Quantum phase transition in dimerised spin-1/2 chains

NASA Astrophysics Data System (ADS)

Das, Aparajita; Bhadra, Sreeparna; Saha, Sonali

2015-11-01

Quantum phase transition in dimerised antiferromagnetic Heisenberg spin chain has been studied. A staircase structure in the variation of concurrence within strongly coupled pairs with that of external magnetic field has been observed indicating multiple critical (or critical like) points. Emergence of entanglement due to external magnetic field or magnetic entanglement is observed for weakly coupled spin pairs too in the same dimer chain. Though closed dimerised isotropic XXX Heisenberg chains with different dimer strengths were mainly explored, analogous studies on open chains as well as closed anisotropic (XX interaction) chains with tilted external magnetic field have also been studied.

47 CFR 15.119 - Closed caption decoder requirements for analog television receivers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... character or space may appear. A cell is one row high and one column wide. (5) Column: One of 32 vertical... television receivers. 15.119 Section 15.119 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL RADIO FREQUENCY DEVICES Unintentional Radiators § 15.119 Closed caption decoder requirements for analog television...

47 CFR 15.119 - Closed caption decoder requirements for analog television receivers.

Code of Federal Regulations, 2011 CFR

2011-10-01

... character or space may appear. A cell is one row high and one column wide. (5) Column: One of 32 vertical... television receivers. 15.119 Section 15.119 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL RADIO FREQUENCY DEVICES Unintentional Radiators § 15.119 Closed caption decoder requirements for analog television...

Printing and Prototyping of Tissues and Scaffolds

NASA Astrophysics Data System (ADS)

Derby, Brian

2012-11-01

New manufacturing technologies under the banner of rapid prototyping enable the fabrication of structures close in architecture to biological tissue. In their simplest form, these technologies allow the manufacture of scaffolds upon which cells can grow for later implantation into the body. A more exciting prospect is the printing and patterning in three dimensions of all the components that make up a tissue (cells and matrix materials) to generate structures analogous to tissues; this has been termed bioprinting. Such techniques have opened new areas of research in tissue engineering and regenerative medicine.

Identification of Eight Synthetic Cannabinoids, Including 5F-AKB48 in Seized Herbal Products Using DART-TOF-MS and LC-QTOF-MS as Nontargeted Screening Methods.

PubMed

Moore, Katherine N; Garvin, Demetra; Thomas, Brian F; Grabenauer, Megan

2017-09-01

Synthetic cannabinoids are sprayed onto plant material and smoked for their marijuana-like effects. Clandestine manufacturers modify synthetic cannabinoid structures by creating closely related analogs. Forensic laboratories are tasked with detection of these analog compounds, but targeted analytical methods are often thwarted by the structural modifications. Here, direct analysis in real time coupled to accurate mass time-of-flight mass spectrometry (DART-TOF-MS) in combination with liquid chromatography quadruple time-of-flight mass spectrometry (LC-QTOF-MS) are presented as a screening and nontargeted confirmation method, respectively. Methanol extracts of herbal material were run using both methods. Spectral data from four different herbal products were evaluated by comparing fragmentation pattern, accurate mass and retention time to available reference standards. JWH-018, JWH-019, AM2201, JWH-122, 5F-AKB48, AKB48-N-(4-pentenyl) analog, UR144, and XLR11 were identified in the products. Results demonstrate that DART-TOF-MS affords a useful approach for rapid screening of herbal products for the presence and identification of synthetic cannabinoids. © 2017 American Academy of Forensic Sciences.

Twist-induced guidance in coreless photonic crystal fiber: A helical channel for light.

PubMed

Beravat, Ramin; Wong, Gordon K L; Frosz, Michael H; Xi, Xiao Ming; Russell, Philip St J

2016-11-01

A century ago, Einstein proposed that gravitational forces were the result of the curvature of space-time and predicted that light rays would deflect when passing a massive celestial object. We report that twisting the periodically structured "space" within a coreless photonic crystal fiber creates a helical channel where guided modes can form despite the absence of any discernible core structure. Using a Hamiltonian optics analysis, we show that the light rays follow closed spiral or oscillatory paths within the helical channel, in close analogy with the geodesics of motion in a two-dimensional gravitational field. The mode diameter shrinks, and its refractive index rises, as the twist rate increases. The birefringence, orbital angular momentum, and dispersion of these unusual modes are explored.

FGFR1 Kinase Inhibitors: Close Regioisomers Adopt Divergent Binding Modes and Display Distinct Biophysical Signatures.

PubMed

Klein, Tobias; Tucker, Julie; Holdgate, Geoffrey A; Norman, Richard A; Breeze, Alexander L

2014-02-13

The binding of a ligand to its target protein is often accompanied by conformational changes of both the protein and the ligand. This is of particular interest, since structural rearrangements of the macromolecular target and the ligand influence the free energy change upon complex formation. In this study, we use X-ray crystallography, isothermal titration calorimetry, and surface-plasmon resonance biosensor analysis to investigate the binding of pyrazolylaminopyrimidine inhibitors to FGFR1 tyrosine kinase, an important anticancer target. Our results highlight that structurally close analogs of this inhibitor series interact with FGFR1 with different binding modes, which are a consequence of conformational changes in both the protein and the ligand as well as the bound water network. Together with the collected kinetic and thermodynamic data, we use the protein-ligand crystal structure information to rationalize the observed inhibitory potencies on a molecular level.

Fernandina caldera collapse morphology in geometric and dynamic comparison to sandbox models, subsidence sinks over nuclear-explosion cavities, and some other calderas

NASA Astrophysics Data System (ADS)

Howard, K. A.

2009-12-01

The 1968 collapse structure of Fernandina caldera (1.5 km3 collapsed) and also the smaller Darwin Bay caldera in Galápagos each closely resembles morphologically the structural zoning of features found in depressions collapsed into nuclear-explosion cavities (“sinks” of Houser, 1969) and in coherent sandbox-collapse models. Coherent collapses characterized by faulting, folding, and organized structure contrast with spalled pit craters (and lab experiments with collapsed powder) where disorganized piles of floor rubble result from tensile failure of the roof. Subsidence in coherent mode, whether in weak sand in the lab, stronger desert alluvium for nuclear-test sinks, or in hard rock for calderas, exhibits consistent morphologic zones. Characteristically in the sandbox and the nuclear-test analogs these include a first-formed central plug that drops along annular reverse faults. This plug and a surrounding inward-tilted or monoclinal ring (hanging wall of the reverse fault) contract as the structure expands outward by normal faulting, wherein peripheral rings of distending material widen the upper part of the structure along inward-dipping normal faults and compress inner zones and help keep them intact. In Fernandina, a region between the monocline and the outer zone of normal faulting is interpreted, by comparison to the analogs, to overlie the deflation margin of an underlying magma chamber. The same zoning pattern is recognized in structures ranging from sandbox subsidence features centimeters across, to Alae lave lake and nuclear-test sinks tens to hundreds of meters across, to Fenandina’s 2x4 km-wide collapse, to Martian calderas tens of kilometers across. Simple dimensional analysis using the height of cliffs as a proxie for material strength implies that the geometric analogs are good dynamic analogs, and validates that the pattern of both reverse and normal faulting that has been reported consistently from sandbox modeling applies widely to calderas.

Design and Theoretical Analysis of a Resonant Sensor for Liquid Density Measurement

PubMed Central

Zheng, Dezhi; Shi, Jiying; Fan, Shangchun

2012-01-01

In order to increase the accuracy of on-line liquid density measurements, a sensor equipped with a tuning fork as the resonant sensitive component is designed in this paper. It is a quasi-digital sensor with simple structure and high precision. The sensor is based on resonance theory and composed of a sensitive unit and a closed-loop control unit, where the sensitive unit consists of the actuator, the resonant tuning fork and the detector and the closed-loop control unit comprises precondition circuit, digital signal processing and control unit, analog-to-digital converter and digital-to-analog converter. An approximate parameters model of the tuning fork is established and the impact of liquid density, position of the tuning fork, temperature and structural parameters on the natural frequency of the tuning fork are also analyzed. On this basis, a tuning fork liquid density measurement sensor is developed. In addition, experimental testing on the sensor has been carried out on standard calibration facilities under constant 20 °C, and the sensor coefficients are calibrated. The experimental results show that the repeatability error is about 0.03% and the accuracy is about 0.4 kg/m3. The results also confirm that the method to increase the accuracy of liquid density measurement is feasible. PMID:22969378

Design and theoretical analysis of a resonant sensor for liquid density measurement.

PubMed

Zheng, Dezhi; Shi, Jiying; Fan, Shangchun

2012-01-01

In order to increase the accuracy of on-line liquid density measurements, a sensor equipped with a tuning fork as the resonant sensitive component is designed in this paper. It is a quasi-digital sensor with simple structure and high precision. The sensor is based on resonance theory and composed of a sensitive unit and a closed-loop control unit, where the sensitive unit consists of the actuator, the resonant tuning fork and the detector and the closed-loop control unit comprises precondition circuit, digital signal processing and control unit, analog-to-digital converter and digital-to-analog converter. An approximate parameters model of the tuning fork is established and the impact of liquid density, position of the tuning fork, temperature and structural parameters on the natural frequency of the tuning fork are also analyzed. On this basis, a tuning fork liquid density measurement sensor is developed. In addition, experimental testing on the sensor has been carried out on standard calibration facilities under constant 20 °C, and the sensor coefficients are calibrated. The experimental results show that the repeatability error is about 0.03% and the accuracy is about 0.4 kg/m(3). The results also confirm that the method to increase the accuracy of liquid density measurement is feasible.

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

Brandao, T.; Robinson, H; Johnson, S

Catalysis by the Yersinia protein-tyrosine phosphatase YopH is significantly impaired by the mutation of the conserved Trp354 residue to Phe. Though not a catalytic residue, this Trp is a hinge residue in a conserved flexible loop (the WPD-loop) that must close during catalysis. To learn why this seemingly conservative mutation reduces catalysis by 2 orders of magnitude, we have solved high-resolution crystal structures for the W354F YopH in the absence and in the presence of tungstate and vanadate. Oxyanion binding to the P-loop in W354F is analogous to that observed in the native enzyme. However, the WPD-loop in the presencemore » of oxyanions assumes a half-closed conformation, in contrast to the fully closed state observed in structures of the native enzyme. This observation provides an explanation for the impaired general acid catalysis observed in kinetic experiments with Trp mutants. A 1.4 Angstroms structure of the W354F mutant obtained in the presence of vanadate reveals an unusual divanadate species with a cyclic [VO]2 core, which has precedent in small molecules but has not been previously reported in a protein crystal structure.« less

Finding and estimating chemical property data for environmental assessment.

PubMed

Boethling, Robert S; Howard, Philip H; Meylan, William M

2004-10-01

The ability to predict the behavior of a chemical substance in a biological or environmental system largely depends on knowledge of the physicochemical properties and reactivity of that substance. We focus here on properties, with the objective of providing practical guidance for finding measured values and using estimation methods when necessary. Because currently available computer software often makes it more convenient to estimate than to retrieve measured values, we try to discourage irrational exuberance for these tools by including comprehensive lists of Internet and hard-copy data resources. Guidance for assessors is presented in the form of a process to obtain data that includes establishment of chemical identity, identification of data sources, assessment of accuracy and reliability, substructure searching for analogs when experimental data are unavailable, and estimation from chemical structure. Regarding property estimation, we cover estimation from close structural analogs in addition to broadly applicable methods requiring only the chemical structure. For the latter, we list and briefly discuss the most widely used methods. Concluding thoughts are offered concerning appropriate directions for future work on estimation methods, again with an emphasis on practical applications.

Visualizing along-strike change in deformation style using analog modeling and digital visualization software

NASA Astrophysics Data System (ADS)

Burberry, C. M.

2012-12-01

It is a well-known phenomenon that deformation style varies in space; both along the strike of a deformed belt and along the strike of individual structures within that belt. This variation in deformation style is traditionally visualized with a series of closely spaced 2D cross-sections. However, the use of 2D section lines implies plane strain along those lines, and the true 3D nature of the deformation is not necessarily captured. By using a combination of remotely sensed data, analog modeling of field datasets and this remote data, and numerical and digital visualization of the finished model, a 3D understanding and restoration of the deformation style within the region can be achieved. The workflow used for this study begins by considering the variation in deformation style which can be observed from satellite images and combining this data with traditional field data, in order to understand the deformation in the region under consideration. The conceptual model developed at this stage is then modeled using a sand and silicone modeling system, where the kinematics and dynamics of the deformation processes can be examined. A series of closely-spaced cross-sections, as well as 3D images of the deformation, are created from the analog model, and input into a digital visualization and modeling system for restoration. In this fashion, a valid 3D model is created where the internal structure of the deformed system can be visualized and mined for information. The region used in the study is the Sawtooth Range, Montana. The region forms part of the Montana Disturbed Belt in the Front Ranges of the Rocky Mountains, along strike from the Alberta Syncline in the Canadian Rocky Mountains. Interpretation of satellite data indicates that the deformation front structures include both folds and thrust structures. The thrust structures vary from hinterland-verging triangle zones to foreland-verging imbricate thrusts along strike, and the folds also vary in geometry along strike. The analog models, constrained by data from exploration wells, indicate that this change in geometry is related to a change in mechanical stratigraphy along the strike of the belt. Results from the kinematic and dynamic analysis of the digital model will also be presented. Additional implications of such a workflow and visualization system include the possibility of creating and viewing multiple cross-sections, including sections created at oblique angles to the original model. This allows the analysis of the non-plane strain component of the models and thus a more complete analysis, understanding and visualization of the deformed region. This workflow and visualization system is applicable to any region where traditional field methods must be coupled with remote data, intensely processed depth data, or analog modeling systems in order to generate valid geologic or geophsyical models.

A Method to Formulate the Unit Cell for Density Functional Theory (DFT) Calculations of the Electronic Band Structure of Heterostructures of Two-dimensional Nanosheets

DTIC Science & Technology

2015-04-01

distribution is unlimited. i CONTENTS Page Introduction 1 Two-dimensional Material Geometry and Analogs with Close-packed Systems 1 Matching... System Lattice Vectors: An Optimization Problem 1 Generating the System Unit Cell 3 Transition Metal Dichalcogenides (TMDCS) with Mismatched... system being analyzed. The creation of a unit cell that accurately describes the system remains one of the largest challenges for DFT calculations

Spectroscopic studies on the conformational transitions of a bovine growth hormone releasing factor analog

NASA Astrophysics Data System (ADS)

Sarver, Ronald W.; Friedman, Alan R.; Thamann, Thomas J.

1997-10-01

The secondary structure of the bovine growth hormone releasing factor analog, [Ile 2, Ser 8,28, Ala 15, Leu 27, Hse 30] bGRF(1-30)-NH-Ethyl, acetate salt (U-90699F) was studied in solution by Fourier transform infrared and Raman spectroscopies. Spectroscopic studies revealed that concentrated aqueous solutions of U-90699F (100 mg ml -1) undergo a secondary structure transition from disordered coil/α-helix to intermolecular β-sheet. Disordered coil and α-helical structure were grouped together in the infrared and Raman studies since the amide I vibrations are close in frequency and overlap in assignments was possible. Before the conformational transition, the facile exchange of the peptide's amide hydrogens for deuterium indicated that the majority of amide hydrogens were readily accessible to solvent. The kinetics of the conformational transition coincided with an increase in solution viscosity and turbidity. An initiation phase preceded the conformational transition during which only minor spectral changes were observed by infrared spectroscopy. The initiation phase and reaction kinetics were consistent with a highly cooperative nucleation ultimately leading to a network of intermolecular β-sheet structure and gel formation. Increased temperature accelerated the conformational transition. The conformational transition was thermally irreversible but the β-sheet structure of aggregated or gelled peptide could be disrupted by dilution and agitation.

Natural analog studies: Licensing perspective

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

Bradbury, J.W.

1995-09-01

This report describes the licensing perspective of the term {open_quotes}natural analog studies{close_quotes} as used in CFR Part 60. It describes the misunderstandings related to its definition which has become evident during discussions at the U.S Nuclear Regulatory Commission meetings and tries to clarify the appropriate applications of natural analog studies to aspects of repository site characterization.

Coronal Structures in Cool Stars: XMM-NEWTON Hybrid Stars and Coronal Evolution

NASA Technical Reports Server (NTRS)

Dupree, Andrea K.; Mushotzky, Richard (Technical Monitor)

2003-01-01

This program addresses the evolution of stellar coronas by comparing a solar-like corona in the supergiant Beta Dra (G2 Ib-IIa) to the corona in the allegedly more evolved state of a hybrid star, alpha TrA (K2 II-III). Because the hybrid star has a massive wind, it appears likely that the corona will be cooler and less dense as the magnetic loop structures are no longer closed. By analogy with solar coronal holes, when the topology of the magnetic field is configured with open magnetic structures, both the coronal temperature and density are lower than in atmospheres dominated by closed loops. The hybrid stars assume a pivotal role in the definition of coronal evolution, atmospheric heating processes and mechanisms to drive winds of cool stars. We are attempting to determine if this model of coronal evolution is correct by using XMM-NEWTON RGS spectra for the 2 targets we were allocated through the Guest Observer program.

On non-homogeneous tachyon condensation in closed string theory

NASA Astrophysics Data System (ADS)

Giribet, Gaston; Rado, Laura

2017-08-01

Lorentzian continuation of the Sine-Liouville model describes non-homogeneous rolling closed string tachyon. Via T-duality, this relates to the gauged H + 3 Wess-Zumino-Witten model at subcritical level. This model is exactly solvable. We give a closed formula for the 3-point correlation functions for the model at level k within the range 0 < k < 2, which relates to the analogous quantity for k > 2 in a similar way as how the Harlow-Maltz-Witten 3-point function of timelike Liouville field theory relates to the analytic continuation of the Dorn-Otto-Zamolodchikov-Zamolodchikov structure constants: we find that the ratio between both 3-point functions can be written in terms of quotients of Jacobi's θ-functions, while their product exhibits remarkable cancellations and eventually factorizes. Our formula is consistent with previous proposals made in the literature.

How Does the Ionic Liquid Organizational Landscape Change when Nonpolar Cationic Alkyl Groups Are Replaced by Polar Isoelectronic Diethers?

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

Kashyap, Hemant K.; Santos, Cherry S.; Daly, Ryan P.

2012-12-21

The X-ray scattering experiments and molecular dynamics simulations have been performed to investigate the structure of four room temperature ionic liquids (ILs) comprising the bis(trifluoromethylsulfonyl)amide (NTf 2 –) anion paired with the triethyloctylammonium (N 2228 +) and triethyloctylphosphonium (P 2228 +) cations and their isoelectronic diether analogs, the (2-ethoxyethoxy)ethyltriethylammonium (N 222(2O2O2) +) and (2-ethoxyethoxy)ethyltriethylphosphonium (P 222(2O2O2) +) cations. Agreement between simulations and experiments is good and permits a clear interpretation of the important topological differences between these systems. The first sharp diffraction peak (or prepeak) in the structure function S(q) that is present in the case of the liquids containingmore » the alkyl-substituted cations is absent in the case of the diether substituted analogs. Using different theoretical partitioning schemes for the X-ray structure function, we show that the prepeak present in the alkyl-substituted ILs arises from polarity alternations between charged groups and nonpolar alkyl tails. In the case of the diether substituted ILs, we find considerable curling of tails. Anions can be found with high probability in two different environments: close to the cationic nitrogen (phosphorus) and also close to the two ether groups. Moreover, for the two diether systems, anions are found in locations from which they are excluded in the alkyl-substituted systems. This removes the longer range (polar/nonpolar) pattern of alternation that gives rise to the prepeak in alkyl-substituted systems.« less

First Identification of 5,11-Dideoxytetrodotoxin in Marine Animals, and Characterization of Major Fragment Ions of Tetrodotoxin and Its Analogs by High Resolution ESI-MS/MS

PubMed Central

Yotsu-Yamashita, Mari; Abe, Yuka; Kudo, Yuta; Ritson-Williams, Raphael; Paul, Valerie J.; Konoki, Keiichi; Cho, Yuko; Adachi, Masaatsu; Imazu, Takuya; Nishikawa, Toshio; Isobe, Minoru

2013-01-01

Even though tetrodotoxin (TTX) is a widespread toxin in marine and terrestrial organisms, very little is known about the biosynthetic pathway used to produce it. By describing chemical structures of natural analogs of TTX, we can start to identify some of the precursors that might be important for TTX biosynthesis. In the present study, an analog of TTX, 5,11-dideoxyTTX, was identified for the first time in natural sources, the ovary of the pufferfish and the pharynx of a flatworm (planocerid sp. 1), by comparison with totally synthesized (−)-5,11-dideoxyTTX, using high resolution ESI-LC-MS. Based on the presence of 5,11-dideoxyTTX together with a series of known deoxy analogs, 5,6,11-trideoxyTTX, 6,11-dideoxyTTX, 11-deoxyTTX, and 5-deoxyTTX, in these animals, we predicted two routes of stepwise oxidation pathways in the late stages of biosynthesis of TTX. Furthermore, high resolution masses of the major fragment ions of TTX, 6,11-dideoxyTTX, and 5,6,11-trideoxyTTX were also measured, and their molecular formulas and structures were predicted to compare them with each other. Although both TTX and 5,6,11-trideoxyTTX give major fragment ions that are very close, m/z 162.0660 and 162.1020, respectively, they are distinguishable and predicted to be different molecular formulas. These data will be useful for identification of TTXs using high resolution LC-MS/MS. PMID:23924959

Structural asymmetry and intersubunit communication in muscle creatine kinase.

PubMed

Ohren, Jeffrey F; Kundracik, Melisa L; Borders, Charles L; Edmiston, Paul; Viola, Ronald E

2007-03-01

The structure of a transition-state analog complex of a highly soluble mutant (R134K) of rabbit muscle creatine kinase (rmCK) has been determined to 1.65 A resolution in order to elucidate the structural changes that are required to support and regulate catalysis. Significant structural asymmetry is seen within the functional homodimer of rmCK, with one monomer found in a closed conformation with the active site occupied by the transition-state analog components creatine, MgADP and nitrate. The other monomer has the two loops that control access to the active site in an open conformation and only MgADP is bound. The N-terminal region of each monomer makes a substantial contribution to the dimer interface; however, the conformation of this region is dramatically different in each subunit. Based on this structural evidence, two mutational modifications of rmCK were conducted in order to better understand the role of the amino-terminus in controlling creatine kinase activity. The deletion of the first 15 residues of rmCK and a single point mutant (P20G) both disrupt subunit cohesion, causing the dissociation of the functional homodimer into monomers with reduced catalytic activity. This study provides support for a structural role for the amino-terminus in subunit association and a mechanistic role in active-site communication and catalytic regulation.

Single-molecule comparison of DNA Pol I activity with native and analog nucleotides

NASA Astrophysics Data System (ADS)

Gul, Osman; Olsen, Tivoli; Choi, Yongki; Corso, Brad; Weiss, Gregory; Collins, Philip

2014-03-01

DNA polymerases are critical enzymes for DNA replication, and because of their complex catalytic cycle they are excellent targets for investigation by single-molecule experimental techniques. Recently, we studied the Klenow fragment (KF) of DNA polymerase I using a label-free, electronic technique involving single KF molecules attached to carbon nanotube transistors. The electronic technique allowed long-duration monitoring of a single KF molecule while processing thousands of template strands. Processivity of up to 42 nucleotide bases was directly observed, and statistical analysis of the recordings determined key kinetic parameters for the enzyme's open and closed conformations. Subsequently, we have used the same technique to compare the incorporation of canonical nucleotides like dATP to analogs like 1-thio-2'-dATP. The analog had almost no affect on duration of the closed conformation, during which the nucleotide is incorporated. On the other hand, the analog increased the rate-limiting duration of the open conformation by almost 40%. We propose that the thiolated analog interferes with KF's recognition and binding, two key steps that determine its ensemble turnover rate.

Biochemical properties and crystal structure of ethylmethylglyoxal bis(guanylhydrazone) sulfate--an extremely powerful novel inhibitor of adenosylmethionine decarboxylase.

PubMed

Elo, H; Mutikainen, I; Alhonen-Hongisto, L; Laine, R; Jänne, J; Lumme, P

1986-01-01

Ethylmethylglyoxal bis(guanylhydrazone) (EMGBG) sulfate, an analog of the well-known anti-leukemic drug methylglyoxal bis(guanylhydrazone), was synthesized. It was shown to be an extremely powerful competitive inhibitor of eukaryotic S-adenosylmethionine decarboxylase, with an apparent Ki value 12 nM. Thus, it appears to be the most powerful known inhibitor of the enzyme, being almost an order of magnitude more powerful than the corresponding ethylglyoxal derivative. It neither inhibited the proliferation of mouse L1210 leukemia cells in vitro, nor did it potentiate the growth inhibition produced by alpha-difluoromethyl ornithine. In this respect, its properties are closely related to those of dimethylglyoxal, ethylglyoxal and propylglyoxal bis(guanylhydrazones), while in striking contrast to those of the antiproliferative glyoxal and methylglyoxal analogs. EMGBG also inhibited intestinal diamine oxidase activity (Ki 0.7 microM). EMGBG sulfate was crystallized from water, giving orthorhombic crystals (space group Pbcn). Their crystal and molecular structure was determined by X-ray diffraction methods. The carbon-nitrogen double bonds between the ethylmethylglyoxal part and the aminoguanidine moieties were found to have the same configuration as they are known to have in the salts of glyoxal, methylglyoxal and propylglyoxal bis(guanylhydrazones). The glyoxal bis(guanylhydrazone) chain of the EMGBG cation deviated strongly from planarity, thus differing dramatically from the corresponding chains of the glyoxal, methylglyoxal and propylglyoxal analogs.

Bond-orientational analysis of hard-disk and hard-sphere structures.

PubMed

Senthil Kumar, V; Kumaran, V

2006-05-28

We report the bond-orientational analysis results for the thermodynamic, random, and homogeneously sheared inelastic structures of hard-disks and hard-spheres. The thermodynamic structures show a sharp rise in the order across the freezing transition. The random structures show the absence of crystallization. The homogeneously sheared structures get ordered at a packing fraction higher than the thermodynamic freezing packing fraction, due to the suppression of crystal nucleation. On shear ordering, strings of close-packed hard-disks in two dimensions and close-packed layers of hard-spheres in three dimensions, oriented along the velocity direction, slide past each other. Such a flow creates a considerable amount of fourfold order in two dimensions and body-centered-tetragonal (bct) structure in three dimensions. These transitions are the flow analogs of the martensitic transformations occurring in metals due to the stresses induced by a rapid quench. In hard-disk structures, using the bond-orientational analysis we show the presence of fourfold order. In sheared inelastic hard-sphere structures, even though the global bond-orientational analysis shows that the system is highly ordered, a third-order rotational invariant analysis shows that only about 40% of the spheres have face-centered-cubic (fcc) order, even in the dense and near-elastic limits, clearly indicating the coexistence of multiple crystalline orders. When layers of close-packed spheres slide past each other, in addition to the bct structure, the hexagonal-close-packed (hcp) structure is formed due to the random stacking faults. Using the Honeycutt-Andersen pair analysis and an analysis based on the 14-faceted polyhedra having six quadrilateral and eight hexagonal faces, we show the presence of bct and hcp signatures in shear ordered inelastic hard-spheres. Thus, our analysis shows that the dense sheared inelastic hard-spheres have a mixture of fcc, bct, and hcp structures.

A digitalized silicon microgyroscope based on embedded FPGA.

PubMed

Xia, Dunzhu; Yu, Cheng; Wang, Yuliang

2012-09-27

This paper presents a novel digital miniaturization method for a prototype silicon micro-gyroscope (SMG) with the symmetrical and decoupled structure. The schematic blocks of the overall system consist of high precision analog front-end interface, high-speed 18-bit analog to digital convertor, a high-performance core Field Programmable Gate Array (FPGA) chip and other peripherals such as high-speed serial ports for transmitting data. In drive mode, the closed-loop drive circuit are implemented by automatic gain control (AGC) loop and software phase-locked loop (SPLL) based on the Coordinated Rotation Digital Computer (CORDIC) algorithm. Meanwhile, the sense demodulation module based on varying step least mean square demodulation (LMSD) are addressed in detail. All kinds of algorithms are simulated by Simulink and DSPbuilder tools, which is in good agreement with the theoretical design. The experimental results have fully demonstrated the stability and flexibility of the system.

A Digitalized Silicon Microgyroscope Based on Embedded FPGA

PubMed Central

Xia, Dunzhu; Yu, Cheng; Wang, Yuliang

2012-01-01

This paper presents a novel digital miniaturization method for a prototype silicon micro-gyroscope (SMG) with the symmetrical and decoupled structure. The schematic blocks of the overall system consist of high precision analog front-end interface, high-speed 18-bit analog to digital convertor, a high-performance core Field Programmable Gate Array (FPGA) chip and other peripherals such as high-speed serial ports for transmitting data. In drive mode, the closed-loop drive circuit are implemented by automatic gain control (AGC) loop and software phase-locked loop (SPLL) based on the Coordinated Rotation Digital Computer (CORDIC) algorithm. Meanwhile, the sense demodulation module based on varying step least mean square demodulation (LMSD) are addressed in detail. All kinds of algorithms are simulated by Simulink and DSPbuilder tools, which is in good agreement with the theoretical design. The experimental results have fully demonstrated the stability and flexibility of the system. PMID:23201990

Magnetic suspension system for an Annular Momentum Control Device (AMCD)

NASA Technical Reports Server (NTRS)

1979-01-01

A technique to control a rim suspended in a magnetic field was developed. A complete system was developed, incorporating a support structure, magnetic actuators, a rim drive mechanism, an emergency fail-safe system, servo control system, and control electronics. Open loop and closed loop response of the system at zero speed and at 500 revolutions per minute (r/min) of the rim was obtained and analyzed. The rim was then dynamically balanced and a rim speed of 725 r/min was achieved. An analog simulation of the hardware was developed and tested with the actual control electronics connected to the analog computer. The system under development is stable at rim speeds below 700 r/min. Test results indicate that the rim under test is not rigid. The rim has a warp and a number of binding modes which prevented achievement of higher speeds. Further development efforts are required to achieve higher rim speeds.

Collective behaviours: from biochemical kinetics to electronic circuits.

PubMed

Agliari, Elena; Barra, Adriano; Burioni, Raffaella; Di Biasio, Aldo; Uguzzoni, Guido

2013-12-10

In this work we aim to highlight a close analogy between cooperative behaviors in chemical kinetics and cybernetics; this is realized by using a common language for their description, that is mean-field statistical mechanics. First, we perform a one-to-one mapping between paradigmatic behaviors in chemical kinetics (i.e., non-cooperative, cooperative, ultra-sensitive, anti-cooperative) and in mean-field statistical mechanics (i.e., paramagnetic, high and low temperature ferromagnetic, anti-ferromagnetic). Interestingly, the statistical mechanics approach allows a unified, broad theory for all scenarios and, in particular, Michaelis-Menten, Hill and Adair equations are consistently recovered. This framework is then tested against experimental biological data with an overall excellent agreement. One step forward, we consistently read the whole mapping from a cybernetic perspective, highlighting deep structural analogies between the above-mentioned kinetics and fundamental bricks in electronics (i.e. operational amplifiers, flashes, flip-flops), so to build a clear bridge linking biochemical kinetics and cybernetics.

Teleparallel theories of gravity as analogue of nonlinear electrodynamics

NASA Astrophysics Data System (ADS)

Hohmann, Manuel; Järv, Laur; Krššák, Martin; Pfeifer, Christian

2018-05-01

The teleparallel formulation of gravity theories reveals close structural analogies to electrodynamics, which are more hidden in their usual formulation in terms of the curvature of spacetime. We show how every locally Lorentz invariant teleparallel theory of gravity with second-order field equations can be understood as built from a gravitational field strength and excitation tensor which are related to each other by a constitutive relation, analogous to the premetric construction of theories of electrodynamics. We demonstrate how the previously studied models of f (T ) and f (Tax,Tten,Tvec) gravity as well as teleparallel dark energy can be formulated in this language. The advantage of this approach to gravity is that the field equations for different models all take the same compact form and general results can be obtained. An important new such result we find is a constraint which relates the field equations of the tetrad and the spin connection.

Opioid Crisis: No Easy Fix to Its Social and Economic Determinants

PubMed Central

Beletsky, Leo; Ciccarone, Daniel

2018-01-01

The accepted wisdom about the US overdose crisis singles out prescribing as the causative vector. Although drug supply is a key factor, we posit that the crisis is fundamentally fueled by economic and social upheaval, its etiology closely linked to the role of opioids as a refuge from physical and psychological trauma, concentrated disadvantage, isolation, and hopelessness. Overreliance on opioid medications is emblematic of a health care system that incentivizes quick, simplistic answers to complex physical and mental health needs. In an analogous way, simplistic measures to cut access to opioids offer illusory solutions to this multidimensional societal challenge. We trace the crisis’ trajectory through the intertwined use of opioid analgesics, heroin, and fentanyl analogs, and we urge engaging the structural determinants lens to address this formidable public health emergency. A broad focus on suffering should guide both patient- and community-level interventions. PMID:29267060

Collective behaviours: from biochemical kinetics to electronic circuits

NASA Astrophysics Data System (ADS)

Agliari, Elena; Barra, Adriano; Burioni, Raffaella; di Biasio, Aldo; Uguzzoni, Guido

2013-12-01

In this work we aim to highlight a close analogy between cooperative behaviors in chemical kinetics and cybernetics; this is realized by using a common language for their description, that is mean-field statistical mechanics. First, we perform a one-to-one mapping between paradigmatic behaviors in chemical kinetics (i.e., non-cooperative, cooperative, ultra-sensitive, anti-cooperative) and in mean-field statistical mechanics (i.e., paramagnetic, high and low temperature ferromagnetic, anti-ferromagnetic). Interestingly, the statistical mechanics approach allows a unified, broad theory for all scenarios and, in particular, Michaelis-Menten, Hill and Adair equations are consistently recovered. This framework is then tested against experimental biological data with an overall excellent agreement. One step forward, we consistently read the whole mapping from a cybernetic perspective, highlighting deep structural analogies between the above-mentioned kinetics and fundamental bricks in electronics (i.e. operational amplifiers, flashes, flip-flops), so to build a clear bridge linking biochemical kinetics and cybernetics.

Parametrically coupled fermionic oscillators: Correlation functions and phase-space description

NASA Astrophysics Data System (ADS)

Ghosh, Arnab

2015-01-01

A fermionic analog of a parametric amplifier is used to describe the joint quantum state of the two interacting fermionic modes. Based on a two-mode generalization of the time-dependent density operator, time evolution of the fermionic density operator is determined in terms of its two-mode Wigner and P function. It is shown that the equation of motion of the Wigner function corresponds to a fermionic analog of Liouville's equation. The equilibrium density operator for fermionic fields developed by Cahill and Glauber is thus extended to a dynamical context to show that the mathematical structures of both the correlation functions and the weight factors closely resemble their bosonic counterpart. It has been shown that the fermionic correlation functions are marked by a characteristic upper bound due to Fermi statistics, which can be verified in the matter wave counterpart of photon down-conversion experiments.

Opioid Crisis: No Easy Fix to Its Social and Economic Determinants.

PubMed

Dasgupta, Nabarun; Beletsky, Leo; Ciccarone, Daniel

2018-02-01

The accepted wisdom about the US overdose crisis singles out prescribing as the causative vector. Although drug supply is a key factor, we posit that the crisis is fundamentally fueled by economic and social upheaval, its etiology closely linked to the role of opioids as a refuge from physical and psychological trauma, concentrated disadvantage, isolation, and hopelessness. Overreliance on opioid medications is emblematic of a health care system that incentivizes quick, simplistic answers to complex physical and mental health needs. In an analogous way, simplistic measures to cut access to opioids offer illusory solutions to this multidimensional societal challenge. We trace the crisis' trajectory through the intertwined use of opioid analgesics, heroin, and fentanyl analogs, and we urge engaging the structural determinants lens to address this formidable public health emergency. A broad focus on suffering should guide both patient- and community-level interventions.

Nanoparticles of layered compounds with hollow cage structures (inorganic fullerene-like structures)

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

Tenne, R.; Homyonfer, M.; Feldman, Y.

Using the paradigm of carbon fullerenes, it is shown that nanoparticles of inorganic compounds with a layered structure, like MoS{sub 2}, are unstable against bending and form hollow closed clusters, designated inorganic fullerene-like structures (IF). The analogy can be extended to similar nanostructures, like nanotubes (NT), nested fullerenes, fullerenes with negative curvature (Schwartzites), etc. Various synthetic routes are described to obtain isolated phases of IF. Pentagons and heptagons are expected to play a primodal role in the folding of these nanostructures but no direct evidence for their presence or their detailed structure exits so far. Depending on the structure ofmore » the unit cell of the layered compound, apexes of a different topology, like triangles or rectangles, are believed to be stable elements in IF. Applications of such nanoparticles as solid lubricants in mixtures with lubricating fluids are described.« less

Video Surveillance: All Eyes Turn to IP

ERIC Educational Resources Information Center

Raths, David

2011-01-01

Many university officials recognize the need to upgrade their older analog video surveillance systems. In a 2010 survey by "Campus Safety" magazine, half of university respondents expressed dissatisfaction with the quality and coverage of their current video surveillance systems. Among the limitations of analog closed-circuit television…

GeneBee-net: Internet-based server for analyzing biopolymers

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

Brodsky, L.I.; Ivanov, V.V.; Nikolaev, V.K.

This work describes a network server for searching databanks of biopolymer structures and performing other biocomputing procedures; it is available via direct Internet connection. Basic server procedures are dedicated to homology (similarity) search of sequence and 3D structure of proteins. The homologies found could be used to build multiple alignments, predict protein and RNA secondary structure, and construct phylogenetic trees. In addition to traditional methods of sequence similarity search, the authors propose {open_quotes}non-matrix{close_quotes} (correlational) search. An analogous approach is used to identify regions of similar tertiary structure of proteins. Algorithm concepts and usage examples are presented for new methods. Servicemore » logic is based upon interaction of a client program and server procedures. The client program allows the compilation of queries and the processing of results of an analysis.« less

Experiments in Sound and Structural Vibrations Using an Air-Analog Model Ducted Propulsion System

DTIC Science & Technology

2007-08-01

Department of Aerospace S~and Mechanical Engineering I 20070904056 I EXPERIMENTS IN SOUND AND STRUCTURAL VIBRATIONS USING AN AIR -ANALOG MODEL DUCTED...SOUND AND STRUCTURAL * VIBRATIONS USING AN AIR -ANALOG MODEL DUCTED PROPULSION SYSTEM FINAL TECHNICAL REPORT Prepared by: Scott C. Morris Assistant...Vibration Using Air - 5b. GRANT NUMBER Analog Model Ducted Propulsion Systems N00014-1-0522 5C. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER

How learning one category influences the learning of another: intercategory generalization based on analogy and specific stimulus information.

PubMed

Nahinsky, Irwin D; Lucas, Barbara A; Edgell, Stephen E; Overfelt, Joseph; Loeb, Richard

2004-01-01

We investigated the effect of learning one category structure on the learning of a related category structure. Photograph-name combinations, called identifiers, were associated with values of four demographic attributes. Two problems were related by analogous demographic attributes, common identifiers, or both to examine the impact of common identifier, related general characteristics, and the interaction of the two variables in mediating learning transfer from one category structure to another. Problems sharing the same identifier information prompted greater positive transfer than those not sharing the same identifier information. In contrast, analogous defining characteristics in the two problems did not facilitate transfer. We computed correlations between responses to first-problem stimuli and responses to analogous second-problem stimuli for each participant. The analogous characteristics produced a tendency to respond in the same way to corresponding stimuli in the two problems. The results support an alignment between category structures related by analogous defining characteristics, which is facilitated by specific identifier information shared by two category structures.

Crystal structure of a new variety of lead dodecaborate Pb{sub 6}(Li{sub 0.65}Na{sub 0.19})[B{sub 12}O{sub 24}]I{sub 0.84} {center_dot} 0.168H{sub 2}O and its comparison with beryl and cordierite

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

Belokoneva, E. L., E-mail: elbel@geol.msu.ru; Derkach, I. K.; Dimitrova, O. V.

2013-05-15

Crystals of a new representative of ring-radical dodecaborates Pb{sub 6}(Li{sub 0.65}Na{sub 0.19})[B{sub 12}O{sub 24}]I{sub 0.84} {center_dot} 0.168H{sub 2}O, space group R3bar m , are obtained under hydrothermal conditions. The structure is determined with-out preliminary knowledge of the chemical formula. It is close to that of the Pb{sub 6}[B{sub 12}O{sub 24}] {center_dot} H{sub 2}O dodecaborate studied earlier, but unlike the latter structure it contains admixtures of iodide anion, lithium cation, and water molecule, which incompletely populate positions in channels. The formation of the second variety, which brings to light ion-exchange properties of the crystals, is due to mineralizing ions available inmore » the concen-trated solution in the course of crystallization. The new compound is compared with beryl and cordierite, which have close structures with channels capable of capturing various groups. Structures of synthetic Na and Ag dodecaborates with analogous but distorted ring dodecaborate radicals are discussed.« less

Crystal Structure of a Human IκB Kinase β Asymmetric Dimer

PubMed Central

Liu, Shenping; Misquitta, Yohann R.; Olland, Andrea; Johnson, Mark A.; Kelleher, Kerry S.; Kriz, Ron; Lin, Laura L.; Stahl, Mark; Mosyak, Lidia

2013-01-01

Phosphorylation of inhibitor of nuclear transcription factor κB (IκB) by IκB kinase (IKK) triggers the degradation of IκB and migration of cytoplasmic κB to the nucleus where it promotes the transcription of its target genes. Activation of IKK is achieved by phosphorylation of its main subunit, IKKβ, at the activation loop sites. Here, we report the 2.8 Å resolution crystal structure of human IKKβ (hIKKβ), which is partially phosphorylated and bound to the staurosporine analog K252a. The hIKKβ protomer adopts a trimodular structure that closely resembles that from Xenopus laevis (xIKKβ): an N-terminal kinase domain (KD), a central ubiquitin-like domain (ULD), and a C-terminal scaffold/dimerization domain (SDD). Although hIKKβ and xIKKβ utilize a similar dimerization mode, their overall geometries are distinct. In contrast to the structure resembling closed shears reported previously for xIKKβ, hIKKβ exists as an open asymmetric dimer in which the two KDs are further apart, with one in an active and the other in an inactive conformation. Dimer interactions are limited to the C-terminal six-helix bundle that acts as a hinge between the two subunits. The observed domain movements in the structures of IKKβ may represent trans-phosphorylation steps that accompany IKKβ activation. PMID:23792959

47 CFR 79.101 - Closed caption decoder requirements for analog television receivers.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) BROADCAST RADIO SERVICES CLOSED CAPTIONING AND VIDEO DESCRIPTION OF VIDEO PROGRAMMING § 79.101 Closed... display the captioning for whichever channel the user selects. The TV Mode of operation allows the video... and rows. The characters must be displayed clearly separated from the video over which they are placed...

Insights into the Behavior of Potential Structural Failures Originating from Localized High Stress Regions in Configurations Relevant to Solid Rocket Motor Nozzles

NASA Technical Reports Server (NTRS)

McCutcheon, David Matthew

2017-01-01

During the structural certification effort for the Space Launch System solid rocket booster nozzle, it was identified that no consistent method for addressing local negative margins of safety in non-metallic materials had been developed. Relevant areas included bond-line terminations and geometric features in the composite nozzle liners. In order to gain understanding, analog test specimens were designed that very closely mimic the conditions in the actual full scale hardware. Different locations in the nozzle were represented by different analog specimen designs. This paper describes those tests and corresponding results. Finite element analysis results for the tests are presented. Strain gage correlation of the analysis to the test results is addressed. Furthermore, finite fracture mechanics (a coupled stress and energy failure criterion) is utilized to predict the observed crack pop-in loads for the different configurations. The finite fracture mechanics predictions are found to be within a 10% error relative to the average measured pop-in load for each of four configurations. Initiation locations, arrest behaviors, and resistances to further post-arrest crack propagation are also discussed.

Characterization of opiates, neuroleptics, and synthetic analogs at ORL1 and opioid receptors

PubMed Central

Zaveri, Nurulain; Polgar, Willma E.; Olsen, Cris M.; Kelson, Andrew B.; Grundt, Peter; Lewis, John W.; Toll, Lawrence

2013-01-01

Nociceptin/orphanin FQ (N/OFQ) was recently identified as the endogenous ligand for the opioid-receptor like (ORL1) receptor. Although the ORL1 receptor shows sequence homology with the opioid receptors, the nociceptin/ORL1 ligand–receptor system has very distinct pharmacological actions compared to the opioid receptor system. Recently, several small-molecule ORL1 receptor ligands were reported by pharmaceutical companies. Most of these ligands had close structural similarities with known neuroleptics and opiates. In this study, we screened several available neuroleptics and opiates for their binding affinity and functional activity at ORL1 and the opioid receptors. We also synthesized several analogs of known opiates with modified piperidine N-substituents in order to characterize the ORL1 receptor ligand binding pocket. Substitution with the large, lipophilic cyclooctylmethyl moiety increased ORL1 receptor affinity and decreased μ receptor affinity and efficacy in the fentanyl series of ligands but had a different effect in the oripavine class of opiate ligands. Our results indicate that opiates and neuroleptics may be good starting points for ORL1 receptor ligand design, and the selectivity may be modulated by appropriate structural modifications. PMID:11779034

40 CFR 159.179 - Metabolites, degradates, contaminants, and impurities.

Code of Federal Regulations, 2010 CFR

2010-07-01

... chemical properties of the metabolite or degradate. (B) Data regarding structurally analogous chemicals. (C) Data regarding chemical reactivity of the metabolite or degradate and structurally analogous substances... any person described in § 159.158(a) that the metabolite or degradate, or analogous chemicals, may...

40 CFR 159.179 - Metabolites, degradates, contaminants, and impurities.

Code of Federal Regulations, 2011 CFR

2011-07-01

... chemical properties of the metabolite or degradate. (B) Data regarding structurally analogous chemicals. (C) Data regarding chemical reactivity of the metabolite or degradate and structurally analogous substances... any person described in § 159.158(a) that the metabolite or degradate, or analogous chemicals, may...

Effect of the cellular structure on thermal conductivity of rigid closed-cell foam polymers during long-term aging

NASA Astrophysics Data System (ADS)

Dementyev, A. G.; Dementyev, M. A.; Zinger, P. A.; Metlyakova, I. R.

1999-03-01

The thermal conductivity of rigid closed-cell polyurethane foams during long-term aging has been studied. The similarity between the kinetics of changes in the physical and mechanical characteristics of PU foams on progressive aging is established, which is attributed to the effect of matrix destruction. It is found that rigid foams have cell walls of various strength, whose impact on the kinetics of changes in the physical characteristics of the foams during long-term aging is ascertained. The results of predicting the thermal conductivity of PU foams by the method of temperature-time analogy and establishing the limits of its application are discussed. The research presented is of interest both in determining the foam durability and in replacing freons by alternative, ecologically less harmful blowing agents.

DockoMatic: automated peptide analog creation for high throughput virtual screening.

PubMed

Jacob, Reed B; Bullock, Casey W; Andersen, Tim; McDougal, Owen M

2011-10-01

The purpose of this manuscript is threefold: (1) to describe an update to DockoMatic that allows the user to generate cyclic peptide analog structure files based on protein database (pdb) files, (2) to test the accuracy of the peptide analog structure generation utility, and (3) to evaluate the high throughput capacity of DockoMatic. The DockoMatic graphical user interface interfaces with the software program Treepack to create user defined peptide analogs. To validate this approach, DockoMatic produced cyclic peptide analogs were tested for three-dimensional structure consistency and binding affinity against four experimentally determined peptide structure files available in the Research Collaboratory for Structural Bioinformatics database. The peptides used to evaluate this new functionality were alpha-conotoxins ImI, PnIA, and their published analogs. Peptide analogs were generated by DockoMatic and tested for their ability to bind to X-ray crystal structure models of the acetylcholine binding protein originating from Aplysia californica. The results, consisting of more than 300 simulations, demonstrate that DockoMatic predicts the binding energy of peptide structures to within 3.5 kcal mol(-1), and the orientation of bound ligand compares to within 1.8 Å root mean square deviation for ligand structures as compared to experimental data. Evaluation of high throughput virtual screening capacity demonstrated that Dockomatic can collect, evaluate, and summarize the output of 10,000 AutoDock jobs in less than 2 hours of computational time, while 100,000 jobs requires approximately 15 hours and 1,000,000 jobs is estimated to take up to a week. Copyright © 2011 Wiley Periodicals, Inc.

Counting spanning trees on fractal graphs and their asymptotic complexity

NASA Astrophysics Data System (ADS)

Anema, Jason A.; Tsougkas, Konstantinos

2016-09-01

Using the method of spectral decimation and a modified version of Kirchhoff's matrix-tree theorem, a closed form solution to the number of spanning trees on approximating graphs to a fully symmetric self-similar structure on a finitely ramified fractal is given in theorem 3.4. We show how spectral decimation implies the existence of the asymptotic complexity constant and obtain some bounds for it. Examples calculated include the Sierpiński gasket, a non-post critically finite analog of the Sierpiński gasket, the Diamond fractal, and the hexagasket. For each example, the asymptotic complexity constant is found.

Invisibility cloaking in the diffusive-light limit (presentation video)

NASA Astrophysics Data System (ADS)

Schittny, Robert; Kadic, Muamer; Wegener, Martin

2014-09-01

Albert Einstein's theory of relativity imposes stringent limitations to making macroscopic objects invisible with respect to electromagnetic light waves propagating in vacuum. These limitations are not relevant though for propagation of light in diffusive media like fog or milk because the effective energy speed is significantly lower than in vacuum due to multiple scattering events. Here, by exploiting the close mathematical analogy between the electrostatic or near-field limit of optics on the one hand and light diffusion on the other hand, we design, fabricate, and characterize simple core-shell cloaking structures for diffusive light propagation in cylindrical and spherical geometry.

Resistive RAMs as analog trimming elements

NASA Astrophysics Data System (ADS)

Aziza, H.; Perez, A.; Portal, J. M.

2018-04-01

This work investigates the use of Resistive Random Access Memory (RRAM) as an analog trimming device. The analog storage feature of the RRAM cell is evaluated and the ability of the RRAM to hold several resistance states is exploited to propose analog trim elements. To modulate the memory cell resistance, a series of short programming pulses are applied across the RRAM cell allowing a fine calibration of the RRAM resistance. The RRAM non volatility feature makes the analog device powers up already calibrated for the system in which the analog trimmed structure is embedded. To validate the concept, a test structure consisting of a voltage reference is evaluated.

47 CFR 79.101 - Closed caption decoder requirements for analog television receivers.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) BROADCAST RADIO SERVICES CLOSED CAPTIONING AND VIDEO DESCRIPTION OF VIDEO PROGRAMMING § 79.101 Closed... user selects. The TV Mode of operation allows the video to be viewed in its original form. The Caption... from the video over which they are placed. In addition, the user must have the capability to select a...

Collective behaviours: from biochemical kinetics to electronic circuits

PubMed Central

Agliari, Elena; Barra, Adriano; Burioni, Raffaella; Di Biasio, Aldo; Uguzzoni, Guido

2013-01-01

In this work we aim to highlight a close analogy between cooperative behaviors in chemical kinetics and cybernetics; this is realized by using a common language for their description, that is mean-field statistical mechanics. First, we perform a one-to-one mapping between paradigmatic behaviors in chemical kinetics (i.e., non-cooperative, cooperative, ultra-sensitive, anti-cooperative) and in mean-field statistical mechanics (i.e., paramagnetic, high and low temperature ferromagnetic, anti-ferromagnetic). Interestingly, the statistical mechanics approach allows a unified, broad theory for all scenarios and, in particular, Michaelis-Menten, Hill and Adair equations are consistently recovered. This framework is then tested against experimental biological data with an overall excellent agreement. One step forward, we consistently read the whole mapping from a cybernetic perspective, highlighting deep structural analogies between the above-mentioned kinetics and fundamental bricks in electronics (i.e. operational amplifiers, flashes, flip-flops), so to build a clear bridge linking biochemical kinetics and cybernetics. PMID:24322327

Equalizer design techniques for dispersive cables with application to the SPS wideband kicker

NASA Astrophysics Data System (ADS)

Platt, Jason; Hofle, Wolfgang; Pollock, Kristin; Fox, John

2017-10-01

A wide-band vertical instability feedback control system in development at CERN requires 1-1.5 GHz of bandwidth for the entire processing chain, from the beam pickups through the feedback signal digital processing to the back-end power amplifiers and kicker structures. Dispersive effects in cables, amplifiers, pickup and kicker elements can result in distortions in the time domain signal as it proceeds through the processing system, and deviations from linear phase response reduce the allowable bandwidth for the closed-loop feedback system. We have developed an equalizer analog circuit that compensates for these dispersive effects. Here we present a design technique for the construction of an analog equalizer that incorporates the effect of parasitic circuit elements in the equalizer to increase the fidelity of the implemented equalizer. Finally, we show results from the measurement of an assembled backend equalizer that corrects for dispersive elements in the cables over a bandwidth of 10-1000 MHz.

Vibration isolation/suppression: research experience for undergraduates in mechatronics and smart structures

NASA Astrophysics Data System (ADS)

Fonda, James; Rao, Vittal S.; Sana, Sridhar

2001-08-01

This paper provides an account of a student research project conducted under the sponsoring of the National Science Foundation (NSF) program on Research Experience for Undergraduates (REU) in Mechatronics and Smart Strictures in the summer of 2000. The objective of the research is to design and test a stand-alone controller for a vibration isolation/suppression system. The design specification for the control system is to suppress the vibrations induced by the external disturbances by at least fiver times and hence to achieve vibration isolation. Piezo-electric sensors and actuators are utilized for suppression of unwanted vibrations. Various steps such as modeling of the system, controller design, simulation, closed-loop testing using d- Space rapid prototyping system, and analog control implementation are discussed in the paper. Procedures for data collection, the trade-offs carried out in the design, and analog controller implementation issues are also presented in the paper. The performances of various controllers are compared. The experiences of an undergraduate student are summarized in the conclusion of the paper.

Maxwell's contrived analogy: An early version of the methodology of modeling

NASA Astrophysics Data System (ADS)

Hon, Giora; Goldstein, Bernard R.

2012-11-01

The term "analogy" stands for a variety of methodological practices all related in one way or another to the idea of proportionality. We claim that in his first substantial contribution to electromagnetism James Clerk Maxwell developed a methodology of analogy which was completely new at the time or, to borrow John North's expression, Maxwell's methodology was a "newly contrived analogue". In his initial response to Michael Faraday's experimental researches in electromagnetism, Maxwell did not seek an analogy with some physical system in a domain different from electromagnetism as advocated by William Thomson; rather, he constructed an entirely artificial one to suit his needs. Following North, we claim that the modification which Maxwell introduced to the methodology of analogy has not been properly appreciated. In view of our examination of the evidence, we argue that Maxwell gave a new meaning to analogy; in fact, it comes close to modeling in current usage.

Reynolds analogy for the Rayleigh problem at various flow modes.

PubMed

Abramov, A A; Butkovskii, A V

2016-07-01

The Reynolds analogy and the extended Reynolds analogy for the Rayleigh problem are considered. For a viscous incompressible fluid we derive the Reynolds analogy as a function of the Prandtl number and the Eckert number. We show that for any positive Eckert number, the Reynolds analogy as a function of the Prandtl number has a maximum. For a monatomic gas in the transitional flow regime, using the direct simulation Monte Carlo method, we investigate the extended Reynolds analogy, i.e., the relation between the shear stress and the energy flux transferred to the boundary surface, at different velocities and temperatures. We find that the extended Reynolds analogy for a rarefied monatomic gas flow with the temperature of the undisturbed gas equal to the surface temperature depends weakly on time and is close to 0.5. We show that at any fixed dimensionless time the extended Reynolds analogy depends on the plate velocity and temperature and undisturbed gas temperature mainly via the Eckert number. For Eckert numbers of the order of unity or less we generalize an extended Reynolds analogy. The generalized Reynolds analogy depends mainly only on dimensionless time for all considered Eckert numbers of the order of unity or less.

Analytical modeling of soliton interactions in a nonlocal nonlinear medium analogous to gravitational force

NASA Astrophysics Data System (ADS)

Zeng, Shihao; Chen, Manna; Zhang, Ting; Hu, Wei; Guo, Qi; Lu, Daquan

2018-01-01

We illuminate an analytical model of soliton interactions in lead glass by analogizing to a gravitational force system. The orbits of spiraling solitons under a long-range interaction are given explicitly and demonstrated to follow Newton's second law of motion and the Binet equation by numerical simulations. The condition for circular orbits is obtained and the oscillating orbits are proved not to be closed. We prove the analogy between the nonlocal nonlinear optical system and gravitational system and specify the quantitative relation of the quantity between the two models.

Amplification of Reynolds number dependent processes by wave distortion. [acoustic instability of liquid propellant rocket engines

NASA Technical Reports Server (NTRS)

Ventrice, M. B.; Fang, J. C.; Purdy, K. R.

1975-01-01

A system using a hot-wire transducer as an analog of a liquid droplet of propellant was employed to investigate the ingredients of the acoustic instability of liquid-propellant rocket engines. It was assumed that the combustion process was vaporization-limited and that the combustion chamber was acoustically similar to a closed-closed right-circular cylinder. Before studying the hot-wire closed-loop system (the analog system), a microphone closed-loop system, which used the response of a microphone as the source of a linear feedback exciting signal, was investigated to establish the characteristics of self-sustenance of acoustic fields. Self-sustained acoustic fields were found to occur only at resonant frequencies of the chamber. In the hot-wire closed-loop system, the response of hot-wire anemometer was used as the source of the feedback exciting signal. The self-sustained acoustic fields which developed in the system were always found to be harmonically distorted and to have as their fundamental frquency a resonant frequency for which there also existed a second resonant frequency which was approximately twice the fundamental frequency.

A one-dimensional diffusion analogy model for estimation of tide heights in selected tidal marshes in Connecticut

USGS Publications Warehouse

Bjerklie, David M.; O’Brien, Kevin; Rozsa, Ron

2013-01-01

A one-dimensional diffusion analogy model for estimating tide heights in coastal marshes was developed and calibrated by using data from previous tidal-marsh studies. The method is simpler to use than other one- and two-dimensional hydrodynamic models because it does not require marsh depth and tidal prism information; however, the one-dimensional diffusion analogy model cannot be used to estimate tide heights, flow velocities, and tide arrival times for tide conditions other than the highest tide for which it is calibrated. Limited validation of the method indicates that it has an accuracy within 0.3 feet. The method can be applied with limited calibration information that is based entirely on remote sensing or geographic information system data layers. The method can be used to estimate high-tide heights in tidal wetlands drained by tide gates where tide levels cannot be observed directly by opening the gates without risk of flooding properties and structures. A geographic information system application of the method is demonstrated for Sybil Creek marsh in Branford, Connecticut. The tidal flux into this marsh is controlled by two tide gates that prevent full tidal inundation of the marsh. The method application shows reasonable tide heights for the gates-closed condition (the normal condition) and the one-gate-open condition on the basis of comparison with observed heights. The condition with all tide gates open (two gates) was simulated with the model; results indicate where several structures would be flooded if the gates were removed as part of restoration efforts or if the tide gates were to fail.

Computational study of solution behavior of magainin 2 monomers.

PubMed

Petkov, P; Marinova, R; Kochev, V; Ilieva, N; Lilkova, E; Litov, L

2018-03-27

Antimicrobial peptides (AMPs) play crucial role as mediators of the primary host defense against microbial invasion. They are considered a promising alternative to antibiotics for multidrug resistant bacterial strains. For complete understanding of the antimicrobial defense mechanism, a detailed knowledge of the dynamics of peptide-membrane interactions, including atomistic studies on AMPs geometry and both peptide and membrane structural changes during the whole process is a prerequisite. We aim at clarifying the conformation dynamics of small linear AMPs in solution as a first step of in silico protocol for establishing a correspondence between certain amino-acid sequence motifs, secondary-structure elements, conformational dynamics in solution and the intensity and mode of interaction with the bacterial membrane. To this end, we use molecular dynamics simulations augmented by well-tempered metadynamics to study the free-energy landscape of two AMPs with close primary structure and different antibacterial activity - the native magainin 2 (MG2) and an analog (MG2m, with substitutions F5Y and F16W) in aqueous solution. We observe that upon solvation, the initial α-helical structures change differently. The native form remains structured, with three shorter α-helical motifs, connected by random coils, while the synthetic analog tends predominantly to a disordered conformation. Our results indicate the importance of the side-chains at positions 5 and 16 for maintaining the solvated peptide conformation. They also provide a modeling background for recent experimental observations, relating the higher α-helical content in solution (peptide pre-folding) in the case of small linear AMPs to a lower antibacterial activity.

Nonequilibrium molecular dynamics study of ring polymer melts under shear and elongation flows: A comparison with their linear analogs

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

Yoon, Jeongha; Kim, Jinseong; Baig, Chunggi, E-mail: cbaig@unist.ac.kr

We present detailed results for the structural and rheological properties of unknotted and unconcatenated ring polyethylene (PE) melts under shear and elongation flows via direct atomistic nonequilibrium molecular dynamics simulations. Short (C{sub 78}H{sub 156}) and long (C{sub 400}H{sub 800}) ring PE melts were subjected to planar Couette flow (PCF) and planar elongational flow (PEF) across a wide range of strain rates from linear to highly nonlinear flow regimes. The results are analyzed in detail through a direct comparison with those of the corresponding linear polymers. We found that, in comparison to their linear analogs, ring melts possess rather compact chainmore » structures at or near the equilibrium state and exhibit a considerably lesser degree of structural deformation with respect to the applied flow strength under both PCF and PEF. The large structural resistance of ring polymers against an external flow field is attributed to the intrinsic closed-loop configuration of the ring and the topological constraint of nonconcatenation between ring chains in the melt. As a result, there appears to be a substantial discrepancy between ring and linear systems in terms of their structural and rheological properties such as chain orientation, the distribution of chain dimensions, viscosity, flow birefringence, hydrostatic pressure, the pair correlation function, and potential interaction energies. The findings and conclusions drawn in this work would be a useful guide in future exploration of the characteristic dynamical and relaxation mechanisms of ring polymers in bulk or confined systems under flowing conditions.« less

Development of structural schemes of parallel structure manipulators using screw calculus

NASA Astrophysics Data System (ADS)

Rashoyan, G. V.; Shalyukhin, K. A.; Gaponenko, EV

2018-03-01

The paper considers the approach to the structural analysis and synthesis of parallel structure robots based on the mathematical apparatus of groups of screws and on a concept of reciprocity of screws. The results are depicted of synthesis of parallel structure robots with different numbers of degrees of freedom, corresponding to the different groups of screws. Power screws are applied with this aim, based on the principle of static-kinematic analogy; the power screws are similar to the orts of axes of not driven kinematic pairs of a corresponding connecting chain. Accordingly, kinematic screws of the outlet chain of a robot are simultaneously determined which are reciprocal to power screws of kinematic sub-chains. Solution of certain synthesis problems is illustrated with practical applications. Closed groups of screws can have eight types. The three-membered groups of screws are of greatest significance, as well as four-membered screw groups [1] and six-membered screw groups. Three-membered screw groups correspond to progressively guiding mechanisms, to spherical mechanisms, and to planar mechanisms. The four-membered group corresponds to the motion of the SCARA robot. The six-membered group includes all possible motions. From the works of A.P. Kotelnikov, F.M. Dimentberg, it is known that closed fifth-order screw groups do not exist. The article presents examples of the mechanisms corresponding to the given groups.

Electronic shell structure in Ga12 icosahedra and the relation to the bulk forms of gallium.

PubMed

Schebarchov, D; Gaston, N

2012-07-28

The electronic structure of known cluster compounds with a cage-like icosahedral Ga(12) centre is studied by first-principles theoretical methods, based on density functional theory. We consider these hollow metalloid nanostructures in the context of the polymorphism of the bulk, and identify a close relation to the α phase of gallium. This previously unrecognised connection is established using the electron localisation function, which reveals the ubiquitous presence of radially-pointing covalent bonds around the Ga(12) centre--analogous to the covalent bonds between buckled deltahedral planes in α-Ga. Furthermore, we find prominent superatom shell structure in these clusters, despite their hollow icosahedral motif and the presence of covalent bonds. The exact nature of the electronic shell structure is contrasted with simple electron shell models based on jellium, and we demonstrate how the interplay between gallium dimerisation, ligand- and crystal-field effects can alter the splitting of the partially filled 1F shell. Finally, in the unique compound where the Ga(12) centre is bridged by six phosphorus ligands, the electronic structure most closely resembles that of δ-Ga and there are no well-defined superatom orbitals. The results of this comprehensive study bring new insights into the nature of chemical bonding in metalloid gallium compounds and the relation to bulk gallium metal, and they may also guide the development of more general models for ligand-protected clusters.

Synthesis, molecular structure and physicochemical properties of bis(3‧-azido-3‧-deoxythymidin-5‧-yl) carbonate

NASA Astrophysics Data System (ADS)

Raviolo, Mónica A.; Williams, Patricia A. M.; Etcheverry, Susana B.; Piro, Oscar E.; Castellano, Eduardo E.; Gualdesi, Maria S.; Briñón, Margarita C.

2010-04-01

3'-Azido-3'-deoxythymidine (zidovudine, AZT), a synthetic analog of natural nucleoside thymidine, has been used extensively in AIDS treatments. We report here the synthesis, X-ray crystal and molecular structure, NMR, IR and Raman spectra and the thermal behavior of a novel carbonate of AZT [(AZT-O) 2C dbnd O], prepared by the reaction of zidovudine with carbonyldiimidazole. The carbonate compound, C 21H 24N 10O 9, crystallizes in the tetragonal space group P4 12 12 with a = b = 15.284(1), c = 21.695(1) Å, and Z = 8 molecules per unit cell. It consists of two AZT moieties of closely related conformations which are bridged by a carbonyl group to adopt a folded Z-like shape.

Bending at the base of a dragged-out viscous thread

NASA Astrophysics Data System (ADS)

Blount, Maurice; Lister, John

2007-11-01

We consider steady flow of a slender viscous thread falling from a nozzle onto a moving horizontal belt. We analyse the asymptotic limit of a very slender thread, and show that it has a boundary-layer structure in which bending stresses only become important near the belt, where they support a vertical stress and allow the velocity and rolling conditions to be satisfied. The outer solution is analogous to a viscous catenary, with velocity fixed at the belt and at the nozzle. There are three asymptotic regimes, with distinct structures, corresponding to the cases that the belt speed is larger than, smaller than, or close to the velocity of a freely falling thread. The implications for the onset and amplitude of meanders in the `fluid-mechanical sewing machine' are explored.

Analogical Reasoning: What Develops? A Review of Research and Theory.

ERIC Educational Resources Information Center

Goswami, Usha

1991-01-01

Children's analogical reasoning has traditionally been measured by classical four-term analogy tasks or problem-solving tasks. Current theories of analogical development and the evidence on which they are based are reviewed. It is concluded that structural views of analogical development are wrong, and knowledge-based accounts of what develops are…

Tuning of active vibration controllers for ACTEX by genetic algorithm

NASA Astrophysics Data System (ADS)

Kwak, Moon K.; Denoyer, Keith K.

1999-06-01

This paper is concerned with the optimal tuning of digitally programmable analog controllers on the ACTEX-1 smart structures flight experiment. The programmable controllers for each channel include a third order Strain Rate Feedback (SRF) controller, a fifth order SRF controller, a second order Positive Position Feedback (PPF) controller, and a fourth order PPF controller. Optimal manual tuning of several control parameters can be a difficult task even though the closed-loop control characteristics of each controller are well known. Hence, the automatic tuning of individual control parameters using Genetic Algorithms is proposed in this paper. The optimal control parameters of each control law are obtained by imposing a constraint on the closed-loop frequency response functions using the ACTEX mathematical model. The tuned control parameters are then uploaded to the ACTEX electronic control electronics and experiments on the active vibration control are carried out in space. The experimental results on ACTEX will be presented.

NMR Structural Studies of Antimicrobial Peptides: LPcin Analogs.

PubMed

Jeong, Ji-Ho; Kim, Ji-Sun; Choi, Sung-Sub; Kim, Yongae

2016-01-19

Lactophoricin (LPcin), a component of proteose peptone (113-135) isolated from bovine milk, is a cationic amphipathic antimicrobial peptide consisting of 23 amino acids. We designed a series of N- or C-terminal truncated variants, mutated analogs, and truncated mutated analogs using peptide-engineering techniques. Then, we selected three LPcin analogs of LPcin-C8 (LPcin-YK1), LPcin-T2WT6W (LPcin-YK2), and LPcin-T2WT6W-C8 (LPcin-YK3), which may have better antimicrobial activities than LPcin, and successfully expressed them in E. coli with high yield. We elucidated the 3D structures and topologies of the three LPcin analogs in membrane environments by conducting NMR structural studies. We investigated the purity of the LPcin analogs and the α-helical secondary structures by performing (1)H-(15)N 2D HSQC and HMQC-NOESY liquid-state NMR spectroscopy using protein-containing micelle samples. We measured the 3D structures and tilt angles in membranes by conducting (15)N 1D and 2D (1)H-(15)N SAMMY type solid-state NMR spectroscopy with an 800 MHz in-house-built (1)H-(15)N double-resonance solid-state NMR probe with a strip-shield coil, using protein-containing large bicelle samples aligned and confirmed by molecular-dynamics simulations. The three LPcin analogs were found to be curved α-helical structures, with tilt angles of 55-75° for normal membrane bilayers, and their enhanced activities may be correlated with these topologies. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Concept of internal structural controls for evaluation of inactive synthetic peptide analogs: synthesis of [Orn13,14]apamin and its guanidination to an apamin derivative with full neurotoxic activity.

PubMed Central

Cosand, W L; Merrifield, R B

1977-01-01

The importance of arginine residues 13 and 14 in the bee venom neurotoxin, apamin, was teste by the synthesis of replacement analogs. [13,14-di-Ndelta-trifluoroacetylornithine]Apamin was synthesized by the solid phase method on a benzhydrylamine resin. It was deprotected to [13,14-diornithine]apamin, which was then guanidinated to produce the 4-homoarginine-13,14-diarginine analog, [Har4]apamin. Neither the trifluoroacetylornithine analog nor the ornithine analog produced any detectable symptoms when injected intravenously into mice. However, the synthetic [Har4]apamin exhibited the full neurotoxic activity of native apamin and of [Har4]apamin derived from the natural toxin. This provided an internal structural control for the correctness of the primary structure of the inactive synthetic analogs and strengthened the conclusion that one, or both, of the arginine residues plays an important role in the action of apamin. Images PMID:268626

A microprocessor-based real-time simulator of a turbofan engine

NASA Technical Reports Server (NTRS)

Litt, Jonathan S.; Delaat, John C.; Merrill, Walter C.

1988-01-01

A real-time digital simulator of a Pratt and Whitney F 100 engine is discussed. This self-contained unit can operate in an open-loop stand-alone mode or as part of a closed-loop control system. It can also be used in control system design and development. It accepts five analog control inputs and its sixteen outputs are returned as analog signals.

Hawking radiation in sonic black holes.

PubMed

Giovanazzi, S

2005-02-18

I present a microscopic description of Hawking radiation in sonic black holes. A one-dimensional Fermi-degenerate liquid squeezed by a smooth barrier forms a transonic flow, a sonic analog of a black hole. The quantum treatment of the noninteracting case establishes a close relationship between sonic Hawking radiation and quantum tunneling through the barrier. Quasiparticle excitations appear at the barrier and are then radiated with a thermal distribution in exact agreement with Hawking's formula. The signature of the radiation can be found in the dynamic structure factor, which can be measured in a scattering experiment. The possibility for experimental verification of this new transport phenomenon for ultracold atoms is discussed.

Fermi paradox and alternative strategies for SETI programs - The anthropic principle and the search for close solar analogs

NASA Astrophysics Data System (ADS)

Fracassini, Massimo; Pasinetti Fracassini, Laura E.; Pasinetti, Antonio L.

1988-07-01

The Anthropic Principle, a new trend of modern cosmology, claims that the origin of life and the development of intelligent beings on the Earth is the result of highly selective biological processes, strictly tuned in the fundamental physical characteristics of the Universe. This principle could account for the failure of some programs of search for extraterrestrial intelligences (SETI) and suggests the search for strict solar analogs as a primary target for SETI strategies. In this connection, the authors have selected 22 solar analogs and discussed their choice.

Insulin fibrillation and protein design: topological resistance of single-chain analogs to thermal degradation with application to a pump reservoir.

PubMed

Phillips, Nelson B; Whittaker, Jonathan; Ismail-Beigi, Faramarz; Weiss, Michael A

2012-03-01

Insulin is susceptible to thermal fibrillation, a misfolding process that leads to nonnative cross-β assembly analogous to pathological amyloid deposition. Pharmaceutical formulations are ordinarily protected from such degradation by sequestration of the susceptible monomer within native protein assemblies. With respect to the safety and efficacy of insulin pumps, however, this strategy imposes an intrinsic trade-off between pharmacokinetic goals (rapid absorption and clearance) and the requisite physical properties of a formulation (prolonged shelf life and stability within the reservoir). Available rapid-acting formulations are suboptimal in both respects; susceptibility to fibrillation is exacerbated even as absorption is delayed relative to the ideal specifications of a closed-loop system. To circumvent this molecular trade-off, we exploited structural models of insulin fibrils and amyloidogenic intermediates to define an alternative protective mechanism. Single-chain insulin (SCI) analogs were shown to be refractory to thermal fibrillation with maintenance of biological activity for more than 3 months under conditions that promote the rapid fibrillation and inactivation of insulin. The essential idea exploits an intrinsic incompatibility between SCI topology and the geometry of cross-β assembly. A peptide tether was thus interposed between the A- and B-chains whose length was (a) sufficiently long to provide the "play" needed for induced fit of the hormone on receptor binding and yet (b) sufficiently short to impose a topological barrier to fibrillation. Our findings suggest that ultrastable monomeric SCI analogs may be formulated without protective self-assembly and so permit simultaneous optimization of pharmacokinetics and reservoir life. © 2012 Diabetes Technology Society.

Graphene-on-semiconductor substrates for analog electronics

DOEpatents

Lagally, Max G.; Cavallo, Francesca; Rojas-Delgado, Richard

2016-04-26

Electrically conductive material structures, analog electronic devices incorporating the structures and methods for making the structures are provided. The structures include a layer of graphene on a semiconductor substrate. The graphene layer and the substrate are separated by an interfacial region that promotes transfer of charge carriers from the surface of the substrate to the graphene.

Human presence impacts fungal diversity of inflated lunar/Mars analog habitat.

PubMed

Blachowicz, A; Mayer, T; Bashir, M; Pieber, T R; De León, P; Venkateswaran, K

2017-07-11

An inflatable lunar/Mars analog habitat (ILMAH), simulated closed system isolated by HEPA filtration, mimics International Space Station (ISS) conditions and future human habitation on other planets except for the exchange of air between outdoor and indoor environments. The ILMAH was primarily commissioned to measure physiological, psychological, and immunological characteristics of human inhabiting in isolation, but it was also available for other studies such as examining its microbiological aspects. Characterizing and understanding possible changes and succession of fungal species is of high importance since fungi are not only hazardous to inhabitants but also deteriorate the habitats. Observing the mycobiome changes in the presence of human will enable developing appropriate countermeasures with reference to crew health in a future closed habitat. Succession of fungi was characterized utilizing both traditional and state-of-the-art molecular techniques during the 30-day human occupation of the ILMAH. Surface samples were collected at various time points and locations to observe both the total and viable fungal populations of common environmental and opportunistic pathogenic species. To estimate the cultivable fungal population, potato dextrose agar plate counts method was utilized. The internal transcribed spacer region-based iTag Illumina sequencing was employed to measure the community structure and fluctuation of the mycobiome over time in various locations. Treatment of samples with propidium monoazide (PMA; a DNA intercalating dye for selective detection of viable microbial populations) had a significant effect on the microbial diversity compared to non-PMA-treated samples. Statistical analysis confirmed that viable fungal community structure changed (increase in diversity and decrease in fungal burden) over the occupation time. Samples collected at day 20 showed distinct fungal profiles from samples collected at any other time point (before or after). Viable fungal families like Davidiellaceae, Teratosphaeriaceae, Pleosporales, and Pleosporaceae were shown to increase during the occupation time. The results of this study revealed that the overall fungal diversity in the closed habitat changed during human presence; therefore, it is crucial to properly maintain a closed habitat to preserve it from deteriorating and keep it safe for its inhabitants. Differences in community profiles were observed when statistically treated, especially of the mycobiome of samples collected at day 20. On a genus level Epiccocum, Alternaria, Pleosporales, Davidiella, and Cryptococcus showed increased abundance over the occupation time.

Electrophobic interaction induced impurity clustering in metals

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

Zhou, Hong-Bo; Wang, Jin-Long; Jiang, W.

2016-10-01

We introduce the concept of electrophobic interaction, analogous to hydrophobic interaction, for describing the behavior of impurity atoms in a metal, a 'solvent of electrons'. We demonstrate that there exists a form of electrophobic interaction between impurities with closed electron shell structure, which governs their dissolution behavior in a metal. Using He, Be and Ar as examples, we predict by first-principles calculations that the electrophobic interaction drives He, Be or Ar to form a close-packed cluster with a clustering energy that follows a universal power-law scaling with the number of atoms (N) dissolved in a free electron gas, as wellmore » as W or Al lattice, as Ec is proportional to (N2/3-N). This new concept unifies the explanation for a series of experimental observations of close-packed inert-gas bubble formation in metals, and significantly advances our fundamental understanding and capacity to predict the solute behavior of impurities in metals, a useful contribution to be considered in future material design of metals for nuclear, metallurgical, and energy applications.« less

Inviting Argument by Analogy: Analogical-Mapping-Based Comparison Activities as a Scaffold for Small-Group Argumentation

ERIC Educational Resources Information Center

Emig, Brandon R.; McDonald, Scott; Zembal-Saul, Carla; Strauss, Susan G.

2014-01-01

This study invited small groups to make several arguments by analogy about simple machines. Groups were first provided training on analogical (structure) mapping and were then invited to use analogical mapping as a scaffold to make arguments. In making these arguments, groups were asked to consider three simple machines: two machines that they had…

The interplay of conflict and analogy in multidisciplinary teams.

PubMed

Paletz, Susannah B F; Schunn, Christian D; Kim, Kevin H

2013-01-01

Creative teamwork in multidisciplinary teams is a topic of interest to cognitive psychologists on the one hand, and to both social and organizational psychologists on the other. However, the interconnections between cognitive and social layers have been rarely explored. Drawing on mental models and dissonance theories, the current study takes a central variable studied by cognitive psychologists-analogy-and examines its relationship to a central variable examined by social psychologists-conflict. In an observational, field study, over 11h of audio-video data from conversations of the Mars Exploration Rover scientists were coded for different types of analogy and micro-conflicts that reveal the character of underlying psychological mechanisms. Two different types of time-lagged logistic models applied to these data revealed asymmetric patterns of associations between analogy and conflict. Within-domain analogies, but not within-discipline or outside-discipline analogies, preceded science and work process conflicts, suggesting that in multidisciplinary teams, representational gaps in very close domains will be more likely to spark conflict. But analogies also occurred in reaction to conflict: Process and negative conflicts, but not task conflicts, preceded within-discipline analogies, but not to within-domain or outside-discipline analogies. This study demonstrates ways in which cognition can be bidirectionally tied to social processes and discourse. Copyright © 2012 Elsevier B.V. All rights reserved.

Validated linear dynamic model of electrically-shunted magnetostrictive transducers with application to structural vibration control

NASA Astrophysics Data System (ADS)

Scheidler, Justin J.; Asnani, Vivake M.

2017-03-01

This paper presents a linear model of the fully-coupled electromechanical behavior of a generally-shunted magnetostrictive transducer. The impedance and admittance representations of the model are reported. The model is used to derive the effect of the shunt’s electrical impedance on the storage modulus and loss factor of the transducer without neglecting the inherent resistance of the transducer’s coil. The expressions are normalized and then shown to also represent generally-shunted piezoelectric materials that have a finite leakage resistance. The generalized expressions are simplified for three shunts: resistive, series resistive-capacitive, and inductive, which are considered for shunt damping, resonant shunt damping, and stiffness tuning, respectively. For each shunt, the storage modulus and loss factor are plotted for a wide range of the normalized parameters. Then, important trends and their impact on different applications are discussed. An experimental validation of the transducer model is presented for the case of resistive and resonant shunts. The model closely predicts the measured response for a variety of operating conditions. This paper also introduces a model for the dynamic compliance of a vibrating structure that is coupled to a magnetostrictive transducer for shunt damping and resonant shunt damping applications. This compliance is normalized and then shown to be analogous to that of a structure that is coupled to a piezoelectric material. The derived analogies allow for the observations and equations in the existing literature on structural vibration control using shunted piezoelectric materials to be directly applied to the case of shunted magnetostrictive transducers.

Semirelativity in semiconductors: a review.

PubMed

Zawadzki, Wlodek

2017-09-20

An analogy between behavior of electrons in narrow-gap semiconductors (NGS) and relativistic electrons in vacuum is reviewed. Energy band structures [Formula: see text] are considered for various NGS materials and their correspondence to the energy-momentum relation in special relativity is emphasized. It is indicated that special relativity for vacuum is analogous to a two-band [Formula: see text] description for NGS. The maximum electron velocity in NGS is [Formula: see text], which corresponds to the light velocity in vacuum. An effective mass of charge carriers in semiconductors is introduced, relating their velocity to quasimomentum and it is shown that this mass depends on electron energy (or velocity) in a way similar to the mass of free relativistic electrons. In [Formula: see text] alloys one can reach vanishing energy gap at which electrons and light holes become three-dimensional massless Dirac fermions. A wavelength [Formula: see text] is defined for NGS, in analogy to the Compton wavelength in relativistic quantum mechanics. It is estimated that [Formula: see text] is on the order of tens of Angstroms in typical semiconducting materials which is experimentally confirmed in tunneling experiments on energy dispersion in the forbidden gap. Statistical properties of the electron gas in NGS are calculated and their similarity is demonstrated to those of the Juttner gas of relativistic particles. Interband electron tunneling in NGS is described and shown to be in close analogy to the predicted but unobserved tunneling between negative and positive energies resulting from the Dirac equation for free electrons. It is demonstrated that the relativistic analogy holds for orbital and spin properties of electrons in the presence of an external magnetic field. In particular, it is shown that the spin magnetic moment of both NGS electrons and relativistic electrons approaches zero with increasing energy. This conclusion is confirmed experimentally for NGS. Electrons in crossed electric and magnetic fields are described theoretically and experimentally. It is only the two-band description for NGS, equivalent to the Dirac or Klein-Gordon equations for free particles, that gives a correct account of experimental results in this situation. A transverse Doppler shift in the cyclotron resonance observed in crossed fields in InSb indicates that there exists a time dilatation between an oscillating electron and an observer. The phenomenon of Zitterbewegung (ZB, trembling motion) for electrons in NGS is considered theoretically, following the original proposition of Schrödinger for free relativistic electrons in vacuum. The two descriptions are in close analogy, but the frequency of ZB for electrons in NGS is orders of magnitude lower and its amplitude orders of magnitude higher making possible experimental observations in semiconductors considerably more favorable. Finally, graphene and carbon nanotubes, as well as topological insulators are considered in the framework of relativistic analogy. These systems, with their linear energy-quasimomentum dispersions, illustrate the extreme semirelativistic regime. Experimental results for the energy dispersions and the Landau quantizations in the presence of a magnetic field are quoted and their analogy to the behavior of free relativistic electrons is discussed. Approximations and restrictions of the relativistic analogy are emphasized. On the other hand, it is indicated that in various situations it is considerably easier to observe semirelativistic effects in semiconductors than the relativistic effects in vacuum.

Semirelativity in semiconductors: a review

NASA Astrophysics Data System (ADS)

Zawadzki, Wlodek

2017-09-01

An analogy between behavior of electrons in narrow-gap semiconductors (NGS) and relativistic electrons in vacuum is reviewed. Energy band structures \\varepsilon ≤ft(\\mathbf{k}\\right) are considered for various NGS materials and their correspondence to the energy-momentum relation in special relativity is emphasized. It is indicated that special relativity for vacuum is analogous to a two-band \\mathbf{k}\\centerdot \\mathbf{p} description for NGS. The maximum electron velocity in NGS is u≃ 1× {{10}8}~\\text{cm}~{{\\text{s}}-1} , which corresponds to the light velocity in vacuum. An effective mass of charge carriers in semiconductors is introduced, relating their velocity to quasimomentum and it is shown that this mass depends on electron energy (or velocity) in a way similar to the mass of free relativistic electrons. In \\text{H}{{\\text{g}}1-x}\\text{C}{{\\text{d}}x}\\text{Te} alloys one can reach vanishing energy gap at which electrons and light holes become three-dimensional massless Dirac fermions. A wavelength {λz} is defined for NGS, in analogy to the Compton wavelength in relativistic quantum mechanics. It is estimated that {λz} is on the order of tens of Angstroms in typical semiconducting materials which is experimentally confirmed in tunneling experiments on energy dispersion in the forbidden gap. Statistical properties of the electron gas in NGS are calculated and their similarity is demonstrated to those of the Juttner gas of relativistic particles. Interband electron tunneling in NGS is described and shown to be in close analogy to the predicted but unobserved tunneling between negative and positive energies resulting from the Dirac equation for free electrons. It is demonstrated that the relativistic analogy holds for orbital and spin properties of electrons in the presence of an external magnetic field. In particular, it is shown that the spin magnetic moment of both NGS electrons and relativistic electrons approaches zero with increasing energy. This conclusion is confirmed experimentally for NGS. Electrons in crossed electric and magnetic fields are described theoretically and experimentally. It is only the two-band description for NGS, equivalent to the Dirac or Klein-Gordon equations for free particles, that gives a correct account of experimental results in this situation. A transverse Doppler shift in the cyclotron resonance observed in crossed fields in InSb indicates that there exists a time dilatation between an oscillating electron and an observer. The phenomenon of Zitterbewegung (ZB, trembling motion) for electrons in NGS is considered theoretically, following the original proposition of Schrödinger for free relativistic electrons in vacuum. The two descriptions are in close analogy, but the frequency of ZB for electrons in NGS is orders of magnitude lower and its amplitude orders of magnitude higher making possible experimental observations in semiconductors considerably more favorable. Finally, graphene and carbon nanotubes, as well as topological insulators are considered in the framework of relativistic analogy. These systems, with their linear energy-quasimomentum dispersions, illustrate the extreme semirelativistic regime. Experimental results for the energy dispersions and the Landau quantizations in the presence of a magnetic field are quoted and their analogy to the behavior of free relativistic electrons is discussed. Approximations and restrictions of the relativistic analogy are emphasized. On the other hand, it is indicated that in various situations it is considerably easier to observe semirelativistic effects in semiconductors than the relativistic effects in vacuum.

Conformational and chemical selection by a trans-acting editing domain

PubMed Central

Danhart, Eric M.; Bakhtina, Marina; Cantara, William A.; Kuzmishin, Alexandra B.; Ma, Xiao; Sanford, Brianne L.; Vargas-Rodriguez, Oscar; Košutić, Marija; Goto, Yuki; Suga, Hiroaki; Nakanishi, Kotaro; Micura, Ronald; Musier-Forsyth, Karin

2017-01-01

Molecular sieves ensure proper pairing of tRNAs and amino acids during aminoacyl-tRNA biosynthesis, thereby avoiding detrimental effects of mistranslation on cell growth and viability. Mischarging errors are often corrected through the activity of specialized editing domains present in some aminoacyl-tRNA synthetases or via single-domain trans-editing proteins. ProXp-ala is a ubiquitous trans-editing enzyme that edits Ala-tRNAPro, the product of Ala mischarging by prolyl-tRNA synthetase, although the structural basis for discrimination between correctly charged Pro-tRNAPro and mischarged Ala-tRNAAla is unclear. Deacylation assays using substrate analogs reveal that size discrimination is only one component of selectivity. We used NMR spectroscopy and sequence conservation to guide extensive site-directed mutagenesis of Caulobacter crescentus ProXp-ala, along with binding and deacylation assays to map specificity determinants. Chemical shift perturbations induced by an uncharged tRNAPro acceptor stem mimic, microhelixPro, or a nonhydrolyzable mischarged Ala-microhelixPro substrate analog identified residues important for binding and deacylation. Backbone 15N NMR relaxation experiments revealed dynamics for a helix flanking the substrate binding site in free ProXp-ala, likely reflecting sampling of open and closed conformations. Dynamics persist on binding to the uncharged microhelix, but are attenuated when the stably mischarged analog is bound. Computational docking and molecular dynamics simulations provide structural context for these findings and predict a role for the substrate primary α-amine group in substrate recognition. Overall, our results illuminate strategies used by a trans-editing domain to ensure acceptance of only mischarged Ala-tRNAPro, including conformational selection by a dynamic helix, size-based exclusion, and optimal positioning of substrate chemical groups. PMID:28768811

47 CFR 79.101 - Closed caption decoder requirements for analog television receivers.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) BROADCAST RADIO SERVICES ACCESSIBILITY OF VIDEO PROGRAMMING Apparatus § 79.101 Closed caption decoder... TV Mode of operation allows the video to be viewed in its original form. The Caption and Text Modes... video over which they are placed. In addition, the user must have the capability to select a black...

The Substrate-free and -bound Crystal Structures of the Duplicated Taurocyamine Kinase from the Human Parasite Schistosoma mansoni*

PubMed Central

Merceron, Romain; Awama, Ayman M.; Montserret, Roland; Marcillat, Olivier; Gouet, Patrice

2015-01-01

The taurocyamine kinase from the blood fluke Schistosoma mansoni (SmTK) belongs to the phosphagen kinase (PK) family and catalyzes the reversible Mg2+-dependent transfer of a phosphoryl group between ATP and taurocyamine. SmTK is derived from gene duplication, as are all known trematode TKs. Our crystallographic study of SmTK reveals the first atomic structure of both a TK and a PK with a bilobal structure. The two unliganded lobes present a canonical open conformation and interact via their respective C- and N-terminal domains at a helix-mediated interface. This spatial arrangement differs from that observed in true dimeric PKs, in which both N-terminal domains make contact. Our structures of SmTK complexed with taurocyamine or l-arginine compounds explain the mechanism by which an arginine residue of the phosphagen specificity loop is crucial for substrate specificity. An SmTK crystal was soaked with the dead end transition state analog (TSA) components taurocyamine-NO32−-MgADP. One SmTK monomer was observed with two bound TSAs and an asymmetric conformation, with the first lobe semiclosed and the second closed. However, isothermal titration calorimetry and enzyme kinetics experiments showed that the two lobes function independently. A small angle x-ray scattering model of SmTK-TSA in solution with two closed active sites was generated. PMID:25837252

Floor-fractured crater models of the Sudbury structure, Canada

NASA Technical Reports Server (NTRS)

Wichman, R. W.; Schultz, P. H.

1992-01-01

The Sudbury structure in Ontario, Canada, is one of the oldest and largest impact structures recognized in the geological record. It is also one of the most extensively deformed and volcanically modified impact structures on Earth. Although few other terrestrial craters are recognized as volcanically modified, numerous impact craters on the Moon have been volcanically and tectonically modified and provide possible analogs for the observed pattern of modification at Sudbury. We correlate the pattern of early deformation at Sudbury to fracture patterns in two alternative lunar analogs and then use these analogs both to estimate the initial size of the Sudbury structure and to model the nature of early crater modification at Sudbury.

Novel 1,4-naphthoquinone-based sulfonamides: Synthesis, QSAR, anticancer and antimalarial studies.

PubMed

Pingaew, Ratchanok; Prachayasittikul, Veda; Worachartcheewan, Apilak; Nantasenamat, Chanin; Prachayasittikul, Supaluk; Ruchirawat, Somsak; Prachayasittikul, Virapong

2015-10-20

A novel series of 1,4-naphthoquinones (33-44) tethered by open and closed chain sulfonamide moieties were designed, synthesized and evaluated for their cytotoxic and antimalarial activities. All quinone-sulfonamide derivatives displayed a broad spectrum of cytotoxic activities against all of the tested cancer cell lines including HuCCA-1, HepG2, A549 and MOLT-3. Most quinones (33-36 and 38-43) exerted higher anticancer activity against HepG2 cell than that of the etoposide. The open chain analogs 36 and 42 were shown to be the most potent compounds. Notably, the restricted sulfonamide analog 38 with 6,7-dimethoxy groups exhibited the most potent antimalarial activity (IC₅₀ = 2.8 μM). Quantitative structure-activity relationships (QSAR) study was performed to reveal important chemical features governing the biological activities. Five constructed QSAR models provided acceptable predictive performance (Rcv 0.5647-0.9317 and RMSEcv 0.1231-0.2825). Four additional sets of structurally modified compounds were generated in silico (34a-34d, 36a-36k, 40a-40d and 42a-42k) in which their activities were predicted using the constructed QSAR models. A comprehensive discussion of the structure-activity relationships was made and a set of promising compounds (i.e., 33, 36, 38, 42, 36d, 36f, 42e, 42g and 42f) was suggested for further development as anticancer and antimalarial agents. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

A study of digital gyro compensation loops. [data conversion routines and breadboard models

NASA Technical Reports Server (NTRS)

1975-01-01

The feasibility is discussed of replacing existing state-of-the-art analog gyro compensation loops with digital computations. This was accomplished by designing appropriate compensation loops for the dry turned TDF gyro, selecting appropriate data conversion and processing techniques and algorithms, and breadboarding the design for laboratory evaluation. A breadboard design was established in which one axis of a Teledyne turned-gimbal TDF gyro was caged digitally while the other was caged using conventional analog electronics. The digital loop was designed analytically to closely resemble the analog loop in performance. The breadboard was subjected to various static and dynamic tests in order to establish the relative stability characteristics and frequency responses of the digital and analog loops. Several variations of the digital loop configuration were evaluated. The results were favorable.

The Structure-Mapping Engine: Algorithm and Examples.

ERIC Educational Resources Information Center

Falkenhainer, Brian; And Others

This description of the Structure-Mapping Engine (SME), a flexible, cognitive simulation program for studying analogical processing which is based on Gentner's Structure-Mapping theory of analogy, points out that the SME provides a "tool kit" for constructing matching algorithms consistent with this theory. This report provides: (1) a…

The biotin repressor: modulation of allostery by corepressor analogs.

PubMed

Brown, Patrick H; Cronan, John E; Grøtli, Morten; Beckett, Dorothy

2004-04-02

The Escherichia coli biotin repressor functions in biotin retention and regulation of biotin biosynthesis. Biotin retention is accomplished via the two-step biotinylation of the biotin-dependent enzyme, acetyl-CoA carboxylase. In the first step of this reaction the substrates biotin and ATP are utilized in synthesis of the activated biotin, biotinyl-5'-AMP, while in the second step this activated biotin is transferred to a unique lysine residue of the biotin carboxyl carrier protein subunit of the carboxylase. Regulation of biotin biosynthesis is accomplished through binding of the repressor to the transcription control region of the biotin biosynthetic operon. The adenylated or activated biotin functions as the corepressor in this DNA binding process. The activated biotin is a mixed anhydride and thus labile. In efforts to develop tools for structural and thermodynamic studies of the biotin regulatory interactions, two analogs of the adenylate, a sulfamoyl derivative and an ester derivative, have been synthesized and functionally characterized. Results of fluorescence measurements indicate that both analogs bind with high affinity to the repressor and that both are inactive in biotin transfer to the acceptor protein. Functional studies of their corepressor properties indicate that while the sulfamoyl is a weak allosteric activator, the ester closely mimics the physiological corepressor in activation of assembly of the transcription repression complex. Results of these studies also provide further insight into the allosteric mechanism of the biotin repressor.

Antibacterial properties of (2,3)-alpha- and (2,3)-beta-methylene analogs of penicillin G.

PubMed Central

Christenson, J G; Pruess, D L; Talbot, M K; Keith, D D

1988-01-01

The penam nucleus can assume two conformations; these are designated open and closed. The synthetic (2,3)-alpha- and (2,3)-beta-methylenepenams can be regarded as analogs of the open and closed conformations, respectively. It has been shown that the beta-methylenepenams are essentially inactive, suggesting that the closed conformation of penams is also inactive. In this study, we investigated a series of beta-lactams, all of which contained phenylacetamido side chains: penicillin G, the (2,3)-alpha- and (2,3)-beta-methylenepenams, and the 3-acetoxymethyl- and 3-methylcephalosporins. The alpha-methylenepenam and penicillin G were the most active compounds, while the beta-methylene isomer was only poorly active. Results with permeability mutants suggested that the alpha-methylene compound penetrated the outer membrane somewhat more readily than penicillin G did. The intrinsic potency of the alpha-methylenepenam appeared to be similar to that of penicillin G, on the basis of their affinities for penicillin-binding proteins and their abilities to inhibit peptidoglycan synthesis in ether-permeabilized Escherichia coli, while the beta-methylene analog had very poor intrinsic potency. The alpha-methylene analog was about 10-fold more efficient (Vmax/Km) than penicillin G as a substrate for the cephalosporinases from Enterobacter cloacae and Proteus vulgaris, but it was about 40-fold less efficient with penicillinase from Staphylococcus aureus. These results strongly support the hypothesis that the active conformation of penams is the open conformation and suggest that the position in space of the carboxyl group relative to the beta-lactam carbonyl is an important determinant of cephalosporinlike character, as distinct from penicillinlike character. Images PMID:3190190

Morphometry of Left Frontal and Temporal Poles Predicts Analogical Reasoning Abilities.

PubMed

Aichelburg, Clarisse; Urbanski, Marika; Thiebaut de Schotten, Michel; Humbert, Frederic; Levy, Richard; Volle, Emmanuelle

2016-03-01

Analogical reasoning is critical for making inferences and adapting to novelty. It can be studied experimentally using tasks that require creating similarities between situations or concepts, i.e., when their constituent elements share a similar organization or structure. Brain correlates of analogical reasoning have mostly been explored using functional imaging that has highlighted the involvement of the left rostrolateral prefrontal cortex (rlPFC) in healthy subjects. However, whether inter-individual variability in analogical reasoning ability in a healthy adult population is related to differences in brain architecture is unknown. We investigated this question by employing linear regression models of performance in analogy tasks and voxel-based morphometry in 54 healthy subjects. Our results revealed that the ability to reason by analogy was associated with structural variability in the left rlPFC and the anterior part of the inferolateral temporal cortex. Tractography of diffusion-weighted images suggested that these 2 regions have a different set of connections but may exchange information via the arcuate fasciculus. These results suggest that enhanced integrative and semantic abilities supported by structural variation in these areas (or their connectivity) may lead to more efficient analogical reasoning. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Monocarbonyl analogs of curcumin inhibit growth of antibiotic sensitive and resistant strains of Mycobacterium tuberculosis

PubMed Central

Baldwin, Patrick R.; Reeves, Analise Z.; Powell, Kimberly R.; Napier, Ruth J.; Swimm, Alyson I.; Sun, Aiming; Giesler, Kyle; Bommarius, Bettina; Shinnick, Thomas M.; Snyder, James P.; Liotta, Dennis C.; Kalman, Daniel

2016-01-01

Tuberculosis (TB) is a major public health concern worldwide with over 2 billion people currently infected. The rise of strains of Mycobacterium tuberculosis (Mtb) that are resistant to some or all first and second line antibiotics, including multidrug-resistant (MDR), extensively drug resistant (XDR) and totally drug resistant (TDR) strains, is of particular concern and new anti-TB drugs are urgently needed. Curcumin, a natural product used in traditional medicine in India, exhibits anti-microbial activity that includes Mtb, however it is relatively unstable and suffers from poor bioavailability. To improve activity and bioavailability, mono-carbonyl analogs of curcumin were synthesized and screened for their capacity to inhibit the growth of Mtb and the related Mycobacterium marinum (Mm). Using disk diffusion and liquid culture assays, we found several analogs that inhibit in vitro growth of Mm and Mtb, including rifampicin-resistant strains. Structure activity analysis of the analogs indicated that Michael acceptor properties are critical for inhibitory activity. However, no synergistic effects were evident between the monocarbonyl analogs and rifampicin on inhibiting growth. Together, these data provide a structural basis for the development of analogs of curcumin with pronounced anti-mycobacterial activity and provide a roadmap to develop additional structural analogs that exhibit more favorable interactions with other anti-TB drugs. PMID:25618016

Two analogy strategies: the cases of mind metaphors and introspection

NASA Astrophysics Data System (ADS)

Fischer, Eugen

2018-04-01

Analogical reasoning is often employed in problem-solving and metaphor interpretation. This paper submits that, as a default, analogical reasoning addressing these different tasks employs different mapping strategies. In problem-solving, it employs analogy-maximising strategies (like structure mapping, Gentner, D., & Markman, A. B. (1997). Structure mapping in analogy and similarity. American Psychologist, 52, 45-56); in metaphor interpretation, analogy-minimising strategies (like ATT-Meta, Barnden, J. A. (2015). Open-ended elaborations in creative metaphor. In T. R. Besold, M. Schorlemmer, & A. Smaill (Eds.), Computational creativity research: Towards creative machines (pp. 217-242). Berlin: Springer). The two strategies interact in analogical reasoning with conceptual metaphors. This interaction leads to predictable fallacies. The paper supports these hypotheses through case-studies on "mind" metaphors from ordinary discourse, and abstract problem-solving in the philosophy of mind, respectively. It shows that (1) default metaphorical interpretations for vision- and space-cognition metaphors can be derived with a variant of the analogy-minimising ATT-Meta approach, (2) philosophically influential introspective conceptions of the mind can be derived with conceptual metaphors only through an analogy-maximising strategy, and (3) the interaction of these strategies leads to hitherto unrecognised fallacies in analogical reasoning with metaphors. This yields a debunking explanation of introspective conceptions.

Space and time in the quantum universe.

NASA Astrophysics Data System (ADS)

Smolin, L.

This paper is devoted to the problem of constructing a quantum theory that could describe a closed system - a quantum cosmology. The author argues that this problem is an aspect of a much older problem - that of how to eliminate from the physical theories "ideal elements", which are elements of the mathematical structure whose interpretation requires the existence of things outside the dynamical system described by the theory. This discussion is aimed at uncovering criteria that a theory of quantum cosmology must satisfy, if it is to give physically sensible predictions. The author proposes three such criteria and shows that conventional quantum cosmology can only satisfy them, if there is an intrinsic time coordinate on the phase space of the theory. It is shown that approaches based on correlations in the wave function, that do not use an inner product, cannot satisfy these criteria. As example, the author discusses the problem of quantizing a class of relational dynamical models invented by Barbour and Bertotti. The dynamical structure of these theories is closely analogous to general relativity, and the problem of their measurement theory is also similar. It is concluded that these theories can only be sensibly quantized if they contain an intrinsic time.

A Systematic Evaluation of Analogs for the Read-across ...

EPA Pesticide Factsheets

Read-across is a data gap filling technique widely used within category and analog approaches to predict a biological property for a target data-poor chemical using known information from similar (source analog) chemical(s). Potential source analogs are typically identified based on structural similarity. Although much guidance has been published for read-across, practical guiding principles for the identification and evaluation of the scientific validity of source analogs, which is a critical step in deriving a robust read-across prediction, remains largely lacking.This case study explores the extent to which 3 structure descriptor sets (Pubchem, Chemotyper and MoSS) and their combinations are able to identify valid analogs for reading across Estrogen Receptor (ER) activity for a specific class of chemicals: hindered phenols. For each target chemical, two sets of analogs (hindered and non-hindered phenols) were selected using each descriptor set with two cut-offs: (1). Minimum Tanimoto similarity (range 0.1 - 0.9), and (2). Closest N analogs (range 1 - 10). Each target-analog pair was then evaluated for its agreement with measured ER binding and agonism. Subsequently, the analogs were filtered using physchem properties (LogKow & Molecular Volume) and the resultant agreement between each target-analog pair was evaluated. The data set comprised 462 hindered phenols and 296 non-hindered phenols. The results demonstrate that: (1). The concordance in ER activity r

A Systematic Evaluation of Analogs and Automated Read ...

EPA Pesticide Factsheets

Read-across is a data gap filling technique widely used within category and analog approaches to predict a biological property for a data-poor (target) chemical using known information from similar (source analog) chemical(s). Potential source analogs are typically identified based on structural similarity. Although much guidance has been published for read-across, practical principles for the identification and evaluation of the scientific validity of source analogs remains lacking. This case study explores how well 3 structure descriptor sets (Pubchem, Chemotyper and MoSS) are able to identify analogs for read-across and predict Estrogen Receptor (ER) binding activity for a specific class of chemicals: hindered phenols. For each target chemical, analogs were selected using each descriptor set with two cut-offs: (1) Minimum Tanimoto similarity (range 0.1 - 0.9), and (2) Closest N analogs (range 1 - 10). Each target-analog pair was then evaluated for its agreement with measured ER binding and agonism. The analogs were subsequently filtered using: (1) physchem properties (LogKow & Molecular Volume), and (2) number of literature sources as a marker for the quality of the experimental data. A majority vote prediction was made for each target phenol by reading-across from the closest N analogs. The data set comprised 462 hindered phenols and 257 non-hindered phenols. The results demonstrate that: (1) The concordance in ER activity rises with increasing similarity,

High resolution multi-facies realizations of sedimentary reservoir and aquifer analogs

PubMed Central

Bayer, Peter; Comunian, Alessandro; Höyng, Dominik; Mariethoz, Gregoire

2015-01-01

Geological structures are by nature inaccessible to direct observation. This can cause difficulties in applications where a spatially explicit representation of such structures is required, in particular when modelling fluid migration in geological formations. An increasing trend in recent years has been to use analogs to palliate this lack of knowledge, i.e., exploiting the spatial information from sites where the geology is accessible (outcrops, quarry sites) and transferring the observed properties to a study site deemed geologically similar. While this approach is appealing, it is difficult to put in place because of the lack of access to well-documented analog data. In this paper we present comprehensive analog data sets which characterize sedimentary structures from important groundwater hosting formations in Germany and Brazil. Multiple 2-D outcrop faces are described in terms of hydraulic, thermal and chemical properties and interpolated in 3-D using stochastic techniques. These unique data sets can be used by the wider community to implement analog approaches for characterizing reservoir and aquifer formations. PMID:26175910

Staging in polyacetylene-iodine conductors

NASA Astrophysics Data System (ADS)

Baughman, R. H.; Murthy, N. S.; Miller, G. G.; Shacklette, L. W.

1983-07-01

Evidence is presented for the existence of highly conducting polyacetylene complexes with structures related to high-stage graphite, as well as structures related to first-stage graphite. X-ray diffraction measurements on polyacetylene-iodine complexes indicate equatorial lines at 7.7-8.0 and 13.8-14.3 Å. The shorter spacing arises in part from a structure in which iodine-rich planes alternate with planes of polyacetylene chains. The longer spacing, which disappears upon atmospheric exposure, is consistent with a structure analogous to third-stage graphite in which dopant-rich planes are separated by three close-packed planes of polyacetylene chains. The third-stage complex can be viewed as a perturbation of the structure of undoped polyacetylene, with the region between dopant layers consisting essentially of a one unit cell thickness of the parent polymer structure. Packing calculations for this model, in which a linear column of anions (I3- and/or I5-) displaces either every chain or every other chain in the dopant-rich layer, provide an interlayer spacing which is equal to that observed. Evidence consistent with third-stage structures (with both fractional occupation and complete occupation of the dopant plane) is also found by reexamination of published sorption data, which provides slope changes at close to the calculated limiting compositions for these structures [(CHI0.056)x and (CHI0.13)x]. However, a first-stage structure with alternating dopant arrays and polymer chains in the dopant plane [for which (CHI0.13)x is calculated] provides a better explanation for the second slope change, as well as for the composition obtained under dynamic vacuum, (CHI0.14)x. These results for iodine complexes are compared with those derived for the group VA halide complexes of polyacetylene.

Students' Pre- and Post-Teaching Analogical Reasoning when They Draw Their Analogies

ERIC Educational Resources Information Center

Mozzer, Nilmara Braga; Justi, Rosaria

2012-01-01

Analogies are parts of human thought. From them, we can acquire new knowledge or change that which already exists in our cognitive structure. In this sense, understanding the analogical reasoning process becomes an essential condition to understand how we learn. Despite the importance of such an understanding, there is no general agreement in…

Crystal grain growth at the α -uranium phase transformation in praseodymium

NASA Astrophysics Data System (ADS)

Cunningham, Nicholas C.; Velisavljevic, Nenad; Vohra, Yogesh K.

2005-01-01

Structural phase transformations under pressure are examined in praseodymium metal for the range 0-40GPa at ambient temperature. Pressure was generated with a diamond-anvil cell, and data were collected using high-resolution synchrotron x-ray diffraction and the image plate technique. The structural sequence double hexagonal close packed (dhcp)→face centered cubic (fcc)→distorted-fcc (d-fcc)→ α -uranium (α-U) is observed with increasing pressure. Rietveld refinement of all crystallographic phases provided confirmation of the hR24 structure for the d-fcc phase while the previously reported monoclinic phase between the d-fcc and the α-U phase was not confirmed. We observe dramatic crystal grain growth during the volume collapse concurrent with the symmetry-lowering transition to the α-U structure. No preferred orientation axis is observed, and the formation process for these large grains is expected to be via a nucleation and growth mechanism. An analogous effect in rare earth metal cerium suggests that the grain growth during transformation to the α-U structure is a common occurrence in f -electron metals at high pressures.

Exact analysis of the spectral properties of the anisotropic two-bosons Rabi model

NASA Astrophysics Data System (ADS)

Cui, Shuai; Cao, Jun-Peng; Fan, Heng; Amico, Luigi

2017-05-01

We introduce the anisotropic two-photon Rabi model in which the rotating and counter rotating terms enters the Hamiltonian with two different coupling constants. Eigenvalues and eigenvectors are studied with exact means. We employ a variation of the Braak method based on Bogolubov rotation of the underlying su(1, 1) Lie algebra. Accordingly, the spectrum is provided by the analytical properties of a suitable meromorphic function. Our formalism applies to the two-modes Rabi model as well, sharing the same algebraic structure of the two-photon model. Through the analysis of the spectrum, we discover that the model displays close analogies to many-body systems undergoing quantum phase transitions.

Thyroid receptor ligands. Part 8: Thyromimetics derived from N-acylated-alpha-amino acid derivatives displaying modulated pharmacological selectivity compared with KB-141.

PubMed

Garg, Neeraj; Li, Yi-Lin; Garcia Collazo, Ana Maria; Litten, Chris; Ryono, Denis E; Zhang, Minsheng; Caringal, Yolanda; Brigance, Robert P; Meng, Wei; Washburn, William N; Agback, Peter; Mellström, Karin; Rehnmark, Stefan; Rahimi-Ghadim, Mahmoud; Norin, Thomas; Grynfarb, Marlena; Sandberg, Johnny; Grover, Gary; Malm, Johan

2007-08-01

Based on the scaffold of the pharmacologically selective thyromimetic 2b, structurally a close analog to KB-141 (2a), a number of novel N-acylated-alpha-amino acid derivatives were synthesized and tested in a TR radioligand binding assay as well as in a reporter cell assay. On the basis of TRbeta(1)-isoform selectivity and affinity, as well as affinity to the reporter cell assay, 3d was selected for further studies in the cholesterol-fed rat model. In this model 3d revealed an improved therapeutic window between cholesterol and TSH lowering but decreased margins versus tachycardia compared with 2a.

On the Hamiltonian formalism of the tetrad-gravity with fermions

NASA Astrophysics Data System (ADS)

Lagraa, M. H.; Lagraa, M.

2018-06-01

We extend the analysis of the Hamiltonian formalism of the d-dimensional tetrad-connection gravity to the fermionic field by fixing the non-dynamic part of the spatial connection to zero (Lagraa et al. in Class Quantum Gravity 34:115010, 2017). Although the reduced phase space is equipped with complicated Dirac brackets, the first-class constraints which generate the diffeomorphisms and the Lorentz transformations satisfy a closed algebra with structural constants analogous to that of the pure gravity. We also show the existence of a canonical transformation leading to a new reduced phase space equipped with Dirac brackets having a canonical form leading to the same algebra of the first-class constraints.

Charge neutralization in the active site of the catalytic trimer of aspartate transcarbamoylase promotes diverse structural changes.

PubMed

Endrizzi, James A; Beernink, Peter T

2017-11-01

A classical model for allosteric regulation of enzyme activity posits an equilibrium between inactive and active conformations. An alternative view is that allosteric activation is achieved by increasing the potential for conformational changes that are essential for catalysis. In the present study, substitution of a basic residue in the active site of the catalytic (C) trimer of aspartate transcarbamoylase with a non-polar residue results in large interdomain hinge changes in the three chains of the trimer. One conformation is more open than the chains in both the wild-type C trimer and the catalytic chains in the holoenzyme, the second is closed similar to the bisubstrate-analog bound conformation and the third hinge angle is intermediate to the other two. The active-site 240s loop conformation is very different between the most open and closed chains, and is disordered in the third chain, as in the holoenzyme. We hypothesize that binding of anionic substrates may promote similar structural changes. Further, the ability of the three catalytic chains in the trimer to access the open and closed active-site conformations simultaneously suggests a cyclic catalytic mechanism, in which at least one of the chains is in an open conformation suitable for substrate binding whereas another chain is closed for catalytic turnover. Based on the many conformations observed for the chains in the isolated catalytic trimer to date, we propose that allosteric activation of the holoenzyme occurs by release of quaternary constraint into an ensemble of active-site conformations. © 2017 The Protein Society.

Novel 4-Substituted-N,N-dimethyltetrahydronaphthalen-2-amines: Synthesis, Affinity, and In Silico Docking Studies at Serotonin 5-HT2-type and Histamine H1 G Protein-Coupled Receptors

PubMed Central

Sakhuja, Rajeev; Kondabolu, Krishnakanth; Córdova-Sintjago, Tania; Travers, Sean; Vincek, Adam S.; Kim, Myong Sang; Abboud, Khalil A.; Fang, Lijuan; Sun, Zhuming; Canal, Clinton E.; Booth, Raymond G.

2015-01-01

Syntheses were undertaken of derivatives of (2S, 4R)-(−)-trans-4-phenyl-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine (4-phenyl-2-dimethylaminotetralin, PAT), a stereospecific agonist at the serotonin 5-HT2C G protein-coupled receptor (GPCR), with inverse agonist activity at 5-HT2A and 5-HT2B GPCRs. Molecular changes were made at the PAT C(4)-position, while preserving N, N-dimethyl substitution at the 2-position as well as trans-stereochemistry, structural features previously shown to be optimal for 5-HT2 binding. Affinities of analogs were determined at recombinant human 5-HT2 GPCRs in comparison to the phylogenetically closely-related histamine H1 GPCR, and in silico ligand docking studies were conducted at receptor molecular models to help interpret pharmacological results and guide future ligand design. In most cases, C(4)-substituted PAT analogs exhibited the same stereoselectivity ([−]-trans > [+]-trans) as the parent PAT across 5-HT2 and H1 GPCRs, albeit, with variable receptor selectivity. 4-(4′-substituted)-PAT analogs, however, demonstrated reversed stereoselectivity ([2S, 4R]-[+]-trans > [2S, 4R]-[−]-trans), with absolute configuration confirmed by single X-ray crystallographic data for the 4-(4′-Cl)-PAT analog. Pharmacological affinity results and computational results herein support further PAT drug development studies and provide a basis for predicting and interpreting translational results, including, for (+)-trans-4-(4′-Cl)-PAT and (−)-trans-4-(3′-Br)-PAT that were previously shown to be more potent and efficacious than their corresponding enantiomers in rodent models of psychoses, psychostimulant-induced behaviors, and compulsive feeding (‘binge-eating’). PMID:25703249

Exploring the use of multiple analogical models when teaching and learning chemical equilibrium

NASA Astrophysics Data System (ADS)

Harrison, Allan G.; de Jong, Onno

2005-12-01

This study describes the multiple analogical models used to introduce and teach Grade 12 chemical equilibrium. We examine the teacher's reasons for using models, explain each model's development during the lessons, and analyze the understandings students derived from the models. A case study approach was used and the data were drawn from the observation of three consecutive Grade 12 lessons on chemical equilibrium, pre- and post-lesson interviews, and delayed student interviews. The key analogical models used in teaching were: the school dance; the sugar in a teacup; the pot of curry; and the busy highway. The lesson and interview data were subject to multiple, independent analyses and yielded the following outcomes: The teacher planned to use the students' prior knowledge wherever possible and he responded to student questions with stories and extended and enriched analogies. He planned to discuss where each analogy broke down but did not. The students enjoyed the teaching but built variable mental models of equilibrium and some of their analogical mappings were unreliable. A female student disliked masculine analogies, other students tended to see elements of the multiple models in isolation, and some did not recognize all the analogical mappings embedded in the teaching plan. Most students learned that equilibrium reactions are dynamic, occur in closed systems, and the forward and reverse reactions are balanced. We recommend the use of multiple analogies like these and insist that teachers always show where the analogy breaks down and carefully negotiate the conceptual outcomes.

Aligned fibers direct collective cell migration to engineer closing and nonclosing wound gaps

PubMed Central

Sharma, Puja; Ng, Colin; Jana, Aniket; Padhi, Abinash; Szymanski, Paige; Lee, Jerry S. H.; Behkam, Bahareh; Nain, Amrinder S.

2017-01-01

Cell emergence onto damaged or organized fibrous extracellular matrix (ECM) is a crucial precursor to collective cell migration in wound closure and cancer metastasis, respectively. However, there is a fundamental gap in our quantitative understanding of the role of local ECM size and arrangement in cell emergence–based migration and local gap closure. Here, using ECM-mimicking nanofibers bridging cell monolayers, we describe a method to recapitulate and quantitatively describe these in vivo behaviors over multispatial (single cell to cell sheets) and temporal (minutes to weeks) scales. On fiber arrays with large interfiber spacing, cells emerge (invade) either singularly by breaking cell–cell junctions analogous to release of a stretched rubber band (recoil), or in groups of few cells (chains), whereas on closely spaced fibers, multiple chains emerge collectively. Advancing cells on fibers form cell streams, which support suspended cell sheets (SCS) of various sizes and curvatures. SCS converge to form local gaps that close based on both the gap size and shape. We document that cell stream spacing of 375 µm and larger hinders SCS advancement, thus providing abilities to engineer closing and nonclosing gaps. Altogether we highlight the importance of studying cell-fiber interactions and matrix structural remodeling in fundamental and translational cell biology. PMID:28747440

Dissociation reactions of protonated anthracycline antibiotics following electrospray ionization-tandem mass spectrometry

NASA Astrophysics Data System (ADS)

Sleno, Lekha; Campagna-Slater, Valerie; Volmer, Dietrich A.

2006-09-01

Fragmentation pathways of doxorubicin, a common cancer therapy agent, and three closely related analogs (epirubicin, daunorubicin, idarubicin) were compared using electrospray ionization with tandem mass spectrometry. This class of antibiotics with anti-tumour activity has important structural features, with a tetracyclic aromatic, polyketide portion, which is glycosylated with an amino sugar in order to exhibit its biological activity. Collision-induced dissociation spectra revealed very similar product ions for each analog, however, important differences were seen in the relative abundances and the ease at which certain fragments were formed. Fragment ions observed included those from cleavage of the glycosidic bond, loss of the side chain from the aglycone moiety, water losses and loss of a methyl radical. Following cleavage of the glycosidic bond, the charge can either reside on the aglycone portion or the sugar moiety, and each of these primary fragments undergoes several secondary dissociation pathways, depending on the collision energy. By ramping the collision voltage, we were able to correlate the changes in fragmentation behavior with small alterations in the structure of the precursor ion. The detailed study of the fragmentation behavior of doxorubicin was supported by accurate mass measurements, using an electrospray-time of flight instrument, as well as MS3 data from a quadrupole-linear ion trap mass spectrometer. Computational studies were also performed to help explain the role of certain functional groups in the fragmentation reactions.

Analogical Reasoning as a Mechanism in Knowledge Acquisition: A Developmental Perspective. Technical Report No. 438.

ERIC Educational Resources Information Center

Vosniadou, Stella

Analogical reasoning is one mechanism that has been recognized as having the potential of bringing prior knowledge to bear on the acquisition of new information. Analogical reasoning involves the identification and transfer of structural information from a known system to a new and relatively unknown system. The productive use of analogy is often…

Stationary waves on nonlinear quantum graphs. II. Application of canonical perturbation theory in basic graph structures.

PubMed

Gnutzmann, Sven; Waltner, Daniel

2016-12-01

We consider exact and asymptotic solutions of the stationary cubic nonlinear Schrödinger equation on metric graphs. We focus on some basic example graphs. The asymptotic solutions are obtained using the canonical perturbation formalism developed in our earlier paper [S. Gnutzmann and D. Waltner, Phys. Rev. E 93, 032204 (2016)2470-004510.1103/PhysRevE.93.032204]. For closed example graphs (interval, ring, star graph, tadpole graph), we calculate spectral curves and show how the description of spectra reduces to known characteristic functions of linear quantum graphs in the low-intensity limit. Analogously for open examples, we show how nonlinear scattering of stationary waves arises and how it reduces to known linear scattering amplitudes at low intensities. In the short-wavelength asymptotics we discuss how genuine nonlinear effects may be described using the leading order of canonical perturbation theory: bifurcation of spectral curves (and the corresponding solutions) in closed graphs and multistability in open graphs.

Structural design of intrinsically fluorescent oxysterols.

PubMed

Nåbo, Lina J; Modzel, Maciej; Krishnan, Kathiresan; Covey, Douglas F; Fujiwara, Hideji; Ory, Daniel S; Szomek, Maria; Khandelia, Himanshu; Wüstner, Daniel; Kongsted, Jacob

2018-05-01

Oxysterols are oxidized derivatives of cholesterol with many important biological functions. Trafficking of oxysterols in and between cells is not well studied, largely due to the lack of appropriate oxysterol analogs. Intrinsically fluorescent oxysterols present a new route towards direct observation of intracellular oxysterol trafficking by fluorescence microscopy. We characterize the fluorescence properties of the existing fluorescent 25-hydroxycholesterol analog 25-hydroxycholestatrienol, and propose a new probe with an extended conjugated system. The location of both probes inside a membrane is analyzed and compared with that of 25-hydroxycholesterol using molecular dynamics simulations. The analogs' one- and two-photon absorption properties inside the membrane are evaluated using electronic structure calculations with polarizable embedding. Due to predicted keto-enol tautomerisation of the new oxysterol analog, we also evaluate the keto form. Both analogs are found to be good probe candidates for 25-hydroxycholesterol, provided that the new analog remains in the enol-form. Only the new analog with extended conjugated system shows significant two-photon absorption, which is strongly enhanced by the presence of the membrane. Copyright © 2018 Elsevier B.V. All rights reserved.

A serendipitous discovery of antifreeze protein-specific activity in C-linked antifreeze glycoprotein analogs.

PubMed

Eniade, Adewale; Purushotham, Madhusudhan; Ben, Robert N; Wang, J B; Horwath, Kathleen

2003-01-01

Structurally diverse carbon-linked (C-linked) analogs of antifreeze glycoprotein (AFGP) have been prepared via linear or convergent solid phase synthesis. These analogs range in molecular weight from approx 1.5-4.1 KDa and do not possess the beta-D-galactose-1,3-alpha-D-N-acetylgalactosamine carbohydrate moiety or the L-threonine-L-alanine-L-alanine polypeptide backbone native to the AFGP wild-type. Despite these dramatic structural modifications, the 2.7-KDa and 4.1-KDa analogs possess antifreeze protein-specific activity as determined by recrystallization-inhibition (RI) and thermal hysteresis (TH) assays. These analogs are weaker than the wild-type in their activity, but nanoliter osmometry indicates that these compounds are binding to ice and affecting a localized freezing point depression. This is the first example of a C-linked AFGP analog that possesses TH and RI activity and suggests that the rational design and synthesis of chemically and biologically stable AFGP analogs is a feasible and worthwhile endeavor. Given the low degree of TH activity, these compounds may prove useful for the protection of cells during freezing and thawing cycles.

Bandwidth controller for phase-locked-loop

NASA Technical Reports Server (NTRS)

Brockman, Milton H. (Inventor)

1992-01-01

A phase locked loop utilizing digital techniques to control the closed loop bandwidth of the RF carrier phase locked loop in a receiver provides high sensitivity and a wide dynamic range for signal reception. After analog to digital conversion, a digital phase locked loop bandwidth controller provides phase error detection with automatic RF carrier closed loop tracking bandwidth control to accommodate several modes of transmission.

Purification and characterization of galanin from the phylogenetically ancient fish, the bowfin (Amia calva) and dogfish (Scyliorhinus canicula).

PubMed

Wang, Y; Conlon, J M

1994-01-01

Galanin was purified to near homogeneity from an extract of the stomachs of the holostean fish, the bowfin and the elasmobranch fish, the European common dogfish. Bowfin galanin contains an alpha'-amidated C-terminal residue and the primary structure of the peptide (GWTNL SAGYL LGPHA VDNHR SLNDK HGLA) shows only four amino acid substitutions (Val16-->Ile, Leu22-->Phe, Asn23-->His, and His26-->Tyr) compared with pig galanin. Dogfish galanin was isolated in a truncated form for which amino acid sequence was identical to residues (1-20) of bowfin galanin. The isolation of this fragment is indicative of processing at the site of a single arginyl residue, and an analogous peptide has been previously isolated from human intestine. The data demonstrate that peptides with close structural similarity to mammalian galanins are present in the gastrointestinal tracts of phylogenetically ancient fish.

Nanotubes from Inorganic Materials

NASA Astrophysics Data System (ADS)

Tenne, Reshef; Zettl, Alex K.

The inorganic analogs of carbon fullerenes and nanotubes, like MoS2 and BN, are reviewed. It is argued that nanoparticles of 2D layered compounds are inherently unstable in the planar configuration and prefer to form closed cage structures. The progress in the synthesis of these nanomaterials, and, in particular, the large-scale synthesis of BN, WS2 and V2O5 nanotubes, are described. Some of the electronic, optical and mechanical properties of these nanostructures are reviewed. The red-shift of the energy gap with shrinking nanotube diameter is discussed as well as the suggestion that zigzag nanotubes exhibit a direct gap rather than an indirect gap, as is prevalent in many of the bulk 2D materials. Some potential applications of these nanomaterials are presented as well, most importantly the superior tribological properties of WS2 and MoS2 nested fullerene-like structures (onions).

New cytotoxic benzosuberene analogs. Synthesis, molecular modeling and biological evaluation.

PubMed

Chen, Zecheng; Maderna, Andreas; Sukuru, Sai Chetan K; Wagenaar, Melissa; O'Donnell, Christopher J; Lam, My-Hanh; Musto, Sylvia; Loganzo, Frank

2013-12-15

In this Letter we describe the synthesis and biological evaluation of new benzosuberene analogs with structural modifications on the B-ring. The focus was initially to probe the chemical space around the B-ring C-8 position. This position was readily available for derivatization chemistry using our recently developed new synthesis for this compound class. Furthermore, we describe two new B-ring analogs, one containing a diene and the other a cyclic ether group. Both new analogs show excellent potencies in tumor cell proliferation assays. In addition, we describe molecular modeling studies that provide a binding rationale for reference compound 8 in the colchicine binding site using the known colchicine crystal structure. We also examine whether the cell based potency data obtained with selected new analogs are supported by modeling results. Copyright © 2013 Elsevier Ltd. All rights reserved.

A 16-Channel CMOS Chopper-Stabilized Analog Front-End ECoG Acquisition Circuit for a Closed-Loop Epileptic Seizure Control System.

PubMed

Wu, Chung-Yu; Cheng, Cheng-Hsiang; Chen, Zhi-Xin

2018-06-01

In this paper, a 16-channel analog front-end (AFE) electrocorticography signal acquisition circuit for a closed-loop seizure control system is presented. It is composed of 16 input protection circuits, 16 auto-reset chopper-stabilized capacitive-coupled instrumentation amplifiers (AR-CSCCIA) with bandpass filters, 16 programmable transconductance gain amplifiers, a multiplexer, a transimpedance amplifier, and a 128-kS/s 10-bit delta-modulated successive-approximation-register analog-to-digital converter (SAR ADC). In closed-loop seizure control system applications, the stimulator shares the same electrode with the AFE amplifier for effective suppression of epileptic seizures. To prevent from overstress in MOS devices caused by high stimulation voltage, an input protection circuit with a high-voltage-tolerant switch is proposed for the AFE amplifier. Moreover, low input-referred noise is achieved by using the chopper modulation technique in the AR-CSCCIA. To reduce the undesired effects of chopper modulation, an improved offset reduction loop is proposed to reduce the output offset generated by input chopper mismatches. The digital ripple reduction loop is also used to reduce the chopper ripple. The fabricated AFE amplifier has 49.1-/59.4-/67.9-dB programmable gain and 2.02-μVrms input referred noise in a bandwidth of 0.59-117 Hz. The measured power consumption of the AFE amplifier is 3.26 μW per channel, and the noise efficiency factor is 3.36. The in vivo animal test has been successfully performed to verify the functions. It is shown that the proposed AFE acquisition circuit is suitable for implantable closed-loop seizure control systems.

Examples of Complete Solvability of 2D Classical Superintegrable Systems

NASA Astrophysics Data System (ADS)

Chen, Yuxuan; Kalnins, Ernie G.; Li, Qiushi; Miller, Willard, Jr.

2015-11-01

Classical (maximal) superintegrable systems in n dimensions are Hamiltonian systems with 2n-1 independent constants of the motion, globally defined, the maximum number possible. They are very special because they can be solved algebraically. In this paper we show explicitly, mostly through examples of 2nd order superintegrable systems in 2 dimensions, how the trajectories can be determined in detail using rather elementary algebraic, geometric and analytic methods applied to the closed quadratic algebra of symmetries of the system, without resorting to separation of variables techniques or trying to integrate Hamilton's equations. We treat a family of 2nd order degenerate systems: oscillator analogies on Darboux, nonzero constant curvature, and flat spaces, related to one another via contractions, and obeying Kepler's laws. Then we treat two 2nd order nondegenerate systems, an analogy of a caged Coulomb problem on the 2-sphere and its contraction to a Euclidean space caged Coulomb problem. In all cases the symmetry algebra structure provides detailed information about the trajectories, some of which are rather complicated. An interesting example is the occurrence of ''metronome orbits'', trajectories confined to an arc rather than a loop, which are indicated clearly from the structure equations but might be overlooked using more traditional methods. We also treat the Post-Winternitz system, an example of a classical 4th order superintegrable system that cannot be solved using separation of variables. Finally we treat a superintegrable system, related to the addition theorem for elliptic functions, whose constants of the motion are only rational in the momenta. It is a system of special interest because its constants of the motion generate a closed polynomial algebra. This paper contains many new results but we have tried to present most of the materials in a fashion that is easily accessible to nonexperts, in order to provide entrée to superintegrablity theory.

Planar dicyclic B{sub 6}S{sub 6}, B{sub 6}S{sub 6}{sup −}, and B{sub 6}S{sub 6}{sup 2−} clusters: Boron sulfide analogues of naphthalene

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

Li, Da-Zhi; Bai, Hui; Ou, Ting

2015-01-07

Inorganic analogues of hydrocarbons or polycyclic aromatic hydrocarbons (PAHs) are of current interest in chemistry. Based upon global structural searches and B3LYP and CCSD(T) calculations, we present herein the perfectly planar dicyclic boron sulfide clusters: D{sub 2h} B{sub 6}S{sub 6} (1, {sup 1}A{sub g}), D{sub 2h} B{sub 6}S{sub 6}{sup −} (2, {sup 2}B{sub 3u}), and D{sub 2h} B{sub 6}S{sub 6}{sup 2−} (3, {sup 1}A{sub g}). These are the global minima of the systems, being at least 0.73, 0.81, and 0.53 eV lower in energy, respectively, than their alternative isomers at the CCSD(T) level. The D{sub 2h} structures feature twin B{submore » 3}S{sub 2} five-membered rings, which are fused together via a B{sub 2} unit and terminated by two BS groups. Bonding analyses show that the closed-shell B{sub 6}S{sub 6}{sup 2−} (3) cluster possesses 10 delocalized π electrons, closely analogous to the bonding pattern of the aromatic naphthalene C{sub 10}H{sub 8}. The B{sub 6}S{sub 6}{sup −} (2) and B{sub 6}S{sub 6} (1) species are readily obtained upon removal of one or two π electrons from B{sub 6}S{sub 6}{sup 2−} (3). The results build a new analogous relationship between boron sulfide clusters and their PAH counterparts. The B{sub 6}S{sub 6}{sup −} (2) monoanion and B{sub 6}S{sub 6}{sup 2−} (3) dianion can be effectively stabilized in neutral LiB{sub 6}S{sub 6} and Li{sub 2}B{sub 6}S{sub 6} salts, respectively.« less

IADE: a system for intelligent automatic design of bioisosteric analogs

NASA Astrophysics Data System (ADS)

Ertl, Peter; Lewis, Richard

2012-11-01

IADE, a software system supporting molecular modellers through the automatic design of non-classical bioisosteric analogs, scaffold hopping and fragment growing, is presented. The program combines sophisticated cheminformatics functionalities for constructing novel analogs and filtering them based on their drug-likeness and synthetic accessibility using automatic structure-based design capabilities: the best candidates are selected according to their similarity to the template ligand and to their interactions with the protein binding site. IADE works in an iterative manner, improving the fitness of designed molecules in every generation until structures with optimal properties are identified. The program frees molecular modellers from routine, repetitive tasks, allowing them to focus on analysis and evaluation of the automatically designed analogs, considerably enhancing their work efficiency as well as the area of chemical space that can be covered. The performance of IADE is illustrated through a case study of the design of a nonclassical bioisosteric analog of a farnesyltransferase inhibitor—an analog that has won a recent "Design a Molecule" competition.

IADE: a system for intelligent automatic design of bioisosteric analogs.

PubMed

Ertl, Peter; Lewis, Richard

2012-11-01

IADE, a software system supporting molecular modellers through the automatic design of non-classical bioisosteric analogs, scaffold hopping and fragment growing, is presented. The program combines sophisticated cheminformatics functionalities for constructing novel analogs and filtering them based on their drug-likeness and synthetic accessibility using automatic structure-based design capabilities: the best candidates are selected according to their similarity to the template ligand and to their interactions with the protein binding site. IADE works in an iterative manner, improving the fitness of designed molecules in every generation until structures with optimal properties are identified. The program frees molecular modellers from routine, repetitive tasks, allowing them to focus on analysis and evaluation of the automatically designed analogs, considerably enhancing their work efficiency as well as the area of chemical space that can be covered. The performance of IADE is illustrated through a case study of the design of a nonclassical bioisosteric analog of a farnesyltransferase inhibitor--an analog that has won a recent "Design a Molecule" competition.

Synthetic lipids and their role in defining macromolecular assemblies.

PubMed

Parrill, Abby L

2015-10-01

Lipids have a variety of physiological roles, ranging from structural and biophysical contributions to membrane functions to signaling contributions in normal and abnormal physiology. This review highlights some of the contributions made by Robert Bittman to our understanding of lipid assemblies through the production of synthetic lipid analogs in the sterol, sphingolipid, and glycolipid classes. His contributions have included the development of a fluorescent cholesterol analog that shows strong functional analogies to cholesterol that has allowed live imaging of cholesterol distribution in living systems, to stereospecific synthetic approaches to both sphingolipid and glycolipid analogs crucial in defining the structure-activity relationships of lipid biological targets. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Enzyme-ligand interactions that drive active site rearrangements in the Helicobacter pylori 5´-methylthioadenosine/S-adenosylhomocysteine nucleosidase

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

Ronning, Donald R; Iacopelli, Natalie M; Mishra, Vidhi

2012-03-15

The bacterial enzyme 5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MTAN) plays a central role in three essential metabolic pathways in bacteria: methionine salvage, purine salvage, and polyamine biosynthesis. Recently, its role in the pathway that leads to the production of autoinducer II, an important component in quorum-sensing, has garnered much interest. Because of this variety of roles, MTAN is an attractive target for developing new classes of inhibitors that influence bacterial virulence and biofilm formation. To gain insight toward the development of new classes of MTAN inhibitors, the interactions between the Helicobacter pylori-encoded MTAN and its substrates and substrate analogs were probed using X-raymore » crystallography. The structures of MTAN, an MTAN-Formycin A complex, and an adenine bound form were solved by molecular replacement and refined to 1.7, 1.8, and 1.6 Å, respectively. The ribose-binding site in the MTAN and MTAN-adenine cocrystal structures contain a tris[hydroxymethyl]aminomethane molecule that stabilizes the closed form of the enzyme and displaces a nucleophilic water molecule necessary for catalysis. This research gives insight to the interactions between MTAN and bound ligands that promote closing of the enzyme active site and highlights the potential for designing new classes of MTAN inhibitors using a link/grow or ligand assembly development strategy based on the described H. pylori MTAN crystal structures.« less

Structure-Activity Relationship Studies Using Natural and Synthetic Okadaic Acid/Dinophysistoxin Toxins.

PubMed

Twiner, Michael J; Doucette, Gregory J; Pang, Yucheng; Fang, Chao; Forsyth, Craig J; Miles, Christopher O

2016-11-04

Okadaic acid (OA) and the closely related dinophysistoxins (DTXs) are algal toxins that accumulate in shellfish and are known serine/threonine protein phosphatase (ser/thr PP) inhibitors. Phosphatases are important modulators of enzyme activity and cell signaling pathways. However, the interactions between the OA/DTX toxins and phosphatases are not fully understood. This study sought to identify phosphatase targets and characterize their structure-activity relationships (SAR) with these algal toxins using a combination of phosphatase activity and cytotoxicity assays. Preliminary screening of 21 human and yeast phosphatases indicated that only three ser/thr PPs (PP2a, PP1, PP5) were inhibited by physiologically saturating concentrations of DTX2 (200 nM). SAR studies employed naturally-isolated OA, DTX1, and DTX2, which vary in degree and/or position of methylation, in addition to synthetic 2- epi -DTX2. OA/DTX analogs induced cytotoxicity and inhibited PP activity with a relatively conserved order of potency: OA = DTX1 ≥ DTX2 > 2- epi -DTX. The PPs were also differentially inhibited with sensitivities of PP2a > PP5 > PP1. These findings demonstrate that small variations in OA/DTX toxin structures, particularly at the head region (i.e., C1/C2), result in significant changes in toxicological potency, whereas changes in methylation at C31 and C35 (tail region) only mildly affect potency. In addition to this being the first study to extensively test OA/DTX analogs' activities towards PP5, these data will be helpful for accurately determining toxic equivalence factors (TEFs), facilitating molecular modeling efforts, and developing highly selective phosphatase inhibitors.

Fast, Low-Power, Hysteretic Level-Detector Circuit

NASA Technical Reports Server (NTRS)

Arditti, Mordechai

1993-01-01

Circuit for detection of preset levels of voltage or current intended to replace standard fast voltage comparator. Hysteretic analog/digital level detector operates at unusually low power with little sacrifice of speed. Comprises low-power analog circuit and complementary metal oxide/semiconductor (CMOS) digital circuit connected in overall closed feedback loop to decrease rise and fall times, provide hysteresis, and trip-level control. Contains multiple subloops combining linear and digital feedback. Levels of sensed signals and hysteresis level easily adjusted by selection of components to suit specific application.

Sleep promotes analogical transfer in problem solving.

PubMed

Monaghan, Padraic; Sio, Ut Na; Lau, Sum Wai; Woo, Hoi Kei; Linkenauger, Sally A; Ormerod, Thomas C

2015-10-01

Analogical problem solving requires using a known solution from one problem to apply to a related problem. Sleep is known to have profound effects on memory and information restructuring, and so we tested whether sleep promoted such analogical transfer, determining whether improvement was due to subjective memory for problems, subjective recognition of similarity across related problems, or by abstract generalisation of structure. In Experiment 1, participants were exposed to a set of source problems. Then, after a 12-h period involving sleep or wake, they attempted target problems structurally related to the source problems but with different surface features. Experiment 2 controlled for time of day effects by testing participants either in the morning or the evening. Sleep improved analogical transfer, but effects were not due to improvements in subjective memory or similarity recognition, but rather effects of structural generalisation across problems. Copyright © 2015 Elsevier B.V. All rights reserved.

Adult height after spontaneous pubertal growth or GnRH analog treatment in girls with early puberty: a meta-analysis.

PubMed

Bertelloni, Silvano; Massart, Francesco; Miccoli, Mario; Baroncelli, Giampiero I

2017-06-01

Early puberty (EP) has been defined as the onset of puberty in the low-normal range; it may be a cause for concern regarding a possible impairment of adult height (AH). This paper meta-analysed data on AH after spontaneous growth or after gonadotropin-releasing hormone (GnRH) analog treatment in girls with EP. A computerized literature search was conducted from 1980 to June 30, 2016. Only published studies in English were considered. Eight papers were selected (483 cases). In untreated girls (n = 300), predicted adult height (PAH) at start of follow-up (-0.559 SDS (95%CI -1.110 to 0.001); P = 0.050) was close to mid-parental height (MPH) (-0.557 SDS (95%CI -0.736 to -0.419); P < 0.0001) and AH (-0.663 SDS (95%CI -0.803 to -0.524); P < 0.0001). In GnRH analog treated girls (n = 183), PAH before the start of treatment was slightly reduced (-0.939 SDS (95%CI -1.401 to -0.477; P < 0.0001) vs MPH (-0.678 SDS (95%CI -0.942 to -0.414); P < 0.0000), but AH (-0.604 SDS (95%CI -0.877 to -0.338); P < 0.0000) was close to MPH. Present meta-analysis indicates that girls with EP spontaneously reach their MPH and that GnRH analog treatment does not widely change growth outcome. Differences among the selected studies for definition of EP, inclusion criteria, treatment duration, age at discontinuation of therapy, definition of AH may affect results. What is Known: • Early puberty represents a main cause of consultation in paediatric endocrinology offices due to concerns of both practitioners and parents. • Treatment with GnRH analogs is sometimes attempted with the aim to improve adult height. What is New: • Untreated and GnRH analog treated girls with early puberty reached similar adult height. • Adult height was consistent with mid-parental height in both untreated and GnRH analog treated girls with early puberty.

Crystal structure of cGMP-dependent protein kinase Iβ cyclic nucleotide-binding-B domain : Rp-cGMPS complex reveals an apo-like, inactive conformation

DOE PAGES

Campbell, James C.; VanSchouwen, Bryan; Lorenz, Robin; ...

2016-12-23

The R-diastereomer of phosphorothioate analogs of cGMP, Rp-cGMPS, is one of few known inhibitors of cGMP-dependent protein kinase I (PKG I); however, its mechanism of inhibition is currently not fully understood. We determined the crystal structure of the PKG Iβ cyclic nucleotide-binding domain (PKG Iβ CNB-B), considered a ‘gatekeeper’ for cGMP activation, bound to Rp-cGMPS at 1.3 Å. Our structural and NMR data show that PKG Iβ CNB-B bound to Rp-cGMPS displays an apo-like structure with its helical domain in an open conformation. Comparison with the cAMP-dependent protein kinase regulatory subunit (PKA RIα) showed that this conformation resembles the catalyticmore » subunit-bound inhibited state of PKA RIα more closely than the apo or Rp-cAMPS-bound conformations. Our results suggest that Rp-cGMPS inhibits PKG I by stabilizing the inactive conformation of CNB-B.« less

Crystal structure of the true Nasicon: Na/sub 3/Zr/sub 2/Si/sub 2/PO/sub 12/

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

Boilot, J.P.; Collin, G.; Colomban, P.

For the first time, the results of single crystal determination of the true Nasicon are given. The structure refinement yielded the following composition: Na/sub 3.09(8)/Zr/sub 2.01(1)/P/sub 0.91/Si/sub 2.09/O/sub 12/. Evidence of the total occupancy of the Zr octahedron is found, displaying that only the Si/P non-stoichiometry mechanism is present in the Nasicon crystal. For the two temperatures which have been investigated (R.T. and 623K), the structures are very close to that of the Nasicon analog: Na/sub 3/Sc/sub 2/P/sub 3/O/sub 12/. However the Si/P substitution prevents the sodium long range ordering even in the monoclinic low temperature phase and therefore themore » cross over to the rhombohedral symmetry only involves very small atomic displacements. For both structures, a new sodium position (mid-Na) is displayed in the conduction channel, intermediate between the usual Na(1) and Na(2) sites.« less

Synthesis, structural characterization and effect on human granulocyte intracellular cAMP levels of abscisic acid analogs.

PubMed

Bellotti, Marta; Salis, Annalisa; Grozio, Alessia; Damonte, Gianluca; Vigliarolo, Tiziana; Galatini, Andrea; Zocchi, Elena; Benatti, Umberto; Millo, Enrico

2015-01-01

The phytohormone abscisic acid (ABA), in addition to regulating physiological functions in plants, is also produced and released by several mammalian cell types, including human granulocytes, where it stimulates innate immune functions via an increase of the intracellular cAMP concentration ([cAMP]i). We synthesized several ABA analogs and evaluated the structure-activity relationship, by the systematical modification of selected regions of these analogs. The resulting molecules were tested for their ability to inhibit the ABA-induced increase of [cAMP]i in human granulocytes. The analogs with modified configurations at C-2' and C-3' abrogated the ABA-induced increase of the [cAMP]i and also inhibited several pro-inflammatory effects induced by exogenous ABA on granulocytes and monocytes. Accordingly, these analogs could be suitable as novel putative anti-inflammatory compounds. Copyright © 2014 Elsevier Ltd. All rights reserved.

Reconfigurable Analog PDE computation for Baseband and RFComputation

DTIC Science & Technology

2017-03-01

waveguiding PDEs. One-dimensional ladder topologies enable linear delays, linear-phase analog filters , as well as analog beamforming, potentially at RF...performance. This discussion focuses on ODE / PDE analog computation available in SoC FPAA structures. One such computation is a ladder filter (Fig...Implementation of a one-dimensional ladder filter for computing inductor (L) and capacitor (C) lines. These components can be implemented in CABs or as

An overview of structure-activity relationship studies of curcumin analogs as antioxidant and anti-inflammatory agents.

PubMed

Arshad, Laiba; Haque, Md Areeful; Abbas Bukhari, Syed Nasir; Jantan, Ibrahim

2017-04-01

Curcumin, extracted mainly from Curcuma longa rhizomes, has been reported to possess potent anti-inflammatory and anti-oxidant activities. Although safe at higher doses and exhibiting multiple biological activities, curcumin still has the problem of poor bioavailability which has been an attractive area of research over the last few years. A number of efforts have been made by modifying structural features of curcumin. This review highlights the structurally modified and more stable newly synthesized curcumin analogs that have been screened against antioxidant and anti-inflammatory activities. Also the structure-activity relationship to gain insight into future guidelines for scheming new compounds has been discussed, and further these analogs being more stable may serve as promising agents for use in different pathological conditions.

Enabling the On-line Intrinsic Evolution of Analog Controllers

NASA Technical Reports Server (NTRS)

Gwaltney, David A.; Ferguson, Michael I.

2005-01-01

The intrinsic evolution of analog controllers to provide closed-loop control of the speed of a DC motor has been previously demonstrated at NASA Marshall Space Flight Center. A side effect of the evolutionary process is that during evolution there are necessarily poor configurations to be evaluated that could cause damage to the plant, This paper concerns the development and implementation of a safe Evolvable Analog Controller (EAC) architecture able to evolve controllers on-line even in the presence of these poor configurations, The EAC concept is discussed and experimental results are presented that show the feasibility of the approach This EAC architecture represents the first in a series of steps required to make deployment of an evolvable controller a reality.

Enabling the On-Line Intrinsic Evolution of Analog Controllers

NASA Technical Reports Server (NTRS)

Gwaltney, David A.; Ferguson, Michael I.

2005-01-01

The intrinsic evolution of analog controllers to provide closed-loop control of the speed of a DC motor has been previously demonstrated at NASA Marshall Space Flight Center. A side fleet of the evolutionary process is that during evolution there are necessarily poor configurations to be evaluated that could cause damage to the plant. This paper concern the development and implementation of a safe Evolvable Analog Controller (EAC) architecture able to evolve controllers on-line even in the presence of these poor configurations. The EAC concept is discussed and experimental results are presented that show the feasibility of the approach This EAC architecture represents the first in a series of steps required to make deployment of an evolvable controller a reality.

Gott time machines in anti-de Sitter space

NASA Astrophysics Data System (ADS)

Holst, Sören

1996-04-01

In 1991 Gott presented a solution of Einstein's field equations in 2+1 dimensions with λ=0 that contained closed timelike curves ( ctc's). This solution was remarkable because at first it did not seem to be unphysical in any other respect. Later, however, it was shown that Gott's solution is tachyonic in a certain sense. Here the case λ<0 is discussed. We show that it is also possible to construct ctc's in this case, in a way analogous to that used by Gott. We also show a special case of this construction to be tachyonic. λ<0 means that we are dealing with anti-de Sitter space, and since the CTC-construction necessitates some understanding of its structure, a few pages are devoted to this subject.

Electric-field effects in the twist-bend nematic phase

NASA Astrophysics Data System (ADS)

Meyer, Claire; Dozov, Ivan; Davidson, Patrick; Luckhurst, Geoffrey R.; Dokli, Irena; Knezevic, Anamarija; Lesac, Andreja

2018-02-01

In the recently discovered Twist-Bend Nematic (NTB) phase, the nematic director is spontaneously distorted and twisted along a conical helix with an extremely short pitch, 10 nm. We have investigated the behavior of the NTB phase subject to an electric-field. We show that, due to the periodic NTB structure, the electro-optic effects are not nematic-like but are close analogs to those in the smectic and cholesteric phases. In particular, we have studied the fast (sub-microsecond) flexoelectrically-induced rotation of the optic axis, which is similar to the electroclinic effect in the SmA* phase and the flexoelectric response of short-pitch cholesterics. We discuss the possible applications of the fast NTB electro-optic effects.

4-amino-1H-benzo[g]quinazoline-2-one: a fluorescent analog of cytosine to probe protonation sites in triplex forming oligonucleotides.

PubMed

Godde, F; Toulmé, J J; Moreau, S

2000-08-01

We developed a new fluorescent analog of cytosine, the 4-amino-1H-benzo[g]quinazoline-2-one, which constitute a probe sensitive to pH. The 2'-O-Me ribonucleoside derivative of this heterocycle was synthesized and exhibited a fluorescence emission centered at 456 nm, characterized by four major excitation maxima (250, 300, 320 and 370 nm) and a fluorescence quantum yield of Phi = 0.62 at pH 7.1. The fluorescence emission maximum shifted from 456 to 492 nm when pH was decreased from 7.1 to 2.1. The pK(a) (4) was close to that of cytosine (4.17). When introduced in triplex forming oligonucleotides this new nucleoside can be used to reveal the protonation state of triplets in triple-stranded structures. Complex formation was detected by a significant quenching of fluorescence emission (approximately 88%) and the N-3 protonation of the quinazoline ring by a shift of the emission maximum from 485 to 465 nm. Using this probe we unambiguously showed that triplex formation of the pyrimidine motif does not require the protonation of all 4-amino-2-one pyrimidine rings.

Methyl phenlactonoates are efficient strigolactone analogs with simple structure

PubMed Central

Jamil, Muhammad; Kountche, Boubacar A; Haider, Imran; Guo, Xiujie; Ntui, Valentine O; Jia, Kun-Peng; Hameed, Umar S; Nakamura, Hidemitsu; Lyu, Ying; Jiang, Kai; Hirabayashi, Kei; Tanokura, Masaru; Arold, Stefan T; Asami, Tadao

2018-01-01

abstract Strigolactones (SLs) are a new class of phytohormones that also act as germination stimulants for root parasitic plants, such as Striga spp., and as branching factors for symbiotic arbuscular mycorrhizal fungi. Sources for natural SLs are very limited. Hence, efficient and simple SL analogs are needed for elucidating SL-related biological processes as well as for agricultural applications. Based on the structure of the non-canonical SL methyl carlactonoate, we developed a new, easy to synthesize series of analogs, termed methyl phenlactonoates (MPs), evaluated their efficacy in exerting different SL functions, and determined their affinity for SL receptors from rice and Striga hermonthica. Most of the MPs showed considerable activity in regulating plant architecture, triggering leaf senescence, and inducing parasitic seed germination. Moreover, some MPs outperformed GR24, a widely used SL analog with a complex structure, in exerting particular SL functions, such as modulating Arabidopsis roots architecture and inhibiting rice tillering. Thus, MPs will help in elucidating the functions of SLs and are promising candidates for agricultural applications. Moreover, MPs demonstrate that slight structural modifications clearly impact the efficiency in exerting particular SL functions, indicating that structural diversity of natural SLs may mirror a functional specificity. PMID:29300919

Analogical-mapping-based comparison tasks as a scaffold for argumentation

NASA Astrophysics Data System (ADS)

Emig, Brandon R.

Given the centrality of the argumentation process to science and consequent importance to science education, inviting science students to engage in argumentation and scaffolding that argumentation in order that it lead to learning and not frustration is important. The present research invites small groups of science content learners (54 preservice elementary teachers at a large research university) to use analogical-mapping-based comparison tasks in service of argumentation to determine which of two possible analogues, in this case simple machines, is most closely related to a third. These activities and associated instruction scaffolded student small-groups' argumentation in four ways: (1) supporting new analogical correspondences on the heels of prior correspondences; (2) discerning definitions and descriptions for simple machine elements; (3) identifying and dealing with ambiguity in potential correspondences; and (4) making reflections on prior analogical correspondences in service of their final arguments. Analogical-mapping-based comparison activities scaffolded student small groups both in their argumentation and in content learning about simple machines. Implications, limitations, and directions for future related research are also discussed.

Structure of the carboxypeptidase B complex with N-sulfamoyl-L-phenylalanine - a transition state analog of non-specific substrate.

PubMed

Akparov, Valery; Timofeev, Vladimir; Khaliullin, Ilyas; Švedas, Vytas; Kuranova, Inna

2018-03-01

Carboxypeptidase B (EC 3.4.17.2) (CPB) is commonly used in the industrial insulin production and as a template for drug design. However, its ability to discriminate substrates with hydrophobic, hydrophilic, and charged side chains is not well understood. We report structure of CPB complex with a transition state analog N-sulfamoyl-L-phenylalanine solved at 1.74Å. The study provided an insight into structural basis of CPB substrate specificity. Ligand binding is affected by structure-depended conformational changes of Asp255 in S1'-subsite, interactions with Asn144 and Arg145 in C-terminal binding subsite, and Glu270 in the catalytic center. Side chain of the non-specific substrate analog SPhe in comparison with that of specific substrate analog SArg (reported earlier) not only loses favorable electrostatic interactions and two hydrogen bonds with Asp255 and three fixed water molecules, but is forced to be in the unfavorable hydrophilic environment. Thus, Ser207, Gly253, Tyr248, and Asp255 residues play major role in the substrate recognition by S1'-subsite.

Chromomycin SA analogs from a marine-derived Streptomyces sp.

PubMed Central

Hu, Youcai; Espindola, Ana Paula D. M; Stewart, Nathan A.; Wei, Shuguang; Posner, Bruce A.; MacMillan, John B.

2011-01-01

Two chromomycin SA analogs, chromomycin SA3 and chromomycin SA2, along with deacetylchromomycin A3 and five previously reported chromomycin analogs were isolated from a marine-derived Streptomyces sp. The structures of the new compounds were determined by spectroscopic methods including 1D and 2D NMR techniques, HRMS and chemical methods. Chromomycin SA3 and chromomycin SA2 are the first naturally occuring chromomycin analogs with truncated side-chains. Biological evaluation of chromomycin analogs for cytotoxicity against two non-small cell lung cancer (NSCLC) cell-lines, A549 and HCC44, demonstrated a decrease in cytotoxicity for the truncated sides chain chromomycin analogs. PMID:21807523

Formation of nanooctahedra in molybdenum disulfide and molybdenum diselenide using pulsed laser vaporization.

PubMed

Parilla, Philip A; Dillon, Anne C; Parkinson, Bruce A; Jones, Kim M; Alleman, Jeff; Riker, Gerald; Ginley, David S; Heben, Michael J

2004-05-20

Pulsed laser vaporization has been used to produce nanooctahedra of MoS2 and MoSe2. The nanooctahedra primarily form in two- or three-layer nested octahedra, although nesting up to five layers has been observed. Tilting the TEM sample stage and mapping how the images of single particles transformed provided the evidence to verify their octahedral geometry. Analysis of 30 two- and three-layered octahedra showed that their outer edge lengths clustered at approximately 3.8 nm and approximately 5.1 nm, respectively. This discreet sizing and the high symmetry of these closed nanooctahedra represent the closest inorganic analogy yet to the carbon fullerenes. The geometrical implications for forming octahedra from these layered compounds are investigated by considering different atomic arrangements assuming either trigonal prismatic or octahedral coordination around the Mo atom and yields two possible configurations for the actual structure of the nanooctahedra. A preliminary survey of pulsed laser vaporization of other layered metal chalcogenides shows that these dichalcogenides differ in their tendency to form small closed layered fullerene-like structures. These materials can be ranked from highest tendency to lowest as follows: NbSe2, WS2, WSe2, SnS2, TaS2, GaS, ReS2, and MoTe2.

Chromogravity explains {open_quotes}strong gravity{close_quotes}

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

Ne`eman, Y.; Sijacki, D.

1993-03-01

In this paper the authors deal with the question of gravitational type interactions in the case of strong interaction phenomena. They present arguments which indicate that it is not necessary to invoke a gravity type interaction into QCD in order to account for observed phenomena. They argue that the gravitational type phenomena discussed in previous work is a manifestation of a class of Feynmann diagrams. These seem to generate an analog to gravity, a J=2 {open_quotes}chromograviton{close_quotes} or {open_quotes}pseudo-graviton{close_quotes} whose action effectively generates Salam`s {open_quotes}Strong Gravity{close_quotes} or {open_quotes}f-gravity{close_quotes}, withthough having to introduce the theory as an additional input.

Centrally acting serotonergic and dopaminergic agents. 1. Synthesis and structure-activity relationships of 2,3,3a,4,5,9b-hexahydro-1H-benz[e]indole derivatives.

PubMed

Lin, C H; Haadsma-Svensson, S R; Lahti, R A; McCall, R B; Piercey, M F; Schreur, P J; Von Voigtlander, P F; Smith, M W; Chidester, C G

1993-04-16

The synthesis and structure-activity relationships (SAR) of 2,3,3a,4,5,9b-hexahydro-1H-benz[e]indole derivatives (3) are described. These compounds are conformationally restricted, angular tricyclic analogs of 2-aminotetralin. The synthesis was achieved in several steps from the corresponding 2-tetralones. The enantiomers of the cis analogs were obtained from either fractional recrystallizations of the diastereomeric salts of di-p-toluoyl-L-(or D)-tartaric acid or an asymmetric synthesis using chiral (R)-alpha-methylbenzylamine. All analogs were evaluated in the in vitro 5-HT1A and D2 binding assays and selected analogs were investigated further in biochemical and behavioral tests. Analogs with 9-methoxy substitution (R1 in 3) showed mixed 5-HT1A agonist and dopamine antagonist activities whereas the corresponding 9-hydroxy analogs displayed selective 5-HT1A agonist activity. The cis analogs were found to be more potent than the corresponding trans analogs and in the cis series, the (3aR)-(-)-enantiomers displayed higher potency. Nitrogen substitution (R2 in 3) with either an n-propyl or an allyl group produced similar activities whereas replacement with a bulky alpha-methylbenzyl group resulted in loss of activity. Analogs without aromatic substitution (R1 = H in 3) still showed good 5-HT1A agonist activity, although less potent than the 9-methoxy series. In this case, the trans analogs possessed equal or higher in vitro 5-HT1A affinity than the corresponding cis analogs. Analogs with either 6-methoxy or 6-hydroxy substitution (R1 in 3) were found to display dopamine antagonist properties. However, only N-allyl analogs showed this activity. In the 6-methoxy-N-allyl series, the cis analog was found to be more potent than the trans analog. Again, between the pair of cis enantiomers, the (3aR)-(-)-enantiomer showed higher potency. Incorporation of an additional methyl group into 9-methoxy cis analogs at C-2 resulted in retention of potent 5-HT1A agonist activity.

Pharmacology of the meglitinide analogs: new treatment options for type 2 diabetes mellitus.

PubMed

Malaisse, Willy J

2003-01-01

The expression meglitinide analogs was introduced in 1995 to cover new molecules proposed as non-sulfonylurea insulinotropic agents and displaying structural analogy with meglitinide, such as repaglinide, nateglinide, and mitiglinide. Meglitinide analogs display, as judged by conformation analysis, a U-shaped configuration similar to that of antihyperglycemic sulfonylureas such as glibenclamide (glyburide) and glimepiride. In rat pancreatic islets incubated in the presence of 7.0 mmol/L D-glucose, repaglinide and mitiglinide demonstrate comparable concentration-response relationships for stimulation of insulin release, with a threshold value < 10 nmol/L and a maximal secretory response at about 10 nmol/L. Several findings indicate that meglitinide analogs provoke the closing of adenosine triphosphate-sensitive potassium channels, with subsequent gating of voltage-sensitive calcium channels. The effects of meglitinide analogs upon the binding of [3H]glibenclamide to islet cells membranes reinforces this concept. At variance, however, with other meglitinide analogs, the ionic and secretory response to repaglinide (10 micromol/L) is not rapidly reversible in perifused rat islets. In experiments conducted in vivo in control and diabetic rats, repaglinide provokes a greater and more rapid increase in plasma insulin concentration and an earlier fall in glycemia than glibenclamide or glimepiride. Onset of effect is also more rapid and duration of effect shorter with nateglinide versus glibenclamide. In clinical studies, single or repeated daily administration of repaglinide increased plasma insulin concentration in a dose-dependent manner, with an incremental peak reached about 2 hours after repaglinide intake. Plasma concentrations of repaglinide are about 5.0 microg/L 2-2.5 hours after oral intake of the drug. Despite the slow reversibility of repaglinide action in vitro, this drug offers advantages over glibenclamide in terms of the possible occurrence of hypoglycemia if a meal is missed. In volunteers receiving a single oral dose of nateglinide (120mg) 10 minutes before a standardized 800 Kcal breakfast, the plasma insulin concentration was higher 5, 10, and 20 minutes after meal intake than when they received a single dose of repaglinide (0.5 or 2.0mg) or placebo 10 minutes before breakfast. Peak plasma concentrations of nateglinide were reached within 2 hours in most volunteers. Peak plasma concentrations of mitiglinide were reached 30 minutes after a single oral dose in a representative volunteer. Mitiglinide significantly suppressed meal-induced elevations in blood glucose concentrations in a study of patients with type 2 diabetes. In conclusion, two obvious differences among these meglitinide analogs should be underlined. First, on a molar basis, nateglinide is somewhat less potent than repaglinide or mitiglinide, as an insulinotropic agent. The maximal secretory responses evoked by these three meglitinide analogs are, however, identical to one another. Secondly, and as already mentioned, the functional effects of nateglinide and mitiglinide are more rapidly reversible than those of repaglinide, for instance in perifused rat islets. The meglitinide analogs offer the advantage over the long-acting antihyperglycemic sulfonylurea glibenclamide of minimizing the risk of undesirable hypoglycemia.

A Better Understanding of Protein Structure and Function by the Synthesis and Incorporation of Selenium- and Tellurium Containing Tryptophan Analogs

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

Helmey, Sherif Samir; Rice, Ambrose Eugene; Hatch, Duane Michael

Unnatural heavy metal-containing amino acid analogs have shown to be very important in the analysis of protein structure, using methods such as X-ray crystallography, mass spectroscopy, and NMR spectroscopy. Synthesis and incorporation of selenium-containing methionine analogs has already been shown in the literature however with some drawbacks due to toxicity to host organisms. Thus synthesis of heavy metal tryptophan analogs should prove to be more effective since the amino acid tryptophan is naturally less abundant in many proteins. For example, bioincorporation of β-seleno[3,2-b]pyrrolyl-L-alanine ([4,5]SeTrp) and β-selenolo[2,3-b]pyrrolyl-L-alanine ([6,7]SeTrp) has been shown in the following proteins without structural or catalytic perturbations: humanmore » annexin V, barstar, and dihydrofolate reductase. The reported synthesis of these Se-containing analogs is currently not efficient for commercial purposes. Thus a more efficient, concise, high-yield synthesis of selenotryptophan, as well as the corresponding, tellurotryptophan, will be necessary for wide spread use of these unnatural amino acid analogs. This research will highlight our progress towards a synthetic route of both [6,7]SeTrp and [6,7]TeTrp, which ultimately will be used to study the effect on the catalytic activity of Lignin Peroxidase (LiP).« less

Strigolactone and karrikin signal perception: receptors, enzymes, or both?

PubMed Central

Janssen, Bart J.; Snowden, Kimberley C.

2012-01-01

The signaling molecules strigolactone (SL) and karrikin are involved in seed germination, development of axillary meristems, senescence of leaves, and interactions with arbuscular mycorrhizal fungi. The signal transduction pathways for both SLs and karrikins require the same F-box protein (MAX2) and closely related α/β hydrolase fold proteins (DAD2 and KAI2). The crystal structure of DAD2 has been solved revealing an α/β hydrolase fold protein with an internal cavity capable of accommodating SLs. DAD2 responds to the SL analog GR24 by changing conformation and binding to MAX2 in a GR24 concentration-dependent manner. DAD2 can also catalyze hydrolysis of GR24. Structure activity relationships of analogs indicate that the butenolide ring common to both SLs and karrikins is essential for biological activity, but the remainder of the molecules can be significantly modified without loss of activity. The combination of data from the study of DAD2, KAI2, and chemical analogs of SLs and karrikins suggests a model for binding that requires nucleophilic attack by the active site serine of the hydrolase at the carbonyl atom of the butenolide ring. A conformational change occurs in the hydrolase that results in interaction with the F-box protein MAX2. Downstream signal transduction is then likely to occur via SCF (Skp-Cullin-F-box) complex-mediated ubiquitination of target proteins and their subsequent degradation. The role of the catalytic activity of the hydrolase is unclear but it may be integral in binding as well as possibly allowing the signal to be cleared from the receptor. The α/β hydrolase fold family consists mostly of active enzymes, with a few notable exceptions. We suggest that DAD2 and KAI2 represent an intermediate stage where some catalytic activity is retained at the same time as a receptor role has evolved. PMID:23293648

Strigolactone and karrikin signal perception: receptors, enzymes, or both?

PubMed

Janssen, Bart J; Snowden, Kimberley C

2012-01-01

The signaling molecules strigolactone (SL) and karrikin are involved in seed germination, development of axillary meristems, senescence of leaves, and interactions with arbuscular mycorrhizal fungi. The signal transduction pathways for both SLs and karrikins require the same F-box protein (MAX2) and closely related α/β hydrolase fold proteins (DAD2 and KAI2). The crystal structure of DAD2 has been solved revealing an α/β hydrolase fold protein with an internal cavity capable of accommodating SLs. DAD2 responds to the SL analog GR24 by changing conformation and binding to MAX2 in a GR24 concentration-dependent manner. DAD2 can also catalyze hydrolysis of GR24. Structure activity relationships of analogs indicate that the butenolide ring common to both SLs and karrikins is essential for biological activity, but the remainder of the molecules can be significantly modified without loss of activity. The combination of data from the study of DAD2, KAI2, and chemical analogs of SLs and karrikins suggests a model for binding that requires nucleophilic attack by the active site serine of the hydrolase at the carbonyl atom of the butenolide ring. A conformational change occurs in the hydrolase that results in interaction with the F-box protein MAX2. Downstream signal transduction is then likely to occur via SCF (Skp-Cullin-F-box) complex-mediated ubiquitination of target proteins and their subsequent degradation. The role of the catalytic activity of the hydrolase is unclear but it may be integral in binding as well as possibly allowing the signal to be cleared from the receptor. The α/β hydrolase fold family consists mostly of active enzymes, with a few notable exceptions. We suggest that DAD2 and KAI2 represent an intermediate stage where some catalytic activity is retained at the same time as a receptor role has evolved.

Molecular moment similarity between several nucleoside analogs of thymidine and thymidine. sil@watson.ibm.com.

PubMed

Silverman, B D; Pitman, M C; Platt, D E

1999-06-01

Molecular moment descriptors of the shape and charge distributions of twenty five nucleoside structures have been examined. The structures include thymidine as well as the difluorotoluene nucleoside analog which has been found to pair efficiently with adenine by polymerase catalysis. The remaining twenty three structures have been chosen to be as structurally similar to thymidine and to the difluorotoluene nucleoside analog as possible. The moment descriptors which include a description of the relationship of molecular charge to shape show the difluorotoluene nucleoside to be one of the most proximate molecules to thymidine in the space of the molecular moments. The calculations, therefore, suggest that polymerase specificity might be not only a consequence of molecular steric features alone but also of the molecular electrostatic environment and its registration with molecular shape.

On the Suitability of Lanthanides as Actinide Analogs

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

Szigethy, Geza; Raymond, Kenneth N.

2008-04-11

With the current level of actinide materials used in civilian power generation and the need for safe and efficient methods for the chemical separation of these species from their daughter products and for long-term storage requirements, a detailed understanding of actinide chemistry is of great importance. Due to the unique bonding properties of the f-elements, the lanthanides are commonly used as structural and chemical models for the actinides, but differences in the bonding between these 4f and 5f elements has become a question of immediate applicability to separations technology. This brief overview of actinide coordination chemistry in the Raymond groupmore » at UC Berkeley/LBNL examines the validity of using lanthanide analogs as structural models for the actinides, with particular attention paid to single crystal X-ray diffraction structures. Although lanthanides are commonly accepted as reasonable analogs for the actinides, these comparisons suggest the careful study of actinide materials independent of their lanthanide analogs to be of utmost importance to present and future efforts in nuclear industries.« less

Bone accumulation of the Tc-99m complex of carbamyl phosphate and its analogs

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

Hosain, P.; Spencer, R.P.; Ahlquist, K.J.

1978-05-01

Carbamyl phosphate, an organic moecule containing a single phosphate group, has been used in the therapy of sickle-cell disease. Carbamyl phosphate bound Tc-99m and achieved bone uptake in mice, rabbits, and a human volunteer. By examination of the structural formula, a working hypothesis was developed that predicted that the Tc-99m complexes of the analogous compounds acetyl phosphate, propionyl phosphate, and butyryl phosphate, each carrying single phosphate and carbonyl groups, would also show bone specificity. This was confirmed experimentally. Phosphonoacetic acid is a structural analog of these compounds. The structural analysis also predicted that aminomethylphosphonic acid and phosphoenolpyruvate would not havemore » as avid bone affinity, and this was also confirmed. These compounds represent a new class of bone-seeking agents that have the common properties of a lone phosphate and a carbonyl function. Such agents may permit the synthesis of additional analogs in an effort to obtain optimal affinity in the Tc-99m complexes.« less

Structure and coherence of reasoning ability in Down Syndrome adults and typically developing children.

PubMed

Natsopoulo, D; Christou, C; Koutselini, M; Raftopoulos, A; Karefillidou, C

2002-01-01

The present study investigates the ability of Down Syndrome (DS) adults to reason: (a) deductively with transitivity (linear and reverse relations) and categorical syllogisms (all-some relations); (b) inductively with classical verbal analogies and non-verbal analogical reasoning (Raven's Coloured Progressive Matrices); and (c) to retain information in short-term memory. The results have shown that: (i) The Down Syndrome adults did not differ from typically developing children, matched on expressive and verbal ability, in transitivity and non-verbal analogical thinking; (ii) they differed in categorical reasoning, classical verbal analogies and short-term memory. Application of a structural model demonstrated that, despite differences in slope means in the three measures, the structure of functioning within-and-across all domains of cognition tests and its growth pattern, equally reliable and coherent, goes in parallel for the Down Syndrome adults and the typically developing children. The results are discussed within the context of the two-group developmental and difference approach.

Towards fully analog hardware reservoir computing for speech recognition

NASA Astrophysics Data System (ADS)

Smerieri, Anteo; Duport, François; Paquot, Yvan; Haelterman, Marc; Schrauwen, Benjamin; Massar, Serge

2012-09-01

Reservoir computing is a very recent, neural network inspired unconventional computation technique, where a recurrent nonlinear system is used in conjunction with a linear readout to perform complex calculations, leveraging its inherent internal dynamics. In this paper we show the operation of an optoelectronic reservoir computer in which both the nonlinear recurrent part and the readout layer are implemented in hardware for a speech recognition application. The performance obtained is close to the one of to state-of-the-art digital reservoirs, while the analog architecture opens the way to ultrafast computation.

Relationship between structure and P-glycoprotein inhibitory activity of dimeric peptides related to the Dmt-Tic pharmacophore.

PubMed

Ambo, Akihiro; Ohkatsu, Hiromichi; Minamizawa, Motoko; Watanabe, Hideko; Sugawara, Shigeki; Nitta, Kazuo; Tsuda, Yuko; Okada, Yoshio; Sasaki, Yusuke

2012-03-15

To develop novel inhibitors of P-glycoprotein (P-gp), dimeric peptides related to an opioid peptide containing the Dmt-Tic pharmacophore were synthesized and their P-gp inhibitory activities were analyzed. Of the 30 analogs synthesized, N(α),N(ε)-[(CH(3))(2)Mle-Tic](2)Lys-NH(2) and its D-Lys analog were found to exhibit potent P-gp inhibitory activity, twice that of verapamil, in doxorubicin-resistant K562 cells. Structure-activity studies indicated that the correct hydrophobicity and spacer length between two aromatic rings are important structural elements in this series of analogs for inhibition of P-gp. Copyright © 2012 Elsevier Ltd. All rights reserved.

Life experience of sixth-grade students in analog domains of sixth-grade science textbooks

NASA Astrophysics Data System (ADS)

Wagamon, Barbara J.

This study was conducted to determine if analog domains in sixth grade science textbooks were common to the life experience of sixth grade students and if experience differed according to moderating variables. The researcher reviewed three sixth grade general science textbooks and selected analogies that were unsupported by extended text, photos, or diagrams. Analogies were limited to ones which were unsupported because the intent was to identify students who were ready by virtue of life experience to confront analogies unaided by contextual clues. The researcher designed the Life Experiences in Analog Domains (LEAD) Questionnaire to survey students in 50 analog domains. Subjects of the study were 331 sixth grade students from an urban school district. Thirty were tested with the instrument one year later. Data on age, gender, ethnicity and income were analyzed for variance. Standardized achievement test scores were correlated to the LEAD Questionnaire. Results revealed sharp contrasts of experience by analog domain. Experience in analog domains was indicated 52% of the time overall. There were significant differences in the experience of students grouped by moderating variables. Younger students reported more experience than older students. The higher income group reported more experience than the lower income group. Caucasian students reported more experience overall than African American students. Chi-square tests revealed that differences in scores by ethnicity were not controlled by income. of three skills, reading comprehension, mathematics, and science, reading comprehension was most closely correlated to questionnaire score. Results suggest that many of the sixth grade students in the study may be without experience in analog domains when they encounter analogies in a textbook. Assuming subsequent implementations of the Questionnaire confirm these results, teachers should survey life experience of students and help them develop experiences that complement their science text. Textbook authors should explain all but the simplest analogies.

A High Pressure Post-Perovskite Phase Transition in NaMgF3--a MgSiO3 Analog Material

NASA Astrophysics Data System (ADS)

Martin, C.; Liu, H.; Crichton, W.; Parise, J. B.

2005-12-01

Since Murakami et al. (2004) identified a perovskite (pv, Pbnm) to post-perovskite (ppv, Cmcm) structural phase transition in MgSiO3, the transition has been reported to occur in many oxides at ultra-high pressures (>60 GPa). The layered ppv structure is rapidly shaping a better understanding of seismic anisotropy in the controversial D" region of the lower mantle. While the ppv unit cell may be derived from indexing of the powder pattern, the structure adopted at high pressure is experimentally ill-constrained due to compromised powder diffraction statistics typically obtained from small sample volumes at extreme conditions in the diamond anvil cell. NaMgF3, a structural analog material to MgSiO3 pv, exhibits a large compressibility and presents the possibility of reducing the pv-ppv transition pressure, allowing for improved powder statistics from a larger sample volume. In accordance with our previous theoretical and experimental evidence (Liu et al., 2005; Parise et al., 2004), we have observed a phase transition in NaMgF3 during two recent independent high pressure trials utilizing monochromatic x-ray diffraction and in-situ laser heating in the diamond anvil cell at pressures as low as 30 GPa. From our analysis thus far, we have found the unit cell of the high pressure phase cannot be indexed according to pv (Pbnm) or close permutations of ppv (Cmcm) unit cells predicted for NaMgF3 or unit cells observed for ppv MgSiO3 and MgGeO3. In addition, we have precluded a breakdown to high pressure phases of NaF and MgF3 as an explanation for the observed data. Upon pressure release, we observe diffraction peaks from the high pressure phase in the absence of pv NaMgF3, suggesting the high pressure structure is quenchable to ambient conditions. The results of the work in progress will be presented at the meeting.

The Creative Power of Formal Analogies in Physics: The Case of Albert Einstein

ERIC Educational Resources Information Center

Gingras, Yves

2015-01-01

In order to show how formal analogies between different physical systems play an important conceptual work in physics, this paper analyzes the evolution of Einstein's thoughts on the structure of radiation from the point of view of the formal analogies he used as "lenses" to "see" through the "black box" of Planck's…

Comparing Explicit Exemplar-Based and Rule-Based Corrective Feedback: Introducing Analogy-Based Corrective Feedback

ERIC Educational Resources Information Center

Thomas, Kavita E.

2018-01-01

This study introduces an approach to providing corrective feedback to L2 learners termed analogy-based corrective feedback that is motivated by analogical learning theories and syntactic alignment in dialogue. Learners are presented with a structurally similar synonymous version of their output where the erroneous form is corrected, and they must…

The Development of Analogy Making in Children: Cognitive Load and Executive Functions

ERIC Educational Resources Information Center

Thibaut, Jean-Pierre; French, Robert; Vezneva, Milena

2010-01-01

The aim of the current study was to investigate the performance of 6-, 8-, and 14-year-olds on an analogy-making task involving analogies in which there are competing perceptual and relational matches. We hypothesized that the selection of the common relational structure requires the inhibition of other salient features, in particular, perceptual…

Terrestrial analogs of the hellespontus dunes, Mars

USGS Publications Warehouse

Breed, C.S.

1977-01-01

Geomorphic features in the Hellespontus region, Mars, were compared with dunes of the crescentic ridge type in numerous terrestrial sand seas quantitatively by dimensional analysis of dune lengths, widths, and wavelengths. Mean values for the Hellespontus dunes are close to mean values derived from measurements of all sampled terrestrial sand seas. Terrestrial analogs of form and areal distribution of the Hellespontus dunes are shown by comparison of scale ratios derived from the measurements. Dunes of similar form occur in South West Africa, in Pakistan, in the southeastern Arabian peninsula, in the Sahara, in eastern USSR and northern China, and in western North America. Terrestrial analogs closest to form and areal distribution of the Hellespontus dunes are in the Kara Kum Desert, Turkmen SSR, and in the Ala Shan (Gobi) Desert, China. ?? 1977.

Chimeric analogs of human β-defensin 1 and θ-defensin disrupt pre-established bacterial biofilms.

PubMed

Mathew, Basil; Olli, Sudar; Guru, Ankeeta; Nagaraj, Ramakrishanan

2017-08-01

Antibiofilm activity of several human defensin analogs that have the ability to kill planktonic bacteria, against pre-established biofilms of Escherichia coli MG1655 and Staphylococcus aureus NCTC 8530 were examined. Linear and linear fatty acylated analogs did not show any activity while disulfide constrained analogs disrupted pre-established S. aureus biofilms. Chimeric analogs of human β-defensin 1 and θ-defensin, hBTD-1 and [d]hBTD-1 were highly active against S. aureus biofilms. Among the analogs tested, only the d-enantiomer [d]hBTD-1 showed activity against E. coli biofilm. Our study provides insights into the structural requirements for the eradication of pre-established biofilms in defensin analogs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Digitally balanced detection for optical tomography.

PubMed

Hafiz, Rehan; Ozanyan, Krikor B

2007-10-01

Analog balanced Photodetection has found extensive usage for sensing of a weak absorption signal buried in laser intensity noise. This paper proposes schemes for compact, affordable, and flexible digital implementation of the already established analog balanced detection, as part of a multichannel digital tomography system. Variants of digitally balanced detection (DBD) schemes, suitable for weak signals on a largely varying background or weakly varying envelopes of high frequency carrier waves, are introduced analytically and elaborated in terms of algorithmic and hardware flow. The DBD algorithms are implemented on a low-cost general purpose reconfigurable hardware (field-programmable gate array), utilizing less than half of its resources. The performance of the DBD schemes compare favorably with their analog counterpart: A common mode rejection ratio of 50 dB was observed over a bandwidth of 300 kHz, limited mainly by the host digital hardware. The close relationship between the DBD outputs and those of known analog balancing circuits is discussed in principle and shown experimentally in the example case of propane gas detection.

Sensing Methods for Detecting Analog Television Signals

NASA Astrophysics Data System (ADS)

Rahman, Mohammad Azizur; Song, Chunyi; Harada, Hiroshi

This paper introduces a unified method of spectrum sensing for all existing analog television (TV) signals including NTSC, PAL and SECAM. We propose a correlation based method (CBM) with a single reference signal for sensing any analog TV signals. In addition we also propose an improved energy detection method. The CBM approach has been implemented in a hardware prototype specially designed for participating in Singapore TV white space (WS) test trial conducted by Infocomm Development Authority (IDA) of the Singapore government. Analytical and simulation results of the CBM method will be presented in the paper, as well as hardware testing results for sensing various analog TV signals. Both AWGN and fading channels will be considered. It is shown that the theoretical results closely match with those from simulations. Sensing performance of the hardware prototype will also be presented in fading environment by using a fading simulator. We present performance of the proposed techniques in terms of probability of false alarm, probability of detection, sensing time etc. We also present a comparative study of the various techniques.

The Brandeis Dice Problem and Statistical Mechanics

NASA Astrophysics Data System (ADS)

van Enk, Steven J.

2014-11-01

Jaynes invented the Brandeis Dice Problem as a simple illustration of the MaxEnt (Maximum Entropy) procedure that he had demonstrated to work so well in Statistical Mechanics. I construct here two alternative solutions to his toy problem. One, like Jaynes' solution, uses MaxEnt and yields an analog of the canonical ensemble, but at a different level of description. The other uses Bayesian updating and yields an analog of the micro-canonical ensemble. Both, unlike Jaynes' solution, yield error bars, whose operational merits I discuss. These two alternative solutions are not equivalent for the original Brandeis Dice Problem, but become so in what must, therefore, count as the analog of the thermodynamic limit, M-sided dice with M → ∞. Whereas the mathematical analogies between the dice problem and Stat Mech are quite close, there are physical properties that the former lacks but that are crucial to the workings of the latter. Stat Mech is more than just MaxEnt.

Structure-function studies with the unique hexameric form II ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) from Rhodopseudomonas palustris.

PubMed

Satagopan, Sriram; Chan, Sum; Perry, L Jeanne; Tabita, F Robert

2014-08-01

The first x-ray crystal structure has been solved for an activated transition-state analog-bound form II ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). This enzyme, from Rhodopseudomonas palustris, assembles as a unique hexamer with three pairs of catalytic large subunit homodimers around a central 3-fold symmetry axis. This oligomer arrangement is unique among all known Rubisco structures, including the form II homolog from Rhodospirillum rubrum. The presence of a transition-state analog in the active site locked the activated enzyme in a "closed" conformation and revealed the positions of critical active site residues during catalysis. Functional roles of two form II-specific residues (Ile(165) and Met(331)) near the active site were examined via site-directed mutagenesis. Substitutions at these residues affect function but not the ability of the enzyme to assemble. Random mutagenesis and suppressor selection in a Rubisco deletion strain of Rhodobacter capsulatus identified a residue in the amino terminus of one subunit (Ala(47)) that compensated for a negative change near the active site of a neighboring subunit. In addition, substitution of the native carboxyl-terminal sequence with the last few dissimilar residues from the related R. rubrum homolog increased the enzyme's kcat for carboxylation. However, replacement of a longer carboxyl-terminal sequence with termini from either a form III or a form I enzyme, which varied both in length and sequence, resulted in complete loss of function. From these studies, it is evident that a number of subtle interactions near the active site and the carboxyl terminus account for functional differences between the different forms of Rubiscos found in nature. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Purification, structural characterization, and myotropic activity of a peptide related to des-Arg(9)-bradykinin from an elasmobranch fish, the little skate, Leucoraja erinacea.

PubMed

Anderson, W Gary; Leprince, Jérôme; Conlon, J Michael

2008-08-01

A bradykinin (BK)-related peptide was isolated from heat-denaturated plasma from an elasmobranch fish, the little skate, Leucoraja erinacea after incubation with porcine pancreatic kallikrein. The primary structure of the peptide (H-Gly-Ile-Thr-Ser-Trp-Leu-Pro-Phe-OH; skate BK) shows limited structural similarity to the mammalian B1 receptor agonist, des-Arg(9)-BK. The myotropic activities of synthetic skate BK, and the analog skate [Arg(9)]BK, were examined in isolated skate vascular and intestinal smooth muscle preparations. Skate BK produced a concentration-dependent constriction of the mesenteric artery (EC(50)=4.37x10(-8)M; maximum response=103.4+/-10.23% of the response to 60mM KCl) but the response to skate [Arg(9)]BK was appreciably weaker (response to 10(-6)M=73.0+/-23.4% of the response to 60mM KCl). Neither the first branchial gill arch nor the ventral aorta responded to either purified peptide. Skate BK also produced a concentration-dependent constriction of intestinal smooth muscle preparations (EC(50)=2.74x10(-7)M; maximum response 31.0+/-12.2% of the response to 10(-5)M acetylcholine). Skate [Arg(9)]BK was without effect on the intestinal preparation. The data provide evidence for the existence of the kallikrein-kinin system in a phylogenetically ancient vertebrate group and the greater potency of skate BK compared with the analog skate [Arg(9)]BK suggests that the receptor mediating vascular responses resembles the mammalian B1 receptor more closely than the B2 receptor.

Closed Loop Experiment Manager (CLEM)-An Open and Inexpensive Solution for Multichannel Electrophysiological Recordings and Closed Loop Experiments.

PubMed

Hazan, Hananel; Ziv, Noam E

2017-01-01

There is growing need for multichannel electrophysiological systems that record from and interact with neuronal systems in near real-time. Such systems are needed, for example, for closed loop, multichannel electrophysiological/optogenetic experimentation in vivo and in a variety of other neuronal preparations, or for developing and testing neuro-prosthetic devices, to name a few. Furthermore, there is a need for such systems to be inexpensive, reliable, user friendly, easy to set-up, open and expandable, and possess long life cycles in face of rapidly changing computing environments. Finally, they should provide powerful, yet reasonably easy to implement facilities for developing closed-loop protocols for interacting with neuronal systems. Here, we survey commercial and open source systems that address these needs to varying degrees. We then present our own solution, which we refer to as Closed Loop Experiments Manager (CLEM). CLEM is an open source, soft real-time, Microsoft Windows desktop application that is based on a single generic personal computer (PC) and an inexpensive, general-purpose data acquisition board. CLEM provides a fully functional, user-friendly graphical interface, possesses facilities for recording, presenting and logging electrophysiological data from up to 64 analog channels, and facilities for controlling external devices, such as stimulators, through digital and analog interfaces. Importantly, it includes facilities for running closed-loop protocols written in any programming language that can generate dynamic link libraries (DLLs). We describe the application, its architecture and facilities. We then demonstrate, using networks of cortical neurons growing on multielectrode arrays (MEA) that despite its reliance on generic hardware, its performance is appropriate for flexible, closed-loop experimentation at the neuronal network level.

Closed Loop Experiment Manager (CLEM)—An Open and Inexpensive Solution for Multichannel Electrophysiological Recordings and Closed Loop Experiments

PubMed Central

Hazan, Hananel; Ziv, Noam E.

2017-01-01

There is growing need for multichannel electrophysiological systems that record from and interact with neuronal systems in near real-time. Such systems are needed, for example, for closed loop, multichannel electrophysiological/optogenetic experimentation in vivo and in a variety of other neuronal preparations, or for developing and testing neuro-prosthetic devices, to name a few. Furthermore, there is a need for such systems to be inexpensive, reliable, user friendly, easy to set-up, open and expandable, and possess long life cycles in face of rapidly changing computing environments. Finally, they should provide powerful, yet reasonably easy to implement facilities for developing closed-loop protocols for interacting with neuronal systems. Here, we survey commercial and open source systems that address these needs to varying degrees. We then present our own solution, which we refer to as Closed Loop Experiments Manager (CLEM). CLEM is an open source, soft real-time, Microsoft Windows desktop application that is based on a single generic personal computer (PC) and an inexpensive, general-purpose data acquisition board. CLEM provides a fully functional, user-friendly graphical interface, possesses facilities for recording, presenting and logging electrophysiological data from up to 64 analog channels, and facilities for controlling external devices, such as stimulators, through digital and analog interfaces. Importantly, it includes facilities for running closed-loop protocols written in any programming language that can generate dynamic link libraries (DLLs). We describe the application, its architecture and facilities. We then demonstrate, using networks of cortical neurons growing on multielectrode arrays (MEA) that despite its reliance on generic hardware, its performance is appropriate for flexible, closed-loop experimentation at the neuronal network level. PMID:29093659

UV IRRADIATION OF AROMATIC NITROGEN HETEROCYCLES IN INTERSTELLAR ICE ANALOGS

NASA Technical Reports Server (NTRS)

Elsila, J. E.; Bernstein, M. P.; Sanford, S. A.

2005-01-01

Here, we present information on the properties of the ANH quinoline frozen in interstellar water-ice analogs. Quinoline is a two-ring compound structurally analogous to the PAH naphthalene. In this work, binary mixtures of water and quinoline were frozen to create interstellar ice analogs, which were then subjected to ultraviolet photolysis. We will present the infrared spectra of the resulting ices at various temperatures, as well as chromatographic analysis of the residues remaining upon warm-up of these ices to room temperature.

Programing Procedures Manual (PPM).

DTIC Science & Technology

1981-12-15

terms ’reel’, ’unit’, and ’volume’ are synonymous and completely interchangeable in the CLOSE statement. Treatment of sequential mass storage files is...logically equivalent to the treatment of a file on tape or analogous sequential media. * For the purpose of showing the effect of various types of CLOSE...Overlay Area CA6 Address of Abend Relative to beginning of overlay segment The programer can now refer to the compile source listing for the overlay

Design of an Active Ultrastable Single-chain Insulin Analog

PubMed Central

Hua, Qing-xin; Nakagawa, Satoe H.; Jia, Wenhua; Huang, Kun; Phillips, Nelson B.; Hu, Shi-quan; Weiss, Michael A.

2008-01-01

Single-chain insulin (SCI) analogs provide insight into the inter-relation of hormone structure, function, and dynamics. Although compatible with wild-type structure, short connecting segments (<3 residues) prevent induced fit upon receptor binding and so are essentially without biological activity. Substantial but incomplete activity can be regained with increasing linker length. Here, we describe the design, structure, and function of a single-chain insulin analog (SCI-57) containing a 6-residue linker (GGGPRR). Native receptor-binding affinity (130 ± 8% relative to the wild type) is achieved as hindrance by the linker is offset by favorable substitutions in the insulin moiety. The thermodynamic stability of SCI-57 is markedly increased (ΔΔGu = 0.7 ± 0.1 kcal/mol relative to the corresponding two-chain analog and 1.9 ± 0.1 kcal/mol relative to wild-type insulin). Analysis of inter-residue nuclear Overhauser effects demonstrates that a native-like fold is maintained in solution. Surprisingly, the glycine-rich connecting segment folds against the insulin moiety: its central Pro contacts ValA3 at the edge of the hydrophobic core, whereas the final Arg extends the A1-A8 α-helix. Comparison between SCI-57 and its parent two-chain analog reveals striking enhancement of multiple native-like nuclear Overhauser effects within the tethered protein. These contacts are consistent with wild-type crystal structures but are ordinarily attenuated in NMR spectra of two-chain analogs, presumably due to conformational fluctuations. Linker-specific damping of fluctuations provides evidence for the intrinsic flexibility of an insulin monomer. In addition to their biophysical interest, ultrastable SCIs may enhance the safety and efficacy of insulin replacement therapy in the developing world. PMID:18332129

Microcomputer data acquisition and control.

PubMed

East, T D

1986-01-01

In medicine and biology there are many tasks that involve routine well defined procedures. These tasks are ideal candidates for computerized data acquisition and control. As the performance of microcomputers rapidly increases and cost continues to go down the temptation to automate the laboratory becomes great. To the novice computer user the choices of hardware and software are overwhelming and sadly most of the computer sales persons are not at all familiar with real-time applications. If you want to bill your patients you have hundreds of packaged systems to choose from; however, if you want to do real-time data acquisition the choices are very limited and confusing. The purpose of this chapter is to provide the novice computer user with the basics needed to set up a real-time data acquisition system with the common microcomputers. This chapter will cover the following issues necessary to establish a real time data acquisition and control system: Analysis of the research problem: Definition of the problem; Description of data and sampling requirements; Cost/benefit analysis. Choice of Microcomputer hardware and software: Choice of microprocessor and bus structure; Choice of operating system; Choice of layered software. Digital Data Acquisition: Parallel Data Transmission; Serial Data Transmission; Hardware and software available. Analog Data Acquisition: Description of amplitude and frequency characteristics of the input signals; Sampling theorem; Specification of the analog to digital converter; Hardware and software available; Interface to the microcomputer. Microcomputer Control: Analog output; Digital output; Closed-Loop Control. Microcomputer data acquisition and control in the 21st Century--What is in the future? High speed digital medical equipment networks; Medical decision making and artificial intelligence.

Integrability in conformally coupled gravity: Taub-NUT spacetimes and rotating black holes

NASA Astrophysics Data System (ADS)

Bardoux, Yannis; Caldarelli, Marco M.; Charmousis, Christos

2014-05-01

We consider four dimensional stationary and axially symmetric spacetimes for conformally coupled scalar-tensor theories. We show that, in analogy to the Lewis-Papapetrou problem in General Relativity (GR), the theory at hand can be recast in an analogous integrable form. We give the relevant rod formalism, introduced by Weyl for vacuum GR, explicitly giving the rod structure of the black hole of Bocharova et al. and Bekenstein (BBMB), in complete analogy to the Schwarzschild solution. The additional scalar field is shown to play the role of an extra Weyl potential. We then employ the Ernst method as a concrete solution generating example to obtain the Taub-NUT version of the BBMB hairy black hole. The solution is easily extended to include a cosmological constant. We show that the anti-de Sitter hyperbolic version of this solution is free of closed timelike curves that plague usual Taub-NUT metrics, and thus consists of a rotating, asymptotically locally anti-de Sitter black hole. This stationary solution has no curvature singularities whatsoever in the conformal frame, and the NUT charge is shown here to regularize the central curvature singularity of the corresponding static black hole. Given our findings we discuss the anti-de Sitter hyperbolic version of Taub-NUT in four dimensions, and show that the curvature singularity of the NUT-less solution is now replaced by a neighbouring chronological singularity screened by horizons. We argue that the properties of this rotating black hole are very similar to those of the rotating BTZ black hole in three dimensions.

p-brane actions and higher Roytenberg brackets

NASA Astrophysics Data System (ADS)

Jurčo, Branislav; Schupp, Peter; Vysoký, Jan

2013-02-01

Motivated by the quest to understand the analog of non-geometric flux compactification in the context of M-theory, we study higher dimensional analogs of generalized Poisson sigma models and corresponding dual string and p-brane models. We find that higher generalizations of the algebraic structures due to Dorfman, Roytenberg and Courant play an important role and establish their relation to Nambu-Poisson structures.

Morphology, structure, and metal binding mechanisms of biogenic manganese oxides in a superfund site treatment system.

PubMed

Duckworth, O W; Rivera, N A; Gardner, T G; Andrews, M Y; Santelli, C M; Polizzotto, M L

2017-01-25

Manganese oxides, which may be biogenically produced in both pristine and contaminated environments, have a large affinity for many trace metals. In this study, water and Mn oxide-bearing biofilm samples were collected from the components of a pump and treat remediation system at a superfund site. To better understand the factors leading to their formation and their effects on potentially toxic metal fate, we conducted a chemical, microscopic, and spectroscopic characterization of these biofilm samples. Scanning electron microscopy revealed the presence of Mn oxides in close association with biological structures with morphologies consistent with fungi. X-ray absorption spectroscopy (XAS) and X-ray diffraction (XRD) revealed the oxides to be a mixture of layer and tunnel structure Mn(iv) oxides. In addition, XAS suggested that Ba, Co, and Zn all primarily bind to oxides in the biofilm in a manner that is analogous to synthetic or laboratory grown bacteriogenic Mn oxides. The results indicate that Mn oxides produced by organisms in the system may effectively scavenge metals, thus highlighting the potential utility of these organisms in designed remediation systems.

Plate tectonics of virus shell assembly and reorganization in phage φ8, a distant relative of mammalian reoviruses.

PubMed

El Omari, Kamel; Sutton, Geoff; Ravantti, Janne J; Zhang, Hanwen; Walter, Thomas S; Grimes, Jonathan M; Bamford, Dennis H; Stuart, David I; Mancini, Erika J

2013-08-06

The hallmark of a virus is its capsid, which harbors the viral genome and is formed from protein subunits, which assemble following precise geometric rules. dsRNA viruses use an unusual protein multiplicity (120 copies) to form their closed capsids. We have determined the atomic structure of the capsid protein (P1) from the dsRNA cystovirus Φ8. In the crystal P1 forms pentamers, very similar in shape to facets of empty procapsids, suggesting an unexpected assembly pathway that proceeds via a pentameric intermediate. Unlike the elongated proteins used by dsRNA mammalian reoviruses, P1 has a compact trapezoid-like shape and a distinct arrangement in the shell, with two near-identical conformers in nonequivalent structural environments. Nevertheless, structural similarity with the analogous protein from the mammalian viruses suggests a common ancestor. The unusual shape of the molecule may facilitate dramatic capsid expansion during phage maturation, allowing P1 to switch interaction interfaces to provide capsid plasticity. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Geometric Patterns for Neighboring Bases Near the Stacked State in Nucleic Acid Strands.

PubMed

Sedova, Ada; Banavali, Nilesh K

2017-03-14

Structural variation in base stacking has been analyzed frequently in isolated double helical contexts for nucleic acids, but not as often in nonhelical geometries or in complex biomolecular environments. In this study, conformations of two neighboring bases near their stacked state in any environment are comprehensively characterized for single-strand dinucleotide (SSD) nucleic acid crystal structure conformations. An ensemble clustering method is used to identify a reduced set of representative stacking geometries based on pairwise distances between select atoms in consecutive bases, with multiple separable conformational clusters obtained for categories divided by nucleic acid type (DNA/RNA), SSD sequence, stacking face orientation, and the presence or absence of a protein environment. For both DNA and RNA, SSD conformations are observed that are either close to the A-form, or close to the B-form, or intermediate between the two forms, or further away from either form, illustrating the local structural heterogeneity near the stacked state. Among this large variety of distinct conformations, several common stacking patterns are observed between DNA and RNA, and between nucleic acids in isolation or in complex with proteins, suggesting that these might be stable stacking orientations. Noncanonical face/face orientations of the two bases are also observed for neighboring bases in the same strand, but their frequency is much lower, with multiple SSD sequences across categories showing no occurrences of such unusual stacked conformations. The resulting reduced set of stacking geometries is directly useful for stacking-energy comparisons between empirical force fields, prediction of plausible localized variations in single-strand structures near their canonical states, and identification of analogous stacking patterns in newly solved nucleic acid containing structures.

[Billroth and Brahms: personal encounter of medicine and music].

PubMed

Hadaschik, B A; Hadaschik, E N; Hohenfellner, M

2012-02-01

Theodor Billroth and Johannes Brahms shared a decades long personal friendship. The music-loving Billroth influenced the work of the famous composer and in turn Brahms also left traces within Billroth's lifetime achievements. To shed light on the close relationship of medicine and music, this manuscript describes both Billroth's life and surgical career as they were influenced and stimulated by his close friendship to Brahms.Theodor Billroth and Johannes Brahms first met in 1865 in Zurich, Switzerland. After Billroth accepted the chair of surgery at the University of Vienna in 1867, Brahms moved to Vienna in 1869. During the following years, Billroth analyzed most of Brahms' compositions prior to publication. Similar to his effective way of teaching medical students and assistants, Billroth stimulated Brahms to publish many of his later compositions. Brahms on the other hand supported Billroth in writing his essay"Who is musical?". Furthermore, music helped Billroth to cope with the demanding working life of a surgeon.Music and surgery share both structural and emotional analogies. While both professions require meticulous techniques, personal interaction is a prerequisite for success. "Science and art scoop from the same well."

A Highly Linear and Wide Input Range Four-Quadrant CMOS Analog Multiplier Using Active Feedback

NASA Astrophysics Data System (ADS)

Huang, Zhangcai; Jiang, Minglu; Inoue, Yasuaki

Analog multipliers are one of the most important building blocks in analog signal processing circuits. The performance with high linearity and wide input range is usually required for analog four-quadrant multipliers in most applications. Therefore, a highly linear and wide input range four-quadrant CMOS analog multiplier using active feedback is proposed in this paper. Firstly, a novel configuration of four-quadrant multiplier cell is presented. Its input dynamic range and linearity are improved significantly by adding two resistors compared with the conventional structure. Then based on the proposed multiplier cell configuration, a four-quadrant CMOS analog multiplier with active feedback technique is implemented by two operational amplifiers. Because of both the proposed multiplier cell and active feedback technique, the proposed multiplier achieves a much wider input range with higher linearity than conventional structures. The proposed multiplier was fabricated by a 0.6µm CMOS process. Experimental results show that the input range of the proposed multiplier can be up to 5.6Vpp with 0.159% linearity error on VX and 4.8Vpp with 0.51% linearity error on VY for ±2.5V power supply voltages, respectively.

Design, synthesis and structure-activity relationship of indoxacarb analogs as voltage-gated sodium channel blocker.

PubMed

Hao, Wenbo; Fu, Chunling; Yu, Huijuan; Chen, Jian; Xu, Hanhong; Shao, Guang; Jiang, Dingxin

2015-10-15

Indoxacarb, the first commercialized pyrazoline-type sodium-channel blocker, is a commonly used insecticide because of high selectivity. To discover sodium-channel blocker with high insecticidal activity, a series of novel indoxacarb analogs were designed and synthesized by judicious structural modifications of the substituent group of C5, C6 in indenone and C'4 in benzene ring. Some analogs exhibited significant insecticidal activities against Spodoptera litura F. and excellent BgNav1-1a channel inhibitory activity. The structure-activity analysis indicated that the presence of strong electron-withdrawing group and decreased steric hindrance of indenone ring (R(1), R(2)) in 5- and 6-position could enhance larvicidal activity and BgNav1-1a channel inhibitory activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

High Resolution Features from Low Affinity Interactions: Photoactive Analogs of the Haloether Anesthetics

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

Xi,J.; Liu, R.; Rossi, M.

2006-01-01

The difficulty in obtaining binding target and site information for low-affinity drugs, like the inhaled anesthetics, has limited identification of their molecular effectors. Because such information can be provided by photoactive analogues, we designed, synthesized, and characterized a novel diazirnyl haloether that closely mimics isoflurane, the most widely used clinical general anesthetic. This compound, H-diaziflurane, is a nontoxic, potent anesthetic that potentiates GABA-gated ion channels in primary cultures of hippocampal neurons. Calorimetric and structural characterizations show that H-diaziflurane binds a model anesthetic host protein with similar energetics as isoflurane and forms photoadducts with residues lining the isoflurane binding site. H-diazifluranemore » will be immediately useful for identifying targets and sites important for the molecular pharmacology of the inhaled haloether anesthetics.« less

Ligand-linked phase changes in a biological system: applications to sickle cell hemoglobin.

PubMed Central

Wyman, J; Gill, S J

1980-01-01

Polyphasic linkage is a close analog of the allosteric and polysteric linkages shown by many biological macromolecules. Like them, it gives rise to both homotropic and heterotropic effects. It is governed by a group of linkage potentials applicable to each separate phase and also, subject to certain conditions, by a group of lower order applicable to the whole system, globally. A good example of polyphasic linkage is provided by sickle cell hemoglobin which, under suitable conditions and subject to control by oxygen, precipitates out of solution to form what appear to be microtubules. This is but one instance of the way in which macromolecular assembly and the formation of subcellular structures generally can be regulated by various small molecules acting as ligands. PMID:6933555

Teamwork in high-risk environments analogous to space

NASA Technical Reports Server (NTRS)

Kanki, Barbara G.

1990-01-01

Mountaineering expeditions combine a number of factors which make them potentially good analogs to the planetary exploration facet of long-duration space missions. A study of mountain climbing teams was conducted in order to evaluate the usefulness of the environment as a space analog and to specifically identify the factors and issues surrounding teamwork and 'successful' team performance in two mountaineering environments. This paper focuses on social/organizational factors, including team size and structure, leadership styles and authority structure which were found in the sample of 22 climb teams (122 individuals). The second major issue discussed is the construction of a valid performance measure in this high-risk environment.

Modeling and control design of a wind tunnel model support

NASA Technical Reports Server (NTRS)

Howe, David A.

1990-01-01

The 12-Foot Pressure Wind Tunnel at Ames Research Center is being restored. A major part of the restoration is the complete redesign of the aircraft model supports and their associated control systems. An accurate trajectory control servo system capable of positioning a model (with no measurable overshoot) is needed. Extremely small errors in scaled-model pitch angle can increase airline fuel costs for the final aircraft configuration by millions of dollars. In order to make a mechanism sufficiently accurate in pitch, a detailed structural and control-system model must be created and then simulated on a digital computer. The model must contain linear representations of the mechanical system, including masses, springs, and damping in order to determine system modes. Electrical components, both analog and digital, linear and nonlinear must also be simulated. The model of the entire closed-loop system must then be tuned to control the modes of the flexible model-support structure. The development of a system model, the control modal analysis, and the control-system design are discussed.

Comparison of natural and nonnative two-species communities of Anolis lizards.

PubMed

Poe, Steven

2014-07-01

Human-mediated colonizations present an informative model system for understanding assembly of organismal communities. However, it is unclear whether communities including naturalized species are accurate analogs of natural communities or unique combinations not present in nature. I compared morphology and phylogenetic structure of natural and naturalized two-species communities of Anolis lizards. Natural communities are phylogenetically clustered, whereas naturalized communities show no significant phylogenetic structure. This result likely reflects differences in colonization pools for these communities-that is, invasion from anywhere for naturalized communities but from proximal and thus phylogenetically close lineages in natural communities. Both natural and naturalized communities each include pairs of species that are significantly similar to each other in morphology, and both sets of communities are composed of species that possess traits of good colonizers. These similarities suggest that the formation of natural and naturalized communities may be at least partially governed by similar processes. Human-mediated invasions may be credibly viewed as modern incarnations of natural colonizations in this case.

Structure of the skeletal muscle calcium release channel activated with Ca2+ and AMP-PCP.

PubMed Central

Serysheva, I I; Schatz, M; van Heel, M; Chiu, W; Hamilton, S L

1999-01-01

The functional state of the skeletal muscle Ca2+ release channel is modulated by a number of endogenous molecules during excitation-contraction. Using electron cryomicroscopy and angular reconstitution techniques, we determined the three-dimensional (3D) structure of the skeletal muscle Ca2+ release channel activated by a nonhydrolyzable analog of ATP in the presence of Ca2+. These ligands together produce almost maximum activation of the channel and drive the channel population toward a predominately open state. The resulting 30-A 3D reconstruction reveals long-range conformational changes in the cytoplasmic region that might affect the interaction of the Ca2+ release channel with the t-tubule voltage sensor. In addition, a central opening and mass movements, detected in the transmembrane domain of both the Ca(2+)- and the Ca2+/nucleotide-activated channels, suggest a mechanism for channel opening similar to opening-closing of the iris in a camera diaphragm. PMID:10512814

Structure-activity relationship of indoloquinoline analogs anti-MRSA.

PubMed

Zhao, Min; Kamada, Tomonori; Takeuchi, Aya; Nishioka, Hiromi; Kuroda, Teruo; Takeuchi, Yasuo

2015-12-01

Indolo[3,2-b]quinoline analogs (3a-3s), 4-(acridin-9-ylamino) phenol hydrochloride (4), benzofuro[3,2-b]quinoline (3t), indeno[1,2-b]quinolines (3u and 3v) have been synthesized. Those compounds were found to exhibit anti-bacterial activity towards Methicillin-resistant Staphylococcus aureus (anti-MRSA activity). Structure-activity relationship studies were conducted that indoloquinoline ring, benzofuroquinoline ring and 4-aminophenol group are essential structure for anti-MRSA activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Syntheses and anti-MRSA activities of the C3 analogs of mansonone F, a potent anti-bacterial sesquiterpenoid: insights into its structural requirements for anti-MRSA activity.

PubMed

Shin, Dong-Yun; Kim, Sun Nam; Chae, Jung-Hyun; Hyun, Soon-Sil; Seo, Seung-Yong; Lee, Yong-Sil; Lee, Kwang-Ok; Kim, Seok-Ho; Lee, Yun-Sang; Jeong, Jae Min; Choi, Nam-Song; Suh, Young-Ger

2004-09-06

Syntheses and excellent anti-MRSA activities of the mansonone F analogs are reported. In addition, the minimal structural requirements for its anti-MRSA activities as well as its structure-activity relationship including the C3 substituents effects on anti-MRSA activity are also described. In particular, this study revealed that both ortho-quinone and tricyclic systems of mansonone F are essential for anti-MRSA activities.

The 3D Structure of the Binding Pocket of the Human Oxytocin Receptor for Benzoxazine Antagonists, Determined by Molecular Docking, Scoring Functions and 3D-QSAR Methods

NASA Astrophysics Data System (ADS)

Jójárt, Balázs; Martinek, Tamás A.; Márki, Árpád

2005-05-01

Molecular docking and 3D-QSAR studies were performed to determine the binding mode for a series of benzoxazine oxytocin antagonists taken from the literature. Structural hypotheses were generated by docking the most active molecule to the rigid receptor by means of AutoDock 3.05. The cluster analysis yielded seven possible binding conformations. These structures were refined by using constrained simulated annealing, and the further ligands were aligned in the refined receptor by molecular docking. A good correlation was found between the estimated Δ G bind and the p K i values for complex F. The Connolly-surface analysis, CoMFA and CoMSIA models q CoMFA 2 = 0.653, q CoMSA 2 = 0.630 and r pred,CoMFA 2 = 0.852 , r pred,CoMSIA 2 = 0.815) confirmed the scoring function results. The structural features of the receptor-ligand complex and the CoMFA and CoMSIA fields are in closely connected. These results suggest that receptor-ligand complex F is the most likely binding hypothesis for the studied benzoxazine analogs.

Comparative Structural Models of Similarities and Differences between "Vehicle" and "Target" in Order to Teach Darwinian "Evolution"

ERIC Educational Resources Information Center

Marcelos, Maria Fatima; Nagem, Ronaldo L.

2010-01-01

Our objective is to contribute to the teaching of Classical Darwinian "Evolution" by means of a study of analogies and metaphors. Throughout the history of knowledge about "Evolution" and in Science teaching, tree structures have been used an analogs to refer to "Evolution," such as by Darwin in the "Tree of Life" passage contained in "On The…

On the suitability of lanthanides as actinide analogs

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

Raymond, Kenneth; Szigethy, Geza

2008-07-01

With the current level of actinide materials used in civilian power generation and the need for safe and efficient methods for the chemical separation of these species from their daughter products and for long-term storage requirements, a detailed understanding of actinide chemistry is of great importance. Due to the unique bonding properties of the f-elements, the lanthanides are commonly used as structural and chemical models for the actinides, but differences in the bonding between these 4f and 5f elements has become a question of immediate applicability to separations technology. This brief overview of actinide coordination chemistry in the Raymond groupmore » at UC Berkeley/LBNL examines the validity of using lanthanide analogs as structural models for the actinides, with particular attention paid to single crystal X-ray diffraction structures. Although lanthanides are commonly accepted as reasonable analogs for the actinides, these comparisons suggest the careful study of actinide materials independent of their lanthanide analogs to be of utmost importance to present and future efforts in nuclear industries. (authors)« less

Seeking instructional specificity: An example from analogical instruction

NASA Astrophysics Data System (ADS)

Kuo, Eric; Wieman, Carl E.

2015-12-01

Broad instructional methods like "interactive engagement" have been shown to be effective, but such general characterization provides little guidance on the details of how to structure instructional materials. In this study, we seek instructional specificity by comparing two ways of using an analogy to learn a target physical principle: (i) applying the analogy to the target physical domain on a case-by-case basis and (ii) using the analogy to create a general rule in the target physical domain. In the discussion sections of a large, introductory physics course (N =2 3 1 ), students who sought a general rule were better able to discover and apply a correct physics principle than students who analyzed the examples case by case. The difference persisted at a reduced level after subsequent direct instruction. We argue that students who performed case-by-case analyses were more likely to focus on idiosyncratic problem-specific features rather than the deep structural features. This study provides an example of investigations into how the specific structure of instructional materials can be consequential for what is learned.

Implementation of structure-mapping inference by event-file binding and action planning: a model of tool-improvisation analogies.

PubMed

Fields, Chris

2011-03-01

Structure-mapping inferences are generally regarded as dependent upon relational concepts that are understood and expressible in language by subjects capable of analogical reasoning. However, tool-improvisation inferences are executed by members of a variety of non-human primate and other species. Tool improvisation requires correctly inferring the motion and force-transfer affordances of an object; hence tool improvisation requires structure mapping driven by relational properties. Observational and experimental evidence can be interpreted to indicate that structure-mapping analogies in tool improvisation are implemented by multi-step manipulation of event files by binding and action-planning mechanisms that act in a language-independent manner. A functional model of language-independent event-file manipulations that implement structure mapping in the tool-improvisation domain is developed. This model provides a mechanism by which motion and force representations commonly employed in tool-improvisation structure mappings may be sufficiently reinforced to be available to inwardly directed attention and hence conceptualization. Predictions and potential experimental tests of this model are outlined.

pH-induced conformational changes in human ABO(H) blood group glycosyltransferases confirm the importance of electrostatic interactions in the formation of the semi-closed state.

PubMed

Johal, Asha R; Blackler, Ryan J; Alfaro, Javier A; Schuman, Brock; Borisova, Svetlana; Evans, Stephen V

2014-03-01

The homologous human ABO(H) A and B blood group glycosyltransferases GTA and GTB have two mobile polypeptide loops surrounding their active sites that serve to allow substrate access and product egress and to recognize and sequester substrates for catalysis. Previous studies have established that these enzymes can move from the "open" state to the "semi-closed" then "closed" states in response to addition of a substrate. The contribution of electrostatic interactions to these conformational changes has now been demonstrated by the determination at various pH of the structures of GTA, GTB and the chimeric enzyme ABBA. At near-neutral pH, GTA displays the closed state in which both mobile loops order around the active site, whereas ABBA and GTB display the open state. At low pH, the apparent protonation of the DXD motif in GTA leads to the expulsion of the donor analog to yield the open state, whereas at high pH, both ABBA and GTB form the semi-closed state in which the first mobile loop becomes an ordered α-helix. Step-wise deprotonation of GTB in increments of 0.5 between pH 6.5 and 10.0 shows that helix ordering is gradual, which indicates that the formation of the semi-closed state is dependent on electrostatic forces consistent with the binding of substrate. Spectropolarimetric studies of the corresponding stand-alone peptide in solution reveal no tendency toward helix formation from pH 7.0 to 10.0, which shows that pH-dependent stability is a product of the larger protein environment and underlines the importance of substrate in active site ordering.

Purely cubic action for string field theory

NASA Technical Reports Server (NTRS)

Horowitz, G. T.; Lykken, J.; Rohm, R.; Strominger, A.

1986-01-01

It is shown that Witten's (1986) open-bosonic-string field-theory action and a closed-string analog can be written as a purely cubic interaction term. The conventional form of the action arises by expansion around particular solutions of the classical equations of motion. The explicit background dependence of the conventional action via the Becchi-Rouet-Stora-Tyutin operator is eliminated in the cubic formulation. A closed-form expression is found for the full nonlinear gauge-transformation law.

Analog simulation of flux-summing servo-model, phases 1 and 2

NASA Technical Reports Server (NTRS)

Hriber, E. J.

1984-01-01

The analog simulation was developed for a closed-loop system having an electrohydraulic flux-summing servo valve and actuator with associated inertial load. One-fourth of the system's total forward gain is carried by each of four channels. The present study successfully applied failure mode management techniques to the problem of channel failure. Digital logic circuitry was developed to maintain the overall forward gain of the system at a constant value, in the presence of channel failure. Finally, the stability of the system was verified, and performance characteristics were determined through the use of frequency response methods.

Digital controller design: Analysis of the annular suspension pointing system. [analog controllers with feedback

NASA Technical Reports Server (NTRS)

Kuo, B. C.

1978-01-01

The analog controllers of the annular suspension pointing system are designed for control of the chi, phi sub 1, and phi sub 2 bandwidth dynamics through decoupling and pole placement. Since it is virtually impossible to find an equivalent bandwidth of the overall system and establish a general eigenvalue requirement for the system, the subsystem dynamics are decoupled through state feedback and the poles are placed simultaneously to realize the desired bandwidths for the three system components. Decoupling and pole placement are also used to design the closed-loop digital system through approximation.

Flow Glottogram Characteristics and Perceived Degree of Phonatory Pressedness.

PubMed

Millgård, Moa; Fors, Tobias; Sundberg, Johan

2016-05-01

Phonatory pressedness is a clinically relevant aspect of voice, which generally is analyzed by auditory perception. The present investigation aimed at identifying voice source and formant characteristics related to experts' ratings of phonatory pressedness. Experimental study of the relations between visual analog scale ratings of phonatory pressedness and voice source parameters in healthy voices. Audio, electroglottogram, and subglottal pressure, estimated from oral pressure during /p/ occlusion, were recorded from five female and six male subjects, each of whom deliberately varied phonation type between neutral, flow, and pressed in the syllable /pae/, produced at three loudness levels and three pitches. Speech-language pathologists rated, along a visual analog scale, the degree of perceived phonatory pressedness in these samples. The samples were analyzed by means of inverse filtering with regard to closed quotient, dominance of the voice source fundamental, normalized amplitude quotient, peak-to-peak flow amplitude, as well as formant frequencies and the alpha ratio of spectrum energy above and below 1000 Hz. The results were compared with the rating data, which showed that the ratings were closely related to voice source parameters. Approximately, 70% of the variance of the ratings could be explained by the voice source parameters. A multiple linear regression analysis suggested that perceived phonatory pressedness is related most closely to subglottal pressure, closed quotient, and the two lowest formants. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Structural modelling and comparative analysis of homologous, analogous and specific proteins from Trypanosoma cruzi versus Homo sapiens: putative drug targets for chagas' disease treatment

PubMed Central

2010-01-01

Background Trypanosoma cruzi is the etiological agent of Chagas' disease, an endemic infection that causes thousands of deaths every year in Latin America. Therapeutic options remain inefficient, demanding the search for new drugs and/or new molecular targets. Such efforts can focus on proteins that are specific to the parasite, but analogous enzymes and enzymes with a three-dimensional (3D) structure sufficiently different from the corresponding host proteins may represent equally interesting targets. In order to find these targets we used the workflows MHOLline and AnEnΠ obtaining 3D models from homologous, analogous and specific proteins of Trypanosoma cruzi versus Homo sapiens. Results We applied genome wide comparative modelling techniques to obtain 3D models for 3,286 predicted proteins of T. cruzi. In combination with comparative genome analysis to Homo sapiens, we were able to identify a subset of 397 enzyme sequences, of which 356 are homologous, 3 analogous and 38 specific to the parasite. Conclusions In this work, we present a set of 397 enzyme models of T. cruzi that can constitute potential structure-based drug targets to be investigated for the development of new strategies to fight Chagas' disease. The strategies presented here support the concept of structural analysis in conjunction with protein functional analysis as an interesting computational methodology to detect potential targets for structure-based rational drug design. For example, 2,4-dienoyl-CoA reductase (EC 1.3.1.34) and triacylglycerol lipase (EC 3.1.1.3), classified as analogous proteins in relation to H. sapiens enzymes, were identified as new potential molecular targets. PMID:21034488

Structural modelling and comparative analysis of homologous, analogous and specific proteins from Trypanosoma cruzi versus Homo sapiens: putative drug targets for chagas' disease treatment.

PubMed

Capriles, Priscila V S Z; Guimarães, Ana C R; Otto, Thomas D; Miranda, Antonio B; Dardenne, Laurent E; Degrave, Wim M

2010-10-29

Trypanosoma cruzi is the etiological agent of Chagas' disease, an endemic infection that causes thousands of deaths every year in Latin America. Therapeutic options remain inefficient, demanding the search for new drugs and/or new molecular targets. Such efforts can focus on proteins that are specific to the parasite, but analogous enzymes and enzymes with a three-dimensional (3D) structure sufficiently different from the corresponding host proteins may represent equally interesting targets. In order to find these targets we used the workflows MHOLline and AnEnΠ obtaining 3D models from homologous, analogous and specific proteins of Trypanosoma cruzi versus Homo sapiens. We applied genome wide comparative modelling techniques to obtain 3D models for 3,286 predicted proteins of T. cruzi. In combination with comparative genome analysis to Homo sapiens, we were able to identify a subset of 397 enzyme sequences, of which 356 are homologous, 3 analogous and 38 specific to the parasite. In this work, we present a set of 397 enzyme models of T. cruzi that can constitute potential structure-based drug targets to be investigated for the development of new strategies to fight Chagas' disease. The strategies presented here support the concept of structural analysis in conjunction with protein functional analysis as an interesting computational methodology to detect potential targets for structure-based rational drug design. For example, 2,4-dienoyl-CoA reductase (EC 1.3.1.34) and triacylglycerol lipase (EC 3.1.1.3), classified as analogous proteins in relation to H. sapiens enzymes, were identified as new potential molecular targets.

Design and characterization of α-melanotropin peptide analogs cyclized through rhenium and technetium metal coordination

PubMed Central

Giblin, Michael F.; Wang, Nannan; Hoffman, Timothy J.; Jurisson, Silvia S.; Quinn, Thomas P.

1998-01-01

α-Melanocyte stimulating hormone (α-MSH) analogs, cyclized through site-specific rhenium (Re) and technetium (Tc) metal coordination, were structurally characterized and analyzed for their abilities to bind α-MSH receptors present on melanoma cells and in tumor-bearing mice. Results from receptor-binding assays conducted with B16 F1 murine melanoma cells indicated that receptor-binding affinity was reduced to approximately 1% of its original levels after Re incorporation into the cyclic Cys4,10, d-Phe7–α-MSH4-13 analog. Structural analysis of the Re–peptide complex showed that the disulfide bond of the original peptide was replaced by thiolate–metal–thiolate cyclization. A comparison of the metal-bound and metal-free structures indicated that metal complexation dramatically altered the structure of the receptor-binding core sequence. Redesign of the metal binding site resulted in a second-generation Re–peptide complex (ReCCMSH) that displayed a receptor-binding affinity of 2.9 nM, 25-fold higher than the initial Re–α-MSH analog. Characterization of the second-generation Re–peptide complex indicated that the peptide was still cyclized through Re coordination, but the structure of the receptor-binding sequence was no longer constrained. The corresponding 99mTc- and 188ReCCMSH complexes were synthesized and shown to be stable in phosphate-buffered saline and to challenges from diethylenetriaminepentaacetic acid (DTPA) and free cysteine. In vivo, the 99mTcCCMSH complex exhibited significant tumor uptake and retention and was effective in imaging melanoma in a murine-tumor model system. Cyclization of α-MSH analogs via 99mTc and 188Re yields chemically stable and biologically active molecules with potential melanoma-imaging and therapeutic properties. PMID:9788997

So Close to a Deal: Spatial-Distance Cues Influence Economic Decision-Making in a Social Context.

PubMed

Fatfouta, Ramzi; Schulreich, Stefan; Meshi, Dar; Heekeren, Hauke

2015-01-01

Social distance (i.e., the degree of closeness to another person) affects the way humans perceive and respond to fairness during financial negotiations. Feeling close to someone enhances the acceptance of monetary offers. Here, we explored whether this effect also extends to the spatial domain. Specifically, using an iterated version of the Ultimatum Game in a within-subject design, we investigated whether different visual spatial distance-cues result in different rates of acceptance of otherwise identical monetary offers. Study 1 found that participants accepted significantly more offers when they were cued with spatial closeness than when they were cued with spatial distance. Study 2 replicated this effect using identical procedures but different spatial-distance cues in an independent sample. Importantly, our results could not be explained by feelings of social closeness. Our results demonstrate that mere perceptions of spatial closeness produce analogous-but independent-effects to those of social closeness.

Single halo SDODEL n-MOSFET: an alternative low-cost pseudo-SOI with better analog performance

NASA Astrophysics Data System (ADS)

Sarkar, Partha; Mallik, Abhijit; Sarkar, Chandan Kumar

2009-03-01

In this paper, with the help of extensive TCAD simulations, we investigate the analog performance of source/drain on depletion layer (SDODEL) MOSFETs with a single-halo (SH) implant near the source side of the channel. We use the SH implant in such a structure for the first time. The analog performance parameters in SH SDODEL MOSFETs are compared to those in SH MOSFETs as well as in SH SOI MOSFETs. In addition to reduced junction capacitance for the SH SDODEL structure as compared to that in bulk SH devices, it has been shown that such devices lead to improved performance and lower power dissipation for sub-100 nm CMOS technologies. Our results show that, in SH SDODEL MOSFETs, there is significant improvement in the intrinsic device performance for analog applications (such as device gain, gm/ID, etc) for the sub-100 nm technologies.

Variations in the GLA gene correlate with globotriaosylceramide and globotriaosylsphingosine analog levels in urine and plasma

PubMed Central

Ferreira, Susana; Auray-Blais, Christiane; Boutin, Michel; Lavoie, Pamela; Nunes, José Pedro; Martins, Elisabete; Garman, Scott; Oliveira, João Paulo

2016-01-01

Recent data have shown that lyso-Gb3, the deacylated derivative of globotriaosylceramide (Gb3), is possibly involved in the pathogenesis of Fabry disease (FD) and might be a clinically useful biomarker of its metabolic load. To test this hypothesis, we assayed Gb3 and lyso-Gb3 and related analogs in plasma and/or urine samples of 12 clinically well-characterized subjects carrying several different GLA variant alleles associated with a wide range of residual α-galactosidase A activities. Urinary Gb3 was measured by HPLC–MS/MS; plasma and urinary lyso-Gb3 and related analogs were measured by UPLC–MS/MS. Individual profiles of Gb3 and lyso-Gb3 and related analogs closely correlated with the phenotypic data for each subject, discerning the classical FD patient from the two patients carrying cardiac variants as well as these from all the others without FD. The lyso-Gb3 analog at m/z 836 was found at increased levels only in patients manifesting clinically severe heart disease, irrespective of the pathogenicity of the GLA variant they carried. This finding suggests that this lyso-Gb3 analog might be an earlier biomarker of progressive heart disease, non-specific of the FD cardiomyopathy. The possibility that urinary Gb3 is a specific marker of kidney involvement in FD deserves further study. PMID:26070511

Synthesis and Live-Cell Imaging of Fluorescent Sterols for Analysis of Intracellular Cholesterol Transport.

PubMed

Modzel, Maciej; Lund, Frederik W; Wüstner, Daniel

2017-01-01

Cellular cholesterol homeostasis relies on precise control of the sterol content of organelle membranes. Obtaining insight into cholesterol trafficking pathways and kinetics by live-cell imaging relies on two conditions. First, one needs to develop suitable analogs that resemble cholesterol as closely as possible with respect to their biophysical and biochemical properties. Second, the cholesterol analogs should have good fluorescence properties. This interferes, however, often with the first requirement, such that the imaging instrumentation must be optimized to collect photons from suboptimal fluorophores, but good cholesterol mimics, such as the intrinsically fluorescent sterols, cholestatrienol (CTL) or dehydroergosterol (DHE). CTL differs from cholesterol only in having two additional double bonds in the ring system, which is why it is slightly fluorescent in the ultraviolet (UV). In the first part of this protocol, we describe how to synthesize and image CTL in living cells relative to caveolin, a structural component of caveolae. In the second part, we explain in detail how to perform time-lapse experiments of commercially available BODIPY-tagged cholesterol (TopFluor-cholesterol ® ; TF-Chol) in comparison to DHE. Finally, using two-photon time-lapse imaging data of TF-Chol, we demonstrate how to use our imaging toolbox SpatTrack for tracking sterol rich vesicles in living cells over time.

Promoting interdomain analogical transfer: When creating a problem helps to solve a problem.

PubMed

Minervino, Ricardo A; Olguín, Valeria; Trench, Máximo

2017-02-01

Research on analogical thinking has devised several ways of promoting an abstract encoding of base analogs, thus rendering them more retrievable during later encounters with similar situations lacking surface similarities. Recent studies have begun to explore ways of facilitating transfer at retrieval time, which could facilitate the retrieval of distant analogs learned within contexts that were not specially directed to emphasize their abstract structure. Such studies demonstrate that comparing a target problem to an analogous problem helps students retrieve base analogs that lack surface similarities. To devise more portable ways of enhancing analogical transfer, Experiment 1 replicated Kurtz and Loewenstein's (Memory & Cognition, 35, 334-341, 2007) target-comparison procedure with an additional condition in which participants compared the target to a nonanalogous problem before attempting to reach its solution. Although comparing two analogous targets outperformed the standard transfer condition in promoting analogical transfer, comparing nonanalogous problems did not yield a transfer advantage. Based on prior studies that showed that the activity of creating analogous problems during their initial encoding elicits a more abstract representation of base analogs, in Experiment 2 we assessed whether constructing a second analogous target problem at retrieval time helps participants retrieve superficially dissimilar base analogs. As predicted, target invention increased the retrieval of distant sources. In both experiments we found an association between the quality of the generated schemas and the probability of retrieving a distant base analog from memory.

Microwave-assisted synthesis of water-soluble, fluorescent gold nanoclusters capped with small organic molecules and a revealing fluorescence and X-ray absorption study

NASA Astrophysics Data System (ADS)

Helmbrecht, C.; Lützenkirchen-Hecht, D.; Frank, W.

2015-03-01

Colourless solutions of blue light-emitting, water-soluble gold nanoclusters (AuNC) were synthesized from gold colloids under microwave irradiation using small organic molecules as ligands. Stabilized by 1,3,5-triaza-7-phosphaadamantane (TPA) or l-glutamine (GLU), fluorescence quantum yields up to 5% were obtained. AuNC are considered to be very promising for biological labelling, optoelectronic devices and light-emitting materials but the structure-property relationships have still not been fully clarified. To expand the knowledge about the AuNC apart from their fluorescent properties they were studied by X-ray absorption spectroscopy elucidating the oxidation state of the nanoclusters' gold atoms. Based on curve fitting of the XANES spectra in comparison to several gold references, optically transparent fluorescent AuNC are predicted to be ligand-stabilized Au5+ species. Additionally, their near edge structure compared with analogous results of polynuclear clusters known from the literature discloses an increasing intensity of the feature close to the absorption edge with decreasing cluster size. As a result, a linear relationship between the cluster size and the X-ray absorption coefficient can be established for the first time.Colourless solutions of blue light-emitting, water-soluble gold nanoclusters (AuNC) were synthesized from gold colloids under microwave irradiation using small organic molecules as ligands. Stabilized by 1,3,5-triaza-7-phosphaadamantane (TPA) or l-glutamine (GLU), fluorescence quantum yields up to 5% were obtained. AuNC are considered to be very promising for biological labelling, optoelectronic devices and light-emitting materials but the structure-property relationships have still not been fully clarified. To expand the knowledge about the AuNC apart from their fluorescent properties they were studied by X-ray absorption spectroscopy elucidating the oxidation state of the nanoclusters' gold atoms. Based on curve fitting of the XANES spectra in comparison to several gold references, optically transparent fluorescent AuNC are predicted to be ligand-stabilized Au5+ species. Additionally, their near edge structure compared with analogous results of polynuclear clusters known from the literature discloses an increasing intensity of the feature close to the absorption edge with decreasing cluster size. As a result, a linear relationship between the cluster size and the X-ray absorption coefficient can be established for the first time. Electronic supplementary information (ESI) available: The deconvoluted reference spectra are given in ESI Fig. 1-9. See DOI: 10.1039/c4nr07051h

Microbial succession in an inflated lunar/Mars analog habitat during a 30-day human occupation.

PubMed

Mayer, Teresa; Blachowicz, Adriana; Probst, Alexander J; Vaishampayan, Parag; Checinska, Aleksandra; Swarmer, Tiffany; de Leon, Pablo; Venkateswaran, Kasthuri

2016-06-02

For potential future human missions to the Moon or Mars and sustained presence in the International Space Station, a safe enclosed habitat environment for astronauts is required. Potential microbial contamination of closed habitats presents a risk for crewmembers due to reduced human immune response during long-term confinement. To make future habitat designs safer for crewmembers, lessons learned from characterizing analogous habitats is very critical. One of the key issues is that how human presence influences the accumulation of microorganisms in the closed habitat. Molecular technologies, along with traditional microbiological methods, were utilized to catalog microbial succession during a 30-day human occupation of a simulated inflatable lunar/Mars habitat. Surface samples were collected at different time points to capture the complete spectrum of viable and potential opportunistic pathogenic bacterial population. Traditional cultivation, propidium monoazide (PMA)-quantitative polymerase chain reaction (qPCR), and adenosine triphosphate (ATP) assays were employed to estimate the cultivable, viable, and metabolically active microbial population, respectively. Next-generation sequencing was used to elucidate the microbial dynamics and community profiles at different locations of the habitat during varying time points. Statistical analyses confirm that occupation time has a strong influence on bacterial community profiles. The Day 0 samples (before human occupation) have a very different microbial diversity compared to the later three time points. Members of Proteobacteria (esp. Oxalobacteraceae and Caulobacteraceae) and Firmicutes (esp. Bacillaceae) were most abundant before human occupation (Day 0), while other members of Firmicutes (Clostridiales) and Actinobacteria (esp. Corynebacteriaceae) were abundant during the 30-day occupation. Treatment of samples with PMA (a DNA-intercalating dye for selective detection of viable microbial population) had a significant effect on the microbial diversity compared to non-PMA-treated samples. Statistical analyses revealed a significant difference in community structure of samples over time, particularly of the bacteriomes existing before human occupation of the habitat (Day 0 sampling) and after occupation (Day 13, Day 20, and Day 30 samplings). Actinobacteria (mainly Corynebacteriaceae) and Firmicutes (mainly Clostridiales Incertae Sedis XI and Staphylococcaceae) were shown to increase over the occupation time period. The results of this study revealed a strong relationship between human presence and succession of microbial diversity in a closed habitat. Consequently, it is necessary to develop methods and tools for effective maintenance of a closed system to enable safe human habitation in enclosed environments on Earth and beyond.

Structural transformations of carbon and boron nitride nanoscrolls at high impact collisions.

PubMed

Woellner, C F; Machado, L D; Autreto, P A S; de Sousa, J M; Galvao, D S

2018-02-14

The behavior of nanostructures under high strain-rate conditions has been the object of theoretical and experimental investigations in recent years. For instance, it has been shown that carbon and boron nitride nanotubes can be unzipped into nanoribbons at high-velocity impacts. However, the response of many nanostructures to high strain-rate conditions is still unknown. In this work, we have investigated the mechanical behavior of carbon (CNS) and boron nitride nanoscrolls (BNS) colliding against solid targets at high velocities, using fully atomistic reactive (ReaxFF) molecular dynamics (MD) simulations. CNS (BNS) are graphene (boron nitride) membranes rolled up into papyrus-like structures. Their open-ended topology leads to unique properties not found in their close-ended analogs, such as nanotubes. Our results show that collision products are mainly determined by impact velocities and by two orientation angles, which define the position of the scroll (i) axis and (ii) open edge relative to the target. Our MD results showed that for appropriate velocities and orientations, large-scale deformations and nanoscroll fractures could occur. We also observed unscrolling (scrolls going back to quasi-planar membranes), scroll unzipping into nanoribbons, and significant reconstruction due to breaking and/or formation of new chemical bonds. For particular edge orientations and velocities, conversion from open to close-ended topology is also possible, due to the fusion of nanoscroll walls.

Selenophene transition metal complexes

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

White, Carter James

1994-07-27

This research shows that selenophene transition metal complexes have a chemistry that is similar to their thiophene analogs. Selenophene coordination has been demonstrated and confirmed by molecular structure in both the η 5- and the η 1(Se)-coordination modes. The reaction chemistry of selenophene complexes closely resembles that of the analogous thiophene complexes. One major difference, however, is that selenophene is a better donor ligand than thiophene making the selenophene complexes more stable than the corresponding thiophene complexes. The 77Se NMR chemical shift values for selenophene complexes fall within distinct regions primarily depending on the coordination mode of the selenophene ligand.more » In the final paper, the C-H bond activation of η 1(S)-bound thiophenes, η 1(S)-benzothiophene and η 1(Se)-bound selenophenes has been demonstrated. The deprotonation and rearrangement of the η 1(E)-bound ligand to the carbon bound L-yl complex readily occurs in the presence of base. Reprotonation with a strong acid gives a carbene complex that is unreactive towards nucleophilic attack at the carbene carbon and is stable towards exposure to air. The molecular structure of [Cp(NO)(PPh 3)Re(2-benzothioenylcarbene)]O 3SCF 3 was determined and contains a Re-C bond with substantial double bond character. Methyl substitution for the thienylcarbene or selenylcarbene gives a carbene that rearranges thermally to give back the η 1(E)-bound complex. Based on these model reactions, a new mechanism for the H/D exchange of thiophene over the hydrodesulfurization catalyst has been proposed.« less

Hybrid recursive active filters for duplexing in RF transmitter front-ends

NASA Astrophysics Data System (ADS)

Gottardo, Giuseppe; Donati, Giovanni; Musolff, Christian; Fischer, Georg; Felgentreff, Tilman

2016-08-01

Duplex filters in modern base transceiver stations shape the channel in order to perform common frequency division duplex operations. Usually, they are designed as cavity filters, which are expensive and have large dimensions. Thanks to the emerging digital technology and fast digital converters, it is possible to transfer the efforts of designing analog duplex filters into digital numeric algorithms applied to feedback structures, operating on power. This solution provides the shaping of the signal spectrum directly at the output of the radio frequency (RF) power amplifiers (PAs) relaxing the transmitter design especially in the duplexer and in the antenna sections. The design of a digital baseband feedback applied to the analog power RF amplifiers (hybrid filter) is presented and verified by measurements. A model to describe the hybrid system is investigated, and the relation between phase and resonance peaks of the resulting periodic band-pass transfer function is described. The stability condition of the system is analyzed using Nyquist criterion. A solution involving a number of digital feedback and forward branches is investigated defining the parameters of the recursive structure. This solution allows the closed loop system to show a periodic band pass with up to 500 kHz bandwidth at the output of the RF amplifier. The band-pass magnitude reaches up to 17 dB selectivity. The rejection of the PA noise in the out-of-band frequencies is verified by measurements. The filter is tested with a modulated LTE (Long Term Evolution) signal showing an ACPR (Adjacent Channel Power Ratio) enhancement of 10 dB of the transmitted signal.

An analog silicon retina with multichip configuration.

PubMed

Kameda, Seiji; Yagi, Tetsuya

2006-01-01

The neuromorphic silicon retina is a novel analog very large scale integrated circuit that emulates the structure and the function of the retinal neuronal circuit. We fabricated a neuromorphic silicon retina, in which sample/hold circuits were embedded to generate fluctuation-suppressed outputs in the previous study [1]. The applications of this silicon retina, however, are limited because of a low spatial resolution and computational variability. In this paper, we have fabricated a multichip silicon retina in which the functional network circuits are divided into two chips: the photoreceptor network chip (P chip) and the horizontal cell network chip (H chip). The output images of the P chip are transferred to the H chip with analog voltages through the line-parallel transfer bus. The sample/hold circuits embedded in the P and H chips compensate for the pattern noise generated on the circuits, including the analog communication pathway. Using the multichip silicon retina together with an off-chip differential amplifier, spatial filtering of the image with an odd- and an even-symmetric orientation selective receptive fields was carried out in real time. The analog data transfer method in the present multichip silicon retina is useful to design analog neuromorphic multichip systems that mimic the hierarchical structure of neuronal networks in the visual system.

Exploring the binding mechanisms of diaminopimelic acid analogs to meso-diaminopimelate dehydrogenase by molecular modeling.

PubMed

Wang, Huiqun; Kellogg, Glen E; Xu, Ping; Zhang, Yan

2018-06-02

Meso-Diaminopimelic acid (meso-2,6-diamino-heptanedioic acid, DAP) is an important component of the cell wall of many bacteria. Meso-diaminopimelate dehydrogenase (m-Ddh) is a critical enzyme in the process of converting tetrahydrodipicolinate to DAP. Here, we are proposing that DAP analogs targeting m-Ddh may be considered as potential antibiotics. Four DAP analogs without significant structural change from DAP have been obtained and their inhibitory potencies against m-Ddh from the P. gingivalis strain W83 show significant differences from that of DAP. However, their inhibitory mechanisms as for how simple structural change influences the inhibitory potency remain unknown. Therefore, we employed molecular modeling methods to obtain insight into the inhibitory mechanisms of DAP and analogs with m-Ddh. The predicted binding mode of DAP was highly consistent with the experimental structural data and disclosed the important roles played by the binding pocket residues. According to our predictions, the isoxazoline ring of compounds 1 and 2 and the double bonds in compounds 3 and 4 had distinct influences on these compounds' binding to m-Ddh. This enriched understanding of the inhibitory mechanisms of DAP and these four analogs to m-Ddh has provided new and relevant information for future rational development of potent inhibitors targeting m-Ddh. Copyright © 2018. Published by Elsevier Inc.

Phosphoryl transfer reaction snapshots in crystals: Insights into the mechanism of protein kinase a catalytic subunit

DOE PAGES

Das, Amit; Gerlits, Oksana O.; Heller, William T.; ...

2015-06-19

To study the catalytic mechanism of phosphorylation catalyzed by cAMP-dependent protein kinase (PKA) a structure of the enzyme-substrate complex representing the Michaelis complex is of specific interest as it can shed light on the structure of the transition state. However, all previous crystal structures of the Michaelis complex mimics of the PKA catalytic subunit (PKAc) were obtained with either peptide inhibitors or ATP analogs. Here we utilized Ca 2+ ions and sulfur in place of the nucleophilic oxygen in a 20-residue pseudo-substrate peptide (CP20) and ATP to produce a close mimic of the Michaelis complex. In the ternary reactant complex,more » the thiol group of Cys-21 of the peptide is facing Asp-166 and the sulfur atom is positioned for an in-line phosphoryl transfer. Replacement of Ca 2+ cations with Mg 2+ ions resulted in a complex with trapped products of ATP hydrolysis: phosphate ion and ADP. As a result, the present structural results in combination with the previously reported structures of the transition state mimic and phosphorylated product complexes complete the snapshots of the phosphoryl transfer reaction by PKAc, providing us with the most thorough picture of the catalytic mechanism to date.« less

Analogy for Drude's free electron model to promote students' understanding of electric circuits in lower secondary school

NASA Astrophysics Data System (ADS)

de Almeida, Maria José BM; Salvador, Andreia; Costa, Maria Margarida RR

2014-12-01

Aiming at a deep understanding of some basic concepts of electric circuits in lower secondary schools, this work introduces an analogy between the behavior of children playing in a school yard with a central lake, subject to different conditions, rules, and stimuli, and Drude's free electron model of metals. Using this analogy from the first school contacts with electric phenomena, one can promote students' understanding of concepts such as electric current, the role of generators, potential difference effects, energy transfer, open and closed circuits, resistances, and their combinations in series and parallel. One believes that through this analogy well-known previous misconceptions of young students about electric circuit behaviors can be overcome. Furthermore, students' understanding will enable them to predict, and justify with self-constructed arguments, the behavior of different elementary circuits. The students' predictions can be verified—as a challenge of self-produced understanding schemes—using laboratory experiments. At a preliminary stage, our previsions were confirmed through a pilot study with three classrooms of 9th level Portuguese students.

A structure-function study of PACAP using conformationally-restricted analogs: identification of PAC1 receptor-selective PACAP agonists

PubMed Central

Ramos-Álvarez, Irene; Mantey, Samuel A.; Nakamura, Taichi; Nuche-Berenguer, Bernardo; Moreno, Paola; Moody, Terry W.; Maderdrut, Jerome L.; Coy, David H.; Jensen, Robert T.

2015-01-01

Pituitary adenylate-cyclase-activating polypeptide (PACAP) has widespread physiological/pathophysiological actions and there is increased interest for its use therapeutically, especially in the CNS (neuroprotection). Unfortunately, no selective PACAP-analogs exist for PACAP-preferring PAC1-receptors, primarily because of its high sequence identity to VIP and particularly, because of the inability of structure-function studies to separate the pharmacophore of PAC1-R from VPAC1-R, which has high affinity for PACAP and VIP. The present study attempted to develop PAC1-R-selective agonists primarily by making conformationally-restricted PACAP -analogs in positions important for receptor-selectivity/affinity. Forty-six PACAP-related-analogs were synthesized with substitutions in positions 1–4, 14–17, 20–22 ,28,34,38 and receptor-selectivity determined in PAC1-R,VPAC1-R,VPAC2-R-transfected or native cells from binding or cAMP-generation experiments. Fifteen PACAP-analogs had 6–78-fold higher affinities for PAC1-R than VPAC1-R and 13 were agonists. Although binding-affinities correlated significantly with agonist potency, the degree of receptor-spareness varied markedly for the different PACAP-analogs, resulting in selective potencies for activating the PAC1 receptor over the VPAC1 receptor from 0- to-103-fold. In addition, a number of PACAP-analogs were identified that had high selectivity for PAC1-R over VPAC2-R as well as PACAP-analogs that could prove more useful therapeutically because of substitutions known to extend their half-lives (substitutions at potential sites of proteolysis and attachment of long-chain fatty acids). This study provides for the first time a separation of the pharmacophores for PAC1-R and VPAC1-R, resulting in PACAP-related analogs that are PAC1-R-preferring. Some of these analogs, or their modifications, could prove useful as therapeutic agents for various diseases. PMID:25698233

The hemagglutinin structure of an avian H1N1 influenza A virus

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

Lin, Tianwei; Wang, Gengyan; Li, Anzhang

2009-09-15

The interaction between hemagglutinin (HA) and receptors is a kernel in the study of evolution and host adaptation of H1N1 influenza A viruses. The notion that the avian HA is associated with preferential specificity for receptors with Sia{alpha}2,3Gal glycosidic linkage over those with Sia{alpha}2,6Gal linkage is not all consistent with the available data on H1N1 viruses. By x-ray crystallography, the HA structure of an avian H1N1 influenza A virus, as well as its complexes with the receptor analogs, was determined. The structures revealed no preferential binding of avian receptor analogs over that of the human analog, suggesting that the HA/receptormore » binding might not be as stringent as is commonly believed in determining the host receptor preference for some subtypes of influenza viruses, such as the H1N1 viruses. The structure also showed difference in glycosylation despite the preservation of related sequences, which may partly contribute to the difference between structures of human and avian origin.« less

European corn borer sex pheromone : Inhibition and elicitation of behavioral response by analogs.

PubMed

Schwarz, M; Klun, J A; Uebel, E C

1990-05-01

The male sexual behavior-stimulating and inhibiting properties of a series of analogs of the European corn borer sex pheromone were determined in a flight tunnel. The structural requirements for inhibition of pheromonal response were far less restrictive than those for elicitation of that response. Analogs that by themselves elicited upwind flight response from males at a low dose were generally less inhibitory to male response than many of the analogs that had no pheromonal activity. These findings suggest that many pheromone analogs bind to pheromone receptors without provoking behavioral response and possibly undergo slower degradation on the antenna than pheromonally active compounds. The disparity of response to analogs by two pheromonal types of the European corn borer indicates that the pheromone receptor and pheromone catabolic systems are biochemically very different in the two types.

A novel effect of thalidomide and its analogs: suppression of cereblon ubiquitination enhances ubiquitin ligase function

PubMed Central

Liu, Yaobin; Huang, Xiangao; He, Xian; Zhou, Yanqing; Jiang, Xiaogang; Chen-Kiang, Selina; Jaffrey, Samie R.; Xu, Guoqiang

2015-01-01

The immunomodulatory drug (IMiD) thalidomide and its structural analogs lenalidomide and pomalidomide are highly effective in treating clinical indications. Thalidomide binds to cereblon (CRBN), a substrate receptor of the cullin-4 really interesting new gene (RING) E3 ligase complex. Here, we examine the effect of thalidomide and its analogs on CRBN ubiquitination and its functions in human cell lines. We find that the ubiquitin modification of CRBN includes K48-linked polyubiquitin chains and that thalidomide blocks the formation of CRBN-ubiquitin conjugates. Furthermore, we show that ubiquitinated CRBN is targeted for proteasomal degradation. Treatment of human myeloma cell lines such as MM1.S, OPM2, and U266 with thalidomide (100 μM) and its structural analog lenalidomide (10 μM) results in stabilization of CRBN and elevation of CRBN protein levels. This in turn leads to the reduced level of CRBN target proteins and enhances the sensitivity of human multiple myeloma cells to IMiDs. Our results reveal a novel mechanism by which thalidomide and its analogs modulate the CRBN function in cells. Through inhibition of CRBN ubiquitination, thalidomide and its analogs allow CRBN to accumulate, leading to the increased cullin-4 RING E3 ligase-mediated degradation of target proteins.—Liu, Y., Huang, X., He, X., Zhou, Y., Jiang, X., Chen-Kiang, S., Jaffrey, S. R., Xu, G. A novel effect of thalidomide and its analogs: suppression of cereblon ubiquitination enhances ubiquitin ligase function. PMID:26231201

A note on closed-string interactions a la witten

NASA Astrophysics Data System (ADS)

Romans, L. J.

1987-08-01

We consider the problem of formulating a field theory of interacting closed strings analogous to Witten's open-string field theory. Two natural candidates have been suggested for an off-shell three-string interaction vertex: one scheme involves a cyclic geometric overlap in spacetime, while the other is obtained by ``stuttering'' the Fock-space realization of the open-string vertex. We demonstrate that these two approaches are in fact equivalent, utilizing the operator formalism as developed to describe Witten's theory. Implications of this result for the construction of closed-string theories are briefly discussed. Address after August 1, 1987: Department of Physics, University of Southern California, Los Angeles, CA 90089, USA.

Secure chaotic transmission of electrocardiography signals with acousto-optic modulation under profiled beam propagation.

PubMed

Almehmadi, Fares S; Chatterjee, Monish R

2015-01-10

Electrocardiography (ECG) signals are used for both medical purposes and identifying individuals. It is often necessary to encrypt this highly sensitive information before it is transmitted over any channel. A closed-loop acousto-optic hybrid device acting as a chaotic modulator is applied to ECG signals to achieve this encryption. Recently improved modeling of this approach using profiled optical beams has shown it to be very sensitive to key parameters that characterize the encryption and decryption process, exhibiting its potential for secure transmission of analog and digital signals. Here the encryption and decryption is demonstrated for ECG signals, both analog and digital versions, illustrating strong encryption without significant distortion. Performance analysis pertinent to both analog and digital transmission of the ECG waveform is also carried out using output signal-to-noise, signal-to-distortion, and bit-error-rate measures relative to the key parameters and presence of channel noise in the system.

An analog of photon-assisted tunneling in a periodically modulated waveguide array

PubMed Central

Li, Liping; Luo, Xiaobing; Yang, Xiaoxue; Wang, Mei; Lü, Xinyou; Wu, Ying

2016-01-01

We theoretically report an analog of photon-assisted tunneling (PAT) originated from dark Floquet state in a periodically driven lattice array without a static biased potential by studying a three-channel waveguide system in a non-high-frequency regime. This analog of PAT can be achieved by only periodically modulating the top waveguide and adjusting the distance between the bottom and its adjacent waveguide. It is numerically shown that the PAT resonances also exist in the five-channel waveguide system and probably exist in the waveguide arrays with other odd numbers of waveguides, but they will become weak as the number of waveguides increases. With origin different from traditional PAT, this type of PAT found in our work is closely linked to the existence of the zero-energy (dark) Floquet states. It is readily observable under currently accessible experimental conditions and may be useful for controlling light propagation in waveguide arrays. PMID:27767189

Structure Property Relationships of Carboxylic Acid Isosteres.

PubMed

Lassalas, Pierrik; Gay, Bryant; Lasfargeas, Caroline; James, Michael J; Tran, Van; Vijayendran, Krishna G; Brunden, Kurt R; Kozlowski, Marisa C; Thomas, Craig J; Smith, Amos B; Huryn, Donna M; Ballatore, Carlo

2016-04-14

The replacement of a carboxylic acid with a surrogate structure, or (bio)-isostere, is a classical strategy in medicinal chemistry. The general underlying principle is that by maintaining the features of the carboxylic acid critical for biological activity, but appropriately modifying the physicochemical properties, improved analogs may result. In this context, a systematic assessment of the physicochemical properties of carboxylic acid isosteres would be desirable to enable more informed decisions of potential replacements to be used for analog design. Herein we report the structure-property relationships (SPR) of 35 phenylpropionic acid derivatives, in which the carboxylic acid moiety is replaced with a series of known isosteres. The data set generated provides an assessment of the relative impact on the physicochemical properties that these replacements may have compared to the carboxylic acid analog. As such, this study presents a framework for how to rationally apply isosteric replacements of the carboxylic acid functional group.

Illness, the problem of evil, and the analogical structure of healing: on the difference Christianity makes in bioethics.

PubMed

Khushf, George

1995-03-01

A Christian bioethic needs to place the medical approach to sickness, suffering, and death within the context of redemption and the renewal of humanity in the image of God. This can be done by accounting for the way in which the disruptions of the human life-world that attend the illness experience manifest the structure of the problem of evil and point toward an answer that transcends the individual and the medical community. Further, the disease-oriented approach to medicine, when understood in the context of the analogia entis, can be taken as an analogy for a deeper spiritual healing, and can thus become a vehicle through which one can minister to the disruptions of a patient's life-world. An appreciation of the analogical structure of healing provides the basis for a Christian ethic of care.

The structure-activity relationships of mansonone F, a potent anti-MRSA sesquiterpenoid quinone: SAR studies on the C6 and C9 analogs.

PubMed

Suh, Young-Ger; Kim, Sun Nam; Shin, Dong-Yun; Hyun, Soon-Sil; Lee, Do-Sang; Min, Kyung-Hoon; Han, Sae Mi; Li, Funan; Choi, Eung-Chil; Choi, Seong-Hak

2006-01-01

For the systematic SAR study on mansonone F, a series of C6 and C9 analogs of mansonone F have been synthesized and their anti-MRSA activities were evaluated. Most of the analogs exhibited good or excellent anti-MRSA activities. In particular, the 6-n-butylmansonone F showed fourfold higher antibacterial activities compared to that of vancomycin.

Chemistry, Biochemistry, Pharmacology, and Toxicology of CS and Synthesis of Its Novel Analogs

DTIC Science & Technology

2007-10-01

fluorine and fluorine -containing groups have been synthesized using microwave irradiation and novel catalysts. The structures and physical properties and...safe, and biologically more potent CS analogs. To this end, the synthesis of a novel group of CS-agents incorporating fluorine and fluorine ...CONCLUSION The new CS-analogs are expected to be more potent than CS. This observation is based on the following considerations. First, fluorine is

32 CFR 37.1210 - Advanced research.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 1 2011-07-01 2011-07-01 false Advanced research. 37.1210 Section 37.1210... research. Research that creates new technology or demonstrates the viability of applying existing technology to new products and processes in a general way. Advanced research is most closely analogous to...

32 CFR 37.1210 - Advanced research.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 1 2013-07-01 2013-07-01 false Advanced research. 37.1210 Section 37.1210... research. Research that creates new technology or demonstrates the viability of applying existing technology to new products and processes in a general way. Advanced research is most closely analogous to...

32 CFR 37.1210 - Advanced research.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 1 2010-07-01 2010-07-01 false Advanced research. 37.1210 Section 37.1210... research. Research that creates new technology or demonstrates the viability of applying existing technology to new products and processes in a general way. Advanced research is most closely analogous to...

32 CFR 37.1210 - Advanced research.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 1 2014-07-01 2014-07-01 false Advanced research. 37.1210 Section 37.1210... research. Research that creates new technology or demonstrates the viability of applying existing technology to new products and processes in a general way. Advanced research is most closely analogous to...

32 CFR 37.1210 - Advanced research.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 1 2012-07-01 2012-07-01 false Advanced research. 37.1210 Section 37.1210... research. Research that creates new technology or demonstrates the viability of applying existing technology to new products and processes in a general way. Advanced research is most closely analogous to...

Superconductivity by rare earth doping in the 1038-type compounds (Ca1-xREx) 10(FeAs)10(Pt3As8) with RE=Y, La-Nd, Sm-Lu

NASA Astrophysics Data System (ADS)

Stürzer, Tobias; Derondeau, Gerald; Bertschler, Eva-Maria; Johrendt, Dirk

2015-01-01

We report superconductivity in polycrystalline samples of the 1038-type compounds (Ca1-xREx) 10(FeAs)10(Pt3As8) up to Tc=35 K with RE=Y, La-Nd, Sm, Gd-Lu. The critical temperatures are nearly independent of the trivalent rare earth element used, yielding a common Tc(xRE) phase diagram for electron doping in all these systems. The absence of superconductivity in Eu2+ doped samples, as well as the close resemblance of (Ca1-xREx) 10(FeAs)10(Pt3As8) to the 1048 compound substantiate that the electron doping scenario in the RE-1038 and 1048 phases is analogous to other iron-based superconductors with simpler crystal structures.

High Reynolds number turbulence model of rotating shear flows

NASA Astrophysics Data System (ADS)

Masuda, S.; Ariga, I.; Koyama, H. S.

1983-09-01

A Reynolds stress closure model for rotating turbulent shear flows is developed. Special attention is paid to keeping the model constants independent of rotation. First, general forms of the model of a Reynolds stress equation and a dissipation rate equation are derived, the only restrictions of which are high Reynolds number and incompressibility. The model equations are then applied to two-dimensional equilibrium boundary layers and the effects of Coriolis acceleration on turbulence structures are discussed. Comparisons with the experimental data and with previous results in other external force fields show that there exists a very close analogy between centrifugal, buoyancy and Coriolis force fields. Finally, the model is applied to predict the two-dimensional boundary layers on rotating plane walls. Comparisons with existing data confirmed its capability of predicting mean and turbulent quantities without employing any empirical relations in rotating fields.

The Emergence of Dirac points in Photonic Crystals with Mirror Symmetry

PubMed Central

He, Wen-Yu; Chan, C. T.

2015-01-01

We show that Dirac points can emerge in photonic crystals possessing mirror symmetry when band gap closes. The mechanism of generating Dirac points is discussed in a two-dimensional photonic square lattice, in which four Dirac points split out naturally after the touching of two bands with different parity. The emergence of such nodal points, characterized by vortex structure in momentum space, is attributed to the unavoidable band crossing protected by mirror symmetry. The Dirac nodes can be unbuckled through breaking the mirror symmetry and a photonic analog of Chern insulator can be achieved through time reversal symmetry breaking. Breaking time reversal symmetry can lead to unidirectional helical edge states and breaking mirror symmetry can reduce the band gap to amplify the finite size effect, providing ways to engineer helical edge states. PMID:25640993

Solution, solid phase and computational structures of apicidin and its backbone-reduced analogs.

PubMed

Kranz, Michael; Murray, Peter John; Taylor, Stephen; Upton, Richard J; Clegg, William; Elsegood, Mark R J

2006-06-01

The recently isolated broad-spectrum antiparasitic apicidin (1) is one of the few naturally occurring cyclic tetrapeptides (CTP). Depending on the solvent, the backbone of 1 exhibits two gamma-turns (in CH(2)Cl(2)) or a beta-turn (in DMSO), differing solely in the rotation of the plane of one of the amide bonds. In the X-ray crystal structure, the peptidic C==Os and NHs are on opposite sides of the backbone plane, giving rise to infinite stacks of cyclotetrapeptides connected by three intermolecular hydrogen bonds between the backbones. Conformational searches (Amber force field) on a truncated model system of 1 confirm all three backbone conformations to be low-energy states. The previously synthesized analogs of 1 containing a reduced amide bond exhibit the same backbone conformation as 1 in DMSO, which is confirmed further by the X-ray crystal structure of a model system of the desoxy analogs of 1. This similarity helps in explaining why the desoxy analogs retain some of the antiprotozoal activities of apicidin. The backbone-reduction approach designed to facilitate the cyclization step of the acyclic precursors of the CTPs seems to retain the conformational preferences of the parent peptide backbone.

Structuring students’ analogical reasoning in solving algebra problem

NASA Astrophysics Data System (ADS)

Lailiyah, S.; Nusantara, T.; Sa'dijah, C.; Irawan, E. B.; Kusaeri; Asyhar, A. H.

2018-01-01

The average achievement of Indonesian students’ mathematics skills according to Benchmark International Trends in Mathematics and Science Study (TIMSS) is ranked at the 38th out of 42 countries and according to the survey result in Program for International Student Assessment (PISA) is ranked at the 64th out of 65 countries. The low mathematics skill of Indonesian student has become an important reason to research more deeply about reasoning and algebra in mathematics. Analogical reasoning is a very important component in mathematics because it is the key to creativity and it can make the learning process in the classroom become effective. The major part of the analogical reasoning is about structuring including the processes of inferencing and decision-making happens. Those processes involve base domain and target domain. Methodologically, the subjects of this research were 42 students from class XII. The sources of data were derived from the results of thinks aloud, the transcribed interviews, and the videos taken while the subject working on the instruments and interviews. The collected data were analyzed using qualitative techniques. The result of this study described the structuring characteristics of students’ analogical reasoning in solving algebra problems from all the research subjects.

Biosynthesis of pteridines. Reaction mechanism of GTP cyclohydrolase I.

PubMed

Rebelo, Jorge; Auerbach, Günter; Bader, Gerd; Bracher, Andreas; Nar, Herbert; Hösl, Cornelia; Schramek, Nicholas; Kaiser, Johannes; Bacher, Adelbert; Huber, Robert; Fischer, Markus

2003-02-14

GTP cyclohydrolase I catalyses the hydrolytic release of formate from GTP followed by cyclization to dihydroneopterin triphosphate. The enzymes from bacteria and animals are homodecamers containing one zinc ion per subunit. Replacement of Cys110, Cys181, His112 or His113 of the enzyme from Escherichia coli by serine affords catalytically inactive mutant proteins with reduced capacity to bind zinc. These mutant proteins are unable to convert GTP or the committed reaction intermediate, 2-amino-5-formylamino-6-(beta-ribosylamino)-4(3H)-pyrimidinone 5'-triphosphate, to dihydroneopterin triphosphate. The crystal structures of GTP complexes of the His113Ser, His112Ser and Cys181Ser mutant proteins determined at resolutions of 2.5A, 2.8A and 3.2A, respectively, revealed the conformation of substrate GTP in the active site cavity. The carboxylic group of the highly conserved residue Glu152 anchors the substrate GTP, by hydrogen bonding to N-3 and to the position 2 amino group. Several basic amino acid residues interact with the triphosphate moiety of the substrate. The structure of the His112Ser mutant in complex with an undefined mixture of nucleotides determined at a resolution of 2.1A afforded additional details of the peptide folding. Comparison between the wild-type and mutant enzyme structures indicates that the catalytically active zinc ion is directly coordinated to Cys110, Cys181 and His113. Moreover, the zinc ion is complexed to a water molecule, which is in close hydrogen bond contact to His112. In close analogy to zinc proteases, the zinc-coordinated water molecule is suggested to attack C-8 of the substrate affording a zinc-bound 8R hydrate of GTP. Opening of the hydrated imidazole ring affords a formamide derivative, which remains coordinated to zinc. The subsequent hydrolysis of the formamide motif has an absolute requirement for zinc ion catalysis. The hydrolysis of the formamide bond shows close mechanistic similarity with peptide hydrolysis by zinc proteases.

How the creative use of analogies can shape medical practice.

PubMed

Prasad, G V Ramesh

2015-06-01

Analogical reasoning is central to medical progress, and is either creative or conservative. According to Hofmann et al., conservative analogy relates concepts from old technology to new technologies with emphasis on preservation of comprehension and conduct. Creative analogy however brings new understanding to new technology, brings similarities existing in the source domain to a target domain where they previously had no bearing, and imports something entirely different from the content of the analogy itself. I defend the claim that while conservative analogies are useful by virtue of being comfortable to use from familiarity and experience, and are more easily accepted by society, they only lead to incremental advances in medicine. However, creative analogies are more exciting and productive because they generate previously unexpected associations across widely separated domains, emphasize relations over physical similarities, and structure over superficiality. I use kidney transplantation and anti-rejection medication development as an exemplar of analogical reasoning used to improve medical practice. Anti-rejection medication has not helped highly sensitized patients because of their propensity to rejecting most organs. I outline how conservative analogical reasoning led to anti-rejection medication development, but creative analogical reasoning helped highly sensitized and blood type incompatible patients through domino transplants, by which they obtain a kidney to which they are not sensitized. Creative analogical reasoning is more likely than conservative analogical reasoning to lead to revolutionary progress. While these analogies overlap and creative analogies eventually become conservative, progress is best facilitated by combining conservative and creative analogical reasoning. © 2015 John Wiley & Sons, Ltd.

Infrared Avionics Signal Distribution Using WDM

NASA Technical Reports Server (NTRS)

Atiquzzaman, Mohammed; Sluss, James J., Jr.

2004-01-01

Supporting analog RF signal transmission over optical fibers, this project demonstrates a successful application of wavelength division multiplexing (WDM) to the avionics environment. We characterize the simultaneous transmission of four RF signals (channels) over a single optical fiber. At different points along a fiber optic backbone, these four analog channels are sequentially multiplexed and demultiplexed to more closely emulate the conditions in existing onboard aircraft. We present data from measurements of optical power, transmission response (loss and gain), reflection response, group delay that defines phase distortion, signal-to-noise ratio (SNR), and dynamic range that defines nonlinear distortion. The data indicate that WDM is very suitable for avionics applications.

A high capacity data recording device based on a digital audio processor and a video cassette recorder.

PubMed

Bezanilla, F

1985-03-01

A modified digital audio processor, a video cassette recorder, and some simple added circuitry are assembled into a recording device of high capacity. The unit converts two analog channels into digital form at 44-kHz sampling rate and stores the information in digital form in a common video cassette. Bandwidth of each channel is from direct current to approximately 20 kHz and the dynamic range is close to 90 dB. The total storage capacity in a 3-h video cassette is 2 Gbytes. The information can be retrieved in analog or digital form.

A high capacity data recording device based on a digital audio processor and a video cassette recorder.

PubMed Central

Bezanilla, F

1985-01-01

A modified digital audio processor, a video cassette recorder, and some simple added circuitry are assembled into a recording device of high capacity. The unit converts two analog channels into digital form at 44-kHz sampling rate and stores the information in digital form in a common video cassette. Bandwidth of each channel is from direct current to approximately 20 kHz and the dynamic range is close to 90 dB. The total storage capacity in a 3-h video cassette is 2 Gbytes. The information can be retrieved in analog or digital form. PMID:3978213

The Application of Fiber Optic Wavelength Division Multiplexing in RF Avionics

NASA Technical Reports Server (NTRS)

Ngo, Duc; Nguyen, Hung; Atiquzzaman, Mohammed; Sluss, James J., Jr.; Refai, Hakki H.

2004-01-01

This paper demonstrates a successful application of wavelength division multiplexing (WDM) to the avionics environment to support analog RF signal transmission. We investigate the simultaneous transmission of four RF signals (channels) over a single optical fiber. These four analog channels are sequentially multiplexed and demultiplexed at different points along a fiber optic backbone to more closely emulate the conditions found onboard aircraft. We present data from measurements of signal-to-noise ratio (SNR), transmission response (loss and gain), group delay that defines phase distortion, and dynamic range that defines nonlinear distortion. The data indicate that WDM is well-suited for avionics applications.

Analogies between Kirchhoff plates and functionally graded Saint-Venant beams under torsion

NASA Astrophysics Data System (ADS)

Barretta, Raffaele; Luciano, Raimondo

2015-05-01

Exact solutions of elastic Kirchhoff plates are available only for special geometries, loadings and kinematic boundary constraints. An effective solution procedure, based on an analogy between functionally graded orthotropic Saint-Venant beams under torsion and inhomogeneous isotropic Kirchhoff plates, with no kinematic boundary constraints, is proposed. The result extends the one contributed in Barretta (Acta Mech 224(12):2955-2964, 2013) for the special case of homogeneous Saint-Venant beams under torsion. Closed-form solutions for displacement, bending-twisting moment and curvature fields of an elliptic plate, corresponding to a functionally graded orthotropic beam, are evaluated. A new benchmark for computational mechanics is thus provided.

Analogs of methyllycaconitine as novel noncompetitive inhibitors of nicotinic receptors: pharmacological characterization, computational modeling, and pharmacophore development.

PubMed

McKay, Dennis B; Chang, Cheng; González-Cestari, Tatiana F; McKay, Susan B; El-Hajj, Raed A; Bryant, Darrell L; Zhu, Michael X; Swaan, Peter W; Arason, Kristjan M; Pulipaka, Aravinda B; Orac, Crina M; Bergmeier, Stephen C

2007-05-01

As a novel approach to drug discovery involving neuronal nicotinic acetylcholine receptors (nAChRs), our laboratory targeted nonagonist binding sites (i.e., noncompetitive binding sites, negative allosteric binding sites) located on nAChRs. Cultured bovine adrenal cells were used as neuronal models to investigate interactions of 67 analogs of methyllycaconitine (MLA) on native alpha3beta4* nAChRs. The availability of large numbers of structurally related molecules presents a unique opportunity for the development of pharmacophore models for noncompetitive binding sites. Our MLA analogs inhibited nicotine-mediated functional activation of both native and recombinant alpha3beta4* nAChRs with a wide range of IC(50) values (0.9-115 microM). These analogs had little or no inhibitory effects on agonist binding to native or recombinant nAChRs, supporting noncompetitive inhibitory activity. Based on these data, two highly predictive 3D quantitative structure-activity relationship (comparative molecular field analysis and comparative molecular similarity index analysis) models were generated. These computational models were successfully validated and provided insights into the molecular interactions of MLA analogs with nAChRs. In addition, a pharmacophore model was constructed to analyze and visualize the binding requirements to the analog binding site. The pharmacophore model was subsequently applied to search structurally diverse molecular databases to prospectively identify novel inhibitors. The rapid identification of eight molecules from database mining and our successful demonstration of in vitro inhibitory activity support the utility of these computational models as novel tools for the efficient retrieval of inhibitors. These results demonstrate the effectiveness of computational modeling and pharmacophore development, which may lead to the identification of new therapeutic drugs that target novel sites on nAChRs.

Biomonitoring of human exposures to chlorinated derivatives and structural analogs of bisphenol A.

PubMed

Andra, Syam S; Charisiadis, Pantelis; Arora, Manish; van Vliet-Ostaptchouk, Jana V; Makris, Konstantinos C

2015-12-01

The high reactivity of bisphenol A (BPA) with disinfectant chlorine is evident in the instantaneous formation of chlorinated BPA derivatives (ClxBPA) in various environmental media that show increased estrogen-activity when compared with that of BPA. The documented health risks associated with BPA exposures have led to the gradual market entry of BPA structural analogs, such as bisphenol S (BPS), bisphenol F (BPF), bisphenol B (BPB), etc. A suite of exposure sources to ClxBPA and BPA analogs in the domestic environment is anticipated to drive the nature and range of halogenated BPA derivatives that can form when residual BPA comes in contact with disinfectant in tap water and/or consumer products. The primary objective of this review was to survey all available studies reporting biomonitoring protocols of ClxBPA and structural BPA analogs (BPS, BPF, BPB, etc.) in human matrices. Focus was paid on describing the analytical methodologies practiced for the analysis of ClxBPA and BPA analogs using hyphenated chromatography and mass spectrometry techniques, because current methodologies for human matrices are complex. During the last decade, an increasing number of ecotoxicological, cell-culture and animal-based and human studies dealing with ClxBPA exposure sources and routes of exposure, metabolism and toxicity have been published. Up to date findings indicated the association of ClxBPA with metabolic conditions, such as obesity, lipid accumulation, and type 2 diabetes mellitus, particularly in in-vitro and in-vivo studies. We critically discuss the limitations, research needs and future opportunities linked with the inclusion of ClxBPA and BPA analogs into exposure assessment protocols of relevant epidemiological studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cocaine-like discriminative stimulus effects of amphetamine, cathinone, methamphetamine, and their 3,4-methylenedioxy analogs in male rhesus monkeys.

PubMed

Smith, Douglas A; Blough, Bruce E; Banks, Matthew L

2017-01-01

Synthetic cathinones have emerged as the newest class of abused monoamine transporter substrates. Structurally, these compounds are all beta-ketone amphetamine (cathinone) analogs. Whether synthetic cathinone analogs produce differential behavioral effects from their amphetamine analog counterparts has not been systematically examined. Preclinical drug discrimination procedures have been useful for determining the structure activity relationships (SARs) of abused drugs; however, direct comparisons between amphetamine and cathinone analogs are lacking and, in particular, in non-human primate models. The study aim was to determine the potency and time course of (±)-amphetamine, (±)-cathinone, and (±)-methamphetamine and their 3,4-methylenedioxy analogs (±)-MDA, (±)-MDC, and (±)-MDMA, respectively, to produce cocaine-like discriminative stimulus effects. If cathinone analogs have similar behavioral pharmacological properties to their amphetamine counterparts, then we would predict similar potencies and efficacies to produce cocaine-like discriminative stimulus effects. Male rhesus monkeys (n = 4) were trained to discriminate intramuscular cocaine (0.32 mg/kg) from saline in a two-key food-reinforced discrimination procedure. Racemic amphetamine, cathinone, and methamphetamine produced dose-dependent and full substitution, ≥90 % cocaine-appropriate responding, in all monkeys. Addition of 3,4-methylenedioxy moiety attenuated both the potency and efficacy of amphetamine (MDA), cathinone (MDC), and methamphetamine (MDMA) to produce full cocaine-like effects. Moreover, the cocaine-like effects of amphetamine and cathinone were attenuated to a greater extent than those of methamphetamine or previously published methcathinone (Smith et al. 2016). The presence of an N-methyl group blunted both the potency and the efficacy shift of the 3,4-methylenedioxy addition for both amphetamine and cathinone analogs.

Convergent synthesis of double point modified analogs of 1α,25-dihydroxyvitamin D2 for biological evaluation.

PubMed

Nadkarni, Sharmin; Chodyński, Michał; Krajewski, Krzysztof; Cmoch, Piotr; Marcinkowska, Ewa; Brown, Geoffrey; Kutner, Andrzej

2016-11-01

There is a long lasting controversy over the biological activity of vitamin D 2 as compared to vitamin D 3 in terms of maintaining of calcium homeostasis and raising the level of circulating 25-OH-D. To shed more light on this relationship we synthesized 1α,25-dihydroxyvitamin D 2 , by a novel convergent strategy, to compare this compound directly with the activity of 1α,25-dihydroxyvitamin D 3 . The same synthetic strategy also provided a series of (5E,7E) geometric isomers of the natural 1α,25-dihydroxyvitamin D 2 as well as a series of double point modified analogs of its (24R)-epimer, including C-22 hydroxy derivatives. The structure of the new analogs was determined by 1 H and 13 C NMR as well as by mass spectrometry. The influence of (5E,7E) modification, alone or in combination with additional modifications in the side chain, on the activity profile and metabolic deactivation of analogs of 1α,25-dihydroxyvitamin D 2 still remains unknown. (5E,7E) modification in the structure of new analogs of 1α,25-dihydroxyvitamin D 2 is expected to give analogs with no influence on calcium level, as was previously obtained for the analogs of 1α,25-dihydroxyvitamin D 3 . Investigation of the affinities for the vitamin D receptor and cell differentiation, transcriptional and calcium activities of the most active form of vitamin D 2 and of (5E,7E) analogs, compared to 1α,25-dihydroxyvitamin D 3 , is underway in the collaborating laboratories. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cocaine-like discriminative stimulus effects of amphetamine, cathinone, methamphetamine, and their 3,4-methylenedioxy analogs in male rhesus monkeys

PubMed Central

Smith, Douglas A.; Blough, Bruce. E.; Banks, Matthew L.

2016-01-01

Rationale Synthetic cathinones have emerged as the newest class of abused monoamine transporter substrates. Structurally, these compounds are all beta-ketone amphetamine (cathinone) analogs. Whether synthetic cathinone analogs produce differential behavioral effects from their amphetamine analog counterparts has not been systematically examined. Preclinical drug discrimination procedures have been useful for determining the structure activity relationships (SAR) of abused drugs; however, direct comparisons between amphetamine and cathinone analogs are lacking and, in particular, in nonhuman primate models. Objectives The study aim was to determine the potency and time course of (±)-amphetamine, (±)-cathinone, (±)-methamphetamine, and their 3,4-methylenedioxy analogs (±)-MDA, (±)-MDC, and (±)-MDMA, respectively to produce cocaine-like discriminative stimulus effects. If cathinone analogs have similar behavioral pharmacological properties to their amphetamine counterparts, then we would predict similar potencies and efficacies to produce cocaine-like discriminative stimulus effects. Methods Male rhesus monkeys (n=4) were trained to discriminate intramuscular cocaine (0.32 mg/kg) from saline in a two-key food-reinforced discrimination procedure. Results Racemic amphetamine, cathinone, and methamphetamine produced dose-dependent and full, ≥90% cocaine-appropriate responding, in all monkeys. Addition of 3,4-methylenedioxy moiety attenuated both the potency and efficacy of amphetamine (MDA), cathinone (MDC), and methamphetamine (MDMA) to produce full cocaine-like effects. Moreover, the cocaine-like effects of amphetamine and cathinone were attenuated to a greater extent than methamphetamine or previously published methcathinone (Smith et al. 2016). Conclusion The presence of an N-methyl group blunted both the potency and efficacy shift of the 3,4-methylenedioxy addition for both amphetamine and cathinone analogs. PMID:27709249

Using Pressure and Volumetric Approaches to Estimate CO2 Storage Capacity in Deep Saline Aquifers

DOE PAGES

Thibeau, Sylvain; Bachu, Stefan; Birkholzer, Jens; ...

2014-12-31

Various approaches are used to evaluate the capacity of saline aquifers to store CO 2, resulting in a wide range of capacity estimates for a given aquifer. The two approaches most used are the volumetric “open aquifer” and “closed aquifer” approaches. We present four full-scale aquifer cases, where CO 2 storage capacity is evaluated both volumetrically (with “open” and/or “closed” approaches) and through flow modeling. These examples show that the “open aquifer” CO 2 storage capacity estimation can strongly exceed the cumulative CO 2 injection from the flow model, whereas the “closed aquifer” estimates are a closer approximation to themore » flow-model derived capacity. An analogy to oil recovery mechanisms is presented, where the primary oil recovery mechanism is compared to CO 2 aquifer storage without producing formation water; and the secondary oil recovery mechanism (water flooding) is compared to CO 2 aquifer storage performed simultaneously with extraction of water for pressure maintenance. This analogy supports the finding that the “closed aquifer” approach produces a better estimate of CO 2 storage without water extraction, and highlights the need for any CO 2 storage estimate to specify whether it is intended to represent CO 2 storage capacity with or without water extraction.« less

Simulation analysis of formycin 5?-monophosphate analog substrates in the ricin A-chain active site

NASA Astrophysics Data System (ADS)

Olson, Mark A.; Scovill, John P.; Hack, Dallas C.

1995-06-01

Ricin is an RNA N-glycosidase that hydrolyzes a single adenine base from a conserved loop of 28S ribosomal RNA, thus inactivating protein synthesis. Molecular-dynamics simulation methods are used to analyze the structural interactions and thermodynamics that govern the binding of formycin 5'-monophosphate (FMP) and several of its analogs to the active site of ricin A-chain. Simulations are carried out initiated from the X-ray crystal structure of the ricin-FMP complex with the ligand modeled as a dianion, monoanion and zwitterion. Relative changes in binding free energies are estimated for FMP analogs constructed from amino substitutions at the 2- and 2'-positions, and from hydroxyl substitution at the 2'-position.

Simulation analysis of formycin 5'-monophosphate analog substrates in the ricin A-chain active site.

PubMed

Olson, M A; Scovill, J P; Hack, D C

1995-06-01

Ricin is an RNA N-glycosidase that hydrolyzes a single adenine base from a conserved loop of 28S ribosomal RNA, thus inactivating protein synthesis. Molecular-dynamics simulation methods are used to analyze the structural interactions and thermodynamics that govern the binding of formycin 5'-monophosphate (FMP) and several of its analogs to the active site of ricin A-chain. Simulations are carried out initiated from the X-ray crystal structure of the ricin-FMP complex with the ligand modeled as a dianion, monoanion and zwitterion. Relative changes in binding free energies are estimated for FMP analogs constructed from amino substitutions at the 2- and 2'-positions, and from hydroxyl substitution at the 2'-position.

MSC/NASTRAN DMAP Alter Used for Closed-Form Static Analysis With Inertia Relief and Displacement-Dependent Loads

NASA Technical Reports Server (NTRS)

1996-01-01

Solving for the displacements of free-free coupled systems acted upon by static loads is a common task in the aerospace industry. Often, these problems are solved by static analysis with inertia relief. This technique allows for a free-free static analysis by balancing the applied loads with the inertia loads generated by the applied loads. For some engineering applications, the displacements of the free-free coupled system induce additional static loads. Hence, the applied loads are equal to the original loads plus the displacement-dependent loads. A launch vehicle being acted upon by an aerodynamic loading can have such applied loads. The final displacements of such systems are commonly determined with iterative solution techniques. Unfortunately, these techniques can be time consuming and labor intensive. Because the coupled system equations for free-free systems with displacement-dependent loads can be written in closed form, it is advantageous to solve for the displacements in this manner. Implementing closed-form equations in static analysis with inertia relief is analogous to implementing transfer functions in dynamic analysis. An MSC/NASTRAN (MacNeal-Schwendler Corporation/NASA Structural Analysis) DMAP (Direct Matrix Abstraction Program) Alter was used to include displacement-dependent loads in static analysis with inertia relief. It efficiently solved a common aerospace problem that typically has been solved with an iterative technique.

Identification of a Raloxifene Analog That Promotes AhR-Mediated Apoptosis in Cancer Cells.

PubMed

Jang, Hyo Sang; Pearce, Martin; O'Donnell, Edmond F; Nguyen, Bach Duc; Truong, Lisa; Mueller, Monica J; Bisson, William H; Kerkvliet, Nancy I; Tanguay, Robert L; Kolluri, Siva Kumar

2017-12-01

We previously reported that raloxifene, an estrogen receptor modulator, is also a ligand for the aryl hydrocarbon receptor (AhR). Raloxifene induces apoptosis in estrogen receptor-negative human cancer cells through the AhR. We performed structure-activity studies with seven raloxifene analogs to better understand the structural requirements of raloxifene for induction of AhR-mediated transcriptional activity and apoptosis. We identified Y134 as a raloxifene analog that activates AhR-mediated transcriptional activity and induces apoptosis in MDA-MB-231 human triple negative breast cancer cells. Suppression of AhR expression strongly reduced apoptosis induced by Y134, indicating the requirement of AhR for Y134-induced apoptosis. Y134 also induced apoptosis in hepatoma cells without having an effect on cell cycle regulation. Toxicity testing on zebrafish embryos revealed that Y134 has a significantly better safety profile than raloxifene. Our studies also identified an analog of raloxifene that acts as a partial antagonist of the AhR, and is capable of inhibiting AhR agonist-induced transcriptional activity. We conclude that Y134 is a promising raloxifene analog for further optimization as an anti-cancer agent targeting the AhR.

Further studies on the structural requirements for mast cell degranulating (MCD) peptide-mediated histamine release.

PubMed

Buku, A; Price, J A

2001-12-01

Mast cell degranulating (MCD) peptide was modified in its two disulfide bridges and in the two arginine residues in order to measure the ability of these analogs to induce histamine release from mast cells in vitro. Analogs prepared were [Ala(3,15)]MCD, [Ala(5,19)]MCD, [Orn(16)]MCD, and [Orn(7,16)]MCD. Their histamine-releasing activity was determined spectrofluorometrically with peritoneal mast cells. The monocyclic analogs in which the cysteine residues were replaced pairwise with alanine residues showed three-to ten-fold diminished histamine-releasing activity respectively, compared with the parent MCD peptide. Substantial increases in activity were observed where arginine residues were replaced by ornithines. The ornithine-mono substituted analog showed an almost six-fold increase and the ornithine-doubly substituted analog three-fold increase in histamine-releasing activity compared with the parent MCD peptide. The structural changes associated with these activities were followed by circular dichroism (CD) spectroscopy. Changes in the shape and ellipticity of the CD spectra reflected a role for the disulfide bonds and the two arginine residues in the overall conformation and biological activity of the molecule.

Bioactivation of bisphenol A and its analogs (BPF, BPAF, BPZ and DMBPA) in human liver microsomes.

PubMed

Schmidt, Jan; Kotnik, Petra; Trontelj, Jurij; Knez, Željko; Mašič, Lucija Peterlin

2013-06-01

Bisphenol A analogs are a class of chemicals known as diphenylmethanes, which contain two benzene rings separated by one central carbon atom, usually with a para-hydroxy group on both benzene rings. Bisphenol A (BPA) can induce an uterotrophic response in immature CD-1 mice and elicits estrogenic responses in many other experimental systems. Besides highlighting endocrine effects, a number of metabolic studies provide strong support for the idea that reactive species of BPA are formed in vitro and in vivo that can form covalent adducts with nucleophilic macromolecules and/or produce oxidative stress. We used a liquid chromatography with a triple quadrupole tandem mass spectrometry (LC-MS/MS) for the detection of metabolites and glutathione conjugates of BPA and its analogs (BPF, BPAF, BPZ and DMBPA) in human liver microsomes (HLM) or with recombinant CYP isozymes in the presence of NADPH and GSH as a trapping agent. We have confirmed that BPA and its structural analogs form hydroxylated metabolites and electrophilic species during bioactivation in HLM and CYP isozymes. These results provided important mechanistic insight into the metabolic fate of BPA structural analogs in vitro. Copyright © 2013 Elsevier Ltd. All rights reserved.

Relaxation of structural parameters and potential coefficients of nonrigid molecules. General symmetry properties and application to ab initio study of 1,2-difluoroethane

NASA Astrophysics Data System (ADS)

Ha, T.-K.; Günthard, H. H.

1989-07-01

Structural parameters like bond length, bond angles, etc. and harmonic and anharmonic potential coefficients of molecules with internal rotation, inversion or puckering modes are generally assumed to vary with the large amplitude internal coordinates in a concerted manner (relaxation). Taking the coordinate vectors of the nuclear configuration of semirigid molecules with relaxation (SRMRs) as functions of relaxing structural parameters and finite amplitude internal coordinate, the isometric group of SRMRs is discussed and the irreducible representations of the latter are shown to classify into engendered and nonengendered ones. On this basis a concept of equivalent sets of nuclei SRMRs is introduced and an analytical expression is derived which defines the most general functional form of relaxation increments of all common types of structural parameters compatible with isometric symmetry. This formula is shown to be a close analog of an analytical expression defining the transformations induced by the isometric group of infinitesimal internal coordinates associated with typical structural parameters. Furthermore analogous formulae are given for the most general form of the relaxation of harmonic potential coefficients as a function of finite internal coordinates. The general relations are illustrated by ab initio calculations for 1,2-difluoroethane at the MP4/DZP//HF/4-31G* level for twelve values of the dihedral angle including complete structure optimization. The potential to internal rotation is found to be in essential agreement with experimentally derived data. For a complete set of ab initio structural parameters the associated relaxation increments are represented as Fourier series, which are shown to confirm the form predicted by the general formula and the isometric group of 1,2-difluoroethane. Depending on type of the structural parameters (bond length, bond angles, etc.), the associated relaxation increments appear to follow some simple rules. Similarly a complete set of harmonic potential coefficients derived from the ab initio calculations will be analyzed in terms of Fourier series and shown to conform to the symmetry requirements of the symmetry group. Relaxation of potential coefficients is found to amount to up to ≈5% for some types of diagonal and nondiagonal terms and to reflect certain "topological" rules similar to regularities of harmonic potential constants of quasi-rigid molecules found in empirical determinations of valence force fields.

Sampling command generator corrects for noise and dropouts in recorded data

NASA Technical Reports Server (NTRS)

Anderson, T. O.

1973-01-01

Generator measures period between zero crossings of reference signal and accepts as correct timing points only those zero crossings which occur acceptably close to nominal time predicted from last accepted command. Unidirectional crossover points are used exclusively so errors from analog nonsymmetry of crossover detector are avoided.

Benchmarking Attrition: What Can We Learn From Other Industries?

ERIC Educational Resources Information Center

Delta Cost Project at American Institutes for Research, 2012

2012-01-01

This brief summarizes Internet-based research into other industries that may offer useful analogies for thinking about student attrition in higher education, in particular for setting realistic benchmarks for reductions in attrition. Reducing attrition to zero or close to zero is not a realistic possibility in higher education. Students are…

The Nature of Mercury's Hollows, and Space Weathering Close to the Sun

NASA Astrophysics Data System (ADS)

Blewett, D. T.; Chabot, N. L.; Denevi, B. W.; Ernst, C. M.

2018-05-01

Hollows are a landform that appear to form by loss of a volatile-bearing phase from silicate rock. Hollows are very young and are likely to be forming in the present day. Hollows may be an analog for extreme weathering on near-Sun asteroids.

Decoding the Structure of Abuse Potential for New Psychoactive Substances: Structure—Activity Relationships for Abuse-Related Effects of 4-Substituted Methcathinone Analogs

PubMed Central

Banks, Matthew L.

2017-01-01

Many cathinone analogs act as substrates or inhibitors at dopamine, norepinephrine, and serotonin transporters (DAT, NET, SERT, respectively). Drug selectivity at DAT vs. SERT is a key determinant of abuse potential for monoamine transporter substrates and inhibitors, such that potency at DAT > SERT is associated with high abuse potential, whereas potency at DAT < SERT is associated with low abuse potential. Quantitative structure—activity relationship (QSAR) studies with a series of 4-substituted methcathinone analogs identified volume of the 4-position substituent on the methcathinone phenyl ring as one structural determinant of both DAT vs. SERT selectivity and abuse-related behavioral effects in an intracranial self-stimulation procedure in rats. Subsequent modeling studies implicated specific amino acids in DAT and SERT that might interact with 4-substituent volume to determine effects produced by this series of cathinone analogs. These studies illustrate use of QSAR analysis to investigate pharmacology of cathinones and function of monoamine transporters. PMID:27696217

Effects of Bisphenol A and its Analogs on Reproductive Health: A Mini Review.

PubMed

Siracusa, Jacob Steven; Yin, Lei; Measel, Emily; Liang, Shenuxan; Yu, Xiaozhong

2018-06-17

Known endocrine disruptor bisphenol A (BPA) has been shown to be a reproductive toxicant in animal models. Its structural analogs: bisphenol S (BPS), bisphenol F (BPF), bisphenol AF (BPAF), and tetrabromobisphenol A (TBBPA) are increasingly being used in consumer products. However, these analogs may exert similar adverse effects on the reproductive system, and their toxicological data are still limited. This mini-review examined studies on both BPA and BPA analog exposure and reproductive toxicity. It outlines the current state of knowledge on human exposure, toxicokinetics, endocrine activities, and reproductive toxicities of BPA and its analogs. BPA analogs showed similar endocrine potencies when compared to BPA, and emerging data suggest they may pose threats as reproductive hazards in animal models. While evidence based on epidemiological studies is still weak, we have utilized current studies to highlight knowledge gaps and research needs for future risk assessments. Copyright © 2018. Published by Elsevier Inc.

Flyover Modeling of Planetary Pits - Undergraduate Student Instrument Project

NASA Astrophysics Data System (ADS)

Bhasin, N.; Whittaker, W.

2015-12-01

On the surface of the moon and Mars there are hundreds of skylights, which are collapsed holes that are believed to lead to underground caves. This research uses Vision, Inertial, and LIDAR sensors to build a high resolution model of a skylight as a landing vehicle flies overhead. We design and fabricate a pit modeling instrument to accomplish this task, implement software, and demonstrate sensing and modeling capability on a suborbital reusable launch vehicle flying over a simulated pit. Future missions on other planets and moons will explore pits and caves, led by the technology developed by this research. Sensor software utilizes modern graph-based optimization techniques to build 3D models using camera, LIDAR, and inertial data. The modeling performance was validated with a test flyover of a planetary skylight analog structure on the Masten Xombie sRLV. The trajectory profile closely follows that of autonomous planetary powered descent, including translational and rotational dynamics as well as shock and vibration. A hexagonal structure made of shipping containers provides a terrain feature that serves as an appropriate analog for the rim and upper walls of a cylindrical planetary skylight. The skylight analog floor, walls, and rim are modeled in elevation with a 96% coverage rate at 0.25m2 resolution. The inner skylight walls have 5.9cm2 color image resolution and the rims are 6.7cm2 with measurement precision superior to 1m. The multidisciplinary student team included students of all experience levels, with backgrounds in robotics, physics, computer science, systems, mechanical and electrical engineering. The team was commited to authentic scientific experimentation, and defined specific instrument requirements and measurable experiment objectives to verify successful completion.This work was made possible by the NASA Undergraduate Student Instrument Project Educational Flight Opportunity 2013 program. Additional support was provided by the sponsorship of an IMU by KVH industries and mentorship was provided by members of the NASA ALHAT team. In addition to external support, this project was supported by two CMU Small Undergraduate Research Grants, the availability of a high-power CMU LIDAR sensor, dedicated workspace, and mentorship from research and shop faculty.

Suvanine analogs from a Coscinoderma sp. marine sponge and their cytotoxicities against human cancer cell lines.

PubMed

Lee, Jeong-Woo; Lee, Hyi-Seung; Shin, Jongheon; Kang, Jong Soon; Yun, Jieun; Shin, Hee Jae; Lee, Jong Seok; Lee, Yeon-Ju

2015-06-01

Nine suvanine analogs including suvanine phenethylammonium salt and two new compounds were isolated from the marine sponge Coscinoderma sp., collected from Chuuk State, Federated States of Micronesia. The structures of the new compounds were elucidated by 2D NMR and HRMS analyses. Suvanine and a new analog exhibited weak but selective cytotoxicity against colon (HCT-15), lung (NCI-H23), stomach (NUGC-3), and prostate (PC-3) cancer cell lines.

Differential effects of two types of formative assessment in predicting performance of first-year medical students.

PubMed

Krasne, Sally; Wimmers, Paul F; Relan, Anju; Drake, Thomas A

2006-05-01

Formative assessments are systematically designed instructional interventions to assess and provide feedback on students' strengths and weaknesses in the course of teaching and learning. Despite their known benefits to student attitudes and learning, medical school curricula have been slow to integrate such assessments into the curriculum. This study investigates how performance on two different modes of formative assessment relate to each other and to performance on summative assessments in an integrated, medical-school environment. Two types of formative assessment were administered to 146 first-year medical students each week over 8 weeks: a timed, closed-book component to assess factual recall and image recognition, and an un-timed, open-book component to assess higher order reasoning including the ability to identify and access appropriate resources and to integrate and apply knowledge. Analogous summative assessments were administered in the ninth week. Models relating formative and summative assessment performance were tested using Structural Equation Modeling. Two latent variables underlying achievement on formative and summative assessments could be identified; a "formative-assessment factor" and a "summative-assessment factor," with the former predicting the latter. A latent variable underlying achievement on open-book formative assessments was highly predictive of achievement on both open- and closed-book summative assessments, whereas a latent variable underlying closed-book assessments only predicted performance on the closed-book summative assessment. Formative assessments can be used as effective predictive tools of summative performance in medical school. Open-book, un-timed assessments of higher order processes appeared to be better predictors of overall summative performance than closed-book, timed assessments of factual recall and image recognition.

Human β-defensin 4 with non-native disulfide bridges exhibit antimicrobial activity.

PubMed

Sharma, Himanshu; Nagaraj, Ramakrishnan

2015-01-01

Human defensins play multiple roles in innate immunity including direct antimicrobial killing and immunomodulatory activity. They have three disulfide bridges which contribute to the stability of three anti-parallel β-strands. The exact role of disulfide bridges and canonical β-structure in the antimicrobial action is not yet fully understood. In this study, we have explored the antimicrobial activity of human β-defensin 4 (HBD4) analogs that differ in the number and connectivity of disulfide bridges. The cysteine framework was similar to the disulfide bridges present in μ-conotoxins, an unrelated class of peptide toxins. All the analogs possessed enhanced antimicrobial potency as compared to native HBD4. Among the analogs, the single disulfide bridged peptide showed maximum potency. However, there were no marked differences in the secondary structure of the analogs. Subtle variations were observed in the localization and membrane interaction of the analogs with bacteria and Candida albicans, suggesting a role for disulfide bridges in modulating their antimicrobial action. All analogs accumulated in the cytosol where they can bind to anionic molecules such as nucleic acids which would affect several cellular processes leading to cell death. Our study strongly suggests that native disulfide bridges or the canonical β-strands in defensins have not evolved for maximal activity but they play important roles in determining their antimicrobial potency.

Human β-Defensin 4 with Non-Native Disulfide Bridges Exhibit Antimicrobial Activity

PubMed Central

Sharma, Himanshu; Nagaraj, Ramakrishnan

2015-01-01

Human defensins play multiple roles in innate immunity including direct antimicrobial killing and immunomodulatory activity. They have three disulfide bridges which contribute to the stability of three anti-parallel β-strands. The exact role of disulfide bridges and canonical β-structure in the antimicrobial action is not yet fully understood. In this study, we have explored the antimicrobial activity of human β-defensin 4 (HBD4) analogs that differ in the number and connectivity of disulfide bridges. The cysteine framework was similar to the disulfide bridges present in μ-conotoxins, an unrelated class of peptide toxins. All the analogs possessed enhanced antimicrobial potency as compared to native HBD4. Among the analogs, the single disulfide bridged peptide showed maximum potency. However, there were no marked differences in the secondary structure of the analogs. Subtle variations were observed in the localization and membrane interaction of the analogs with bacteria and Candida albicans, suggesting a role for disulfide bridges in modulating their antimicrobial action. All analogs accumulated in the cytosol where they can bind to anionic molecules such as nucleic acids which would affect several cellular processes leading to cell death. Our study strongly suggests that native disulfide bridges or the canonical β-strands in defensins have not evolved for maximal activity but they play important roles in determining their antimicrobial potency. PMID:25785690

The molecular structure of the isopoly complex ion, decavanadate (V10O286-)

USGS Publications Warehouse

Evans, H.T.

1966-01-01

The structure of the decavanadate ion V10O286- has been found by a determination of the crystal structure of K2Zn2V10O28?? 16H2O. The soluble, orange crystals are triclinic with space group P1 and have a unit cell with a = 10.778 A, b = 11.146 A, c = 8.774 A, ?? = 104?? 57???, ?? = 109?? 3???', and ?? = 65?? 0??? (Z = 1). The structure was solved from a three-dimensional Patterson map based on 5143 Weissenberg-film data. The full-matrix, least-squares refinement gave R = 0.094 and ?? for V-O bond lengths of 0.008 A. The unit cell contains one V10O286- unit, two Zn(H2O)62+ groups, two K+ ions, and four additional water molecules. The decavanadate ion is an isolated group of ten condensed VO6 octahedra, six in a rectangular 2 x 3 array sharing edges, and four more, two fitted in above and two below by sharing sloping edges. The structure, which is based on a sodium-chloride-like arrangement of V and O atoms, has a close relationship to other isopoly complex molybdates, niobates, and tantalates. Strong distortions in the VO6 octahedra are analogous to square-pyramid and other special coordination features known in other vanadate structures.

Structurally optimized analogs of the retrograde trafficking inhibitor Retro-2cycl limit Leishmania infections.

PubMed

Craig, Evan; Huyghues-Despointes, Charles-Eugene; Yu, Chun; Handy, Emma L; Sello, Jason K; Kima, Peter E

2017-05-01

In infected mammalian cells, Leishmania parasites reside within specialized compartments called parasitophorous vacuoles (LPVs). We have previously shown that Retro-2, a member of a novel class of small retrograde pathway inhibitors caused reduced LPV sizes and lower parasite numbers during experimental L. mexicana sp. infections. The purpose of this study was to determine if structural analogs of Retro-2cycl reported to have superior potency in the inhibition of retrograde pathway-dependent phenomena (i.e., polyomavirus cellular infection by polyomavrius and Shiga toxin trafficking in cells) are also more effective than the parent compound at controlling Leishmania infections. In addition to their effects on LPV development, we show that two optimized analogs of Retro-2cycl, DHQZ 36 and DHQZ 36.1 limit Leishmania amazonensis infection in macrophages at EC50 of 13.63+/-2.58μM and10.57+/-2.66μM, respectively, which is significantly lower than 40.15μM the EC50 of Retro-2cycl. In addition, these analogs caused a reversal in Leishmania induced suppression of IL-6 release by infected cells after LPS activation. Moreover, we show that in contrast to Retro-2cycl that is Leishmania static, the analogs can kill Leishmania parasites in axenic cultures, which is a desirable attribute for any drug to treat Leishmania infections. Together, these studies validate and extend the published structure-activity relationship analyses of Retro-2cycl.

Synthesis of mixed MOR/KOR efficacy cyclic opioid peptide analogs with antinociceptive activity after systemic administration.

PubMed

Perlikowska, Renata; Piekielna, Justyna; Gentilucci, Luca; De Marco, Rossella; Cerlesi, Maria Camilla; Calo, Girolamo; Artali, Roberto; Tömböly, Csaba; Kluczyk, Alicja; Janecka, Anna

2016-02-15

Cyclic pentapeptide Tyr-c[D-Lys-Phe-Phe-Asp]NH2, based on the structure of endomorphin-2 (EM-2), which shows high affinity to the μ-opioid receptor (MOR) and a very strong antinociceptive activity in mice was used as a parent compound for the structure-activity relationship studies. In this report we synthesized analogs of a general sequence Dmt-c[D-Lys-Xaa-Yaa-Asp]NH2, with D-1- or D-2-naphthyl-3-alanine (D-1-Nal or D-2-Nal) in positions 3 or 4. In our earlier papers we have indicated that replacing a phenylalanine residue by the more extended aromatic system of naphthylalanines may result in increased bioactivities of linear analogs. The data obtained here showed that only cyclopeptides modified in position 4 retained the sub-nanomolar MOR and nanomolar κ-opioid receptor (KOR) affinity, similar but not better than that of a parent cyclopeptide. In the in vivo mouse hot-plate test, the most potent analog, Dmt-c[D-Lys-Phe-D-1-Nal-Asp]NH2, exhibited higher than EM-2 but slightly lower than the cyclic parent peptide antinociceptive activity after peripheral (ip) and also central administration (icv). Conformational analyses in a biomimetic environment and molecular docking studies disclosed the structural determinants responsible for the different pharmacological profiles of position 3- versus position 4-modified analogs. Copyright © 2015. Published by Elsevier Masson SAS.

Relationships between mineralization and silicic volcanism in the central Andes

NASA Technical Reports Server (NTRS)

Francis, P. W.; Halls, C.; Baker, M. C. W.

1983-01-01

Existing models for the genesis of porphyry copper deposits indicate that they formed in granodioritic stocks located in the infrastructure of andesitic stratovolcanoes. It is noted that sites of porphyry-type subvolcanic tin mineralization in the Eastern Cordillera of Bolivia are distinguished by the absence of such andesitic structures. The surface expression of a typical subvolcanic porphyry tin deposit is thought to be an extrusive dome of quartz latite porphyry, sometimes related to a larger caldera structure. Evidence from the El Salvador porphyry copper deposit in the Eocene magmatic belt in Chile indicates that it too may be more closely related to a silicic volcanic structure than to an andesitic stratovolcano. The dome of La Soufriere, Guadeloupe is offered as a modern analog for the surface expression of subvolcanic mineralization processes, with the phreatic eruptions there indicating the formation of hydrothermal breccia bodies in depths. It is pointed out that the occurrence of mineralized porphyries, millions of years after caldera formation, does not necessarily indicate that tin intrusions and mineralization are not genetically related to the subcaldera pluton, but may be a consequence of the long thermal histories (1-10 million years) of the lowermost parts of large plutons.

Topological ring currents in the "empty" ring of benzo-annelated perylenes.

PubMed

Dickens, Timothy K; Mallion, Roger B

2011-01-27

Cyclic conjugation in benzo-annelated perylenes is examined by means of the topological π-electron ring currents calculated for each of their constituent rings, in a study that is an exact analogy of a recent investigation by Gutman et al. based on energy-effect values for the corresponding rings in each of these structures. "Classical" approaches, such as Kekulé structures, Clar "sextet" formulas, and circuits of conjugation, predict that the central ring in perylene is "empty" and thus contributes negligibly to cyclic conjugation. However, conclusions from the present calculations of topological ring currents agree remarkably with those arising from the earlier study involving energy-effect values in that, contrary to what would be predicted from the classical approaches, rings annelated in an angular fashion relative to the central ring of these perylene structures materially increase the extent of that ring's involvement in cyclic conjugation. It is suggested that such close quantitative agreement between the predictions of these two superficially very different indices (energy effect and topological ring current) might be due to the fact that, ultimately, both depend, albeit in ostensibly quite different ways, only on an adjacency matrix that contains information about the carbon-carbon connectivity of the conjugated system in question.

Enantioselective syntheses and biological studies of aeruginosin 298-A and its analogs: application of catalytic asymmetric phase-transfer reaction.

PubMed

Fukuta, Yuhei; Ohshima, Takashi; Gnanadesikan, Vijay; Shibuguchi, Tomoyuki; Nemoto, Tetsuhiro; Kisugi, Takaya; Okino, Tatsufumi; Shibasaki, Masakatsu

2004-04-13

Aeruginosin 298-A was isolated from the freshwater cyanobacterium Microcystis aeruginosa (NIES-298) and is an equipotent thrombin and trypsin inhibitor. A variety of analogs were synthesized to gain insight into the structure-activity relations. We developed a versatile synthetic process for aeruginosin 298-A as well as several attractive analogs, in which all stereocenters were controlled by catalytic asymmetric phase-transfer reaction promoted by two-center asymmetric catalysts and catalytic asymmetric epoxidation promoted by a lanthanide-BINOL complex. Furthermore, serine protease inhibitory activities of aeruginosin 298-A and its analogs were examined.

Mathematical Analogy and Metaphorical Insight

ERIC Educational Resources Information Center

Zwicky, Jan

2010-01-01

How are we to understand the power of certain literary metaphors? The author argues that the apprehension of good metaphors is importantly similar to the apprehension of fruitful mathematical analogies: both involve a structural realignment of vision. The author then explores consequences of this claim, drawing conceptually significant parallels…

Structure Mapping in Autism Spectrum Disorder: Levels of Information Processing and Relations to Executive Functions.

PubMed

Hetzroni, Orit E; Shalahevich, Kiril

2018-03-01

Analogical reasoning was investigated among children with autism spectrum disorders (ASD) without intellectual disabilities and typical development (TD). Children were asked to select one of two targets in two conditions: (1) with and without spatial structure similarity; (2) with and without a perceptual distractor. Results demonstrate that children with ASD were able to select targets based on structural similarity, but this ability decreased to chance level when presented with a perceptual distractor. Everyday executive functions were positively correlated with structural selections among children with ASD. Results suggest that although children with ASD were able to select based on systematicity principle, perceptual distractor decreased their selection so that their cognitive system produced less structure similarities, that negatively affects spatial analogical reasoning.

An active site-tail interaction in the structure of hexahistidine-tagged Thermoplasma acidophilum citrate synthase

DOE PAGES

Murphy, Jesse R.; Donini, Stefano; Kappock, T. Joseph

2015-10-01

Citrate synthase (CS) plays a central metabolic role in aerobes and many other organisms. The CS reaction comprises two half-reactions: a Claisen aldol condensation of acetyl-CoA (AcCoA) and oxaloacetate (OAA) that forms citryl-CoA (CitCoA), and CitCoA hydrolysis. Protein conformational changes that `close' the active site play an important role in the assembly of a catalytically competent condensation active site. CS from the thermoacidophile Thermoplasma acidophilum (TpCS) possesses an endogenous Trp fluorophore that can be used to monitor the condensation reaction. The 2.2 Å resolution crystal structure of TpCS fused to a C-terminal hexahistidine tag (TpCSH6) reported here is an `open'more » structure that, when compared with several liganded TpCS structures, helps to define a complete path for active-site closure. One active site in each dimer binds a neighboring His tag, the first nonsubstrate ligand known to occupy both the AcCoA and OAA binding sites. Solution data collectively suggest that this fortuitous interaction is stabilized by the crystalline lattice. In conclusion, as a polar but almost neutral ligand, the active site-tail interaction provides a new starting point for the design of bisubstrate-analog inhibitors of CS.« less

Engineering Cu surfaces for the electrocatalytic conversion of CO2: Controlling selectivity toward oxygenates and hydrocarbons

PubMed Central

Hahn, Christopher; Hatsukade, Toru; Kim, Youn-Geun; Vailionis, Arturas; Baricuatro, Jack H.; Higgins, Drew C.; Nitopi, Stephanie A.; Soriaga, Manuel P.; Jaramillo, Thomas F.

2017-01-01

In this study we control the surface structure of Cu thin-film catalysts to probe the relationship between active sites and catalytic activity for the electroreduction of CO2 to fuels and chemicals. Here, we report physical vapor deposition of Cu thin films on large-format (∼6 cm2) single-crystal substrates, and confirm epitaxial growth in the <100>, <111>, and <751> orientations using X-ray pole figures. To understand the relationship between the bulk and surface structures, in situ electrochemical scanning tunneling microscopy was conducted on Cu(100), (111), and (751) thin films. The studies revealed that Cu(100) and (111) have surface adlattices that are identical to the bulk structure, and that Cu(751) has a heterogeneous kinked surface with (110) terraces that is closely related to the bulk structure. Electrochemical CO2 reduction testing showed that whereas both Cu(100) and (751) thin films are more active and selective for C–C coupling than Cu(111), Cu(751) is the most selective for >2e− oxygenate formation at low overpotentials. Our results demonstrate that epitaxy can be used to grow single-crystal analogous materials as large-format electrodes that provide insights on controlling electrocatalytic activity and selectivity for this reaction. PMID:28533377

Multiple Aromaticity and Antiaromaticity in Silicon Clusters

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

Zhai, Hua JIN.; Kuznetsov, A E.; Boldyrev, Alexander I.

A series of silicon clusters containing four atoms but with different charge states (Si{sub 4}{sup 2+}, Si{sub 4}, Si{sub 4}{sup 2-}, and NaSi{sub 4}{sup -}) were studied by photoelectron spectroscopy and ab initio calculations. Structure evolution and chemical bonding in this series were interpreted in terms of aromaticity and antiaromaticity, which allowed the prediction of how structures of the four-atom silicon clusters change upon addition or removal of two electrons. It is shown that Si{sub 4}{sup 2+} is square-planar, analogous to the recently discovered aromatic Al{sub 4}{sup 2-} cluster. Upon addition of two electrons, neutral Si{sub 4} becomes {sigma}-antiaromatic andmore » exhibits a rhombus distortion. Adding two more electrons to Si{sub 4} leads to two energetically close structures of Si{sub 4}{sup 2-}: either a double antiaromatic parallelogram structure or an aromatic system with a butterfly distortion. Because of the electronic instability of doubly charged Si{sub 4}{sup 2-}, a stabilizing cation (Na{sup +}) was used to produce Si{sub 4}{sup 2-} in the gas phase in the form of Na{sup +}[Si{sub 4}{sup 2-}], which was characterized experimentally by photoelectron spectroscopy. Multiple antiaromaticity in the parallelogram Na{sup +}[Si{sub 4}{sup 2-}] species is highly unusual.« less

An active site-tail interaction in the structure of hexahistidine-tagged Thermoplasma acidophilum citrate synthase.

PubMed

Murphy, Jesse R; Donini, Stefano; Kappock, T Joseph

2015-10-01

Citrate synthase (CS) plays a central metabolic role in aerobes and many other organisms. The CS reaction comprises two half-reactions: a Claisen aldol condensation of acetyl-CoA (AcCoA) and oxaloacetate (OAA) that forms citryl-CoA (CitCoA), and CitCoA hydrolysis. Protein conformational changes that `close' the active site play an important role in the assembly of a catalytically competent condensation active site. CS from the thermoacidophile Thermoplasma acidophilum (TpCS) possesses an endogenous Trp fluorophore that can be used to monitor the condensation reaction. The 2.2 Å resolution crystal structure of TpCS fused to a C-terminal hexahistidine tag (TpCSH6) reported here is an `open' structure that, when compared with several liganded TpCS structures, helps to define a complete path for active-site closure. One active site in each dimer binds a neighboring His tag, the first nonsubstrate ligand known to occupy both the AcCoA and OAA binding sites. Solution data collectively suggest that this fortuitous interaction is stabilized by the crystalline lattice. As a polar but almost neutral ligand, the active site-tail interaction provides a new starting point for the design of bisubstrate-analog inhibitors of CS.

Aluminum manganese oxides with mixed crystal structure: high-energy-density cathodes for rechargeable sodium batteries.

PubMed

Han, Dong-Wook; Ku, Jun-Hwan; Kim, Ryoung-Hee; Yun, Dong-Jin; Lee, Seok-Soo; Doo, Seok-Gwang

2014-07-01

We report a new discovery for enhancing the energy density of manganese oxide (Nax MnO2 ) cathode materials for sodium rechargeable batteries by incorporation of aluminum. The Al incorporation results in NaAl(0.1) Mn(0.9) O2 with a mixture of tunnel and layered crystal structures. NaAl(0.1) Mn(0.9) O2 shows a much higher initial discharge capacity and superior cycling performance compared to pristine Na(0.65) MnO2 . We ascribe this enhancement in performance to the formation of a new orthorhombic layered NaMnO2 phase merged with a small amount of tunnel Na(0.44) MnO2 phase in NaAl(0.1) Mn(0.9) O2 , and to improvements in the surface stability of the NaAl(0.1) Mn(0.9) O2 particles caused by the formation of Al-O bonds on their surfaces. Our findings regarding the phase transformation and structure stabilization induced by incorporation of aluminum, closely related to the structural analogy between orthorhombic Na(0.44) MnO2 and NaAl(0.1) Mn(0.9) O2 , suggest a strategy for achieving sodium rechargeable batteries with high energy density and stability. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structure of the C-terminal Domain of Transcription Facto IIB from Trypanosoma brucei

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

Ibrahim, B.; Kanneganti, N; Rieckhof, G

In trypanosomes, the production of mRNA relies on the synthesis of the spliced leader (SL) RNA. Expression of the SL RNA is initiated at the only known RNA polymerase II promoter in these parasites. In the pathogenic trypanosome, Trypanosoma brucei, transcription factor IIB (tTFIIB) is essential for SL RNA gene transcription and cell viability, but has a highly divergent primary sequence in comparison to TFIIB in well-studied eukaryotes. Here we describe the 2.3 A resolution structure of the C-terminal domain of tTFIIB (tTFIIBC). The tTFIIBC structure consists of 2 closely packed helical modules followed by a C-terminal extension of 32more » aa. Using the structure as a guide, alanine substitutions of basic residues in regions analogous to functionally important regions of the well-studied eukaryotic TFIIB support conservation of a general mechanism of TFIIB function in eukaryotes. Strikingly, tTFIIBC contains additional loops and helices, and, in contrast to the highly basic DNA binding surface of human TFIIB, contains a neutral surface in the corresponding region. These attributes probably mediate trypanosome-specific interactions and have implications for the apparent bidirectional transcription by RNA polymerase II in protein-encoding gene expression in these organisms.« less

Elucidating the neurotoxic effects of MDMA and its analogs.

PubMed

Karuppagounder, Senthilkumar S; Bhattacharya, Dwipayan; Ahuja, Manuj; Suppiramaniam, Vishnu; Deruiter, Jack; Clark, Randall; Dhanasekaran, Muralikrishnan

2014-04-17

There is a rapid increase in the use of methylenedioxymethamphetamine (MDMA) and its structural congeners/analogs globally. MDMA and MDMA-analogs have been synthesized illegally in furtive dwellings and are abused due to its addictive potential. Furthermore, MDMA and MDMA-analogs have shown to have induced several adverse effects. Hence, understanding the mechanisms mediating this neurotoxic insult of MDMA-analogs is of immense importance for the public health in the world. We synthesized and investigated the neurotoxic effects of MDMA and its analogs [4-methylenedioxyamphetamine (MDA), 2, 6-methylenedioxyamphetamine (MDMA), and N-ethyl-3, 4-methylenedioxyamphetamine (MDEA)]. The stimulatory or the dopaminergic agonist effects of MDMA and MDMA-analogs were elucidated using the established 6-hydroxydopamine lesioned animal model. Additionally, we also investigated the neurotoxic mechanisms of MDMA and MDMA-analogs on mitochondrial complex-I activity and reactive oxygen species generation. MDMA and MDMA-analogs exhibited stimulatory activity as compared to amphetamines and also induced several behavioral changes in the rodents. MDMA and MDMA-analogs enhanced the reactive oxygen generation and inhibited mitochondrial complex-I activity which can lead to neurodegeneration. Hence the mechanism of neurotoxicity, MDMA and MDMA-analogs can enhance the release of monoamines, alter the monoaminergic neurotransmission, and augment oxidative stress and mitochondrial abnormalities leading to neurotoxicity. Thus, our study will help in developing effective pharmacological and therapeutic approaches for the treatment of MDMA and MDMA-analog abuse. Copyright © 2014 Elsevier Inc. All rights reserved.

Botulinum Neurotoxin Serotype A Inhibitors: Small-Molecule Mercaptoacetamide Analogs

PubMed Central

Moe, Scott T.; Thompson, Andrew B.; Smith, Genessa M.; Fredenburg, Ross A.; Stein, Ross L.; Jacobson, Alan R

2009-01-01

Botulinum neurotoxin elicits its paralytic activity through a zinc-dependant metalloprotease that cleaves proteins involved in neurotransmitter release. Currently, no drugs are available to reverse the effects of botulinum intoxication. Herein we report the design of a novel series of mercaptoacetamide small-molecule inhibitors active against botulinum neurotoxin serotype A. These analogs show low micromolar inhibitory activity against the isolated enzyme. Structure-activity relationship studies for a series of mercaptoacetamide analogs of 5-amino-3-phenylpyrazole reveal components essential for potent inhibitory activity. PMID:19329331

Drug Development of the Antimalarial Agent Artemisinin: Total Synthesis, Analog Synthesis, and Structure-Activity Relationship Studies

DTIC Science & Technology

1990-08-15

16. SUPPLEMENTARY NOTATION 17 COSATi CODES FiELD 07 06 CROUP 03 01 SUB-GROUP IB SUBJECT TERMS (Cont/nu* on rtvtnt if ntctiwy *ne identity b ...number of requisite substituents resulted in the synthesis of ring cleaved analogs and partial structures of artemisinin: (+)-C/D, (+)-A/ B /C, (+)-A/C...in the preparation of the unstable aldehyde 2, and in commendable fashion others have employed an enol ether photo-oxygenation as entry to that

Vertical Electron Detachment Energies for Octahedral Closed-Shell Multiply Charged Anions

DTIC Science & Technology

1994-04-22

however, at low theoretical levels, motivating us to extend the investigations to: a) higher levels of theory, b) analogous closed-shell singly- and...hundredths of an eV. This further supports our choice of SBKJ+diff as the basis set for the production runs. The SCF relaxation energies for F- and Cl...intensities for the product molecules ML 5(’)" (D3h) and ML 4 (n-2 )" 15 (Td) were determined at the SCF/SBKJ level and are reported in Table V

A dark business, full of shadows: analogy and theology in William Harvey.

PubMed

Goldberg, Benjamin

2013-09-01

In a short work called De conceptione appended to the end of his Exercitationes de generatione animalium (1651), William Harvey developed a rather strange analogy. To explain how such marvelous productions as living beings were generated from the rather inauspicious ingredients of animal reproduction, Harvey argued that conception in the womb was like conception in the brain. It was mostly rejected at the time; it now seems a ludicrous theory based upon homonymy. However, this analogy offers insight into the structure and function of analogies in early modern natural philosophy. In this essay I hope to not only describe the complex nature of Harvey's analogy, but also offer a novel interpretation of his use of analogical reasoning, substantially revising the account offered by Guido Giglioni (1993). I discuss two points of conceptual change and negotiation in connection with Harvey's analogy, understanding it as both a confrontation between the border of the natural and the supernatural, as well as a moment in the history of psychology. My interpretation touches upon a number of important aspects, including why the analogy was rejected, how Harvey systematically deployed analogies according to his notions of natural philosophical method, how the analogy fits into contemporary discussions of analogies in science, and finally, how the analogy must be seen in the context of changing Renaissance notions of the science of the soul, ultimately confronting the problem of how to understand final causality in Aristotelian science. In connection with the last, I conclude the essay by turning to how Harvey embeds the analogy within a natural theological cosmology. Copyright © 2013. Published by Elsevier Ltd.

A mechanism-based 3D-QSAR approach for classification and prediction of acetylcholinesterase inhibitory potency of organophosphate and carbamate analogs

NASA Astrophysics Data System (ADS)

Lee, Sehan; Barron, Mace G.

2016-04-01

Organophosphate (OP) and carbamate esters can inhibit acetylcholinesterase (AChE) by binding covalently to a serine residue in the enzyme active site, and their inhibitory potency depends largely on affinity for the enzyme and the reactivity of the ester. Despite this understanding, there has been no mechanism-based in silico approach for classification and prediction of the inhibitory potency of ether OPs or carbamates. This prompted us to develop a three dimensional prediction framework for OPs, carbamates, and their analogs. Inhibitory structures of a compound that can form the covalent bond were identified through analysis of docked conformations of the compound and its metabolites. Inhibitory potencies of the selected structures were then predicted using a previously developed three dimensional quantitative structure-active relationship. This approach was validated with a large number of structurally diverse OP and carbamate compounds encompassing widely used insecticides and structural analogs including OP flame retardants and thio- and dithiocarbamate pesticides. The modeling revealed that: (1) in addition to classical OP metabolic activation, the toxicity of carbamate compounds can be dependent on biotransformation, (2) OP and carbamate analogs such as OP flame retardants and thiocarbamate herbicides can act as AChEI, (3) hydrogen bonds at the oxyanion hole is critical for AChE inhibition through the covalent bond, and (4) π-π interaction with Trp86 is necessary for strong inhibition of AChE. Our combined computation approach provided detailed understanding of the mechanism of action of OP and carbamate compounds and may be useful for screening a diversity of chemical structures for AChE inhibitory potency.

MCD spectroscopy and TD-DFT calculations of low symmetry subnaphthalocyanine analogs.

PubMed

Mack, John; Otaki, Tatsuya; Durfee, William S; Kobayashi, Nagao; Stillman, Martin J

2014-07-01

Magnetic circular dichroism (MCD) spectroscopy and time-dependent density functional theory (TD-DFT) calculations are used to analyze the electronic structure and optical properties of low-symmetry subnaphthalocyanine analogs with AAB and ABB structures formed during mixed condensations of tetrafluorophthalonitrile and 2,3-naphthalenedicarbonitrile. The results demonstrate that trends observed in the properties of phthalocyanine analogs can be used to fine tune the optical properties so that the Q(0,0) bands lie in the red region, in a manner that does not significantly destabilize the highest occupied molecular orbital (HOMO) energy relative to that of the parent subphthalocyanine ligand. Attempts to study the spectroscopy of anion radical species proved unsuccessful, since they proved to be unstable. Copyright © 2014 Elsevier Inc. All rights reserved.

Enantioselective synthesis of pactamycin, a complex antitumor antibiotic.

PubMed

Malinowski, Justin T; Sharpe, Robert J; Johnson, Jeffrey S

2013-04-12

Medicinal application of many complex natural products is precluded by the impracticality of their chemical synthesis. Pactamycin, the most structurally intricate aminocyclopentitol antibiotic, displays potent antiproliferative properties across multiple phylogenetic domains, but it is highly cytotoxic. A limited number of analogs produced by genetic engineering technologies show reduced cytotoxicity against mammalian cells, renewing promise for therapeutic applications. For decades, an efficient synthesis of pactamycin amenable to analog derivatizations has eluded researchers. Here, we present a short asymmetric total synthesis of pactamycin. An enantioselective Mannich reaction and symmetry-breaking reduction sequence was designed to enable assembly of the entire carbon core skeleton in under five steps and control critical three-dimensional (stereochemical) functional group relationships. This modular route totals 15 steps and is immediately amenable for structural analog synthesis.

Spectroscopic and time-dependent density functional theory investigation of the photophysical properties of zearalenone and its analogs

USDA-ARS?s Scientific Manuscript database

Structures of the mycotoxin zearalenone and its analogs were investigated using density functional theory methods to gain insight into the ground state and excited state properties related to detection. Zearalenone is an estrogenic mycotoxin that can occur in agricultural commodities, and ultraviole...

Ideal gas thermodynamic properties for the phenyl, phenoxy, and o-biphenyl radicals

NASA Technical Reports Server (NTRS)

Burcat, A.; Zeleznik, F. J.; Mcbride, B. J.

1985-01-01

Ideal gas thermodynamic properties of the phenyl and o-biphenyl radicals, their deuterated analogs and the phenoxy radical were calculated to 5000 K using estimated vibrational frequencies and structures. The ideal gas thermodynamic properties of benzene, biphenyl, their deuterated analogs and phenyl were also calculated.

Temperature dependent Raman spectroscopy of melamine and structural analogs in milk powder

USDA-ARS?s Scientific Manuscript database

Hyperspectral Raman imaging has the potential for rapid screening of solid-phase samples for potential adulterants. We found that the Raman spectra of melamine analogs changed dramatically and uniquely as a function of elevated temperature. Raman spectra were acquired for urea, biuret, cyanuric acid...

Structural Basis for a Unique ATP Synthase Core Complex from Nanoarcheaum equitans*

PubMed Central

Mohanty, Soumya; Jobichen, Chacko; Chichili, Vishnu Priyanka Reddy; Velázquez-Campoy, Adrián; Low, Boon Chuan; Hogue, Christopher W. V.; Sivaraman, J.

2015-01-01

ATP synthesis is a critical and universal life process carried out by ATP synthases. Whereas eukaryotic and prokaryotic ATP synthases are well characterized, archaeal ATP synthases are relatively poorly understood. The hyperthermophilic archaeal parasite, Nanoarcheaum equitans, lacks several subunits of the ATP synthase and is suspected to be energetically dependent on its host, Ignicoccus hospitalis. This suggests that this ATP synthase might be a rudimentary machine. Here, we report the crystal structures and biophysical studies of the regulatory subunit, NeqB, the apo-NeqAB, and NeqAB in complex with nucleotides, ADP, and adenylyl-imidodiphosphate (non-hydrolysable analog of ATP). NeqB is ∼20 amino acids shorter at its C terminus than its homologs, but this does not impede its binding with NeqA to form the complex. The heterodimeric NeqAB complex assumes a closed, rigid conformation irrespective of nucleotide binding; this differs from its homologs, which require conformational changes for catalytic activity. Thus, although N. equitans possesses an ATP synthase core A3B3 hexameric complex, it might not function as a bona fide ATP synthase. PMID:26370083

Heterogeneous population dynamics and scaling laws near epidemic outbreaks.

PubMed

Widder, Andreas; Kuehn, Christian

2016-10-01

In this paper, we focus on the influence of heterogeneity and stochasticity of the population on the dynamical structure of a basic susceptible-infected-susceptible (SIS) model. First we prove that, upon a suitable mathematical reformulation of the basic reproduction number, the homogeneous system and the heterogeneous system exhibit a completely analogous global behaviour. Then we consider noise terms to incorporate the fluctuation effects and the random import of the disease into the population and analyse the influence of heterogeneity on warning signs for critical transitions (or tipping points). This theory shows that one may be able to anticipate whether a bifurcation point is close before it happens. We use numerical simulations of a stochastic fast-slow heterogeneous population SIS model and show various aspects of heterogeneity have crucial influences on the scaling laws that are used as early-warning signs for the homogeneous system. Thus, although the basic structural qualitative dynamical properties are the same for both systems, the quantitative features for epidemic prediction are expected to change and care has to be taken to interpret potential warning signs for disease outbreaks correctly.

Formation of a disordered solid via a shock-induced transition in a dense particle suspension

NASA Astrophysics Data System (ADS)

Petel, Oren E.; Frost, David L.; Higgins, Andrew J.; Ouellet, Simon

2012-02-01

Shock wave propagation in multiphase media is typically dominated by the relative compressibility of the two components of the mixture. The difference in the compressibility of the components results in a shock-induced variation in the effective volume fraction of the suspension tending toward the random-close-packing limit for the system, and a disordered solid can take form within the suspension. The present study uses a Hugoniot-based model to demonstrate this variation in the volume fraction of the solid phase as well as a simple hard-sphere model to investigate the formation of disordered structures within uniaxially compressed model suspensions. Both models are discussed in terms of available experimental plate impact data in dense suspensions. Through coordination number statistics of the mesoscopic hard-sphere model, comparisons are made with the trends of the experimental pressure-volume fraction relationship to illustrate the role of these disordered structures in the bulk properties of the suspensions. A criterion for the dynamic stiffening of suspensions under high-rate dynamic loading is suggested as an analog to quasi-static jamming based on the results of the simulations.

Biocompatible nanocrystalline natural bonelike carbonated hydroxyapatite synthesized by mechanical alloying in a record minimum time.

PubMed

Lala, S; Brahmachari, S; Das, P K; Das, D; Kar, T; Pradhan, S K

2014-09-01

Single phase nanocrystalline biocompatible A-type carbonated hydroxyapatite (A-cHAp) powder has been synthesized by mechanical alloying the stoichiometric mixture of CaCO3 and CaHPO4.2H2O powders in open air at room temperature within 2h of milling. The A-type carbonation in HAp is confirmed by FTIR analysis. Structural and microstructure parameters of as-milled powders are obtained from both Rietveld's powder structure refinement analysis and transmission electron microscopy. Size and lattice strain of nanocrystalline HAp particles are found to be anisotropic in nature. Mechanical alloying causes amorphization of a part of crystalline A-cHAp which is analogous to native bone mineral. Some primary bond lengths of as-milled samples are critically measured. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay test reveals high percentage of cell viability and hence confirms the biocompatibility of the sample. The overall results indicate that the processed A-cHAp has a chemical composition very close to that of biological apatite. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of capsid confinement on the chromatin organization of the SV40 minichromosome

PubMed Central

Saper, Gadiel; Kler, Stanislav; Asor, Roi; Oppenheim, Ariella; Raviv, Uri; Harries, Daniel

2013-01-01

Using small-angle X-ray scattering, we determined the three-dimensional packing architecture of the minichromosome confined within the SV40 virus. In solution, the minichromosome, composed of closed circular dsDNA complexed in nucleosomes, was shown to be structurally similar to cellular chromatin. In contrast, we find a unique organization of the nanometrically encapsidated chromatin, whereby minichromosomal density is somewhat higher at the center of the capsid and decreases towards the walls. This organization is in excellent agreement with a coarse-grained computer model, accounting for tethered nucleosomal interactions under viral capsid confinement. With analogy to confined liquid crystals, but contrary to the solenoid structure of cellular chromatin, our simulations indicate that the nucleosomes within the capsid lack orientational order. Nucleosomes in the layer adjacent to the capsid wall, however, align with the boundary, thereby inducing a ‘molten droplet’ state of the chromatin. These findings indicate that nucleosomal interactions suffice to predict the genome organization in polyomavirus capsids and underscore the adaptable nature of the eukaryotic chromatin architecture to nanoscale confinement. PMID:23258701

Finite-time barriers to front propagation in two-dimensional fluid flows

NASA Astrophysics Data System (ADS)

Mahoney, John R.; Mitchell, Kevin A.

2015-08-01

Recent theoretical and experimental investigations have demonstrated the role of certain invariant manifolds, termed burning invariant manifolds (BIMs), as one-way dynamical barriers to reaction fronts propagating within a flowing fluid. These barriers form one-dimensional curves in a two-dimensional fluid flow. In prior studies, the fluid velocity field was required to be either time-independent or time-periodic. In the present study, we develop an approach to identify prominent one-way barriers based only on fluid velocity data over a finite time interval, which may have arbitrary time-dependence. We call such a barrier a burning Lagrangian coherent structure (bLCS) in analogy to Lagrangian coherent structures (LCSs) commonly used in passive advection. Our approach is based on the variational formulation of LCSs using curves of stationary "Lagrangian shear," introduced by Farazmand et al. [Physica D 278-279, 44 (2014)] in the context of passive advection. We numerically validate our technique by demonstrating that the bLCS closely tracks the BIM for a time-independent, double-vortex channel flow with an opposing "wind."

Observed Free-Play Patterns of Children with ADHD and Their Real-Life Friends.

PubMed

Normand, Sébastien; Soucisse, Marie Michèle; Melançon, Marie Pier Vézina; Schneider, Barry H; Lee, Matthew D; Maisonneuve, Marie-France

2018-04-26

Previous observational studies conducted in highly structured, analog situations indicate that children with Attention-Deficit/Hyperactivity Disorder (ADHD) mismanage their relationships with same-age peers and friends. Such structured situations may not, however, fully represent the true nature of children's play, which is typically characterized by free choice, intrinsic motivation, and spontaneity. The unique objective of the current observational study was to describe how 87 children with ADHD and 46 comparison (76% boys) aged 7-13 years behave when interacting with their real-life dyadic friends during an unstructured, free-play situation. Results indicate that dyads comprising one referred child with ADHD and an invited friend ("ADHD dyads") engaged in less cooperative play, displayed less companionship, and showed less sensitivity to friends than comparison dyads. ADHD dyads also engaged in more conflict and exhibited significantly more negative affect than comparison dyads. These findings complement and extend, possibly with somewhat enhanced ecological validity, results obtained in previous studies on the friendships of children with ADHD featuring closed-field observations and questionnaire methodology.

Geometrical aspects of the frustration in the cubic phases of lyotropic liquid crystals.

PubMed Central

Anderson, D M; Gruner, S M; Leibler, S

1988-01-01

Bicontinuous cubic phases, composed of bilayers arranged in the geometries of periodic minimal surfaces, are found in a variety of different lipid/water systems. It has been suggested recently that these cubic structures arrive as the result of competition between two free-energy terms: the curvature energy of each monolayer and the stretching energy of the lipid chains. This scenario, closely analogous to the one that explains the origin of the hexagonal phases, is investigated here by means of simple geometrical calculations. It is first assumed that the lipid bilayer is of constant thickness and the distribution of the (local) mean curvature of the phospholipid-water interfaces is calculated. Then, assuming the mean curvature of these interfaces is constant, the distribution of the bilayer's thickness is calculated. Both calculations quantify the fact that the two energy terms are frustrated and cannot be satisfied simultaneously. However, the amount of the frustration can be smaller for the cubic phase than for the lamellar and hexagonal structures. Therefore, this phase can appear in the phase diagram between the other two, as observed in many recent experiments. PMID:3399497

The Structural Basis for Matrix Metalloproteinase 1 Catalyzed Collagenolysis

PubMed Central

Bertini, Ivano; Fragai, Marco; Luchinat, Claudio; Melikian, Maxime; Toccafondi, Mirco; Lauer, Janelle L.; Fields, Gregg B.

2012-01-01

The proteolysis of collagen triple-helical structure (collagenolysis) is a poorly understood yet critical physiological process. Presently, matrix metalloproteinase 1 (MMP-1) and collagen triple-helical peptide models have been utilized to characterize the events and calculate the energetics of collagenolysis via NMR spectroscopic analysis of 12 enzyme-substrate complexes. The triple-helix is bound initially by the MMP-1 hemopexin-like (HPX) domain via a four amino acid stretch (analogous to type I collagen residues 782–785). The triple-helix is then presented to the MMP-1 catalytic (CAT) domain in a distinct orientation. The HPX and CAT domains are rotated with respect to one another compared with the X-ray “closed” conformation of MMP-1. Back-rotation of the CAT and HPX domains to the X-ray closed conformation releases one chain out of the triple-helix, and this chain is properly positioned in the CAT domain active site for subsequent hydrolysis. The aforementioned steps provide a detailed, experimentally-derived, and energetically favorable collagenolytic mechanism, as well as significant insight into the roles of distinct domains in extracellular protease function. PMID:22239621

Effect of capsid confinement on the chromatin organization of the SV40 minichromosome.

PubMed

Saper, Gadiel; Kler, Stanislav; Asor, Roi; Oppenheim, Ariella; Raviv, Uri; Harries, Daniel

2013-02-01

Using small-angle X-ray scattering, we determined the three-dimensional packing architecture of the minichromosome confined within the SV40 virus. In solution, the minichromosome, composed of closed circular dsDNA complexed in nucleosomes, was shown to be structurally similar to cellular chromatin. In contrast, we find a unique organization of the nanometrically encapsidated chromatin, whereby minichromosomal density is somewhat higher at the center of the capsid and decreases towards the walls. This organization is in excellent agreement with a coarse-grained computer model, accounting for tethered nucleosomal interactions under viral capsid confinement. With analogy to confined liquid crystals, but contrary to the solenoid structure of cellular chromatin, our simulations indicate that the nucleosomes within the capsid lack orientational order. Nucleosomes in the layer adjacent to the capsid wall, however, align with the boundary, thereby inducing a 'molten droplet' state of the chromatin. These findings indicate that nucleosomal interactions suffice to predict the genome organization in polyomavirus capsids and underscore the adaptable nature of the eukaryotic chromatin architecture to nanoscale confinement.

Digital redesign of the control system for the Robotics Research Corporation model K-1607 robot

NASA Technical Reports Server (NTRS)

Carroll, Robert L.

1989-01-01

The analog control system for positioning each link of the Robotics Research Corporation Model K-1607 robot manipulator was redesigned for computer control. In order to accomplish the redesign, a linearized model of the dynamic behavior of the robot was developed. The parameters of the model were determined by examination of the input-output data collected in closed-loop operation of the analog control system. The robot manipulator possesses seven degrees of freedom in its motion. The analog control system installed by the manufacturer of the robot attempts to control the positioning of each link without feedback from other links. Constraints on the design of a digital control system include: the robot cannot be disassembled for measurement of parameters; the digital control system must not include filtering operations if possible, because of lack of computer capability; and criteria of goodness of control system performing is lacking. The resulting design employs sampled-data position and velocity feedback. The criteria of the design permits the control system gain margin and phase margin, measured at the same frequencies, to be the same as that provided by the analog control system.

DACS II - A distributed thermal/mechanical loads data acquisition and control system

NASA Technical Reports Server (NTRS)

Zamanzadeh, Behzad; Trover, William F.; Anderson, Karl F.

1987-01-01

A distributed data acquisition and control system has been developed for the NASA Flight Loads Research Facility. The DACS II system is composed of seven computer systems and four array processors configured as a main computer system, three satellite computer systems, and 13 analog input/output systems interconnected through three independent data networks. Up to three independent heating and loading tests can be run concurrently on different test articles or the entire system can be used on a single large test such as a full scale hypersonic aircraft. Thermal tests can include up to 512 independent adaptive closed loop control channels. The control system can apply up to 20 MW of heating to a test specimen while simultaneously applying independent mechanical loads. Each thermal control loop is capable of heating a structure at rates of up to 150 F per second over a temperature range of -300 to +2500 F. Up to 64 independent mechanical load profiles can be commanded along with thermal control. Up to 1280 analog inputs monitor temperature, load, displacement and strain on the test specimens with real time data displayed on up to 15 terminals as color plots and tabular data displays. System setup and operation is accomplished with interactive menu-driver displays with extensive facilities to assist the users in all phases of system operation.

Normal modes and mode transformation of pure electron vortex beams

PubMed Central

Thirunavukkarasu, G.; Mousley, M.; Babiker, M.

2017-01-01

Electron vortex beams constitute the first class of matter vortex beams which are currently routinely produced in the laboratory. Here, we briefly review the progress of this nascent field and put forward a natural quantum basis set which we show is suitable for the description of electron vortex beams. The normal modes are truncated Bessel beams (TBBs) defined in the aperture plane or the Fourier transform of the transverse structure of the TBBs (FT-TBBs) in the focal plane of a lens with the said aperture. As these modes are eigenfunctions of the axial orbital angular momentum operator, they can provide a complete description of the two-dimensional transverse distribution of the wave function of any electron vortex beam in such a system, in analogy with the prominent role Laguerre–Gaussian (LG) beams played in the description of optical vortex beams. The characteristics of the normal modes of TBBs and FT-TBBs are described, including the quantized orbital angular momentum (in terms of the winding number l) and the radial index p>0. We present the experimental realization of such beams using computer-generated holograms. The mode analysis can be carried out using astigmatic transformation optics, demonstrating close analogy with the astigmatic mode transformation between LG and Hermite–Gaussian beams. This article is part of the themed issue ‘Optical orbital angular momentum’. PMID:28069769

Normal modes and mode transformation of pure electron vortex beams.

PubMed

Thirunavukkarasu, G; Mousley, M; Babiker, M; Yuan, J

2017-02-28

Electron vortex beams constitute the first class of matter vortex beams which are currently routinely produced in the laboratory. Here, we briefly review the progress of this nascent field and put forward a natural quantum basis set which we show is suitable for the description of electron vortex beams. The normal modes are truncated Bessel beams (TBBs) defined in the aperture plane or the Fourier transform of the transverse structure of the TBBs (FT-TBBs) in the focal plane of a lens with the said aperture. As these modes are eigenfunctions of the axial orbital angular momentum operator, they can provide a complete description of the two-dimensional transverse distribution of the wave function of any electron vortex beam in such a system, in analogy with the prominent role Laguerre-Gaussian (LG) beams played in the description of optical vortex beams. The characteristics of the normal modes of TBBs and FT-TBBs are described, including the quantized orbital angular momentum (in terms of the winding number l) and the radial index p>0. We present the experimental realization of such beams using computer-generated holograms. The mode analysis can be carried out using astigmatic transformation optics, demonstrating close analogy with the astigmatic mode transformation between LG and Hermite-Gaussian beams.This article is part of the themed issue 'Optical orbital angular momentum'. © 2017 The Author(s).

Disruption of endolysosomal trafficking pathways in glioma cells by methuosis-inducing indole-based chalcones.

PubMed

Mbah, Nneka E; Overmeyer, Jean H; Maltese, William A

2017-06-01

Methuosis is a form of non-apoptotic cell death involving massive vacuolization of macropinosome-derived endocytic compartments, followed by a decline in metabolic activity and loss of membrane integrity. To explore the induction of methuosis as a potential therapeutic strategy for killing cancer cells, we have developed small molecules (indole-based chalcones) that trigger this form of cell death in glioblastoma and other cancer cell lines. Here, we report that in addition to causing fusion and expansion of macropinosome compartments, the lead compound, 3-(5-methoxy-2-methyl-1H-indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one (MOMIPP), disrupts vesicular trafficking at the lysosomal nexus, manifested by impaired degradation of EGF and LDL receptors, defective processing of procathepsins, and accumulation of autophagosomes. In contrast, secretion of the ectodomain derived from a prototypical type-I membrane glycoprotein, β-amyloid precursor protein, is increased rather than diminished. A closely related MOMIPP analog, which causes substantial vacuolization without reducing cell viability, also impedes cathepsin processing and autophagic flux, but has more modest effects on receptor degradation. A third analog, which causes neither vacuolization nor loss of viability, has no effect on endolysosomal trafficking. The results suggest that differential cytotoxicity of structurally similar indole-based chalcones is related, at least in part, to the severity of their effects on endolysosomal trafficking pathways.

Total synthesis of natural derivatives and artificial analogs of 13-oxyingenol and their biological evaluation.

PubMed

Ohyoshi, Takayuki; Tamura, Yuki; Hayakawa, Ichiro; Hirai, Go; Miyazawa, Yamato; Funakubo, Shota; Sodeoka, Mikiko; Kigoshi, Hideo

2016-12-28

We have established an efficient synthetic methodology for the 13-oxyingenol natural derivative (13-oxyingenol-13-dodecanoate-20-hexanoate), featuring a ring-closing olefin metathesis reaction for the "direct" construction of a highly strained inside-outside framework and a Mislow-Evans-type [2,3]-sigmatropic rearrangement for the stereoselective introduction of the hydroxy group at C5. We also synthesized artificial analogs of 13-oxyingenol and ingenol by using our synthetic strategy. In vitro activation assays of protein kinase C (PKC) α and δ revealed that the dodecanoyl group at O13 on 13-oxyingenol analogs had a significant role in PKCδ activation. The PKCα- or PKCδ-activating 13-oxyingenol and ingenol analogs induced both distinct morphological changes and increases of CD11b expression in HL-60 cells, which would be typical signs of HL-60 cell differentiation to macrophage-like cells, as expected by previous reports. Intriguingly, however, similar differentiation phenotypes were observed with the use of 13-oxyingenol natural derivatives and 13-oxyingenol-13-dodecanoate showing a remarkably less potent PKCα or PKCδ activation ability, which the PKC inhibitor Gö6983 diminished. This indicated the involvement of other PKC isozymes or related kinase activities. 13-Oxyingenol analogs, which induced HL-60 cell differentiation, also induced HL-60 cell death, similar to the action of a phorbol ester, a strong PKC activator.

A Bidirectional Neural Interface IC with Chopper Stabilized BioADC Array and Charge Balanced Stimulator

PubMed Central

Greenwald, Elliot; So, Ernest; Wang, Qihong; Mollazadeh, Mohsen; Maier, Christoph; Etienne-Cummings, Ralph; Cauwenberghs, Gert; Thakor, Nitish

2016-01-01

We present a bidirectional neural interface with a 4-channel biopotential analog-to-digital converter (bioADC) and a 4-channel current-mode stimulator in 180nm CMOS. The bioADC directly transduces microvolt biopotentials into a digital representation without a voltage-amplification stage. Each bioADC channel comprises a continuous-time first-order ΔΣ modulator with a chopper-stabilized OTA input and current feedback, followed by a second-order comb-filter decimator with programmable oversampling ratio. Each stimulator channel contains two independent digital-to-analog converters for anodic and cathodic current generation. A shared calibration circuit matches the amplitude of the anodic and cathodic currents for charge balancing. Powered from a 1.5V supply, the analog and digital circuits in each recording channel draw on average 1.54 μA and 2.13 μA of supply current, respectively. The bioADCs achieve an SNR of 58 dB and a SFDR of >70 dB, for better than 9-b ENOB. Intracranial EEG recordings from an anesthetized rat are shown and compared to simultaneous recordings from a commercial reference system to validate performance in-vivo. Additionally, we demonstrate bidirectional operation by recording cardiac modulation induced through vagus nerve stimulation, and closed-loop control of cardiac rhythm. The micropower operation, direct digital readout, and integration of electrical stimulation circuits make this interface ideally suited for closed-loop neuromodulation applications. PMID:27845676

Synthesis of Five Known Brassinosteroid Analogs from Hyodeoxycholic Acid and Their Activities as Plant-Growth Regulators.

PubMed

Duran, María Isabel; González, Cesar; Acosta, Alison; Olea, Andrés F; Díaz, Katy; Espinoza, Luis

2017-03-08

Brassinosteroids (BRs) are plant hormones that promote growth in different plant organs and tissues. The structural requirements that these compounds should possess to exhibit this biological activity have been studied. In this work, a series of known BR analogs 5 - 15 , were synthesized starting from hyodeoxycholic acid 4 , and maintaining the alkyl side chain as cholic acid or its methyl ester. The growth-promoting effects of brassinolide ( 1 ) and synthesized analogs were evaluated by using the rice lamina inclination assay at concentrations ranging from 1 × 10 -8 -1 × 10 -6 M. Our results indicate that in this concentration range the induced bending angle of rice seedlings increases with increasing concentration of BRs. Analysis of the activities, determined at the lowest tested concentration, in terms of BR structures shows that the 2α,3α-dihydroxy-7-oxa-6-ketone moiety existing in brassinolide is required for the plant growing activity of these compounds, as it has been proposed by some structure-activity relationship studies. The effect of compound 8 on cell elongation was assessed by microscopy analysis, and the results indicate that the growth-promoting effect of analog 8 is mainly due to cell elongation of the adaxial sides, instead of an increase on cell number.

Synthesis of Five Known Brassinosteroid Analogs from Hyodeoxycholic Acid and Their Activities as Plant-Growth Regulators

PubMed Central

Duran, María Isabel; González, Cesar; Acosta, Alison; Olea, Andrés F.; Díaz, Katy; Espinoza, Luis

2017-01-01

Brassinosteroids (BRs) are plant hormones that promote growth in different plant organs and tissues. The structural requirements that these compounds should possess to exhibit this biological activity have been studied. In this work, a series of known BR analogs 5–15, were synthesized starting from hyodeoxycholic acid 4, and maintaining the alkyl side chain as cholic acid or its methyl ester. The growth-promoting effects of brassinolide (1) and synthesized analogs were evaluated by using the rice lamina inclination assay at concentrations ranging from 1 × 10−8–1 × 10−6 M. Our results indicate that in this concentration range the induced bending angle of rice seedlings increases with increasing concentration of BRs. Analysis of the activities, determined at the lowest tested concentration, in terms of BR structures shows that the 2α,3α-dihydroxy-7-oxa-6-ketone moiety existing in brassinolide is required for the plant growing activity of these compounds, as it has been proposed by some structure-activity relationship studies. The effect of compound 8 on cell elongation was assessed by microscopy analysis, and the results indicate that the growth-promoting effect of analog 8 is mainly due to cell elongation of the adaxial sides, instead of an increase on cell number. PMID:28282853

Decentralized real-time simulation of forest machines

NASA Astrophysics Data System (ADS)

Freund, Eckhard; Adam, Frank; Hoffmann, Katharina; Rossmann, Juergen; Kraemer, Michael; Schluse, Michael

2000-10-01

To develop realistic forest machine simulators is a demanding task. A useful simulator has to provide a close- to-reality simulation of the forest environment as well as the simulation of the physics of the vehicle. Customers demand a highly realistic three dimensional forestry landscape and the realistic simulation of the complex motion of the vehicle even in rough terrain in order to be able to use the simulator for operator training under close-to- reality conditions. The realistic simulation of the vehicle, especially with the driver's seat mounted on a motion platform, greatly improves the effect of immersion into the virtual reality of a simulated forest and the achievable level of education of the driver. Thus, the connection of the real control devices of forest machines to the simulation system has to be supported, i.e. the real control devices like the joysticks or the board computer system to control the crane, the aggregate etc. Beyond, the fusion of the board computer system and the simulation system is realized by means of sensors, i.e. digital and analog signals. The decentralized system structure allows several virtual reality systems to evaluate and visualize the information of the control devices and the sensors. So, while the driver is practicing, the instructor can immerse into the same virtual forest to monitor the session from his own viewpoint. In this paper, we are describing the realized structure as well as the necessary software and hardware components and application experiences.

Biological Characterization of Microenvironments in a Hypersaline Cold Spring Mars Analog

PubMed Central

Sapers, Haley M.; Ronholm, Jennifer; Raymond-Bouchard, Isabelle; Comrey, Raven; Osinski, Gordon R.; Whyte, Lyle G.

2017-01-01

While many habitable niches on Earth are characterized by permanently cold conditions, little is known about the spatial structure of seasonal communities and the importance of substrate-cell associations in terrestrial cyroenvironments. Here we use the 16S rRNA gene as a marker for genetic diversity to compare two visually distinct but spatially integrated surface microbial mats on Axel Heiberg Island, Canadian high arctic, proximal to a perennial saline spring. This is the first study to describe the bacterial diversity in microbial mats on Axel Heiberg Island. The hypersaline springs on Axel Heiberg represent a unique analog to putative subsurface aquifers on Mars. The Martian subsurface represents the longest-lived potentially habitable environment on Mars and a better understanding of the microbial communities on Earth that thrive in analog conditions will help direct future life detection missions. The microbial mats sampled on Axel Heiberg are only visible during the summer months in seasonal flood plains formed by melt water and run-off from the proximal spring. Targeted-amplicon sequencing revealed that not only does the bacterial composition of the two mat communities differ substantially from the sediment community of the proximal cold spring, but that the mat communities are distinct from any other microbial community in proximity to the Arctic springs studied to date. All samples are dominated by Gammaproteobacteria: Thiotichales is dominant within the spring samples while Alteromonadales comprises a significant component of the mat communities. The two mat samples differ in their Thiotichales:Alteromonadales ratio and contribution of Bacteroidetes to overall diversity. The red mats have a greater proportion of Alteromonadales and Bacteroidetes reads. The distinct bacterial composition of the mat bacterial communities suggests that the spring communities are not sourced from the surface, and that seasonal melt events create ephemerally habitable niches with distinct microbial communities in the Canadian high arctic. The finding that these surficial complex microbial communities exist in close proximity to perennial springs demonstrates the existence of a transiently habitable niche in an important Mars analog site. PMID:29312221

Biological Characterization of Microenvironments in a Hypersaline Cold Spring Mars Analog.

PubMed

Sapers, Haley M; Ronholm, Jennifer; Raymond-Bouchard, Isabelle; Comrey, Raven; Osinski, Gordon R; Whyte, Lyle G

2017-01-01

While many habitable niches on Earth are characterized by permanently cold conditions, little is known about the spatial structure of seasonal communities and the importance of substrate-cell associations in terrestrial cyroenvironments. Here we use the 16S rRNA gene as a marker for genetic diversity to compare two visually distinct but spatially integrated surface microbial mats on Axel Heiberg Island, Canadian high arctic, proximal to a perennial saline spring. This is the first study to describe the bacterial diversity in microbial mats on Axel Heiberg Island. The hypersaline springs on Axel Heiberg represent a unique analog to putative subsurface aquifers on Mars. The Martian subsurface represents the longest-lived potentially habitable environment on Mars and a better understanding of the microbial communities on Earth that thrive in analog conditions will help direct future life detection missions. The microbial mats sampled on Axel Heiberg are only visible during the summer months in seasonal flood plains formed by melt water and run-off from the proximal spring. Targeted-amplicon sequencing revealed that not only does the bacterial composition of the two mat communities differ substantially from the sediment community of the proximal cold spring, but that the mat communities are distinct from any other microbial community in proximity to the Arctic springs studied to date. All samples are dominated by Gammaproteobacteria: Thiotichales is dominant within the spring samples while Alteromonadales comprises a significant component of the mat communities. The two mat samples differ in their Thiotichales:Alteromonadales ratio and contribution of Bacteroidetes to overall diversity. The red mats have a greater proportion of Alteromonadales and Bacteroidetes reads. The distinct bacterial composition of the mat bacterial communities suggests that the spring communities are not sourced from the surface, and that seasonal melt events create ephemerally habitable niches with distinct microbial communities in the Canadian high arctic. The finding that these surficial complex microbial communities exist in close proximity to perennial springs demonstrates the existence of a transiently habitable niche in an important Mars analog site.

Functional Dissection of the Bipartite Active Site of the Class I Coenzyme A (CoA)-Transferase Succinyl-CoA:Acetate CoA-Transferase.

PubMed

Murphy, Jesse R; Mullins, Elwood A; Kappock, T Joseph

2016-01-01

Coenzyme A (CoA)-transferases catalyze the reversible transfer of CoA from acyl-CoA thioesters to free carboxylates. Class I CoA-transferases produce acylglutamyl anhydride intermediates that undergo attack by CoA thiolate on either the internal or external carbonyl carbon atoms, forming distinct tetrahedral intermediates <3 Å apart. In this study, crystal structures of succinyl-CoA:acetate CoA-transferase (AarC) from Acetobacter aceti are used to examine how the Asn347 carboxamide stabilizes the internal oxyanion intermediate. A structure of the active mutant AarC-N347A bound to CoA revealed both solvent replacement of the missing contact and displacement of the adjacent Glu294, indicating that Asn347 both polarizes and orients the essential glutamate. AarC was crystallized with the nonhydrolyzable acetyl-CoA (AcCoA) analog dethiaacetyl-CoA (1a) in an attempt to trap a closed enzyme complex containing a stable analog of the external oxyanion intermediate. One active site contained an acetylglutamyl anhydride adduct and truncated 1a, an unexpected result hinting at an unprecedented cleavage of the ketone moiety in 1a. Solution studies confirmed that 1a decomposition is accompanied by production of near-stoichiometric acetate, in a process that seems to depend on microbial contamination but not AarC. A crystal structure of AarC bound to the postulated 1a truncation product (2a) showed complete closure of one active site per dimer but no acetylglutamyl anhydride, even with acetate added. These findings suggest that an activated acetyl donor forms during 1a decomposition; a working hypothesis involving ketone oxidation is offered. The ability of 2a to induce full active site closure furthermore suggests that it subverts a system used to impede inappropriate active site closure on unacylated CoA.

Functional Dissection of the Bipartite Active Site of the Class I Coenzyme A (CoA)-Transferase Succinyl-CoA:Acetate CoA-Transferase

PubMed Central

Murphy, Jesse R.; Mullins, Elwood A.; Kappock, T. Joseph

2016-01-01

Coenzyme A (CoA)-transferases catalyze the reversible transfer of CoA from acyl-CoA thioesters to free carboxylates. Class I CoA-transferases produce acylglutamyl anhydride intermediates that undergo attack by CoA thiolate on either the internal or external carbonyl carbon atoms, forming distinct tetrahedral intermediates <3 Å apart. In this study, crystal structures of succinyl-CoA:acetate CoA-transferase (AarC) from Acetobacter aceti are used to examine how the Asn347 carboxamide stabilizes the internal oxyanion intermediate. A structure of the active mutant AarC-N347A bound to CoA revealed both solvent replacement of the missing contact and displacement of the adjacent Glu294, indicating that Asn347 both polarizes and orients the essential glutamate. AarC was crystallized with the nonhydrolyzable acetyl-CoA (AcCoA) analog dethiaacetyl-CoA (1a) in an attempt to trap a closed enzyme complex containing a stable analog of the external oxyanion intermediate. One active site contained an acetylglutamyl anhydride adduct and truncated 1a, an unexpected result hinting at an unprecedented cleavage of the ketone moiety in 1a. Solution studies confirmed that 1a decomposition is accompanied by production of near-stoichiometric acetate, in a process that seems to depend on microbial contamination but not AarC. A crystal structure of AarC bound to the postulated 1a truncation product (2a) showed complete closure of one active site per dimer but no acetylglutamyl anhydride, even with acetate added. These findings suggest that an activated acetyl donor forms during 1a decomposition; a working hypothesis involving ketone oxidation is offered. The ability of 2a to induce full active site closure furthermore suggests that it subverts a system used to impede inappropriate active site closure on unacylated CoA. PMID:27242998

Functional dissection of the bipartite active site of the class I coenzyme A (CoA)-transferase succinyl-CoA:acetate CoA-transferase

DOE PAGES

Murphy, Jesse R.; Mullins, Elwood A.; Kappock, T. Joseph

2016-05-23

Coenzyme A (CoA)-transferases catalyze the reversible transfer of CoA from acyl-CoA thioesters to free carboxylates. Class I CoA-transferases produce acylglutamyl anhydride intermediates that undergo attack by CoA thiolate on either the internal or external carbonyl carbon atoms, forming distinct tetrahedral intermediates <3 Å apart. Here in this study, crystal structures of succinyl-CoA:acetate CoA-transferase (AarC) from Acetobacter aceti are used to examine how the Asn347 carboxamide stabilizes the internal oxyanion intermediate. A structure of the active mutant AarC-N347A bound to CoA revealed both solvent replacement of the missing contact and displacement of the adjacent Glu294, indicating that Asn347 both polarizes andmore » orients the essential glutamate. AarC was crystallized with the nonhydrolyzable acetyl-CoA (AcCoA) analog dethiaacetyl-CoA (1a) in an attempt to trap a closed enzyme complex containing a stable analog of the external oxyanion intermediate. One active site contained an acetylglutamyl anhydride adduct and truncated 1a, an unexpected result hinting at an unprecedented cleavage of the ketone moiety in 1a. Solution studies confirmed that 1a decomposition is accompanied by production of near-stoichiometric acetate, in a process that seems to depend on microbial contamination but not AarC. A crystal structure of AarC bound to the postulated 1a truncation product (2a) showed complete closure of one active site per dimer but no acetylglutamyl anhydride, even with acetate added. These findings suggest that an activated acetyl donor forms during 1a decomposition; a working hypothesis involving ketone oxidation is offered. Finally, the ability of 2a to induce full active site closure furthermore suggests that it subverts a system used to impede inappropriate active site closure on unacylated CoA.« less

Antibacterial and Antibiofilm Activities of Makaluvamine Analogs

PubMed Central

Nijampatnam, Bhavitavya; Nadkarni, Dwayaja H.; Wu, Hui; Velu, Sadanandan E.

2014-01-01

Streptococcus mutans is a key etiological agent in the formation of dental caries. The major virulence factor is its ability to form biofilms. Inhibition of S. mutans biofilms offers therapeutic prospects for the treatment and the prevention of dental caries. In this study, 14 analogs of makaluvamine, a marine alkaloid, were evaluated for their antibacterial activity against S. mutans and for their ability to inhibit S. mutans biofilm formation. All analogs contained the tricyclic pyrroloiminoquinone core of makaluvamines. The structural variations of the analogs are on the amino substituents at the 7-position of the ring and the inclusion of a tosyl group on the pyrrole ring N of the makaluvamine core. The makaluvamine analogs displayed biofilm inhibition with IC50 values ranging from 0.4 μM to 88 μM. Further, the observed bactericidal activity of the majority of the analogs was found to be consistent with the anti-biofilm activity, leading to the conclusion that the anti-biofilm activity of these analogs stems from their ability to kill S. mutans. However, three of the most potent N-tosyl analogs showed biofilm IC50 values at least an order of magnitude lower than that of bactericidal activity, indicating that the biofilm activity of these analogs is more selective and perhaps independent of bactericidal activity. PMID:25767719

The Sounds of Nanoscience: Acoustic STM Analogues

ERIC Educational Resources Information Center

Euler, Manfred

2013-01-01

A hands-on model of scanning tunnelling microscopy (STM) is presented. It uses near-field imaging with sound and computer assisted visualization to create acoustic mappings of resonator arrangements. Due to the (partial) analogy of matter and sound waves the images closely resemble STM scans of atoms. Moreover, the method can be extended to build…

Inflation without self-reproduction in F( R) gravity

NASA Astrophysics Data System (ADS)

Nojiri, Shin'ichi; Odintsov, Sergei D.

2015-05-01

We investigate inflation in frames of two classes of F( R) gravity and check its consistency with Planck data. It is shown that F( R) inflation without self-reproduction may be constructed in close analogy with the corresponding scalar example proposed by Mukhanov for the resolution of the problems of multiverse, predictability and initial conditions.

Shakespeare as Teacher.

ERIC Educational Resources Information Center

Hurley, John

When readers encounter Shakespeare's "Sonnet 73," they often fail to realize that it is an excellent model of what a good composition ought to be. The closing couplet functions the same way a thesis would in a prose work. The repetition of wording within the analogies in the three quatrains helps to make the work coherent. In addition,…

The nature of the virus receptors of red cells; evidence on the chemical nature of the virus receptors of red cells and of the existence of a closely analogous substance in normal serum.

PubMed

HIRST, G K

1948-04-01

THE INFLUENZA VIRUS RECEPTORS OF FOWL RED CELLS AND THE INFLUENZA VIRUS INHIBITOR OF NORMAL RABBIT SERUM HAVE THE FOLLOWING ATTRIBUTES IN COMMON: They are stable at high temperatures and in solutions of pH as high as 10.0. They both resist destruction by a number of oxidizing agents but are readily destroyed by sodium periodate, trypsin, and influenza virus. These facts suggest that the red cell receptor and the normal serum inhibitor are either the same or analogous substances and that they may belong to the mucoprotein class of compounds.

Quantum friction on monoatomic layers and its classical analog

NASA Astrophysics Data System (ADS)

Maslovski, Stanislav I.; Silveirinha, Mário G.

2013-07-01

We consider the effect of quantum friction at zero absolute temperature resulting from polaritonic interactions in closely positioned two-dimensional arrays of polarizable atoms (e.g., graphene sheets) or thin dielectric sheets modeled as such arrays. The arrays move one with respect to another with a nonrelativistic velocity v≪c. We confirm that quantum friction is inevitably related to material dispersion, and that such friction vanishes in nondispersive media. In addition, we consider a classical analog of the quantum friction which allows us to establish a link between the phenomena of quantum friction and classical parametric generation. In particular, we demonstrate how the quasiparticle generation rate typically obtained from the quantum Fermi golden rule can be calculated classically.

Probing the holographic principle using dynamical gauge effects from open spin-orbit coupling

NASA Astrophysics Data System (ADS)

Zhao, Jianshi; Price, Craig; Liu, Qi; Gemelke, Nathan

2016-05-01

Dynamical gauge fields result from locally defined symmetries and an effective over-labeling of quantum states. Coupling atoms weakly to a reservoir of laser modes can create an effective dynamical gauge field purely due to the disregard of information in the optical states. Here we report measurements revealing effects of open spin-orbit coupling in a system where an effective model can be formed from a non-abelian SU(2) × U(1) field theory following the Yang-Mills construct. Forming a close analogy to dynamical gauge effects in quantum chromodynamics, we extract a measure of atomic motion which reveals the analog of a closing mass gap for the relevant gauge boson, shedding insight on long standing open problems in gauge-fixing scale anomalies. Using arguments following the holographic principle, we measure scaling relations which can be understood by quantifying information present in the local potential. New prospects using these techniques for developing fractionalization of multi-particle and macroscopic systems using dissipative and non-abelian gauge fields will also be discussed. We acknowledge support from NSF Award No. 1068570, and the Charles E. Kaufman Foundation.

Semi-classical dynamics of superradiant Rayleigh scattering in a Bose-Einstein condensate

NASA Astrophysics Data System (ADS)

Müller, J. H.; Witthaut, D.; le Targat, R.; Arlt, J. J.; Polzik, E. S.; Hilliard, A. J.

2016-10-01

Due to its coherence properties and high optical depth, a Bose-Einstein condensate [BEC] provides an ideal setting to investigate collective atom-light interactions. Superradiant light scattering [SLS] in a BEC is a fascinating example of such an interaction. It is an analogous process to Dicke superradiance, in which an electronically inverted sample decays collectively, leading to the emission of one or more light pulses in a well-defined direction. Through time-resolved measurements of the superradiant light pulses emitted by an end-pumped BEC, we study the close connection of SLS with Dicke superradiance. A 1D model of the system yields good agreement with the experimental data and shows that the dynamics result from the structures that build up in the light and matter-wave fields along the BEC. This paves the way for exploiting the atom-photon correlations generated by the superradiance.

Dynamics of poroelastic foams

NASA Astrophysics Data System (ADS)

Forterre, Yoel; Sobac, Benjamin

2010-11-01

Soft poroelastic structures are widespread in biological tissues such as cartilaginous joints in bones, blood-filled placentae or plant organs. Here we investigate the dynamics of open elastic foams immersed in viscous fluids, as model soft poroelastic materials. The experiment consists in slowly compacting blocs of polyurethane solid foam embedded in silicon oil-tanks and studying their relaxation to equilibrium when the confining stress is suddenly released. Measurements of the local fluid pressure and foam velocity field are compared with a simple two-phase flow approach. For small initial compactions, the results show quantitative agreement with the classical diffusion theory of soil consolidation (Terzaghi, Biot). On the other hand, for large initial compactions, the dynamics exhibits long relaxation times and decompaction fronts, which are mainly controlled by the highly non-linear mechanical response of the foam. The analogy between this process and the evaporation of a polymer melt close to the glass transition will be briefly discussed.

Semi-synthetic salinomycin analogs exert cytotoxic activity against human colorectal cancer stem cells.

PubMed

Klose, Johannes; Kattner, Sarah; Borgström, Björn; Volz, Claudia; Schmidt, Thomas; Schneider, Martin; Oredsson, Stina; Strand, Daniel; Ulrich, Alexis

2018-01-01

Salinomycin, a polyether antibiotic, is a well-known inhibitor of human cancer stem cells. Chemical modification of the allylic C20 hydroxyl of salinomycin has enabled access to synthetic analogs that display increased cytotoxic activity compared to the native structure. The aim of this study was to investigate the activity of a cohort of C20-O-acyl analogs of salinomycin on human colorectal cancer cell lines in vitro. Two human colorectal cancer cell lines (SW480 and SW620) were exposed to three C20-O-acylated analogs and salinomycin. The impact of salinomycin and its analogs on tumor cell number, migration, cell death, and cancer stem cell specifity was analyzed. Exposure of human colorectal cancer cells to the C20-O-acylated analogs of salinomycin resulted in reduced tumor cell number and impaired tumor cell migration at lower concentrations than salinomycin. When used at higher (micromolar) concentrations, these effects were accompanied by induction of apoptotic cell death. Salinomycin analogs further expose improved activity against cancer stem cells compared to salinomycin. Copyright © 2017 Elsevier Inc. All rights reserved.

Synthesis and anti-HIV activity of novel N-1 side chain-modified analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT).

PubMed

Pontikis, R; Benhida, R; Aubertin, A M; Grierson, D S; Monneret, C

1997-06-06

A series of 33 N-1 side chain-modified analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (1, HEPT) were synthesized and evaluated for their anti-HIV-1 activity. In particular, the influence of substitution of the terminal hydroxy group of the acyclic structure of HEPT and the structural rigidity of this side chain were investigated. Halo (7, 8), azido (9), and amino (10-15) derivatives were synthesized from HEPT via the p-tosylate derivative 6. Acylation of the primary amine 15 afforded the amido analogs 16-20. The diaryl derivatives 26-29 were prepared by reaction of HEPT, or of the 6-(2-pyridylthio) analog 23, with diaryl disulfides in the presence of tri-n-butylphosphine. Compounds 39-41, in which the N-1 side chain is rigidified by incorporation of an E-configured double bond, were obtained by palladium(0)-catalyzed coupling of several different 6-(arylthio)uracil derivatives (37, 38) with allyl acetates 33. Compounds 13, 40a,c,d,f, and 41, incorporating an aromatic ring at the end of the acyclic side chain, were found to be more potent than the known diphenyl-substituted HEPT analog BPT (2), two of them, 40c,d, being 10-fold more active.

An analog gamma correction scheme for high dynamic range CMOS logarithmic image sensors.

PubMed

Cao, Yuan; Pan, Xiaofang; Zhao, Xiaojin; Wu, Huisi

2014-12-15

In this paper, a novel analog gamma correction scheme with a logarithmic image sensor dedicated to minimize the quantization noise of the high dynamic applications is presented. The proposed implementation exploits a non-linear voltage-controlled-oscillator (VCO) based analog-to-digital converter (ADC) to perform the gamma correction during the analog-to-digital conversion. As a result, the quantization noise does not increase while the same high dynamic range of logarithmic image sensor is preserved. Moreover, by combining the gamma correction with the analog-to-digital conversion, the silicon area and overall power consumption can be greatly reduced. The proposed gamma correction scheme is validated by the reported simulation results and the experimental results measured for our designed test structure, which is fabricated with 0.35 μm standard complementary-metal-oxide-semiconductor (CMOS) process.

Synthesis and structure-activity relationships of fenbufen amide analogs.

PubMed

Lin, Kun-I; Yang, Chao-Hsun; Huang, Chia-Wen; Jian, Jhen-Yi; Huang, Yu-Chun; Yu, Chung-Shan

2010-12-02

The previous discoveries of butyl fenbufen amide analogs with antitumor effects were further examined. The amide analogs with 1, 3, 4 and 8 carbons chains were prepared in 70-80% yield. Fenbufen had no cytotoxic effects at concentrations ranging from 10 to 100 μM. Methyl fenbufen amide had significant cytotoxic effects at a concentration of 100 μM. As the length of the alkyl amide side chain increased, the cytotoxic effects increased, and the octyl fenbufen amide had the greatest cytotoxic effect. After treatment with 30 μM octyl fenbufen amide, nearly seventy percent of the cells lost their viability. At the concentration of 10 μM, fenbufen amide analogs did not show cytotoxicity according to the MTT assay results. The NO scavenging activities of the fenbufen amide analogs were not significantly different from those of fenbufen.

An Analog Gamma Correction Scheme for High Dynamic Range CMOS Logarithmic Image Sensors

PubMed Central

Cao, Yuan; Pan, Xiaofang; Zhao, Xiaojin; Wu, Huisi

2014-01-01

In this paper, a novel analog gamma correction scheme with a logarithmic image sensor dedicated to minimize the quantization noise of the high dynamic applications is presented. The proposed implementation exploits a non-linear voltage-controlled-oscillator (VCO) based analog-to-digital converter (ADC) to perform the gamma correction during the analog-to-digital conversion. As a result, the quantization noise does not increase while the same high dynamic range of logarithmic image sensor is preserved. Moreover, by combining the gamma correction with the analog-to-digital conversion, the silicon area and overall power consumption can be greatly reduced. The proposed gamma correction scheme is validated by the reported simulation results and the experimental results measured for our designed test structure, which is fabricated with 0.35 μm standard complementary-metal-oxide-semiconductor (CMOS) process. PMID:25517692

Three-Dimensional Self-Assembled Photonic Crystal Waveguide

NASA Astrophysics Data System (ADS)

Baek, Kang-Hyun

Photonic crystals (PCs), two- or three-dimensionally periodic, artificial, and dielectric structures, have a specific forbidden band for electromagnetic waves, referred to as photonic bandgap (PBG). The PBG is analogous to the electronic bandgap in natural crystal structures with periodic atomic arrangement. A well-defined and embedded planar, line, or point defect within the PCs causes a break in its structural periodicity, and introduces a state in the PBG for light localization. It offers various applications in integrated optics and photonics including optical filters, sharp bending light guides and very low threshold lasers. Using nanofabrication processes, PCs of the 2-D slab-type and 3-D layer-by-layer structures have been investigated widely. Alternatively, simple and low-cost self-assembled PCs with full 3-D PBG, inverse opals, have been suggested. A template with face centered cubic closed packed structure, opal, may initially be built by self-assembly of colloidal spheres, and is selectively removed after infiltrating high refractive index materials into the interstitials of spheres. In this dissertation, the optical waveguides utilizing the 3-D self-assembled PCs are discussed. The waveguides were fabricated by microfabrication technology. For high-quality colloidal silica spheres and PCs, reliable synthesis, self-assembly, and characterization techniques were developed. Its theoretical and experimental demonstrations are provided and correlated. They suggest that the self-assembled PCs with PBG are feasible for the applications in integrated optics and photonics.

Impact craters as biospheric microenvironments, Lawn Hill Structure, Northern Australia.

PubMed

Lindsay, John; Brasier, Martin

2006-04-01

Impact craters on Mars act as traps for eolian sediment and in the past may have provided suitable microenvironments that could have supported and preserved a stressed biosphere. If this is so, terrestrial impact structures such as the 18-km-diameter Lawn Hill Structure, in northern Australia, may prove useful as martian analogs. We sampled outcrop and drill core from the carbonate fill of the Lawn Hill Structure and recorded its gamma-log signature. Facies data along with whole rock geochemistry and stable isotope signatures show that the crater fill is an outlier of the Georgina Basin and was formed by impact at, or shortly before, approximately 509-506 million years ago. Subsequently, it was rapidly engulfed by the Middle Cambrian marine transgression, which filled it with shallow marine carbonates and evaporites. The crater formed a protected but restricted microenvironment in which sediments four times the thickness of the nearby basinal succession accumulated. Similar structures, common on the martian surface, may well have acted as biospheric refuges as the planet's water resources declined. Low-pH aqueous environments on Earth similar to those on Mars, while extreme, support diverse ecologies. The architecture of the eolian crater fill would have been defined by long-term ground water cycles resulting from intermittent precipitation in an extremely arid climate. Nutrient recycling, critical to a closed lacustrine sub-ice biosphere, could be provided by eolian transport onto the frozen water surface.

Designing novel Sn-Bi, Si-C and Ge-C nanostructures, using simple theoretical chemical similarities

NASA Astrophysics Data System (ADS)

Zdetsis, Aristides D.

2011-04-01

A framework of simple, transparent and powerful concepts is presented which is based on isoelectronic (or isovalent) principles, analogies, regularities and similarities. These analogies could be considered as conceptual extensions of the periodical table of the elements, assuming that two atoms or molecules having the same number of valence electrons would be expected to have similar or homologous properties. In addition, such similar moieties should be able, in principle, to replace each other in more complex structures and nanocomposites. This is only partly true and only occurs under certain conditions which are investigated and reviewed here. When successful, these concepts are very powerful and transparent, leading to a large variety of nanomaterials based on Si and other group 14 elements, similar to well known and well studied analogous materials based on boron and carbon. Such nanomaterias designed in silico include, among many others, Si-C, Sn-Bi, Si-C and Ge-C clusters, rings, nanowheels, nanorodes, nanocages and multidecker sandwiches, as well as silicon planar rings and fullerenes similar to the analogous sp2 bonding carbon structures. It is shown that this pedagogically simple and transparent framework can lead to an endless variety of novel and functional nanomaterials with important potential applications in nanotechnology, nanomedicine and nanobiology. Some of the so called predicted structures have been already synthesized, not necessarily with the same rational and motivation. Finally, it is anticipated that such powerful and transparent rules and analogies, in addition to their predictive power, could also lead to far-reaching interpretations and a deeper understanding of already known results and information.

Designing novel Sn-Bi, Si-C and Ge-C nanostructures, using simple theoretical chemical similarities.

PubMed

Zdetsis, Aristides D

2011-04-27

A framework of simple, transparent and powerful concepts is presented which is based on isoelectronic (or isovalent) principles, analogies, regularities and similarities. These analogies could be considered as conceptual extensions of the periodical table of the elements, assuming that two atoms or molecules having the same number of valence electrons would be expected to have similar or homologous properties. In addition, such similar moieties should be able, in principle, to replace each other in more complex structures and nanocomposites. This is only partly true and only occurs under certain conditions which are investigated and reviewed here. When successful, these concepts are very powerful and transparent, leading to a large variety of nanomaterials based on Si and other group 14 elements, similar to well known and well studied analogous materials based on boron and carbon. Such nanomaterias designed in silico include, among many others, Si-C, Sn-Bi, Si-C and Ge-C clusters, rings, nanowheels, nanorodes, nanocages and multidecker sandwiches, as well as silicon planar rings and fullerenes similar to the analogous sp2 bonding carbon structures. It is shown that this pedagogically simple and transparent framework can lead to an endless variety of novel and functional nanomaterials with important potential applications in nanotechnology, nanomedicine and nanobiology. Some of the so called predicted structures have been already synthesized, not necessarily with the same rational and motivation. Finally, it is anticipated that such powerful and transparent rules and analogies, in addition to their predictive power, could also lead to far-reaching interpretations and a deeper understanding of already known results and information.

Structure-activity relationship of ibogaine analogs interacting with nicotinic acetylcholine receptors in different conformational states.

PubMed

Arias, Hugo R; Feuerbach, Dominik; Targowska-Duda, Katarzyna M; Jozwiak, Krzysztof

2011-09-01

The interaction of ibogaine analogs with nicotinic acetylcholine receptors (AChRs) in different conformational states was studied by functional and structural approaches. The results established that ibogaine analogs: (a) inhibit (±)-epibatidine-induced Ca²⁺ influx in human embryonic muscle AChRs with the following potency sequence (IC(50) in μM): (±)-18-methylaminocoronaridine (5.9±0.3)∼(±)-18-methoxycoronaridine (18-MC) (6.8±0.8)>(-)-ibogaine (17±3)∼(+)-catharanthine (20±1)>(±)-albifloranine (46±13), (b) bind to the [³H]TCP binding site with higher affinity when the Torpedo AChR is in the desensitized state compared to that in the resting state. Similar results were obtained using [³H]18-MC. These and docking results suggest a steric interaction between TCP and ibogaine analogs for the same site, (c) enhance [³H]cytisine binding to resting but not to desensitized AChRs, with desensitizing potencies (apparent EC₅₀) that correlate very well with the pK(i) values in the desensitized state, and (d) there are good bilinear correlations between the ligand molecular volumes and their affinities in the desensitized and resting states, with an optimal volume of ∼345 ų for the ibogaine site. These results indicate that the size of the binding sites for ibogaine analogs, located between the serine and nonpolar rings and shared with TCP, is an important structural feature for binding and for inducing desensitization. Copyright © 2011 Elsevier Ltd. All rights reserved.

Reasoning by analogy requires the left frontal pole: lesion-deficit mapping and clinical implications.

PubMed

Urbanski, Marika; Bréchemier, Marie-Laure; Garcin, Béatrice; Bendetowicz, David; Thiebaut de Schotten, Michel; Foulon, Chris; Rosso, Charlotte; Clarençon, Frédéric; Dupont, Sophie; Pradat-Diehl, Pascale; Labeyrie, Marc-Antoine; Levy, Richard; Volle, Emmanuelle

2016-06-01

SEE BURGESS DOI101093/BRAIN/AWW092 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE  : Analogical reasoning is at the core of the generalization and abstraction processes that enable concept formation and creativity. The impact of neurological diseases on analogical reasoning is poorly known, despite its importance in everyday life and in society. Neuroimaging studies of healthy subjects and the few studies that have been performed on patients have highlighted the importance of the prefrontal cortex in analogical reasoning. However, the critical cerebral bases for analogical reasoning deficits remain elusive. In the current study, we examined analogical reasoning abilities in 27 patients with focal damage in the frontal lobes and performed voxel-based lesion-behaviour mapping and tractography analyses to investigate the structures critical for analogical reasoning. The findings revealed that damage to the left rostrolateral prefrontal region (or some of its long-range connections) specifically impaired the ability to reason by analogies. A short version of the analogy task predicted the existence of a left rostrolateral prefrontal lesion with good accuracy. Experimental manipulations of the analogy tasks suggested that this region plays a role in relational matching or integration. The current lesion approach demonstrated that the left rostrolateral prefrontal region is a critical node in the analogy network. Our results also suggested that analogy tasks should be translated to clinical practice to refine the neuropsychological assessment of patients with frontal lobe lesions. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Love-hate for man-machine metaphors in Soviet physiology: from Pavlov to "physiological cybernetics".

PubMed

Gerovitch, Slava

2002-06-01

This article reinterprets the debate between orthodox followers of the Pavlovian reflex theory and Soviet "cybernetic physiologists" in the 1950s and 60s as a clash of opposing man-machine metaphors. While both sides accused each other of "mechanistic," reductionist methodology, they did not see anything "mechanistic" about their own central metaphors: the telephone switchboard metaphor for nervous activity (the Pavlovians), and the analogies between the human brain and a computer (the cyberneticians). I argue that the scientific utility of machine analogies was closely intertwined with their philosophical and political meanings and that new interpretations of these metaphors emerged as a result of political conflicts and a realignment of forces within the scientific community and in society at large. I suggest that the constant travel of man-machine analogies, back and forth between physiology and technology has blurred the traditional categories of the "mechanistic" and the "organic" in Soviet neurophysiology, as perhaps in the history of physiology in general.

Immobilization of actinides in stable mineral type and ceramic materials (high temperature synthesis)

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

Starkov, O.; Konovalov, E.

1996-05-01

Alternative vitrification technologies are being developed in the world for the immobilization of high radioactive waste in materials with improved thermodynamic stability, as well as improved chemical and thermal stability and stability to radiation. Oxides, synthesized in the form of analogs to rock-forming minerals and ceramics, are among those materials that have highly stable properties and are compatible with the environment. In choosing the appropriate material, we need to be guided by its geometric stability, the minimal number of cations in the structure of the material and the presence of structural elements in the mineral that are isomorphs of uraniummore » and thorium, actinoids found in nature. Rare earth elements, yttrium, zirconium and calcium are therefore suitable. The minerals listed in the table (with the exception of the zircon) are pegatites by origin, i.e. they are formed towards the end of the magma crystallization of silicates form the residual melt, enriched with Ta, Nb, Ti, Zr, Ce, Y, U and Th. Uranium and thorium in the form of isomorphic admixtures form part of the lattice of the mineral. These minerals, which are rather simple in composition and structure and are formed under high temperatures, may be viewed as natural physio-chemical systems that are stable and long-lived in natural environments. The similarity of the properties of actinoids and lanthanoids plays an important role in the geochemistry of uranium and thorium; however, uranium (IV) is closer to the {open_quotes}heavy{close_quotes} group of lanthanoids (the yttrium group) while thorium (IV) is closer to the {open_quotes}light{close_quotes} group (the cerium group). That is why rare earth minerals contain uranium and thorium in the form of isomorphic admixtures.« less

The Cost of Concreteness: The Effect of Nonessential Information on Analogical Transfer

ERIC Educational Resources Information Center

Kaminski, Jennifer A.; Sloutsky, Vladimir M.; Heckler, Andrew F.

2013-01-01

Most theories of analogical transfer focus on similarities between the learning and transfer domains, where transfer is more likely between domains that share common surface features, similar elements, or common interpretations of structure. We suggest that characteristics of the learning instantiation alone can give rise to different levels of…

Stawamycin analog, JBIR-11 from Streptomyces viridochromogenes subsp. sulfomycini NBRC 13830.

PubMed

Izumikawa, Miho; Komaki, Hisayuki; Hashimoto, Junko; Takagi, Motoki; Shin-ya, Kazuo

2008-05-01

A stawamycin analog, JBIR-11 (1) was isolated from mycelium of Streptomyces viridochromogenes subsp. sulfomycini NBRC 13830. The structure was determined on the basis of the spectroscopic data. Compound 1 exhibited growth inhibitory effect against human fibrosarcoma HT1080 cells with an IC50 value of 25 microM.

Structure-based analysis of catalysis and substrate definition in the HIT protein family.

PubMed

Lima, C D; Klein, M G; Hendrickson, W A

1997-10-10

The histidine triad (HIT) protein family is among the most ubiquitous and highly conserved in nature, but a biological activity has not yet been identified for any member of the HIT family. Fragile histidine triad protein (FHIT) and protein kinase C interacting protein (PKCI) were used in a structure-based approach to elucidate characteristics of in vivo ligands and reactions. Crystallographic structures of apo, substrate analog, pentacovalent transition-state analog, and product states of both enzymes reveal a catalytic mechanism and define substrate characteristics required for catalysis, thus unifying the HIT family as nucleotidyl hydrolases, transferases, or both. The approach described here may be useful in identifying structure-function relations between protein families identified through genomics.

Synthesis and antioxidant activity of curcumin analogs.

PubMed

Zheng, Qu-Tong; Yang, Ze-Hua; Yu, Liu-Ying; Ren, Yu-Yan; Huang, Qiu-Xia; Liu, Qiu; Ma, Xiang-Yu; Chen, Zi-Kang; Wang, Zong-Bao; Zheng, Xing

2017-05-01

Numerous biological activities including antioxidant, antitumor, anti-inflammation, and antivirus of the natural product curcumin were reported. However, the clinical application of it was significantly limited by its instability, poor solubility, less body absorbing, and low bioavailability. This review focuses on the structure modification and antioxidant activity evaluation of curcumin. To study the structure-activity relationship (SAR), five series of curcumin analogs were synthesized and their antioxidant activity were evaluated in vitro. The results showed that electron-donating groups, especially the phenolic hydroxyl group are an essential component to improve the antioxidant activity.

[The function of analogies in natural sciences, also in contrast to metaphors and models].

PubMed

Hentschel, Klaus

2010-01-01

This introduction surveys the various functions of analogies in science, medicine and technology. The focus is on their heuristic importance. The productiveness of analogies is linked to the systematic depth and breadth of the established connections. Various examples are presented from different periods in the history of science, most notably Galileo; such late-Victorian Maxwellians as George Francis FitzGerald and Oliver Lodge; and Heinrich HERTZ and Niels BOHR. These examples are examined in terms of the specific differing temporal ranges of their claimed validities. They serve as evidence or counterevidence for various systematic analyses of analogies as put forward by various philosophers of science, most notably Francis Bacon, John Stuart Mill, Ernst Mach, Harald Høffding, Ernest Nagel, Mary Hesse and Peter Achinstein. The analytic framework for analogies supported here is what the cognitive scientist Dedre Gentner has termed structure-mapping.

Divergent effects of compounds on the hydrolysis and transpeptidation reactions of γ-glutamyl transpeptidase.

PubMed

Wickham, Stephanie; Regan, Nicholas; West, Matthew B; Kumar, Vidya Prasanna; Thai, Justin; Li, Pui Kai; Cook, Paul F; Hanigan, Marie H

2012-08-01

A novel class of inhibitors of the enzyme γ-glutamyl transpeptidase (GGT) were evaluated. The analog OU749 was shown previously to be an uncompetitive inhibitor of the GGT transpeptidation reaction. The data in this study show that it is an equally potent uncompetitive inhibitor of the hydrolysis reaction, the primary reaction catalyzed by GGT in vivo. A series of structural analogs of OU749 were evaluated. For many of the analogs, the potency of the inhibition differed between the hydrolysis and transpeptidation reactions, providing insight into the malleability of the active site of the enzyme. Analogs with electron withdrawing groups on the benzosulfonamide ring, accelerated the hydrolysis reaction, but inhibited the transpeptidation reaction by competing with a dipeptide acceptor. Several of the OU749 analogs inhibited the transpeptidation reaction by slow onset kinetics, similar to acivicin. Further development of inhibitors of the GGT hydrolysis reaction is necessary to provide new therapeutic compounds.

New size-expanded RNA nucleobase analogs: a detailed theoretical study.

PubMed

Zhang, Laibin; Zhang, Zhenwei; Ren, Tingqi; Tian, Jianxiang; Wang, Mei

2015-04-05

Fluorescent nucleobase analogs have attracted much attention in recent years due to their potential applications in nucleic acids research. In this work, four new size-expanded RNA base analogs were computationally designed and their structural, electronic, and optical properties are investigated by means of DFT calculations. The results indicate that these analogs can form stable Watson-Crick base pairs with natural counterparts and they have smaller ionization potentials and HOMO-LUMO gaps than natural ones. Particularly, the electronic absorption spectra and fluorescent emission spectra are calculated. The calculated excitation maxima are greatly red-shifted compared with their parental and natural bases, allowing them to be selectively excited. In gas phase, the fluorescence from them would be expected to occur around 526, 489, 510, and 462 nm, respectively. The influences of water solution and base pairing on the relevant absorption spectra of these base analogs are also examined. Copyright © 2015 Elsevier B.V. All rights reserved.

A simple structure wavelet transform circuit employing function link neural networks and SI filters

NASA Astrophysics Data System (ADS)

Mu, Li; Yigang, He

2016-12-01

Signal processing by means of analog circuits offers advantages from a power consumption viewpoint. Implementing wavelet transform (WT) using analog circuits is of great interest when low-power consumption becomes an important issue. In this article, a novel simple structure WT circuit in analog domain is presented by employing functional link neural network (FLNN) and switched-current (SI) filters. First, the wavelet base is approximated using FLNN algorithms for giving a filter transfer function that is suitable for simple structure WT circuit implementation. Next, the WT circuit is constructed with the wavelet filter bank, whose impulse response is the approximated wavelet and its dilations. The filter design that follows is based on a follow-the-leader feedback (FLF) structure with multiple output bilinear SI integrators and current mirrors as the main building blocks. SI filter is well suited for this application since the dilation constant across different scales of the transform can be precisely implemented and controlled by the clock frequency of the circuit with the same system architecture. Finally, to illustrate the design procedure, a seventh-order FLNN-approximated Gaussian wavelet is implemented as an example. Simulations have successfully verified that the designed simple structure WT circuit has low sensitivity, low-power consumption and litter effect to the imperfections.

A Mechanism-based 3D-QSAR Approach for Classification ...

EPA Pesticide Factsheets

Organophosphate (OP) and carbamate esters can inhibit acetylcholinesterase (AChE) by binding covalently to a serine residue in the enzyme active site, and their inhibitory potency depends largely on affinity for the enzyme and the reactivity of the ester. Despite this understanding, there has been no mechanism-based in silico approach for classification and prediction of the inhibitory potency of ether OPs or carbamates. This prompted us to develop a three dimensional prediction framework for OPs, carbamates, and their analogs. Inhibitory structures of a compound that can form the covalent bond were identified through analysis of docked conformations of the compound and its metabolites. Inhibitory potencies of the selected structures were then predicted using a previously developed three dimensional quantitative structure-active relationship. This approach was validated with a large number of structurally diverse OP and carbamate compounds encompassing widely used insecticides and structural analogs including OP flame retardants and thio- and dithiocarbamate pesticides. The modeling revealed that: (1) in addition to classical OP metabolic activation, the toxicity of carbamate compounds can be dependent on biotransformation, (2) OP and carbamate analogs such as OP flame retardants and thiocarbamate herbicides can act as AChEI, (3) hydrogen bonds at the oxyanion hole is critical for AChE inhibition through the covalent bond, and (4) π–π interaction with Trp86

Pt-black catalysts sintered at different temperatures: Surface analysis and activity in reactions of n-hexane

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

Paal, Z.; Xu, X.L.; Paal-Lukacs, J.

Pt-black catalysts sintered at 473 and 633 K ({open_quotes}Pt-473{close_quotes} and {open_quotes}Pt-633{close_quotes}), respectively, have been characterized by X-ray diffraction and analyzed by XPS, UPS, and AES after carrying out n-hexane reactions. The analysis has been repeated after O{sub 2}-H{sub 2} regeneration in the preparation chamber of the UHV apparatus. The surface of the blacks contains some carbon and oxygen impurities even after regeneration. Both Pt-473 and Pt-633 show high Pt 4f line intensity. Decomposition of the C 1s line reveals a higher amount of oxidized carbon polymers on Pt-633. This sample is free from lattice strain. The likely higher abundance ofmore » exposed hexagonal symmetry faces, namely the (111) plane and analogous stepped and kinked structures, may be one of the reasons why fragmentation and aromatization are favored on Pt-633, as opposed to the higher selectivity of isomerization and C{sub 5}-cyclization on Pt-473. The higher amount of oxidized carbonaceous polymer overlayer (serving as {open_quotes}hydrogen catcher{close_quotes}) on Pt-633 as well as the less-retained hydrogen by its crystallites without lattice strain may also contribute to the different selectivity and hydrogen pressure response of the n-hexane reaction over the two samples. Product ratios are suggested as an additional diagnostic tool for characterizing the hydrogen availability on the catalysts. 59 refs., 9 figs., 5 tabs.« less

78 FR 21455 - Self-Regulatory Organizations; BATS-Y Exchange, Inc.; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-10

... Maker Peg Order to more closely resemble analogous order types offered by NASDAQ Stock Market LLC...\\ The Exchange notes that EDGA Exchange, Inc. also has an order type identical to that of EDGX, however, for the purposes of this filing, the Exchange is referring only to the order type functionality...

78 FR 21447 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-10

... Maker Peg Order to more closely resemble analogous order types offered by NASDAQ Stock Market LLC...\\ The Exchange notes that EDGA Exchange, Inc. also has an order type identical to that of EDGX, however, for the purposes of this filing, the Exchange is referring only to the order type functionality...

The Electron Runaround: Understanding Electric Circuit Basics through a Classroom Activity

ERIC Educational Resources Information Center

Singh, Vandana

2010-01-01

Several misconceptions abound among college students taking their first general physics course, and to some extent pre-engineering physics students, regarding the physics and applications of electric circuits. Analogies used in textbooks, such as those that liken an electric circuit to a piped closed loop of water driven by a water pump, do not…

Welcome Home, Harry (Henry)

ERIC Educational Resources Information Center

Markey, Mia K.

2008-01-01

As the author prepares to head back to Illinois Mathematics and Science Academy (IMSA) for homecoming, she finds the analogy of Hogwarts for IMSA to be apropos. Going to IMSA opened doors for her that she hadn't even known were closed. Yet it's not easy to pin down what made her IMSA experience magical. Certainly there are some elements that are…

Recent Synthesis and Discovery of Brefeldin A Analogs

PubMed Central

Paek, Seung-Mann

2018-01-01

The recent development of analogs of brefeldin A (BFA), a fungal metabolite, for the improvement of BFA apoptosis-inducing activity is described. BFA has been isolated from various soil or, more recently, marine fungi and has shown versatile beneficial activities. More importantly, the apoptosis-inducing activity of BFA in cancer cells highlights the possibility of further developing this natural product as an anticancer agent. Besides its biological importance, its structural features have also gathered tremendous interest from both medicinal and synthetic chemists. By a medicinal chemistry and total synthesis approach, numerous analogs from BFA have been developed to improve its inferior bioavailability and its antiproliferative ability. In this review, the recent medicinal chemistry efforts in relation to the production of BFA analogs are extensively presented. PMID:29670019

Screening hybridomas for anabolic androgenic steroids by steroid analog antigen microarray.

PubMed

Du, Hongwu; Chen, Guangyu; Bian, Yongzhong; Xing, Cenzan; Ding, Xue; Zhu, Mengliang; Xun, Yiping; Chen, Peng; Zhou, Yabin; Li, Shaoxu

2015-01-01

Currently, dozens of anabolic androgenic steroids (AAS) are forbidden in the World Anti-Doping Agency Prohibited List, however, despite extensive investigation, there are still lots of AAS without corresponding monoclonal antibodies. A steroid analog antigen microarray made up of ten AAS was fabricated to screen the hybridoma and it was found an original unsuccessful clone turned out to be a candidate anti-boldenone antibody, without any cross-reactions with endogenous AAS or 44 different AAS standard reference materials tested. Our findings suggested that steroid analog antigen microarray could be a promising tool to screen and characterize new applications of antibodies for structure analogs, and this also exhibits the potential to fast identify effective epitopes of hybridomas in a single assay.

Structural studies of viperin, an antiviral radical SAM enzyme.

PubMed

Fenwick, Michael K; Li, Yue; Cresswell, Peter; Modis, Yorgo; Ealick, Steven E

2017-06-27

Viperin is an IFN-inducible radical S -adenosylmethionine (SAM) enzyme that inhibits viral replication. We determined crystal structures of an anaerobically prepared fragment of mouse viperin (residues 45-362) complexed with S -adenosylhomocysteine (SAH) or 5'-deoxyadenosine (5'-dAdo) and l-methionine (l-Met). Viperin contains a partial (βα) 6 -barrel fold with a disordered N-terminal extension (residues 45-74) and a partially ordered C-terminal extension (residues 285-362) that bridges the partial barrel to form an overall closed barrel structure. Cys84, Cys88, and Cys91 located after the first β-strand bind a [4Fe-4S] cluster. The active site architecture of viperin with bound SAH (a SAM analog) or 5'-dAdo and l-Met (SAM cleavage products) is consistent with the canonical mechanism of 5'-deoxyadenosyl radical generation. The viperin structure, together with sequence alignments, suggests that vertebrate viperins are highly conserved and that fungi contain a viperin-like ortholog. Many bacteria and archaebacteria also express viperin-like enzymes with conserved active site residues. Structural alignments show that viperin is similar to several other radical SAM enzymes, including the molybdenum cofactor biosynthetic enzyme MoaA and the RNA methyltransferase RlmN, which methylates specific nucleotides in rRNA and tRNA. The viperin putative active site contains several conserved positively charged residues, and a portion of the active site shows structural similarity to the GTP-binding site of MoaA, suggesting that the viperin substrate may be a nucleoside triphosphate of some type.

Frequency set on systems

NASA Astrophysics Data System (ADS)

Wilby, W. A.; Brett, A. R. H.

Frequency set on techniques used in ECM applications include repeater jammers, frequency memory loops (RF and optical), coherent digital RF memories, and closed loop VCO set on systems. Closed loop frequency set on systems using analog phase and frequency locking are considered to have a number of cost and performance advantages. Their performance is discussed in terms of frequency accuracy, bandwidth, locking time, stability, and simultaneous signals. Some experimental results are presented which show typical locking performance. Future ECM systems might require a response to very short pulses. Acoustooptic and fiber-optic pulse stretching techniques can be used to meet such requirements.

The Northern Plains MSATT Meeting, and a call for a field-oriented successor to MSATT

NASA Technical Reports Server (NTRS)

Kargel, J. S.

1993-01-01

The workshop was devoted to a review of our knowledge of the Martian northern plains and presentation of recent ideas pertaining to the geologic and climatic evolution of this interesting region. The meeting was held in Fairbanks to allow easy access to Mars-like terrains in central and northern Alaska. There is no place on Earth that is a close analog of the Martian northern plains, but parts of Alaska come reasonably close in some respects, so we may expect that some of the processes occurring there are similar to processes that have occurred on Mars.

Gold as hydrogen: Structural and electronic properties and chemical bonding in Si3Au3+/0/- and comparisons to Si3H3+/0/-

NASA Astrophysics Data System (ADS)

Kiran, Boggavarapu; Li, Xi; Zhai, Hua-Jin; Wang, Lai-Sheng

2006-10-01

A single Au atom has been shown to behave like H in its bonding to Si in several mono- and disilicon gold clusters. In the current work, we investigate the Au /H analogy in trisilicon gold clusters, Si3Au3+/0/-. Photoelectron spectroscopy and density functional calculations are combined to examine the geometric and electronic structure of Si3Au3-. We find that there are three isomers competing for the ground state of Si3Au3- as is the case for Si3H3-. Extensive structural searches show that the potential energy surfaces of the trisilicon gold clusters (Si3Au3-, Si3Au3, and Si3Au3+) are similar to those of the corresponding silicon hydrides. The lowest energy isomers for Si3Au3- and Si3Au3 are structurally similar to a Si3Au four-membered ring serving as a common structural motif. For Si3Au3+, the 2π aromatic cyclotrisilenylium auride ion, analogous to the aromatic cyclotrisilenylium ion (Si3H3+), is the most stable species. Comparison of the structures and chemical bonding between Si3Au3+/0/- and the corresponding silicon hydrides further extends the isolobal analogy between Au and H.

A two-dimensional (2D) analytical subthreshold swing and transconductance model of underlap dual-material double-gate (DMDG) MOSFET for analog/RF applications

NASA Astrophysics Data System (ADS)

Narendar, Vadthiya; Rai, Saurabh; Tiwari, Siddharth; Mishra, R. A.

2016-12-01

The double-gate (DG) metal-oxide-semiconductor field effect transistors (MOSFETs) are the choice of technology in sub -100 nm regime of leading microelectronics industry. To enhance the analog and RF performance of DG MOSFET, an underlap dual-material (DM) DG MOSFET device structure has been considered because, it has the advantages of both underlap as well as that of dual-material gate (DMG). A 2D analytical surface potential, subthreshold current, subthreshold swing as well as transconductance modelling of underlap DMDG MOSFET has been done by solving the Poisson's equation. It has also been found that, numerically simulated data approves the analytically modelled data with commendable accuracy. As underlap length (Lun) increases, a substantial reduction of subthreshold current due to enhanced gate control over channel regime is observed. DMG structure facilitates to improve the average velocity of carriers which leads to superior drive current of the device. The underlap DMDG MOSFET device structure demonstrates an ameliorated subthreshold characteristic. The analog figure of merits (FOMs) such as transconductance (gm), transconductance generation factor (TGF), output conductance (gd), early voltage (VEA), intrinsic gain (AV) and RF FOMs namely cut-off frequency (fT), gain frequency product (GFP), transconductance frequency product (TFP) and gain transconductance frequency product (GTFP) have been evaluated. The aforesaid analysis revels that, the device is best suited for communication related Analog/RF applications.

Analogical Transfer: Are There Performance Differences among High-Ability Students?

ERIC Educational Resources Information Center

McVey, Mary D.

This study investigated the role of problem structure and metacognitive control in the analogical transfer of performance of 40 13- and 14-year-old gifted and highly gifted math students. Average and above average 16-, 17-, and 18-year-olds served as comparison groups. Students were given three algebra problems with solutions, followed by two…

Mars inflatable greenhouse analog.

PubMed

Sadler, Philip D; Giacomelli, Gene A

2002-01-01

Light intensities on the Martian surface can possibly support a bioregenerative life support system (BLSS) utilizing natural sunlight for hydroponic crop production, if a suitable controlled environment can be provided. Inflatable clear membrane structures offer low mass, are more easily transported than a rigid structure, and are good candidates for providing a suitable controlled environment for crop production. Cable culture is one hydroponic growing system that can take advantage of the beneficial attributes of the inflatable structure. An analog of a Mars inflatable greenhouse can provide researchers data on issues such as crew time requirements for operation, productivity for BLSS, human factors, and much more at a reasonable cost. This is a description of one such design.

Structure-activity relationship analysis of mitochondrial toxicity caused by antiviral ribonucleoside analogs.

PubMed

Jin, Zhinan; Kinkade, April; Behera, Ishani; Chaudhuri, Shuvam; Tucker, Kathryn; Dyatkina, Natalia; Rajwanshi, Vivek K; Wang, Guangyi; Jekle, Andreas; Smith, David B; Beigelman, Leo; Symons, Julian A; Deval, Jerome

2017-07-01

Recent cases of severe toxicity during clinical trials have been associated with antiviral ribonucleoside analogs (e.g. INX-08189 and balapiravir). Some have hypothesized that the active metabolites of toxic ribonucleoside analogs, the triphosphate forms, inadvertently target human mitochondrial RNA polymerase (POLRMT), thus inhibiting mitochondrial RNA transcription and protein synthesis. Others have proposed that the prodrug moiety released from the ribonucleoside analogs might instead cause toxicity. Here, we report the mitochondrial effects of several clinically relevant and structurally diverse ribonucleoside analogs including NITD-008, T-705 (favipiravir), R1479 (parent nucleoside of balapiravir), PSI-7851 (sofosbuvir), and INX-08189 (BMS-986094). We found that efficient substrates and chain terminators of POLRMT, such as the nucleoside triphosphate forms of R1479, NITD-008, and INX-08189, are likely to cause mitochondrial toxicity in cells, while weaker chain terminators and inhibitors of POLRMT such as T-705 ribonucleoside triphosphate do not elicit strong in vitro mitochondrial effects. Within a fixed 3'-deoxy or 2'-C-methyl ribose scaffold, changing the base moiety of nucleotides did not strongly affect their inhibition constant (K i ) against POLRMT. By swapping the nucleoside and prodrug moieties of PSI-7851 and INX-08189, we demonstrated that the cell-based toxicity of INX-08189 is mainly caused by the nucleoside component of the molecule. Taken together, these results show that diverse 2' or 4' mono-substituted ribonucleoside scaffolds cause mitochondrial toxicity. Given the unpredictable structure-activity relationship of this ribonucleoside liability, we propose a rapid and systematic in vitro screen combining cell-based and biochemical assays to identify the early potential for mitochondrial toxicity. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Energy level diagrams for black hole orbits

NASA Astrophysics Data System (ADS)

Levin, Janna

2009-12-01

A spinning black hole with a much smaller black hole companion forms a fundamental gravitational system, like a colossal classical analog to an atom. In an appealing if imperfect analogy with atomic physics, this gravitational atom can be understood through a discrete spectrum of periodic orbits. Exploiting a correspondence between the set of periodic orbits and the set of rational numbers, we are able to construct periodic tables of orbits and energy level diagrams of the accessible states around black holes. We also present a closed-form expression for the rational q, thereby quantifying zoom-whirl behavior in terms of spin, energy and angular momentum. The black hole atom is not just a theoretical construct, but corresponds to extant astrophysical systems detectable by future gravitational wave observatories.

Synthesis and biological evaluation of largazole zinc-binding group analogs.

PubMed

Kim, Bumki; Ratnayake, Ranjala; Lee, Hyunji; Shi, Guqin; Zeller, Sabrina L; Li, Chenglong; Luesch, Hendrik; Hong, Jiyong

2017-06-15

Histone acetylation is an extensively investigated post-translational modification that plays an important role as an epigenetic regulator. It is controlled by histone acetyl transferases (HATs) and histone deacetylases (HDACs). The overexpression of HDACs and consequent hypoacetylation of histones have been observed in a variety of different diseases, leading to a recent focus of HDACs as attractive drug targets. The natural product largazole is one of the most potent natural HDAC inhibitors discovered so far and a number of largazole analogs have been prepared to define structural requirements for its HDAC inhibitory activity. However, previous structure-activity relationship studies have heavily investigated the macrocycle region of largazole, while there have been only limited efforts to probe the effect of various zinc-binding groups (ZBGs) on HDAC inhibition. Herein, we prepared a series of largazole analogs with various ZBGs and evaluated their HDAC inhibition and cytotoxicity. While none of the analogs tested were as potent or selective as largazole, the Zn 2+ -binding affinity of each ZBG correlated with HDAC inhibition and cytotoxicity. We expect that our findings will aid in building a deeper understanding of the role of ZBGs in HDAC inhibition as well as provide an important basis for the future development of new largazole analogs with non-thiol ZBGs as novel therapeutics for cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Structural analogs of pyrazole and sulfonamide cannabinoids: Effects on acute food intake in mice

PubMed Central

Wiley, Jenny L.; Marusich, Julie A.; Zhang, Yanan; Fulp, Alan; Maitra, Rangan; Thomas, Brian F.; Mahadevan, Anu

2012-01-01

Obesity contributes to a multitude of serious health problems. Given the demonstrated role of the endogenous cannabinoid system in appetite regulation, the purpose of the present study was to evaluate structural analogs of two cannabinoids, rimonabant (cannabinoid CB1 receptor antagonist) and O-2050 (sulfonamide analog of Δ8-tetrahydrocannabinol), that showed appetite suppressant effects in previous studies. Structure–activity relationships of these two lead compounds were examined in several assays, including cannabinoid CB1 and CB2 receptor binding, food intake, and an in vivo test battery (locomotor activity, antinociception, ring immobility, and body temperature) in mice. Rimonabant and O-2050 reliably decreased feeding in mice; however, their analogs decreased feeding only at higher doses, even though some compounds had quite good cannabinoid CB1 binding affinity. Results of the in vivo test battery were inconsistent, with some of the compounds producing effects characteristic of cannabinoid agonists while other compounds were inactive or were antagonists against an active dose of Δ9-tetrahydrocannabinol. These results demonstrate that reduction of food intake is not a characteristic effect of pyrazole and sulfonamide cannabinoid analogs with favorable cannabinoid CB1 binding affinity, suggesting that development of these classes of cannabinoids for the treatment of obesity will require evaluation of their effects in a broad spectrum of pharmacological assays. PMID:22975289

Ultra-fast analog-to-digital converter based on a nonlinear triplexer and an optical coder with a photonic crystal structure.

PubMed

Mehdizadeh, Farhad; Soroosh, Mohammad; Alipour-Banaei, Hamed; Farshidi, Ebrahim

2017-03-01

In this paper, we propose what we believe is a novel all-optical analog-to-digital converter (ADC) based on photonic crystals. The proposed structure is composed of a nonlinear triplexer and an optical coder. The nonlinear triplexer is for creating discrete levels in the continuous optical input signal, and the optical coder is for generating a 2-bit standard binary code out of the discrete levels coming from the nonlinear triplexer. Controlling the resonant mode of the resonant rings through optical intensity is the main objective and working mechanism of the proposed structure. The maximum delay time obtained for the proposed structure was about 5 ps and the total footprint is about 1520  μm².

Digital transceiver implementation for wavelet packet modulation

NASA Astrophysics Data System (ADS)

Lindsey, Alan R.; Dill, Jeffrey C.

1998-03-01

Current transceiver designs for wavelet-based communication systems are typically reliant on analog waveform synthesis, however, digital processing is an important part of the eventual success of these techniques. In this paper, a transceiver implementation is introduced for the recently introduced wavelet packet modulation scheme which moves the analog processing as far as possible toward the antenna. The transceiver is based on the discrete wavelet packet transform which incorporates level and node parameters for generalized computation of wavelet packets. In this transform no particular structure is imposed on the filter bank save dyadic branching, and a maximum level which is specified a priori and dependent mainly on speed and/or cost considerations. The transmitter/receiver structure takes a binary sequence as input and, based on the desired time- frequency partitioning, processes the signal through demultiplexing, synthesis, analysis, multiplexing and data determination completely in the digital domain - with exception of conversion in and out of the analog domain for transmission.

Modes in light wave propagating in semiconductor laser

NASA Technical Reports Server (NTRS)

Manko, Margarita A.

1994-01-01

The study of semiconductor laser based on an analogy of the Schrodinger equation and an equation describing light wave propagation in nonhomogeneous medium is developed. The active region of semiconductor laser is considered as optical waveguide confining the electromagnetic field in the cross-section (x,y) and allowing waveguide propagation along the laser resonator (z). The mode structure is investigated taking into account the transversal and what is the important part of the suggested consideration longitudinal nonhomogeneity of the optical waveguide. It is shown that the Gaussian modes in the case correspond to spatial squeezing and correlation. Spatially squeezed two-mode structure of nonhomogeneous optical waveguide is given explicitly. Distribution of light among the laser discrete modes is presented. Properties of the spatially squeezed two-mode field are described. The analog of Franck-Condon principle for finding the maxima of the distribution function and the analog of Ramsauer effect for control of spatial distribution of laser emission are discussed.

Honaucins A–C, Potent Inhibitors of Eukaryotic Inflammation and Bacterial Quorum Sensing: Synthetic Derivatives and Structure-Activity Relationships

PubMed Central

Choi, Hyukjae; Mascuch, Samantha J.; Villa, Francisco A.; Byrum, Tara; Teasdale, Margaret E.; Smith, Jennifer E.; Preskitt, Linda B.; Rowley, David C.; Gerwick, Lena; Gerwick, William H.

2012-01-01

SUMMARY Honaucins A–C were isolated from the cyanobacterium Leptolyngbya crossbyana which was found overgrowing corals on the Hawaiian coast. Honaucin A consists of (S)-3-hydroxy-γ-butyrolactone and 4-chlorocrotonic acid which are connected via an ester linkage. Honaucin A and its two natural analogs exhibit potent inhibition of bioluminescence, a quorum sensing-dependent phenotype, in Vibrio harveyi BB120 as well as of lipopolysaccharide-stimulated nitric oxide production in the murine macrophage cell line RAW264.7. The decrease in nitric oxide production was accompanied by a decrease in the transcripts of several pro-inflammatory cytokines, most dramatically interleukin-1β. Synthesis of honaucin A as well as a number of analogs and subsequent evaluation in anti-inflammation and quorum sensing inhibition bioassays revealed the essential structural features for activity in this chemical class, and provided analogs with greater potency in both assays. PMID:22633410

Generalized analog thresholding for spike acquisition at ultralow sampling rates

PubMed Central

He, Bryan D.; Wein, Alex; Varshney, Lav R.; Kusuma, Julius; Richardson, Andrew G.

2015-01-01

Efficient spike acquisition techniques are needed to bridge the divide from creating large multielectrode arrays (MEA) to achieving whole-cortex electrophysiology. In this paper, we introduce generalized analog thresholding (gAT), which achieves millisecond temporal resolution with sampling rates as low as 10 Hz. Consider the torrent of data from a single 1,000-channel MEA, which would generate more than 3 GB/min using standard 30-kHz Nyquist sampling. Recent neural signal processing methods based on compressive sensing still require Nyquist sampling as a first step and use iterative methods to reconstruct spikes. Analog thresholding (AT) remains the best existing alternative, where spike waveforms are passed through an analog comparator and sampled at 1 kHz, with instant spike reconstruction. By generalizing AT, the new method reduces sampling rates another order of magnitude, detects more than one spike per interval, and reconstructs spike width. Unlike compressive sensing, the new method reveals a simple closed-form solution to achieve instant (noniterative) spike reconstruction. The base method is already robust to hardware nonidealities, including realistic quantization error and integration noise. Because it achieves these considerable specifications using hardware-friendly components like integrators and comparators, generalized AT could translate large-scale MEAs into implantable devices for scientific investigation and medical technology. PMID:25904712

The immunity-related GTPase Irga6 dimerizes in a parallel head-to-head fashion.

PubMed

Schulte, Kathrin; Pawlowski, Nikolaus; Faelber, Katja; Fröhlich, Chris; Howard, Jonathan; Daumke, Oliver

2016-03-02

The immunity-related GTPases (IRGs) constitute a powerful cell-autonomous resistance system against several intracellular pathogens. Irga6 is a dynamin-like protein that oligomerizes at the parasitophorous vacuolar membrane (PVM) of Toxoplasma gondii leading to its vesiculation. Based on a previous biochemical analysis, it has been proposed that the GTPase domains of Irga6 dimerize in an antiparallel fashion during oligomerization. We determined the crystal structure of an oligomerization-impaired Irga6 mutant bound to a non-hydrolyzable GTP analog. Contrary to the previous model, the structure shows that the GTPase domains dimerize in a parallel fashion. The nucleotides in the center of the interface participate in dimerization by forming symmetric contacts with each other and with the switch I region of the opposing Irga6 molecule. The latter contact appears to activate GTP hydrolysis by stabilizing the position of the catalytic glutamate 106 in switch I close to the active site. Further dimerization contacts involve switch II, the G4 helix and the trans stabilizing loop. The Irga6 structure features a parallel GTPase domain dimer, which appears to be a unifying feature of all dynamin and septin superfamily members. This study contributes important insights into the assembly and catalytic mechanisms of IRG proteins as prerequisite to understand their anti-microbial action.

Numerical Simulations of Silverpit Crater Collapse

NASA Technical Reports Server (NTRS)

Collins, G. S.; Turtle, E. P.; Melosh, H. J.

2003-01-01

The Silverpit crater is a recently discovered, 60-65 Myr old complex crater, which lies buried beneath the North Sea, about 150 km east of Britain. High-resolution images of Silverpit's subsurface structure, provided by three-dimensional seismic reflection data, reveal an inner-crater morphology similar to that expected for a 5-8 km diameter terrestrial crater. The crater walls show evidence of terracestyle slumping and there is a distinct central uplift, which may have produced a central peak in the pristine crater morphology. However, Silverpit is not a typical 5-km diameter terrestrial crater, because it exhibits multiple, concentric rings outside the main cavity. External concentric rings are normally associated with much larger impact structures, for example Chicxulub on Earth, or Orientale on the Moon. Furthermore, external rings associated with large impacts on the terrestrial planets and moons are widely-spaced, predominantly inwardly-facing, asymmetric scarps. However, the seismic data show that the external rings at Silverpit represent closely-spaced, concentric fault-bound graben, with both inwardly and outwardly facing faults-carps. This type of multi-ring structure is directly analogous to the Valhalla-type multi-ring basins found on the icy satellites. Thus, the presence and style of the multiple rings at Silverpit is surprising given both the size of the crater and its planetary setting.

Axisymmetric Plasma Equilibria in General Relativity

NASA Astrophysics Data System (ADS)

Elsässer, Klaus

Axisymmetric plasma equilibria near a rotating black hole are considered within the multifluid description. An isothermal two-component plasma with electrons and positrons or ions is determined by four structure functions and the boundary conditions. These structure functions are the Bernoulli function and the toroidal canonical momentum per mass for each species; they remain arbitrary if no gain and loss processes are considered, in close analogy to the free flux functions in ideal magnetohydrodynamics. Several simplifying assumptions allow the reduction of the basic equations to one single scalar equation for the stream function χ of positrons or ions, respectively, playing the rôle of the Grad/Shafranov equation in magnetohydrodynamics; in particular, Maxwell's equations can be solved analytically for a quasineutral plasma when both the charge density and the toroidal electric current density are negligible (in contrast to the Tokamak situation). The basic smallness parameter is the ratio of the skin depth of electrons to the scale length of the metric and fluid quantities, and, in the case of an electron-ion plasma, the mass ratio me/mi. The χ-equation can be solved by standard methods, and simple solutions for a Kerr geometry are available; they show characteristic flow patterns, depending on the structure functions and the boundary conditions.

Global force-torque phase diagram for the DNA double helix: structural transitions, triple points and collapsed plectonemes

PubMed Central

Marko, John F.; Neukirch, Sébastien

2014-01-01

We present a free energy model for structural transitions of the DNA double helix driven by tensile and torsional stress. Our model is coarse grained, and is based on semiflexible polymer descriptions of B-DNA, underwound L-DNA, and highly overwound P-DNA. The statistical-mechanical model of plectonemic supercoiling previously developed for B-DNA is applied to semiflexible polymer models of P and L-DNA, to obtain a model of DNA structural transitions in quantitative accord with experiment. We identify two distinct plectonemic states, one “inflated” by electrostatic repulsion and thermal fluctuations, and the other “collapsed”, with the two double helices inside the supercoils driven to close contact. We find that supercoiled B and L are stable only in inflated form, while supercoiled P is always collapsed. We also predict the behavior and experimental signatures of highly underwound “Q”-DNA, the left-handed analog of P-DNA; as for P, supercoiled Q is always collapsed. Overstretched “S”-DNA and strand-separated “stress-melted” DNA are also included in our model, allowing prediction of a global phase diagram for forces up to 1000 pN and torques between ±60 pN nm, or in terms of linking number density, from σ = −5 to +3. PMID:24483501

Druggable protein interaction sites are more predisposed to surface pocket formation than the rest of the protein surface.

PubMed

Johnson, David K; Karanicolas, John

2013-01-01

Despite intense interest and considerable effort via high-throughput screening, there are few examples of small molecules that directly inhibit protein-protein interactions. This suggests that many protein interaction surfaces may not be intrinsically "druggable" by small molecules, and elevates in importance the few successful examples as model systems for improving our fundamental understanding of druggability. Here we describe an approach for exploring protein fluctuations enriched in conformations containing surface pockets suitable for small molecule binding. Starting from a set of seven unbound protein structures, we find that the presence of low-energy pocket-containing conformations is indeed a signature of druggable protein interaction sites and that analogous surface pockets are not formed elsewhere on the protein. We further find that ensembles of conformations generated with this biased approach structurally resemble known inhibitor-bound structures more closely than equivalent ensembles of unbiased conformations. Collectively these results suggest that "druggability" is a property encoded on a protein surface through its propensity to form pockets, and inspire a model in which the crude features of the predisposed pocket(s) restrict the range of complementary ligands; additional smaller conformational changes then respond to details of a particular ligand. We anticipate that the insights described here will prove useful in selecting protein targets for therapeutic intervention.

Application of Particle Image Velocimetry and Reference Image Topography to jet shock cells using the hydraulic analogy

NASA Astrophysics Data System (ADS)

Kumar, Vaibhav; Ng, Ivan; Sheard, Gregory J.; Brocher, Eric; Hourigan, Kerry; Fouras, Andreas

2011-08-01

This paper examines the shock cell structure, vorticity and velocity field at the exit of an underexpanded jet nozzle using a hydraulic analogy and the Reference Image Topography technique. Understanding the flow in this region is important for the mitigation of screech, an aeroacoustic problem harmful to aircraft structures. Experiments are conducted on a water table, allowing detailed quantitative investigation of this important flow regime at a greatly reduced expense. Conventional Particle Image Velocimetry is employed to determine the velocity and vorticity fields of the nozzle exit region. Applying Reference Image Topography, the wavy water surface is reconstructed and when combined with the hydraulic analogy, provides a pressure map of the region. With this approach subtraction of surfaces is used to highlight the unsteady regions of the flow, which is not as convenient or quantitative with conventional Schlieren techniques. This allows a detailed analysis of the shock cell structures and their interaction with flow instabilities in the shear layer that are the underlying cause of jet screech.

Closed ecological systems: From test tubes to Earth's biosphere

NASA Technical Reports Server (NTRS)

Frye, Robert J.; Mignon, George

1992-01-01

Artificially constructed closed ecological systems (CES) have been researched both experimentally and theoretically for over 25 years. The size of these systems have varied from less than one liter to many thousands of cubic meters in volume. The diversity of the included components has a similarly wide range from purely aquatic systems to soil based systems that incorporate many aspects of Earth's biosphere. While much has been learned about the functioning of these closed systems, much remains to be learned. In this paper, we compare and contrast the behavior of closed ecological systems of widely different sizes through an analysis of their atmospheric composition. In addition, we will compare the performance of relatively small CES with the behavior of Earth's biosphere. We address the applicability of small CES as replicable analogs for planetary biospheres and discuss the use of small CES as an experimental milieu for an examination of the evolution of extra-terrestrial colonies.

Inner Edges of Compact Debris Disks around Metal-rich White Dwarfs

NASA Astrophysics Data System (ADS)

Rafikov, Roman R.; Garmilla, José A.

2012-12-01

A number of metal-rich white dwarfs (WDs) are known to host compact, dense particle disks, which are thought to be responsible for metal pollution of these stars. In many such systems, the inner radii of disks inferred from their spectra are so close to the WD that particles directly exposed to starlight must be heated above 1500 K and are expected to be unstable against sublimation. To reconcile this expectation with observations, we explore particle sublimation in H-poor debris disks around WDs. We show that because of the high metal vapor pressure the characteristic sublimation temperature in these disks is 300-400 K higher than in their protoplanetary analogs, allowing particles to survive at higher temperatures. We then look at the structure of the inner edges of debris disks and show that they should generically feature superheated inner rims directly exposed to starlight with temperatures reaching 2500-3500 K. Particles migrating through the rim toward the WD (and rapidly sublimating) shield the disk behind them from strong stellar heating, making the survival of solids possible close to the WD. Our model agrees well with observations of WD+disk systems provided that disk particles are composed of Si-rich material such as olivine, and have sizes in the range ~0.03-30 cm.

Organization of fluorescent cholesterol analogs in lipid bilayers - lessons from cyclodextrin extraction.

PubMed

Milles, Sigrid; Meyer, Thomas; Scheidt, Holger A; Schwarzer, Roland; Thomas, Lars; Marek, Magdalena; Szente, Lajos; Bittman, Robert; Herrmann, Andreas; Günther Pomorski, Thomas; Huster, Daniel; Müller, Peter

2013-08-01

To characterize the structure and dynamics of cholesterol in membranes, fluorescent analogs of the native molecule have widely been employed. The cholesterol content in membranes is in general manipulated by using water-soluble cyclodextrins. Since the interactions between cyclodextrins and fluorescent-labeled cholesterol have not been investigated in detail so far, we have compared the cyclodextrin-mediated membrane extraction of three different fluorescent cholesterol analogs (one bearing a NBD and two bearing BODIPY moieties). Extraction of these analogs was followed by measuring the Förster resonance energy transfer between a rhodamine moiety linked to phosphatidylethanolamine and the labeled cholesterol. The extraction kinetics revealed that the analogs are differently extracted from membranes. We examined the orientation of the analogs within the membrane and their influence on lipid condensation using NMR and EPR spectroscopies. Our data indicate that the extraction of fluorescent sterols from membranes is determined by several parameters, including their impact on lipid order, their hydrophobicity, their intermolecular interactions with surrounding lipids, their orientation within the bilayer, and their affinity with the exogenous acceptor. Copyright © 2013 Elsevier B.V. All rights reserved.

Crystal Structures of a Quorum-Quenching Antibody

PubMed Central

Debler, Erik W.; Kaufmann, Gunnar F.; Kirchdoerfer, Robert N.; Mee, Jenny M.; Janda, Kim D.; Wilson, Ian A.

2007-01-01

Summary A large number of Gram-negative bacteria employ N-acyl homoserine lactones (AHLs) as signaling molecules in quorum sensing, which is a population density-dependent mechanism to coordinate gene expression. Antibody RS2-1G9 was elicited against a lactam mimetic of the N-acyl homoserine lactone and represents the only reported monoclonal antibody that recognizes the naturally-occuring N-acyl homoserine lactone with high affinity. Due to its high cross-reactivity, RS2-1G9 showed remarkable inhibition of quorum sensing signaling in Pseudomonas aeruginosa, a common opportunistic pathogen in humans. The crystal structure of Fab RS2-1G9 in complex with a lactam analog revealed complete encapsulation of the polar lactam moiety in the antibody combining site. This mode of recognition provides an elegant immunological solution for tight binding to an aliphatic, lipid-like ligand with a small head group lacking typical haptenic features, such as aromaticity or charge, which are often incorporated into hapten design to generate high-affinity antibodies. The ability of RS2-1G9 to discriminate between closely-related AHLs is conferred by six hydrogen bonds to the ligand. Conversely, cross-reactivity of RS2-1G9 towards the lactone is likely to originate from conservation of these hydrogen bonds as well as an additional hydrogen bond to the oxygen of the lactone ring. A short and narrow tunnel exiting at the protein surface harbors a portion of the acyl chain and would not allow for entry of the head group. The crystal structure of the antibody without its cognate lactam or lactone ligands revealed a considerably altered antibody combining site with a closed binding pocket, suggestive of an induced fit mechanism for ligand binding. Curiously, a completely buried ethylene glycol molecule mimics the lactam ring and, thus, serves as a surrogate ligand. The detailed structural delineation of this quorum-quenching antibody will now aid in further development of an antibody-based therapy against bacterial pathogens by interference with quorum sensing. PMID:17400249

Late Miocene-Pleistocene evolution of a Rio Grande rift subbasin, Sunshine Valley-Costilla Plain, San Luis Basin, New Mexico and Colorado

USGS Publications Warehouse

Ruleman, C.A.; Thompson, R.A.; Shroba, R.R.; Anderson, M.; Drenth, B.J.; Rotzien, J.; Lyon, J.

2013-01-01

The Sunshine Valley-Costilla Plain, a structural subbasin of the greater San Luis Basin of the northern Rio Grande rift, is bounded to the north and south by the San Luis Hills and the Red River fault zone, respectively. Surficial mapping, neotectonic investigations, geochronology, and geophysics demonstrate that the structural, volcanic, and geomorphic evolution of the basin involves the intermingling of climatic cycles and spatially and temporally varying tectonic activity of the Rio Grande rift system. Tectonic activity has transferred between range-bounding and intrabasin faults creating relict landforms of higher tectonic-activity rates along the mountain-piedmont junction. Pliocene–Pleistocene average long-term slip rates along the southern Sangre de Cristo fault zone range between 0.1 and 0.2 mm/year with late Pleistocene slip rates approximately half (0.06 mm/year) of the longer Quaternary slip rate. During the late Pleistocene, climatic influences have been dominant over tectonic influences on mountain-front geomorphic processes. Geomorphic evidence suggests that this once-closed subbasin was integrated into the Rio Grande prior to the integration of the once-closed northern San Luis Basin, north of the San Luis Hills, Colorado; however, deep canyon incision, north of the Red River and south of the San Luis Hills, initiated relatively coeval to the integration of the northern San Luis Basin.Long-term projections of slip rates applied to a 1.6 km basin depth defined from geophysical modeling suggests that rifting initiated within this subbasin between 20 and 10 Ma. Geologic mapping and geophysical interpretations reveal a complex network of northwest-, northeast-, and north-south–trending faults. Northwest- and northeast-trending faults show dual polarity and are crosscut by north-south– trending faults. This structural model possibly provides an analog for how some intracontinental rift structures evolve through time.

Folding and Hydrodynamics of a DNA i-Motif from the c-MYC Promoter Determined by Fluorescent Cytidine Analogs

PubMed Central

Reilly, Samantha M.; Lyons, Daniel F.; Wingate, Sara E.; Wright, Robert T.; Correia, John J.; Jameson, David M.; Wadkins, Randy M.

2014-01-01

The four-stranded i-motif (iM) conformation of cytosine-rich DNA has importance to a wide variety of biochemical systems that range from their use in nanomaterials to potential roles in oncogene regulation. The iM structure is formed at slightly acidic pH, where hemiprotonation of cytosine results in a stable C-C+ basepair. Here, we performed fundamental studies to examine iM formation from a C-rich strand from the promoter of the human c-MYC gene. We used a number of biophysical techniques to characterize both the hydrodynamic properties and folding kinetics of a folded iM. Our hydrodynamic studies using fluorescence anisotropy decay and analytical ultracentrifugation show that the iM structure has a compact size in solution and displays the rigidity of a double strand. By studying the rates of circular dichroism spectral changes and quenching of fluorescent cytidine analogs, we also established a mechanism for the folding of a random coil oligo into the iM. In the course of determining this folding pathway, we established that the fluorescent dC analogs tC° and PdC can be used to monitor individual residues of an iM structure and to determine the pKa of an iM. We established that the C-C+ hydrogen bonding of certain bases initiates the folding of the iM structure. We also showed that substitutions in the loop regions of iMs give a distinctly different kinetic signature during folding compared with bases that are intercalated. Our data reveal that the iM passes through a distinct intermediate form between the unfolded and folded forms. Taken together, our results lay the foundation for using fluorescent dC analogs to follow structural changes during iM formation. Our technique may also be useful for examining folding and structural changes in more complex iMs. PMID:25296324

A data mining method to facilitate SAR transfer.

PubMed

Wassermann, Anne Mai; Bajorath, Jürgen

2011-08-22

A challenging practical problem in medicinal chemistry is the transfer of SAR information from one chemical series to another. Currently, there are no computational methods available to rationalize or support this process. Herein, we present a data mining approach that enables the identification of alternative analog series with different core structures, corresponding substitution patterns, and comparable potency progression. Scaffolds can be exchanged between these series and new analogs suggested that incorporate preferred R-groups. The methodology can be applied to search for alternative analog series if one series is known or, alternatively, to systematically assess SAR transfer potential in compound databases.

Energy distributions in rods and beams

NASA Technical Reports Server (NTRS)

Wohlever, J. C.; Bernhard, R. J.

1989-01-01

A hypothesis proposed by Nefske and Sung (1987) that the mechanical energy flow in acoustic/structural systems can be modeled using a thermal energy flow analogy was tested for both longitudinal vibration in rods and transverse flexural vibrations in beams. It was found that the rod behaves according to the energy flow analogy. However, the beam solutions behaved significantly differently than predicted by the thermal analogy, unless spatially averaged energy and power flow were considered. Otherwise, the beam analysis is restricted to frequencies where the near-field terms in the displacement solution are negligible over most of the beam.

Synthesis and activity of novel analogs of hemiasterlin as inhibitors of tubulin polymerization: modification of the A segment.

PubMed

Yamashita, Ayako; Norton, Emily B; Kaplan, Joshua A; Niu, Chuan; Loganzo, Frank; Hernandez, Richard; Beyer, Carl F; Annable, Tami; Musto, Sylvia; Discafani, Carolyn; Zask, Arie; Ayral-Kaloustian, Semiramis

2004-11-01

Analogs of hemiasterlin (1) and HTI-286 (2), which contain various aromatic rings in the A segment, were synthesized as potential inhibitors of tubulin polymerization. The structure-activity relationships related to stereo- and regio-chemical effects of substituents on the aromatic ring in the A segment were studied. Analogs, which carry a meta-substituted phenyl ring in the A segment show comparable activity for inhibition of tubulin polymerization to 2, as well as in the cell proliferation assay using KB cells containing P-glycoprotein, compared to those of 1 and 2.

Helping Young Children to See What Is Relevant and Why: Supporting Cognitive Change in Earth Science Using Analogy. Research Report

ERIC Educational Resources Information Center

Blake, Anthony

2004-01-01

This experimental study explores how 60 primary-age children's (9-11 years old) understanding of rocks was effected by instruction that used the conceptual structure of the rock cycle together with the analogy of aluminium can recycling. Using a combination of probes into children's understanding, including concept maps and semi-structured…

Photonic Bandgaps in Photonic Molecules

NASA Technical Reports Server (NTRS)

Smith, David D.; Chang, Hongrok; Gates, Amanda L.; Fuller, Kirk A.; Gregory, Don A.; Witherow, William K.; Paley, Mark S.; Frazier, Donald O.; Curreri, Peter A. (Technical Monitor)

2002-01-01

This talk will focus on photonic bandgaps that arise due to nearly free photon and tight-binding effects in coupled microparticle and ring-resonator systems. The Mie formulation for homogeneous spheres is generalized to handle core/shell systems and multiple concentric layers in a manner that exploits an analogy with stratified planar systems, thereby allowing concentric multi-layered structures to be treated as photonic bandgap (PBG) materials. Representative results from a Mie code employing this analogy demonstrate that photonic bands arising from nearly free photon effects are easily observed in the backscattering, asymmetry parameter, and albedo for periodic quarter-wave concentric layers, though are not readily apparent in extinction spectra. Rather, the periodicity simply alters the scattering profile, enhancing the ratio of backscattering to forward scattering inside the bandgap, in direct analogy with planar quarter-wave multilayers. PBGs arising from tight-binding may also be observed when the layers (or rings) are designed such that the coupling between them is weak. We demonstrate that for a structure consisting of N coupled micro-resonators, the morphology dependent resonances split into N higher-Q modes, in direct analogy with other types of oscillators, and that this splitting ultimately results in PBGs which can lead to enhanced nonlinear optical effects.

The Creative Power of Formal Analogies in Physics: The Case of Albert Einstein

NASA Astrophysics Data System (ADS)

Gingras, Yves

2015-07-01

In order to show how formal analogies between different physical systems play an important conceptual work in physics, this paper analyzes the evolution of Einstein's thoughts on the structure of radiation from the point of view of the formal analogies he used as "lenses" to "see" through the "black box" of Planck's blackbody radiation law. A comparison is also made with his 1925 paper on the quantum gas where he used the same formal methods. Changes of formal points of view are most of the time taken for granted or passed over in silence in studies on the mathematization of physics as if they had no special significance. Revisiting Einstein's classic papers on the nature of light and matter from the angle of the various theoretical tools he used, namely entropy and energy fluctuation calculations, helps explain why he was in a unique position to make visible the particle structure of radiation and the dual (particle and wave) nature of light and matter. Finally, this case study calls attention to the more general question of the surprising creative power of formal analogies and their frequent use in theoretical physics. This aspect of intellectual creation can be useful in the teaching of physics.

Molecular Hybridization of Potent and Selective γ-Hydroxybutyric Acid (GHB) Ligands: Design, Synthesis, Binding Studies, and Molecular Modeling of Novel 3-Hydroxycyclopent-1-enecarboxylic Acid (HOCPCA) and trans-γ-Hydroxycrotonic Acid (T-HCA) Analogs.

PubMed

Krall, Jacob; Jensen, Claus Hatt; Bavo, Francesco; Falk-Petersen, Christina Birkedahl; Haugaard, Anne Stæhr; Vogensen, Stine Byskov; Tian, Yongsong; Nittegaard-Nielsen, Mia; Sigurdardóttir, Sara Björk; Kehler, Jan; Kongstad, Kenneth Thermann; Gloriam, David E; Clausen, Rasmus Prætorius; Harpsøe, Kasper; Wellendorph, Petrine; Frølund, Bente

2017-11-09

γ-Hydroxybutyric acid (GHB) is a neuroactive substance with specific high-affinity binding sites. To facilitate target identification and ligand optimization, we herein report a comprehensive structure-affinity relationship study for novel ligands targeting these binding sites. A molecular hybridization strategy was used based on the conformationally restricted 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) and the linear GHB analog trans-4-hydroxycrotonic acid (T-HCA). In general, all structural modifications performed on HOCPCA led to reduced affinity. In contrast, introduction of diaromatic substituents into the 4-position of T-HCA led to high-affinity analogs (medium nanomolar K i ) for the GHB high-affinity binding sites as the most high-affinity analogs reported to date. The SAR data formed the basis for a three-dimensional pharmacophore model for GHB ligands, which identified molecular features important for high-affinity binding, with high predictive validity. These findings will be valuable in the further processes of both target characterization and ligand identification for the high-affinity GHB binding sites.

A Linear trans-Bis(imido) Neptunium(V) Actinyl Analog: Np(V)(NDipp)2((t)Bu2bipy)2Cl (Dipp = 2,6-(i)Pr2C6H3).

PubMed

Brown, Jessie L; Batista, Enrique R; Boncella, James M; Gaunt, Andrew J; Reilly, Sean D; Scott, Brian L; Tomson, Neil C

2015-08-05

The discovery that imido analogs of actinyl dioxo cations can be extended beyond uranium into the transuranic elements is presented. Synthesis of the Np(V) complex, Np(NDipp)2((t)Bu2bipy)2Cl (1), is achieved through treatment of a Np(IV) precursor with a bipyridine coligand and lithium-amide reagent. Complex 1 has been structurally characterized, analyzed by (1)H NMR and UV-vis-NIR spectroscopies, and the electronic structure evaluated by DFT calculations.

Potent μ-Opioid Receptor Agonists from Cyclic Peptides Tyr-c[D-Lys-Xxx-Tyr-Gly]: Synthesis, Biological, and Structural Evaluation.

PubMed

Li, Yangmei; Cazares, Margret; Wu, Jinhua; Houghten, Richard A; Toll, Laurence; Dooley, Colette

2016-02-11

To optimize the structure of a μ-opioid receptor ligand, analogs H-Tyr-c[D-Lys-Xxx-Tyr-Gly] were synthesized and their biological activity was tested. The analog containing a Phe(3) was identified as not only exhibiting binding affinity 14-fold higher than the original hit but also producing agonist activity 3-fold more potent than morphine. NMR study suggested that a trans conformation at D-Lys(2)-Xxx(3) is crucial for these cyclic peptides to maintain high affinity, selectivity, and functional activity toward the μ-opioid receptor.

Stabilization of flat aromatic Si6 rings analogous to benzene: ab initio theoretical prediction.

PubMed

Zdetsis, Aristides D

2007-12-07

It is shown by ab initio calculations, based on density functional (DFT/B3LYP), and high level coupled-cluster [CCSD(T)] and quadratic CI [QCISD(T)] methods, that flat aromatic silicon structures analogous to benzene (C6H6) can be stabilized in the presence of lithium. The resulting planar Si6Li6 structure is both stable and aromatic, sharing many key characteristics with benzene. To facilitate possible synthesis and characterization of these species, routes of formation with high exothermicity are suggested and several spectral properties (including optical absorption, infrared, and Raman) are calculated.

A Linear trans -Bis(imido) Neptunium(V) Actinyl Analog: Np V (NDipp) 2 ( tBu 2 bipy) 2Cl (Dipp = 2,6- i Pr 2C 6H 3)

DOE PAGES

Brown, Jessie L.; Batista, Enrique R.; Boncella, James M.; ...

2015-07-22

We present the discovery that imido analogs of actinyl dioxo cations can be extended beyond uranium into the transuranic elements. Synthesis of the Np(V) complex, Np(NDipp) 2( tBu 2bipy) 2Cl (1), is achieved through treatment of a Np(IV) precursor with a bipyridine co-ligand and lithium-amide reagent. Complex 1 has been structurally characterized, analyzed by 1H NMR and UV/vis/NIR spectroscopies, and the electronic structure evaluated by DFT calculations.

Communication, Correlation and Complementarity

NASA Astrophysics Data System (ADS)

Schumacher, Benjamin Wade

1990-01-01

In quantum communication, a sender prepares a quantum system in a state corresponding to his message and conveys it to a receiver, who performs a measurement on it. The receiver acquires information about the message based on the outcome of his measurement. Since the state of a single quantum system is not always completely determinable from measurement, quantum mechanics limits the information capacity of such channels. According to a theorem of Kholevo, the amount of information conveyed by the channel can be no greater than the entropy of the ensemble of possible physical signals. The connection between information and entropy allows general theorems to be proved regarding the energy requirements of communication. For example, it can be shown that one particular quantum coding scheme, called thermal coding, uses energy with maximum efficiency. A close analogy between communication and quantum correlation can be made using Everett's notion of relative states. Kholevo's theorem can be used to prove that the mutual information of a pair of observables on different systems is bounded by the entropy of the state of each system. This confirms and extends an old conjecture of Everett. The complementarity of quantum observables can be described by information-theoretic uncertainty relations, several of which have been previously derived. These relations imply limits on the degree to which different messages can be coded in complementary observables of a single channel. Complementarity also restricts the amount of information that can be recovered from a given channel using a given decoding observable. Information inequalities can be derived which are analogous to the well-known Bell inequalities for correlated quantum systems. These inequalities are satisfied for local hidden variable theories but are violated by quantum systems, even where the correlation is weak. These information inequalities are metric inequalities for an "information distance", and their structure can be made exactly analogous to that of the familiar covariance Bell inequalities by introducing a "covariance distance". Similar inequalities derived for successive measurements on a single system are also violated in quantum mechanics.

Don't Read University Rankings like Reading Football League Tables: Taking a Close Look at the Indicators

ERIC Educational Resources Information Center

Soh, Kay Cheng

2011-01-01

The outcome of university ranking is of much interest and concern to the many stakeholders, including university's sponsors, administrators, staff, current and prospective students, and the public. The results of rankings presented in the form of league tables, analogous to football league tables, attract more attention than do the processes by…

The Relation of Story Structure to a Model of Conceptual Change in Science Learning

NASA Astrophysics Data System (ADS)

Klassen, Stephen

2010-03-01

Although various reasons have been proposed to explain the potential effectiveness of science stories to promote learning, no explicit relationship of stories to learning theory in science has been propounded. In this paper, two structurally analogous models are developed and compared: a structural model of stories and a temporal conceptual change model of learning. On the basis of the similarity of the models, as elaborated, it is proposed that the structure of science stories may promote a re-enactment of the learning process, and, thereby, such stories serve to encourage active learning through the generation of hypotheses and explanations. The practical implications of this theoretical analogy can be applied to the classroom in that the utilization of stories provides the opportunity for a type of re-enactment of the learning process that may encourage both engagement with the material and the development of long-term memory structures.

Synthesis, iron(III) complexation properties, molecular dynamics simulations and P. aeruginosa siderophore-like activity of two pyoverdine analogs.

PubMed

Antonietti, Viviane; Boudesocque, Stéphanie; Dupont, Laurent; Farvacques, Natacha; Cézard, Christine; Da Nascimento, Sophie; Raimbert, Jean-François; Socrier, Larissa; Robin, Thierry-Johann; Morandat, Sandrine; El Kirat, Karim; Mullié, Catherine; Sonnet, Pascal

2017-09-08

P. aeruginosa ranks among the top five organisms causing nosocomial infections. Among the many novel strategies for developing new therapeutics against infection, targeting iron uptake mechanism seems promising as P. aeruginosa needs iron for its growth and survival. To scavenge iron, the bacterium produces siderophores possessing a very high affinity towards Fe(III) ions such as pyoverdines. In this work, we decided to study two pyoverdine analogs, aPvd2 and aPvd3, structurally close to the endogen pyoverdine. The pFe constants calculated with the values of formation showed a high affinity of aPvd3 towards Fe(III). Molecular dynamics calculations demonstrated that aPvd3-Fe forms with Fe(III) stable 1:1 complexes in water, whereas aPvd2 does not. Only aPvd3 is able to increase the bacterial growth and represents thus an alternative to pyoverdine for iron acquisition by the bacterium. The aPvd2-3 interaction studies with a lipid membrane indicated that they were unable to interact and to cross the plasma membrane of bacteria by passive diffusion. Consequently, the penetration of aPvd3 is ruled by a transport membrane protein. These results showed that aPvd3 may be used to inhibit pyoverdine uptake or to promote the accumulation and release of antibiotics into the cell following a Trojan horse strategy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Pituitary adenylate cyclase-activating polypeptide is a potent broad-spectrum antimicrobial peptide: Structure-activity relationships.

PubMed

Starr, Charles G; Maderdrut, Jerome L; He, Jing; Coy, David H; Wimley, William C

2018-06-01

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a naturally occurring cationic peptide with potent immunosuppressant and cytoprotective activities. We now show that full length PACAP38 and to a lesser extent, the truncated form PACAP27, and the closely related vasoactive intestinal peptide (VIP) and secretin had antimicrobial activity against the Gram-negative bacteria Escherichia coli in the radial diffusion assay. PACAP38 was more potent than either the bovine neutrophil antimicrobial peptide indolicidin or the synthetic antimicrobial peptide ARVA against E. coli. PACAP38 also had activity against the Gram-positive bacteria Staphylococcus aureus in the same assay with comparable potency to indolicidin and ARVA. In the more stringent broth dilution assay, PACAP38 had moderate sterilizing activity against E. coli, and potent sterilizing activity against the Gram-negative bacteria Pseudomonas aeruginosa. PACAP27, VIP and secretin were much less active than PACAP38 in this assay. PACAP38 also had some activity against the Gram-positive bacteria Bacillus cereus in the broth dilution assay. Many exopeptidase-resistant analogs of PACAP38, including both receptor agonists and antagonists, had antimicrobial activities equal to, or better than PACAP38, in both assays. PACAP38 made the membranes of E. coli permeable to SYTOX Green, suggesting a classical membrane lytic mechanism. These data suggest that analogs of PACPAP38 with a wide range of useful biological activities can be made by judicious substitutions in the sequence. Copyright © 2018 Elsevier Inc. All rights reserved.

Design by Analogy: Achieving More Patentable Ideas from One Creative Design

NASA Astrophysics Data System (ADS)

Jia, Li-Zhen; Wu, Chun-Long; Zhu, Xue-Hong; Tan, Run-Hua

2018-12-01

A patent is a kind of technical document to protect intellectual property for individuals or enterprises. Patentable idea generation is a crucial step for patent application and analogy is confirmed to be an effective technique to inspire creative ideas. Analogy-based design usually starts from representation of an analogy source and is followed by the retrieval of appropriate analogs, mapping of design knowledge and adaptation of target solution. To diffuse one core idea into other new contexts and achieve more patentable ideas, this paper mainly centered on the first two stages of analogy-based design and proposed a patentable ideation framework. The analogical information of the source system, including source design problems and solution, was mined comprehensively through International Patent Classification analysis and represented in the form of function, behavior and structure. Three heuristics were suggested for searching the set of candidate target systems with a similar design problem, where the source design could be transferred. To systematize the process of source representation, analogs retrieval, idea transfer, and solution generation, an ideation model was put forward. Finally, the bladeless fan was selected as a source design to illustrate the application of this work. The design output shows that the representation and heuristics are beneficial, and this systematic ideation method can help the engineer or designer enhance creativity and discover more patentable opportunities.

VESTOIDS, PART II: THE BASALTIC NATURE AND HED METEORITE ANALOGS FOR EIGHT V{sub p}-TYPE ASTEROIDS AND THEIR ASSOCIATIONS WITH (4) VESTA

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

Hardersen, Paul S.; Reddy, Vishnu; Roberts, Rachel, E-mail: Hardersen@space.edu

Improving the constraints on the abundance of basaltic asteroids in the main asteroid belt is necessary for better understanding the thermal and collisional environment in the early solar system, for more rigorously identifying the genetic family for (4) Vesta, for determining the effectiveness of Yarkovsky/YORP in dispersing asteroid families, and for better quantifying the population of basaltic asteroids in the outer main belt (a > 2.5 AU) that is likely unrelated to (4) Vesta. Near-infrared (NIR) spectral observations in this work were obtained for the V{sub p}-type asteroids (2011) Veteraniya, (5875) Kuga, (8149) Ruff, (9147) Kourakuen, (9553) Colas, (15237) 1988 RL{sub 6},more » (31414) Rotaryusa, and (32940) 1995 UW{sub 4} during 2014 August/September utilizing the SpeX spectrograph at the NASA Infrared Telescope Facility, Mauna Kea, Hawaii. Spectral band parameter (band centers, band area ratios) and mineralogical analysis (pyroxene chemistry) for each average asteroid NIR reflectance spectrum suggest a howardite–eucrite–diogenite meteorite analog for each asteroid. (5875) Kuga is most closely associated with the eucrite meteorites, (31414) Rotaryusa is most closely associated with the diogenites, and the remaining other six asteroids are most closely associated with the howardite meteorites. Along with their orbital locations in the inner main belt and in the vicinity of (4) Vesta, the existing evidence suggests that these eight V{sub p}-type asteroids are also likely Vestoids.« less

The well-tuned blues: the role of structural colours as optical signals in the species recognition of a local butterfly fauna (Lepidoptera: Lycaenidae: Polyommatinae)

PubMed Central

Bálint, Zsolt; Kertész, Krisztián; Piszter, Gábor; Vértesy, Zofia; Biró, László P.

2012-01-01

The photonic nanoarchitectures responsible for the blue colour of the males of nine polyommatine butterfly species living in the same site were investigated structurally by electron microscopy and spectrally by reflectance spectroscopy. Optical characterization was carried out on 110 exemplars. The structural data extracted by dedicated software and the spectral data extracted by standard software were inputted into an artificial neural network software to test the specificity of the structural and optical characteristics. It was found that both the structural and the spectral data allow species identification with an accuracy better than 90 per cent. The reflectance data were further analysed using a colour representation diagram built in a manner analogous to that of the human Commission Internationale de l'Eclairage diagram, but the additional blue visual pigment of lycaenid butterflies was taken into account. It was found that this butterfly-specific colour representation diagram yielded a much clearer distinction of the position of the investigated species compared with previous calculations using the human colour space. The specific colours of the investigated species were correlated with the 285 flight-period data points extracted from museum collections. The species with somewhat similar colours fly in distinct periods of the year such that the blue colours are well tuned for safe mate/competitor recognition. This allows for the creation of an effective pre-zygotic isolation mechanism for closely related synchronic and syntopic species. PMID:22319114

NPPB structure-specifically activates TRPA1 channels.

PubMed

Liu, Kun; Samuel, Manoj; Ho, Melisa; Harrison, Richard K; Paslay, Jeff W

2010-07-01

TRPA1 channels have been found to play an important role in mammalian pain sensation, especially when the pain is caused by chemicals on site of inflammation. A large number of structurally diverse chemicals are found to activate TRPA1 channels, implicating a potential chemosensor in neuronal nociception. Identification of the channel activation by cysteine modification through covalent chemical reaction provides arguments for the diversity of the agonist structures. However, it is largely unknown how nonreactive compounds activate TRPA1 channels. Here, we report that NPPB, a classic Cl(-) channel blocker, potently activated human TRPA1 channels overexpressed in mammalian HEK-293 cells. This effect was confirmed in Ca(2+) imaging assay, patch clamp whole cell and single channel recordings. The NPPB response was quick, fully reversible and replicable, contrary to the effect of covalent modification by AITC. The mutagenesis studies revealed a refreshed look at several mutations known to be critical for the actions of AITC and menthol. The blocking profile of NPPB on these mutants showed that the NPPB activation was similar to that of FTS and different from AITC and menthol. The results indicated a possible close interaction between S5 and N-terminal domains of the channel. We also tested a group of NPPB analogs on TRPA1 channel activities. The results demonstrated that NPPB activation was tightly associated with chemical structure. None of the single chemical group was sufficient to activate the channel, indicating that NPPB activated TRPA1 through a structure-specific mechanism. (c) 2010 Elsevier Inc. All rights reserved.

Aromatic Bagels: An Edible Resonance Analogy

ERIC Educational Resources Information Center

Lin, Shirley

2007-01-01

Two Lewis structures, resonance contributors, are used to describe benzene (the Kekule structure) in order to explain resonance theory to chemistry students. The students could create two bagel halves representing the Kekule structures of benzene in which the numbered toothpicks corresponds to the carbon atoms in the two structures and the x…

Information-System Structure by Communication-Technology Concepts: A Cybernetic Model Approach.

ERIC Educational Resources Information Center

Reisig, Gerhard H. R.

1978-01-01

Presents the "Evidence-of-Existence" information system in which the structure is developed, with application of cybernetic concepts, as an isomorphic model in analogy to the system structure of communication technology. Three criteria of structuring are postulated: (1) source-channel-sink, with input-output characteristics, (2) filter-type…

Molecular characterization of the receptor binding structure-activity relationships of influenza B virus hemagglutinin.

PubMed

Carbone, V; Kim, H; Huang, J X; Baker, M A; Ong, C; Cooper, M A; Li, J; Rockman, S; Velkov, T

2013-01-01

Selectivity of α2,6-linked human-like receptors by B hemagglutinin (HA) is yet to be fully understood. This study integrates binding data with structure-recognition models to examine the impact of regional-specific sequence variations within the receptor-binding pocket on selectivity and structure activity relationships (SAR). The receptor-binding selectivity of influenza B HAs corresponding to either B/Victoria/2/1987 or the B/Yamagata/16/88 lineages was examined using surface plasmon resonance, solid-phase ELISA and gel-capture assays. Our SAR data showed that the presence of asialyl sugar units is the main determinant of receptor preference of α2,6 versus α2,3 receptor binding. Changes to the type of sialyl-glycan linkage present on receptors exhibit only a minor effect upon binding affinity. Homology-based structural models revealed that structural properties within the HA pocket, such as a glyco-conjugate at Asn194 on the 190-helix, sterically interfere with binding to avian receptor analogs by blocking the exit path of the asialyl sugars. Similarly, naturally occurring substitutions in the C-terminal region of the 190-helix and near the N-terminal end of the 140-loop narrows the horizontal borders of the binding pocket, which restricts access of the avian receptor analog LSTa. This study helps bridge the gap between ligand structure and receptor recognition for influenza B HA; and provides a consensus SAR model for the binding of human and avian receptor analogs to influenza B HA.

Low-temperature and low atmospheric pressure infrared reflectance spectroscopy of Mars soil analog materials

NASA Technical Reports Server (NTRS)

Bishop, Janice L.; Pieters, Carle M.

1995-01-01

Infrared reflectance spectra of carefully selected Mars soil analog materials have been measured under low atmospheric pressures and temperatures. Chemically altered montmorillonites containing ferrihydrite and hydrated ferric sulfate complexes are examined, as well as synthetic ferrihydrate and a palagonitic soil from Haleakala, Maui. Reflectance spectra of these analog materials exhibit subtle visible to near-infrared features, which are indicative of nanophase ferric oxides or oxyhydroxides and are similar to features observed in the spectra of the bright regions of Mars. Infrared reflectance spectra of these analogs include hydration features due to structural OH, bound H2O and adsorbed H2O. The spectal character of these hydration features is highly dependent on the sample environment and on the nature of the H2O/OH in the analogs. The behavior of the hydration features near 1.9 micrometers, 2.2 micrometers, 2.7 micrometers, 3 micrometers, and 6 micrometers are reported here in spetra measured under Marslike atmospheric environment. In spectra of these analogs measured under dry Earth atmospheric conditions the 1.9-micrometer band depth is 8-17%; this band is much stonger under moist conditions. Under Marslike atmospheric conditions the 1.9-micrometer feature is broad and barely discernible (1-3% band depth) in spectra of the ferrihydrite and palagonitic soil samples. In comparable spectra of the ferric sulfate-bearing montmorillonite the 1.9-micrometer feature is also broad, but stronger (6% band depth). In the low atmospheric pressure and temperature spectra of the ferrihydrite-bearing montmorillonite this feature is sharper than the other analogs and relatively stronger (6% band depth). Although the intensity of the 3- micrometer band is weaker in spectra of each of the analogs when measured under Marslike conditions, the 3-micromter band remains a dominant feature and is especially broad in spectra of the ferrihydrite and palagonitic soil. The structural OH features observed in these materials at 2.2-2.3 micrometers and 2.27 micrometers remain largely unaffected by the environmental conditions. A shift in the Christiansen feature towards shorter wavelengths has also been observed with decreasing atmospheric pressure and temperature in the midinfrared spectra of these samples.

Low-temperature and low atmospheric pressure infrared reflectance spectroscopy of Mars soil analog materials

NASA Technical Reports Server (NTRS)

Bishop, Janice L.; Pieters, Carle M.

1995-01-01

Infrared reflectance spectra of carefully selected Mars soil analog materials have been measured under low atmospheric pressures and temperatures. Chemically altered montmorillonites containing ferrihydrite and hydrated ferric sulfate complexes are examined, as well as synthetic ferrihydrite and a palagonitic soil from Haleakala, Maui. Reflectance spectra of these analog materials exhibit subtle visible to near-infrared features, which are indicative of nanophase ferric oxides or oxyhydroxides and are similar to features observed in the spectra of the bright regions of Mars. Infrared reflectance spectra of these analogs include hydration features due to structural OH, bound H2O, and adsorbed H2O. The spectral character of these hydration features is highly dependent on the sample environment and on the nature of the H2O/OH in the analogs. The behavior of the hydration features near 1.9 micron, 2.2 micron, 2.7 micron, 3 micron, and 6 microns are reported here in spectra measured under a Marslike atmospheric environment. In spectra of these analogs measured under dry Earth atmospheric conditions the 1.9-micron band depth is 8-17%; this band is much stronger under moist conditions. Under Marslike atmospheric conditions the 1.9-micron feature is broad and barely discernible (1-3% band depth) in spectra of the ferrihydrite and palagonitic soil samples. In comparable spectra of the ferric sulfate-bearing montmorillonite the 1.9-micron feature is also broad, but stronger (6% band depth). In the low atmospheric pressure and temperature spectra of the ferrihydrite-bearing montmorillonite this feature is sharper than the other analogs and relatively stronger (6% band depth). Although the intensity of the 3-micron band is weaker in spectra of each of the analogs when measured under Marslike conditions, the 3-micron band remains a dominant feature and is especially broad in spectra of the ferrihydrite and palagonitic soil. The structural OH features observed in these materials at 2.2-2.3 micron and 2.75 microns remain largely unaffected by the environmental conditions. A shift in the Christiansen feature towards shorter wavelengths has also been observed with decreasing atmospheric pressure and temperature in the midinfrared spectra of these samples.

Structural data collection with mobile devices: Accuracy, redundancy, and best practices

NASA Astrophysics Data System (ADS)

Allmendinger, Richard W.; Siron, Christopher R.; Scott, Chelsea P.

2017-09-01

Smart phones are equipped with numerous sensors that enable orientation data collection for structural geology at a rate up to an order of magnitude faster than traditional analog compasses. The rapidity of measurement enables field structural geologists, for the first time, to enjoy the benefits of data redundancy and quantitative uncertainty estimates. Recent work, however, has called into question the reliability of sensors on Android devices. We present here our experience with programming a new smart phone app from scratch, and using it and commercial apps on iOS devices along with analog compasses in a series of controlled tests and typical field use cases. Additionally, we document the relationships between iPhone measurements and visible structures in satellite, drawing on a database of 3700 iPhone measurements of coseismic surface cracks we made in northern Chile following the Mw8.1 Pisagua earthquake in 2014. By comparing phone-collected attitudes to orientations determined independently of the magnetic field, we avoid having to assume that the analog compass, which is subject to its own uncertainties, is the canonical instrument. Our results suggest that iOS devices are suitable for all but the most demanding applications as long as particular care is taken with respect to metal and electronic objects that could affect the magnetic field.

Identification of metabolically stable 5′-phosphate analogs that support single-stranded siRNA activity

PubMed Central

Prakash, Thazha P.; Lima, Walt F.; Murray, Heather M.; Li, Wenyu; Kinberger, Garth A.; Chappell, Alfred E.; Gaus, Hans; Seth, Punit P.; Bhat, Balkrishen; Crooke, Stanley T.; Swayze, Eric E.

2015-01-01

The ss-siRNA activity in vivo requires a metabolically stable 5′-phosphate analog. In this report we used crystal structure of the 5′-phosphate binding pocket of Ago-2 bound with guide strand to design and synthesize ss-siRNAs containing various 5′-phosphate analogs. Our results indicate that the electronic and spatial orientation of the 5′-phosphate analog was critical for ss-siRNA activity. Chemically modified ss-siRNA targeting human apoC III mRNA demonstrated good potency for inhibiting ApoC III mRNA and protein in transgenic mice. Moreover, ApoC III ss-siRNAs were able to reduce the triglyceride and LDL cholesterol in transgenic mice demonstrating pharmacological effect of ss-siRNA. Our study provides guidance to develop surrogate phosphate analog for ss-siRNA and demonstrates that ss-siRNA provides an alternative strategy for therapeutic gene silencing. PMID:25753666

Harmonics analysis of the photonic time stretch system.

PubMed

Mei, Yuan; Xu, Boyu; Chi, Hao; Jin, Tao; Zheng, Shilie; Jin, Xiaofeng; Zhang, Xianmin

2016-09-10

Photonic time stretch (PTS) has been intensively investigated in recent decades due to its potential application to ultra-wideband analog-to-digital conversion. A high-speed analog signal can be captured by an electronic analog-to-digital converter (ADC) with the help of the PTS technique, which slows down the speed of signal in the photonic domain. Unfortunately, the process of the time stretch is not linear due to the nonlinear modulation of the electro-optic intensity modulator in the PTS system, which means the undesired harmonics distortion. In this paper, we present an exact analytical model to fully characterize the harmonics generation in the PTS systems for the first time, to the best of our knowledge. We obtain concise and closed-form expressions for all harmonics of the PTS system with either a single-arm Mach-Zehnder modulator (MZM) or a push-pull MZM. The presented model can largely simplify the PTS system design and the system parameters estimation, such as system bandwidth, harmonics power, time-bandwidth product, and dynamic range. The correctness of the mathematic model is verified by the numerical and experimental results.

A 32-channel front-end ASIC for GEM detectors used in beam monitoring applications

NASA Astrophysics Data System (ADS)

Ciciriello, F.; Altieri, P. R.; Corsi, F.; De Robertis, G.; Felici, G.; Loddo, F.; Lorusso, L.; Marzocca, C.; Matarrese, G.; Ranieri, A.; Stamerra, A.

2017-11-01

A multichannel, mixed-signal, front-end ASIC for GEM detectors, intended for beam monitoring in hadron therapy applications, has been designed and prototyped in a standard 0.35 μm CMOS technology. The analog channels are based on the classic CSA + shaper processing chain, followed by a peak detector which can work as an analog memory, to simplifiy the analog-to-digital conversion of the peak voltage of the output pulse, proportional to the energy of the detected event. The available hardware resources include an 8-bit A/D converter and a standard-cell digital part, which manages the read-out procedure, in sparse or serial mode. The ASIC is self-triggered and transfers energy and address data to the external DAQ via a fast 100 MHz LVDS link. Preliminary characterization results show that the non-linearity error is limited to 5% for a maximum input charge of about 70 fC, the measured ENC is about 1400e- and the time jitter of the trigger signal generated in response to an injected charge of 60 fC is close to 200 ps.

Detecting peptidic drugs, drug candidates and analogs in sports doping: current status and future directions.

PubMed

Thevis, Mario; Thomas, Andreas; Schänzer, Wilhelm

2014-12-01

With the growing availability of mature systems and strategies in biotechnology and the continuously expanding knowledge of cellular processes and involved biomolecules, human sports drug testing has become a considerably complex field in the arena of analytical chemistry. Proving the exogenous origin of peptidic drugs and respective analogs at lowest concentration levels in biological specimens (commonly blood, serum and urine) of rather limited volume is required to pursue an action against cheating athletes. Therefore, approaches employing chromatographic-mass spectrometric, electrophoretic, immunological and combined test methods have been required and developed. These allow detecting the misuse of peptidic compounds of lower (such as growth hormone-releasing peptides, ARA-290, TB-500, AOD-9604, CJC-1295, desmopressin, luteinizing hormone-releasing hormones, synacthen, etc.), intermediate (e.g., insulins, IGF-1 and analogs, 'full-length' mechano growth factor, growth hormone, chorionic gonadotropin, erythropoietin, etc.) and higher (e.g., stamulumab) molecular mass with desired specificity and sensitivity. A gap between the technically possible detection and the day-to-day analytical practice, however, still needs to be closed.

[Micromonospora resistence to definite antibiotics and their ability to produce structurally analogous antibiotics].

PubMed

Bibikova, M V; Ivanitskaia, L P; Tikhonova, A S

1980-01-01

Thirty six cultures of Micromonospora freshly isolated from soil samples were studied with respect to their sensitivity to a number of antibiotics of various structures and modes of action. It was found that all of them were highly sensitive to penicillin, ristomycin, tetracycline, rifampicin, streptomycin, olivomycin, carminomycin and dactinomycin. Significant differences in sensitivity of the Micromonospora cultures were revealed only with respect to gentamicin, tobramicin, erythromycin and lincomycin. Seven cultures were resistant to gentamicin and tobramicin and sensitive to all of the other antibiotics. Broad spectrum antibiotics were isolated from these cultures. The study of the antibiotic chemistry showed that they were 2-desoxystreptamine-containing aminoglycosides. Two cultures proved to be resistant to erythromycin and lincomycin. When identified with the use of antibiotic resistant staphylococcal strains, the crude antibiotic substances isolated from these cultures appeared to be not active against staphylococci resistant to erythromycin and lincomycin. By their chromatograpi- behaviour the antibiotics were close to macrolides. Therefore, it was found that production of aminoglycoside and macrolide antibiotics was most characteristic of Micromonospora. A certain correlation between resistance of Micromonospora to these 2 antibiotic groups and capacity for their production was shown.

Jet Surface Interaction Scrubbing Noise from High Aspect-Ratio Rectangular Jets

NASA Technical Reports Server (NTRS)

Khavaran, Abbas; Bozak, Richard F.

2015-01-01

Concepts envisioned for the future of civil air transport consist of unconventional propulsion systems in the close proximity of the airframe. Distributed propulsion system with exhaust configurations that resemble a high aspect ratio rectangular jet are among geometries of interest. Nearby solid surfaces could provide noise shielding for the purpose of reduced community noise. Interaction of high-speed jet exhaust with structure could also generate new sources of sound as a result of flow scrubbing past the structure, and or scattered noise from sharp edges. The present study provides a theoretical framework to predict the scrubbing noise component from a high aspect ratio rectangular exhaust in proximity of a solid surface. The analysis uses the Greens function (GF) to the variable density Pridmore-Brown equation in a transversely sheared mean flow. Sources of sound are defined as the auto-covariance function of second-rank velocity fluctuations in the jet plume, and are modeled using a RANS-based acoustic analogy approach. Acoustic predictions are presented in an 8:1 aspect ratio rectangular exhaust at three subsonic Mach numbers. The effect of nearby surface on the scrubbing noise component is shown on both reflected and shielded sides of the plate.

Ultra-Low Power Dynamic Knob in Adaptive Compressed Sensing Towards Biosignal Dynamics.

PubMed

Wang, Aosen; Lin, Feng; Jin, Zhanpeng; Xu, Wenyao

2016-06-01

Compressed sensing (CS) is an emerging sampling paradigm in data acquisition. Its integrated analog-to-information structure can perform simultaneous data sensing and compression with low-complexity hardware. To date, most of the existing CS implementations have a fixed architectural setup, which lacks flexibility and adaptivity for efficient dynamic data sensing. In this paper, we propose a dynamic knob (DK) design to effectively reconfigure the CS architecture by recognizing the biosignals. Specifically, the dynamic knob design is a template-based structure that comprises a supervised learning module and a look-up table module. We model the DK performance in a closed analytic form and optimize the design via a dynamic programming formulation. We present the design on a 130 nm process, with a 0.058 mm (2) fingerprint and a 187.88 nJ/event energy-consumption. Furthermore, we benchmark the design performance using a publicly available dataset. Given the energy constraint in wireless sensing, the adaptive CS architecture can consistently improve the signal reconstruction quality by more than 70%, compared with the traditional CS. The experimental results indicate that the ultra-low power dynamic knob can provide an effective adaptivity and improve the signal quality in compressed sensing towards biosignal dynamics.

Towards a category theory approach to analogy: Analyzing re-representation and acquisition of numerical knowledge.

PubMed

Navarrete, Jairo A; Dartnell, Pablo

2017-08-01

Category Theory, a branch of mathematics, has shown promise as a modeling framework for higher-level cognition. We introduce an algebraic model for analogy that uses the language of category theory to explore analogy-related cognitive phenomena. To illustrate the potential of this approach, we use this model to explore three objects of study in cognitive literature. First, (a) we use commutative diagrams to analyze an effect of playing particular educational board games on the learning of numbers. Second, (b) we employ a notion called coequalizer as a formal model of re-representation that explains a property of computational models of analogy called "flexibility" whereby non-similar representational elements are considered matches and placed in structural correspondence. Finally, (c) we build a formal learning model which shows that re-representation, language processing and analogy making can explain the acquisition of knowledge of rational numbers. These objects of study provide a picture of acquisition of numerical knowledge that is compatible with empirical evidence and offers insights on possible connections between notions such as relational knowledge, analogy, learning, conceptual knowledge, re-representation and procedural knowledge. This suggests that the approach presented here facilitates mathematical modeling of cognition and provides novel ways to think about analogy-related cognitive phenomena.

Processing-optimised imaging of analog geological models by electrical capacitance tomography

NASA Astrophysics Data System (ADS)

Ortiz Alemán, C.; Espíndola-Carmona, A.; Hernández-Gómez, J. J.; Orozco Del Castillo, MG

2017-06-01

In this work, the electrical capacitance tomography (ECT) technique is applied in monitoring internal deformation of geological analog models, which are used to study structural deformation mechanisms, in particular for simulating migration and emplacement of allochtonous salt bodies. A rectangular ECT sensor was used for internal visualization of analog geologic deformation. The monitoring of analog models consists in the reconstruction of permittivity images from the capacitance measurements obtained by introducing the model inside the ECT sensor. A simulated annealing (SA) algorithm is used as a reconstruction method, and is optimized by taking full advantage of some special features in a linearized version of this inverse approach. As a second part of this work our SA image reconstruction algorithm is applied to synthetic models, where its performance is evaluated in comparison to other commonly used algorithms such as linear back-projection and iterative Landweber methods. Finally, the SA method is applied to visualise two simple geological analog models. Encouraging results were obtained in terms of the quality of the reconstructed images, as interfaces corresponding to main geological units in the analog model were clearly distinguishable in them. We found reliable results quite useful for real time non-invasive monitoring of internal deformation of analog geological models.

Towards a category theory approach to analogy: Analyzing re-representation and acquisition of numerical knowledge

PubMed Central

2017-01-01

Category Theory, a branch of mathematics, has shown promise as a modeling framework for higher-level cognition. We introduce an algebraic model for analogy that uses the language of category theory to explore analogy-related cognitive phenomena. To illustrate the potential of this approach, we use this model to explore three objects of study in cognitive literature. First, (a) we use commutative diagrams to analyze an effect of playing particular educational board games on the learning of numbers. Second, (b) we employ a notion called coequalizer as a formal model of re-representation that explains a property of computational models of analogy called “flexibility” whereby non-similar representational elements are considered matches and placed in structural correspondence. Finally, (c) we build a formal learning model which shows that re-representation, language processing and analogy making can explain the acquisition of knowledge of rational numbers. These objects of study provide a picture of acquisition of numerical knowledge that is compatible with empirical evidence and offers insights on possible connections between notions such as relational knowledge, analogy, learning, conceptual knowledge, re-representation and procedural knowledge. This suggests that the approach presented here facilitates mathematical modeling of cognition and provides novel ways to think about analogy-related cognitive phenomena. PMID:28841643

Discovery of a Manduca sexta Allatotropin Antagonist from a Manduca sexta Allatotropin Receptor Homology Model.

PubMed

Kai, Zhen-Peng; Zhu, Jing-Jing; Deng, Xi-Le; Yang, Xin-Ling; Chen, Shan-Shan

2018-04-03

Insect G protein coupled receptors (GPCRs) have important roles in modulating biology, physiology and behavior. They have been identified as candidate targets for next-generation insecticides, yet these targets have been relatively poorly exploited for insect control. In this study, we present a pipeline of novel Manduca sexta allatotropin (Manse-AT) antagonist discovery with homology modeling, docking, molecular dynamics simulation and structure-activity relationship. A series of truncated and alanine-replacement analogs of Manse-AT were assayed for the stimulation of juvenile hormone biosynthesis. The minimum sequence required to retain potent biological activity is the C -terminal amidated octapeptide Manse-AT (6-13). We identified three residues essential for bioactivity (Thr⁴, Arg6 and Phe⁸) by assaying alanine-replacement analogs of Manse-AT (6-13). Alanine replacement of other residues resulted in reduced potency but bioactivity was retained. The 3D structure of the receptor (Manse-ATR) was built and the binding pocket was identified. The binding affinities of all the analogs were estimated by calculating the free energy of binding. The calculated binding affinities corresponded to the biological activities of the analogs, which supporting our localization of the binding pocket. Then, based on the docking and molecular dynamics studies of Manse-AT (10-13), we described it can act as a potent Manse-AT antagonist. The antagonistic effect on JH biosynthesis of Manse-AT (10-13) validated our hypothesis. The IC 50 value of antagonist Manse-AT (10-13) is 0.9 nM. The structure-activity relationship of antagonist Manse-AT (10-13) was also studied for the further purpose of investigating theoretically the structure factors influencing activity. These data will be useful for the design of new Manse-AT agonist and antagonist as potential pest control agents.

Face Centered Cubic and Hexagonal Close Packed Skyrmion Crystals in Centrosymmetric Magnets

NASA Astrophysics Data System (ADS)

Lin, Shi-Zeng; Batista, Cristian D.

2018-02-01

Skyrmions are disklike objects that typically form triangular crystals in two-dimensional systems. This situation is analogous to the so-called pancake vortices of quasi-two-dimensional superconductors. The way in which Skyrmion disks or "pancake Skyrmions" pile up in layered centrosymmetric materials is dictated by the interlayer exchange. Unbiased Monte Carlo simulations and simple stabilization arguments reveal face centered cubic and hexagonal close packed Skyrmion crystals for different choices of the interlayer exchange, in addition to the conventional triangular crystal of Skyrmion lines. Moreover, an inhomogeneous current induces a sliding motion of pancake Skyrmions, indicating that they behave as effective mesoscale particles.

Analyzing threshold pressure limitations in microfluidic transistors for self-regulated microfluidic circuits.

PubMed

Kim, Sung-Jin; Yokokawa, Ryuji; Takayama, Shuichi

2012-12-03

This paper reveals a critical limitation in the electro-hydraulic analogy between a microfluidic membrane-valve (μMV) and an electronic transistor. Unlike typical transistors that have similar on and off threshold voltages, in hydraulic μMVs, the threshold pressures for opening and closing are significantly different and can change, even for the same μMVs depending on overall circuit design and operation conditions. We explain, in particular, how the negative values of the closing threshold pressures significantly constrain operation of even simple hydraulic μMV circuits such as autonomously switching two-valve microfluidic oscillators. These understandings have significant implications in designing self-regulated microfluidic devices.

An experimental device for characterizing degassing processes and related elastic fingerprints: Analog volcano seismo-acoustic observations.

PubMed

Spina, Laura; Morgavi, Daniele; Cannata, Andrea; Campeggi, Carlo; Perugini, Diego

2018-05-01

A challenging objective of modern volcanology is to quantitatively characterize eruptive/degassing regimes from geophysical signals (in particular seismic and infrasonic), for both research and monitoring purposes. However, the outcomes of the attempts made so far are still considered very uncertain because volcanoes remain inaccessible when deriving quantitative information on crucial parameters such as plumbing system geometry and magma viscosity. In order to improve our knowledge of volcanic systems, a novel experimental device, which is capable of mimicking volcanic degassing processes with different regimes and gas flow rates, and allowing for the investigation of the related seismo-acoustic emissions, was designed and developed. The benefits of integrating observations on real volcanoes with seismo-acoustic signals generated in laboratory are many and include (i) the possibility to fix the controlling parameters such as the geometry of the structure where the gas flows, the gas flow rate, and the fluid viscosity; (ii) the possibility of performing acoustic measurements at different azimuthal and zenithal angles around the opening of the analog conduit, hence constraining the radiation pattern of different acoustic sources; (iii) the possibility to measure micro-seismic signals in distinct points of the analog conduit; (iv) finally, thanks to the transparent structure, it is possible to directly observe the degassing pattern through the optically clear analog magma and define the degassing regime producing the seismo-acoustic radiations. The above-described device represents a step forward in the analog volcano seismo-acoustic measurements.

An experimental device for characterizing degassing processes and related elastic fingerprints: Analog volcano seismo-acoustic observations

NASA Astrophysics Data System (ADS)

Spina, Laura; Morgavi, Daniele; Cannata, Andrea; Campeggi, Carlo; Perugini, Diego

2018-05-01

A challenging objective of modern volcanology is to quantitatively characterize eruptive/degassing regimes from geophysical signals (in particular seismic and infrasonic), for both research and monitoring purposes. However, the outcomes of the attempts made so far are still considered very uncertain because volcanoes remain inaccessible when deriving quantitative information on crucial parameters such as plumbing system geometry and magma viscosity. In order to improve our knowledge of volcanic systems, a novel experimental device, which is capable of mimicking volcanic degassing processes with different regimes and gas flow rates, and allowing for the investigation of the related seismo-acoustic emissions, was designed and developed. The benefits of integrating observations on real volcanoes with seismo-acoustic signals generated in laboratory are many and include (i) the possibility to fix the controlling parameters such as the geometry of the structure where the gas flows, the gas flow rate, and the fluid viscosity; (ii) the possibility of performing acoustic measurements at different azimuthal and zenithal angles around the opening of the analog conduit, hence constraining the radiation pattern of different acoustic sources; (iii) the possibility to measure micro-seismic signals in distinct points of the analog conduit; (iv) finally, thanks to the transparent structure, it is possible to directly observe the degassing pattern through the optically clear analog magma and define the degassing regime producing the seismo-acoustic radiations. The above-described device represents a step forward in the analog volcano seismo-acoustic measurements.

Dicyanovinylnaphthalenes for neuroimaging of amyloids and relationships of electronic structures and geometries to binding affinities

PubMed Central

Petrič, Andrej; Johnson, Scott A.; Pham, Hung V.; Li, Ying; Čeh, Simon; Golobič, Amalija; Agdeppa, Eric D.; Timbol, Gerald; Liu, Jie; Keum, Gyochang; Satyamurthy, Nagichettiar; Kepe, Vladimir; Houk, Kendall N.; Barrio, Jorge R.

2012-01-01

The positron-emission tomography (PET) probe 2-(1-[6-[(2-fluoroethyl)(methyl)amino]-2-naphthyl]ethylidene) (FDDNP) is used for the noninvasive brain imaging of amyloid-β (Aβ) and other amyloid aggregates present in Alzheimer’s disease and other neurodegenerative diseases. A series of FDDNP analogs has been synthesized and characterized using spectroscopic and computational methods. The binding affinities of these molecules have been measured experimentally and explained through the use of a computational model. The analogs were created by systematically modifying the donor and the acceptor sides of FDDNP to learn the structural requirements for optimal binding to Aβ aggregates. FDDNP and its analogs are neutral, environmentally sensitive, fluorescent molecules with high dipole moments, as evidenced by their spectroscopic properties and dipole moment calculations. The preferred solution-state conformation of these compounds is directly related to the binding affinities. The extreme cases were a nonplanar analog t-butyl-FDDNP, which shows low binding affinity for Aβ aggregates (520 nM Ki) in vitro and a nearly planar tricyclic analog cDDNP, which displayed the highest binding affinity (10 pM Ki). Using a previously published X-ray crystallographic model of 1,1-dicyano-2-[6-(dimethylamino)naphthalen-2-yl]propene (DDNP) bound to an amyloidogenic Aβ peptide model, we show that the binding affinity is inversely related to the distortion energy necessary to avoid steric clashes along the internal surface of the binding channel. PMID:23012452

Bursts of activity in collective cell migration

PubMed Central

Chepizhko, Oleksandr; Giampietro, Costanza; Mastrapasqua, Eleonora; Nourazar, Mehdi; Ascagni, Miriam; Sugni, Michela; Fascio, Umberto; Leggio, Livio; Malinverno, Chiara; Scita, Giorgio; Santucci, Stéphane; Alava, Mikko J.; Zapperi, Stefano; La Porta, Caterina A. M.

2016-01-01

Dense monolayers of living cells display intriguing relaxation dynamics, reminiscent of soft and glassy materials close to the jamming transition, and migrate collectively when space is available, as in wound healing or in cancer invasion. Here we show that collective cell migration occurs in bursts that are similar to those recorded in the propagation of cracks, fluid fronts in porous media, and ferromagnetic domain walls. In analogy with these systems, the distribution of activity bursts displays scaling laws that are universal in different cell types and for cells moving on different substrates. The main features of the invasion dynamics are quantitatively captured by a model of interacting active particles moving in a disordered landscape. Our results illustrate that collective motion of living cells is analogous to the corresponding dynamics in driven, but inanimate, systems. PMID:27681632

Dust Impact Monitor (SESAME-DIM) on-board Rosetta/Philae: Aerogel as comet analog material

NASA Astrophysics Data System (ADS)

Flandes, Alberto; Albin, Thomas; Arnold, Walter; Fischer, Hans-Herbert; Hirn, Attila; Loose, Alexander; Mewes, Cornelia; Podolak, Morris; Seidensticker, Klaus J.; Volkert, Cynthia; Krüger, Harald

2018-03-01

On 12 November 2014, during the descent of the Rosetta lander Philae to the surface of comet 67P/Churyumov-Gerasimenko the Dust Impact Monitor (DIM) on board Philae recorded an impact of a cometary dust impact of a cometary dust particle at 2.4 km from the comet surface (5 km from the nucleus' barycentre). In this work, we report further experiments that support the identification of this particle. We use aerogel as a comet analog material to characterise the properties of this particle. Our experiments show that this particle has a radius of 0.9 mm, a low density of 0.25 g/cm3 and a high porosity close to 90%. The particle likely moved at near 4 m/s with respect to the comet.

The Mojave Desert: A Martian Analog Site for Future Astrobiology Themed Missions

NASA Technical Reports Server (NTRS)

Salas, E.; Abbey, W.; Bhartia, R.; Beegle, L. W.

2011-01-01

Astrobiological interest in Mars is highlighted by evidence that Mars was once warm enough to have liquid water present on its surface long enough to create geologic formations that could only exist in the presense of extended fluvial periods. These periods existed at the same time life on Earth arose. If life began on Mars as well during this period, it is reasonable to assume it may have adapted to the subsurface as environments at the surface changed into the inhospitable state we find today. If the next series of Mars missions (Mars Science Laboratory, the ExoMars Trace Gas Orbiter proposed for launch in 2016, and potential near surface sample return) fail to discover either extinct or extant life on Mars, a subsurface mission would be necessary to attempt to "close the book" on the existence of martian life. Mars is much colder and drier than Earth, with a very low pressure CO2 environment and no obvious habitats. Terrestrial regions with limited precipitation, and hence reduced active biota, are some of the best martian low to mid latitude analogs to be found on Earth, be they the Antarctic dry valleys, the Atacama or Mojave Deserts. The Mojave Desert/Death Valley region is considered a Mars analog site by the Terrestrial Analogs Panel of the NSF-sponsored decadal survey; a field guide was even developed and a workshop was held on its applicability as a Mars analog. This region has received a great deal of attention due to its accessibility and the variety of landforms and processes observed relevant to martian studies.

A High-Performance Neural Prosthesis Incorporating Discrete State Selection With Hidden Markov Models.

PubMed

Kao, Jonathan C; Nuyujukian, Paul; Ryu, Stephen I; Shenoy, Krishna V

2017-04-01

Communication neural prostheses aim to restore efficient communication to people with motor neurological injury or disease by decoding neural activity into control signals. These control signals are both analog (e.g., the velocity of a computer mouse) and discrete (e.g., clicking an icon with a computer mouse) in nature. Effective, high-performing, and intuitive-to-use communication prostheses should be capable of decoding both analog and discrete state variables seamlessly. However, to date, the highest-performing autonomous communication prostheses rely on precise analog decoding and typically do not incorporate high-performance discrete decoding. In this report, we incorporated a hidden Markov model (HMM) into an intracortical communication prosthesis to enable accurate and fast discrete state decoding in parallel with analog decoding. In closed-loop experiments with nonhuman primates implanted with multielectrode arrays, we demonstrate that incorporating an HMM into a neural prosthesis can increase state-of-the-art achieved bitrate by 13.9% and 4.2% in two monkeys ( ). We found that the transition model of the HMM is critical to achieving this performance increase. Further, we found that using an HMM resulted in the highest achieved peak performance we have ever observed for these monkeys, achieving peak bitrates of 6.5, 5.7, and 4.7 bps in Monkeys J, R, and L, respectively. Finally, we found that this neural prosthesis was robustly controllable for the duration of entire experimental sessions. These results demonstrate that high-performance discrete decoding can be beneficially combined with analog decoding to achieve new state-of-the-art levels of performance.

Photoaffinity labeling and partial purification of the beta cell sulfonylurea receptor using a novel, biologically active glyburide analog

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

Aguilar-Bryan, L.; Nelson, D.A.; Vu, Q.A.

1990-05-15

An iodinated analog of the sulfonylurea, glyburide, has been synthesized which can be labeled to high specific activity and used to photolabel the sulfonylurea receptor. 5-Iodo-2-hydroxy-glyburide, has an iodo group replacing the chlorine at position 5 and a methoxy residue replacing the hydroxy group at position 2 on the benzamido ring. This analog retains biologic activity stimulating insulin secretion from a hamster beta cell line (HIT cells) at the same ED50 (0.4 nM) as glyburide. Scatchard analysis demonstrated high and low affinity binding sites on HIT cell membranes (Kd values of 0.36 nM and 277 nM and Bmax values ofmore » 1.6 and 100 pmol/mg of membrane protein, respectively). Competitive binding assays with unlabeled glyburide or 5-iodo-2-hydroxyglyburide yield Ki values of 0.5 and 1.0 nM, respectively. The analog can be covalently linked by ultraviolet irradiation to a membrane protein of Mr = 140,000. The photolabeling is completely blocked by unlabeled glyburide or the analog. Two other species of Mr = 65,000 and 43,000 are also photolabeled; these may be the low affinity sites. After photolabeling, the receptor has been purified partially by chromatographic procedures and is suitable for obtaining peptide sequence. The 140,000 molecular weight protein is identified as the sulfonylurea receptor since its binding constant, 0.36 nM, is closely correlated with its ability to stimulate insulin secretion (ED50 congruent to 0.4 nM).« less

Evolution of structural diversity of trichothecene mycotoxins

USDA-ARS?s Scientific Manuscript database

Fungal secondary metabolites (SMs) are diverse in structure and biological activity. Most can be divided into families of analogs that share a core structure but vary in patterns of functional groups (substituents) attached to the core. Typically, fungal genes responsible for synthesis of the same S...

Lone pair effect, structural distortions, and potential for superconductivity in Tl perovskites.

PubMed

Schoop, Leslie M; Müchler, Lukas; Felser, Claudia; Cava, R J

2013-05-06

Drawing the analogy to BaBiO3, we investigate via ab initio electronic structure calculations potential new superconductors of the type ATlX3 with A = Rb and Cs and X = F, Cl, and Br, with a particular emphasis on RbTlCl3. On the basis of chemical reasoning, supported by the calculations, we show that Tl-based perovskites have structural and charge instabilities driven by the lone pair effect, similar to the case of BaBiO3, effectively becoming A2Tl(+)Tl(3+)X6. We find that upon hole doping of RbTlCl3, structures without Tl(+) and Tl(3+) charge disproportionation become more stable, although the ideal cubic perovskite, often viewed as the best host for superconductivity, should not be the most stable phase in the system. The known superconductor (Sr,K)BiO3 and hole doped RbTlCl3, predicted to be most stable in the same tetragonal structure, display highly analogous calculated electronic band structures.

Metabolomic Discovery of Novel Urinary Galabiosylceramide Analogs as Fabry Disease Biomarkers

NASA Astrophysics Data System (ADS)

Boutin, Michel; Auray-Blais, Christiane

2015-03-01

Fabry disease is an X-linked, complex, multisystemic lysosomal storage disorder presenting marked phenotypic and genotypic variability among affected male and female patients. Glycosphingolipids, mainly globotriaosylceramide (Gb3) isoforms/analogs, globotriaosylsphingosine (lyso-Gb3) and analogs, as well as galabiosylceramide (Ga2) isoforms/analogs accumulate in the vascular endothelium, nerves, cardiomyocytes, renal glomerular and tubular epithelial cells, and biological fluids. The search for biomarkers reflecting disease severity and progression is still on-going. A metabolomic study using quadrupole time-of-flight mass spectrometry has revealed 22 galabiosylceramide isoforms/analogs in urine of untreated Fabry patients classified in seven groups according to their chemical structure: (1) Saturated fatty acid; (2) one extra double bond; (3) two extra double bonds; (4) hydroxylated saturated fatty acid; (5) hydroxylated fatty acid and one extra double bond; (6) hydrated sphingosine and hydroxylated fatty acid; (7) methylated amide linkage. Relative quantification of both Ga2 and Gb3 isoforms/analogs was performed. All these biomarkers are significantly more abundant in urine samples from untreated Fabry males compared with healthy male controls. A significant amount of Ga2 isoforms/analogs, accounting for 18% of all glycosphingolipids analyzed (Ga2 + Gb3 and respective isoforms/analogs), were present in urine of Fabry patients. Gb3 isoforms containing saturated fatty acids are the most abundant (60.9%) compared with 26.3% for Ga2. A comparison between Ga2 isoforms/analogs and their Gb3 counterparts also showed that the proportion of analogs with hydroxylated fatty acids is significantly greater for Ga2 (35.8%) compared with Gb3 (1.9%). These results suggest different biological pathways involved in the synthesis and/or degradation of Gb3 and Ga2 metabolites.

Hygroscopicity of Early Earth and Titan Laboratory Aerosol Analogs

NASA Astrophysics Data System (ADS)

Hasenkopf, C. A.; Beaver, M. R.; Freedman, M. A.; Toon, O. B.; Tolbert, M. A.

2009-12-01

We have explored the ability of organic hazes, known to exist in the atmosphere of Titan and postulated to have existed in the Archean Earth atmosphere, to act as cloud condensation nuclei (CCN). These laboratory aerosol analogs are generated via UV-photolysis of early Earth and Titan analog gas mixtures and are designed to mimic the present day atmospheric conditions on Titan and the early Earth atmosphere before the rise of oxygen. Water uptake is observed to occur on the early Earth and Titan aerosol analogs at relative humidities of 80% - 90% via optical growth measurements using cavity ring-down aerosol extinction spectroscopy. We find the optical growth of these aerosols is similar to known slightly-soluble organic acids, such as phthalic and pyromellitic acids. On average, the optical growth of the early Earth analog is slightly larger than the Titan analog. In order to translate our measurements obtained in a subsaturated regime into the CCN ability of these particles, we rely on the hygroscopicity parameter κ, developed by Petters & Kreidenweis (2007). We retrieve κ = 0.17±0.03 and 0.06±0.01 for the early Earth and Titan analogs, respectively. This early Earth analog hygroscopicity value indicates that the aerosol could activate at reasonable water vapor supersaturations. We use previous aerosol mass spectrometry results to correlate the chemical structure of the two types of analog with their hygroscopicity. The hygroscopicity of the early Earth aerosol analog, coupled with the apparent lack of other good CCN during the Archean, helps explain the role of the organic haze in the indirect effect of clouds on the early Earth and indicates that it may have had a significant impact on the hydrological cycle.

Analogs of diadenosine tetraphosphate (Ap4A).

PubMed

Guranowski, Andrzej

2003-01-01

This review summarizes our knowledge of analogs and derivatives of diadenosine 5',5"'-P1,P4-tetraphosphate (Ap4A), the most extensively studied member of the dinucleoside 5',5"'-P1,Pn-polyphosphate (NpnN) family. After a short discussion of enzymes that may be responsible for the accumulation and degradation of Np4)N's in the cell, this review focuses on chemically and/or enzymatically produced analogs and their practical applications. Particular attention is paid to compounds that have aided the study of enzymes involved in the metabolism of Ap4A (Np4N'). Certain Ap4A analogs were alternative substrates of Ap4A-degrading enzymes and/or acted as enzyme inhibitors, some other helped to establish enzyme mechanisms, increased the sensitivity of certain enzyme assays or produced stable enzyme:ligand complexes for structural analysis.

Design and synthesis of alkoxyindolyl-3-acetic acid analogs as peroxisome proliferator-activated receptor-γ/δ agonists.

PubMed

Gim, Hyo Jin; Li, Hua; Lee, Eun; Ryu, Jae-Ha; Jeon, Raok

2013-01-15

A series of carbazole or phenoxazine containing alkoxyindole-3-acetic acid analogs were prepared as PPARγ/δ agonists and their transactivation activities for PPAR receptor subtypes (α, γ and δ) were investigated. Structure-activity relationship studies disclosed the effect of the lipophilic tail, attaching position of the alkoxy group and N-benzyl substitution at indole. Compound 1b was the most potent for PPARδ and 3b for PPARγ. Molecular modeling suggested two different binding modes of our alkoxyindole-3-acetic acid analogs providing the insight into their PPAR activity. Copyright © 2012 Elsevier Ltd. All rights reserved.

TOXEMIA OF PREGNANCY IN THE RABBIT

PubMed Central

Greene, Harry S. N.

1937-01-01

The clinical manifestations and pathology of a disorder associated with pregnancy in the rabbit have been described. The disorder bears a close analogy to toxemia of pregnancy in man and offers an experimental approach to the problems associated with that condition. The evidence at hand indicates that the disorder is of endogenous origin and arises from a disturbance of functions concerned in reproductive processes. PMID:19870636

On the kinetics of infection by pathogenic prion protein molecules

NASA Astrophysics Data System (ADS)

Durup, Jean

1997-03-01

Literature data on the transmission of spongiform encephalopathies between mammal species point to the importance of methionine residuies in species barriers. This in turn favours the assumption of an oligomerization of identical metastable pathogenic prion protein molecules as the rate-determining step in those diseases. Published experimental data on the analogous case of yeast prion proteins closely agree with the proposed scheme.

Comet Wild 2 - Stardust Approach Image

NASA Technical Reports Server (NTRS)

2004-01-01

This image was taken during the close approach phase of Stardust's Jan 2, 2004 flyby of comet Wild 2. It is a distant side view of the roughly spherical comet nucleus. One hemisphere is in sunlight and the other is in shadow analogous to a view of the quarter moon. Several large depressed regions can be seen. Comet Wild 2 is about five kilometers (3.1 miles) in diameter.

Hardware Evolution of Closed-Loop Controller Designs

NASA Technical Reports Server (NTRS)

Gwaltney, David; Ferguson, Ian

2002-01-01

Poster presentation will outline on-going efforts at NASA, MSFC to employ various Evolvable Hardware experimental platforms in the evolution of digital and analog circuitry for application to automatic control. Included will be information concerning the application of commercially available hardware and software along with the use of the JPL developed FPTA2 integrated circuit and supporting JPL developed software. Results to date will be presented.

Antitumor Agents 293. Non-toxic Dimethyl-4,4′-dimethoxy-5,6,5′,6′-dimethylenedioxybiphenyl-2,2′-dicarboxylate (DDB) Analogs Chemosensitize Multidrug Resistant Cancer Cells to Clinical Anticancer Drugs

PubMed Central

Hung, Hsin-Yi; Ohkoshi, Emika; Goto, Masuo; Bastow, Kenneth F.; Nakagawa-Goto, Kyoko; Lee, Kuo-Hsiung

2012-01-01

Novel dimethyl-4,4′-dimethoxy-5,6,5′,6′-dimethylenedioxybiphenyl-2,2′-dicarboxylate (DDB) analogs were designed and synthesized to improve their chemosensitizing action on KBvin (vincristine resistant nasopharyngeal carcinoma) cells, a multi-drug resistant cell line over-expressing P-glycoprotein (P-gp). Structure-activity relationship analysis showed that aromatic and bulky aliphatic side chains at the 2,2′-positions effectively and significantly sensitized P-gp overexpressing multidrug resistant (MDR) cells to anticancer drugs, such as paclitaxel (TAX), vincristine (VCR), and doxorubicin (DOX). DDB derivatives 16 and 23 showed 5–10 times more effective reversal ability than verapamil (VRP) for TAX and VCR. Analog 6 also exhibited five times greater chemosensitizing effect against DOX than VRP. Importantly, no cytotoxicity was observed by the active DDB analogs against both non-MDR and MDR cells, suggesting that DDB analogs serve as the novel lead compounds for the development of chemosensitizers to overcome MDR phenotype. The mechanism of action studies demonstrated that effective inhibition of P-glycoprotein by DDB analogs dramatically elevated cellular concentration of anticancer drugs. PMID:22612652

Validity and reliability of the Rosenberg Self-Esteem Scale-Thai version as compared to the Self-Esteem Visual Analog Scale.

PubMed

Piyavhatkul, Nawanant; Aroonpongpaisal, Suwanna; Patjanasoontorn, Niramol; Rongbutsri, Somchit; Maneeganondh, Somchit; Pimpanit, Wijitra

2011-07-01

To compare the validity and reliability of the Thai version of the Rosenberg Self-Esteem Scale with the Self-Esteem Visual Analog Scale. The Rosenberg Self-Esteem Scale was translated into Thai and its content-validity checked by bacA translation. The reliability of the Rosenberg Self-Esteem Scale compared with the Self-Esteem Visual Analog Scale was ther tested between February and March 2008 on 270 volunteers, including 135 patients with psychiatric illness and 135 normal volunteers. The authors analyzed the internal consistency and factor structure of the Rosenberg Self-Esteem Scale-Thai version and the correlation between it and the Visual Analog Scale. The Cronbach's Alpha for the Rosenberg Self-Esteem scale-Thai version was 0.849 and the Pearson's correlation between it and the Self-Esteem Visual Analog Scale 0.618 (p = 0.01). Two factors, viz, the positively and negatively framea items, from the Rosenberg Self-Esteem Scale-Thai version accounted for 44.04% and 12.10% of the variance, respectively. The Rosenberg Self-Esteem Scale-Thai version has acceptable reliability. The Self-Esteem Visual Analog Scale provides an effective measure of self-esteem.

All-optical analog comparator.

PubMed

Li, Pu; Yi, Xiaogang; Liu, Xianglian; Zhao, Dongliang; Zhao, Yongpeng; Wang, Yuncai

2016-08-23

An analog comparator is one of the core units in all-optical analog-to-digital conversion (AO-ADC) systems, which digitizes different amplitude levels into two levels of logical '1' or '0' by comparing with a defined decision threshold. Although various outstanding photonic ADC approaches have been reported, almost all of them necessitate an electrical comparator to carry out this binarization. The use of an electrical comparator is in contradiction to the aim of developing all-optical devices. In this work, we propose a new concept of an all-optical analog comparator and numerically demonstrate an implementation based on a quarter-wavelength-shifted distributed feedback laser diode (QWS DFB-LD) with multiple quantum well (MQW) structures. Our results show that the all-optical comparator is very well suited for true AO-ADCs, enabling the whole digital conversion from an analog optical signal (continuous-time signal or discrete pulse signal) to a binary representation totally in the optical domain. In particular, this all-optical analog comparator possesses a low threshold power (several mW), high extinction ratio (up to 40 dB), fast operation rate (of the order of tens of Gb/s) and a step-like transfer function.

All-optical analog comparator

PubMed Central

Li, Pu; Yi, Xiaogang; Liu, Xianglian; Zhao, Dongliang; Zhao, Yongpeng; Wang, Yuncai

2016-01-01

An analog comparator is one of the core units in all-optical analog-to-digital conversion (AO-ADC) systems, which digitizes different amplitude levels into two levels of logical ‘1’ or ‘0’ by comparing with a defined decision threshold. Although various outstanding photonic ADC approaches have been reported, almost all of them necessitate an electrical comparator to carry out this binarization. The use of an electrical comparator is in contradiction to the aim of developing all-optical devices. In this work, we propose a new concept of an all-optical analog comparator and numerically demonstrate an implementation based on a quarter-wavelength-shifted distributed feedback laser diode (QWS DFB-LD) with multiple quantum well (MQW) structures. Our results show that the all-optical comparator is very well suited for true AO-ADCs, enabling the whole digital conversion from an analog optical signal (continuous-time signal or discrete pulse signal) to a binary representation totally in the optical domain. In particular, this all-optical analog comparator possesses a low threshold power (several mW), high extinction ratio (up to 40 dB), fast operation rate (of the order of tens of Gb/s) and a step-like transfer function. PMID:27550874

All-optical analog comparator

NASA Astrophysics Data System (ADS)

Li, Pu; Yi, Xiaogang; Liu, Xianglian; Zhao, Dongliang; Zhao, Yongpeng; Wang, Yuncai

2016-08-01

An analog comparator is one of the core units in all-optical analog-to-digital conversion (AO-ADC) systems, which digitizes different amplitude levels into two levels of logical ‘1’ or ‘0’ by comparing with a defined decision threshold. Although various outstanding photonic ADC approaches have been reported, almost all of them necessitate an electrical comparator to carry out this binarization. The use of an electrical comparator is in contradiction to the aim of developing all-optical devices. In this work, we propose a new concept of an all-optical analog comparator and numerically demonstrate an implementation based on a quarter-wavelength-shifted distributed feedback laser diode (QWS DFB-LD) with multiple quantum well (MQW) structures. Our results show that the all-optical comparator is very well suited for true AO-ADCs, enabling the whole digital conversion from an analog optical signal (continuous-time signal or discrete pulse signal) to a binary representation totally in the optical domain. In particular, this all-optical analog comparator possesses a low threshold power (several mW), high extinction ratio (up to 40 dB), fast operation rate (of the order of tens of Gb/s) and a step-like transfer function.

A novel prediction method about single components of analog circuits based on complex field modeling.

PubMed

Zhou, Jingyu; Tian, Shulin; Yang, Chenglin

2014-01-01

Few researches pay attention to prediction about analog circuits. The few methods lack the correlation with circuit analysis during extracting and calculating features so that FI (fault indicator) calculation often lack rationality, thus affecting prognostic performance. To solve the above problem, this paper proposes a novel prediction method about single components of analog circuits based on complex field modeling. Aiming at the feature that faults of single components hold the largest number in analog circuits, the method starts with circuit structure, analyzes transfer function of circuits, and implements complex field modeling. Then, by an established parameter scanning model related to complex field, it analyzes the relationship between parameter variation and degeneration of single components in the model in order to obtain a more reasonable FI feature set via calculation. According to the obtained FI feature set, it establishes a novel model about degeneration trend of analog circuits' single components. At last, it uses particle filter (PF) to update parameters for the model and predicts remaining useful performance (RUP) of analog circuits' single components. Since calculation about the FI feature set is more reasonable, accuracy of prediction is improved to some extent. Finally, the foregoing conclusions are verified by experiments.

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

Merkle, J.G.

In order to study effects of constraint on fracture toughness, it is important to select the right location within the crack-tip field for investigation. In 1950 Hill postulated that close to a circular notch tip the principal stress directions would be radial and circumferential, so that the plastic slip lines (maximum shear stress trajectories) would be logarithmic spirals. The resulting equation for stress normal to the notch symmetry plane, neglecting strain hardening, was identical to that for the circumferential stress near the bore of an ideally plastic thick-walled hollow cylinder under external radial tension, because the relevant geometries are identical.more » In 1969, Rice and Johnson developed a near crack-tip, plane strain, large-strain rigid-plastic analysis considering strain hardening and assuming an infinitely sharp initial crack tip. Shortly afterwards, Merkle, following Hill's suggestion, proposed an approximate analysis of the stresses and strains ahead of a blunted crack tip on the plane of symmetry, based on a circular blunted crack tip. The analysis amounted to a hollow cylinder analogy, including the effects of strain hardening. The original hollow cylinder analogy was based on small strain theory, and the calculated strain distributions did not agree well with the Rice and Johnson results very near the blunted crack tip. Therefore, the hollow cylinder analogy equations have been rederived, based on large strain theory, and the agreement with the Rice and Johnson results and other more recent numerical results is good. Calculations illustrate the effects of transverse strain on the principal stresses very close to a blunting crack tip and show that, theoretically, a singularity still exists at the tip of a blunting crack. 10 refs., 9 figs.« less

Channel Networks on Large Fans: Refining Analogs for the Ridge-forming Unit, Sinus Meridiani

NASA Technical Reports Server (NTRS)

Wilkinson, Justin

2009-01-01

Stream channels are generally thought of as forming within confined valley settings, separated by interfluves. Sinuous ridges on Mars and Earth are often interpreted as stream channels inverted by subsequent erosion of valley sides. In the case of the ridge-forming unit (RFU), this interpretation fails to explain the (i) close spacing of the ridges, which are (ii) organized in networks, and which (iii) cover large areas (approximately 175,000 km (exp 2)). Channel networks on terrestrial fans develop unconfined by valley slopes. Large fans (100s km long) are low-angle, fluvial features, documented worldwide, with characteristics that address these aspects of the RFU. Ridge patterns Channels on large fans provide an analog for the sinuous and elongated morphology of RFU ridges, but more especially for other patterns such as subparallel, branching and crossing networks. Branches are related to splays (delta-like distributaries are rare), whose channels can rejoin the main channel. Crossing patterns can be caused by even slight sinuosity splay-related side channels often intersect. An avulsion node distant from the fan apex, gives rise to channels with slightly different, and hence intersecting, orientations. Channels on neighboring fans intersect along the common fan margin. 2. Network density Channels are the dominant feature on large terrestrial fans (lakes and dune fields are minor). Inverted landscapes on subsequently eroded fans thus display indurated channels as networks of significantly close-spaced ridges. 3. Channel networks covering large areas Areas of individual large terrestrial fans can reach >200,000 km 2 (105-6 km 2 with nested fans), providing an analog for the wide area distribution of the RFU.

An in vivo quantitative structure-activity relationship for a congeneric series of pyropheophorbide derivatives as photosensitizers for photodynamic therapy.

PubMed

Henderson, B W; Bellnier, D A; Greco, W R; Sharma, A; Pandey, R K; Vaughan, L A; Weishaupt, K R; Dougherty, T J

1997-09-15

An in vivo quantitative structure-activity relationship (QSAR) study was carried out on a congeneric series of pyropheophorbide photosensitizers to identify structural features critical for their antitumor activity in photodynamic therapy (PDT). The structural elements evaluated in this study include the length and shape (alkyl, alkenyl, cyclic, and secondary analogs) of the ether side chain. C3H mice, harboring the radiation-induced fibrosarcoma tumor model, were used to study three biological response endpoints: tumor growth delay, tumor cell lethality, and vascular perfusion. All three endpoints revealed highly similar QSAR patterns that constituted a function of the alkyl ether chain length and drug lipophilicity, which is defined as the log of the octanol:water partition coefficient (log P). When the illumination of tumor, tumor cells, or cutaneous vasculature occurred 24 h after sensitizer administration, activities were minimal with analogs of log P < or = 5, increased dramatically between log P of 5-6, and peaked between log P of 5.6-6.6. Activities declined gradually with higher log P. The lack of activity of the least-lipophilic analogs was explained in large part by their poor biodistribution characteristics, which yielded negligible tumor and plasma drug levels at the time of treatment with light. The progressively lower potencies of the most lipophilic analogs cannot be explained through the overall tumor and plasma pharmacokinetics of photosensitizer because tumor and plasma concentrations progressively increased with lipophilicity. When compensated for differences in tumor photosensitizer concentration, the 1-hexyl derivative (optimal lipophilicity) was 5-fold more potent than the 1-dodecyl derivative (more lipophilic) and 3-fold more potent than the 1-pentyl analog (less lipophilic), indicating that, in addition to the overall tumor pharmacokinetics, pharmacodynamic factors may influence PDT activity. Drug lipophilicity was highly predictive for photodynamic activity. QSAR modeling revealed that direct antitumor effects and vascular PDT effects may be governed by common mechanisms, and that the mere association of high levels of photosensitizer in the tumor tissue is not sufficient for optimal PDT efficiency.

Cortical geometry as a determinant of brain activity eigenmodes: Neural field analysis

NASA Astrophysics Data System (ADS)

Gabay, Natasha C.; Robinson, P. A.

2017-09-01

Perturbation analysis of neural field theory is used to derive eigenmodes of neural activity on a cortical hemisphere, which have previously been calculated numerically and found to be close analogs of spherical harmonics, despite heavy cortical folding. The present perturbation method treats cortical folding as a first-order perturbation from a spherical geometry. The first nine spatial eigenmodes on a population-averaged cortical hemisphere are derived and compared with previous numerical solutions. These eigenmodes contribute most to brain activity patterns such as those seen in electroencephalography and functional magnetic resonance imaging. The eigenvalues of these eigenmodes are found to agree with the previous numerical solutions to within their uncertainties. Also in agreement with the previous numerics, all eigenmodes are found to closely resemble spherical harmonics. The first seven eigenmodes exhibit a one-to-one correspondence with their numerical counterparts, with overlaps that are close to unity. The next two eigenmodes overlap the corresponding pair of numerical eigenmodes, having been rotated within the subspace spanned by that pair, likely due to second-order effects. The spatial orientations of the eigenmodes are found to be fixed by gross cortical shape rather than finer-scale cortical properties, which is consistent with the observed intersubject consistency of functional connectivity patterns. However, the eigenvalues depend more sensitively on finer-scale cortical structure, implying that the eigenfrequencies and consequent dynamical properties of functional connectivity depend more strongly on details of individual cortical folding. Overall, these results imply that well-established tools from perturbation theory and spherical harmonic analysis can be used to calculate the main properties and dynamics of low-order brain eigenmodes.

Terrestrial bitumen analogue of orgueil organic material demonstrates high sensitivity to usual HF-HCl treatment

NASA Technical Reports Server (NTRS)

Korochantsev, A. V.; Nikolaeva, O. V.

1993-01-01

The relationship between the chemical composition and the interlayer spacing (d002) of organic materials (OM's) is known for various terrestrial OM's. We improved this general trend by correlation with corresponding trend of natural solid bitumens (asphaltite-kerite-anthraxolite) up to graphite. Using the improved trend we identified bitumen analogs of carbonaceous chondrite OM's residued after HF-HCl treatment. Our laboratory experiment revealed that these analogs and, hence, structure and chemical composition of carbonaceous chondrite OM's are very sensitive to the HF-HCl treatment. So, usual extraction of OM from carbonaceous chondrites may change significantly structural and chemical composition of extracted OM.

Synthetic analogs of bacterial quorum sensors

DOEpatents

Iyer, Rashi [Los Alamos, NM; Ganguly, Kumkum [Los Alamos, NM; Silks, Louis A [Los Alamos, NM

2011-12-06

Bacterial quorum-sensing molecule analogs having the following structures: ##STR00001## and methods of reducing bacterial pathogenicity, comprising providing a biological system comprising pathogenic bacteria which produce natural quorum-sensing molecule; providing a synthetic bacterial quorum-sensing molecule having the above structures and introducing the synthetic quorum-sensing molecule into the biological system comprising pathogenic bacteria. Further is provided a method of targeted delivery of an antibiotic, comprising providing a synthetic quorum-sensing molecule; chemically linking the synthetic quorum-sensing molecule to an antibiotic to produce a quorum-sensing molecule-antibiotic conjugate; and introducing the conjugate into a biological system comprising pathogenic bacteria susceptible to the antibiotic.

Synthetic analogs of bacterial quorum sensors

DOEpatents

Iyer, Rashi S.; Ganguly, Kumkum; Silks, Louis A.

2013-01-08

Bacterial quorum-sensing molecule analogs having the following structures: ##STR00001## and methods of reducing bacterial pathogenicity, comprising providing a biological system comprising pathogenic bacteria which produce natural quorum-sensing molecule; providing a synthetic bacterial quorum-sensing molecule having the above structures and introducing the synthetic quorum-sensing molecule into the biological system comprising pathogenic bacteria. Further is provided a method of targeted delivery of an antibiotic, comprising providing a synthetic quorum-sensing molecule; chemically linking the synthetic quorum-sensing molecule to an antibiotic to produce a quorum-sensing molecule-antibiotic conjugate; and introducing the conjugate into a biological system comprising pathogenic bacteria susceptible to the antibiotic.

Probing the structure of RecA-DNA filaments. Advantages of a fluorescent guanine analog.

PubMed

Singleton, Scott F; Roca, Alberto I; Lee, Andrew M; Xiao, Jie

2007-04-23

The RecA protein of Escherichia coli plays a crucial roles in DNA recombination and repair, as well as various aspects of bacterial pathogenicity. The formation of a RecA-ATP-ssDNA complex initiates all RecA activities and yet a complete structural and mechanistic description of this filament has remained elusive. An analysis of RecA-DNA interactions was performed using fluorescently labeled oligonucleotides. A direct comparison was made between fluorescein and several fluorescent nucleosides. The fluorescent guanine analog 6-methylisoxanthopterin (6MI) demonstrated significant advantages over the other fluorophores and represents an important new tool for characterizing RecA-DNA interactions.

Sequential structures provide insights into the fidelity of RNA replication.

PubMed

Ferrer-Orta, Cristina; Arias, Armando; Pérez-Luque, Rosa; Escarmís, Cristina; Domingo, Esteban; Verdaguer, Nuria

2007-05-29

RNA virus replication is an error-prone event caused by the low fidelity of viral RNA-dependent RNA polymerases. Replication fidelity can be decreased further by the use of mutagenic ribonucleoside analogs to a point where viral genetic information can no longer be maintained. For foot-and-mouth disease virus, the antiviral analogs ribavirin and 5-fluorouracil have been shown to be mutagenic, contributing to virus extinction through lethal mutagenesis. Here, we report the x-ray structure of four elongation complexes of foot-and-mouth disease virus polymerase 3D obtained in presence of natural substrates, ATP and UTP, or mutagenic nucleotides, ribavirin triphosphate and 5-fluorouridine triphosphate with different RNAs as template-primer molecules. The ability of these complexes to synthesize RNA in crystals allowed us to capture different successive replication events and to define the critical amino acids involved in (i) the recognition and positioning of the incoming nucleotide or analog; (ii) the positioning of the acceptor base of the template strand; and (iii) the positioning of the 3'-OH group of the primer nucleotide during RNA replication. The structures identify key interactions involved in viral RNA replication and provide insights into the molecular basis of the low fidelity of viral RNA polymerases.

SerpentinaDB: a database of plant-derived molecules of Rauvolfia serpentina.

PubMed

Pathania, Shivalika; Ramakrishnan, Sai Mukund; Randhawa, Vinay; Bagler, Ganesh

2015-08-04

Plant-derived molecules (PDMs) are known to be a rich source of diverse scaffolds that could serve as a basis for rational drug design. Structured compilation of phytochemicals from traditional medicinal plants can facilitate prospection for novel PDMs and their analogs as therapeutic agents. Rauvolfia serpentina is an important medicinal plant, endemic to Himalayan mountain ranges of Indian subcontinent, reported to be of immense therapeutic value against various diseases. We present SerpentinaDB, a structured compilation of 147 R. serpentina PDMs, inclusive of their plant part source, chemical classification, IUPAC, SMILES, physicochemical properties, and 3D chemical structures with associated references. It also provides refined search option for identification of analogs of natural molecules against ZINC database at user-defined cut-off. SerpentinaDB is an exhaustive resource of R. serpentina molecules facilitating prospection for therapeutic molecules from a medicinally important source of natural products. It also provides refined search option to explore the neighborhood of chemical space against ZINC database to identify analogs of natural molecules obtained as leads. In a previous study, we have demonstrated the utility of this resource by identifying novel aldose reductase inhibitors towards intervention of complications of diabetes.

Visual Exploration of Semantic Relationships in Neural Word Embeddings

DOE PAGES

Liu, Shusen; Bremer, Peer-Timo; Thiagarajan, Jayaraman J.; ...

2017-08-29

Constructing distributed representations for words through neural language models and using the resulting vector spaces for analysis has become a crucial component of natural language processing (NLP). But, despite their widespread application, little is known about the structure and properties of these spaces. To gain insights into the relationship between words, the NLP community has begun to adapt high-dimensional visualization techniques. Particularly, researchers commonly use t-distributed stochastic neighbor embeddings (t-SNE) and principal component analysis (PCA) to create two-dimensional embeddings for assessing the overall structure and exploring linear relationships (e.g., word analogies), respectively. Unfortunately, these techniques often produce mediocre or evenmore » misleading results and cannot address domain-specific visualization challenges that are crucial for understanding semantic relationships in word embeddings. We introduce new embedding techniques for visualizing semantic and syntactic analogies, and the corresponding tests to determine whether the resulting views capture salient structures. Additionally, we introduce two novel views for a comprehensive study of analogy relationships. Finally, we augment t-SNE embeddings to convey uncertainty information in order to allow a reliable interpretation. Combined, the different views address a number of domain-specific tasks difficult to solve with existing tools.« less

Fast Rotational Diffusion of Water Molecules in a 2D Hydrogen Bond Network at Cryogenic Temperatures

NASA Astrophysics Data System (ADS)

Prisk, T. R.; Hoffmann, C.; Kolesnikov, A. I.; Mamontov, E.; Podlesnyak, A. A.; Wang, X.; Kent, P. R. C.; Anovitz, L. M.

2018-05-01

Individual water molecules or small clusters of water molecules contained within microporous minerals present an extreme case of confinement where the local structure of hydrogen bond networks are dramatically altered from bulk water. In the zinc silicate hemimorphite, the water molecules form a two-dimensional hydrogen bond network with hydroxyl groups in the crystal framework. Here, we present a combined experimental and theoretical study of the structure and dynamics of water molecules within this network. The water molecules undergo a continuous phase transition in their orientational configuration analogous to a two-dimensional Ising model. The incoherent dynamic structure factor reveals two thermally activated relaxation processes, one on a subpicosecond timescale and another on a 10-100 ps timescale, between 70 and 130 K. The slow process is an in-plane reorientation of the water molecule involving the breaking of hydrogen bonds with a framework that, despite the low temperatures involved, is analogous to rotational diffusion of water molecules in the bulk liquid. The fast process is a localized motion of the water molecule with no apparent analogs among known bulk or confined phases of water.

Isolation of Insecticidal Constituent from Ruta graveolens and Structure-Activity Relationship Studies against Stored-Food Pests (Coleoptera).

PubMed

Jeon, Ju-Hyun; Lee, Sang-Guei; Lee, Hoi-Seon

2015-08-01

Isolates from essential oil extracted from the flowers and leaves of Ruta graveolens and commercial phenolic analogs were evaluated using fumigant and contact toxicity bioassays against adults of the stored-food pests Sitophilus zeamais, Sitophilus oryzae, and Lasioderma serricorne. The insecticidal activity of these compounds was then compared with that of the synthetic insecticide dichlorvos. To investigate the structure-activity relationships, the activity of 2-isopropyl-5-methylphenol and its analogs was examined against these stored-food pests. Based on the 50% lethal dose, the most toxic compound against S. zeamais was 3-isopropylephenol, followed by 2-isopropylphenol, 4-isopropylphenol, 5-isopropyl-2-methylphenol, 2-isopropyl-5-methylphenol, 3-methylphenol, and 2-methylphenol. Similar results were observed with phenolic compounds against S. oryzae. However, when 2-isopropyl-5-methylphenol isolated from R. graveolens oil and its structurally related analogs were used against L. serricorne, little or no insecticidal activity was found regardless of bioassay. These results indicate that introducing and changing the positions of functional groups in the phenol skeleton have an important effect on insecticidal activity of these compounds against stored-food pests.

Fast Rotational Diffusion of Water Molecules in a 2D Hydrogen Bond Network at Cryogenic Temperatures

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

Prisk, Timothy; Hoffmann, Christina; Kolesnikov, Alexander I.

Individual water molecules or small clusters of water molecules contained within microporous minerals present an extreme case of confinement where the local structure of hydrogen bond networks are dramatically altered from bulk water. In the zinc silicate hemimorphite, the water molecules form a two-dimensional hydrogen bond network with hydroxyl groups in the crystal framework. Here in this paper, we present a combined experimental and theoretical study of the structure and dynamics of water molecules within this network. The water molecules undergo a continuous phase transition in their orientational configuration analogous to a two-dimensional Ising model. The incoherent dynamic structure factormore » reveals two thermally activated relaxation processes, one on a subpicosecond timescale and another on a 10–100 ps timescale, between 70 and 130 K. The slow process is an in-plane reorientation of the water molecule involving the breaking of hydrogen bonds with a framework that, despite the low temperatures involved, is analogous to rotational diffusion of water molecules in the bulk liquid. The fast process is a localized motion of the water molecule with no apparent analogs among known bulk or confined phases of water.« less

Fast Rotational Diffusion of Water Molecules in a 2D Hydrogen Bond Network at Cryogenic Temperatures

DOE PAGES

Prisk, Timothy; Hoffmann, Christina; Kolesnikov, Alexander I.; ...

2018-05-09

Individual water molecules or small clusters of water molecules contained within microporous minerals present an extreme case of confinement where the local structure of hydrogen bond networks are dramatically altered from bulk water. In the zinc silicate hemimorphite, the water molecules form a two-dimensional hydrogen bond network with hydroxyl groups in the crystal framework. Here in this paper, we present a combined experimental and theoretical study of the structure and dynamics of water molecules within this network. The water molecules undergo a continuous phase transition in their orientational configuration analogous to a two-dimensional Ising model. The incoherent dynamic structure factormore » reveals two thermally activated relaxation processes, one on a subpicosecond timescale and another on a 10–100 ps timescale, between 70 and 130 K. The slow process is an in-plane reorientation of the water molecule involving the breaking of hydrogen bonds with a framework that, despite the low temperatures involved, is analogous to rotational diffusion of water molecules in the bulk liquid. The fast process is a localized motion of the water molecule with no apparent analogs among known bulk or confined phases of water.« less

Synthesis and biological evaluation of ranitidine analogs as multiple-target-directed cognitive enhancers for the treatment of Alzheimer's disease.

PubMed

Gao, Jie; Midde, Narasimha; Zhu, Jun; Terry, Alvin V; McInnes, Campbell; Chapman, James M

2016-11-15

Using molecular modeling and rationally designed structural modifications, the multi-target structure-activity relationship for a series of ranitidine analogs has been investigated. Incorporation of a variety of isosteric groups indicated that appropriate aromatic moieties provide optimal interactions with the hydrophobic and π-π interactions with the peripheral anionic site of the AChE active site. The SAR of a series of cyclic imides demonstrated that AChE inhibition is increased by additional aromatic rings, where 1,8-naphthalimide derivatives were the most potent analogs and other key determinants were revealed. In addition to improving AChE activity and chemical stability, structural modifications allowed determination of binding affinities and selectivities for M1-M4 receptors and butyrylcholinesterase (BuChE). These results as a whole indicate that the 4-nitropyridazine moiety of the JWS-USC-75IX parent ranitidine compound (JWS) can be replaced with other chemotypes while retaining effective AChE inhibition. These studies allowed investigation into multitargeted binding to key receptors and warrant further investigation into 1,8-naphthalimide ranitidine derivatives for the treatment of Alzheimer's disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Visual Exploration of Semantic Relationships in Neural Word Embeddings

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

Liu, Shusen; Bremer, Peer-Timo; Thiagarajan, Jayaraman J.

Constructing distributed representations for words through neural language models and using the resulting vector spaces for analysis has become a crucial component of natural language processing (NLP). But, despite their widespread application, little is known about the structure and properties of these spaces. To gain insights into the relationship between words, the NLP community has begun to adapt high-dimensional visualization techniques. Particularly, researchers commonly use t-distributed stochastic neighbor embeddings (t-SNE) and principal component analysis (PCA) to create two-dimensional embeddings for assessing the overall structure and exploring linear relationships (e.g., word analogies), respectively. Unfortunately, these techniques often produce mediocre or evenmore » misleading results and cannot address domain-specific visualization challenges that are crucial for understanding semantic relationships in word embeddings. We introduce new embedding techniques for visualizing semantic and syntactic analogies, and the corresponding tests to determine whether the resulting views capture salient structures. Additionally, we introduce two novel views for a comprehensive study of analogy relationships. Finally, we augment t-SNE embeddings to convey uncertainty information in order to allow a reliable interpretation. Combined, the different views address a number of domain-specific tasks difficult to solve with existing tools.« less

Novel designed VmCT1 analogs with increased antimicrobial activity.

PubMed

Pedron, Cibele Nicolaski; Torres, Marcelo Der Torossian; Lima, Julia Aparecida da Silva; Silva, Pedro Ismael; Silva, Fernanda Dias; Oliveira, Vani Xavier

2017-01-27

Antimicrobial peptides are biologically active molecules produced by a wide range of organisms as an essential component of the innate immune response. They have recently attracted great interest, since they have antimicrobial activity against a broad spectrum of microorganisms. VmCT1 is a cationic peptide from the venom of Vaejovis mexicanus smithi scorpions, which presents antibacterial activity and tends to helical structures. Its analogs were synthesized, characterized and the conformational studies were performed by circular dichroism. The peptides were designed to verify if the single and double substitutions proposed at the hydrophilic and hydrophobic portions of the amphipathic structure would alter antimicrobial activity against Gram-negative and Gram-positive bacteria, yeast and filamentous fungus, besides the hemolytic activity in human erythrocytes. Total charge of the peptides were modified from +2 to +3 by the introduction of a Lysine residue in the hydrophilic face of the amphiphilic helical structure leading to enhanced antimicrobial activity. [K] 11 -VmCT1-NH 2 presented the lower MIC value against the microorganisms (from 0.39 to 6.25 μmol L -1 ), however it showed higher hemolytic activity. The other Lysine-substituted analogs presented also lower MIC values ranging from 0.39 to 25 μmol L -1 for the microorganisms assessed. The circular dichroism spectra analyses suggest that the Lysine-substituted analogs tend to adopt helical structures in trifluoroethanol solution and vesicles (f H : 0.43-1), however they were coiled in water. Alanine substitution by a Glutamic acid residue in the hydrophilic face promotes the increase of polar angle in [E] 4 -VmCT1-NH 2 analog, which was important to led lower hemolytic activity (MHC value = 25 μmol L -1 ). [W] 9 -VmCT1-NH 2 and [E] 4 [W] 9 -VmCT1-NH 2 were designed to favors hydrophobic interactions by the introduction of Tryptophan residue. [W] 9 -VmCT1-NH 2 presented MIC values lower or similar than the model molecule in the most of microorganisms tested. These results provided information about the structure-activity relationship and showed the influence of physicochemical parameters on antimicrobial and hemolytic activity. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Hands-On Exercise in Environmental Structural Geology Using a Fracture Block Model.

ERIC Educational Resources Information Center

Gates, Alexander E.

2001-01-01

Describes the use of a scale analog model of an actual fractured rock reservoir to replace paper copies of fracture maps in the structural geology curriculum. Discusses the merits of the model in enabling students to gain experience performing standard structural analyses. (DDR)

Structure-guided design of fluorescent S-adenosylmethionine analogs for a high-throughput screen to target SAM-I riboswitch RNAs.

PubMed

Hickey, Scott F; Hammond, Ming C

2014-03-20

Many classes of S-adenosylmethionine (SAM)-binding RNAs and proteins are of interest as potential drug targets in diverse therapeutic areas, from infectious diseases to cancer. In the former case, the SAM-I riboswitch is an attractive target because this structured RNA element is found only in bacterial mRNAs and regulates multiple genes in several human pathogens. Here, we describe the synthesis of stable and fluorescent analogs of SAM in which the fluorophore is introduced through a functionalizable linker to the ribose. A Cy5-labeled SAM analog was shown to bind several SAM-I riboswitches via in-line probing and fluorescence polarization assays, including one from Staphylococcus aureus that controls the expression of SAM synthetase in this organism. A fluorescent ligand displacement assay was developed and validated for high-throughput screening of compounds to target the SAM-I riboswitch class. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mining of the Pyrrolamide Antibiotics Analogs in Streptomyces netropsis Reveals the Amidohydrolase-Dependent “Iterative Strategy” Underlying the Pyrrole Polymerization

PubMed Central

Deng, Zixin; Zhao, Changming; Yu, Yi

2014-01-01

In biosynthesis of natural products, potential intermediates or analogs of a particular compound in the crude extracts are commonly overlooked in routine assays due to their low concentration, limited structural information, or because of their insignificant bio-activities. This may lead into an incomplete and even an incorrect biosynthetic pathway for the target molecule. Here we applied multiple compound mining approaches, including genome scanning and precursor ion scan-directed mass spectrometry, to identify potential pyrrolamide compounds in the fermentation culture of Streptomyces netropsis. Several novel congocidine and distamycin analogs were thus detected and characterized. A more reasonable route for the biosynthesis of pyrrolamides was proposed based on the structures of these newly discovered compounds, as well as the functional characterization of several key biosynthetic genes of pyrrolamides. Collectively, our results implied an unusual “iterative strategy” underlying the pyrrole polymerization in the biosynthesis of pyrrolamide antibiotics. PMID:24901640

Metaphor and analogy in everyday problem solving.

PubMed

Keefer, Lucas A; Landau, Mark J

2016-11-01

Early accounts of problem solving focused on the ways people represent information directly related to target problems and possible solutions. Subsequent theory and research point to the role of peripheral influences such as heuristics and bodily states. We discuss how metaphor and analogy similarly influence stages of everyday problem solving: Both processes mentally map features of a target problem onto the structure of a relatively more familiar concept. When individuals apply this structure, they use a well-known concept as a framework for reasoning about real world problems and candidate solutions. Early studies found that analogy use helped people gain insight into novel problems. More recent research on metaphor goes further to show that activating mappings has subtle, sometimes surprising effects on judgment and reasoning in everyday problem solving. These findings highlight situations in which mappings can help or hinder efforts to solve problems. WIREs Cogn Sci 2016, 7:394-405. doi: 10.1002/wcs.1407 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

Metal-Assisted Channel Stabilization: Disposition of a Single Histidine on the N-terminus of Alamethicin Yields Channels with Extraordinarily Long Lifetimes

PubMed Central

Noshiro, Daisuke; Asami, Koji; Futaki, Shiroh

2010-01-01

Abstract Alamethicin, a member of the peptaibol family of antibiotics, is a typical channel-forming peptide with a helical structure. The self-assembly of the peptide in the membranes yields voltage-dependent channels. In this study, three alamethicin analogs possessing a charged residue (His, Lys, or Glu) on their N-termini were designed with the expectation of stabilizing the transmembrane structure. A slight elongation of channel lifetime was observed for the Lys and Glu analogs. On the other hand, extensive stabilization of certain channel open states was observed for the His analog. This stabilization was predominantly observed in the presence of metal ions such as Zn2+, suggesting that metal coordination with His facilitates the formation of a supramolecular assembly in the membranes. Channel stability was greatly diminished by acetylation of the N-terminal amino group, indicating that the N-terminal amino group also plays an important role in metal coordination. PMID:20441743

The Terrestrial Planets Formation in the Solar-System Analogs

NASA Astrophysics Data System (ADS)

Ji, Jianghui; Liu, L.; Chambers, J. E.; Butler, R. P.

2006-09-01

In this work, we numerically studied the terrestrial planets formation in the Solar-Systems Analogs using MERCURY (Chambers 1999). The Solar-System Analogs are herein defined as a solar-system like planetary system, where the system consists of two wide-separated Jupiter-like planets (e.g., 47 UMa, Ji et al. 2005) move about the central star on nearly circular orbits with low inclinations, then low-mass terrestrial planets can be formed there, and life would be possibly evolved. We further explored the terrestrial planets formation due to the current uncertainties of the eccentricities for two giant planets. In addition, we place a great many of the planetesimals between two Jupiter-like planets to investigate the potential asteroidal structure in such systems. We showed that the secular resonances and mean motion resonances can play an important role in shaping the asteroidal structure. We acknowledge the financial support by National Natural Science Foundation of China (Grant No.10573040, 10233020, 10203005) and Foundation of Minor Planets of Purple Mountain Observatory.

Discovery of a new chemical series of BRD4(1) inhibitors using protein-ligand docking and structure-guided design.

PubMed

Duffy, Bryan C; Liu, Shuang; Martin, Gregory S; Wang, Ruifang; Hsia, Ming Min; Zhao, He; Guo, Cheng; Ellis, Michael; Quinn, John F; Kharenko, Olesya A; Norek, Karen; Gesner, Emily M; Young, Peter R; McLure, Kevin G; Wagner, Gregory S; Lakshminarasimhan, Damodharan; White, Andre; Suto, Robert K; Hansen, Henrik C; Kitchen, Douglas B

2015-07-15

Bromodomains are key transcriptional regulators that are thought to be druggable epigenetic targets for cancer, inflammation, diabetes and cardiovascular therapeutics. Of particular importance is the first of two bromodomains in bromodomain containing 4 protein (BRD4(1)). Protein-ligand docking in BRD4(1) was used to purchase a small, focused screening set of compounds possessing a large variety of core structures. Within this set, a small number of weak hits each contained a dihydroquinoxalinone ring system. We purchased other analogs with this ring system and further validated the new hit series and obtained improvement in binding inhibition. Limited exploration by new analog synthesis showed that the binding inhibition in a FRET assay could be improved to the low μM level making this new core a potential hit-to-lead series. Additionally, the predicted geometries of the initial hit and an improved analog were confirmed by X-ray co-crystallography with BRD4(1). Copyright © 2015 Elsevier Ltd. All rights reserved.

Design and synthesis of tetraol derivatives of 1,12-dicarba-closo-dodecaborane as non-secosteroidal vitamin D analogs.

PubMed

Fujii, Shinya; Kano, Atsushi; Masuno, Hiroyuki; Songkram, Chalermkiat; Kawachi, Emiko; Hirano, Tomoya; Tanatani, Aya; Kagechika, Hiroyuki

2014-09-15

Vitamin D receptor (VDR), a nuclear receptor for 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3, 1), is a promising target for multiple clinical applications. We recently developed non-secosteroidal VDR ligands based on a carbon-containing boron cluster, 1,12-dicarba-closo-dodecaborane (p-carborane), and examined the binding of one of them to VDR by means of crystallographic analysis. Here, we utilized that X-ray structure to design novel p-carborane-based tetraol-type vitamin D analogs, and we examined the biological activities of the synthesized compounds. Structure-activity relationship study revealed that introduction of an ω-hydroxyalkoxy functionality enhanced the biological activity, and the configuration of the substituent significantly influenced the potency. Among the synthesized compounds, 4-hydroxybutoxy derivative 9a exhibited the most potent activity, which was equal to that of the secosteroidal vitamin D analog, 19-nor-1α,25-dihydroxyvitamin D3 (2). Copyright © 2014 Elsevier Ltd. All rights reserved.

Structure-Activity Relationships of 6- and 8-Gingerol Analogs as Anti-Biofilm Agents.

PubMed

Choi, Hyunsuk; Ham, So-Young; Cha, Eunji; Shin, Yujin; Kim, Han-Shin; Bang, Jeong Kyu; Son, Sang-Hyun; Park, Hee-Deung; Byun, Youngjoo

2017-12-14

Pseudomonas aeruginosa is a causative agent of chronic infections in immunocompromised patients. Disruption of quorum sensing circuits is an attractive strategy for treating diseases associated with P. aeruginosa infection. In this study, we designed and synthesized a series of gingerol analogs targeting LasR, a master regulator of quorum sensing networks in P. aeruginosa. Structure-activity relationship studies showed that a hydrogen-bonding interaction in the head section, stereochemistry and rotational rigidity in the middle section, and optimal alkyl chain length in the tail section are important factors for the enhancement of LasR-binding affinity and for the inhibition of biofilm formation. The most potent compound 41, an analog of (R)-8-gingerol with restricted rotation, showed stronger LasR-binding affinity and inhibition of biofilm formation than the known LasR antagonist (S)-6-gingerol. This new LasR antagonist can be used as an early lead compound for the development of anti-biofilm agents to treat P. aeruginosa infections.

Nanophysics in graphene: neutrino physics in quantum rings and superlattices.

PubMed

Fertig, H A; Brey, Luis

2010-12-13

Electrons in graphene at low energy obey a two-dimensional Dirac equation, closely analogous to that of neutrinos. As a result, quantum mechanical effects when the system is confined or subjected to potentials at the nanoscale may be quite different from what happens in conventional electronic systems. In this article, we review recent progress on two systems where this is indeed the case: quantum rings and graphene electrons in a superlattice potential. In the former case, we demonstrate that the spectrum reveals signatures of 'effective time-reversal symmetry breaking', in which the spectra are most naturally interpreted in terms of effective magnetic flux contained in the ring, even when no real flux is present. A one-dimensional superlattice potential is shown to induce strong band-structure changes, allowing the number of Dirac points at zero energy to be manipulated by the strength and/or period of the potential. The emergence of new Dirac points is shown to be accompanied by strong signatures in the conduction properties of the system.

The biophysical basis of Benveniste experiments: Entropy, structure, and information in water

NASA Astrophysics Data System (ADS)

Widom, Allan; Srivastava, Yogendra; Valenzi, Vincenzo

Benveniste had observed that highly dilute (and even in the absence of physical molecules) biological agents still triggered relevant biological systems. Some of these experiments were reproduced in three other laboratories who cosigned the article, (Davenas et al., Nature 1988, 333, 816). Further works, [(Medical Hypotheses 2000, 54, 33), (Rivista di Biologia/Biology Forum 97, 2004, 169)], showed that molecular activity in more than 50 biochemical systems and even in bacteria could be induced by electromagnetic signals transferred through water solutes. The sources of the electromagnetic signals were recordings of specific biological activities. These results suggest that electromagnetic transmission of biochemical information can be stored in the electric dipole moments of water in close analogy to the manner in which magnetic moments store information on a computer disk. The electromagnetic transmission would enable in vivo transmissions of the specific molecular information between two functional biomolecules. In the present work, the physical nature of such biological information storage and retrieval in ordered quantum electromagnetic domains of water will be discussed.

Utterance selection model of language change

NASA Astrophysics Data System (ADS)

Baxter, G. J.; Blythe, R. A.; Croft, W.; McKane, A. J.

2006-04-01

We present a mathematical formulation of a theory of language change. The theory is evolutionary in nature and has close analogies with theories of population genetics. The mathematical structure we construct similarly has correspondences with the Fisher-Wright model of population genetics, but there are significant differences. The continuous time formulation of the model is expressed in terms of a Fokker-Planck equation. This equation is exactly soluble in the case of a single speaker and can be investigated analytically in the case of multiple speakers who communicate equally with all other speakers and give their utterances equal weight. Whilst the stationary properties of this system have much in common with the single-speaker case, time-dependent properties are richer. In the particular case where linguistic forms can become extinct, we find that the presence of many speakers causes a two-stage relaxation, the first being a common marginal distribution that persists for a long time as a consequence of ultimate extinction being due to rare fluctuations.

Design, synthesis, and antihypertensive activity of curcumin-inspired compounds via ACE inhibition and vasodilation, along with a bioavailability study for possible benefit in cardiovascular diseases.

PubMed

Zhuang, Xiao-Dong; Liao, Li-Zhen; Dong, Xiao-Bian; Hu, Xun; Guo, Yue; Du, Zhi-Min; Liao, Xin-Xue; Wang, Li-Chun

2016-01-01

This study describes the synthesis of a novel series of curcumin-inspired compounds via a facile synthetic route. The structures of these derivatives were ascertained using various spectroscopic and analytic techniques. The pharmacological effects of the target analogs were assessed by assaying their inhibition of angiotensin-converting enzyme (ACE). All of the synthesized derivatives exhibited considerable inhibition of ACE, with half-maximal inhibitory concentrations ranging from 1.23 to 120.32 μM. In a docking analysis with testicular ACE (tACE), the most promising inhibitor (4j) was efficiently accommodated in the deep cleft of the protein cavity, making close interatomic contacts with Glu162, His353, and Ala356, comparable with lisinopril. Compounds 4i, 4j, 4k, and 4l were further selected for determination of their vasodilator activity (cardiac output and stroke volume) on isolated rat hearts using the Langendorff technique. The bioavailability of compound 4j was determined in experimental mice.

Modeling the interaction of seven bisphosphonates with the hydroxyapatite(100) face.

PubMed

Chen, Chunyu; Xia, Mingzhu; Wu, Lei; Zhou, Chao; Wang, Fengyun

2012-09-01

The interaction of seven pamidronate bisphosphonate (Pami-BPs) and its analogs with the hydroxyapatite (HAP) (100) surface was studied using density functional theory (DFT) and molecular dynamic (MD) methods. Partial Mulliken oxygen atomic charges in protonated structures were calculated at the level of B3LYP/6-31G*. The MD simulation was performed using the Discover module of Material Studio by compass force field. The results indicate the abilities of donating electrons of the oxygen atoms of the phosphate groups that are closely associated with the antiresorptive potency. The binding energies, including vdw and electrostatic, are used to discuss the mechanism of antiresorption. The results of calculations show that the strength of interaction of the HAP (100) face with the bisphosphonates is N(4) > N(6) > N(7) > N(5) > N(3) > N(2) > N(1) according to their experimental pIC(50) values.

Molecular solar thermal energy storage in photoswitch oligomers increases energy densities and storage times.

PubMed

Mansø, Mads; Petersen, Anne Ugleholdt; Wang, Zhihang; Erhart, Paul; Nielsen, Mogens Brøndsted; Moth-Poulsen, Kasper

2018-05-16

Molecular photoswitches can be used for solar thermal energy storage by photoisomerization into high-energy, meta-stable isomers; we present a molecular design strategy leading to photoswitches with high energy densities and long storage times. High measured energy densities of up to 559 kJ kg -1 (155 Wh kg -1 ), long storage lifetimes up to 48.5 days, and high quantum yields of conversion of up to 94% per subunit are demonstrated in norbornadiene/quadricyclane (NBD/QC) photo-/thermoswitch couples incorporated into dimeric and trimeric structures. By changing the linker unit between the NBD units, we can at the same time fine-tune light-harvesting and energy densities of the dimers and trimers so that they exceed those of their monomeric analogs. These new oligomers thereby meet several of the criteria to be met for an optimum molecule to ultimately enter actual devices being able to undergo closed cycles of solar light-harvesting, energy storage, and heat release.

Toward the rational design of carbapenem uptake in Pseudomonas aeruginosa.

PubMed

Isabella, Vincent M; Campbell, Arthur J; Manchester, John; Sylvester, Mark; Nayar, Asha S; Ferguson, Keith E; Tommasi, Ruben; Miller, Alita A

2015-04-23

Understanding how compound penetration occurs across the complex cell walls of Gram-negative bacteria is one of the greatest challenges in discovering new drugs to treat the infections they cause. A combination of next-generation transposon sequencing, computational metadynamics simulations (CMDS), and medicinal chemistry was used to define genetic and structural elements involved in facilitated carbapenem entry into Pseudomonas aeruginosa. Here we show for the first time that these compounds are taken up not only by the major outer membrane channel OccD1 (also called OprD or PA0958) but also by a closely related channel OccD3 (OpdP or PA4501). Transport-mediating molecular interactions predicted by CMDS for these channels were first confirmed genetically, then used to guide the design of carbapenem analogs with altered uptake properties. These results bring us closer to the rational design of channel transmissibility and may ultimately lead to improved permeability of compounds across bacterial outer membranes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Paracrystalline Disorder from Phosphate Ion Orientation and Substitution in Synthetic Bone Mineral.

PubMed

Marisa, Mary E; Zhou, Shiliang; Melot, Brent C; Peaslee, Graham F; Neilson, James R

2016-12-05

Hydroxyapatite is an inorganic mineral closely resembling the mineral phase in bone. However, as a biological mineral, it is highly disordered, and its composition and atomistic structure remain poorly understood. Here, synchrotron X-ray total scattering and pair distribution function analysis methods provide insight into the nature of atomistic disorder in a synthetic bone mineral analogue, chemically substituted hydroxyapatite. By varying the effective hydrolysis rate and/or carbonate concentration during growth of the mineral, compounds with varied degrees of paracrystallinity are prepared. From advanced simulations constrained by the experimental pair distribution function and density functional theory, the paracrystalline disorder prevalent in these materials appears to result from accommodation of carbonate in the lattice through random displacement of the phosphate groups. Though many substitution modalities are likely to occur in concert, the most predominant substitution places carbonate into the mirror plane of an ideal phosphate site. Understanding the mineralogical imperfections of a biologically analogous hydroxyapatite is important not only to potential bone grafting applications but also to biological mineralization processes themselves.