde and anterograde episodic memory changes in response to emotional stimuli. These changes are amygdala dependent and vary as a function of emotional arousal and valence. Method To determine whether there is amygdala hyper-responsiveness to emotional stimuli as the underlying pathological substrate of cognitive dysfunction in BPD, 16 unmedicated female patients with BPD were tested on the behavioural indices of emotion-induced amnesia and hypermnesia established in 16 healthy controls. Results BPD patients displayed enhanced retrograde and anterograde amnesia in response to presentation of negative stimuli, while positive stimuli elicited no episodic memory-modulating effects. Conclusion These findings suggest that an amygdala hyper-responsiveness to negative stimuli may serve as a crucial aetiological contributor to emotion-induced cognitive dysfunction in BPD. PMID:17224096

Use of spring-roll EAP actuator applied as end-effector of a hyper-redundant robot

NASA Astrophysics Data System (ADS)

Errico, Gianmarco; Fava, Victor; Resta, Ferruccio; Ripamonti, Francesco

2015-04-01

This paper presents a hyper-redundant continuous robot used to perform work in places which humans can not reach. This type of robot is generally a bio-inspired solution, it is composed by a lot of flexible segments driven by multiple actuators and its dynamics is described by a lot degrees of freedom. In this paper a model composed of some rigid links connected to each other by revolution joint is presented. In each link a torsional spring is added in order to simulate the resistant torque between the links and the interactions among the cables and the robot during the relative rotation. Moreover a type of EAP actuator, called spring roll, is used as the end-effector of the robot. Through a suitable sensor, such as a camera, the spring roll allows to track a target and it closes the control loop on the robot to follow it.

High-Power, High-Intensity Laser Propagation and Interactions

DTIC Science & Technology

2014-03-10

wave Brillouin mixing [89,90]. transmitted beam is phase conjugated target initial wave front nn  1 turbulent air Figure 14. Using phase and...discussed in connection with both high-power and high-intensity lasers is propagation in a turbulent atmosphere . Laser propagation in atmospheric ... turbulence can results in beam centroid wander, spreading and intensity scintillation. A phase conjugation technique to mitigate the effects of atmospheric

4D Hyperspherical Harmonic (HyperSPHARM) Representation of Surface Anatomy: A Holistic Treatment of Multiple Disconnected Anatomical Structures

PubMed Central

Hosseinbor, A. Pasha; Chung, Moo K.; Koay, Cheng Guan; Schaefer, Stacey M.; van Reekum, Carien M.; Schmitz, Lara Peschke; Sutterer, Matt; Alexander, Andrew L.; Davidson, Richard J.

2015-01-01

Image-based parcellation of the brain often leads to multiple disconnected anatomical structures, which pose significant challenges for analyses of morphological shapes. Existing shape models, such as the widely used spherical harmonic (SPHARM) representation, assume topological invariance, so are unable to simultaneously parameterize multiple disjoint structures. In such a situation, SPHARM has to be applied separately to each individual structure. We present a novel surface parameterization technique using 4D hyperspherical harmonics in representing multiple disjoint objects as a single analytic function, terming it HyperSPHARM. The underlying idea behind Hyper-SPHARM is to stereographically project an entire collection of disjoint 3D objects onto the 4D hypersphere and subsequently simultaneously parameterize them with the 4D hyperspherical harmonics. Hence, HyperSPHARM allows for a holistic treatment of multiple disjoint objects, unlike SPHARM. In an imaging dataset of healthy adult human brains, we apply HyperSPHARM to the hippocampi and amygdalae. The HyperSPHARM representations are employed as a data smoothing technique, while the HyperSPHARM coefficients are utilized in a support vector machine setting for object classification. HyperSPHARM yields nearly identical results as SPHARM, as will be shown in the paper. Its key advantage over SPHARM lies computationally; Hyper-SPHARM possess greater computational efficiency than SPHARM because it can parameterize multiple disjoint structures using much fewer basis functions and stereographic projection obviates SPHARM's burdensome surface flattening. In addition, HyperSPHARM can handle any type of topology, unlike SPHARM, whose analysis is confined to topologically invariant structures. PMID:25828650

Role of a non-canonical surface of Rad6 in ubiquitin conjugating activity

PubMed Central

Kumar, Pankaj; Magala, Pearl; Geiger-Schuller, Kathryn R.; Majumdar, Ananya; Tolman, Joel R.; Wolberger, Cynthia

2015-01-01

Rad6 is a yeast E2 ubiquitin conjugating enzyme that monoubiquitinates histone H2B in conjunction with the E3, Bre1, but can non-specifically modify histones on its own. We determined the crystal structure of a Rad6∼Ub thioester mimic, which revealed a network of interactions in the crystal in which the ubiquitin in one conjugate contacts Rad6 in another. The region of Rad6 contacted is located on the distal face of Rad6 opposite the active site, but differs from the canonical E2 backside that mediates free ubiquitin binding and polyubiquitination activity in other E2 enzymes. We find that free ubiquitin interacts weakly with both non-canonical and canonical backside residues of Rad6 and that mutations of non-canonical residues have deleterious effects on Rad6 activity comparable to those observed to mutations in the canonical E2 backside. The effect of non-canonical backside mutations is similar in the presence and absence of Bre1, indicating that contacts with non-canonical backside residues govern the intrinsic activity of Rad6. Our findings shed light on the determinants of intrinsic Rad6 activity and reveal new ways in which contacts with an E2 backside can regulate ubiquitin conjugating activity. PMID:26286193

Next generation calmodulin affinity purification: Clickable calmodulin facilitates improved protein purification

PubMed Central

Kinzer-Ursem, Tamara L.

2018-01-01

As the proteomics field continues to expand, scientists are looking to integrate cross-disciplinary tools for studying protein structure, function, and interactions. Protein purification remains a key tool for many characterization studies. Calmodulin (CaM) is a calcium-binding messenger protein with over a hundred downstream binding partners, and is involved in a host of physiological processes, from learning and memory to immune and cardiac function. To facilitate biophysical studies of calmodulin, researchers have designed a site-specific labeling process for use in bioconjugation applications while maintaining high levels of protein activity. Here, we present a platform for selective conjugation of calmodulin directly from clarified cell lysates under bioorthogonal reaction conditions. Using a chemoenzymatically modified calmodulin, we employ popular click chemistry reactions for the conjugation of calmodulin to Sepharose resin, thereby streamlining a previously multi-step purification and conjugation process. We show that this “next-generation” calmodulin-Sepharose resin is not only easy to produce, but is also able to purify more calmodulin-binding proteins per volume of resin than traditional calmodulin-Sepharose resins. We expect these methods to be translatable to other proteins of interest and to other conjugation applications such as surface-based assays for the characterization of protein-protein interaction dynamics. PMID:29864125

Electrochemical activity evaluation of chemically damaged carbon nanotube with palladium nanoparticles for ethanol oxidation

NASA Astrophysics Data System (ADS)

Ahmed, Mohammad Shamsuddin; Jeon, Seungwon

2015-05-01

The carbon nanotube (CNT) has unique electrical and structural properties due to it's sp2 π-conjugative structure that leads to the higher electrocatalysis. The π-conjugative structure, that allows the CNT interact with various compounds and metal nanoparticles (NPs) through π-π electronic interaction. However, the damage of π-conjugative sidewall of CNT that can be hinder the electrocatalytic activity has found. For this study, the CNT, as base material, has been prepared through a conventional acid treatment method up to 15 h; the higher degree of sidewall damage has been observed in last 5 h during treatment period. The short and long term acid treated (denoted as CNT and CNT-COOH, respectively) CNTs have been subsequently fabricated with palladium NPs (denoted as CNT/Pd and CNT-Pd, respectively) and employed as ethanol oxidation reaction (EOR) catalysts. The CNT-Pd displays a poor electrocatalytic performance towards EOR than that of CNT/Pd due to the damage of π-conjugative sidewall. The kinetic parameters including poisoning tolerance have also been hampered by the surface damage. The CNT/Pd (∼3.3 folds) and CNT-Pd (∼1.5 folds) are express higher electrocatalytic activity and poisoning tolerance than that of Pd/C while Pd mass loading remains in the same amount.

Split2 Protein-Ligation Generates Active IL-6-Type Hyper-Cytokines from Inactive Precursors.

PubMed

Moll, Jens M; Wehmöller, Melanie; Frank, Nils C; Homey, Lisa; Baran, Paul; Garbers, Christoph; Lamertz, Larissa; Axelrod, Jonathan H; Galun, Eithan; Mootz, Henning D; Scheller, Jürgen

2017-12-15

Trans-signaling of the major pro- and anti-inflammatory cytokines Interleukin (IL)-6 and IL-11 has the unique feature to virtually activate all cells of the body and is critically involved in chronic inflammation and regeneration. Hyper-IL-6 and Hyper-IL-11 are single chain designer trans-signaling cytokines, in which the cytokine and soluble receptor units are trapped in one complex via a flexible peptide linker. Albeit, Hyper-cytokines are essential tools to study trans-signaling in vitro and in vivo, the superior potency of these designer cytokines are accompanied by undesirable stress responses. To enable tailor-made generation of Hyper-cytokines, we developed inactive split-cytokine-precursors adapted for posttranslational reassembly by split-intein mediated protein trans-splicing (PTS). We identified cutting sites within IL-6 (E 134 /S 135 ) and IL-11 (G 116 /S 117 ) and obtained inactive split-Hyper-IL-6 and split-Hyper-IL-11 cytokine precursors. After fusion with split-inteins, PTS resulted in reconstitution of active Hyper-cytokines, which were efficiently secreted from transfected cells. Our strategy comprises the development of a background-free cytokine signaling system from reversibly inactivated precursor cytokines.

Novel coumarin modified GLP-1 derivatives with enhanced plasma stability and prolonged in vivo glucose-lowering ability.

PubMed

Han, Jing; Sun, Lidan; Huang, Xun; Li, Zheng; Zhang, Chenyu; Qian, Hai; Huang, Wenlong

2014-12-01

The short biological half-life limits the therapeutic use of glucagon-like peptide-1 (GLP-1) and chemical modification to improve the interaction of peptides with serum albumin represents an effective strategy to develop long-acting peptide analogues. Coumarin, a natural product, is known to bind tightly to plasma proteins and possesses many biological activities. Therefore, we designed and synthesized a series of coumarin-modified GLP-1 derivatives, hypothesizing that conjugation with coumarin would retain the therapeutic effects and prolong the biological half-life of the conjugates. Four cysteine-modified GLP-1 analogues (1-4) were prepared using Gly8 -GLP-1(7-36)-NH2 peptide as a starting point. These analogues were conjugated with two coumarin maleimides to yield eight compounds (conjugates 6-13) for testing. Activation of human GLP-1 receptors, stability to enzymic inactivation in plasma and binding to human albumin were assessed in vitro. In vivo, effects on oral glucose tolerance tests (OGTT) in rats and on blood glucose levels in db/db mice were studied. Most conjugates showed well preserved receptor activation efficacy, enhanced albumin-binding properties and improved in vitro plasma stability and conjugate 7 was selected to undergo further assessment. In rats, conjugate 7 had a longer circulating t1/2 than exendin-4 or liraglutide. A prolonged antidiabetic effect of conjugate 7 was observed after OGTT in rats and a prolonged hypoglycaemic effect in db/db mice. Cysteine-specific coumarin conjugation with GLP-1 offers a useful approach to the development of long-acting incretin-based antidiabetic agents. Conjugate 7 is a promising long-lasting GLP-1 derivative deserving further investigation. © 2014 The British Pharmacological Society.

Novel coumarin modified GLP-1 derivatives with enhanced plasma stability and prolonged in vivo glucose-lowering ability

PubMed Central

Han, Jing; Sun, Lidan; Huang, Xun; Li, Zheng; Zhang, Chenyu; Qian, Hai; Huang, Wenlong

2014-01-01

Background and Purpose The short biological half-life limits the therapeutic use of glucagon-like peptide-1 (GLP-1) and chemical modification to improve the interaction of peptides with serum albumin represents an effective strategy to develop long-acting peptide analogues. Coumarin, a natural product, is known to bind tightly to plasma proteins and possesses many biological activities. Therefore, we designed and synthesized a series of coumarin-modified GLP-1 derivatives, hypothesizing that conjugation with coumarin would retain the therapeutic effects and prolong the biological half-life of the conjugates. Experimental Approach Four cysteine-modified GLP-1 analogues (1–4) were prepared using Gly8-GLP-1(7–36)-NH2 peptide as a starting point. These analogues were conjugated with two coumarin maleimides to yield eight compounds (conjugates 6–13) for testing. Activation of human GLP-1 receptors, stability to enzymic inactivation in plasma and binding to human albumin were assessed in vitro. In vivo, effects on oral glucose tolerance tests (OGTT) in rats and on blood glucose levels in db/db mice were studied. Key Results Most conjugates showed well preserved receptor activation efficacy, enhanced albumin-binding properties and improved in vitro plasma stability and conjugate 7 was selected to undergo further assessment. In rats, conjugate 7 had a longer circulating t1/2 than exendin-4 or liraglutide. A prolonged antidiabetic effect of conjugate 7 was observed after OGTT in rats and a prolonged hypoglycaemic effect in db/db mice. Conclusions and Implications Cysteine-specific coumarin conjugation with GLP-1 offers a useful approach to the development of long-acting incretin-based antidiabetic agents. Conjugate 7 is a promising long-lasting GLP-1 derivative deserving further investigation. PMID:25039358

Multivalent ligands control stem cell behaviour in vitro and in vivo

NASA Astrophysics Data System (ADS)

Conway, Anthony; Vazin, Tandis; Spelke, Dawn P.; Rode, Nikhil A.; Healy, Kevin E.; Kane, Ravi S.; Schaffer, David V.

2013-11-01

There is broad interest in designing nanostructured materials that can interact with cells and regulate key downstream functions. In particular, materials with nanoscale features may enable control over multivalent interactions, which involve the simultaneous binding of multiple ligands on one entity to multiple receptors on another and are ubiquitous throughout biology. Cellular signal transduction of growth factor and morphogen cues (which have critical roles in regulating cell function and fate) often begins with such multivalent binding of ligands, either secreted or cell-surface-tethered to target cell receptors, leading to receptor clustering. Cellular mechanisms that orchestrate ligand-receptor oligomerization are complex, however, so the capacity to control multivalent interactions and thereby modulate key signalling events within living systems is currently very limited. Here, we demonstrate the design of potent multivalent conjugates that can organize stem cell receptors into nanoscale clusters and control stem cell behaviour in vitro and in vivo. The ectodomain of ephrin-B2, normally an integral membrane protein ligand, was conjugated to a soluble biopolymer to yield multivalent nanoscale conjugates that potently induce signalling in neural stem cells and promote their neuronal differentiation both in culture and within the brain. Super-resolution microscopy analysis yielded insights into the organization of the receptor-ligand clusters at the nanoscale. We also found that synthetic multivalent conjugates of ephrin-B1 strongly enhance human embryonic and induced pluripotent stem cell differentiation into functional dopaminergic neurons. Multivalent bioconjugates are therefore powerful tools and potential nanoscale therapeutics for controlling the behaviour of target stem cells in vitro and in vivo.

Fabrication, Characterization and Cytotoxicity of Spherical-Shaped Conjugated Gold-Cockle Shell Derived Calcium Carbonate Nanoparticles for Biomedical Applications

NASA Astrophysics Data System (ADS)

Kiranda, Hanan Karimah; Mahmud, Rozi; Abubakar, Danmaigoro; Zakaria, Zuki Abubakar

2018-01-01

The evolution of nanomaterial in science has brought about a growing increase in nanotechnology, biomedicine, and engineering fields. This study was aimed at fabrication and characterization of conjugated gold-cockle shell-derived calcium carbonate nanoparticles (Au-CSCaCO3NPs) for biomedical application. The synthetic technique employed used gold nanoparticle citrate reduction method and a simple precipitation method coupled with mechanical use of a Programmable roller-ball mill. The synthesized conjugated nanomaterial was characterized for its physicochemical properties using transmission electron microscope (TEM), field emission scanning electron microscope (FESEM) equipped with energy dispersive X-ray (EDX) and Fourier transform infrared spectroscopy (FTIR). However, the intricacy of cellular mechanisms can prove challenging for nanomaterial like Au-CSCaCO3NPs and thus, the need for cytotoxicity assessment. The obtained spherical-shaped nanoparticles (light-green purplish) have an average diameter size of 35 ± 16 nm, high carbon and oxygen composition. The conjugated nanomaterial, also possesses a unique spectra for aragonite polymorph and carboxylic bond significantly supporting interactions between conjugated nanoparticles. The negative surface charge and spectra absorbance highlighted their stability. The resultant spherical shaped conjugated Au-CSCaCO3NPs could be a great nanomaterial for biomedical applications.

A simple elution strategy for biotinylated proteins bound to streptavidin conjugated beads using excess biotin and heat.

PubMed

Cheah, Joleen S; Yamada, Soichiro

2017-12-02

Protein-protein interactions are the molecular basis of cell signaling. Recently, proximity based biotin identification (BioID) has emerged as an alternative approach to traditional co-immunoprecipitation. In this protocol, a mutant biotin ligase promiscuously labels proximal binding partners with biotin, and resulting biotinylated proteins are purified using streptavidin conjugated beads. This approach does not require preservation of protein complexes in vitro, making it an ideal approach to identify transient or weak protein complexes. However, due to the high affinity bond between streptavidin and biotin, elution of biotinylated proteins from streptavidin conjugated beads requires harsh denaturing conditions, which are often incompatible with downstream processing. To effectively release biotinylated proteins bound to streptavidin conjugated beads, we designed a series of experiments to determine optimal binding and elution conditions. Interestingly, the concentrations of SDS and IGEPAL-CA630 during the incubation with streptavidin conjugated beads were the key to effective elution of biotinylated proteins using excess biotin and heating. This protocol provides an alternative method to isolate biotinylated proteins from streptavidin conjugated beads that is suitable for further downstream analysis. Copyright © 2017 Elsevier Inc. All rights reserved.

Multivalency of Sonic hedgehog conjugated to linear polymer chains modulates protein potency.

PubMed

Wall, Samuel T; Saha, Krishanu; Ashton, Randolph S; Kam, Kimberly R; Schaffer, David V; Healy, Kevin E

2008-04-01

A potently active multivalent form of the protein Sonic hedgehog (Shh) was produced by bioconjugation of a modified recombinant form of Shh to the linear polymers poly(acrylic acid) (pAAc) and hyaluronic acid (HyA) via a two-step reaction exploiting carboimiide and maleimide chemistry. Efficiency of the conjugation was approximately 75% even at stoichiometric ratios of 30 Shh molecules per linear HyA chain (i.e., 30:1 Shh/HyA). Bioactivity of the conjugates was tested via a cellular assay across a range of stoichiometric ratios of Shh molecules to HyA linear chains, which was varied from 0.6:1 Shh/HyA to 22:1 Shh/HyA. Results indicate that low conjugation ratios decrease Shh bioactivity and high ratios increase this activity beyond the potency of monomeric Shh, with approximately equal activity between monomeric soluble Shh and conjugated Shh at 7:1 Shh/HyA. In addition, high-ratio constructs increased angiogenesis determined by the in vivo chick chorioallantoic membrane (CAM) assay. These results are captured by a kinetic model of multiple interactions between the Shh/HyA conjugates and cell surface receptors resulting in higher cell signaling at lower bulk Shh concentrations.

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

Omelchenko, Yuri A.

Global interactions of energetic ions with magnetoplasmas and neutral gases lie at the core of many space and laboratory plasma phenomena ranging from solar wind entry into and transport within planetary magnetospheres and exospheres to fast-ion driven instabilities in fusion devices to astrophysics-in-lab experiments. The ability of computational models to properly account for physical effects that underlie such interactions, namely ion kinetic, ion cyclotron, Hall, collisional and ionization processes is important for the success and planning of experimental research in plasma physics. Understanding the physics of energetic ions, in particular their nonlinear resonance interactions with Alfvén waves, is central tomore » improving the heating performance of magnetically confined plasmas for future energy generation. Fluid models are not adequate for high-beta plasmas as they cannot fully capture ion kinetic and cyclotron physics (e.g., ion behavior in the presence of magnetic nulls, shock structures, plasma interpenetration, etc.). Recent results from global reconnection simulations show that even in a MHD-like regime there may be significant differences between kinetic and MHD simulations. Therefore, kinetic modeling becomes essential for meeting modern day challenges in plasma physics. The hybrid approximation is an intermediate approximation between the fluid and fully kinetic approximations. It eliminates light waves, removes the electron inertial temporal and spatial scales from the problem and enables full-orbit ion kinetics. As a result, hybrid codes have become effective tools for exploring ion-scale driven phenomena associated with ion beams, shocks, reconnection and turbulence that control the large-scale behavior of laboratory and space magnetoplasmas. A number of numerical issues, however, make three-dimensional (3D) large-scale hybrid simulations of inhomogeneous magnetized plasmas prohibitively expensive or even impossible. To resolve these difficulties we have developed a novel Event-driven Multiscale Asynchronous Parallel Simulation (EMAPS) technology that replaces time stepping with self-adaptive update events. Local calculations are carried out only on an “as needed basis”. EMAPS (i) guarantees accurate and stable processing of physical variables in time accurate simulations, and (ii) eliminates unnecessary computation. Applying EMAPS to the hybrid model has resulted in the development of a unique parallel code, dimension-independent (compile-time-configurable) HYPERS (Hybrid Parallel Event-Resolved Simulator) that scales to hundreds of thousands of parallel processors. HYPERS advances electromagnetic fields and particles asynchronously on time scales determined by local physical laws and mesh properties. To achieve high computational accuracy in complex device geometries, HYPERS employs high-fidelity Cartesian grids with masked conductive cells. The HYPERS model includes multiple ion species, energy and momentum conserving ion-ion collisions, and provides a number of approximations for plasma resistivity and vacuum regions. Both local and periodic boundary conditions are allowed. The HYPERS solver preserves zero divergence of magnetic field. The project has demonstrated HYPERS capabilities on a number of applications of interest to fusion and astrophysical plasma physics applications listed below. 1. Theta-pinch formation of FRCs The formation, spontaneous spin-up, and stability of theta-pinch formed field-reversed configurations have been studied self-consistently in 3D. The end-to-end hybrid simulations reveal poloidal profiles of implosion-driven fast toroidal plasma rotation and demonstrate three discharge regimes as a function of experimental parameters: the decaying stable configuration, the tilt unstable configuration, and the nonlinear evolution of a fast growing tearing mode. 2. FRC collisions with magnetic mirrors Interactions of fast plasma streams and objects with magnetic obstacles (dipoles, mirrors, etc) lie at the core of many space and laboratory plasma phenomena ranging from magnetoshells and solar wind interactions with planetary magnetospheres to compact fusion plasmas. HYPERS simulations are compared with data from the MSX experiment (LANL) that focuses on the physics of magnetized collisionless shocks through the acceleration and subsequent stagnation of FRC plasmoids against a strong magnetic mirrors and flux-conserving boundaries. 3. Exploding magnetoplasmas Results from hybrid simulations of two experiments at the LAPD and Nevada Terawatt Facility are discussed where short-pulse lasers are used to ablate solid targets to produce plasmas that expand across external magnetic fields. The first simulation recreates flutelike density striations observed at the leading edge of a carbon plasma and predicts an early destruction of the magnetic cavity in agreement with experimental evidence. In the second simulation a polyethylene target is ablated into a mixture of protons and carbon ions. A mechanism is demonstrated that allows protons to penetrate the magnetic field in the form of a collimated flow. The results are compared to experimental data and single-fluid MHD simulations. The EMAPS framework has the potential for wide application in many other engineering and scientific fields, such as climate models, biological systems, electronic devices, seismic events, oil reservation simulators that all involve advancing solutions of partial differential equations in time where the rate of activity can be adapted widely over the spatial domain depending on locally space/time phenomena (“events”).« less

Role of glutathione in lung retention of 99mTc-hexamethylpropyleneamine oxime in two unique rat models of hyperoxic lung injury

PubMed Central

Roerig, David L.; Haworth, Steven T.; Clough, Anne V.

2012-01-01

Rat exposure to 60% oxygen (O2) for 7 days (hyper-60) or to >95% O2 for 2 days followed by 24 h in room air (hyper-95R) confers susceptibility or tolerance, respectively, of the otherwise lethal effects of subsequent exposure to 100% O2. The objective of this study was to determine if lung retention of the radiopharmaceutical agent technetium-labeled-hexamethylpropyleneamine oxime (HMPAO) is differentially altered in hyper-60 and hyper-95R rats. Tissue retention of HMPAO is dependent on intracellular content of the antioxidant GSH and mitochondrial function. HMPAO was injected intravenously in anesthetized rats, and planar images were acquired. We investigated the role of GSH in the lung retention of HMPAO by pretreating rats with the GSH-depleting agent diethyl maleate (DEM) prior to imaging. We also measured GSH content and activities of mitochondrial complexes I and IV in lung homogenate. The lung retention of HMPAO increased by ∼50% and ∼250% in hyper-60 and hyper-95R rats, respectively, compared with retention in rats exposed to room air (normoxic). DEM decreased retention in normoxic (∼26%) and hyper-95R (∼56%) rats compared with retention in the absence of DEM. GSH content increased by 19% and 40% in hyper-60 and hyper-95R lung homogenate compared with normoxic lung homogenate. Complex I activity decreased by ∼50% in hyper-60 and hyper-95R lung homogenate compared with activity in normoxic lung homogenate. However, complex IV activity was increased by 32% in hyper-95R lung homogenate only. Furthermore, we identified correlations between the GSH content in lung homogenate and the DEM-sensitive fraction of HMPAO retention and between the complex IV/complex I activity ratio and the DEM-insensitive fraction of HMPAO retention. These results suggest that an increase in the GSH-dependent component of the lung retention of HMPAO may be a marker of tolerance to sustained exposure to hyperoxia. PMID:22628374

Role of glutathione in lung retention of 99mTc-hexamethylpropyleneamine oxime in two unique rat models of hyperoxic lung injury.

PubMed

Audi, Said H; Roerig, David L; Haworth, Steven T; Clough, Anne V

2012-08-15

Rat exposure to 60% oxygen (O(2)) for 7 days (hyper-60) or to >95% O(2) for 2 days followed by 24 h in room air (hyper-95R) confers susceptibility or tolerance, respectively, of the otherwise lethal effects of subsequent exposure to 100% O(2). The objective of this study was to determine if lung retention of the radiopharmaceutical agent technetium-labeled-hexamethylpropyleneamine oxime (HMPAO) is differentially altered in hyper-60 and hyper-95R rats. Tissue retention of HMPAO is dependent on intracellular content of the antioxidant GSH and mitochondrial function. HMPAO was injected intravenously in anesthetized rats, and planar images were acquired. We investigated the role of GSH in the lung retention of HMPAO by pretreating rats with the GSH-depleting agent diethyl maleate (DEM) prior to imaging. We also measured GSH content and activities of mitochondrial complexes I and IV in lung homogenate. The lung retention of HMPAO increased by ≈ 50% and ≈ 250% in hyper-60 and hyper-95R rats, respectively, compared with retention in rats exposed to room air (normoxic). DEM decreased retention in normoxic (≈ 26%) and hyper-95R (≈ 56%) rats compared with retention in the absence of DEM. GSH content increased by 19% and 40% in hyper-60 and hyper-95R lung homogenate compared with normoxic lung homogenate. Complex I activity decreased by ≈ 50% in hyper-60 and hyper-95R lung homogenate compared with activity in normoxic lung homogenate. However, complex IV activity was increased by 32% in hyper-95R lung homogenate only. Furthermore, we identified correlations between the GSH content in lung homogenate and the DEM-sensitive fraction of HMPAO retention and between the complex IV/complex I activity ratio and the DEM-insensitive fraction of HMPAO retention. These results suggest that an increase in the GSH-dependent component of the lung retention of HMPAO may be a marker of tolerance to sustained exposure to hyperoxia.

Point interactions, metamaterials, and PT-symmetry

NASA Astrophysics Data System (ADS)

Mostafazadeh, Ali

2016-05-01

We express the boundary conditions for TE and TM waves at the interfaces of an infinite planar slab of homogeneous metamaterial as certain point interactions and use them to compute the transfer matrix of the system. This allows us to demonstrate the omnidirectional reflectionlessness of Veselago's slab for waves of arbitrary wavelength, reveal the translational and reflection symmetry of this slab, explore the laser threshold condition and coherent perfect absorption for active negative-index metamaterials, introduce a point interaction modeling phase-conjugation, determine the corresponding antilinear transfer matrix, and offer a simple proof of the equivalence of Veselago's slab with a pair of parallel phase-conjugating plates. We also study the connection between certain optical setups involving metamaterials and a class of PT-symmetric quantum systems defined on wedge-shape contours in the complex plane. This provides a physical interpretation for the latter.

DNA sequence-selective C8-linked pyrrolobenzodiazepine-heterocyclic polyamide conjugates show anti-tubercular-specific activities.

PubMed

Brucoli, Federico; Guzman, Juan D; Basher, Mohammad A; Evangelopoulos, Dimitrios; McMahon, Eleanor; Munshi, Tulika; McHugh, Timothy D; Fox, Keith R; Bhakta, Sanjib

2016-12-01

New chemotherapeutic agents with novel mechanisms of action are in urgent need to combat the tuberculosis pandemic. A library of 12 C8-linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD)-heterocyclic polyamide conjugates (1-12) was evaluated for anti-tubercular activity and DNA sequence selectivity. The PBD conjugates were screened against slow-growing Mycobacterium bovis Bacillus Calmette-Guérin and M. tuberculosis H 37 Rv, and fast-growing Escherichia coli, Pseudomonas putida and Rhodococcus sp. RHA1 bacteria. DNase I footprinting and DNA thermal denaturation experiments were used to determine the molecules' DNA recognition properties. The PBD conjugates were highly selective for the mycobacterial strains and exhibited significant growth inhibitory activity against the pathogenic M. tuberculosis H 37 Rv, with compound 4 showing MIC values (MIC=0.08 mg l -1 ) similar to those of rifampin and isoniazid. DNase I footprinting results showed that the PBD conjugates with three heterocyclic moieties had enhanced sequence selectivity and produced larger footprints, with distinct cleavage patterns compared with the two-heterocyclic chain PBD conjugates. DNA melting experiments indicated a covalent binding of the PBD conjugates to two AT-rich DNA-duplexes containing either a central GGATCC or GTATAC sequence, and showed that the polyamide chains affect the interactions of the molecules with DNA. The PBD-C8 conjugates tested in this study have a remarkable anti-mycobacterial activity and can be further developed as DNA-targeted anti-tubercular drugs.

Impact of topographic mask models on scanner matching solutions

NASA Astrophysics Data System (ADS)

Tyminski, Jacek K.; Pomplun, Jan; Renwick, Stephen P.

2014-03-01

Of keen interest to the IC industry are advanced computational lithography applications such as Optical Proximity Correction of IC layouts (OPC), scanner matching by optical proximity effect matching (OPEM), and Source Optimization (SO) and Source-Mask Optimization (SMO) used as advanced reticle enhancement techniques. The success of these tasks is strongly dependent on the integrity of the lithographic simulators used in computational lithography (CL) optimizers. Lithographic mask models used by these simulators are key drivers impacting the accuracy of the image predications, and as a consequence, determine the validity of these CL solutions. Much of the CL work involves Kirchhoff mask models, a.k.a. thin masks approximation, simplifying the treatment of the mask near-field images. On the other hand, imaging models for hyper-NA scanner require that the interactions of the illumination fields with the mask topography be rigorously accounted for, by numerically solving Maxwell's Equations. The simulators used to predict the image formation in the hyper-NA scanners must rigorously treat the masks topography and its interaction with the scanner illuminators. Such imaging models come at a high computational cost and pose challenging accuracy vs. compute time tradeoffs. Additional complication comes from the fact that the performance metrics used in computational lithography tasks show highly non-linear response to the optimization parameters. Finally, the number of patterns used for tasks such as OPC, OPEM, SO, or SMO range from tens to hundreds. These requirements determine the complexity and the workload of the lithography optimization tasks. The tools to build rigorous imaging optimizers based on first-principles governing imaging in scanners are available, but the quantifiable benefits they might provide are not very well understood. To quantify the performance of OPE matching solutions, we have compared the results of various imaging optimization trials obtained with Kirchhoff mask models to those obtained with rigorous models involving solutions of Maxwell's Equations. In both sets of trials, we used sets of large numbers of patterns, with specifications representative of CL tasks commonly encountered in hyper-NA imaging. In this report we present OPEM solutions based on various mask models and discuss the models' impact on hyper- NA scanner matching accuracy. We draw conclusions on the accuracy of results obtained with thin mask models vs. the topographic OPEM solutions. We present various examples representative of the scanner image matching for patterns representative of the current generation of IC designs.

Two dissimilar approaches to dynamical systems on hyper MV -algebras and their information entropy

NASA Astrophysics Data System (ADS)

Mehrpooya, Adel; Ebrahimi, Mohammad; Davvaz, Bijan

2017-09-01

Measuring the flow of information that is related to the evolution of a system which is modeled by applying a mathematical structure is of capital significance for science and usually for mathematics itself. Regarding this fact, a major issue in concern with hyperstructures is their dynamics and the complexity of the varied possible dynamics that exist over them. Notably, the dynamics and uncertainty of hyper MV -algebras which are hyperstructures and extensions of a central tool in infinite-valued Lukasiewicz propositional calculus that models many valued logics are of primary concern. Tackling this problem, in this paper we focus on the subject of dynamical systems on hyper MV -algebras and their entropy. In this respect, we adopt two varied approaches. One is the set-based approach in which hyper MV -algebra dynamical systems are developed by employing set functions and set partitions. By the other method that is based on points and point partitions, we establish the concept of hyper injective dynamical systems on hyper MV -algebras. Next, we study the notion of entropy for both kinds of systems. Furthermore, we consider essential ergodic characteristics of those systems and their entropy. In particular, we introduce the concept of isomorphic hyper injective and hyper MV -algebra dynamical systems, and we demonstrate that isomorphic systems have the same entropy. We present a couple of theorems in order to help calculate entropy. In particular, we prove a contemporary version of addition and Kolmogorov-Sinai Theorems. Furthermore, we provide a comparison between the indispensable properties of hyper injective and semi-independent dynamical systems. Specifically, we present and prove theorems that draw comparisons between the entropies of such systems. Lastly, we discuss some possible relationships between the theories of hyper MV -algebra and MV -algebra dynamical systems.

Psychotic experiences and hyper-theory-of-mind in preadolescence--a birth cohort study.

PubMed

Clemmensen, L; van Os, J; Drukker, M; Munkholm, A; Rimvall, M K; Væver, M; Rask, C U; Bartels-Velthuis, A A; Skovgaard, A M; Jeppesen, P

2016-01-01

Knowledge on the risk mechanisms of psychotic experiences (PE) is still limited. The aim of this population-based study was to explore developmental markers of PE with a particular focus on the specificity of hyper-theory-of-mind (HyperToM) as correlate of PE as opposed to correlate of any mental disorder. We assessed 1630 children from the Copenhagen Child Cohort 2000 regarding PE and HyperToM at the follow-up at 11-12 years. Mental disorders were diagnosed by clinical ratings based on standardized parent-, teacher- and self-reported psychopathology. Logistic regression analyses were performed to test the correlates of PE and HyperToM, and the specificity of correlates of PE v. correlates of any Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) mental disorder. Univariate analyses showed the following correlates of PE: familial psychiatric liability; parental mental illness during early child development; change in family composition; low family income; regulatory problems in infancy; onset of puberty; bullying; concurrent mental disorder; and HyperToM. When estimating the adjusted effects, only low family income, concurrent mental disorder, bullying and HyperToM remained significantly associated with PE. Further analyses of the specificity of these correlates with regard to outcome revealed that HyperToM was the only variable specifically associated with PE without concurrent mental disorder. Finally, HyperToM did not share any of the investigated precursors with PE. HyperToM may have a specific role in the risk trajectories of PE, being specifically associated with PE in preadolescent children, independently of other family and child risk factors associated with PE and overall psychopathology at this age.

A hypermedia reference system to the Forest Ecosystem Management Assessment team report and some related publications.

Treesearch

K.M. Reynolds; H.M. Rauscher; C.V. Worth

1995-01-01

The hypermedia system, ForestEM, was developed in HyperWriter for use in Microsoft Windows. ForestEM version 1.0 includes text and figures from the FEMAT report and the Record of Decision and Standards and Guidelines. Hypermedia introduces two fundamental changes to knowledge management. The first is the capability to interactively store and retrieve large amounts of...

Systematic in J-PARC/Hyper-K

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

Minamino, Akihiro

The Hyper-Kamiokande (Hyper-K) detector is a next generation underground water Chrenkov detector. The J-PARC to Hyper-K experiment has good potential for precision measurements of neutrino oscillation parameters and discovery reach for CP violation in the lepton sector. With a total exposure of 10 years to a neutrino beam produced by the 750 kW J-PARC proton synchrotron, it is expected that the CP phase δ can be determined to better than 18 degree for all possible values of δ if sin{sup 2} 2θ{sub 13} > 0.03 and the mass hierarchy is known. Control of systematic uncertainties is critical to make maximummore » use of the Hyper-K potential. Based on learning from T2K experience, a strategy to reduce systematic uncertainties in J-PARC/Hyper-K are developed.« less

Recent progress of push-broom infrared hyper-spectral imager in SITP

NASA Astrophysics Data System (ADS)

Wang, Yueming; Hu, Weida; Shu, Rong; Li, Chunlai; Yuan, Liyin; Wang, Jianyu

2017-02-01

In the past decades, hyper-spectral imaging technologies were well developed in SITP, CAS. Many innovations for system design and key parts of hyper-spectral imager were finished. First airborne hyper-spectral imager operating from VNIR to TIR in the world was emerged in SITP. It is well known as OMIS(Operational Modular Imaging Spectrometer). Some new technologies were introduced to improve the performance of hyper-spectral imaging system in these years. A high spatial space-borne hyper-spectral imager aboard Tiangong-1 spacecraft was launched on Sep.29, 2011. Thanks for ground motion compensation and high optical efficiency prismatic spectrometer, a large amount of hyper-spectral imagery with high sensitivity and good quality were acquired in the past years. Some important phenomena were observed. To diminish spectral distortion and expand field of view, new type of prismatic imaging spectrometer based curved prism were proposed by SITP. A prototype of hyper-spectral imager based spherical fused silica prism were manufactured, which can operate from 400nm 2500nm. We also made progress in the development of LWIR hyper-spectral imaging technology. Compact and low F number LWIR imaging spectrometer was designed, manufactured and integrated. The spectrometer operated in a cryogenically-cooled vacuum box for background radiation restraint. The system performed well during flight experiment in an airborne platform. Thanks high sensitivity FPA and high performance optics, spatial resolution and spectral resolution and SNR of system are improved enormously. However, more work should be done for high radiometric accuracy in the future.

Parallel Evolution of Sperm Hyper-Activation Ca2+ Channels

PubMed Central

Phadnis, Nitin

2017-01-01

Abstract Sperm hyper-activation is a dramatic change in sperm behavior where mature sperm burst into a final sprint in the race to the egg. The mechanism of sperm hyper-activation in many metazoans, including humans, consists of a jolt of Ca2+ into the sperm flagellum via CatSper ion channels. Surprisingly, all nine CatSper genes have been independently lost in several animal lineages. In Drosophila, sperm hyper-activation is performed through the cooption of the polycystic kidney disease 2 (pkd2) Ca2+ channel. The parallels between CatSpers in primates and pkd2 in Drosophila provide a unique opportunity to examine the molecular evolution of the sperm hyper-activation machinery in two independent, nonhomologous calcium channels separated by > 500 million years of divergence. Here, we use a comprehensive phylogenomic approach to investigate the selective pressures on these sperm hyper-activation channels. First, we find that the entire CatSper complex evolves rapidly under recurrent positive selection in primates. Second, we find that pkd2 has parallel patterns of adaptive evolution in Drosophila. Third, we show that this adaptive evolution of pkd2 is driven by its role in sperm hyper-activation. These patterns of selection suggest that the evolution of the sperm hyper-activation machinery is driven by sexual conflict with antagonistic ligands that modulate channel activity. Together, our results add sperm hyper-activation channels to the class of fast evolving reproductive proteins and provide insights into the mechanisms used by the sexes to manipulate sperm behavior. PMID:28810709

Access to site-specific Fc-cRGD peptide conjugates through streamlined expressed protein ligation.

PubMed

Frutos, S; Jordan, J B; Bio, M M; Muir, T W; Thiel, O R; Vila-Perelló, M

2016-10-12

An ideal drug should be highly effective, non-toxic and be delivered by a convenient and painless single dose. We are still far from such optimal treatment but peptides, with their high target selectivity and low toxicity profiles, provide a very attractive platform from which to strive towards it. One of the major limitations of peptide drugs is their high clearance rates, which limit dosage regimen options. Conjugation to antibody Fc domains is a viable strategy to improve peptide stability by increasing their hydrodynamic radius and hijacking the Fc recycling pathway. We report the use of a split-intein based semi-synthetic approach to site-specifically conjugate a synthetic integrin binding peptide to an Fc domain. The strategy described here allows conjugating synthetic peptides to Fc domains, which is not possible via genetic methods, fully maintaining the ability of both the Fc domain and the bioactive peptide to interact with their binding partners.

Photocatalysts Based on Cobalt-Chelating Conjugated Polymers for Hydrogen Evolution from Water

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

Li, Lianwei; Hadt, Ryan G.; Yao, Shiyu

Developing photocatalytic systems for water splitting to generate oxygen and hydrogen is one of the biggest chemical challenges in solar energy utilization. In this work, we report the first example of heterogeneous photocatalysts for hydrogen evolution based on in-chain cobalt-chelating conjugated polymers. Four conjugated polymers chelated with earth abundant cobalt ions were synthesized and found to evolve hydrogen photocatalytically from water. These polymers are designed to combine functions of the conjugated backbone as light-harvesting antenna and electron transfer conduit with the in-chain bipyridyl chelated transition metal centers as catalytic active sites. In addition, these polymers are soluble in organic solvents,more » enabling effective interactions with the substrates as well as detailed characterization. We also found a polymer-dependent optimal cobalt chelating concentration at which the highest photocatalytic hydrogen production (PHP) activity can be achieved.« less

Synthesis, structure and antimicrobial evaluation of a new gossypol triazole conjugates functionalized with aliphatic chains and benzyloxy groups.

PubMed

Pyta, Krystian; Blecha, Marietta; Janas, Anna; Klich, Katarzyna; Pecyna, Paulina; Gajecka, Marzena; Przybylski, Piotr

2016-09-01

Synthetic limitations in the copper-catalyzed azide alkyne cycloaddition (CuAAC) on gossypol's skeleton functionalized with alkyne (2) or azide (3) groups have been indicated. Modified approach to the synthesis of new gossypol-triazole conjugates yielded new compounds (24-31) being potential fungicides. Spectroscopic studies of triazole conjugates 24-31 have revealed their structures in solution, i.e., the presence of enamine-enamine tautomeric forms and π-π stacking intramolecular interactions between triazole arms. Biological evaluation of the new gossypol-triazole conjugates revealed the potency of 30 and 31 derivatives, having triazole-benzyloxy moieties, comparable with that of miconazole against Fusarium oxysporum. The results of HPLC evaluation of ergosterol content in different fungi strains upon treatment of gossypol and its derivatives enabled to propose a mechanism of antifungal activity of these compounds. Copyright © 2016 Elsevier Ltd. All rights reserved.

Electro-optical interfacial effects on a graphene/π-conjugated organic semiconductor hybrid system

PubMed Central

Araujo, Karolline A S; Cury, Luiz A; Matos, Matheus J S; Fernandes, Thales F D; Cançado, Luiz G

2018-01-01

The influence of graphene and retinoic acid (RA) – a π-conjugated organic semiconductor – interface on their hybrid system is investigated. The physical properties of the interface are assessed via scanning probe microscopy, optical spectroscopy (photoluminescence and Raman) and ab initio calculations. The graphene/RA interaction induces the formation of a well-organized π-conjugated self-assembled monolayer (SAM) at the interface. Such structural organization leads to the high optical emission efficiency of the RA SAM, even at room temperature. Additionally, photo-assisted electrical force microscopy, photo-assisted scanning Kelvin probe microscopy and Raman spectroscopy indicate a RA-induced graphene doping and photo-charge generation. Finally, the optical excitation of the RA monolayer generates surface potential changes on the hybrid system. In summary, interface-induced organized structures atop 2D materials may have an important impact on both design and operation of π-conjugated nanomaterial-based hybrid systems. PMID:29600157

The ubiquitin conjugating enzyme UbcH10 competes with UbcH3 for binding to the SCF complex, a ubiquitin ligase involved in cell cycle progression

USDA-ARS?s Scientific Manuscript database

Ubiquitylation, which regulates most biological pathways, occurs through an enzymatic cascade involving a ubiquitin (ub) activating enzyme (E1), a ub conjugating enzyme (E2) and a ub ligase (E3). UbcH3 is the E2 that interacts with SCF (Skp1/Cul1/F-box protein) complex and ubiquitylates many protein...

A water-soluble conjugated polymer for protein identification and denaturation detection.

PubMed

Xu, Qingling; Wu, Chunxian; Zhu, Chunlei; Duan, Xinrui; Liu, Libing; Han, Yuchun; Wang, Yilin; Wang, Shu

2010-12-03

Rapid and sensitive methods to detect proteins and protein denaturation have become increasingly needful in the field of proteomics, medical diagnostics, and biology. In this paper, we have reported the synthesis of a new cationic water-soluble conjugated polymer that contains fluorene and diene moieties in the backbone (PFDE) for protein identification by sensing an array of PFDE solutions in different ionic strengths using the linear discriminant analysis technique (LDA). The PFDE can form complexes with proteins by electrostatic and/or hydrophobic interactions and exhibits different fluorescence response. Three main factors contribute to the fluorescence response of PFDE, namely, the net charge density on the protein surface, the hydrophobic nature of the protein, and the metalloprotein characteristics. The denaturation of proteins can also be detected using PFDE as a fluorescent probe. The interactions between PFDE and proteins were also studied by dynamic light scattering (DLS) and isothermal titration microcalorimetry (ITC) techniques. In contrast to other methods based on conjugated polymers, the synthesis of a series of quencher or dye-labeled acceptors or protein substrates has been avoided in our method, which significantly reduces the cost and the synthetic complexity. Our method provides promising applications on protein identification and denaturation detection in a simple, fast, and label-free manner based on non-specific interaction-induced perturbation of PFDE fluorescence response.

How PEGylation enhances the stability and potency of insulin: a molecular dynamics simulation.

PubMed

Yang, Cheng; Lu, Diannan; Liu, Zheng

2011-04-05

While the effectiveness of PEGylation in enhancing the stability and potency of protein pharmaceuticals has been validated for years, the underlying mechanism remains poorly understood, particularly at the molecular level. A molecular dynamics simulation was developed using an annealing procedure that allowed an all-atom level examination of the interaction between PEG polymers of different chain lengths and a conjugated protein represented by insulin. It was shown that PEG became entangled around the protein surface through hydrophobic interaction and concurrently formed hydrogen bonds with the surrounding water molecules. In addition to enhancing its structural stability, as indicated by the root-mean-square difference (rmsd) and secondary structure analyses, conjugation increased the size of the protein drug while decreasing the solvent accessible surface area of the protein. All these thus led to prolonged circulation life despite kidney filtration, proteolysis, and immunogenic side effects, as experimentally demonstrated elsewhere. Moreover, the simulation results indicated that an optimal chain length exists that would maximize drug potency underpinned by the parameters mentioned above. The simulation provided molecular insight into the interaction between PEG and the conjugated protein at the all-atom level and offered a tool that would allow for the design of PEGylated protein pharmaceuticals for given applications.

Facile synthesis of a conjugation-grafted-TiO2 nanohybrid with enhanced visible-light photocatalytic properties from nanotube titanic acid precursors

NASA Astrophysics Data System (ADS)

Guo, Yanru; Zhang, Min; Zhang, Zhihua; Li, Qiuye; Yang, Jianjun

2016-08-01

A conjugation-grafted-TiO2 nanohybrid was synthesized by chemically grafting conjugated structures on the surface of nanotube titanic acid (NTA) precursor-based TiO2 through the controlled thermal degradation of a coacervated polymer layer of polyvinyl alcohol (PVA). The interfacial interactions between the NTA precursor-based TiO2 and conjugated structures were characterized using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. Moreover, the effects of the NTA's pretreatment temperature and the weight ratio of NTA to PVA on the photocatalytic degradation of methyl orange were also investigated. A higher NTA pretreatment temperature and a lower NTA to PVA weight ratio were found to enhance photogenerated electron-hole separation efficiency and photocatalytic activity. Moreover, the conjugation-grafted-TiO2 nanohybrid synthesized from the NTA precursor displayed a much higher visible-light photocatalytic activity than that of the sample obtained from the P25 precursor. The origin of the enhanced photocatalytic activity under visible-light irradiation is also discussed in detail.

Carbon nanotubes as carriers of Panax ginseng metabolites and enhancers of ginsenosides Rb1 and Rg1 anti-cancer activity

NASA Astrophysics Data System (ADS)

Lahiani, Mohamed H.; Eassa, Souzan; Parnell, Charlette; Nima, Zeid; Ghosh, Anindya; Biris, Alexandru S.; Khodakovskaya, Mariya V.

2017-01-01

A major benefit to nanomaterial based-medicine is the ability to provide nanosized vehicles for sporadic metabolites. Here, we describe how the conjugation of valuable ginseng secondary metabolites (ginsenoside Rb1 or Rg1) with carbon nanotubes (CNT) can enhance their anti-proliferative and anti-cancer effects. Ginsenoside-CNT conjugate (Rb-CNT or Rg-CNT) permitted the ginsenosides to be used at a low dose, yet achieve a higher incidence of cancer killing. We were able to demonstrate that the ginsenoside-CNT conjugate can decrease cell viability up to 62% in breast cancer cells (MCF-7) and enhance antiproliferation of drug-resistant pancreatic cancer cells (PANC-1) by 61%. The interaction of the ginsenoside-CNT conjugate with breast cancer cells was studied using Raman Spectroscopy mapping. Total transcriptome profiling (Affymetrix platform) of MCF-7 cells treated with the ginsenoside-CNT conjugate shows that a number of cellular, apoptotic and response to stimulus processes were affected. Therefore, our data confirmed the potential use of CNT as a drug delivery system.

Propulsion System Airframe Integration Issues and Aerodynamic Database Development for the Hyper-X Flight Research Vehicle

NASA Technical Reports Server (NTRS)

Engelund, Walter C.; Holland, Scott D.; Cockrell, Charles E., Jr.; Bittner, Robert D.

1999-01-01

NASA's Hyper-X Research Vehicle will provide a unique opportunity to obtain data on an operational airframe integrated scramjet propulsion system at true flight conditions. The airframe integrated nature of the scramjet engine with the Hyper-X vehicle results in a strong coupling effect between the propulsion system operation and the airframe s basic aerodynamic characteristics. Comments on general airframe integrated scramjet propulsion system effects on vehicle aerodynamic performance, stability, and control are provided, followed by examples specific to the Hyper-X research vehicle. An overview is provided of the current activities associated with the development of the Hyper-X aerodynamic database, including wind tunnel test activities and parallel CFD analysis efforts. A brief summary of the Hyper-X aerodynamic characteristics is provided, including the direct and indirect effects of the airframe integrated scramjet propulsion system operation on the basic airframe stability and control characteristics.

Multicenter analysis of treatment outcomes in adult patients with lymphoblastic lymphoma who received hyper-CVAD induction followed by hematopoietic stem cell transplantation.

PubMed

Jeong, Seong Hyun; Moon, Joon Ho; Kim, Jin Seok; Yang, Deok-Hwan; Park, Yong; Cho, Seok Goo; Kwak, Jae-Yong; Eom, Hyeon Seok; Won, Jong Ho; Hong, Jun Shik; Oh, Sung Yong; Lee, Ho Sup; Kim, Seok Jin

2015-04-01

The hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) regimen has been widely used for lymphoblastic lymphoma (LBL) as a primary treatment. However, there is few data about its treatment outcome in Asian patients. Thus, we conducted this study to evaluate the efficacy of hyper-CVAD induction and stem cell transplantation (SCT) consolidation in LBL patients. The treatment responses of 49 patients treated with the hyper-CVAD regimen were retrospectively analyzed in 13 institutions. Given 24 patients who responded to hyper-CVAD underwent consolidation treatment with SCT, overall survival (OS) and progression-free survival (PFS) of patients who received SCT were compared with patients who did not. The overall response rate was 79 %: 73 % (36/49) complete responses, 6 % (3/49) partial responses, and 4 % (2/49) induction deaths. The major limitation for the delivery of the planned hyper-CVAD cycles was hematological toxicity. Among 39 responders, 24 patients underwent autologous (n = 16) and allogeneic SCT (n = 8) consolidation. Their 3-year OS and PFS rates were 76 and 78 %, respectively, and there was no difference in survival outcomes between autologous and allogeneic SCT. However, 15 patients without SCT consolidation showed poorer PFS even though they all achieved complete response. Thus, only seven patients maintained their response at the time of analysis. In conclusion, the hyper-CVAD regimen is effective for remission induction in LBL, and SCT consolidation after hyper-CVAD induction produced better clinical outcomes than did continuation of hyper-CVAD.

Responses of heart rate and blood pressure to KC-135 hyper-gravity

NASA Technical Reports Server (NTRS)

Satake, Hirotaka; Matsunami, Ken'ichi; Reschke, Millard F.

1992-01-01

Many investigators have clarified the effects of hyper gravitational-inertial forces (G) upon the cardiovascular system, using the centrifugal apparatus with short rotating radius. We investigated the cardiovascular responses to KC-135 hyper-G flight with negligibly small angular velocity. Six normal, healthy subjects 29 to 40 years old (5 males and 1 female) took part in this experiment. Hyper gravitational-inertial force was generated by the KC-135 hyper-G flight, flown in a spiral path with a very long radius of 1.5 miles. Hyper-G was sustained for 3 minutes with 1.8 +Gz in each session and was repeatedly exposed to very subject sitting on a chair 5 times. The preliminary results of blood pressure and R-R interval are discussed. An exposure of 1.8 +Gz stress resulted in a remarkable increase of systolic and diastolic blood pressure, while the pulse pressure did not change and remained equal to the control level regardless of an exposure of hyper-G. These results in blood pressure indicate an increase of resistance in the peripheral vessels, when an exposure of hyper-G was applied. The R-R interval was calculated from ECG. R-R interval in all subjects was changed but not systematically, and R-R interval became obviously shorter during the hyper-G period than during the 1 +Gz control period although R-R interval varied widely in some cases. The coefficient of variation of R-R interval was estimated to determine the autonomic nerve activity, but no significant change was detectable.

Parallel Evolution of Sperm Hyper-Activation Ca2+ Channels.

PubMed

Cooper, Jacob C; Phadnis, Nitin

2017-07-01

Sperm hyper-activation is a dramatic change in sperm behavior where mature sperm burst into a final sprint in the race to the egg. The mechanism of sperm hyper-activation in many metazoans, including humans, consists of a jolt of Ca2+ into the sperm flagellum via CatSper ion channels. Surprisingly, all nine CatSper genes have been independently lost in several animal lineages. In Drosophila, sperm hyper-activation is performed through the cooption of the polycystic kidney disease 2 (pkd2) Ca2+ channel. The parallels between CatSpers in primates and pkd2 in Drosophila provide a unique opportunity to examine the molecular evolution of the sperm hyper-activation machinery in two independent, nonhomologous calcium channels separated by > 500 million years of divergence. Here, we use a comprehensive phylogenomic approach to investigate the selective pressures on these sperm hyper-activation channels. First, we find that the entire CatSper complex evolves rapidly under recurrent positive selection in primates. Second, we find that pkd2 has parallel patterns of adaptive evolution in Drosophila. Third, we show that this adaptive evolution of pkd2 is driven by its role in sperm hyper-activation. These patterns of selection suggest that the evolution of the sperm hyper-activation machinery is driven by sexual conflict with antagonistic ligands that modulate channel activity. Together, our results add sperm hyper-activation channels to the class of fast evolving reproductive proteins and provide insights into the mechanisms used by the sexes to manipulate sperm behavior. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

FT-IR, FT-Raman, NMR studies and ab initio-HF, DFT-B3LYP vibrational analysis of 4-chloro-2-fluoroaniline

NASA Astrophysics Data System (ADS)

Arivazhagan, M.; Anitha Rexalin, D.

2012-10-01

The Fourier transform infrared (FT-IR) and Fourier transform Raman (FT-Raman) spectra of 4-chloro-2-fluoroaniline (CFA) have been recorded and analyzed. The equilibrium geometry, bonding features and harmonic vibrational frequencies have been investigated with the help of ab initio and density functional theory (DFT) methods. The assignments of the vibrational spectra have been carried out with the help of normal coordinate analysis (NCA) following the scaled quantum mechanical force field methodology. The 1H and 13C nuclear magnetic resonance (NMR) chemical shifts of the molecule are calculated by the Gauge including atomic orbital (GIAO) method. The first order hyperpolarizability (β0) of this novel molecular system and related properties (β, α0 and Δα) of CFA are calculated using B3LYP/6-311++G(d,p) and HF/6-311++G(d,p) methods on the finite-field approach. The calculated results also show that the CFA molecule might have microscopic nonlinear optical (NLO) behavior with non-zero values. Stability of the molecule arising from hyper conjugative interactions, charge delocalization has been analyzed using natural bond orbital (NBO) analysis. The result confirms the occurrence of intramolecular charge transfer (ICT) within the molecule. The HOMO-LUMO energies UV-vis spectral analysis and MEP are performed by B3LYP/6-311++G(d,p) approach. A detailed interpretation of the infrared and Raman spectra of CFA is also reported based on total energy distribution (TED). The difference between the observed and scaled wave number values of the most of the fundamentals is very small.

Experimental spectroscopic (FTIR, FT-Raman, FT-NMR, UV-Visible) and DFT studies of 1-ethyl-1,4-dihydro-7-methyl-4oxo-1,8 napthyridine-3-carboxylic acids.

PubMed

Muthu, S; Elamurugu Porchelvi, E

2013-12-01

The solid phase FTIR and FT-Raman spectra of 1-ethyl-1,4-dihydro-7-methyl-4oxo-1,8 napthyridine-3-carboxylic acid (EDMONCA) have been recorded in the regions 4000-500 and 4000-400 cm(-1) respectively. The equilibrium geometry, harmonic vibrational frequencies have been investigated by DFT/B3LYP and B3PW91 methods with 6-311G (d,p) basis set. The different between the observed and scaled wave number values of most of the fundamental is very small. The assignments of the vibrational spectra have been carried out with the aid of normal coordinate analysis (NCA) following the scaled quantum mechanical force field methodology (SQMFFM). Stability of the molecule arising from hyper conjugative interactions, charge delocalization has been analyzed using natural bond orbital (NBO) analysis. UV-Visible spectrum of the compound was recorded and the electronic properties HOMO and LOMO energies were measured. The electric dipole moment (μD) and first hyperpolarizability (βtot) values of the investigated molecule were computed using ab initio quantum mechanical calculations. The calculated results also show that the EDMONCA molecule may have microscopic nonlinear optics (NLO) behavior with non-zero values. (1)H and (13)C NMR spectra were recorded and (1)H and (13)C nuclear magnetic resonance chemical shift of the molecule were calculated using the gauge independent atomic orbital (GIAO) method. Thermal stability of EDMONCA was studied by thermogravimetric analysis (TGA). Next Fukui function was calculated to explain the chemical selectivity or reactivity site in EDMONCA. Finally molecular electrostatic potential (MEP) and other molecular properties were performed. Copyright © 2013 Elsevier B.V. All rights reserved.

Spectroscopic (FT-IR, FT-Raman and UV) investigation, NLO, NBO, molecular orbital and MESP analysis of 2-{2-[(2,6-dichlorophenyl)amino]phenyl}acetic acid

NASA Astrophysics Data System (ADS)

Govindasamy, P.; Gunasekaran, S.

2015-02-01

In this work, FT-IR and FT-Raman spectra of 2-{2-[(2,6-dichlorophenyl)amino]phenyl}acetic acid (abbreviated as 2DCPAPAA) have been reported in the regions 4000-450 cm-1 and 4000-50 cm-1, respectively. The molecular structure, geometry optimization, intensities, vibrational frequencies were obtained by the ab initio and DFT levels of theory B3LYP with 6-311++G(d,p) standard basis set and a different scaling of the calculated wave numbers. The complete vibrational assignments were performed on the basis of the potential energy distribution (PED) of the vibrational modes calculated using vibrational energy distribution analysis (VEDA 4) program. The harmonic frequencies were calculated and the scaled values were compared with experimental FT-IR and FT-Raman data. The observed and the calculated frequencies are found to be in good agreement. Stability of the molecule arising from hyper conjugative interactions, charge delocalization has been analyzed using natural bond orbital (NBO) analysis. The thermodynamic properties of the title compound at different temperature reveal the correlations between standard heat capacities (C) standard entropies (S) standard enthalpy changes (ΔH). The important non-linear optical properties such as electric dipole momentum, polarizability and first hyperpolarizability of 2DCPAPAA have been computed using B3LYP/6-311++G(d,p) quantum chemical calculations. The Natural charges, HOMO, LUMO, chemical hardness (η), chemical potential (μ), Electro negativity (χ) and electrophilicity values (ω) are calculated and reported. The oscillator's strength, wave length, and energy calculated by TD-DFT and 2DCPAPAA is approach complement with the experimental findings. The molecular electrostatic potential (MESP) surfaces of the molecule were constructed.

Spectroscopic (FT-IR, FT-Raman and UV) investigation, NLO, NBO, molecular orbital and MESP analysis of 2-{2-[(2,6-dichlorophenyl)amino]phenyl}acetic acid.

PubMed

Govindasamy, P; Gunasekaran, S

2015-02-05

In this work, FT-IR and FT-Raman spectra of 2-{2-[(2,6-dichlorophenyl)amino]phenyl}acetic acid (abbreviated as 2DCPAPAA) have been reported in the regions 4000-450cm(-1) and 4000-50cm(-1), respectively. The molecular structure, geometry optimization, intensities, vibrational frequencies were obtained by the ab initio and DFT levels of theory B3LYP with 6-311++G(d,p) standard basis set and a different scaling of the calculated wave numbers. The complete vibrational assignments were performed on the basis of the potential energy distribution (PED) of the vibrational modes calculated using vibrational energy distribution analysis (VEDA 4) program. The harmonic frequencies were calculated and the scaled values were compared with experimental FT-IR and FT-Raman data. The observed and the calculated frequencies are found to be in good agreement. Stability of the molecule arising from hyper conjugative interactions, charge delocalization has been analyzed using natural bond orbital (NBO) analysis. The thermodynamic properties of the title compound at different temperature reveal the correlations between standard heat capacities (C) standard entropies (S) standard enthalpy changes (ΔH). The important non-linear optical properties such as electric dipole momentum, polarizability and first hyperpolarizability of 2DCPAPAA have been computed using B3LYP/6-311++G(d,p) quantum chemical calculations. The Natural charges, HOMO, LUMO, chemical hardness (η), chemical potential (μ), Electro negativity (χ) and electrophilicity values (ω) are calculated and reported. The oscillator's strength, wave length, and energy calculated by TD-DFT and 2DCPAPAA is approach complement with the experimental findings. The molecular electrostatic potential (MESP) surfaces of the molecule were constructed. Copyright © 2014 Elsevier B.V. All rights reserved.

A combined experimental and theoretical studies on FT-IR, FT-Raman and UV-vis spectra of 2-chloro-3-quinolinecarboxaldehyde

NASA Astrophysics Data System (ADS)

Prasad, M. V. S.; Udaya Sri, N.; Veeraiah, V.

2015-09-01

In the present study, the FT-IR and FT-Raman spectra of 2-chloro-3-quinolinecarboxaldehyde (2Cl3QC) have been recorded in the region 4000-400 and 3500-50 cm-1, respectively. The fundamental modes of vibrational frequencies of 2Cl3QC are assigned. Theoretical information on the optimized geometry, harmonic vibrational frequencies, infrared and Raman intensities were obtained by means of density functional theory (DFT) gradient calculations with complete relaxation in the potential energy surface using 6-31G(d,p) basis set. The vibrational frequencies which were determined experimentally from the spectral data are compared with those obtained theoretically from DFT calculations. A close agreement was achieved between the observed and calculated frequencies by refinement of the scale factors. The infrared and Raman spectra were also predicted from the calculated intensities. Thermodynamic properties like entropy, heat capacity, zero point energy, have been calculated for the molecule. The predicted first hyperpolarizability also shows that the molecule might have a reasonably good non-linear optical (NLO) behavior. The calculated HOMO-LUMO energy gap reveals that charge transfer occurs within the molecule. Stability of the molecule arising from hyper conjugative interactions, charge delocalization have been analyzed using natural bond orbitals (NBO) analysis. The results show that charge in electron density (ED) in the π∗ antibonding orbitals and E(2) energies confirms the occurrence of ICT (intra-molecular charge transfer) within the molecule. UV-visible spectrum of the title molecule has also been calculated using TD-DFT/CAM-B3LYP/6-31G(d,p) method. The calculated energy and oscillator strength almost exactly reproduces reported experimental data.

FT-IR, FT-Raman, NMR studies and ab initio-HF, DFT-B3LYP vibrational analysis of 4-chloro-2-fluoroaniline.

PubMed

Arivazhagan, M; Anitha Rexalin, D

2012-10-01

The Fourier transform infrared (FT-IR) and Fourier transform Raman (FT-Raman) spectra of 4-chloro-2-fluoroaniline (CFA) have been recorded and analyzed. The equilibrium geometry, bonding features and harmonic vibrational frequencies have been investigated with the help of ab initio and density functional theory (DFT) methods. The assignments of the vibrational spectra have been carried out with the help of normal coordinate analysis (NCA) following the scaled quantum mechanical force field methodology. The (1)H and (13)C nuclear magnetic resonance (NMR) chemical shifts of the molecule are calculated by the Gauge including atomic orbital (GIAO) method. The first order hyperpolarizability (β(0)) of this novel molecular system and related properties (β, α(0) and Δα) of CFA are calculated using B3LYP/6-311++G(d,p) and HF/6-311++G(d,p) methods on the finite-field approach. The calculated results also show that the CFA molecule might have microscopic nonlinear optical (NLO) behavior with non-zero values. Stability of the molecule arising from hyper conjugative interactions, charge delocalization has been analyzed using natural bond orbital (NBO) analysis. The result confirms the occurrence of intramolecular charge transfer (ICT) within the molecule. The HOMO-LUMO energies UV-vis spectral analysis and MEP are performed by B3LYP/6-311++G(d,p) approach. A detailed interpretation of the infrared and Raman spectra of CFA is also reported based on total energy distribution (TED). The difference between the observed and scaled wave number values of the most of the fundamentals is very small. Copyright © 2012 Elsevier B.V. All rights reserved.

A combined experimental and theoretical studies on FT-IR, FT-Raman and UV-vis spectra of 2-chloro-3-quinolinecarboxaldehyde.

PubMed

Prasad, M V S; Udaya Sri, N; Veeraiah, V

2015-09-05

In the present study, the FT-IR and FT-Raman spectra of 2-chloro-3-quinolinecarboxaldehyde (2Cl3QC) have been recorded in the region 4000-400 and 3500-50 cm(-1), respectively. The fundamental modes of vibrational frequencies of 2Cl3QC are assigned. Theoretical information on the optimized geometry, harmonic vibrational frequencies, infrared and Raman intensities were obtained by means of density functional theory (DFT) gradient calculations with complete relaxation in the potential energy surface using 6-31G(d,p) basis set. The vibrational frequencies which were determined experimentally from the spectral data are compared with those obtained theoretically from DFT calculations. A close agreement was achieved between the observed and calculated frequencies by refinement of the scale factors. The infrared and Raman spectra were also predicted from the calculated intensities. Thermodynamic properties like entropy, heat capacity, zero point energy, have been calculated for the molecule. The predicted first hyperpolarizability also shows that the molecule might have a reasonably good non-linear optical (NLO) behavior. The calculated HOMO-LUMO energy gap reveals that charge transfer occurs within the molecule. Stability of the molecule arising from hyper conjugative interactions, charge delocalization have been analyzed using natural bond orbitals (NBO) analysis. The results show that charge in electron density (ED) in the π(∗) antibonding orbitals and E((2)) energies confirms the occurrence of ICT (intra-molecular charge transfer) within the molecule. UV-visible spectrum of the title molecule has also been calculated using TD-DFT/CAM-B3LYP/6-31G(d,p) method. The calculated energy and oscillator strength almost exactly reproduces reported experimental data. Copyright © 2015 Elsevier B.V. All rights reserved.

Photophysics of single-walled carbon nanotubes: similarity with π-conjugated polymer

NASA Astrophysics Data System (ADS)

Zhao, Hongbo

2006-03-01

Coulomb electron-electron (e-e) interactions among the π-electrons have a strong effect on the energy spectra of semiconducting single-walled carbon nanotubes (S-SWCNTs), because of their quasi-one-dimensionality. The primary photoexcitations in S-SWCNTs as a consequence of e-e interactions are excitons, as opposed to free electrons and holes. There already exists a vast literature on excitons in π-conjugated polymers, the other class of carbon-based quasi-one-dimensional semiconductors. In order to seek guidance from this knowledge base, we have performed theoretical calculations of the excited state electronic structures, linear absorptions and excited state absorptions for ten different S-SWCNTs with a wide range in diameters, within the same correlated π-electron model that has previously been applied to π-conjugated polymers. We found remarkable similarities in the excitonic energy spectra and nonlinear optical properties of S-SWCNTs on the one hand, and π-conjugated polymers on the other. The ``essential states'' model of third-order optical nonlinearity, previously developed for π-conjugated polymers, applies also to S-SWCNTs (with minor modifications for chiral S-SWCNTs which lack center of inversion). Our theory is able to explain semiquantitatively the results of nonlinear spectroscopic measurements on both S-SWCNTs and π-conjugated polymers. For wide S-SWCNTs with diameters ranging from 0.8--1.0 nm, we calculate exciton binding energies of 0.3--0.4 eV, in strong agreement with the values predicted from the experiments. We also remark on the occurrence of dark excitons below the optical excitons in the S-SWCNTs, and the consequence thereof on the photoluminescence of these materials. H. Zhao, et al., cond-mat/0506097; J. W. Kennedy, et al., cond-mat/0505071. S. N. Dixit, D. Guo, and S. Mazumdar, Phys. Rev. B 43, R6781 (1991) H. Zhao and S. Mazumdar, Phys. Rev. Lett. 93, 157402 (2004).

Rapid quantification of plant-powdery mildew interactions by qPCR and conidiospore counts.

PubMed

Weßling, Ralf; Panstruga, Ralph

2012-08-31

The powdery mildew disease represents a valuable patho-system to study the interaction between plant hosts and obligate biotrophic fungal pathogens. Numerous discoveries have been made on the basis of the quantitative evaluation of plant-powdery mildew interactions, especially in the context of hyper-susceptible and/or resistant plant mutants. However, the presently available methods to score the pathogenic success of powdery mildew fungi are laborious and thus not well suited for medium- to high-throughput analysis. Here we present two new protocols that allow the rapid quantitative assessment of powdery mildew disease development. One procedure depends on quantitative polymerase chain reaction (qPCR)-based evaluation of fungal biomass, while the other relies on the quantification of fungal conidiospores. We validated both techniques using the powdery mildew pathogen Golovinomyces orontii on a set of hyper-susceptible and resistant Arabidopsis thaliana mutants and found that both cover a wide dynamic range of one to two (qPCR) and four to five (quantification of conidia) orders of magnitude, respectively. The two approaches yield reproducible results and are easy to perform without specialized equipment. The qPCR and spore count assays rapidly and reproducibly quantify powdery mildew pathogenesis. Our methods are performed at later stages of infection and discern mutant phenotypes accurately. The assays therefore complement currently used procedures of powdery mildew quantification and can overcome some of their limitations. In addition, they can easily be adapted to other plant-powdery mildew patho-systems.

[Application of hyper-spectral remote sensing technology in environmental protection].

PubMed

Zhao, Shao-Hua; Zhang, Feng; Wang, Qiao; Yao, Yun-Jun; Wang, Zhong-Ting; You, Dai-An

2013-12-01

Hyper-spectral remote sensing (RS) technology has been widely used in environmental protection. The present work introduces its recent application in the RS monitoring of pollution gas, green-house gas, algal bloom, water quality of catch water environment, safety of drinking water sources, biodiversity, vegetation classification, soil pollution, and so on. Finally, issues such as scarce hyper-spectral satellites, the limits of data processing and information extract are related. Some proposals are also presented, including developing subsequent satellites of HJ-1 satellite with differential optical absorption spectroscopy, greenhouse gas spectroscopy and hyper-spectral imager, strengthening the study of hyper-spectral data processing and information extraction, and promoting the construction of environmental application system.

A convenient method for synthesis of glyconanoparticles for colorimetric measuring carbohydrate-protein interactions

PubMed Central

Chuang, Yen-Jun; Zhou, Xichun; Pan, Zhengwei; Turchi, Craig

2009-01-01

Carbohydrate functionalized nanoparticles, i.e., the glyconanoparticles, have wide application ranging from studies of carbohydrate-protein interactions, in vivo cell imaging, biolabeling, etc. Currently reported methods for preparation of glyconanoaprticles require multi-step modifications of carbohydrates moieties to conjugate to nanoparticle surface. However, the required synthetic manipulations are difficult and time consuming. We report herewith a simple and versatile method for preparing glyconanoparticles. This method is based on the utilization of clean and convenient microwave irradiation energy for one-step, site-specific conjugation of unmodified carbohydrates onto hydrazide-functionalized Au nanoparticles. A colorimetric assay that utilizes the ensemble of gold glyconanoparticles and Concanavalin A (ConA) was also presented. This feasible assay system was developed to analyze multivalent interactions and to determine the dissociation constant (Kd) for five kind of Au glyconanoparticles with lectin. Surface plasmon changes of the Au glyconanparticles as a function of lectin-carbohydrate interactions were measured and the dissociation constants were determined based on non-linear curve fitting. The strength of the interaction of carbohydrates with ConA was found to be as follows: Maltose > Mannose > Glucose > Lactose > MAN5. PMID:19698698

Enhanced Reciprocal Interactions between Molecular Stresses and Optoelectronic Energy Transfers for High Efficiency Long Life Devices Based on Conjugated Polymers

DTIC Science & Technology

2014-10-15

led to lower PL efficiencies. The latter, however, posed no problems for solar cells aplications . Furthermore, the molecular dipoles composed of...illuminated under the light of the energy falling in the absorption range of the conjugated polymer, the polymer chain mobility decreased...the other hand, increased concomitantly (Figs. 33, 35). The driving force for the molecular flows is the diffusion of the mobile PS chains toward

Organic Diode Rectifiers Based on a High-Performance Conjugated Polymer for a Near-Field Energy-Harvesting Circuit.

PubMed

Higgins, Stuart G; Agostinelli, Tiziano; Markham, Steve; Whiteman, Robert; Sirringhaus, Henning

2017-12-01

Organic diodes manufactured on a plastic substrate capable of rectifying a high-frequency radio-frequency identification signal (13.56 MHz), with sufficient power to operate an interactive smart tag, are reported. A high-performance conjugated semiconductor (an indacenodithiophene-benzothiadiazole copolymer) is combined with a carefully optimized architecture to satisfy the electrical requirements for an organic-semiconductor-based logic chip. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Measuring the Adhesion Forces for the Multivalent Binding of Vancomycin-Conjugated Dendrimer to Bacterial Cell-Wall Peptide.

PubMed

Peterson, Elizabeth; Joseph, Christine; Peterson, Hannah; Bouwman, Rachael; Tang, Shengzhuang; Cannon, Jayme; Sinniah, Kumar; Choi, Seok Ki

2018-06-19

Multivalent ligand-receptor interaction provides the fundamental basis for the hypothetical notion that high binding avidity relates to the strong force of adhesion. Despite its increasing importance in the design of targeted nanoconjugates, an understanding of the physical forces underlying the multivalent interaction remains a subject of urgent investigation. In this study, we designed three vancomycin (Van)-conjugated dendrimers G5(Van) n ( n = mean valency = 0, 1, 4) for bacterial targeting with generation 5 (G5) poly(amidoamine) dendrimer as a multivalent scaffold and evaluated both their binding avidity and physical force of adhesion to a bacterial model surface by employing surface plasmon resonance (SPR) spectroscopy and atomic force microscopy. The SPR experiment for these conjugates was performed in a biosensor chip surface immobilized with a bacterial cell-wall peptide Lys-d-Ala-d-Ala. Of these, G5(Van) 4 bound most tightly with a K D of 0.34 nM, which represents an increase in avidity by 2 or 3 orders of magnitude relative to a monovalent conjugate G5(Van) 1 or free vancomycin, respectively. By single-molecule force spectroscopy, we measured the adhesion force between G5(Van) n and the same cell-wall peptide immobilized on the surface. The distribution of adhesion forces increased in proportion to vancomycin valency with the mean force of 134 pN at n = 4 greater than 96 pN at n = 1 at a loading rate of 5200 pN/s. In summary, our results are strongly supportive of the positive correlation between the avidity and adhesion force in the multivalent interaction of vancomycin nanoconjugates.

Ferrocene-oligonucleotide conjugates for electrochemical probing of DNA.

PubMed Central

Ihara, T; Maruo, Y; Takenaka, S; Takagi, M

1996-01-01

Toward the development of a universal, sensitive and convenient method of DNA (or RNA) detection, electrochemically active oligonucleotides were prepared by covalent linkage of a ferrocenyl group to the 5'-aminohexyl-terminated synthetic oligonucleotides. Using these electrochemically active probes, we have been able to demonstrate the detection of DNA and RNA at femtomole levels by HPLC equipped with an ordinary electrochemical detector (ECD) [Takenaka,S., Uto,Y., Kondo,H., Ihara,T. and Takagi,M. (1994) Anal. Biochem., 218, 436-443]. Thermodynamic and electrochemical studies of the interaction between the probes and the targets are presented here. The thermodynamics obtained revealed that the conjugation stabilizes the triple-helix complexes by 2-3 kcal mol-1 (1-2 orders increment in binding constant) at 298 K, which corresponds to the effect of elongation of additional several base triplets. The main cause of this thermodynamic stabilization by the conjugation is likely to be the overall conformational change of whole structure of the conjugate rather than the additional local interaction. The redox potential of the probe was independent of the target structure, which is either single- or double stranded. However, the potential is slightly dependent (with a 10-30 mV negative shift on complexation) on the extra sequence in the target, probably because the individual sequence is capable of contacting or interacting with the ferrocenyl group in a slightly different way from each other. This small potential shift itself, however, does not cause any inconvenience on practical applications in detecting the probes by using ECD. These results lead to the conclusion that the redox-active probes are very useful for the microanalysis of nucleic acids due to the stability of the complexes, high detection sensitivity and wide applicability to the target structures (DNA and RNA; single- and double strands) and the sequences. PMID:8932383

Preparation and sonodynamic activities of water-soluble tetra-α-(3-carboxyphenoxyl) zinc(II) phthalocyanine and its bovine serum albumin conjugate.

PubMed

Xu, He-Nan; Chen, Hai-Jun; Zheng, Bi-Yuan; Zheng, Yun-Quan; Ke, Mei-Rong; Huang, Jian-Dong

2015-01-01

Sonodynamic therapy (SDT) is a new approach for cancer treatment, involving the synergistic effect of ultrasound and certain chemical compounds termed as sonosensitizers. A water-soluble phthalocyanine, namely tetra-α-(3-carboxyphenoxyl) zinc(II) phthalocyanine (ZnPcC4), has been prepared and characterized. The interactions between ZnPcC4 and bovine serum albumin (BSA) were also investigated by absorption and fluorescence spectroscopy. It was found that there were strong interactions between ZnPcC4 and BSA with a binding constant of 6.83×10(7)M(-1). A non-covalent BSA conjugate of ZnPcC4 (ZnPcC4-BSA) was prepared. Both ZnPcC4 and ZnPcC4-BSA exhibited efficient sonodynamic activities against HepG2 human hepatocarcinoma cells. Compared with ZnPcC4, conjugate ZnPcC4-BSA showed a higher sonodynamic activity with an IC50 value of 7.5μM. Upon illumination with ultrasound, ZnPcC4-BSA can induce an increase of intracellular reactive oxygen species (ROS) level, resulting in cellular apoptosis. The results suggest that the albumin conjugates of zinc(II) phthalocyanines functionalized with carboxyls can serve as promising sonosensitizers for sonodynamic therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

Multivalent peptoid conjugates which overcome enzalutamide resistance in prostate cancer cells

PubMed Central

Wang, Yu; Dehigaspitiya, Dilani C.; Levine, Paul M.; Profit, Adam A.; Haugbro, Michael; Imberg-Kazdan, Keren; Logan, Susan K.; Kirshenbaum, Kent; Garabedian, Michael J.

2016-01-01

Development of resistance to anti-androgens for treating advanced prostate cancer is a growing concern, and extends to recently developed therapeutics, including enzalutamide. Therefore, new strategies to block androgen receptor (AR) function in prostate cancer are required. Here we report the characterization of a multivalent conjugate presenting two bioactive ethisterone ligands arrayed as spatially defined pendant groups on a peptoid oligomer. The conjugate, named Multivalent Peptoid Conjugate 6 (MPC6), suppressed the proliferation of multiple AR-expressing prostate cancer cell lines including those that failed to respond to enzalutamide and ARN509. The structure-activity relationships of MPC6 variants were evaluated, revealing that increased spacing between ethisterone moieties and changes in peptoid topology eliminated its anti-proliferative effect, suggesting that both ethisterone ligand presentation and scaffold characteristics contribute to MPC6 activity. Mechanistically, MPC6 blocked AR coactivator-peptide interaction, and prevented AR intermolecular interactions. Protease sensitivity assays suggested that the MPC6-bound AR induced a receptor conformation distinct from that of dihydrotestosterone- or enzalutamide-bound AR. Pharmacological studies revealed that MPC6 was metabolically stable and displayed a low plasma clearance rate. Notably, MPC6 treatment reduced tumor growth and decreased Ki67 and AR expression in mouse xenograft models of enzalutamide-resistant LNCaP-abl cells. Thus, MPC6 represents a new class of compounds with the potential to combat treatment-resistant prostate cancer. PMID:27488525

Construction of a Cordyceps sinensis exopolysaccharide-conjugated selenium nanoparticles and enhancement of their antioxidant activities.

PubMed

Xiao, Yidong; Huang, Qilin; Zheng, Zhaomin; Guan, Han; Liu, Shiyu

2017-06-01

A Cordyceps sinensis exopolysaccharide (EPS)-conjugated selenium nanoparticles (SeNPs) were successfully constructed through the reduction of SeO 3 2- . The EPS-SeNPs were characterized in terms of formation, morphology, size, Se distribution and phase by UV-vis, FT-IR, transmission electron microscopy (TEM), dynamic light scattering (DLS), energy dispersive X-ray (EDX) and wide angle X-ray diffraction (WAXD) measurements. Results revealed that the SeNPs conjugated to EPS were amorphous and could be well dispersed at a size range of 80-125nm. The interactions between the OH groups of EPS and SeNPs substituted for intermolecular interaction in native EPS to form new CO⋯Se bonds, resulting in good dispersion of SeNPs in the EPS matrix. Besides, the EPS-SeNPs at different Se/P ratios exhibited significant scavenging ability on superoxide anion radical (O 2 - ) and ABTS radical cation (ABTS + ) when compared to pure EPS, indicating that the conjugated SeNPs reinforced antioxidant effect of EPS. This work not only provides a simple and efficient way to construct well-dispersed SeNPs in aqueous system, and demonstrates the vital role of the EPS as a biopolymer template for dispersion, stabilization and size control of SeNPs, but also finds the EPS-SeNPs can potentially serve as a good antioxidant towards O 2 - and ABTS + . Copyright © 2017 Elsevier B.V. All rights reserved.

An enrichment method based on synergistic and reversible covalent interactions for large-scale analysis of glycoproteins.

PubMed

Xiao, Haopeng; Chen, Weixuan; Smeekens, Johanna M; Wu, Ronghu

2018-04-27

Protein glycosylation is ubiquitous in biological systems and essential for cell survival. However, the heterogeneity of glycans and the low abundance of many glycoproteins complicate their global analysis. Chemical methods based on reversible covalent interactions between boronic acid and glycans have great potential to enrich glycopeptides, but the binding affinity is typically not strong enough to capture low-abundance species. Here, we develop a strategy using dendrimer-conjugated benzoboroxole to enhance the glycopeptide enrichment. We test the performance of several boronic acid derivatives, showing that benzoboroxole markedly increases glycopeptide coverage from human cell lysates. The enrichment is further improved by conjugating benzoboroxole to a dendrimer, which enables synergistic benzoboroxole-glycan interactions. This robust and simple method is highly effective for sensitive glycoproteomics analysis, especially capturing low-abundance glycopeptides. Importantly, the enriched glycopeptides remain intact, making the current method compatible with mass-spectrometry-based approaches to identify glycosylation sites and glycan structures.

Preparation, Characterization and Application of Optical Switch Probes.

PubMed

Petchprayoon, Chutima; Marriott, Gerard

2010-08-01

Optical switches represent a new class of molecular probe with applications in high contrast imaging and optical manipulation of protein interactions. Small molecule, organic optical switches based on nitrospirobenzopyran (NitroBIPS) and their reactive derivatives and conjugates undergo efficient, rapid and reversible, orthogonal optically-driven transitions between a colorless spiro (SP) state and a colored merocyanine (MC) state. The excited MC-state also emits fluorescence, which serves as readout of the state of the switch. Defined optical perturbations of SP and MC generate a defined waveform of MC-fluorescence that can be isolated against unmodulated background signals by using a digital optical lock-in detection approach or to control specific dipolar interactions on proteins. The protocols describe general procedures for the synthesis and spectroscopic characterization of NitroBIPS and specifically labeled conjugates along with methods for the manipulation of dipolar interactions on proteins and imaging of the MC-state of NitroBIPS within living cells.

Solution Adsorption Formation of a π-Conjugated Polymer/Graphene Composite for High-Performance Field-Effect Transistors.

PubMed

Liu, Yun; Hao, Wei; Yao, Huiying; Li, Shuzhou; Wu, Yuchen; Zhu, Jia; Jiang, Lei

2018-01-01

Semiconducting polymers with π-conjugated electronic structures have potential application in the large-scale printable fabrication of high-performance electronic and optoelectronic devices. However, owing to their poor environmental stability and high-cost synthesis, polymer semiconductors possess limited device implementation. Here, an approach for constructing a π-conjugated polymer/graphene composite material to circumvent these limitations is provided, and then this material is patterned into 1D arrays. Driven by the π-π interaction, several-layer polymers can be adsorbed onto the graphene planes. The low consumption of the high-cost semiconductor polymers and the mass production of graphene contribute to the low-cost fabrication of the π-conjugated polymer/graphene composite materials. Based on the π-conjugated system, a reduced π-π stacking distance between graphene and the polymer can be achieved, yielding enhanced charge-transport properties. Owing to the incorporation of graphene, the composite material shows improved thermal stability. More generally, it is believed that the construction of the π-conjugated composite shows clear possibility of integrating organic molecules and 2D materials into microstructure arrays for property-by-design fabrication of functional devices with large area, low cost, and high efficiency. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multiplexed protein detection using antibody-conjugated microbead arrays in a microfabricated electrophoretic device

PubMed Central

Barbee, Kristopher D.; Hsiao, Alexander P.; Roller, Eric E.; Huang, Xiaohua

2011-01-01

We report the development of a microfabricated electrophoretic device for assembling high-density arrays of antibody-conjugated microbeads for chip-based protein detection. The device consists of a flow cell formed between a gold-coated silicon chip with an array of microwells etched in a silicon dioxide film and a glass coverslip with a series of thin gold counter electrode lines. We have demonstrated that 0.4 and 1 μm beads conjugated with antibodies can be rapidly assembled into the microwells by applying a pulsed electric field across the chamber. By assembling step-wise a mixture of fluorescently labeled antibody-conjugated microbeads, we incorporated both spatial and fluorescence encoding strategies to demonstrate significant multiplexing capabilities. We have shown that these antibody-conjugated microbead arrays can be used to perform on-chip sandwich immunoassays to detect test antigens at concentrations as low as 40 pM (6 ng/mL). A finite element model was also developed to examine the electric field distribution within the device for different counter electrode configurations over a range of line pitches and chamber heights. This device will be useful for assembling high-density, encoded antibody arrays for multiplexed detection of proteins and other types of protein-conjugated microbeads for applications such as the analysis of protein-protein interactions. PMID:20820631

Temporal switching of homo-FRET pathways in single-chromophore dimer models of π-conjugated polymers.

PubMed

Stangl, Thomas; Bange, Sebastian; Schmitz, Daniela; Würsch, Dominik; Höger, Sigurd; Vogelsang, Jan; Lupton, John M

2013-01-09

A set of π-conjugated oligomer dimers templated in molecular scaffolds is presented as a model system for studying the interactions between chromophores in conjugated polymers (CPs). Single-molecule spectroscopy was used to reveal energy transfer dynamics between two oligomers in either a parallel or oblique-angle geometry. In particular, the conformation of single molecules embedded in a host matrix was investigated via polarized excitation and emission fluorescence microscopy in combination with fluorescence correlation spectroscopy. While the intramolecular interchromophore conformation was found to have no impact on the fluorescence quantum yield, lifetime, or photon statistics (antibunching), the long-term nonequilibrium dynamics of energy transfer within these bichromophoric systems was accessible by studying the linear dichroism in emission at the single-molecule level, which revealed reversible switching of the emission between the two oligomers. In bulk polymer films, interchromophore coupling promotes the migration of excitation energy to quenching sites. Realizing the presence and dynamics of such interactions is crucial for understanding limitations on the quantum efficiency of larger CP materials.

Light and dark-activated biocidal activity of conjugated polyelectrolytes.

PubMed

Ji, Eunkyung; Corbitt, Thomas S; Parthasarathy, Anand; Schanze, Kirk S; Whitten, David G

2011-08-01

This Spotlight on Applications provides an overview of a research program that has focused on the development and mechanistic study of cationic conjugated polyelectrolytes (CPEs) that function as light- and dark-active biocidal agents. Investigation has centered on poly-(phenylene ethynylene) (PPE) type conjugated polymers that are functionalized with cationic quaternary ammonium solubilizing groups. These polymers are found to interact strongly with Gram-positive and Gram-negative bacteria, and upon illumination with near-UV and visible light act to rapidly kill the bacteria. Mechanistic studies suggest that the cationic PPE-type polymers efficiently sensitize singlet oxygen ((1)O(2)), and this cytotoxic agent is responsible for initiating the sequence of events that lead to light-activated bacterial killing. Specific CPEs also exhibit dark-active antimicrobial activity, and this is believed to arise due to interactions between the cationic/lipophilic polymers and the negatively charged outer membrane characteristic of Gram-negative bacteria. Specific results are shown where a cationic CPE with a degree of polymerization of 49 exhibits pronounced light-activated killing of E. coli when present in the cell suspension at a concentration of 1 μg mL(-1).

Interaction of Vaccination and Reduction of Antibiotic Use Drives Unexpected Increase of Pneumococcal Meningitis

PubMed Central

de Cellès, Matthieu Domenech; Pons-Salort, Margarita; Varon, Emmanuelle; Vibet, Marie-Anne; Ligier, Caroline; Letort, Véronique; Opatowski, Lulla; Guillemot, Didier

2015-01-01

Antibiotic-use policies may affect pneumococcal conjugate-vaccine effectiveness. The reported increase of pneumococcal meningitis from 2001 to 2009 in France, where a national campaign to reduce antibiotic use was implemented in parallel to the introduction of the 7-valent conjugate vaccine, provides unique data to assess these effects. We constructed a mechanistic pneumococcal transmission model and used likelihood to assess the ability of competing hypotheses to explain that increase. We find that a model integrating a fitness cost of penicillin resistance successfully explains the overall and age-stratified pattern of serotype replacement. By simulating counterfactual scenarios of public health interventions in France, we propose that this fitness cost caused a gradual and pernicious interaction between the two interventions by increasing the spread of nonvaccine, penicillin-susceptible strains. More generally, our results indicate that reductions of antibiotic use may counteract the benefits of conjugate vaccines introduced into countries with low vaccine-serotype coverages and high-resistance frequencies. Our findings highlight the key role of antibiotic use in vaccine-induced serotype replacement and suggest the need for more integrated approaches to control pneumococcal infections. PMID:26063589

Interaction of Vaccination and Reduction of Antibiotic Use Drives Unexpected Increase of Pneumococcal Meningitis.

PubMed

de Cellès, Matthieu Domenech; Pons-Salort, Margarita; Varon, Emmanuelle; Vibet, Marie-Anne; Ligier, Caroline; Letort, Véronique; Opatowski, Lulla; Guillemot, Didier

2015-06-11

Antibiotic-use policies may affect pneumococcal conjugate-vaccine effectiveness. The reported increase of pneumococcal meningitis from 2001 to 2009 in France, where a national campaign to reduce antibiotic use was implemented in parallel to the introduction of the 7-valent conjugate vaccine, provides unique data to assess these effects. We constructed a mechanistic pneumococcal transmission model and used likelihood to assess the ability of competing hypotheses to explain that increase. We find that a model integrating a fitness cost of penicillin resistance successfully explains the overall and age-stratified pattern of serotype replacement. By simulating counterfactual scenarios of public health interventions in France, we propose that this fitness cost caused a gradual and pernicious interaction between the two interventions by increasing the spread of nonvaccine, penicillin-susceptible strains. More generally, our results indicate that reductions of antibiotic use may counteract the benefits of conjugate vaccines introduced into countries with low vaccine-serotype coverages and high-resistance frequencies. Our findings highlight the key role of antibiotic use in vaccine-induced serotype replacement and suggest the need for more integrated approaches to control pneumococcal infections.

How the Knowledge of Interactions between Meningococcus and the Human Immune System Has Been Used to Prepare Effective Neisseria meningitidis Vaccines

PubMed Central

Gasparini, R.; Panatto, D.; Bragazzi, N. L.; Lai, P. L.; Bechini, A.; Levi, M.; Durando, P.; Amicizia, D.

2015-01-01

In the last decades, tremendous advancement in dissecting the mechanisms of pathogenicity of Neisseria meningitidis at a molecular level has been achieved, exploiting converging approaches of different disciplines, ranging from pathology to microbiology, immunology, and omics sciences (such as genomics and proteomics). Here, we review the molecular biology of the infectious agent and, in particular, its interactions with the immune system, focusing on both the innate and the adaptive responses. Meningococci exploit different mechanisms and complex machineries in order to subvert the immune system and to avoid being killed. Capsular polysaccharide and lipooligosaccharide glycan composition, in particular, play a major role in circumventing immune response. The understanding of these mechanisms has opened new horizons in the field of vaccinology. Nowadays different licensed meningococcal vaccines are available and used: conjugate meningococcal C vaccines, tetravalent conjugate vaccines, an affordable conjugate vaccine against the N. menigitidis serogroup A, and universal vaccines based on multiple antigens each one with a different and peculiar function against meningococcal group B strains. PMID:26351643

A New Class of Antibody-Drug Conjugates with Potent DNA Alkylating Activity.

PubMed

Miller, Michael L; Fishkin, Nathan E; Li, Wei; Whiteman, Kathleen R; Kovtun, Yelena; Reid, Emily E; Archer, Katie E; Maloney, Erin K; Audette, Charlene A; Mayo, Michele F; Wilhelm, Alan; Modafferi, Holly A; Singh, Rajeeva; Pinkas, Jan; Goldmacher, Victor; Lambert, John M; Chari, Ravi V J

2016-08-01

The promise of tumor-selective delivery of cytotoxic agents in the form of antibody-drug conjugates (ADC) has now been realized, evidenced by the approval of two ADCs, both of which incorporate highly cytotoxic tubulin-interacting agents, for cancer therapy. An ongoing challenge remains in identifying potent agents with alternative mechanisms of cell killing that can provide ADCs with high therapeutic indices and favorable tolerability. Here, we describe the development of a new class of potent DNA alkylating agents that meets these objectives. Through chemical design, we changed the mechanism of action of our novel DNA cross-linking agent to a monofunctional DNA alkylator. This modification, coupled with linker optimization, generated ADCs that were well tolerated in mice and demonstrated robust antitumor activity in multiple tumor models at doses 1.5% to 3.5% of maximally tolerated levels. These properties underscore the considerable potential of these purpose-created, unique DNA-interacting conjugates for broadening the clinical application of ADC technology. Mol Cancer Ther; 15(8); 1870-8. ©2016 AACR. ©2016 American Association for Cancer Research.

A Speeding Binary in the Galactic Halo

NASA Astrophysics Data System (ADS)

Kohler, Susanna

2016-04-01

The recent discovery of a hyper-velocity binary star system in the halo of the Milky Way poses a mystery: how was this system accelerated to its high speed?Accelerating StarsUnlike the uniform motion in the Galactic disk, stars in the Milky Ways halo exhibit a huge diversity of orbits that are usually tilted relative to the disk and have a variety of speeds. One type of halo star, so-called hyper-velocity stars, travel with speeds that can approach the escape velocity of the Galaxy.How do these hyper-velocity stars come about? Assuming they form in the Galactic disk, there are multiple proposed scenarios through which they could be accelerated and injected into the halo, such as:Ejection after a close encounter with the supermassive black hole at the Galactic centerEjection due to a nearby supernova explosionEjection as the result of a dynamical interaction in a dense stellar population.Further observations of hyper-velocity stars are necessary to identify the mechanism responsible for their acceleration.J1211s SurpriseModels of J1211s orbit show it did not originate from the Galactic center (black dot). The solar symbol shows the position of the Sun and the star shows the current position of J1211. The bottom two panels show two depictions(x-y plane and r-z plane) of estimated orbits of J1211 over the past 10 Gyr. [Nmeth et al. 2016]To this end, a team of scientists led by Pter Nmeth (Friedrich Alexander University, Erlangen-Nrnberg) recently studied the candidate halo hyper-velocity star SDSS J121150.27+143716.2. The scientists obtained spectroscopy of J1211 using spectrographs at the Keck Telescope in Hawaii and ESOs Very Large Telescope in Chile. To their surprise, they discovered the signature of a companion in the spectra: J1211 is actually a binary!Nmeth and collaborators found that J1211, located roughly 18,000 light-years away, is moving at a rapid ~570 km/s relative to the galactic rest frame. The binary system consists of a hot (30,600 K) subdwarf and a cool (4,800 K) companion star in a wide orbit, likely separated by several AU.An Unknown Past and FutureWhy are these new observations of J1211 such a big deal? Because all the acceleration scenarios for a star originating in the Galactic disk fail in the case of J1211. The authors find by modeling J1211s motion that the system cant have originated in the Galactic center, so interactions with the supermassive black hole are out. And supernova explosions or dynamical interactions would tear the wide binary apart in the process of accelerating it. Nmeth and collaborators suggest instead that J1211 was either born in the halo population or accreted later from the debris of a destroyed satellite galaxy.J1211s speed is so extreme that its orbit could be either bound or unbound. Interestingly, when the authors model the binarys orbit, they find that the assumed mass of the Milky Ways dark-matter halo determines whether J1211s orbit is bound. This means that future observations of J1211 may provide a new way to probe the Galactic potential and determine the mass of the dark matter halo, in addition to revealing unexpected origins of high-velocity halo stars.CitationPter Nmeth et al 2016 ApJ 821 L13. doi:10.3847/2041-8205/821/1/L13

Modeling Aggressive Medulloblastoma Using Human Induced Pluripotent Stem Cells

DTIC Science & Technology

2017-09-01

and Myc in turn induces expression of AT1R creating a positive feedback loop and development of aggression tumor phenotype. The therapeutic...strengths are the relevant expertise of the applicant and his collaborating team, the novel paracrine positive feedback loop in EC-tumor cell...to as MYC-driven MB. The molecular mechanisms that drive MYC hyper -activation in MB remain incompletely understood. MB cells in actual tumors interact

Hyper-resolution hydrological modeling: Completeness of Formulation, Appropriateness of Descritization, and Physical LImits of Predictability

NASA Astrophysics Data System (ADS)

Ogden, F. L.

2017-12-01

HIgh performance computing and the widespread availabilities of geospatial physiographic and forcing datasets have enabled consideration of flood impact predictions with longer lead times and more detailed spatial descriptions. We are now considering multi-hour flash flood forecast lead times at the subdivision level in so-called hydroblind regions away from the National Hydrography network. However, the computational demands of such models are high, necessitating a nested simulation approach. Research on hyper-resolution hydrologic modeling over the past three decades have illustrated some fundamental limits on predictability that are simultaneously related to runoff generation mechanism(s), antecedent conditions, rates and total amounts of precipitation, discretization of the model domain, and complexity or completeness of the model formulation. This latter point is an acknowledgement that in some ways hydrologic understanding in key areas related to land use, land cover, tillage practices, seasonality, and biological effects has some glaring deficiencies. This presentation represents a review of what is known related to the interacting effects of precipitation amount, model spatial discretization, antecedent conditions, physiographic characteristics and model formulation completeness for runoff predictions. These interactions define a region in multidimensional forcing, parameter and process space where there are in some cases clear limits on predictability, and in other cases diminished uncertainty.

Neuromodulation of detrusor hyper-reflexia by functional magnetic stimulation of the sacral roots.

PubMed

Sheriff, M K; Shah, P J; Fowler, C; Mundy, A R; Craggs, M D

1996-07-01

To investigate the acute effects of functional magnetic stimulation (FMS) on detrusor hyper-reflexia using a multi-pulse magnetic stimulator. Seven male patients with established and intractable detrusor hyper-reflexia following spinal cord injury were studied. No patient was on medication and none had had previous surgery for detrusor hyper-reflexia. After optimization of magnetic stimulation of S2-S4 sacral anterior roots by recording toe flexor electromyograms, unstable detrusor activity was provoked during cystometry by rapid infusion of fluid into the bladder. The provocation test produced consistent and predictable detrusor hyper-reflexia. On some provocations, supramaximal FMS at 20 pulses/s for 5 s was applied at detrusor pressures which were > 15 cmH2O. Following FMS there was an obvious acute suppression of detrusor hyper-reflexia. There was a profound reduction in detrusor contraction, as assessed by the area under the curves of detrusor pressure with time. Functional magnetic stimulation applied over the sacrum can profoundly suppress detrusor hyper-reflexia in man. It may provide a non-invasive method of assessing patients for implantable electrical neuromodulation devices and as a therapeutic option in its own right.

Spectral engineering in π-conjugated polymers with intramolecular donor-acceptor interactions.

PubMed

Beaujuge, Pierre M; Amb, Chad M; Reynolds, John R

2010-11-16

With the development of light-harvesting organic materials for solar cell applications and molecular systems with fine-tuned colors for nonemissive electrochromic devices (e.g., smart windows, e-papers), a number of technical challenges remain to be overcome. Over the years, the concept of "spectral engineering" (tailoring the complex interplay between molecular physics and the various optical phenomena occurring across the electromagnetic spectrum) has become increasingly relevant in the field of π-conjugated organic polymers. Within the spectral engineering toolbox, the "donor-acceptor" approach uses alternating electron-rich and electron-deficient moieties along a π-conjugated backbone. This approach has proved especially valuable in the synthesis of dual-band and broadly absorbing chromophores with useful photovoltaic and electrochromic properties. In this Account, we highlight and provide insight into a present controversy surrounding the origin of the dual band of absorption sometimes encountered in semiconducting polymers structured using the "donor-acceptor" approach. Based on empirical evidence, we provide some schematic representations to describe the possible mechanisms governing the evolution of the two-band spectral absorption observed on varying the relative composition of electron-rich and electron-deficient substituents along the π-conjugated backbone. In parallel, we draw attention to the choice of the method employed to estimate and compare the absorption coefficients of polymer chromophores exhibiting distinct repeat unit lengths, and containing various extents of solubilizing side-chains along their backbone. Finally, we discuss the common assumption that "donor-acceptor" systems should have systematically lower absorption coefficients than their "all-donor" counterparts. The proposed models point toward important theoretical parameters which could be further explored at the macromolecular level to help researchers take full advantage of the complex interactions taking place in π-conjugated polymers with intramolecular "donor-acceptor" characteristics.

Noncovalent Protein and Peptide Functionalization of Single-Walled Carbon Nanotubes for Biodelivery and Optical Sensing Applications.

PubMed

Antonucci, Alessandra; Kupis-Rozmysłowicz, Justyna; Boghossian, Ardemis A

2017-04-05

The exquisite structural and optical characteristics of single-walled carbon nanotubes (SWCNTs), combined with the tunable specificities of proteins and peptides, can be exploited to strongly benefit technologies with applications in fields ranging from biomedicine to industrial biocatalysis. The key to exploiting the synergism of these materials is designing protein/peptide-SWCNT conjugation schemes that preserve biomolecule activity while keeping the near-infrared optical and electronic properties of SWCNTs intact. Since sp 2 bond-breaking disrupts the optoelectronic properties of SWCNTs, noncovalent conjugation strategies are needed to interface biomolecules to the nanotube surface for optical biosensing and delivery applications. An underlying understanding of the forces contributing to protein and peptide interaction with the nanotube is thus necessary to identify the appropriate conjugation design rules for specific applications. This article explores the molecular interactions that govern the adsorption of peptides and proteins on SWCNT surfaces, elucidating contributions from individual amino acids as well as secondary and tertiary protein structure and conformation. Various noncovalent conjugation strategies for immobilizing peptides, homopolypeptides, and soluble and membrane proteins on SWCNT surfaces are presented, highlighting studies focused on developing near-infrared optical sensors and molecular scaffolds for self-assembly and biochemical analysis. The analysis presented herein suggests that though direct adsorption of proteins and peptides onto SWCNTs can be principally applied to drug and gene delivery, in vivo imaging and targeting, or cancer therapy, nondirect conjugation strategies using artificial or natural membranes, polymers, or linker molecules are often better suited for biosensing applications that require conservation of biomolecular functionality or precise control of the biomolecule's orientation. These design rules are intended to provide the reader with a rational approach to engineering biomolecule-SWCNT platforms, broadening the breadth and accessibility of both wild-type and engineered biomolecules for SWCNT-based applications.

DNA detection using water-soluble conjugated polymers and peptide nucleic acid probes

PubMed Central

Gaylord, Brent S.; Heeger, Alan J.; Bazan, Guillermo C.

2002-01-01

The light-harvesting properties of cationic conjugated polymers are used to sensitize the emission of a dye on a specific peptide nucleic acid (PNA) sequence for the purpose of homogeneous, “real-time” DNA detection. Signal transduction is controlled by hybridization of the neutral PNA probe and the negative DNA target. Electrostatic interactions bring the hybrid complex and cationic polymer within distances required for Förster energy transfer. Conjugated polymer excitation provides fluorescein emission >25 times higher than that obtained by exciting the dye, allowing detection of target DNA at concentrations of 10 pM with a standard fluorometer. A simple and highly sensitive assay with optical amplification that uses the improved hybridization behavior of PNA/DNA complexes is thus demonstrated. PMID:12167673

Conjugated polymer sensors built on pi-extended borasiloxane cages.

PubMed

Liu, Wenjun; Pink, Maren; Lee, Dongwhan

2009-06-24

An efficient 2 + 2 cyclocondensation with dihydroxysilane converted simple arylboronic acids to bifunctional borasiloxane cage molecules, which were subsequently electropolymerized to furnish air-stable thin films. The extended [p,pi]-conjugation that defines the rigid backbone of this new conjugated polymer (CP) motif gives rise to longer-wavelength UV-vis transitions upon oxidative doping, the spectral window and intensity of which can be modified by interaction with Lewis basic reagents. Notably, this boron-containing CP undergoes a rapid and reversible color change from green to orange upon exposure to volatile amine samples under ambient conditions. This direct naked-eye detection scheme can best be explained by invoking the reversible B-N dative bond formation that profoundly influences the p-pi* orbital overlap.

The intense world theory - a unifying theory of the neurobiology of autism.

PubMed

Markram, Kamila; Markram, Henry

2010-01-01

Autism covers a wide spectrum of disorders for which there are many views, hypotheses and theories. Here we propose a unifying theory of autism, the Intense World Theory. The proposed neuropathology is hyper-functioning of local neural microcircuits, best characterized by hyper-reactivity and hyper-plasticity. Such hyper-functional microcircuits are speculated to become autonomous and memory trapped leading to the core cognitive consequences of hyper-perception, hyper-attention, hyper-memory and hyper-emotionality. The theory is centered on the neocortex and the amygdala, but could potentially be applied to all brain regions. The severity on each axis depends on the severity of the molecular syndrome expressed in different brain regions, which could uniquely shape the repertoire of symptoms of an autistic child. The progression of the disorder is proposed to be driven by overly strong reactions to experiences that drive the brain to a hyper-preference and overly selective state, which becomes more extreme with each new experience and may be particularly accelerated by emotionally charged experiences and trauma. This may lead to obsessively detailed information processing of fragments of the world and an involuntarily and systematic decoupling of the autist from what becomes a painfully intense world. The autistic is proposed to become trapped in a limited, but highly secure internal world with minimal extremes and surprises. We present the key studies that support this theory of autism, show how this theory can better explain past findings, and how it could resolve apparently conflicting data and interpretations. The theory also makes further predictions from the molecular to the behavioral levels, provides a treatment strategy and presents its own falsifying hypothesis.

Resting Energy Expenditure of Rats Acclimated to Hyper-Gravity

NASA Technical Reports Server (NTRS)

Wade, Charles E.; Moran, Megan M.; Oyama, Jiro; Schwenke, David; Dalton, Bonnie P. (Technical Monitor)

2000-01-01

To determine the influence of body mass and age on resting energy expenditure (EE) following acclimation to hyper-gravity, oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured to calculate resting energy expenditure (EE), in male rats, ages 40 to 400 days, acclimated to 1.23 or 4.1 G for a minimum of two weeks. Animals were maintained on a centrifuge to produce the hyper-gravity environment. Measurements were made over three hours in hyper-gravity during the period when the lights were on, the inactive period of rats. In rats matched for body mass (approximately 400 g) hyper-gravity increased VO2 by 18% and VCO2 by 27% compared to controls, resulting in an increase in RER, 0.80 to 0.87. There were increases in resting EE with an increase in gravity. This increase was greater when the mass of the rat was larger. Rating EE for 400g animals were increased from 47 +/- 1 kcal/kg/day at 1 G, to 57 +/- 1.5 and 5.8 +/- 2.2 kcal/kg/day at 2,3 and 4.1 G, respectively. There was no difference between the two hyper-gravity environments. When differences in age of the animals were accounted for, the increase in resting EE adjusted for body mass was increased by over 36% in older animals due to exposure to hyper-gravity. Acclimation to hyper-gravity increases the resting EE of rats, dependent upon body mass and age, and appears to alter substrate metabolism. Increasing the level of hyper-gravity, from 2.3 to 4.1 G, produced no further changes raising questions as to a dose effect of gravity level on resting metabolism.

The Intense World Theory – A Unifying Theory of the Neurobiology of Autism

PubMed Central

Markram, Kamila; Markram, Henry

2010-01-01

Autism covers a wide spectrum of disorders for which there are many views, hypotheses and theories. Here we propose a unifying theory of autism, the Intense World Theory. The proposed neuropathology is hyper-functioning of local neural microcircuits, best characterized by hyper-reactivity and hyper-plasticity. Such hyper-functional microcircuits are speculated to become autonomous and memory trapped leading to the core cognitive consequences of hyper-perception, hyper-attention, hyper-memory and hyper-emotionality. The theory is centered on the neocortex and the amygdala, but could potentially be applied to all brain regions. The severity on each axis depends on the severity of the molecular syndrome expressed in different brain regions, which could uniquely shape the repertoire of symptoms of an autistic child. The progression of the disorder is proposed to be driven by overly strong reactions to experiences that drive the brain to a hyper-preference and overly selective state, which becomes more extreme with each new experience and may be particularly accelerated by emotionally charged experiences and trauma. This may lead to obsessively detailed information processing of fragments of the world and an involuntarily and systematic decoupling of the autist from what becomes a painfully intense world. The autistic is proposed to become trapped in a limited, but highly secure internal world with minimal extremes and surprises. We present the key studies that support this theory of autism, show how this theory can better explain past findings, and how it could resolve apparently conflicting data and interpretations. The theory also makes further predictions from the molecular to the behavioral levels, provides a treatment strategy and presents its own falsifying hypothesis. PMID:21191475

Intelligent tutoring using HyperCLIPS

NASA Technical Reports Server (NTRS)

Hill, Randall W., Jr.; Pickering, Brad

1990-01-01

HyperCard is a popular hypertext-like system used for building user interfaces to databases and other applications, and CLIPS is a highly portable government-owned expert system shell. We developed HyperCLIPS in order to fill a gap in the U.S. Army's computer-based instruction tool set; it was conceived as a development environment for building adaptive practical exercises for subject-matter problem-solving, though it is not limited to this approach to tutoring. Once HyperCLIPS was developed, we set out to implement a practical exercise prototype using HyperCLIPS in order to demonstrate the following concepts: learning can be facilitated by doing; student performance evaluation can be done in real-time; and the problems in a practical exercise can be adapted to the individual student's knowledge.

A spectrum fractal feature classification algorithm for agriculture crops with hyper spectrum image

NASA Astrophysics Data System (ADS)

Su, Junying

2011-11-01

A fractal dimension feature analysis method in spectrum domain for hyper spectrum image is proposed for agriculture crops classification. Firstly, a fractal dimension calculation algorithm in spectrum domain is presented together with the fast fractal dimension value calculation algorithm using the step measurement method. Secondly, the hyper spectrum image classification algorithm and flowchart is presented based on fractal dimension feature analysis in spectrum domain. Finally, the experiment result of the agricultural crops classification with FCL1 hyper spectrum image set with the proposed method and SAM (spectral angle mapper). The experiment results show it can obtain better classification result than the traditional SAM feature analysis which can fulfill use the spectrum information of hyper spectrum image to realize precision agricultural crops classification.

X-ray induced singlet oxygen generation by nanoparticle-photosensitizer conjugates for photodynamic therapy: determination of singlet oxygen quantum yield.

PubMed

Clement, Sandhya; Deng, Wei; Camilleri, Elizabeth; Wilson, Brian C; Goldys, Ewa M

2016-01-28

Singlet oxygen is a primary cytotoxic agent in photodynamic therapy. We show that CeF3 nanoparticles, pure as well as conjugated through electrostatic interaction with the photosensitizer verteporfin, are able to generate singlet oxygen as a result of UV light and 8 keV X-ray irradiation. The X-ray stimulated singlet oxygen quantum yield was determined to be 0.79 ± 0.05 for the conjugate with 31 verteporfin molecules per CeF3 nanoparticle, the highest conjugation level used. From this result we estimate the singlet oxygen dose generated from CeF3-verteporfin conjugates for a therapeutic dose of 60 Gy of ionizing radiation at energies of 6 MeV and 30 keV to be (1.2 ± 0.7) × 10(8) and (2.0 ± 0.1) × 10(9) singlet oxygen molecules per cell, respectively. These are comparable with cytotoxic doses of 5 × 10(7)-2 × 10(9) singlet oxygen molecules per cell reported in the literature for photodynamic therapy using light activation. We confirmed that the CeF3-VP conjugates enhanced cell killing with 6 MeV radiation. This work confirms the feasibility of using X- or γ- ray activated nanoparticle-photosensitizer conjugates, either to supplement the radiation treatment of cancer, or as an independent treatment modality.

Inhibition of mRNA export in vertebrate cells by nuclear export signal conjugates

PubMed Central

Pasquinelli, Amy E.; Powers, Maureen A.; Lund, Elsebet; Forbes, Douglass; Dahlberg, James E.

1997-01-01

Leucine-rich nuclear export signals (NESs) are recognized by the NES receptor exportin 1 and are central to the export of multiple shuttling proteins and RNAs. The export of messenger RNA in vertebrates was, however, thought to occur by a different pathway, because inhibition by injection of a synthetic Rev NES conjugate could not be demonstrated. Here we find that peptide conjugates composed of the NES of either protein kinase A inhibitor protein (PKI) or the HIV-1 Rev protein, when coupled to human serum albumin, are potent inhibitors of mRNA and small nuclear RNA export. These results provide direct evidence that mRNA export in vertebrates depends on interactions between an NES and its cognate NES receptors. PKI NES conjugates are significantly more efficient at inhibiting RNA export than are REV NES conjugates, indicating that different NESs may have different abilities to promote protein and RNA export. Surprisingly, an expected control conjugate containing the mutant Rev NES sequence M10 strongly inhibited the export of intronless dihydrofolate reductase mRNA. Nuclear injection of NES peptide conjugates led to mislocalization to the nucleus of 10–20% of the cytoplasmic Ran GTPase-binding protein (RanBP1) indicating that RanBP1 shuttles between the nucleus and the cytoplasm via an NES pathway. These results demonstrate that in vertebrates the export of mRNA, like that of small nuclear RNA, 5S rRNA, and transport factors such as RanBP1, employs NES-mediated molecular machinery. PMID:9405623

Block copolymer modified surfaces for conjugation of biomacromolecules with control of quantity and activity.

PubMed

Li, Xin; Wang, Mengmeng; Wang, Lei; Shi, Xiujuan; Xu, Yajun; Song, Bo; Chen, Hong

2013-01-29

Polymer brush layers based on block copolymers of poly(oligo(ethylene glycol) methacrylate) (POEGMA) and poly(glycidyl methacrylate) (PGMA) were formed on silicon wafers by activators generated by electron transfer atom transfer radical polymerization (AGET ATRP). Different types of biomolecule can be conjugated to these brush layers by reaction of PGMA epoxide groups with amino groups in the biomolecule, while POEGMA, which resists nonspecific protein adsorption, provides an antifouling environment. Surfaces were characterized by water contact angle, ellipsometry, and Fourier transform infrared spectroscopy (FTIR) to confirm the modification reactions. Phase segregation of the copolymer blocks in the layers was observed by AFM. The effect of surface properties on protein conjugation was investigated using radiolabeling methods. It was shown that surfaces with POEGMA layers were protein resistant, while the quantity of protein conjugated to the diblock copolymer modified surfaces increased with increasing PGMA layer thickness. The activity of lysozyme conjugated on the surface could also be controlled by varying the thickness of the copolymer layer. When biotin was conjugated to the block copolymer grafts, the surface remained resistant to nonspecific protein adsorption but showed specific binding of avidin. These properties, that is, well-controlled quantity and activity of conjugated biomolecules and specificity of interaction with target biomolecules may be exploited for the improvement of signal-to-noise ratio in sensor applications. More generally, such surfaces may be useful as biological recognition elements of high specificity for functional biomaterials.

Theoretical studies of surface enhanced hyper-Raman spectroscopy: The chemical enhancement mechanism

NASA Astrophysics Data System (ADS)

Valley, Nicholas; Jensen, Lasse; Autschbach, Jochen; Schatz, George C.

2010-08-01

Hyper-Raman spectra for pyridine and pyridine on the surface of a tetrahedral 20 silver atom cluster are calculated using static hyperpolarizability derivatives obtained from time dependent density functional theory. The stability of the results with respect to choice of exchange-correlation functional and basis set is verified by comparison with experiment and with Raman spectra calculated for the same systems using the same methods. Calculated Raman spectra were found to match well with experiment and previous theoretical calculations. The calculated normal and surface enhanced hyper-Raman spectra closely match experimental results. The chemical enhancement factors for hyper-Raman are generally larger than for Raman (102-104 versus 101-102). Integrated hyper-Raman chemical enhancement factors are presented for a set of substituted pyridines. A two-state model is developed to predict these chemical enhancement factors and this was found to work well for the majority of the molecules considered, providing a rationalization for the difference between hyper-Raman and Raman enhancement factors.

A hyper-spherical adaptive sparse-grid method for high-dimensional discontinuity detection

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

Zhang, Guannan; Webster, Clayton G.; Gunzburger, Max D.

This work proposes and analyzes a hyper-spherical adaptive hierarchical sparse-grid method for detecting jump discontinuities of functions in high-dimensional spaces is proposed. The method is motivated by the theoretical and computational inefficiencies of well-known adaptive sparse-grid methods for discontinuity detection. Our novel approach constructs a function representation of the discontinuity hyper-surface of an N-dimensional dis- continuous quantity of interest, by virtue of a hyper-spherical transformation. Then, a sparse-grid approximation of the transformed function is built in the hyper-spherical coordinate system, whose value at each point is estimated by solving a one-dimensional discontinuity detection problem. Due to the smoothness of themore » hyper-surface, the new technique can identify jump discontinuities with significantly reduced computational cost, compared to existing methods. Moreover, hierarchical acceleration techniques are also incorporated to further reduce the overall complexity. Rigorous error estimates and complexity analyses of the new method are provided as are several numerical examples that illustrate the effectiveness of the approach.« less

Coupled Thermo-Electro-Magneto-Elastic Response of Smart Stiffened Panels

NASA Technical Reports Server (NTRS)

Bednarcyk, Brett A.; Yarrington, Phillip W.

2009-01-01

This report documents the procedures developed for incorporating smart laminate and panel analysis capabilities within the HyperSizer aerospace structural sizing software package. HyperSizer analyzes stiffened panels composed of arbitrary composite laminates through stiffener homogenization, or "smearing " techniques. The result is an effective constitutive equation for the stiffened panel that is suitable for use in a full vehicle-scale finite element analysis via MSC/NASTRAN. The existing thermo-elastic capabilities of HyperSizer have herein been extended to include coupled thermo-electro-magneto-elastic analysis capabilities. This represents a significant step toward realization of design tools capable of guiding the development of the next generation of smart aerospace structures. Verification results are presented that compare the developed smart HyperSizer capability with an ABAQUS piezoelectric finite element solution for a facesheet-flange combination. These results show good agreement between HyperSizer and ABAQUS, but highlight a limitation of the HyperSizer formulation in that constant electric field components are assumed.

The hyper-enrichment of V and Zn in black shales of the Late Devonian-Early Mississippian Bakken Formation (USA)

USGS Publications Warehouse

Scott, Clinton T.; Slack, John F.; Kelley, Karen Duttweiler

2017-01-01

Black shales of the Late Devonian to Early Mississippian Bakken Formation are characterized by high concentrations of organic carbon and the hyper-enrichment (> 500 to 1000s of mg/kg) of V and Zn. Deposition of black shales resulted from shallow seafloor depths that promoted rapid development of euxinic conditions. Vanadium hyper-enrichments, which are unknown in modern environments, are likely the result of very high levels of dissolved H2S (~ 10 mM) in bottom waters or sediments. Because modern hyper-enrichments of Zn are documented only in Framvaren Fjord (Norway), it is likely that the biogeochemical trigger responsible for Zn hyper-enrichment in Framvaren Fjord was also present in the Bakken basin. With Framvaren Fjord as an analogue, we propose a causal link between the activity of phototrophic sulfide oxidizing bacteria, related to the development of photic-zone euxinia, and the hyper-enrichment of Zn in black shales of the Bakken Formation.

Hyper-Rayleigh scattering in centrosymmetric systems

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

Williams, Mathew D.; Ford, Jack S.; Andrews, David L., E-mail: david.andrews@physics.org

Hyper-Rayleigh scattering (HRS) is an incoherent mechanism for optical second harmonic generation. The frequency-doubled light that emerges from this mechanism is not emitted in a laser-like manner, in the forward direction; it is scattered in all directions. The underlying theory for this effect involves terms that are quadratic in the incident field and involves an even-order optical susceptibility (for a molecule, its associated hyperpolarizability). In consequence, HRS is often regarded as formally forbidden in centrosymmetric media. However, for the fundamental three-photon interaction, theory based on the standard electric dipole approximation, representable as E1{sup 3}, does not account for all experimentalmore » observations. The relevant results emerge upon extending the theory to include E1{sup 2}M1 and E1{sup 2}E2 contributions, incorporating one magnetic dipolar or electric quadrupolar interaction, respectively, to a consistent level of multipolar expansion. Both additional interactions require the deployment of higher orders in the multipole expansion, with the E1{sup 2}E2 interaction analogous in rank and parity to a four-wave susceptibility. To elicit the correct form of response from fluid or disordered media invites a tensor representation which does not oversimplify the molecular components, yet which can produce results to facilitate the interpretation of experimental observations. The detailed derivation in this work leads to results which are summarized for the following: perpendicular detection of polarization components both parallel and perpendicular to the pump radiation, leading to distinct polarization ratio results, as well as a reversal ratio for forward scattered circular polarizations. The results provide a route to handling data with direct physical interpretation, to enable the more sophisticated design of molecules with sought nonlinear optical properties.« less

Hyper-Rayleigh scattering in centrosymmetric systems

NASA Astrophysics Data System (ADS)

Williams, Mathew D.; Ford, Jack S.; Andrews, David L.

2015-09-01

Hyper-Rayleigh scattering (HRS) is an incoherent mechanism for optical second harmonic generation. The frequency-doubled light that emerges from this mechanism is not emitted in a laser-like manner, in the forward direction; it is scattered in all directions. The underlying theory for this effect involves terms that are quadratic in the incident field and involves an even-order optical susceptibility (for a molecule, its associated hyperpolarizability). In consequence, HRS is often regarded as formally forbidden in centrosymmetric media. However, for the fundamental three-photon interaction, theory based on the standard electric dipole approximation, representable as E13, does not account for all experimental observations. The relevant results emerge upon extending the theory to include E12M1 and E12E2 contributions, incorporating one magnetic dipolar or electric quadrupolar interaction, respectively, to a consistent level of multipolar expansion. Both additional interactions require the deployment of higher orders in the multipole expansion, with the E12E2 interaction analogous in rank and parity to a four-wave susceptibility. To elicit the correct form of response from fluid or disordered media invites a tensor representation which does not oversimplify the molecular components, yet which can produce results to facilitate the interpretation of experimental observations. The detailed derivation in this work leads to results which are summarized for the following: perpendicular detection of polarization components both parallel and perpendicular to the pump radiation, leading to distinct polarization ratio results, as well as a reversal ratio for forward scattered circular polarizations. The results provide a route to handling data with direct physical interpretation, to enable the more sophisticated design of molecules with sought nonlinear optical properties.

A Case Study of Controlling Crossover in a Selection Hyper-heuristic Framework Using the Multidimensional Knapsack Problem.

PubMed

Drake, John H; Özcan, Ender; Burke, Edmund K

2016-01-01

Hyper-heuristics are high-level methodologies for solving complex problems that operate on a search space of heuristics. In a selection hyper-heuristic framework, a heuristic is chosen from an existing set of low-level heuristics and applied to the current solution to produce a new solution at each point in the search. The use of crossover low-level heuristics is possible in an increasing number of general-purpose hyper-heuristic tools such as HyFlex and Hyperion. However, little work has been undertaken to assess how best to utilise it. Since a single-point search hyper-heuristic operates on a single candidate solution, and two candidate solutions are required for crossover, a mechanism is required to control the choice of the other solution. The frameworks we propose maintain a list of potential solutions for use in crossover. We investigate the use of such lists at two conceptual levels. First, crossover is controlled at the hyper-heuristic level where no problem-specific information is required. Second, it is controlled at the problem domain level where problem-specific information is used to produce good-quality solutions to use in crossover. A number of selection hyper-heuristics are compared using these frameworks over three benchmark libraries with varying properties for an NP-hard optimisation problem: the multidimensional 0-1 knapsack problem. It is shown that allowing crossover to be managed at the domain level outperforms managing crossover at the hyper-heuristic level in this problem domain.

Control of hyper-extended passive margin architecture on subduction initiation with application to the Alps and present-day North Atlantic ocean

NASA Astrophysics Data System (ADS)

Candioti, Lorenzo; Bauville, Arthur; Picazo, Suzanne; Mohn, Geoffroy; Kaus, Boris

2016-04-01

Hyper-extended magma-poor margins are characterized by extremely thinned crust and partially serpentinized mantle exhumation. As this can act as a zone of weakness during a subsequent compression event, a hyper-extended margin can thus potentially facilitate subduction initiation. Hyper-extended margins are also found today as passive margins fringing the Atlantic and North Atlantic ocean, e.g. Iberia and New Foundland margins [1] and Porcupine, Rockwall and Hatton basins. It has been proposed in the literature that hyper-extension in the Alpine Tethys does not exceed ~600 km in width [2]. The geodynamical evolution of the Alpine and Atlantic passive margins are distinct: no subduction is yet initiated in the North Atlantic, whereas the Alpine Tethys basin has undergone subduction. Here, we investigate the control of the presence of a hyper-extended margin on subduction initiation. We perform high resolution 2D simulations considering realistic rheologies and temperature profiles for these locations. We systematically vary the length and thickness of the hyper-extended crust and serpentinized mantle, to better understand the conditions for subduction initiation. References: [1] G. Manatschal. New models for evolution of magma-poor rifted margins based on a review of data and concepts from West Iberia and the Alps. Int J Earth Sci (Geol Rundsch) (2004); 432-466. [2] G. Mohn, G. Manatschal, M. Beltrando, I. Haupert. The role of rift-inherited hyper-extension in alpine-type orogens. Terra Nova (2014); 347-353.

A practical approach to spectral calibration of short wavelength infrared hyper-spectral imaging systems

NASA Astrophysics Data System (ADS)

Bürmen, Miran; Pernuš, Franjo; Likar, Boštjan

2010-02-01

Near-infrared spectroscopy is a promising, rapidly developing, reliable and noninvasive technique, used extensively in the biomedicine and in pharmaceutical industry. With the introduction of acousto-optic tunable filters (AOTF) and highly sensitive InGaAs focal plane sensor arrays, real-time high resolution hyper-spectral imaging has become feasible for a number of new biomedical in vivo applications. However, due to the specificity of the AOTF technology and lack of spectral calibration standardization, maintaining long-term stability and compatibility of the acquired hyper-spectral images across different systems is still a challenging problem. Efficiently solving both is essential as the majority of methods for analysis of hyper-spectral images relay on a priori knowledge extracted from large spectral databases, serving as the basis for reliable qualitative or quantitative analysis of various biological samples. In this study, we propose and evaluate fast and reliable spectral calibration of hyper-spectral imaging systems in the short wavelength infrared spectral region. The proposed spectral calibration method is based on light sources or materials, exhibiting distinct spectral features, which enable robust non-rigid registration of the acquired spectra. The calibration accounts for all of the components of a typical hyper-spectral imaging system such as AOTF, light source, lens and optical fibers. The obtained results indicated that practical, fast and reliable spectral calibration of hyper-spectral imaging systems is possible, thereby assuring long-term stability and inter-system compatibility of the acquired hyper-spectral images.

Application of the Hyper-Poisson Generalized Linear Model for Analyzing Motor Vehicle Crashes.

PubMed

Khazraee, S Hadi; Sáez-Castillo, Antonio Jose; Geedipally, Srinivas Reddy; Lord, Dominique

2015-05-01

The hyper-Poisson distribution can handle both over- and underdispersion, and its generalized linear model formulation allows the dispersion of the distribution to be observation-specific and dependent on model covariates. This study's objective is to examine the potential applicability of a newly proposed generalized linear model framework for the hyper-Poisson distribution in analyzing motor vehicle crash count data. The hyper-Poisson generalized linear model was first fitted to intersection crash data from Toronto, characterized by overdispersion, and then to crash data from railway-highway crossings in Korea, characterized by underdispersion. The results of this study are promising. When fitted to the Toronto data set, the goodness-of-fit measures indicated that the hyper-Poisson model with a variable dispersion parameter provided a statistical fit as good as the traditional negative binomial model. The hyper-Poisson model was also successful in handling the underdispersed data from Korea; the model performed as well as the gamma probability model and the Conway-Maxwell-Poisson model previously developed for the same data set. The advantages of the hyper-Poisson model studied in this article are noteworthy. Unlike the negative binomial model, which has difficulties in handling underdispersed data, the hyper-Poisson model can handle both over- and underdispersed crash data. Although not a major issue for the Conway-Maxwell-Poisson model, the effect of each variable on the expected mean of crashes is easily interpretable in the case of this new model. © 2014 Society for Risk Analysis.

MacMouse. Developing Preschool Readiness Concepts and Skills with HyperCard and MacRecorder.

ERIC Educational Resources Information Center

Fitterman, L. Jeffrey

Through developments with the use of the "Apple Macintosh" computer, "HyperCard," and "MacRecorder," children in preschool handicapped programs are now capable of participating in appropriate computerized learning experiences. "HyperCard" allows educators to produce their own computerized instructional…

A draft map of the mouse pluripotent stem cell spatial proteome

PubMed Central

Christoforou, Andy; Mulvey, Claire M.; Breckels, Lisa M.; Geladaki, Aikaterini; Hurrell, Tracey; Hayward, Penelope C.; Naake, Thomas; Gatto, Laurent; Viner, Rosa; Arias, Alfonso Martinez; Lilley, Kathryn S.

2016-01-01

Knowledge of the subcellular distribution of proteins is vital for understanding cellular mechanisms. Capturing the subcellular proteome in a single experiment has proven challenging, with studies focusing on specific compartments or assigning proteins to subcellular niches with low resolution and/or accuracy. Here we introduce hyperLOPIT, a method that couples extensive fractionation, quantitative high-resolution accurate mass spectrometry with multivariate data analysis. We apply hyperLOPIT to a pluripotent stem cell population whose subcellular proteome has not been extensively studied. We provide localization data on over 5,000 proteins with unprecedented spatial resolution to reveal the organization of organelles, sub-organellar compartments, protein complexes, functional networks and steady-state dynamics of proteins and unexpected subcellular locations. The method paves the way for characterizing the impact of post-transcriptional and post-translational modification on protein location and studies involving proteome-level locational changes on cellular perturbation. An interactive open-source resource is presented that enables exploration of these data. PMID:26754106

Access to site-specific Fc–cRGD peptide conjugates through streamlined expressed protein ligation†

PubMed Central

Frutos, S.; Jordan, J. B.; Bio, M. M.; Muir, T. W.; Thiel, O. R.; Vila-Perelló, M.

2018-01-01

An ideal drug should be highly effective, non-toxic and be delivered by a convenient and painless single dose. We are still far from such optimal treatment but peptides, with their high target selectivity and low toxicity profiles, provide a very attractive platform from which to strive towards it. One of the major limitations of peptide drugs is their high clearance rates, which limit dosage regimen options. Conjugation to antibody Fc domains is a viable strategy to improve peptide stability by increasing their hydrodynamic radius and hijacking the Fc recycling pathway. We report the use of a split-intein based semi-synthetic approach to site-specifically conjugate a synthetic integrin binding peptide to an Fc domain. The strategy described here allows conjugating synthetic peptides to Fc domains, which is not possible via genetic methods, fully maintaining the ability of both the Fc domain and the bioactive peptide to interact with their binding partners. PMID:27722696

Cell-surface engineering by a conjugation-and-release approach based on the formation and cleavage of oxime linkages upon mild electrochemical oxidation and reduction.

PubMed

Pulsipher, Abigail; Dutta, Debjit; Luo, Wei; Yousaf, Muhammad N

2014-09-01

We report a strategy to rewire cell surfaces for the dynamic control of ligand composition on cell membranes and the modulation of cell-cell interactions to generate three-dimensional (3D) tissue structures applied to stem-cell differentiation, cell-surface tailoring, and tissue engineering. We tailored cell surfaces with bioorthogonal chemical groups on the basis of a liposome-fusion and -delivery method to create dynamic, electroactive, and switchable cell-tissue assemblies through chemistry involving chemoselective conjugation and release. Each step to modify the cell surface: activation, conjugation, release, and regeneration, can be monitored and modulated by noninvasive, label-free analytical techniques. We demonstrate the utility of this methodology by the conjugation and release of small molecules to and from cell surfaces and by the generation of 3D coculture spheroids and multilayered cell tissues that can be programmed to undergo assembly and disassembly on demand. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Effect of Fluorine Substitution on the Molecular Interactions and Performance in Polymer Solar Cells.

PubMed

Kim, In-Bok; Jang, Soo-Young; Kim, Yeong-A; Kang, Rira; Kim, In-Sik; Ko, Do-Kyeong; Kim, Dong-Yu

2017-07-19

Fluorine (F) substitution on conjugated polymers in polymer solar cells (PSCs) has a diverse effect on molecular properties and device performance. We present a series of three D-A type conjugated polymers (PBT, PFBT, and PDFBT) based on dithienothiophene and benzothiadiazole units with different numbers of F atoms to explain the influence of F substitution by comparing the molecular interactions of the polymers and the recombination kinetics in PSCs. The preaggregation behavior of PFBT and PDFBT in o-DCB at the UV-vis absorption spectra proves that both polymers have strong intermolecular interactions. Besides, more closely packed structures and change into face-on orientation of fluorinated polymers are observed in polymer:PC 71 BM blends by GIXD which is beneficial for charge transport and, ultimately, for current density in PSCs (4.3, 13.0, and 14.5 mA cm -2 for PBT, PFBT, and PDFBT, respectively). Also, the introduction of F atoms on conjugated backbones affects the recombination kinetics by suppressing bimolecular recombination, thereby improving the fill factor (0.41, 0.68, and 0.69 for PBT, PFBT, and PDFBT, respectively). Consequently, the PCE of PSCs reached 7.3% without any additional treatment (annealing, solvent additive, etc.) in the polymer containing difluorinated BT (PDFBT) that is much higher than nonfluorinated BT (PBT ∼ 1%) and monofluorinated BT (PFBT ∼ 6%).

Recent advances in near-infrared fluorescence-guided imaging surgery using indocyanine green.

PubMed

Namikawa, Tsutomu; Sato, Takayuki; Hanazaki, Kazuhiro

2015-12-01

Near-infrared (NIR) fluorescence imaging has better tissue penetration, allowing for the effective rejection of excitation light and detection deep inside organs. Indocyanine green (ICG) generates NIR fluorescence after illumination by an NIR ray, enabling real-time intraoperative visualization of superficial lymphatic channels and vessels transcutaneously. The HyperEye Medical System (HEMS) can simultaneously detect NIR rays under room light to provide color imaging, which enables visualization under bright light. Thus, NIR fluorescence imaging using ICG can provide for excellent diagnostic accuracy in detecting sentinel lymph nodes in cancer and microvascular circulation in various ischemic diseases, to assist us with intraoperative decision making. Including HEMS in this system could further improve the sentinel lymph node mapping and intraoperative identification of blood supply in reconstructive organs and ischemic diseases, making it more attractive than conventional imaging. Moreover, the development of new laparoscopic imaging systems equipped with NIR will allow fluorescence-guided surgery in a minimally invasive setting. Future directions, including the conjugation of NIR fluorophores to target specific cancer markers might be realistic technology with diagnostic and therapeutic benefits.

Interrupted E2F1-miR-34c-SCF negative feedback loop by hyper-methylation promotes colorectal cancer cell proliferation

PubMed Central

Yang, Shu; Wu, Bo; Sun, Haimei; Ji, Fengqing; Sun, Tingyi; Zhao, Yan; Zhou, Deshan

2015-01-01

Tumour suppressor miR-34c deficiency resulted from hyper-methylation in its promoter is believed to be one of the main causes of colorectal cancer (CRC). Till date, miR-34c has been validated as a direct target of p53; but previous evidence suggested other transcription factor(s) must be involved in miR-34c transcription. In the present study, we in the first place identified a core promoter region (−1118 to −883 bp) of pre-miR-34c which was embedded within a hyper-methylated CpG island. Secondly, E2F1 promoted miR-34c transcription by physical interaction with the miR-34c promoter at site −897 to −889 bp. The transcriptional activating effect of E2F1 on miR-34c was in a p53 independent manner but profoundly promoted in the presence of p53 with exposure to 5-aza-2′-deoxycytidine (DAC). Thirdly, stem cell factor (SCF), a miR-34c target, was specifically reduced upon an introduction of E2F1 which lead to suppression of CRC cell proliferation. The E2F1-suppressed cell proliferation was partially abrogated by additional miR-34c inhibitor, indicating that the anti-proliferation effect of E2F1 was probably through activating miR-34c-SCF axis. Finally, SCF/KIT signalling increased E2F1 production by reducing its proteosomal degradation dependent on PI3K/Akt-GSK3β pathway. In conclusion, our results suggested the existence of E2F1-miR-34c-SCF negative feedback loop which was interrupted by the hyper-methylation of miR-34c promoter in CRC cells and increased cell proliferation. PMID:26704889

What Are HyperCard? (Part 2).

ERIC Educational Resources Information Center

Marcus, Stephen

1989-01-01

Presents the second article in a two-part series on HyperCard materials (computer software used to build structures that create patterns and connections) designed for English and language arts classes. Suggests assignments for use with early HyperCard software that can be adapted to a variety of nonverbal "stackware." (MM)

A Study of the Effect of HyperCard and Pen-Paper Performance Assessment Methods on Expert-Novice Chemistry Problem Solving.

ERIC Educational Resources Information Center

Kumar, David D.; And Others

1994-01-01

Investigates HyperCard as a tool for assessment in science education and determines whether or not a HyperCard assessment instrument could differentiate between expert and novice student performance on balancing stoichiometric equations in science education. (ZWH)

DEVELOPMENT OF BIO-BASED MOLECULAR TECHNOLOGIES FOR REMOVAL AND REAL-TIME MONITORING OF TOXIC METALS

EPA Science Inventory

Transformation of heavy-metal related genes from a hyper-accumulator to a high-biomass species is expected to promote a zinc hyper-accumulating phenotype in the normally non-hyper-accumulating poplar. Coupling fluorescence with heavy metal proteins is anticipated to allow ...

Design and fabrication of a 900-1700 nm hyper-spectral imaging spectrometer

NASA Astrophysics Data System (ADS)

Kim, Tae Hyoung; Kong, Hong Jin; Kim, Tae Hoon; Shin, Jae Sung

2010-02-01

This paper presents a 900-1700 nm hyper-spectral imaging spectrometer which offers low distortions, a low F-number, a compact size, an easily-fabricated design and a low cost (is presented in this paper). The starting point for its optical design is discussed according to the geometrical aberration theory and Rowland circle condition. It is shown that these methods are useful in designing a push-broom hyper-spectral imaging spectrometer that has an aperture of f/2.4, modulation transfer functions of less than 0.8 at 25 cycles/mm, and spot sizes less than 10 μm. A prototype of the optimized hyper-spectral imaging spectrometer has been fabricated using a high precision machine and the experimental demonstration with the fabricated hyper-spectral imaging spectrometer is presented.

Self-assembled tunable photonic hyper-crystals

PubMed Central

Smolyaninova, Vera N.; Yost, Bradley; Lahneman, David; Narimanov, Evgenii E.; Smolyaninov, Igor I.

2014-01-01

We demonstrate a novel artificial optical material, the “photonic hyper-crystal”, which combines the most interesting features of hyperbolic metamaterials and photonic crystals. Similar to hyperbolic metamaterials, photonic hyper-crystals exhibit broadband divergence in their photonic density of states due to the lack of usual diffraction limit on the photon wave vector. On the other hand, similar to photonic crystals, hyperbolic dispersion law of extraordinary photons is modulated by forbidden gaps near the boundaries of photonic Brillouin zones. Three dimensional self-assembly of photonic hyper-crystals has been achieved by application of external magnetic field to a cobalt nanoparticle-based ferrofluid. Unique spectral properties of photonic hyper-crystals lead to extreme sensitivity of the material to monolayer coatings of cobalt nanoparticles, which should find numerous applications in biological and chemical sensing. PMID:25027947

Self-assembled tunable photonic hyper-crystals.

PubMed

Smolyaninova, Vera N; Yost, Bradley; Lahneman, David; Narimanov, Evgenii E; Smolyaninov, Igor I

2014-07-16

We demonstrate a novel artificial optical material, the "photonic hyper-crystal", which combines the most interesting features of hyperbolic metamaterials and photonic crystals. Similar to hyperbolic metamaterials, photonic hyper-crystals exhibit broadband divergence in their photonic density of states due to the lack of usual diffraction limit on the photon wave vector. On the other hand, similar to photonic crystals, hyperbolic dispersion law of extraordinary photons is modulated by forbidden gaps near the boundaries of photonic Brillouin zones. Three dimensional self-assembly of photonic hyper-crystals has been achieved by application of external magnetic field to a cobalt nanoparticle-based ferrofluid. Unique spectral properties of photonic hyper-crystals lead to extreme sensitivity of the material to monolayer coatings of cobalt nanoparticles, which should find numerous applications in biological and chemical sensing.

[Hyper-reactive malarial splenomegaly].

PubMed

Maazoun, F; Deschamps, O; Barros-Kogel, E; Ngwem, E; Fauchet, N; Buffet, P; Froissart, A

2015-11-01

Hyper-reactive malarial splenomegaly is a rare and severe form of chronic malaria. This condition is a common cause of splenomegaly in endemic areas. The pathophysiology of hyper-reactive malarial splenomegaly involves an intense immune reaction (predominantly B cell-driven) to repeated/chronic infections with Plasmodium sp. The diagnosis may be difficult, due to a poorly specific clinical presentation (splenomegaly, fatigue, cytopenias), a long delay between residence in a malaria-endemic area and onset of symptoms, and a frequent absence of parasites on conventional thin and thick blood smears. A strongly contributive laboratory parameter is the presence of high levels of total immunoglobulin M. When the diagnostic of hyper-reactive malarial splenomegaly is considered, search for anti-Plasmodium antibodies and Plasmodium nucleic acids (genus and species) by PCR is useful. Diagnosis of hyper-reactive malarial splenomegaly relies on the simultaneous presence of epidemiological, clinical, biological and follow-up findings. Regression of both splenomegaly and hypersplenism following antimalarial therapy allows the differential diagnosis with splenic lymphoma, a common complication of hyper-reactive malarial splenomegaly. Although rare in Western countries, hyper-reactive malarial splenomegaly deserves increased medical awareness to reduce the incidence of incorrect diagnosis, to prevent progression to splenic lymphoma and to avoid splenectomy. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Renal responses to plasma volume expansion and hyperosmolality in fasting seal pups

NASA Technical Reports Server (NTRS)

Ortiz, Rudy M.; Wade, Charles E.; Costa, Daniel P.; Ortiz, C. Leo

2002-01-01

Renal responses were quantified in northern elephant seal (Mirounga angustirostris) pups during their postweaning fast to examine their excretory capabilities. Pups were infused with either isotonic (0.9%; n = 8; Iso) or hypertonic (16.7%; n = 7; Hyper) saline via an indwelling catheter such that each pup received 3 mmol NaCl/kg. Diuresis after the infusions was similar in magnitude between the two treatments. Osmotic clearance increased by 37% in Iso and 252% in Hyper. Free water clearance was reduced 3.4-fold in Hyper but was not significantly altered in Iso. Glomerular filtration rate increased 71% in the 24-h period after Hyper, but no net change occurred during the same time after Iso. Natriuresis increased 3.6-fold in Iso and 5.3-fold in Hyper. Iso decreased plasma arginine vasopressin (AVP) and cortisol acutely, whereas Hyper increased plasma and excreted AVP and cortisol. Iso was accompanied by the retention of water and electrolytes, whereas the Hyper load was excreted within 24 h. Natriuresis is attributed to increased filtration and is independent of an increase in atrial natriuretic peptide and decreases in ANG II and aldosterone. Fasting pups appear to have well-developed kidneys capable of both extreme conservation and excretion of Na(+).

Evaluation of a Tool for Producing and Presenting Interactive Videodisc Job Aids

DTIC Science & Technology

1994-03-01

and MacroMind Director, which lacks some authoring capablities (Macromedia Inc, approximate cost of Sinclude systems in Macintosh format such as...HyperCair (Claris Corp., approximate cost of $199) or SuperCmd (Aldus Corp., approximate cost of $299) and systems in Windows format such as Guide 3.1...scripting language to be used with a wide variety of hardware components. The ELVIS hypermedia system uses manufaturers ’ external commands to control

Gold nanoparticle–M2e conjugate coformulated with CpG induces protective immunity against influenza A virus

PubMed Central

Tao, Wenqian; Ziemer, Katherine S; Gill, Harvinder S

2014-01-01

Aim: This study aimed to develop a novel influenza A vaccine by conjugating the highly conserved extracellular region of the matrix 2 protein (M2e) of influenza A virus to gold nanoparticles (AuNPs) and to test the vaccine in a mouse influenza challenge model. Materials & methods: Citrate-reduced AuNPs (diameter: 12 nm) were synthesized, and characterized by transmission electron microscopy and dynamic light scattering. M2e was conjugated to AuNPs through thiol–gold interactions to form M2e–AuNP conjugates. Particle stability was confirmed by UV–visible spectra, and M2e conjugation was further characterized by x-ray photoelectron spectroscopy. Mice were immunized with M2e–AuNPs with or without CpG (cytosine-guanine rich oligonucleotide) as an adjuvant with appropriate control groups. Sera was collected and M2e-specific immunoglobulin (IgG) was measured, and immunized mice were challenged with PR8-H1N1 influenza virus. Results: M2e-capped AuNPs could be lyophilized and stably resuspended in water. Intranasal vaccination of mice with M2e–AuNP conjugates induced M2e-specific IgG serum antibodies, which significantly increased upon addition of soluble CpG as adjuvant. Upon challenge with lethal PR8, mice vaccinated with M2e-AuNP conjugates were only partially protected, while mice that received soluble CpG as adjuvant in addition to M2e–AuNP were fully protected. Conclusion: Overall, this study demonstrates the potential of using the M2e–AuNP conjugates with CpG as an adjuvant as a platform for developing an influenza A vaccine. PMID:23829488

[2.2]paracyclophane-bridged mixed-valence compounds: application of a generalized Mulliken-Hush three-level model.

PubMed

Amthor, Stephan; Lambert, Christoph

2006-01-26

A series of [2.2]paracylophane-bridged bis-triarylamine mixed-valence (MV) radical cations were analyzed by a generalized Mulliken-Hush (GMH) three-level model which takes two transitions into account: the intervalence charge transfer (IV-CT) band which is assigned to an optically induced hole transfer (HT) from one triarylamine unit to the second one and a second band associated with a triarylamine radical cation to bridge (in particular, the [2.2]paracyclophane bridge) hole transfer. From the GMH analysis, we conclude that the [2.2]paracyclophane moiety is not the limiting factor which governs the intramolecular charge transfer. AM1-CISD calculations reveal that both through-bond as well as through-space interactions of the [2.2]paracyclophane bridge play an important role for hole transfer processes. These electronic interactions are of course smaller than direct pi-conjugation, but from the order of magnitude of the couplings of the [2.2]paracyclophane MV species, we assume that this bridge is able to mediate significant through-space and through-bond interactions and that the cyclophane bridge acts more like an unsaturated spacer rather than a saturated one. From the exponential dependence of the electronic coupling V between the two triarylamine localized states on the distance r between the two redox centers, we infer that the hole transfer occurs via a superexchange mechanism. Our analysis reveals that even significantly longer pi-conjugated bridges should still mediate significant electronic interactions because the decay constant beta of a series of pi-conjugated MV species is small.

High-Throughput Quantification of SH2 Domain-Phosphopeptide Interactions with Cellulose-Peptide Conjugate Microarrays.

PubMed

Engelmann, Brett W

2017-01-01

The Src Homology 2 (SH2) domain family primarily recognizes phosphorylated tyrosine (pY) containing peptide motifs. The relative affinity preferences among competing SH2 domains for phosphopeptide ligands define "specificity space," and underpins many functional pY mediated interactions within signaling networks. The degree of promiscuity exhibited and the dynamic range of affinities supported by individual domains or phosphopeptides is best resolved by a carefully executed and controlled quantitative high-throughput experiment. Here, I describe the fabrication and application of a cellulose-peptide conjugate microarray (CPCMA) platform to the quantitative analysis of SH2 domain specificity space. Included herein are instructions for optimal experimental design with special attention paid to common sources of systematic error, phosphopeptide SPOT synthesis, microarray fabrication, analyte titrations, data capture, and analysis.

Multivalent Peptoid Conjugates Which Overcome Enzalutamide Resistance in Prostate Cancer Cells.

PubMed

Wang, Yu; Dehigaspitiya, Dilani C; Levine, Paul M; Profit, Adam A; Haugbro, Michael; Imberg-Kazdan, Keren; Logan, Susan K; Kirshenbaum, Kent; Garabedian, Michael J

2016-09-01

Development of resistance to antiandrogens for treating advanced prostate cancer is a growing concern and extends to recently developed therapeutics, including enzalutamide. Therefore, new strategies to block androgen receptor (AR) function in prostate cancer are required. Here, we report the characterization of a multivalent conjugate presenting two bioactive ethisterone ligands arrayed as spatially defined pendant groups on a peptoid oligomer. The conjugate, named Multivalent Peptoid Conjugate 6 (MPC6), suppressed the proliferation of multiple AR-expressing prostate cancer cell lines including those that failed to respond to enzalutamide and ARN509. The structure-activity relationships of MPC6 variants were evaluated, revealing that increased spacing between ethisterone moieties and changes in peptoid topology eliminated its antiproliferative effect, suggesting that both ethisterone ligand presentation and scaffold characteristics contribute to MPC6 activity. Mechanistically, MPC6 blocked AR coactivator-peptide interaction and prevented AR intermolecular interactions. Protease sensitivity assays suggested that the MPC6-bound AR induced a receptor conformation distinct from that of dihydrotestosterone- or enzalutamide-bound AR. Pharmacologic studies revealed that MPC6 was metabolically stable and displayed a low plasma clearance rate. Notably, MPC6 treatment reduced tumor growth and decreased Ki67 and AR expression in mouse xenograft models of enzalutamide-resistant LNCaP-abl cells. Thus, MPC6 represents a new class of compounds with the potential to combat treatment-resistant prostate cancer. Cancer Res; 76(17); 5124-32. ©2016 AACR. ©2016 American Association for Cancer Research.

Emotional hyper-reactivity and cardiometabolic risk in remitted bipolar patients: a machine learning approach.

PubMed

Dargél, A A; Roussel, F; Volant, S; Etain, B; Grant, R; Azorin, J-M; M'Bailara, K; Bellivier, F; Bougerol, T; Kahn, J-P; Roux, P; Aubin, V; Courtet, P; Leboyer, M; Kapczinski, F; Henry, C

2018-05-15

Remitted bipolar disorder (BD) patients frequently present with chronic mood instability and emotional hyper-reactivity, associated with poor psychosocial functioning and low-grade inflammation. We investigated emotional hyper-reactivity as a dimension for characterization of remitted BD patients, and clinical and biological factors for identifying those with and without emotional hyper-reactivity. A total of 635 adult remitted BD patients, evaluated in the French Network of Bipolar Expert Centers from 2010-2015, were assessed for emotional reactivity using the Multidimensional Assessment of Thymic States. Machine learning algorithms were used on clinical and biological variables to enhance characterization of patients. After adjustment, patients with emotional hyper-reactivity (n = 306) had significantly higher levels of systolic and diastolic blood pressure (P < 1.0 × 10 -8 ), high-sensitivity C-reactive protein (P < 1.0 × 10 -8 ), fasting glucose (P < 2.23 × 10 -6 ), glycated hemoglobin (P = 0.0008) and suicide attempts (P = 1.4 × 10 -8 ). Using models of combined clinical and biological factors for distinguishing BD patients with and without emotional hyper-reactivity, the strongest predictors were: systolic and diastolic blood pressure, fasting glucose, C-reactive protein and number of suicide attempts. This predictive model identified patients with emotional hyper-reactivity with 84.9% accuracy. The assessment of emotional hyper-reactivity in remitted BD patients is clinically relevant, particularly for identifying those at higher risk of cardiometabolic dysfunction, chronic inflammation, and suicide. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The role of complement in the success of vaccination with conjugated vs. unconjugated polysaccharide antigen.

PubMed

Salehen, Nur'ain; Stover, Cordula

2008-01-24

The complement system, a well-characterised arm of the innate immune system, significantly influences the adaptive immune response via direct cell-cell interaction and maintenance of lymphoid organ architecture. Development of vaccines is a major advance in modern health care. In this review, we highlight the importance of the marginal zone in response to both, polysaccharide and conjugated vaccines, and discuss the relevance of complement herein, based on findings obtained from animal models with specific deletions of certain complement components and from vaccination reports of complement-deficient individuals. We conclude that both, intactness of the complement system and maturity of expression of its components, are relatively more important to aid in the immune response to polysaccharide vaccine than to conjugated vaccines.

Spectrally selective fluorescence imaging of Chlorobaculum tepidum reaction centers conjugated to chelator-modified silver nanowires.

PubMed

Kowalska, Dorota; Szalkowski, Marcin; Ashraf, Khuram; Grzelak, Justyna; Lokstein, Heiko; Niedziolka-Jonsson, Joanna; Cogdell, Richard; Mackowski, Sebastian

2018-03-01

A polyhistidine tag (His-tag) present on Chlorobaculum tepidum reaction centers (RCs) was used to immobilize photosynthetic complexes on a silver nanowire (AgNW) modified with nickel-chelating nitrilo-triacetic acid (Ni-NTA). The optical properties of conjugated nanostructures were studied using wide-field and confocal fluorescence microscopy. Plasmonic enhancement of RCs conjugated to AgNWs was observed as their fluorescence intensity dependence on the excitation wavelength does not follow the excitation spectrum of RC complexes in solution. The strongest effect of plasmonic interactions on the emission intensity of RCs coincides with the absorption spectrum of AgNWs and is observed for excitation into the carotenoid absorption. From the absence of fluorescence decay shortening, we attribute the emission enhancement to increase of absorption in RC complexes.

Particle-in-a-box model of one-dimensional excitons in conjugated polymers

NASA Astrophysics Data System (ADS)

Pedersen, Thomas G.; Johansen, Per M.; Pedersen, Henrik C.

2000-04-01

A simple two-particle model of excitons in conjugated polymers is proposed as an alternative to usual highly computationally demanding quantum chemical methods. In the two-particle model, the exciton is described as an electron-hole pair interacting via Coulomb forces and confined to the polymer backbone by rigid walls. Furthermore, by integrating out the transverse part, the two-particle equation is reduced to one-dimensional form. It is demonstrated how essentially exact solutions are obtained in the cases of short and long conjugation length, respectively. From a linear combination of these cases an approximate solution for the general case is obtained. As an application of the model the influence of a static electric field on the electron-hole overlap integral and exciton energy is considered.

HyperCard K-12: Classroom Computer Learning Special Supplement Sponsored by Apple Computer.

ERIC Educational Resources Information Center

Classroom Computer Learning, 1989

1989-01-01

Follows the development of hypertext which is the electronic movement of large amounts of text. Probes the use of the Macintosh HyperCard and its applications in education. Notes programs are stackable in the computer. Provides tool, resource, and stack directory along with tips for using HyperCard. (MVL)

(Relatively) Painless Computer-Assisted Instruction with HyperStudio.

ERIC Educational Resources Information Center

Pina, Anthony A.

The College of the Desert (California) has created a multi-station technology training and development facility for faculty. HyperStudio has been adopted as the introductory tool for multimedia/hypermedia authoring for the following reasons: (1) the card/stack metaphor used by HyperStudio is easy for novices to understand and familiar to users of…

A Tour of the Stacks--HyperCard for Libraries.

ERIC Educational Resources Information Center

Ertel, Monica; Oros, Jane

1989-01-01

Description of HyperCard, a software package that runs on Macintosh microcomputers, focuses on its use in the Apple Computer, Inc., Library as a user guide to the library. Examples of screen displays are given, and a list of resources is included to help use and understand HyperCard more completely. (LRW)

Teaching with HyperCard in Place of a Textbook.

ERIC Educational Resources Information Center

Mackey, Neosha; And Others

1992-01-01

To alleviate the staffing pressures of increased demands for tours and classes at the Duane G. Meyer Library, Southwest Missouri State University, two HyperCard programs were developed--a library instruction text and a library orientation tour. A study of the relative effectiveness of the HyperCard text with paper texts for bibliographic…

Hyper-crosslinked cyclodextrin porous polymer: An efficient CO 2 capturing material with tunable porosity

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

Meng, Bo; Li, Haiyang; East China Univ. of Science and Technology, Shanghai

We designed and synthesized the cyclodextrin (CD)-based hyper-crosslinked porous polymers (HCPPs) for selective CO 2 adsorption and storage. We also explored the effect of monomer size on micropore formation, and determined a feasible way to tailor the porosity of the materials during the hyper-crosslinking process.

Hyper-crosslinked cyclodextrin porous polymer: An efficient CO 2 capturing material with tunable porosity

DOE PAGES

Meng, Bo; Li, Haiyang; East China Univ. of Science and Technology, Shanghai; ...

2016-11-11

We designed and synthesized the cyclodextrin (CD)-based hyper-crosslinked porous polymers (HCPPs) for selective CO 2 adsorption and storage. We also explored the effect of monomer size on micropore formation, and determined a feasible way to tailor the porosity of the materials during the hyper-crosslinking process.

Hyper-Activity in Children Having Behavior Disorders

ERIC Educational Resources Information Center

Childers, A. T.

2009-01-01

Frequently, child guidance clinics, pediatricians, teachers, and others have brought to their attention children who manifest hyper-activity as an outstanding feature and of such a degree as to be regarded outside the bounds of normal conduct. The literature on this subject, except for hyper-activity in infancy, has mostly to do with the…

Force spectroscopy of multivalent binding of riboflavin-conjugated dendrimers to riboflavin binding protein.

PubMed

Leistra, Abigail N; Han, Jong Hyun; Tang, Shengzhuang; Orr, Bradford G; Banaszak Holl, Mark M; Choi, Seok Ki; Sinniah, Kumar

2015-05-07

Putative riboflavin receptors are considered as biomarkers due to their overexpression in breast and prostate cancers. Hence, these receptors can be potentially exploited for use in targeted drug delivery systems where dendrimer nanoparticles with multivalent ligand attachments can lead to greater specificity in cellular interactions. In this study, the single molecule force spectroscopy technique was used to assess the physical strength of multivalent interactions by employing a riboflavin (RF)-conjugated generation 5 PAMAM dendrimer G5(RF)n nanoparticle. By varying the average RF ligand valency (n = 0, 3, 5), the rupture force was measured between G5(RF)n and the riboflavin binding protein (RFBP). The rupture force increased when the valency of RF increased. We observed at the higher valency (n = 5) three binding events that increased in rupture force with increasing loading rate. Assuming a single energy barrier, the Bell-Evans model was used to determine the kinetic off-rate and barrier width for all binding interactions. The analysis of our results appears to indicate that multivalent interactions are resulting in changes to rupture force and kinetic off-rates.

Hyper-Fit: Fitting Linear Models to Multidimensional Data with Multivariate Gaussian Uncertainties

NASA Astrophysics Data System (ADS)

Robotham, A. S. G.; Obreschkow, D.

2015-09-01

Astronomical data is often uncertain with errors that are heteroscedastic (different for each data point) and covariant between different dimensions. Assuming that a set of D-dimensional data points can be described by a (D - 1)-dimensional plane with intrinsic scatter, we derive the general likelihood function to be maximised to recover the best fitting model. Alongside the mathematical description, we also release the hyper-fit package for the R statistical language (http://github.com/asgr/hyper.fit) and a user-friendly web interface for online fitting (http://hyperfit.icrar.org). The hyper-fit package offers access to a large number of fitting routines, includes visualisation tools, and is fully documented in an extensive user manual. Most of the hyper-fit functionality is accessible via the web interface. In this paper, we include applications to toy examples and to real astronomical data from the literature: the mass-size, Tully-Fisher, Fundamental Plane, and mass-spin-morphology relations. In most cases, the hyper-fit solutions are in good agreement with published values, but uncover more information regarding the fitted model.

Aerodynamic Database Development for the Hyper-X Airframe Integrated Scramjet Propulsion Experiments

NASA Technical Reports Server (NTRS)

Engelund, Walter C.; Holland, Scott D.; Cockrell, Charles E., Jr.; Bittner, Robert D.

2000-01-01

This paper provides an overview of the activities associated with the aerodynamic database which is being developed in support of NASA's Hyper-X scramjet flight experiments. Three flight tests are planned as part of the Hyper-X program. Each will utilize a small, nonrecoverable research vehicle with an airframe integrated scramjet propulsion engine. The research vehicles will be individually rocket boosted to the scramjet engine test points at Mach 7 and Mach 10. The research vehicles will then separate from the first stage booster vehicle and the scramjet engine test will be conducted prior to the terminal decent phase of the flight. An overview is provided of the activities associated with the development of the Hyper-X aerodynamic database, including wind tunnel test activities and parallel CFD analysis efforts for all phases of the Hyper-X flight tests. A brief summary of the Hyper-X research vehicle aerodynamic characteristics is provided, including the direct and indirect effects of the airframe integrated scramjet propulsion system operation on the basic airframe stability and control characteristics. Brief comments on the planned post flight data analysis efforts are also included.

Comparison of Dextran Perfusion and GSI-B4 Isolectin Staining in a Mouse Model of Oxygen-induced Retinopathy.

PubMed

Huang, Shaofen; Liang, Jiajian; Yam, Gary Hin-Fai; Lu, Zhihao; Pang, Chi Pui; Chen, Haoyu

2015-06-01

Oxygen-induced retinopathy (OIR) is a robust and widely used animal model for the study of retinal neovascularization (NV). Dextran perfusion and Griffonia simplicifolia isolectin B4 (GSI-B4) staining are two common methods for examining the occurrence and extent of OIR. This study provides a quantitative comparison of the two for OIR detection. At postnatal day 7 (PN7), fifteen C57BL/6J mice were exposed to a 75% hyperoxic condition for 5 days and then returned to room air conditions. At PN17, the mice received intravitreal injection of GSI-B4 Alexa Fluor 568 conjugate. After 10 hours, they were infused with FITC-dextran conjugate via the left ventricle. Retinal flat mounts were photographed by confocal microscopy. Areas with fluorescent signals and the total retinal areas were quantified by Image J software. Both GSI-B4 and dextran detected the peripheral neovascular area. The mean hyper fluorescence area was 0.33 ± 0.14% of whole retinal area determined by GSI-B4 staining and 0.25 ± 0.28% determined by dextran perfusion. The difference between the two measures was 0.08% (95% CI:-0.59%, 0.43%). The Pearson correlation coefficient between the two methods was 0.386,P =0.035. The mean coincidence rates were 14.3 ± 13.4% and 24.9 ± 18.5% for GSI-B4 and dextran staining, respectively. Both methods can complement each other in demonstrating and quantitatively evaluating retinal NV. A poor agreement was found between the two methods; GSI-B4 isolectin was more effective than FITC-dextran perfusion in evaluating the extent of retinal NV in a mouse model of OIR.

Extreme Mesozoic crustal thinning in the Eastern Iberia margin: The example of the Columbrets Basin (Valencia Trough)

NASA Astrophysics Data System (ADS)

Mohn, G.; Etheve, N.; Frizon de Lamotte, D.; Roca, E.; Tugend, J.; Gómez-Romeu, J.

2017-12-01

Eastern Iberia preserves a complex succession of Mesozoic rifts partly or completely inverted during the Late Cretaceous and Cenozoic in relation with Africa-Eurasia convergence. Notably, the Valencia Trough, classically viewed as part of the Cenozoic West Mediterranean basins, preserves in its southwestern part a thick Mesozoic succession (locally »10km thick) over a highly thinned continental basement (locally only »3,5km thick). This sub-basin referred to as the Columbrets Basin, represents a Late Jurassic-Early Cretaceous hyper-extended rift basin weakly overprinted by subsequent events. Its initial configuration is well preserved allowing us to unravel its 3D architecture and tectono-stratigraphic evolution in the frame of the Mesozoic evolution of eastern Iberia. The Columbrets Basin benefits from an extensive dataset combining high resolution reflection seismic profiles, drill holes, refraction seismic data and Expanding Spread Profiles. Its Mesozoic architecture is controlled by interactions between extensional deformation and halokinesis involving the Upper Triassic salt. The thick uppermost Triassic to Cretaceous succession describes a general synclinal shape, progressively stretched and dismembered towards the basin borders. The SE-border of the basin is characterized by a large extensional detachment fault acting at crustal scale and interacting locally with the Upper Triassic décollement. This extensional structure accommodates the exhumation of the continental basement and part of the crustal thinning. Eventually our results highlight the complex interaction between extreme crustal thinning and occurrence of a pre-rift salt level for the deformation style and tectono-stratigraphic evolution of hyper-extended rift basins.

Hyper-modulation of brain networks by the amygdala among women with Borderline Personality Disorder: Network signatures of affective interference during cognitive processing.

PubMed

Soloff, Paul H; Abraham, Kristy; Ramaseshan, Karthik; Burgess, Ashley; Diwadkar, Vaibhav A

2017-05-01

Emotion dysregulation is a core characteristic of patients with Borderline Personality Disorder (BPD), and is often attributed to an imbalance in fronto-limbic network function. Hyperarousal of amygdala, especially in response to negative affective stimuli, results in affective interference with cognitive processing of executive functions. Clinical consequences include the impulsive-aggression, suicidal and self-injurious behaviors which characterize BPD. Dysfunctional interactions between amygdala and its network targets have not been well characterized during cognitive task performance. Using psychophysiological interaction analysis (PPI), we mapped network profiles of amygdala interaction with key regulatory regions during a Go No-Go task, modified to use negative, positive and neutral Ekman faces as targets. Fifty-six female subjects, 31 BPD and 25 healthy controls (HC), completed the affectively valenced Go No-Go task during fMRI scanning. In the negative affective condition, the amygdala exerted greater modulation of its targets in BPD compared to HC subjects in Rt. OFC, Rt. dACC, Rt. Parietal cortex, Rt. Basal Ganglia, and Rt. dlPFC. Across the spectrum of affective contrasts, hypermodulation in BPD subjects observed the following ordering: Negative > Neutral > Positive contrast. The amygdala seed exerted modulatory effects on specific target regions important in processing response inhibition and motor impulsiveness. The vulnerability of BPD subjects to affective interference with impulse control may be due to specific network dysfunction related to amygdala hyper-arousal and its effects on prefrontal regulatory regions such as the OFC and dACC. Copyright © 2017 Elsevier Ltd. All rights reserved.

Multivalent conjugates of basic fibroblast growth factor enhance in vitro proliferation and migration of endothelial cells.

PubMed

Zbinden, Aline; Browne, Shane; Altiok, Eda I; Svedlund, Felicia L; Jackson, Wesley M; Healy, Kevin E

2018-05-01

Growth factors hold great promise for regenerative therapies. However, their clinical use has been halted by poor efficacy and rapid clearance from tissue, necessitating the delivery of extremely high doses to achieve clinical effectiveness which has raised safety concerns. Thus, strategies to either enhance growth factor activity at low doses or to increase their residence time within target tissues are necessary for clinical success. In this study, we generated multivalent conjugates (MVCs) of basic fibroblast growth factor (bFGF), a key growth factor involved in angiogenesis and wound healing, to hyaluronic acid (HyA) polymer chains. Multivalent bFGF conjugates (mvbFGF) were fabricated with minimal non-specific interaction observed between bFGF and the HyA chain. The hydrodynamic radii of mvbFGF ranged from ∼50 to ∼75 nm for conjugation ratios of bFGF to HyA chains at low (10 : 1) and high (30 : 1) feed ratios, respectively. The mvbFGF demonstrated enhanced bioactivity compared to unconjugated bFGF in assays of cell proliferation and migration, processes critical to angiogenesis and tissue regeneration. The 30 : 1 mvbFGF outperformed the 10 : 1 conjugate, which could be due to either FGF receptor clustering or interference with receptor mediated internalization and signal deactivation. This study simultaneously investigated the role of both protein to polymer ratio and multivalent conjugate size on their bioactivity, and determined that increasing the protein-to-polymer ratio and conjugate size resulted in greater cell bioactivity.

Synthesis and evaluation of polymers for use in early warning fire alarm devices

NASA Technical Reports Server (NTRS)

Byrd, N. R.; Sheratte, M. B.

1975-01-01

Conjugated polyacetylene polymers and one condensation polyene, all containing a high degree of conjugated unsaturation, were synthesized. These polymers were characterized by chemical analysis and by thermogravimetric analysis, as well as for their film-forming capability and gas/polymer interactions. It was found that those that had a high degree of conjugated unsaturation and had resonance - stabilizing groups were very thermally stable to 200 C, e.g., poly(dicyanoacetylene), poly(ethynylferrocene) and poly(phenylacetylene); while those with labile moieties, such as poly(p-formamidophenylacetylene), among others, suffered some degradation when heated in air. When subjected to gas/polymer interaction effects, the greatest change in electrical conductance was observed when ammonia was used as the gas and poly(p-nitrophenylacetylene) was the detector. Other polymers showed similar behavior. For example, poly(ethynylcarborane), considered to be an electron acceptor also showed a change in electrical conductance when exposed to ammonia, while poly(ethynylpyridine) and poly(ethylidenepyridazine) responded to carbon monoxide. However, for "fire gases" (gases from smoldering cotton), poly(ethynylferrocene) was the most responsive. Thus, the concept of polymers with different electronegativities forming charge-transfer complexes with different gases was found to be operable.

Dynamic light scattering as an efficient tool to study glyconanoparticle-lectin interactions.

PubMed

Wang, Xin; Ramström, Olof; Yan, Mingdi

2011-10-21

Glyconanomaterials, an emerging class of bio-functional nanomaterials, have shown promise in detecting, imaging and targeting proteins, bacteria, and cells. In this article, we report that dynamic light scattering (DLS) can be used as an efficient tool to study glyconanoparticle (GNP)--lectin interactions. Silica and Au nanoparticles (NPs) conjugated with D-mannose (Man) and D-galactose (Gal) were treated with the lectins Concanavalin A (Con A) and Ricinus communis agglutinin (RCA(120)), and the hydrodynamic volumes of the resulting aggregates were measured by DLS. The results showed that the particle size grew with increasing lectin concentration. The limit of detection (LOD) was determined to be 2.9 nM for Con A with Man-conjugated and 6.6 nM for RCA(120) with Gal-conjugated silica NPs (35 nm), respectively. The binding affinity was also determined by DLS and the results showed 3-4 orders of magnitude higher affinity of GNPs than the free ligands with lectins. The assay sensitivity and affinity were particle size dependent and decreased with increasing particle diameter. Because the method relies on the particle size growth, it is therefore general and can be applied to nanomaterials of different compositions.

Application of surface plasmon resonance for the detection of carbohydrates, glycoconjugates, and measurement of the carbohydrate-specific interactions: a comparison with conventional analytical techniques. A critical review.

PubMed

Safina, Gulnara

2012-01-27

Carbohydrates (glycans) and their conjugates with proteins and lipids contribute significantly to many biological processes. That makes these compounds important targets to be detected, monitored and identified. The identification of the carbohydrate content in their conjugates with proteins and lipids (glycoforms) is often a challenging task. Most of the conventional instrumental analytical techniques are time-consuming and require tedious sample pretreatment and utilising various labeling agents. Surface plasmon resonance (SPR) has been intensively developed during last two decades and has received the increasing attention for different applications, from the real-time monitoring of affinity bindings to biosensors. SPR does not require any labels and is capable of direct measurement of biospecific interaction occurring on the sensing surface. This review provides a critical comparison of modern analytical instrumental techniques with SPR in terms of their analytical capabilities to detect carbohydrates, their conjugates with proteins and lipids and to study the carbohydrate-specific bindings. A few selected examples of the SPR approaches developed during 2004-2011 for the biosensing of glycoforms and for glycan-protein affinity studies are comprehensively discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

Characterization of benign thyroid nodules with HyperSPACE (Hyper Spectral Analysis for Characterization in Echography) before and after percutaneous laser ablation: a pilot study.

PubMed

Granchi, Simona; Vannacci, Enrico; Biagi, Elena

2017-04-22

To evaluate the capability of the HyperSPACE (Hyper SPectral Analysis for Characterization in Echography) method in tissue characterization, in order to provide information for the laser treatment of benign thyroid nodules in respect of conventional B-mode images and elastography. The method, based on the spectral analysis of the raw radiofrequency ultrasonic signal, was applied to characterize the nodule before and after laser treatment. Thirty patients (25 females and 5 males, age between 37 and 81 years) with thyroid benign nodule at cytology (Thyr 2) were evaluated by conventional ultrasonography, elastography, and HyperSPACE, before and after laser ablation. The images processed by HyperSPACE exhibit different color distributions that are referred to different tissue features. By calculating the percentages of the color coverages, the analysed nodules were subdivided into 3 groups. Each nodule belonging to the same group experienced, on average, similar necrosis extension. The nodules exhibit different Configurations (colors) distributions that could be indicative of the response of nodular tissue to the laser treatmentConclusions: HyperSPACEcan characterize benign nodules by providing additional information in respect of conventional ultrasound and elastography which is useful for support in the laser treatment of nodules in order to increase the probability of success.

Induction of gentisic acid 5-O-beta-D-xylopyranoside in tomato and cucumber plants infected by different pathogens.

PubMed

Fayos, Joaquín; Bellés, José María; López-Gresa, M Pilar; Primo, Jaime; Conejero, Vicente

2006-01-01

Tomato plants infected with the citrus exocortis viroid exhibited strongly elevated levels of a compound identified as 2,5-dihydroxybenzoic acid (gentisic acid, GA) 5-O-beta-D-xylopyranoside. The compound accumulated early in leaves expressing mild symptoms from both citrus exocortis viroid-infected tomato, and prunus necrotic ringspot virus-infected cucumber plants, and progressively accumulated concomitant with symptom development. The work presented here demonstrates that GA, mainly associated with systemic infections in compatible plant-pathogen interactions [Bellés, J.M., Garro, R., Fayos, J., Navarro, P., Primo, J., Conejero, V., 1999. Gentisic acid as a pathogen-inducible signal, additional to salicylic acid for activation of plant defenses in tomato. Mol. Plant-Microbe Interact. 12, 227-235], is conjugated to xylose. Notably, this result contrasts with those previously found in other plant-pathogen interactions in which phenolics analogues of GA as benzoic or salicylic acids, are conjugated to glucose.

Principles for Instructional Stack Development in HyperCard.

ERIC Educational Resources Information Center

McEneaney, John E.

The purpose of this paper is to provide information about obtaining and using HyperCard stacks that introduce users to principles of stack development. The HyperCard stacks described are available for downloading free of charge from a server at Indiana University South Bend. Specific directions are given for stack use, with advice for beginners. A…

NETL's Hybrid Performance, or Hyper, facility

ScienceCinema

None

2018-02-13

NETL's Hybrid Performance, or Hyper, facility is a one-of-a-kind laboratory built to develop control strategies for the reliable operation of fuel cell/turbine hybrids and enable the simulation, design, and implementation of commercial equipment. The Hyper facility provides a unique opportunity for researchers to explore issues related to coupling fuel cell and gas turbine technologies.

Hyper-Binding across Time: Age Differences in the Effect of Temporal Proximity on Paired-Associate Learning

ERIC Educational Resources Information Center

Campbell, Karen L.; Trelle, Alexandra; Hasher, Lynn

2014-01-01

Older adults show hyper- (or excessive) binding effects for simultaneously and sequentially presented distraction. Here, we addressed the potential role of hyper-binding in paired-associate learning. Older and younger adults learned a list of word pairs and then received an associative recognition task in which rearranged pairs were formed from…

E1-Like Activating Enzyme Atg7 Is Preferentially Sequestered into p62 Aggregates via Its Interaction with LC3-I

PubMed Central

Gao, Wentao; Chen, Zhixia; Wang, Wei; Stang, Michael T.

2013-01-01

p62 is constitutively degraded by autophagy via its interaction with LC3. However, the interaction of p62 with LC3 species in the context of the LC3 lipidation process is not specified. Further, the p62-mediated protein aggregation’s effect on autophagy is unclear. We systemically analyzed the interactions of p62 with all known Atg proteins involved in LC3 lipidation. We find that p62 does not interact with LC3 at the stages when it is being processed by Atg4B or when it is complexed or conjugated with Atg3. p62 does interact with LC3-I and LC3-I:Atg7 complex and is preferentially recruited by LC3-II species under autophagic stimulation. Given that Atg4B, Atg3 and LC3-Atg3 are indispensable for LC3-II conversion, our study reveals a protective mechanism for Atg4B, Atg3 and LC3-Atg3 conjugate from being inappropriately sequestered into p62 aggregates. Our findings imply that p62 could potentially impair autophagy by negatively affecting LC3 lipidation and contribute to the development of protein aggregate diseases. PMID:24023838

E1-like activating enzyme Atg7 is preferentially sequestered into p62 aggregates via its interaction with LC3-I.

PubMed

Gao, Wentao; Chen, Zhixia; Wang, Wei; Stang, Michael T

2013-01-01

p62 is constitutively degraded by autophagy via its interaction with LC3. However, the interaction of p62 with LC3 species in the context of the LC3 lipidation process is not specified. Further, the p62-mediated protein aggregation's effect on autophagy is unclear. We systemically analyzed the interactions of p62 with all known Atg proteins involved in LC3 lipidation. We find that p62 does not interact with LC3 at the stages when it is being processed by Atg4B or when it is complexed or conjugated with Atg3. p62 does interact with LC3-I and LC3-I:Atg7 complex and is preferentially recruited by LC3-II species under autophagic stimulation. Given that Atg4B, Atg3 and LC3-Atg3 are indispensable for LC3-II conversion, our study reveals a protective mechanism for Atg4B, Atg3 and LC3-Atg3 conjugate from being inappropriately sequestered into p62 aggregates. Our findings imply that p62 could potentially impair autophagy by negatively affecting LC3 lipidation and contribute to the development of protein aggregate diseases.

Fluorescent Sensing of Guanine and Guanosine Monophosphate with Conjugated Receptors Incorporating Aniline and Naphthyridine Moieties.

PubMed

Lu, Shao-Hung; Phang, Riping; Fang, Jim-Min

2016-04-15

Ethyne-linked naphthyridine-aniline conjugated molecules are selective sensors of decylguanine in dichloromethane and guanosine monophosphate in water (Kass = 16,000 M(-1)). The 2-acetamido-1,8-naphthyridine moiety binds with guanine in a DAA-ADD triply hydrogen-bonded motif. The aniline moiety enhances an electron-donating effect, and the substituent is tuned to attain extra hydrogen bonds, π-π stacking, and electrostatic interactions. The proposed binding modes are supported by a Job plot, ESI-MS, (1)H NMR, UV-vis, and fluorescence spectral analyses.

Performance of Minicomputers in Finite Element Analysis Pre and Post Processing.

DTIC Science & Technology

1980-07-29

points, and 78 rectangular plate elements. It was generated using the BULKM mesh generation program, which is a part of the GIFTS -5 system [3]. c...The program used, DECOM, is part of the GIFTS system. It uses a hyper-(partitioned) matrix generalization of the Cholesky decomposition algorithm. d...Pub. 2018, Oct. 77. 3. Kamel, H.A. and McCabe, M.W., GIFTS : Graphics Oriented Interactive Finite Element Time-Sharing System. Structural Mechanics

Unique hyper-thermal composting process in Kagoshima City forms distinct bacterial community structures.

PubMed

Tashiro, Yukihiro; Tabata, Hanae; Itahara, Asuka; Shimizu, Natsuki; Tashiro, Kosuke; Sakai, Kenji

2016-11-01

A unique compost, Satsuma soil, is produced from three types of wastewater sludge using hyper-thermal processes at temperatures much higher than that of general thermophilic processes in Kagoshima City, Japan. We analyzed the bacterial community structures of this hyper-thermal compost sample and other sludges and composts by a high-throughput barcoded pyrosequencing method targeting the 16S rRNA gene. In total, 621,076 reads were derived from 17 samples and filtered. Artificial sequences were deleted and the reads were clustered based on the operational taxonomic units (OTUs) at 97% similarity. Phylum-level analysis of the hyper-thermal compost revealed drastic changes of the sludge structures (each relative abundance) from Firmicutes (average 47.8%), Proteobacteria (average 22.3%), and Bacteroidetes (average 10.1%) to two main phyla including Firmicutes (73.6%) and Actinobacteria (25.0%) with less Proteobacteria (∼0.3%) and Bacteroidetes (∼0.1%). Furthermore, we determined the predominant species (each relative abundance) of the hyper-thermal compost including Firmicutes related to Staphylococcus cohnii (13.8%), Jeotgalicoccus coquinae (8.01%), and Staphylococcus lentus (5.96%), and Actinobacteria related to Corynebacterium stationis (6.41%), and found that these species were not predominant in wastewater sludge. In contrast, we did not observe any common structures among eight other composts produced, using the hyper-thermal composts as the inoculums, under thermophilic conditions from different materials. Principle coordinate analysis of the hyper-thermal compost indicated a large difference in bacterial community structures from material sludge and other composts. These results suggested that a distinct bacterial community structure was formed by hyper-thermal composting. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Development of hyper osmotic resistant CHO host cells for enhanced antibody production.

PubMed

Kamachi, Yasuharu; Omasa, Takeshi

2018-04-01

Cell culture platform processes are generally employed to shorten the duration of new product development. A fed-batch process with continuous feeding is a conventional platform process for monoclonal antibody production using Chinese hamster ovary (CHO) cells. To establish a simplified platform process, the feeding method can be changed from continuous feed to bolus feed. However, this change induces a rapid increase of osmolality by the bolus addition of nutrients. The increased osmolality suppresses cell culture growth, and the final product concentration is decreased. In this study, osmotic resistant CHO host cells were developed to attain a high product concentration. To establish hyper osmotic resistant CHO host cells, CHO-S host cells were passaged long-term in a hyper osmotic basal medium. There were marked differences in cell growth of the original and established host cells under iso- (328 mOsm/kg) or hyper-osmolality (over 450 mOsm/kg) conditions. Cell growth of the original CHO host cells was markedly decreased by the induction of osmotic stress, whereas cell growth of the hyper osmotic resistant CHO host cells was not affected. The maximum viable cell concentration of hyper osmotic resistant CHO host cells was 132% of CHO-S host cells after the induction of osmotic stress. Moreover, the hyper osmotic resistant characteristic of established CHO host cells was maintained even after seven passages in iso-osmolality basal medium. The use of hyper osmotic resistance CHO host cells to create a monoclonal antibody production cell line might be a new approach to increase final antibody concentrations with a fed-batch process. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

H2O2 dynamics in the malaria parasite Plasmodium falciparum

PubMed Central

Rahbari, Mahsa; Bogeski, Ivan

2017-01-01

Hydrogen peroxide is an important antimicrobial agent but is also crucially involved in redox signaling and pathogen-host cell interactions. As a basis for systematically investigating intracellular H2O2 dynamics and regulation in living malaria parasites, we established the genetically encoded fluorescent H2O2 sensors roGFP2-Orp1 and HyPer-3 in Plasmodium falciparum. Both ratiometric redox probes as well as the pH control SypHer were expressed in the cytosol of blood-stage parasites. Both redox sensors showed reproducible sensitivity towards H2O2 in the lower micromolar range in vitro and in the parasites. Due to the pH sensitivity of HyPer-3, we used parasites expressing roGFP2-Orp1 for evaluation of short-, medium-, and long-term effects of antimalarial drugs on H2O2 levels and detoxification in Plasmodium. None of the quinolines or artemisinins tested had detectable direct effects on the H2O2 homeostasis at pharmacologically relevant concentrations. However, pre-treatment of the cells with antimalarial drugs or heat shock led to a higher tolerance towards exogenous H2O2. The systematic evaluation and comparison of the two genetically encoded cytosolic H2O2 probes in malaria parasites provides a basis for studying parasite-host cell interactions or drug effects with spatio-temporal resolution while preserving cell integrity. PMID:28369083

Appreciating Hubble at Hyper-speed: A Web-tool for Students and Teachers

NASA Astrophysics Data System (ADS)

Will, Lisa M.; Mechtley, M.; Cohen, S.; Windhorst, R. A.; Malhotra, S.; Rhoads, J.; Pirzkal, N.; Summers, F.

2006-12-01

Even post-instruction, many high school students and non-science college majors lack a firm understanding of the basic concepts of physics and astronomy necessary to appreciate our expanding universe. To mitigate this trend, we are developing a state-of-the-art Web-tool called "Appreciating Hubble at Hyper-speed" (AHaH ) that uses the HST Cycle 14 Treasury Project "PEARS" (Probing Evolution And Reionization through Spectra) data. AHaH will span the fully 3-dimensional PEARS database of the GOODS/HUDF galaxy distribution from redshifts z = 0.05 to z = 6.5, spanning nearly 90% of the history of the Universe. The web-tool AHaH will allow students to interactively zoom in/out of this PEARS data base, rotate, and accelerate/decelerate towards a specified target, and travel forward or backwards in time. Hence, students can make a complete interactive journey in look-back time. AHaH will help students learn and visually understand basic concepts of physics and astronomy, and at the same time allow them to explore how galaxies change when traveling back in time, how their light is redshifted, and how they are formed and clustered in the expanding Universe. This poster will describe the features of the web-tool and the services that will be offered to help teachers implement this tool in their classrooms.

Flow dynamics in hyper-saline aquifers: hydro-geophysical monitoring and modeling

NASA Astrophysics Data System (ADS)

Haaken, Klaus; Piero Deidda, Gian; Cassiani, Giorgio; Deiana, Rita; Putti, Mario; Paniconi, Claudio; Scudeler, Carlotta; Kemna, Andreas

2017-03-01

Saline-freshwater interaction in porous media is a phenomenon of practical interest particularly for the management of water resources in arid and semi-arid environments, where precious freshwater resources are threatened by seawater intrusion and where storage of freshwater in saline aquifers can be a viable option. Saline-freshwater interactions are controlled by physico-chemical processes that need to be accurately modeled. This in turn requires monitoring of these systems, a non-trivial task for which spatially extensive, high-resolution non-invasive techniques can provide key information. In this paper we present the field monitoring and numerical modeling components of an approach aimed at understanding complex saline-freshwater systems. The approach is applied to a freshwater injection experiment carried out in a hyper-saline aquifer near Cagliari (Sardinia, Italy). The experiment was monitored using time-lapse cross-hole electrical resistivity tomography (ERT). To investigate the flow dynamics, coupled numerical flow and transport modeling of the experiment was carried out using an advanced three-dimensional (3-D) density-driven flow-transport simulator. The simulation results were used to produce synthetic ERT inversion results to be compared against real field ERT results. This exercise demonstrates that the evolution of the freshwater bulb is strongly influenced by the system's (even mild) hydraulic heterogeneities. The example also highlights how the joint use of ERT imaging and gravity-dependent flow and transport modeling give fundamental information for this type of study.

Electromagnetic Coupling of Negative Parity Nucleon Resonances N (1535) Based on Nonrelativistic Constituent Quark Model

NASA Astrophysics Data System (ADS)

Parsaei, Sara; Rajabi, Ali Akbar

2018-01-01

The electromagnetic transition between the nucleon and excited baryons has long been recognized as an important source of information for understanding strong interactions in the domain of quark confinement. We study the electromagnetic properties of the excitation of the negative parity the N*(1535) resonances in the nonrelativistic constituent quark model at large momentum transfers and have performed a calculation the longitudinal and transverse helicity amplitudes. Since the helicity amplitudes depend strongly on the quark wave function in this paper, we consider the baryon as a simple, non-relativistically three-body quark model and also consider a hypercentral potential scheme for the internal baryon structure, which makes three-body forces among three quarks. Since the hyper central potential depends only on the hyper radius, therefore, the Cornell potential which is a combination of the Coulombic-like term plus a linear confining term is considered as the potential for interaction between quarks. In our work, in solving the Schrodinger equation with the Cornell potential, the Nikiforov-Uvarov method employed, and the analytic eigen-energies and eigen-functions obtained. By using the obtained eigen-functions, the transition amplitudes calculated. We show that our results in the range {{{Q}}}2> 2 {{GeV}}2 lead to an overall better agreement with the experimental data in comparison with the other three non-relativistic quark models.

Analytic calculations of hyper-Raman spectra from density functional theory hyperpolarizability gradients

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

Ringholm, Magnus; Ruud, Kenneth; Bast, Radovan

We present the first analytic calculations of the geometrical gradients of the first hyperpolarizability tensors at the density-functional theory (DFT) level. We use the analytically calculated hyperpolarizability gradients to explore the importance of electron correlation effects, as described by DFT, on hyper-Raman spectra. In particular, we calculate the hyper-Raman spectra of the all-trans and 11-cis isomers of retinal at the Hartree-Fock (HF) and density-functional levels of theory, also allowing us to explore the sensitivity of the hyper-Raman spectra on the geometrical characteristics of these structurally related molecules. We show that the HF results, using B3LYP-calculated vibrational frequencies and force fields,more » reproduce the experimental data for all-trans-retinal well, and that electron correlation effects are of minor importance for the hyper-Raman intensities.« less

An efficient approach for inverse kinematics and redundancy resolution scheme of hyper-redundant manipulators

NASA Astrophysics Data System (ADS)

Chembuly, V. V. M. J. Satish; Voruganti, Hari Kumar

2018-04-01

Hyper redundant manipulators have a large number of degrees of freedom (DOF) than the required to perform a given task. Additional DOF of manipulators provide the flexibility to work in highly cluttered environment and in constrained workspaces. Inverse kinematics (IK) of hyper-redundant manipulators is complicated due to large number of DOF and these manipulators have multiple IK solutions. The redundancy gives a choice of selecting best solution out of multiple solutions based on certain criteria such as obstacle avoidance, singularity avoidance, joint limit avoidance and joint torque minimization. This paper focuses on IK solution and redundancy resolution of hyper-redundant manipulator using classical optimization approach. Joint positions are computed by optimizing various criteria for a serial hyper redundant manipulators while traversing different paths in the workspace. Several cases are addressed using this scheme to obtain the inverse kinematic solution while optimizing the criteria like obstacle avoidance, joint limit avoidance.

Impact of in situ granulation and temperature quenching on crystal habit and micromeritic properties of ibuprofen-cationic dextran conjugate crystanules.

PubMed

Abioye, Amos Olusegun; Kola-Mustapha, Adeola; Ruparelia, Ketan

2014-02-28

Ibuprofen was recrystallized in the presence of aqueous solution of cationic dextran derivative, Diethylaminoethyl Dextran (Ddex) using the melt-in situ granulation-crystallization technique in order to produce a stable amorphous ibuprofen-Ddex conjugates with improved morphological, micromeritic and thermo-analytical characteristics without the use of organic solvent. Ddex was used in this study because of its ability to form conjugates with various drug molecules and enhance their physicochemical characteristics and therapeutic activities. Cationic dextrans are also biocompatible and biodegradable. Mechanism of conjugation as well as the impact of conjugation on the ibuprofen crystal habit was investigated. Gaussian type normal particle size distribution was obtained and the size of the crystals in the crystanule conjugates decreased steadily, with increasing concentration of Ddex, to a minimum of 480 nm (440-folds reduction, p<0.05, n=20) at Ddex molar concentration of 0.01 mM. FT-IR spectra showed electrostatic interaction and hydrogen bonding between ibuprofen and Ddex which was confirmed with the (1)H NMR and (13)C NMR spectra. DSC curves exhibited single peaks from the binary ibuprofen-Ddex conjugate crystanules suggesting compatibility and formation of an eutectic product. The conjugate crystanules showed broad and diffuse endothermic peaks with a glass transition temperature (T(g)) of 58.3 and 59.14°C at Ddex molar concentrations of 1.56 × 10(-4) and 3.125 × 10(-4)mM respectively confirming the existence of ibuprofen-Ddex crystanule conjugates in amorphous state. Higher concentrations of Ddex decreased T(g) steadily. TGA curves showed first order degradation at low molar concentrations of Ddex up to 3.125 × 10(-4)mM which coincides with the critical granular concentration of the crystanules while higher concentrations exhibited second order degradation profile. This study provides the basis for the development of stable amorphous drug-polymer conjugates with potential practical application in controlled and extended drug release formulations. Copyright © 2014 Elsevier B.V. All rights reserved.

Polycaprolactone electrospun mesh conjugated with an MSC affinity peptide for MSC homing in vivo.

PubMed

Shao, Zhenxing; Zhang, Xin; Pi, Yanbin; Wang, Xiaokun; Jia, Zhuqing; Zhu, Jingxian; Dai, Linghui; Chen, Wenqing; Yin, Ling; Chen, Haifeng; Zhou, Chunyan; Ao, Yingfang

2012-04-01

Mesenchymal stem cell (MSC) is a promising cell source candidate in tissue engineering (TE) and regenerative medicine. However, the inability to target MSCs in tissues of interest with high efficiency and engraftment has become a significant barrier for MSC-based therapies. The mobilization and transfer of MSCs to defective/damaged sites in tissues or organs in vivo with high efficacy and efficiency has been a major concern. In the present study, we identified a peptide sequence (E7) with seven amino acids through phage display technology, which has a high specific affinity to bone marrow-derived MSCs. Subsequent analysis suggested that the peptide could efficiently interact specifically with MSCs without any species specificity. Thereafter, E7 was covalently conjugated onto polycaprolactone (PCL) electrospun meshes to construct an "MSC-homing device" for the recruitment of MSCs both in vitro and in vivo. The E7-conjugated PCL electrospun meshes were implanted into a cartilage defect site of rat knee joints, combined with a microfracture procedure to mobilize the endogenous MSCs. After 7 d of implantation, immunofluorescence staining showed that the cells grown into the E7-conjugated PCL electrospun meshes yielded a high positive rate for specific MSC surface markers (CD44, CD90, and CD105) compared with those in arginine-glycine-aspartic acid (RGD)-conjugated PCL electrospun meshes (63.67% vs. 3.03%; 59.37% vs. 2.98%; and 61.45% vs. 3.82%, respectively). Furthermore, the percentage of CD68 positive cells in the E7-conjugated PCL electrospun meshes was much lower than that in the RGD-conjugated PCL electrospun meshes (5.57% vs. 53.43%). This result indicates that E7-conjugated PCL electrospun meshes absorb much less inflammatory cells in vivo than RGD-conjugated PCL electrospun meshes. The results of the present study suggest that the identified E7 peptide sequence has a high specific affinity to MSCs. Covalently conjugating this peptide on the synthetic PCL mesh significantly enhanced the MSC recruitment of PCL in vivo. This method provides a wide range of potential applications in TE. Copyright © 2012 Elsevier Ltd. All rights reserved.

Design, synthesis and characterization of peptidomimetic conjugate of BODIPY targeting HER2 protein extracellular domain

USDA-ARS?s Scientific Manuscript database

Among the EGFRs, HER2 is a major heterodimer partner and also has important implications in the formation of particular tumors. Interaction of HER2 protein with other EGFR proteins can be modulated by small molecule ligands and, hence, these protein-protein interactions play a key role in biochemica...

The Development of Hyper-MNP: Hyper-Media Navigational Performance Scale

ERIC Educational Resources Information Center

Firat, Mehmet; Yurdakul, Isil Kabakci

2016-01-01

The present study aimed at developing a scale to evaluate navigational performance as a whole, which is one of the factors influencing learning in hyper media. In line with this purpose, depending on the related literature, an item pool of 15 factors was prepared, and these variables were decreased to 5 based on the views of 38 field experts. In…

HyperCard as a Text Analysis Tool for the Qualitative Researcher.

ERIC Educational Resources Information Center

Handler, Marianne G.; Turner, Sandra V.

HyperCard is a general-purpose program for the Macintosh computer that allows multiple ways of viewing and accessing a large body of information. Two ways in which HyperCard can be used as a research tool are illustrated. One way is to organize and analyze qualitative data from observations, interviews, surveys, and other documents. The other way…

Pre-Creating the HyperNews Classroom Community: (Not)Speaking, (Not)Writing the Subtext.

ERIC Educational Resources Information Center

Satie, Stephanie

As two groups of teachers met to set up a HyperNews network for a grant project, it became clear that politics cannot be kept out of the classroom. In creating a community of diverse writers via HyperNews, six composition classes were linked for online discourse among departments: Asian American Studies, Chicano Studies, Pan African Studies, and…

Parallel Nonnegative Least Squares Solvers for Model Order Reduction

DTIC Science & Technology

2016-03-01

NNLS problems that arise when the Energy Conserving Sampling and Weighting hyper -reduction procedure is used when constructing a reduced-order model...ScaLAPACK and performance results are presented. nonnegative least squares, model order reduction, hyper -reduction, Energy Conserving Sampling and...optimal solution. ........................................ 20 Table 6 Reduced mesh sizes produced for each solver in the ECSW hyper -reduction step

Self-assembled Tunable Photonic Hyper-crystals

DTIC Science & Technology

2014-07-16

a cobalt nanoparticle-based ferrofluid. Unique spectral properties of photonic hyper-crystals lead to extreme sensitivity of the material to...monolayer coatings of cobalt nanoparticles, which should find numerous applications in biological and chemical sensing. 2 Approved for public release...assembly of photonic hyper crystals has been achieved by application of external magnetic field to a cobalt nanoparticle based ferrofluid. Unique spectral

A novel ICOS-independent, but CD28- and SAP-dependent, pathway of T cell-dependent, polysaccharide-specific humoral immunity in response to intact Streptococcus pneumoniae versus pneumococcal conjugate vaccine

PubMed Central

Chen, Quanyi; Cannons, Jennifer L.; Paton, James C.; Akiba, Hisaya; Schwartzberg, Pamela L.; Snapper, Clifford M.

2010-01-01

Polysaccharide (PS)- and protein-specific murine IgG responses to intact Streptococcus pneumoniae (Pn) are both dependent upon CD4+ T cell help, B7-dependent costimulation, and CD40/CD40-ligand interactions. However, the primary PS-, relative to protein-specific, IgG response terminates more rapidly, requires a shorter period of T cell help and B7-dependent costimulation, and fails to generate memory. In light of the critical role for ICOS/ICOS-ligand interactions in sustaining T cell-dependent Ig responses and promoting germinal center reactions, we hypothesized that this interaction was non-essential for PS-specific IgG responses to Pn. We now demonstrate that ICOS-/-, relative to WT, mice elicit a normal PS-specific IgG isotype response to Pn, despite marked inhibition of both the primary and secondary IgG anti-protein (i.e. PspA, PspC, and PsaA) response. A blocking anti-ICOS-ligand mAb injected during primary Pn immunization inhibits both the primary anti-protein response and the generation of protein-specific memory, but has no effect when injected during secondary immunization. In contrast to Pn, both PS- and protein-specific IgG responses to a pneumococcal conjugate vaccine are inhibited in ICOS-/- mice. ICOS-/- mice immunized with intact Pn or conjugate exhibit nearly complete abrogation in germinal center formation. Finally, although mice that lack the adaptor molecule SAP resemble ICOS-/- mice (and can exhibit decreased ICOS expression), we observe that the PS-, as well as protein-specific IgG responses to both Pn and conjugate are markedly defective in SAP-/- mice. These data define a novel T cell-, SAP-, and B7-dependent, but ICOS-independent, extrafollicular pathway of Ig induction. PMID:19050242

Hyper-heuristics with low level parameter adaptation.

PubMed

Ren, Zhilei; Jiang, He; Xuan, Jifeng; Luo, Zhongxuan

2012-01-01

Recent years have witnessed the great success of hyper-heuristics applying to numerous real-world applications. Hyper-heuristics raise the generality of search methodologies by manipulating a set of low level heuristics (LLHs) to solve problems, and aim to automate the algorithm design process. However, those LLHs are usually parameterized, which may contradict the domain independent motivation of hyper-heuristics. In this paper, we show how to automatically maintain low level parameters (LLPs) using a hyper-heuristic with LLP adaptation (AD-HH), and exemplify the feasibility of AD-HH by adaptively maintaining the LLPs for two hyper-heuristic models. Furthermore, aiming at tackling the search space expansion due to the LLP adaptation, we apply a heuristic space reduction (SAR) mechanism to improve the AD-HH framework. The integration of the LLP adaptation and the SAR mechanism is able to explore the heuristic space more effectively and efficiently. To evaluate the performance of the proposed algorithms, we choose the p-median problem as a case study. The empirical results show that with the adaptation of the LLPs and the SAR mechanism, the proposed algorithms are able to achieve competitive results over the three heterogeneous classes of benchmark instances.

Research on marine and freshwater fish identification model based on hyper-spectral imaging technology

NASA Astrophysics Data System (ADS)

Fu, Yan; Guo, Pei-yuan; Xiang, Ling-zi; Bao, Man; Chen, Xing-hai

2013-08-01

With the gradually mature of hyper spectral image technology, the application of the meat nondestructive detection and recognition has become one of the current research focuses. This paper for the study of marine and freshwater fish by the pre-processing and feature extraction of the collected spectral curve data, combined with BP network structure and LVQ network structure, a predictive model of hyper spectral image data of marine and freshwater fish has been initially established and finally realized the qualitative analysis and identification of marine and freshwater fish quality. The results of this study show that hyper spectral imaging technology combined with the BP and LVQ Artificial Neural Network Model can be used for the identification of marine and freshwater fish detection. Hyper-spectral data acquisition can be carried out without any pretreatment of the samples, thus hyper-spectral imaging technique is the lossless, high- accuracy and rapid detection method for quality of fish. In this study, only 30 samples are used for the exploratory qualitative identification of research, although the ideal study results are achieved, we will further increase the sample capacity to take the analysis of quantitative identification and verify the feasibility of this theory.

Micromechanics and Piezo Enhancements of HyperSizer

NASA Technical Reports Server (NTRS)

Arnold, Steven M.; Bednarcyk, Brett A.; Yarrington, Phillip; Collier, Craig S.

2006-01-01

The commercial HyperSizer aerospace-composite-material-structure-sizing software has been enhanced by incorporating capabilities for representing coupled thermal, piezoelectric, and piezomagnetic effects on the levels of plies, laminates, and stiffened panels. This enhancement is based on a formulation similar to that of the pre-existing HyperSizer capability for representing thermal effects. As a result of this enhancement, the electric and/or magnetic response of a material or structure to a mechanical or thermal load, or its mechanical response to an applied electric or magnetic field can be predicted. In another major enhancement, a capability for representing micromechanical effects has been added by establishment of a linkage between HyperSizer and Glenn Research Center s Micromechanics Analysis Code With Generalized Method of Cells (MAC/GMC) computer program, which was described in several prior NASA Tech Briefs articles. The linkage enables Hyper- Sizer to localize to the fiber and matrix level rather than only to the ply level, making it possible to predict local failures and to predict properties of plies from those of the component fiber and matrix materials. Advanced graphical user interfaces and database structures have been developed to support the new HyperSizer micromechanics capabilities.

[Case of acute ischemic stroke due to cardiac myxoma treated by intravenous thrombolysis and endovascular therapy].

PubMed

Kamiya, Yuki; Ichikawa, Hiroo; Mizuma, Keita; Itaya, Kazuhiro; Shimizu, Yuki; Kawamura, Mitsuru

2014-01-01

A 48-year-old woman with no previous neurological diseases was transferred to our hospital because of sudden-onset unconsciousness. On arrival, she showed consciousness disturbance (E1V1M3 on the Glasgow Coma Scale), tetraplegia, right conjugate deviation and bilateral pathological reflexes. These symptoms resulted in a NIH stroke scale score of 32. Brain diffusion-weighted MR imaging (DWI) showed multiple hyper-intense lesions, and MR angiography revealed occlusions of the basilar artery (BA) and superior branch of the right middle cerebral artery (MCA). Transthoracic echocardiography disclosed a 51 × 24 mm myxoma in the left atrium. These findings led to diagnosis of acute ischemic stroke due to embolization from cardiac myxoma. Thrombolytic therapy with intravenous tissue plasminogen activator (IV tPA) was started 120 min after onset because there were no contraindications for this treatment. However, the symptoms did not resolve, and thus endovascular therapy was performed immediately after IV tPA. Angiography of the left vertebral artery initially showed BA occlusion, but a repeated angiogram resulted in spontaneous recanalization of the BA. However, the left posterior cerebral artery remained occluded by a residual embolus. Subsequently, occlusion found in the superior branch of the right MCA was treated by intra-arterial local thrombolysis using urokinase and thrombectomy with a foreign body retrieval device, but the MCA remained occluded. DWI after endovascular therapy showed new hyper-intense lesions in the bilateral medial thalamus and left occipital cortex. Clinically, neurological status did not improve, with a score of 5 on the modified Rankin Scale. IV tPA can be used for stroke due to cardiac myxoma, but development of brain aneurysms and metastases caused by myxoma is a concern. Given the difficulty of predicting an embolus composite from a thrombus or tumor particle, aspiration thrombectomy may be safer and more effective for stroke due to cardiac myxoma to avoid delayed formation of brain aneurysms and metastases.

Calibrating the interaction matrix for the LINC-NIRVANA high layer wavefront sensor.

PubMed

Zhang, Xianyu; Arcidiacono, Carmelo; Conrad, Albert R; Herbst, Thomas M; Gaessler, Wolfgang; Bertram, Thomas; Ragazzoni, Roberto; Schreiber, Laura; Diolaiti, Emiliano; Kuerster, Martin; Bizenberger, Peter; Meschke, Daniel; Rix, Hans-Walter; Rao, Changhui; Mohr, Lars; Briegel, Florian; Kittmann, Frank; Berwein, Juergen; Trowitzsch, Jan

2012-03-26

LINC-NIRVANA is a near-infrared Fizeau interferometric imager that will operate at the Large Binocular Telescope. In preparation for the commissioning of this instrument, we conducted experiments for calibrating the high-layer wavefront sensor of the layer-oriented multi-conjugate adaptive optics system. For calibrating the multi-pyramid wavefront sensor, four light sources were used to simulate guide stars. Using this setup, we developed the push-pull method for calibrating the interaction matrix. The benefits of this method over the traditional push-only method are quantified, and also the effects of varying the number of push-pull frames over which aberrations are averaged is reported. Finally, we discuss a method for measuring mis-conjugation between the deformable mirror and the wavefront sensor, and the proper positioning of the wavefront sensor detector with respect to the four pupil positions.

Enormous Hydrogen Bond Strength Enhancement through π-Conjugation Gain: Implications for Enzyme Catalysis.

PubMed

Wu, Chia-Hua; Ito, Keigo; Buytendyk, Allyson M; Bowen, K H; Wu, Judy I

2017-08-22

Surprisingly large resonance-assistance effects may explain how some enzymes form extremely short, strong hydrogen bonds to stabilize reactive oxyanion intermediates and facilitate catalysis. Computational models for several enzymic residue-substrate interactions reveal that when a π-conjugated, hydrogen bond donor (XH) forms a hydrogen bond to a charged substrate (Y - ), XH can become significantly more π-electron delocalized, and this "extra" stabilization may boost the [XH···Y - ] hydrogen bond strength by ≥15 kcal/mol. This reciprocal relationship departs from the widespread pK a concept (i.e., the idea that short, strong hydrogen bonds form when the interacting moieties have matching pK a values), which has been the rationale for enzymic acid-base reactions. The findings presented here provide new insight into how short, strong hydrogen bonds could form in enzymes.

Magnetoconductivity and magnetoluminescence studies in bipolar and almost hole-only sandwich devices made from films of a π-conjugated molecule

PubMed Central

Duc Nguyen, Tho; Sheng, Yugang; Rybicki, James E; Wohlgenannt, Markus

2008-01-01

We present magnetoconductivity and magnetoluminescence measurements in sandwich devices made from films of a π-conjugated molecule and demonstrate effects of more than 30 and 50% magnitude, respectively, in fields of 100 mT at room-temperature. It has previously been recognized that the effect is caused by hyperfine coupling, and that it is phenomenologically similar to other magnetic field effects that act on electron–hole pairs, which are well-known in spin-chemistry. However, we show that the very large magnitude of the effect contradicts present knowledge of the electron–hole pair recombination processes in electroluminescent π-conjugated molecules, and that the effect persists even in almost hole-only devices. Therefore, this effect is likely caused by the interaction of radical pairs of equal charge. PMID:27877957

Synthesis and characterization of novel 2, 2'-bipyrimidine fluorescent derivative for protein binding

PubMed Central

2011-01-01

Background Fluorescent dyes with biocompatible functional group and good fluorescence behavior are used as biosensor for monitoring different biological processes as well as detection of protein assay. All reported fluorophore used as sensors are having high selectivity and sensitivity but till there is more demand to synthesized new fluorophore which have improved fluorescence properties and good biocompatibility. Results Novel 4, 4'-(1, 1'-(5-(2-methoxyphenoxy)-[2, 2'-bipyrimidine]-4, 6-diyl)bis(1H-pyrazol-3, 1-diyl)) dianiline fluorescent dye was synthesized by multistep synthesis from 2-phenylacetonitrile, 2-chloropyrimidine and 2-methoxyphenol. This dye has absorption at 379 nm with intense single emission at 497 nm having fairly good quantum yield (0.375) and Stokes shift. The intermediates and dye were characterized by FT-IR, 1H NMR, 13C NMR and Mass spectral analysis. The pyrazole bipyrimidine based fluorescent dye possessing two amino groups suitable for binding with protein is reported. Its utility as a biocompatible conjugate was explained by conjugation with bovine serum albumin. The method is based on direct fluorescence detection of fluorophore-labelled protein before and after conjugation. Purified fluorescent conjugate was subsequently analyzed by fluorimetry. The analysis showed that the tested conjugation reaction yielded fluorescent conjugates of the dye through carbodiimide chemistry. Conclusion In summery synthesized fluorophore pyrazole-bipyrimidine has very good interaction towards protein bovine serum albumin and it acts as good candidate for protein assay. PMID:22067202

The application of the HyPer fluorescent sensor in the real-time detection of H2O2 in Babesia bovis merozoites in vitro.

PubMed

Asada, Masahito; Hakimi, Hassan; Kawazu, Shin-Ichiro

2018-05-15

In recent years, genetically encoded fluorescent probes have allowed a dramatic advancement in time-lapse imaging, enabling this imaging modality to be used to investigate intracellular events in several apicomplexan parasite species. In this study, we constructed a plasmid vector to stably express a genetically encoded H 2 O 2 sensor probe called HyPer in Babesia bovis. The HyPer-transfected parasite population was successfully developed and subjected to a time-lapse imaging analysis under in vitro culture conditions. HyPer was capable of sensing an increasing H 2 O 2 concentration in the parasite cells which was induced by the administration of paraquat as a superoxide donor. HyPer fluorescence co-staining with MitoTracker Red indicated the mitochondria as the major source of reactive oxygen species (ROS) in parasite cells. The fluctuating ROS dynamics in the parasite gliding toward, attaching to, and invading the target red blood cell was visualized and monitored in real time with the HyPer expressing parasite population. This is the first report to describe the application of the HyPer probe in an imaging analysis involving Babesia parasites. Hyper-expressing parasites can be widely utilized in studies to investigate the mechanisms of emergence and the reduction of oxidative stress, as well as the signal transduction in the parasite cells during host invasion and intercellular development. Copyright © 2018 Elsevier B.V. All rights reserved.

An adaptive band selection method for dimension reduction of hyper-spectral remote sensing image

NASA Astrophysics Data System (ADS)

Yu, Zhijie; Yu, Hui; Wang, Chen-sheng

2014-11-01

Hyper-spectral remote sensing data can be acquired by imaging the same area with multiple wavelengths, and it normally consists of hundreds of band-images. Hyper-spectral images can not only provide spatial information but also high resolution spectral information, and it has been widely used in environment monitoring, mineral investigation and military reconnaissance. However, because of the corresponding large data volume, it is very difficult to transmit and store Hyper-spectral images. Hyper-spectral image dimensional reduction technique is desired to resolve this problem. Because of the High relation and high redundancy of the hyper-spectral bands, it is very feasible that applying the dimensional reduction method to compress the data volume. This paper proposed a novel band selection-based dimension reduction method which can adaptively select the bands which contain more information and details. The proposed method is based on the principal component analysis (PCA), and then computes the index corresponding to every band. The indexes obtained are then ranked in order of magnitude from large to small. Based on the threshold, system can adaptively and reasonably select the bands. The proposed method can overcome the shortcomings induced by transform-based dimension reduction method and prevent the original spectral information from being lost. The performance of the proposed method has been validated by implementing several experiments. The experimental results show that the proposed algorithm can reduce the dimensions of hyper-spectral image with little information loss by adaptively selecting the band images.

Research on hyperspectral dynamic scene and image sequence simulation

NASA Astrophysics Data System (ADS)

Sun, Dandan; Gao, Jiaobo; Sun, Kefeng; Hu, Yu; Li, Yu; Xie, Junhu; Zhang, Lei

2016-10-01

This paper presents a simulation method of hyper-spectral dynamic scene and image sequence for hyper-spectral equipment evaluation and target detection algorithm. Because of high spectral resolution, strong band continuity, anti-interference and other advantages, in recent years, hyper-spectral imaging technology has been rapidly developed and is widely used in many areas such as optoelectronic target detection, military defense and remote sensing systems. Digital imaging simulation, as a crucial part of hardware in loop simulation, can be applied to testing and evaluation hyper-spectral imaging equipment with lower development cost and shorter development period. Meanwhile, visual simulation can produce a lot of original image data under various conditions for hyper-spectral image feature extraction and classification algorithm. Based on radiation physic model and material characteristic parameters this paper proposes a generation method of digital scene. By building multiple sensor models under different bands and different bandwidths, hyper-spectral scenes in visible, MWIR, LWIR band, with spectral resolution 0.01μm, 0.05μm and 0.1μm have been simulated in this paper. The final dynamic scenes have high real-time and realistic, with frequency up to 100 HZ. By means of saving all the scene gray data in the same viewpoint image sequence is obtained. The analysis results show whether in the infrared band or the visible band, the grayscale variations of simulated hyper-spectral images are consistent with the theoretical analysis results.

More than ten million years of hyper-aridity recorded in the Atacama Gravels

NASA Astrophysics Data System (ADS)

Sun, Tao; Bao, Huiming; Reich, Martin; Hemming, Sidney R.

2018-04-01

The Atacama Desert's hyper-aridity is closely linked to the development of world-class copper and nitrate/iodine ores and to regional tectonics and global paleoclimate changes in the Cenozoic era. The timing when the hyper-aridity commenced remains controversial, with proposed ages ranging from Late Oligocene to Pleistocene. In this study, we provide an independent constraint on the initiation of Atacama hyper-aridity utilizing a 100-m deep profile within the Atacama Gravels and underneath porphyry copper deposit in Spence, northern Chile. The overall high concentration of sulfate (up to 10 wt%) and a multimodal distribution of water soluble salt (sulfates, chlorides and nitrates) indicate multiple generations of sedimentation and salt accumulation events under semi-arid to hyper-arid climate conditions. The multiple sulfate isotope compositions (Δ17O, δ18O, δ34S) of the upper section (-15.0 to -34.5 m) are close to those of modern hyperarid surface sulfates, while the lower section (-34.5 to -65 m) displays a depth dependent isotope trend that is best interpreted as marking a period of climate change from semi-arid to hyper-arid. When these data are combined with new chronological 40Ar/39Ar dates obtained from a volcanic ash layer at depth of -28.0 m, our results show that hyper-arid condition in the Atacama Desert was prevailing at least prior to 9.47 Ma and may go back as old as the middle Miocene.

Molecular cloning and characterization of a novel tomato xylosyltransferase specific for gentisic acid.

PubMed

Tárraga, Susana; Lisón, Purificación; López-Gresa, María Pilar; Torres, Cristina; Rodrigo, Ismael; Bellés, José María; Conejero, Vicente

2010-10-01

The importance of salicylic acid (SA) in the signal transduction pathway of plant disease resistance has been well documented in many incompatible plant-pathogen interactions, but less is known about signalling in compatible interactions. In this type of interaction, tomato plants have been found to accumulate high levels of 2,5-dihydroxybenzoic acid (gentisic acid, GA), a metabolic derivative of SA. Exogenous GA treatments induce in tomato plants a set of PR proteins that differ from those induced by salicylic acid. While SA accumulates in tomato plants mainly as 2-O-β-D-glucoside, GA has only been found as 5-O-β-D-xyloside. To characterize this step of the GA signalling pathway further, the present work focuses on the study of the GA-conjugating activity in tomato plants. A gentisate glycosyltransferase (GAGT) cDNA has been isolated and overexpressed in Pichia pastoris, and GA-conjugating activity was confirmed by detecting the xylosylated GA. The purified plant protein is highly specific for GA, showing no activity toward many other phenolic compounds, including SA. In addition, it shows an outstanding selectivity for UDP-xylose as the sugar donor, which differentiates this enzyme from most glycosyltransferases. Both the GA-conjugating activity and the corresponding mRNA show a strong, rapid, and transient induction upon treatment of tomato plants with GA or SA. Furthermore, its expression is rapidly induced by compatible infections. However, neither the gene nor the activity seems to respond to incompatible infections or wounding. The unique properties of this new glycosyltransferase suggest a specific role in regulating the free GA levels in compatible plant-pathogen interactions.

Fatty acid conjugation enhances the activities of antimicrobial peptides.

PubMed

Li, Zhining; Yuan, Penghui; Xing, Meng; He, Zhumei; Dong, Chuanfu; Cao, Yongchang; Liu, Qiuyun

2013-04-01

Antimicrobial peptides are small molecules that play a crucial role in innate immunity in multi-cellular organisms, and usually expressed and secreted constantly at basal levels to prevent infection, but local production can be augmented upon an infection. The clock is ticking as rising antibiotic abuse has led to the emergence of many drug resistance bacteria. Due to their broad spectrum antibiotic and antifungal activities as well as anti-viral and anti-tumor activities, efforts are being made to develop antimicrobial peptides into future microbial agents. This article describes some of the recent patents on antimicrobial peptides with fatty acid conjugation. Potency and selectivity of antimicrobial peptide can be modulated with fatty acid tails of variable length. Interaction between membranes and antimicrobial peptides was affected by fatty acid conjugation. At concentrations above the critical miscelle concentration (CMC), propensity of solution selfassembly hampered binding of the peptide to cell membranes. Overall, fatty acid conjugation has enhanced the activities of antimicrobial peptides, and occasionally it rendered inactive antimicrobial peptides to be bioactive. Antimicrobial peptides can not only be used as medicine but also as food additives.

PPV-Based Conjugated Polymer Nanoparticles as a Versatile Bioimaging Probe: A Closer Look at the Inherent Optical Properties and Nanoparticle-Cell Interactions.

PubMed

Peters, Martijn; Zaquen, Neomy; D'Olieslaeger, Lien; Bové, Hannelore; Vanderzande, Dirk; Hellings, Niels; Junkers, Thomas; Ethirajan, Anitha

2016-08-08

Conjugated polymers have attracted significant interest in the bioimaging field due to their excellent optical properties and biocompatibility. Tailor-made poly(p-phenylenevinylene) (PPV) conjugated polymer nanoparticles (NPs) are in here described. Two different nanoparticle systems using poly[2-methoxy-5-(3',7'-dimethoxyoctyloxy)-1,4-phenylenevinylene] (MDMO-PPV) and a functional statistical copolymer 2-(5'-methoxycarbonylpentyloxy)-5-methoxy-1,4-phenylenevinylene (CPM-MDMO-PPV), containing ester groups on the alkoxy side chains, were synthesized by combining miniemulsion and solvent evaporation processes. The hydrolysis of ester groups into carboxylic acid groups on the CPM-MDMO-PPV NPs surface allows for biomolecule conjugation. The NPs exhibited excellent optical properties with a high fluorescent brightness and photostability. The NPs were in vitro tested as potential fluorescent nanoprobes for studying cell populations within the central nervous system. The cell studies demonstrated biocompatibility and surface charge dependent cellular uptake of the NPs. This study highlights that PPV-derivative based particles are a promising bioimaging probe and can cater potential applications in the field of nanomedicine.

Bisubstrate inhibitors of protein kinases: from principle to practical applications.

PubMed

Lavogina, Darja; Enkvist, Erki; Uri, Asko

2010-01-01

Bisubstrate inhibitors consist of two conjugated fragments, each targeted to a different binding site of a bisubstrate enzyme. The design of bisubstrate inhibitors presupposes the formation of the ternary complex in the course of the catalyzed reaction. The principle advantage of bisubstrate inhibitors is their ability to generate more interactions with the target enzyme that could result in improved affinity and selectivity of the conjugates, when compared with single-site inhibitors. Among phosphotransferases, the approach was first successfully used for adenylate kinase in 1973. Since then, several types of bisubstrate inhibitors have been developed for protein kinases, including conjugates of peptides with nucleotides, adenosine derivatives and potent ATP-competitive inhibitors. Earlier bisubstrate inhibitors had pharmacokinetic qualities that were unsuitable for cellular experiments and hence were mostly used for in vitro studies. The recently constructed conjugates of adenosine derivatives and D-arginine-rich peptides (ARCs) possess high kinase affinity, high biological and chemical stability and good cell plasma membrane penetrative properties that enable their application in the regulation of cellular protein phosphorylation balances in cell and tissue experiments.

Synthesis of biotinylated glycoconjugates and their use in a novel ELISA for direct comparison of HIV-1 Gp120 recognition of GalCer and related carbohydrate analogues.

PubMed

McReynolds, K D; Hadd, M J; Gervay-Hague, J

1999-01-01

As part of our program directed toward the design and synthesis of high-affinity ligands for the GalCer-binding site on the HIV cell surface glycoprotein, gp120, we required a reliable method for qualitatively assessing relative binding affinities for related analogues. Due to the hydrophilic nature of these synthetic conjugates, difficulties were encountered with typical ELISA methods, which rely upon hydrophobic interactions to anchor the ligand to a microtiter plate. Other types of assays were also problematic due to nonspecific binding of gp120. Therefore, we developed a general method for plating water-soluble ligands on microtiter plates using biotin/NeutrAvidin recognition for adhesion. A water-soluble GalCer analogue was prepared by conjugating psychosine to biotin using a novel tetraethylene glycol linker. In a similar manner, LacCer and GlcCer analogues were prepared and these conjugates were plated into microtiter wells containing NeutrAvidin. Unoccupied sites were blocked using biotin functionalized as a primary amide. Gp120 binding to galactosyl sphingosine, GalSph (19), GlcSph (22), and LacSph (23) conjugates was assessed through incubation with recombinant HRP-gp120. It was determined that LacSph has the strongest interaction with gp120. The binding affinities of GalSph and GlcSph were similar to each other and less strong than LacSph. These data contradict earlier studies where HPTLC showed that LacCer and GlcCer do not significantly bind gp120. They also contradict liposome-based assays that reported psychosine is not recognized by gp120. The extent of plating for each biotinylated molecule was quantified using HRP-biotin, allowing direct comparison of ligand plating efficiencies for the first time. Several other synthetic biotin conjugates were prepared and tested, demonstrating the feasibility of performing ELISA on water-soluble ligands.

Absorption of Bile Pigments by the Gall Bladder*

PubMed Central

Ostrow, J. Donald

1967-01-01

A technique is described for preparation in the guinea pig of an in situ, isolated, vascularized gall bladder that exhibits normal absorptive functions. Absorption of labeled bile pigments from the gall bladder was determined by the subsequent excretion of radioactivity in hepatic bile. Over a wide range of concentrations, unconjugated bilirubin-14C was well absorbed, whereas transfer of conjugated bilirubin proceeded slowly. Mesobilirubinogen-3H was absorbed poorly from whole bile, but was absorbed as rapidly as unconjugated bilirubin from a solution of pure conjugated bile salt. Bilirubin absorption was not impaired by iodoacetamide, 1.5 mM, or dinitrophenol, 1.0 mM, even though water transport was affected. This indicated that absorption of bilirubin was not dependent upon water transport, nor upon energy-dependent processes. The linear relationship between absorption and concentration of pigment at low concentrations in bile salt solutions suggested that pigment was transferred by passive diffusion. At higher pigment concentrations or in whole bile, this simple relationship was modified by interactions of pigment with bile salts and other constituents of bile. These interactions did not necessarily involve binding of bilirubin in micelles. The slow absorption of the more polar conjugates and photo-oxidative derivatives of bilirubin suggested that bilirubin was absorbed principally by nonionic, and partially, by ionic diffusion. Concentrations of pure conjugated bile salts above 3.5 mM were found to be injurious to the gall bladder mucosa. This mucosal injury did not affect the kinetics of bilirubin absorption. During in vitro incubation of bile at 37°C, decay of bilirubin and hydrolysis of the conjugate proceeded as first-order reactions. The effects of these processes on the kinetics of bilirubin absorption, and their possible role in the formation of “white bile” and in the demonstrated appearance of unconjugated bilirubin in hepatic bile, are discussed. PMID:6074006

GLP-1 and estrogen conjugate acts in the supramammillary nucleus to reduce food-reward and body weight.

PubMed

Vogel, Heike; Wolf, Stefanie; Rabasa, Cristina; Rodriguez-Pacheco, Francisca; Babaei, Carina S; Stöber, Franziska; Goldschmidt, Jürgen; DiMarchi, Richard D; Finan, Brian; Tschöp, Matthias H; Dickson, Suzanne L; Schürmann, Annette; Skibicka, Karolina P

2016-11-01

The obesity epidemic continues unabated and currently available pharmacological treatments are not sufficiently effective. Combining gut/brain peptide, GLP-1, with estrogen into a conjugate may represent a novel, safe and potent, strategy to treat diabesity. Here we demonstrate that the central administration of GLP-1-estrogen conjugate reduced food reward, food intake, and body weight in rats. In order to determine the brain location of the interaction of GLP-1 with estrogen, we avail of single-photon emission computed tomography imaging of regional cerebral blood flow and pinpoint a brain site unexplored for its role in feeding and reward, the supramammillary nucleus (SUM) as a potential target of the conjugated GLP-1-estrogen. We confirm that conjugated GLP-1 and estrogen directly target the SUM with site-specific microinjections. Additional microinjections of GLP-1-estrogen into classic energy balance controlling nuclei, the lateral hypothalamus (LH) and the nucleus of the solitary tract (NTS) revealed that the metabolic benefits resulting from GLP-1-estrogen injections are mediated through the LH and to some extent by the NTS. In contrast, no additional benefit of the conjugate was noted on food reward when the compound was microinjected into the LH or the NTS, identifying the SUM as the only neural substrate identified here to underlie the reward reducing benefits of GLP-1 and estrogen conjugate. Collectively we discover a surprising neural substrate underlying food intake and reward effects of GLP-1 and estrogen and uncover a new brain area capable of regulating energy balance and reward. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Learning from Experience Case Studies of the Hyper-X Project

NASA Technical Reports Server (NTRS)

Peebles, Curtis

2009-01-01

The Hyper-X project (X-43A) provides a number of "lessons learned" which can be applied to other aerospace project. The specific areas examined were the selection of the goals of the Hyper-X. How the technical unknowns and assumptions were handled. The final lesson was the ambiguous nature of risk assessment, and how trying to remove a technical unknown can have unintended consequences.

X43 Hyper-X

NASA Image and Video Library

2004-02-11

NASA's Hyper-x Program Manager, Vince Rausch talks about the upcoming launch of the X43A vehicle over the Pacific Ocean later this month from his office at NASA Langley Research Center in Hampton, VA. Hyper X is a high risk, high payoff program. The flight of the X43 A will demonstrated in flight for the first time, air breathing hypersonic propulsion technology. (Photo by Jeff Caplan)

Motion Coordination and Adaptation Using Deception and Human Interactions

DTIC Science & Technology

2016-11-18

evolves an interface (front) by embedding it as a hyper - surface in a higher dimension, where time is the augmented dimension. Automatic handling of...the open- loop system trajectories. The results are depicted in Fig. 32. From the shape of the value function in Fig. 32(b) it is seen that the value is...estimate of the value function only over the area of the state space visited by the sampled (open- loop ) trajectories. In that sense, the areas not

Developments in Microcomputing--Discovering New Opportunities for Libraries in the 1990s. Festschrift in Honour of Richard De Gennero. Papers presented at the International Essen Symposium (12th, Essen, West Germany, October 23-26, 1989).

ERIC Educational Resources Information Center

Helal, Ahmed H., Ed.; Weiss, Joachim W., Ed.

The 16 papers in this collection explore the microcomputer revolution as it affects library information systems: (1) "HyperMedia/Multimedia Technology and New Opportunities for Libraries in the 1990s" (Ching-chih Chen); (2) "Use of CD-ROMs in West German Libraries" (David I. Raitt and Ching-chih Chen); (3) "Purposes of Interactive Optical Discs…

An interactive HTML ocean nowcast GUI based on Perl and JavaScript

NASA Astrophysics Data System (ADS)

Sakalaukus, Peter J.; Fox, Daniel N.; Louise Perkins, A.; Smedstad, Lucy F.

1999-02-01

We describe the use of Hyper Text Markup Language (HTML), JavaScript code, and Perl I/O to create and validate forms in an Internet-based graphical user interface (GUI) for the Naval Research Laboratory (NRL) Ocean models and Assimilation Demonstration System (NOMADS). The resulting nowcast system can be operated from any compatible browser across the Internet, for although the GUI was prepared in a Netscape browser, it used no Netscape extensions. Code available at: http://www.iamg.org/CGEditor/index.htm

Experimental Realization of Tunable Metamaterial Hyper-transmitter

PubMed Central

Yoo, Young Joon; Yi, Changhyun; Hwang, Ji Sub; Kim, Young Ju; Park, Sang Yoon; Kim, Ki Won; Rhee, Joo Yull; Lee, YoungPak

2016-01-01

We realized the tunable metamaterial hyper-transmitter in the microwave range utilizing simple planar meta-structure. The single-layer metamaterial hyper-transmitter shows that the transmission peak occurs at 14 GHz. In case of the dual-layer one, it is possible to control the transmission peak from 5 to 10 GHz. Moreover, all the transmission peaks reveal transmission over 100%. We experimentally and theoretically investigated these phenomena through 3-dimensional simulation and measurement. The reason for being over 100% is also elucidated. The suggested hyper-transmitter can be used, for example, in enhancing the operating distance of the electromagnetic wave in Wi-Fi, military radar, wireless power transfer and self-driving car. PMID:27629804

Experimental Realization of Tunable Metamaterial Hyper-transmitter

NASA Astrophysics Data System (ADS)

Yoo, Young Joon; Yi, Changhyun; Hwang, Ji Sub; Kim, Young Ju; Park, Sang Yoon; Kim, Ki Won; Rhee, Joo Yull; Lee, Youngpak

2016-09-01

We realized the tunable metamaterial hyper-transmitter in the microwave range utilizing simple planar meta-structure. The single-layer metamaterial hyper-transmitter shows that the transmission peak occurs at 14 GHz. In case of the dual-layer one, it is possible to control the transmission peak from 5 to 10 GHz. Moreover, all the transmission peaks reveal transmission over 100%. We experimentally and theoretically investigated these phenomena through 3-dimensional simulation and measurement. The reason for being over 100% is also elucidated. The suggested hyper-transmitter can be used, for example, in enhancing the operating distance of the electromagnetic wave in Wi-Fi, military radar, wireless power transfer and self-driving car.

Tele Hyper Virtuality

NASA Technical Reports Server (NTRS)

Terashima, Nobuyoshi

1994-01-01

In the future, remote images sent over communication lines will be reproduced in virtual reality (VR). This form of virtual telecommunications, which will allow observers to engage in an activity as though it were real, is the focus of considerable attention. Taken a step further, real and unreal objects will be placed in a single space to create an extremely realistic environment. Here, imaginary and other life forms as well as people and animals in remote locations will gather via telecommunication lines that create a common environment where life forms can work and interact together. Words, gestures, diagrams and other forms of communication will be used freely in performing work. Actual construction of a system based on this new concept will not only provide people with experiences that would have been impossible in the past, but will also inspire new applications in which people will function in environments where it would have been difficult if not impossible for them to function until now. This paper describes Tele Hyper Virtuality concept, its definition, applications, the key technologies to accomplish it and future prospects.

Computational Study of Pseudo-Phosphorylation and Phosphorylation of the Microtubule Associated Protein Tau

NASA Astrophysics Data System (ADS)

Prokopovich, Dmitriy; Larini, Luca

This study focuses on the effect of pseudo-phosphorylation on the aggregation of protein tau, which is very often found interacting with microtubules in the neuron. Within the axon of the neuron, tau governs the assembly of microtubules that make up the cytoskeleton. This is important for stabilization of and transport across the microtubules. One of the indications of the Alzheimer's disease is the hyper-phosphorylation and aggregation of protein tau into neurofibrillary tangles that destroy the neurons. But even experts in the field do not know if hyper-phosphorylation directly causes the aggregation of tau. In some experiments, pseudo-phosphorylation mimics the effects of phosphorylation. It does so by mutating certain residues of the protein chain into charged residues. In this computational study, we will employ a fragment of tau called PHF43. This fragment belongs to the microtubule binding region and papers published by others have indicated that it readily aggregates. Replica exchange molecular dynamics simulations were performed on the pseudo-phosphorylated, phosphorylated, and dimerized PHF43. The program used to simulate and analyze PHF43 was AMBER14.

Probing the Folding-Unfolding Transition of a Thermophilic Protein, MTH1880

PubMed Central

Jung, Youngjin; Han, Jeongmin; Yun, Ji-Hye; Chang, Iksoo; Lee, Weontae

2016-01-01

The folding mechanism of typical proteins has been studied widely, while our understanding of the origin of the high stability of thermophilic proteins is still elusive. Of particular interest is how an atypical thermophilic protein with a novel fold maintains its structure and stability under extreme conditions. Folding-unfolding transitions of MTH1880, a thermophilic protein from Methanobacterium thermoautotrophicum, induced by heat, urea, and GdnHCl, were investigated using spectroscopic techniques including circular dichorism, fluorescence, NMR combined with molecular dynamics (MD) simulations. Our results suggest that MTH1880 undergoes a two-state N to D transition and it is extremely stable against temperature and denaturants. The reversibility of refolding was confirmed by spectroscopic methods and size exclusion chromatography. We found that the hyper-stability of the thermophilic MTH1880 protein originates from an extensive network of both electrostatic and hydrophobic interactions coordinated by the central β-sheet. Spectroscopic measurements, in combination with computational simulations, have helped to clarify the thermodynamic and structural basis for hyper-stability of the novel thermophilic protein MTH1880. PMID:26766214

Modeling of breakthrough curves of single and quaternary mixtures of ethanol, glucose, glycerol and acetic acid adsorption onto a microporous hyper-cross-linked resin.

PubMed

Zhou, Jingwei; Wu, Jinglan; Liu, Yanan; Zou, Fengxia; Wu, Jian; Li, Kechun; Chen, Yong; Xie, Jingjing; Ying, Hanjie

2013-09-01

The adsorption of quaternary mixtures of ethanol/glycerol/glucose/acetic acid onto a microporous hyper-cross-linked resin HD-01 was studied in fixed beds. A mass transport model based on film solid linear driving force and the competitive Langmuir isotherm equation for the equilibrium relationship was used to develop theoretical fixed bed breakthrough curves. It was observed that the outlet concentration of glucose and glycerol exceeded the inlet concentration (c/c0>1), which is an evidence of competitive adsorption. This phenomenon can be explained by the displacement of glucose and glycerol by ethanol molecules, owing to more intensive interactions with the resin surface. The model proposed was validated using experimental data and can be capable of foresee reasonably the breakthrough curve of specific component under different operating conditions. The results show that HD-01 is a promising adsorbent for recovery of ethanol from the fermentation broth due to its large capacity, high selectivity, and rapid adsorption rate. Copyright © 2013 Elsevier Ltd. All rights reserved.

Cw hyper-Raman laser and four-wave mixing in atomic sodium

NASA Astrophysics Data System (ADS)

Klug, M.; Kablukov, S. I.; Wellegehausen, B.

2005-01-01

Continuous wave hyper-Raman (HR) generation in a ring cavity on the 6s → 4p transition at 1640 nm in sodium is realized for the first time by two-photon excitation of atomic sodium on the 3s → 6s transition with a continuous wave (cw) dye laser at 590 nm and a single frequency argon ion laser at 514 nm. It is shown, that the direction and efficiency of HR lasing depends on the propagation direction of the pump waves and their frequencies. More than 30% HR gain is measured at 250 mW of pump laser powers for counter-propagating pump waves and a medium length of 90 mm. For much shorter interaction lengths and corresponding focussing of the pump waves a dramatic increase of the gain is predicted. For co-propagating pump waves, in addition, generation of 330 nm radiation on the 4p → 3s transition by a four-wave mixing (FWM) process is observed. Dependencies of HR and parametric four-wave generation have been investigated and will be discussed.

Single-photon test of hyper-complex quantum theories using a metamaterial.

PubMed

Procopio, Lorenzo M; Rozema, Lee A; Wong, Zi Jing; Hamel, Deny R; O'Brien, Kevin; Zhang, Xiang; Dakić, Borivoje; Walther, Philip

2017-04-21

In standard quantum mechanics, complex numbers are used to describe the wavefunction. Although this has so far proven sufficient to predict experimental results, there is no theoretical reason to choose them over real numbers or generalizations of complex numbers, that is, hyper-complex numbers. Experiments performed to date have proven that real numbers are insufficient, but the need for hyper-complex numbers remains an open question. Here we experimentally probe hyper-complex quantum theories, studying one of their deviations from complex quantum theory: the non-commutativity of phases. We do so by passing single photons through a Sagnac interferometer containing both a metamaterial with a negative refractive index, and a positive phase shifter. To accomplish this we engineered a fishnet metamaterial to have a negative refractive index at 780 nm. We show that the metamaterial phase commutes with other phases with high precision, allowing us to place limits on a particular prediction of hyper-complex quantum theories.

ECN-2301

NASA Image and Video Library

1969-09-10

The Hyper III was a low-cost test vehicle for an advanced lifting-body shape. Like the earlier M2-F1, it was a "homebuilt" research aircraft, i.e., built at the Flight Research Center (FRC), later redesignated the Dryden Flight Research Center. It had a steel-tube frame covered with Dacron, a fiberglass nose, sheet aluminum fins, and a wing from an HP-11 sailplane. Construction was by volunteers at the FRC. Although the Hyper III was to be flown remotely in its initial tests, it was fitted with a cockpit for a pilot. On the Hyper III's only flight, it was towed aloft attached to a Navy SH-3 helicopter by a 400-foot cable. NASA research pilot Bruce Peterson flew the SH-3. After he released the Hyper III from the cable, NASA research pilot Milt Thompson flew the vehicle by radio control until the final approach when Dick Fischer took over control using a model-airplane radio-control box. The Hyper III flared, then landed and slid to a stop on Rogers Dry Lakebed.

Rapid Molecular Analysis of the STAT3 Gene in Job Syndrome of Hyper-IgE and Recurrent Infectious Diseases

PubMed Central

Kumánovics, Attila; Wittwer, Carl T.; Pryor, Robert J.; Augustine, Nancy H.; Leppert, Mark F.; Carey, John C.; Ochs, Hans D.; Wedgwood, Ralph J.; Faville, Ralph J.; Quie, Paul G.; Hill, Harry R.

2010-01-01

With the recent discovery of mutations in the STAT3 gene in the majority of patients with classic Hyper-IgE syndrome, it is now possible to make a molecular diagnosis in most of these cases. We have developed a PCR-based high-resolution DNA-melting assay to scan selected exons of the STAT3 gene for mutations responsible for Hyper-IgE syndrome, which is then followed by targeted sequencing. We scanned for mutations in 10 unrelated pedigrees, which include 16 patients with classic Hyper-IgE syndrome. These pedigrees include both sporadic and familial cases and their relatives, and we have found STAT3 mutations in all affected individuals. High-resolution melting analysis allows a single day turn-around time for mutation scanning and targeted sequencing of the STAT3 gene, which will greatly facilitate the rapid diagnosis of the Hyper-IgE syndrome, allowing prompt and appropriate therapy, prophylaxis, improved clinical outcome, and accurate genetic counseling. PMID:20093388

Single-photon test of hyper-complex quantum theories using a metamaterial

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

Procopio, Lorenzo M.; Rozema, Lee A.; Wong, Zi Jing

In standard quantum mechanics, complex numbers are used to describe the wavefunction. Although this has so far proven sufficient to predict experimental results, there is no theoretical reason to choose them over real numbers or generalizations of complex numbers, that is, hyper-complex numbers. Experiments performed to date have proven that real numbers are insufficient, but the need for hyper-complex numbers remains an open question. Here we experimentally probe hyper-complex quantum theories, studying one of their deviations from complex quantum theory: the non-commutativity of phases. We do so by passing single photons through a Sagnac interferometer containing both a metamaterial withmore » a negative refractive index, and a positive phase shifter. In order to accomplish this we engineered a fishnet metamaterial to have a negative refractive index at 780 nm. Here, we show that the metamaterial phase commutes with other phases with high precision, allowing us to place limits on a particular prediction of hyper-complex quantum theories.« less

Single-photon test of hyper-complex quantum theories using a metamaterial

DOE PAGES

Procopio, Lorenzo M.; Rozema, Lee A.; Wong, Zi Jing; ...

2017-04-21

In standard quantum mechanics, complex numbers are used to describe the wavefunction. Although this has so far proven sufficient to predict experimental results, there is no theoretical reason to choose them over real numbers or generalizations of complex numbers, that is, hyper-complex numbers. Experiments performed to date have proven that real numbers are insufficient, but the need for hyper-complex numbers remains an open question. Here we experimentally probe hyper-complex quantum theories, studying one of their deviations from complex quantum theory: the non-commutativity of phases. We do so by passing single photons through a Sagnac interferometer containing both a metamaterial withmore » a negative refractive index, and a positive phase shifter. In order to accomplish this we engineered a fishnet metamaterial to have a negative refractive index at 780 nm. Here, we show that the metamaterial phase commutes with other phases with high precision, allowing us to place limits on a particular prediction of hyper-complex quantum theories.« less

Single-photon test of hyper-complex quantum theories using a metamaterial

PubMed Central

Procopio, Lorenzo M.; Rozema, Lee A.; Wong, Zi Jing; Hamel, Deny R.; O'Brien, Kevin; Zhang, Xiang; Dakić, Borivoje; Walther, Philip

2017-01-01

In standard quantum mechanics, complex numbers are used to describe the wavefunction. Although this has so far proven sufficient to predict experimental results, there is no theoretical reason to choose them over real numbers or generalizations of complex numbers, that is, hyper-complex numbers. Experiments performed to date have proven that real numbers are insufficient, but the need for hyper-complex numbers remains an open question. Here we experimentally probe hyper-complex quantum theories, studying one of their deviations from complex quantum theory: the non-commutativity of phases. We do so by passing single photons through a Sagnac interferometer containing both a metamaterial with a negative refractive index, and a positive phase shifter. To accomplish this we engineered a fishnet metamaterial to have a negative refractive index at 780 nm. We show that the metamaterial phase commutes with other phases with high precision, allowing us to place limits on a particular prediction of hyper-complex quantum theories. PMID:28429711

Structural and Functional Analysis of a Novel Interaction Motif within UFM1-activating Enzyme 5 (UBA5) Required for Binding to Ubiquitin-like Proteins and Ufmylation*

PubMed Central

Habisov, Sabrina; Huber, Jessica; Ichimura, Yoshinobu; Akutsu, Masato; Rogova, Natalia; Loehr, Frank; McEwan, David G.; Johansen, Terje; Dikic, Ivan; Doetsch, Volker; Komatsu, Masaaki; Rogov, Vladimir V.; Kirkin, Vladimir

2016-01-01

The covalent conjugation of ubiquitin-fold modifier 1 (UFM1) to proteins generates a signal that regulates transcription, response to cell stress, and differentiation. Ufmylation is initiated by ubiquitin-like modifier activating enzyme 5 (UBA5), which activates and transfers UFM1 to ubiquitin-fold modifier-conjugating enzyme 1 (UFC1). The details of the interaction between UFM1 and UBA5 required for UFM1 activation and its downstream transfer are however unclear. In this study, we described and characterized a combined linear LC3-interacting region/UFM1-interacting motif (LIR/UFIM) within the C terminus of UBA5. This single motif ensures that UBA5 binds both UFM1 and light chain 3/γ-aminobutyric acid receptor-associated proteins (LC3/GABARAP), two ubiquitin (Ub)-like proteins. We demonstrated that LIR/UFIM is required for the full biological activity of UBA5 and for the effective transfer of UFM1 onto UFC1 and a downstream protein substrate both in vitro and in cells. Taken together, our study provides important structural and functional insights into the interaction between UBA5 and Ub-like modifiers, improving the understanding of the biology of the ufmylation pathway. PMID:26929408

Computational Fluid Dynamics (CFD) Image of Hyper-X Research Vehicle at Mach 7 with Engine Operating

NASA Technical Reports Server (NTRS)

1997-01-01

This computational fluid dynamics (CFD) image shows the Hyper-X vehicle at a Mach 7 test condition with the engine operating. The solution includes both internal (scramjet engine) and external flow fields, including the interaction between the engine exhaust and vehicle aerodynamics. The image illustrates surface heat transfer on the vehicle surface (red is highest heating) and flowfield contours at local Mach number. The last contour illustrates the engine exhaust plume shape. This solution approach is one method of predicting the vehicle performance, and the best method for determination of vehicle structural, pressure and thermal design loads. The Hyper-X program is an ambitious series of experimental flights to expand the boundaries of high-speed aeronautics and develop new technologies for space access. When the first of three aircraft flies, it will be the first time a non-rocket engine has powered a vehicle in flight at hypersonic speeds--speeds above Mach 5, equivalent to about one mile per second or approximately 3,600 miles per hour at sea level. Hyper-X, the flight vehicle for which is designated as X-43A, is an experimental flight-research program seeking to demonstrate airframe-integrated, 'air-breathing' engine technologies that promise to increase payload capacity for future vehicles, including hypersonic aircraft (faster than Mach 5) and reusable space launchers. This multiyear program is currently underway at NASA Dryden Flight Research Center, Edwards, California. The Hyper-X schedule calls for its first flight later this year (2000). Hyper-X is a joint program, with Dryden sharing responsibility with NASA's Langley Research Center, Hampton, Virginia. Dryden's primary role is to fly three unpiloted X-43A research vehicles to validate engine technologies and hypersonic design tools as well as the hypersonic test facility at Langley. Langley manages the program and leads the technology development effort. The Hyper-X Program seeks to significantly expand the speed boundaries of air-breathing propulsion by being the first aircraft to demonstrate an airframe-integrated, scramjet-powered free flight. Scramjets (supersonic-combustion ramjets) are ramjet engines in which the airflow through the whole engine remains supersonic. Scramjet technology is challenging because only limited testing can be performed in ground facilities. Long duration, full-scale testing requires flight research. Scramjet engines are air-breathing, capturing their oxygen from the atmosphere. Current spacecraft, such as the Space Shuttle, are rocket powered, so they must carry both fuel and oxygen for propulsion. Scramjet technology-based vehicles need to carry only fuel. By eliminating the need to carry oxygen, future hypersonic vehicles will be able to carry heavier payloads. Another unique aspect of the X-43A vehicle is the airframe integration. The body of the vehicle itself forms critical elements of the engine. The forebody acts as part of the intake for airflow and the aft section serves as the nozzle. The X-43A vehicles were manufactured by Micro Craft, Inc., Tullahoma, Tennessee. Orbital Sciences Corporation, Chandler, Arizona, built the Pegasus rocket booster used to launch the X-43 vehicles. For the Dryden research flights, the Pegasus rocket booster and attached X-43 will be air launched by Dryden's B-52 'Mothership.' After release from the B-52, the booster will accelerate the X-43A vehicle to the established test conditions (Mach 7 to 10) at an altitude of approximately 100,000 feet where the X-43 will separate from the booster and fly under its own power and preprogrammed control.

Flight Test of the Engine Fuel Schedules of the X-43A Hyper-X Research Vehicles

NASA Technical Reports Server (NTRS)

Jones, Thomas

2006-01-01

The Hyper-X program flew two X-43A Hyper-X Research Vehicles (HXRVs) in 2004, referred to as Ship 2 and Ship 3. The scramjet engine of the X-43A research vehicle was autonomously controlled in flight to track a predetermined fueling schedule. Ship 2 flew at approximately Mach 7 and Ship 3 flew at approximately Mach 10.

Controlled growth of novel hyper-branched nanostructures in nanoporous alumina membrane.

PubMed

Zhang, Junping; Day, Cynthia S; Carroll, David L

2009-12-07

This paper proposes a novel approach to fabricate hyper-branched anodic aluminium oxide (AAO) nanostructures with different branches on the vertically-aligned trunk and at the trunk terminal. Silver nanowires with different dimensional and multifunctional complexity have been prepared from this hyper-branched AAO template by varying the electrodeposition time. These kinds of novel nanostructure may be used to build blocks for nanoelectronic and nanophotonic devices.

[Would the Screening of Common Mental Disorders in Primary-Care Health Services Hyper-Frequent Patients Be Useful?].

PubMed

Rincón-Hoyos, Hernán G; López, Mérida R Rodríguez; Ruiz, Ana María Villa; Hernández, Carlos Augusto; Ramos, Martha Lucía

2012-12-01

Hyper-frequentation in health services is a problem for patients, their families and the institutions. This study is aimed at determining the frequency and characteristics of common mental disorders in hyper-frequent patients showing vague symptoms and signs at a primary healthcare service during the year 2007 in the city of Cali (Colombia). Cross sectional. The most frequent mental disorders in hyper-frequent patients were detected through a telephone interview which included several modules of the PRIME MD instrument. In general, healthcare service hyper-frequenters are working women, 38,7-year old in average. Basically, the consultation is due to cephalalgia but they also exhibit a high prevalence of common mental disorders (somatization, depression and anxiety) not easily diagnosed by physicians in primary care. Expenses for additional health activities generated by these patients are attributed basically to medical consultation and required procedures. Considering hyper-frequenters in health care services as a risk group in terms of common mental disorders involves screening as an efficient strategy to prevent abuse in service use and to improve satisfaction with the attention received. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Influence of Averaging Preprocessing on Image Analysis with a Markov Random Field Model

NASA Astrophysics Data System (ADS)

Sakamoto, Hirotaka; Nakanishi-Ohno, Yoshinori; Okada, Masato

2018-02-01

This paper describes our investigations into the influence of averaging preprocessing on the performance of image analysis. Averaging preprocessing involves a trade-off: image averaging is often undertaken to reduce noise while the number of image data available for image analysis is decreased. We formulated a process of generating image data by using a Markov random field (MRF) model to achieve image analysis tasks such as image restoration and hyper-parameter estimation by a Bayesian approach. According to the notions of Bayesian inference, posterior distributions were analyzed to evaluate the influence of averaging. There are three main results. First, we found that the performance of image restoration with a predetermined value for hyper-parameters is invariant regardless of whether averaging is conducted. We then found that the performance of hyper-parameter estimation deteriorates due to averaging. Our analysis of the negative logarithm of the posterior probability, which is called the free energy based on an analogy with statistical mechanics, indicated that the confidence of hyper-parameter estimation remains higher without averaging. Finally, we found that when the hyper-parameters are estimated from the data, the performance of image restoration worsens as averaging is undertaken. We conclude that averaging adversely influences the performance of image analysis through hyper-parameter estimation.

Hyper-Methylated Loci Persisting from Sessile Serrated Polyps to Serrated Cancers.

PubMed

Andrew, Angeline S; Baron, John A; Butterly, Lynn F; Suriawinata, Arief A; Tsongalis, Gregory J; Robinson, Christina M; Amos, Christopher I

2017-03-02

Although serrated polyps were historically considered to pose little risk, it is now understood that progression down the serrated pathway could account for as many as 15%-35% of colorectal cancers. The sessile serrated adenoma/polyp (SSA/P) is the most prevalent pre-invasive serrated lesion. Our objective was to identify the CpG loci that are persistently hyper-methylated during serrated carcinogenesis, from the early SSA/P lesion through the later cancer phases of neoplasia development. We queried the loci hyper-methylated in serrated cancers within our rightsided SSA/Ps from the New Hampshire Colonoscopy Registry, using the Illumina Infinium Human Methylation 450 k panel to comprehensively assess the DNA methylation status. We identified CpG loci and regions consistently hyper-methylated throughout the serrated carcinogenesis spectrum, in both our SSA/P specimens and in serrated cancers. Hyper-methylated CpG loci included the known the tumor suppressor gene RET (p = 5.72 x 10-10), as well as loci in differentially methylated regions for GSG1L, MIR4493, NTNG1, MCIDAS, ZNF568, and RERG. The hyper-methylated loci that we identified help characterize the biology of SSA/P development, and could be useful as therapeutic targets, or for future identification of patients who may benefit from shorter surveillance intervals.

An advanced scanning method for space-borne hyper-spectral imaging system

NASA Astrophysics Data System (ADS)

Wang, Yue-ming; Lang, Jun-Wei; Wang, Jian-Yu; Jiang, Zi-Qing

2011-08-01

Space-borne hyper-spectral imagery is an important means for the studies and applications of earth science. High cost efficiency could be acquired by optimized system design. In this paper, an advanced scanning method is proposed, which contributes to implement both high temporal and spatial resolution imaging system. Revisit frequency and effective working time of space-borne hyper-spectral imagers could be greatly improved by adopting two-axis scanning system if spatial resolution and radiometric accuracy are not harshly demanded. In order to avoid the quality degradation caused by image rotation, an idea of two-axis rotation has been presented based on the analysis and simulation of two-dimensional scanning motion path and features. Further improvement of the imagers' detection ability under the conditions of small solar altitude angle and low surface reflectance can be realized by the Ground Motion Compensation on pitch axis. The structure and control performance are also described. An intelligent integration technology of two-dimensional scanning and image motion compensation is elaborated in this paper. With this technology, sun-synchronous hyper-spectral imagers are able to pay quick visit to hot spots, acquiring both high spatial and temporal resolution hyper-spectral images, which enables rapid response of emergencies. The result has reference value for developing operational space-borne hyper-spectral imagers.

Follicular fluid lipid fingerprinting from women with PCOS and hyper response during IVF treatment.

PubMed

Cordeiro, Fernanda Bertuccez; Cataldi, Thaís Regiani; do Vale Teixeira da Costa, Lívia; de Lima, Camila Bruna; Stevanato, Juliana; Zylbersztejn, Daniel Suslik; Ferreira, Christina Ramires; Eberlin, Marcos Nogueira; Cedenho, Agnaldo Pereira; Turco, Edson Guimarães Lo

2015-01-01

Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder that leads to lower natural reproductive potential and presents a challenge for assisted reproductive medicine because patients may exhibit immature oocyte retrieval and a higher risk of ovarian hyper stimulation syndrome during in vitro fertilization (IVF) treatment. This study aimed to identify potential lipid biomarkers for women with PCOS and a hyper response to controlled ovarian stimulation. Follicular fluid samples were collected from patients who underwent IVF, including normal responder women who became pregnant (control group, n = 11), women with PCOS and a hyper response to gonadotropins (PCOS group, n = 7) and women with only hyper response to gonadotropins (HR group, n = 7). A lipidomic analysis was performed by electrospray ionization mass spectrometry, and candidate biomarkers were analyzed by tandem mass spectrometry experiment. The lipid profiles indicated particularities related to differences in phosphatidylcholine (PCOS and HR), phosphatidylserine, phosphatydilinositol and phosphatidylglycerol (control), sphingolipids (PCOS) and phosphatidylethanolamine (control and HR). These findings contribute to the understanding of the molecular mechanisms associated with lipid metabolism in the PCOS-related hyper response, and strongly suggest that these lipids may be useful as biomarkers, leading to the development of more individualized treatment for pregnancy outcome.

Hyper-X Engine Testing in the NASA Langley 8-Foot High Temperature Tunnel

NASA Technical Reports Server (NTRS)

Huebner, Lawrence D.; Rock, Kenneth E.; Witte, David W.; Ruf, Edward G.; Andrews, Earl H., Jr.

2000-01-01

Airframe-integrated scramjet engine tests have 8 completed at Mach 7 in the NASA Langley 8-Foot High Temperature Tunnel under the Hyper-X program. These tests provided critical engine data as well as design and database verification for the Mach 7 flight tests of the Hyper-X research vehicle (X-43), which will provide the first-ever airframe- integrated scramjet flight data. The first model tested was the Hyper-X Engine Model (HXEM), and the second was the Hyper-X Flight Engine (HXFE). The HXEM, a partial-width, full-height engine that is mounted on an airframe structure to simulate the forebody features of the X-43, was tested to provide data linking flowpath development databases to the complete airframe-integrated three-dimensional flight configuration and to isolate effects of ground testing conditions and techniques. The HXFE, an exact geometric representation of the X-43 scramjet engine mounted on an airframe structure that duplicates the entire three-dimensional propulsion flowpath from the vehicle leading edge to the vehicle base, was tested to verify the complete design as it will be flight tested. This paper presents an overview of these two tests, their importance to the Hyper-X program, and the significance of their contribution to scramjet database development.

Protective effects of tiotropium alone or combined with budesonide against cadmium inhalation induced acute neutrophilic pulmonary inflammation in rats

PubMed Central

Zhi, Jianming; Gustin, Pascal

2018-01-01

As a potent bronchodilator, the anti-inflammatory effects of tiotropium and its interaction with budesonide against cadmium-induced acute pulmonary inflammation were investigated. Compared to values obtained in rats exposed to cadmium, cytological analysis indicated a significant decrease of total cell and neutrophil counts and protein concentration in bronchoalveolar lavage fluid (BALF) in rats pretreated with tiotropium (70μg/15ml or 350μg/15ml). Zymographic tests showed a decrease of MMP-2 activity in BALF in rats pretreated only with high concentration of tiotropium. Histological examination revealed a significant decrease of the severity and extent of inflammatory lung injuries in rats pretreated with both tested concentrations of tiotropium. Though tiotropium (70μg/15ml) or budesonide (250μg/15ml) could not reduce cadmium-induced bronchial hyper-responsiveness, their combination significantly decreased bronchial contractile response to methacholine. These two drugs separately decreased the neutrophil number and protein concentration in BALF but no significant interaction was observed when both drugs were combined. Although no inhibitory effects on MMP-2 and MMP-9 was observed in rats pretreated with budesonide alone, the combination with the ineffective dose of tiotropium induced a significant reduction on these parameters. The inhibitory effect of tiotropium on lung injuries was not influenced by budesonide which alone induced a limited action on the severity and extent of inflammatory sites. Our findings show that tiotropium exerts anti-inflammatory effects on cadmium-induced acute neutrophilic pulmonary inflammation. The combination of tiotropium with budesonide inhibits cadmium-induced inflammatory injuries with a synergistic interaction on MMP-2 and MMP-9 activity and airway hyper-responsiveness. PMID:29489916

Protective effects of tiotropium alone or combined with budesonide against cadmium inhalation induced acute neutrophilic pulmonary inflammation in rats.

PubMed

Zhao, Shiwei; Yang, Qi; Yu, Zhixi; Lv, You; Zhi, Jianming; Gustin, Pascal; Zhang, Wenhui

2018-01-01

As a potent bronchodilator, the anti-inflammatory effects of tiotropium and its interaction with budesonide against cadmium-induced acute pulmonary inflammation were investigated. Compared to values obtained in rats exposed to cadmium, cytological analysis indicated a significant decrease of total cell and neutrophil counts and protein concentration in bronchoalveolar lavage fluid (BALF) in rats pretreated with tiotropium (70μg/15ml or 350μg/15ml). Zymographic tests showed a decrease of MMP-2 activity in BALF in rats pretreated only with high concentration of tiotropium. Histological examination revealed a significant decrease of the severity and extent of inflammatory lung injuries in rats pretreated with both tested concentrations of tiotropium. Though tiotropium (70μg/15ml) or budesonide (250μg/15ml) could not reduce cadmium-induced bronchial hyper-responsiveness, their combination significantly decreased bronchial contractile response to methacholine. These two drugs separately decreased the neutrophil number and protein concentration in BALF but no significant interaction was observed when both drugs were combined. Although no inhibitory effects on MMP-2 and MMP-9 was observed in rats pretreated with budesonide alone, the combination with the ineffective dose of tiotropium induced a significant reduction on these parameters. The inhibitory effect of tiotropium on lung injuries was not influenced by budesonide which alone induced a limited action on the severity and extent of inflammatory sites. Our findings show that tiotropium exerts anti-inflammatory effects on cadmium-induced acute neutrophilic pulmonary inflammation. The combination of tiotropium with budesonide inhibits cadmium-induced inflammatory injuries with a synergistic interaction on MMP-2 and MMP-9 activity and airway hyper-responsiveness.

Hyper-O-GlcNAcylation of YB-1 affects Ser102 phosphorylation and promotes cell proliferation in hepatocellular carcinoma

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

Liu, Qingqing; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qi-xiu Road, Nantong 226001, Jiangsu Province; Tao, Tao

As an essential post-translational modification, O-GlcNAcylation has been thought to be able to modulate various nuclear and cytoplasmic proteins and is emerging as a key regulator of multiple biological processes, such as transcription, cell growth, signal transduction, and cell motility. Recently, authoritative glycomics analyses have reported extensive crosstalk between O-GlcNAcylation and phosphorylation, which always dynamically interplay with each other and regulate signaling, transcription, and other cellular processes. Also, plentiful studies have shown close correlation between YB-1 phosphorylation and tumorigenesis. Therefore, our study aimed to determine whether YB-1 was O-GlcNAc modified and whether such modification could interact with its phosphorylation duringmore » the process of HCC development. Western blot and immunohistochemistry were firstly conducted to reveal obvious up-regulation of YB-1, OGT and O-GlcNAc modification in HCC tissues. What is more, not only YB-1 was identified to be O-GlcNAcylated but hyper-O-GlcNAcylation was demonstrated to facilitate HCC cell proliferation in a YB-1 dependent manner. Moreover, we detected four specific O-GlcNAc sites and confirmed T126A to be the most effective mutant in HCC cell proliferation via close O-GlcNAcylation-phosphorylation interaction. Even more interestingly, we discovered that T126A-induced HCC cell retardation and subdued transcriptional activity of YB-1 could be partially reversed by T126A/S102E mutant. From all above, it is not difficult to find that glycosylated-YB-1 mainly enhanced cell proliferation through congenerous actions with YB-1 phosphorylation and thus played indispensable roles in fine-tuning cell proliferation and procession of HCC. - Highlights: • YB-1 and OGT are associated with HCC prognosis. • YB-1 is O-GlcNAc modified in HCC. • Hyper-O-GlcNAcylation promotes HCC cell proliferation in dependent of YB-1. • The proliferating role of O-GlcNAcylation is based on Ser102 phosphorylation of YB-1.« less

Clinical features and dysfunctions of iron metabolism in Parkinson disease patients with hyper echogenicity in substantia nigra: a cross-sectional study.

PubMed

Yu, Shu-Yang; Cao, Chen-Jie; Zuo, Li-Jun; Chen, Ze-Jie; Lian, Teng-Hong; Wang, Fang; Hu, Yang; Piao, Ying-Shan; Li, Li-Xia; Guo, Peng; Liu, Li; Yu, Qiu-Jin; Wang, Rui-Dan; Chan, Piu; Chen, Sheng-di; Wang, Xiao-Min; Zhang, Wei

2018-01-17

Transcranial ultrasound is a useful tool for providing the evidences for the early diagnosis and differential diagnosis of Parkinson disease (PD). However, the relationship between hyper echogenicity in substantia nigra (SN) and clinical symptoms of PD patients remains unknown, and the role of dysfunction of iron metabolism on the pathogenesis of SN hyper echogenicity is unclear. PD patients was detected by transcranial sonography and divided into with no hyper echogenicity (PDSN-) group and with hyper echogenicity (PDSN+) group. Motor symptoms (MS) and non-motor symptoms (NMS) were evaluated, and the levels of iron and related proteins in serum and cerebrospinal fluid (CSF) were detected for PD patients. Data comparison between the two groups and correlation analyses were performed. PDSN+ group was significantly older, and had significantly older age of onset, more advanced Hohen-Yahr stage, higher SCOPA-AUT score and lower MoCA score than PDSN- group (P < 0.05). Compared with PDSN- group, the levels of transferrin and light-ferritin in serum and iron level in CSF were significantly elevated (P < 0.05), but ferroportin level in CSF was significantly decreased in PDSN+ group (P < 0.05). PD patients with hyper echogenicity in SN are older, at more advanced disease stage, have severer motor symptoms, and non-motor symptoms of cognitive impairment and autonomic dysfunction. Hyper echogenicity of SN in PD patients is related to dysfunction of iron metabolism, involving increased iron transport from peripheral system to central nervous system, reduction of intracellular iron release and excessive iron deposition in brain.

Influence of molecular designs on polaronic and vibrational transitions in a conjugated push-pull copolymer

NASA Astrophysics Data System (ADS)

Cobet, Christoph; Gasiorowski, Jacek; Menon, Reghu; Hingerl, Kurt; Schlager, Stefanie; White, Matthew S.; Neugebauer, Helmut; Sariciftci, N. Serdar; Stadler, Philipp

2016-10-01

Electron-phonon interactions of free charge-carriers in doped pi-conjugated polymers are conceptually described by 1-dimensional (1D) delocalization. Thereby, polaronic transitions fit the 1D-Froehlich model in quasi-confined chains. However, recent developments in conjugated polymers have diversified the backbones to become elaborate heterocylcic macromolecules. Their complexity makes it difficult to investigate the electron-phonon coupling. In this work we resolve the electron-phonon interactions in the ground and doped state in a complex push-pull polymer. We focus on the polaronic transitions using in-situ spectroscopy to work out the differences between single-unit and push-pull systems to obtain the desired structural- electronic correlations in the doped state. We apply the classic 1D-Froehlich model to generate optical model fits. Interestingly, we find the 1D-approach in push-pull polarons in agreement to the model, pointing at the strong 1D-character and plain electronic structure of the push-pull structure. In contrast, polarons in the single-unit polymer emerge to a multi- dimensional problem difficult to resolve due to their anisotropy. Thus, we report an enhancement of the 1D-character by the push-pull concept in the doped state - an important view in light of the main purpose of push-pull polymers for photovoltaic devices.

Uniform two-dimensional square assemblies from conjugated block copolymers driven by π–π interactions with controllable sizes

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

Han, Liang; Wang, Meijing; Jia, Xiangmeng

Two-dimensional (2-D) micro- and nano- architectures are attractive because of their unique properties caused by their ultrathin and flat morphologies. However, the formation of 2-D supramolecular highly symmetrical structures with considerable control is still a major challenge. Here, we presented a simple approach for the preparation of regular and homogeneous 2-D fluorescent square noncrystallization micelles with conjugated diblock copolymers PPV12-b-P2VPn through a process of dissolving-cooling-aging. The scale of the formed micelles could be controlled by the ratio of PPV/P2VP blocks and the concentration of the solution. The forming process of the platelet square micelles was analyzed by UV-Vis, DLS andmore » SLS, while the molecular arrangement was characterized by GIXD. The results revealed that the micelles of PPV12-b-P2VPn initially form 1-D structures and then grow into 2-D structures in solution, and the growth is driven by intermolecular π-π interactions with the PPV12 blocks. The formation of 2-D square micelles is induced by herringbone arrangement of the molecules, which is closely related to the presence of the branched alkyl chains attached to conjugated PPV12 cores.« less

Carbohydrate conjugation through microwave-assisted functionalization of single-walled carbon nanotubes using perfluorophenyl azides.

PubMed

Kong, Na; Shimpi, Manishkumar R; Ramström, Olof; Yan, Mingdi

2015-03-20

Carbohydrate-functionalized single-walled carbon nanotubes (SWNTs) were synthesized using microwave-assisted reaction of perfluorophenyl azide with the nanotubes. The results showed that microwave radiation provides a rapid and effective means to covalently attach carbohydrates to SWNTs, producing carbohydrate-SWNT conjugates for biorecognition. The carbohydrate-functionalized SWNTs were furthermore shown to interact specifically with cognate carbohydrate-specific proteins (lectins), resulting in predicted recognition patterns. The carbohydrate-presenting SWNTs constitute a new platform for sensitive protein- or cell recognition, which pave the way for glycoconjugated carbon nanomaterials in biorecognition applications. Copyright © 2014 Elsevier Ltd. All rights reserved.

Preparation of Conjugates of Cytotoxic Lupane Triterpenes with Biotin.

PubMed

Soural, Miroslav; Hodon, Jiri; Dickinson, Niall J; Sidova, Veronika; Gurska, Sona; Dzubak, Petr; Hajduch, Marian; Sarek, Jan; Urban, Milan

2015-12-16

To better understand the mechanism of action of antitumor triterpenes, we are developing methods to identify their molecular targets. A promising method is based on combination of quantitative proteomics with SILAC and uses active compounds anchored to magnetic beads via biotin-streptavidin interaction. We developed a simple and fast solid-phase synthetic technique to connect terpenes to biotin through a linker. Betulinic acid was biotinylated from three different conjugation sites for use as a standard validation tool since many molecular targets of this triterpene are already known. Then, a set of four other cytotoxic triterpenoids was biotinylated. Biotinylated terpenes were similarly cytotoxic to their nonbiotinylated parents, which suggests that the target identification should not be influenced by linker or biotin. The developed solid-phase synthetic approach is the first attempt to use solid-phase synthesis to connect active triterpenes to biotin and is applicable as a general procedure for routine conjugation of triterpenes with other molecules of choice.

Charge-conjugation symmetric complete impulse approximation for the pion electromagnetic form factor in the covariant spectator theory

DOE PAGES

Biernat, Elmar P.; Gross, Franz; Peña, M. T.; ...

2015-10-26

The pion form factor is calculated in the framework of the charge-conjugation invariant covariant spectator theory. This formalism is established in Minkowski space, and the calculation is set up in momentum space. In a previous calculation we included only the leading pole coming from the spectator quark (referred to as the relativistic impulse approximation). In this study we also include the contributions from the poles of the quark which interacts with the photon and average over all poles in both the upper and lower half-planes in order to preserve charge conjugation invariance (referred to as the C-symmetric complete impulse approximation).more » We find that for small pion mass these contributions are significant at all values of the four-momentum transfer Q 2 but, surprisingly, do not alter the shape obtained from the spectator poles alone.« less

Enhanced photophysics of conjugated polymers

DOEpatents

Chen, Liaohai [Argonne, IL; Xu, Su [Santa Clara, CA; McBranch, Duncan [Santa Fe, NM; Whitten, David [Santa Fe, NM

2003-05-27

The addition of oppositely charged surfactant to fluorescent ionic conjugated polymer forms a polymer-surfactant complex that exhibits at least one improved photophysical property. The conjugated polymer is a fluorescent ionic polymer that typically has at least one ionic side chain or moiety that interacts with the specific surfactant selected. The photophysical property improvements may include increased fluorescence quantum efficiency, wavelength-independent emission and absorption spectra, and more stable fluorescence decay kinetics. The complexation typically occurs in a solution of a polar solvent in which the polymer and surfactant are soluble, but it may also occur in a mixture of solvents. The solution is commonly prepared with a surfactant molecule:monomer repeat unit of polymer ratio ranging from about 1:100 to about 1:1. A polymer-surfactant complex precipitate is formed as the ratio approaches 1:1. This precipitate is recoverable and usable in many forms.

Probing nanoparticles and nanoparticle-conjugated biomolecules using time-of-flight secondary ion mass spectrometry.

PubMed

Kim, Young-Pil; Shon, Hyun Kyong; Shin, Seung Koo; Lee, Tae Geol

2015-01-01

Bio-conjugated nanoparticles have emerged as novel molecular probes in nano-biotechnology and nanomedicine and chemical analyses of their surfaces have become challenges. The time-of-flight (TOF) secondary ion mass spectrometry (SIMS) has been one of the most powerful surface characterization techniques for both nanoparticles and biomolecules. When combined with various nanoparticle-based signal enhancing strategies, TOF-SIMS can probe the functionalization of nanoparticles as well as their locations and interactions in biological systems. Especially, nanoparticle-based SIMS is an attractive approach for label-free drug screening because signal-enhancing nanoparticles can be designed to directly measure the enzyme activity. The chemical-specific imaging analysis using SIMS is also well suited to screen nanoparticles and nanoparticle-biomolecule conjugates in complex environments. This review presents some recent applications of nanoparticle-based TOF-SIMS to the chemical analysis of complex biological systems. © 2014 Wiley Periodicals, Inc.