Sample records for intercalative binding structure
-
Linear and circular dichroism characterization of thionine binding mode with DNA polynucleotides
NASA Astrophysics Data System (ADS)
Tuite, Eimer Mary; Nordén, Bengt
2018-01-01
The binding mode of thionine (3,7-diamino-5-phenothiazinium) with alternating and non-alternating DNA polynucleotides at low binding ratios was conclusively determined using linear and circular dichroism spectroscopies. The binding to [poly(dG-dC)]2 and poly(dG)·poly(dC) was purely intercalative and was insensitive to ionic strength. Intercalative binding to [poly(dA-dT)]2 is observed at low ionic strength, but a shift of some dye to an non-intercalative mode is observed as the background salt concentration increases. With poly(dA)·poly(dT), intercalative binding is unfavourable, although some dye molecules may intercalate at low ionic strength, and groove binding is strongly promoted with increasing concentration of background salt. However, stacking with bases is observed with single-stranded poly(dA) and with triplex poly(dT)*poly(dA)·poly(dT) which suggests that the unusual structure of poly(dA)·poly(dT) precludes intercalation. Thionine behaves similarly to the related dye methylene blue, and small differences may be attributed either to the ability of thionine to form H-bonds that stabilize intercalation or to its improved stacking interactions in the basepair pocket on steric grounds.
-
Roy, Snigdha; Das, Suman
2014-01-01
Here, we report results from experiments designed to explore the association of the phenazinium dye safranin T (ST, 3,7-diamino-2,8-dimethyl-5-phenylphenazinium chloride) with single and double stranded form of polyriboadenylic acid (hereafter poly-A) using several spectroscopic techniques. We demonstrate that the dye binds to single stranded polyriboadenylic acid (hereafter ss poly-A) with high affinity while it does not interact at all with the double stranded (ds) form of the polynucleotide. Fluorescence and absorption spectral studies reveal the molecular aspects of binding of ST to single stranded form of the polynucleotide. This observation is also supported by the circular dichroism study. Thermodynamic data obtained from temperature dependence of binding constant reveals that association is driven by negative enthalpy change and opposed by negative entropy change. Ferrocyanide quenching studies have shown intercalative binding of ST to ss poly-A. Experiments on viscosity measurements confirm the binding mode of the dye to be intercalative. The effect of [Na+] ion concentration on the binding process suggests the role of electrostatic forces in the complexation. Present studies reveal the utility of the dye in probing nucleic acid structure. PMID:24498422
-
Pradhan, Ankur Bikash; Haque, Lucy; Roy, Snigdha; Das, Suman
2014-01-01
Here, we report results from experiments designed to explore the association of the phenazinium dye safranin T (ST, 3,7-diamino-2,8-dimethyl-5-phenylphenazinium chloride) with single and double stranded form of polyriboadenylic acid (hereafter poly-A) using several spectroscopic techniques. We demonstrate that the dye binds to single stranded polyriboadenylic acid (hereafter ss poly-A) with high affinity while it does not interact at all with the double stranded (ds) form of the polynucleotide. Fluorescence and absorption spectral studies reveal the molecular aspects of binding of ST to single stranded form of the polynucleotide. This observation is also supported by the circular dichroism study. Thermodynamic data obtained from temperature dependence of binding constant reveals that association is driven by negative enthalpy change and opposed by negative entropy change. Ferrocyanide quenching studies have shown intercalative binding of ST to ss poly-A. Experiments on viscosity measurements confirm the binding mode of the dye to be intercalative. The effect of [Na⁺] ion concentration on the binding process suggests the role of electrostatic forces in the complexation. Present studies reveal the utility of the dye in probing nucleic acid structure.
-
NASA Astrophysics Data System (ADS)
Gaber, Mohamed; El-Wakiel, Nadia A.; El-Ghamry, Hoda; Fathalla, Shaimaa K.
2014-11-01
Manganese(II), cobalt(II), nickel(II) and copper(II) complexes of [(1H-1,2,4-triazole-3-ylimino)methyl]naphthalene-2-ol have been synthesized. The structure of complexes have been characterized by elemental analysis, molar conductance, magnetic moment measurements and spectral (IR, 1H NMR, EI-mass, UV-Vis and ESR), and thermal studies. The results showed that the chloro and nitrato Cu(II) complexes have octahedral geometry while Ni(II), Co(II) and Mn(II) complexes in addition to acetato Cu(II) complex have tetrahedral geometry. The possible structures of the metal complexes have been computed using the molecular mechanic calculations using the hyper chem. 8.03 molecular modeling program to confirm the proposed structures. The kinetic and thermodynamic parameters of the thermal decomposition steps were calculated from the TG curves. The binding modes of the complexes with DNA have been investigated by UV-Vis absorption titration. The results showed that the mode of binding of the complexes to DNA is intercalative or non-intercalative binding modes. Schiff base and its metal complexes have been screened for their in vitro antimicrobial activities against Gram positive bacteria (Staphylococcus aureus), Gram negative bacteria (Escherichia coli and Pesudomonas aeruginosa), fungi (Asperigllus flavus and Mucer) and yeast (Candida albicans and Malassezia furfur).
-
Structure and dynamics of proflavine association around DNA.
Sasikala, Wilbee D; Mukherjee, Arnab
2016-04-21
Proflavine is a small molecule that intercalates into DNA and, thereby, acts as an anticancer agent. Intercalation of proflavine is shown to be a two-step process in which the first step is believed to be the formation of a pre-intercalative outside bound state. Experimental studies so far have been unable to capture the nature of the outside bound state. However, the sub-millisecond timescale observed in fluorescence kinetic experiments is often attributed to the binding of proflavine outside of DNA. Here, we have performed molecular dynamics simulations with multiple proflavine molecules to study the structure and dynamics of the formation of the outside bound state of DNA at different ion concentrations. We observed that the timescale of the outside bound state formation is, at least, five orders of magnitude faster (in nanoseconds) than the experimentally reported timescale (sub-milliseconds) attributed to binding outside DNA. Moreover, we also observed the stacked arrangement of proflavine all around DNA, which is different from the experimentally predicted stacking arrangement perpendicular to the helical axis of DNA in the close vicinity of the phosphate groups. This study, therefore, provides insight into the molecular structure and dynamics of the pre-intercalative outside bound state and will help in understanding the overall intercalation mechanism.
-
Innovative Funding for Intercity Modes: A Casebook of State, Local, and Private Approaches
DOT National Transportation Integrated Search
1987-07-01
The document reviews non-Federal funding sources for intercity transportation services. The report examines the structure of intercity passenger and freight transportation services, focusing on bus, rail, and short-haul air. It explores public-privat...
-
Footprinting reveals that nogalamycin and actinomycin shuffle between DNA binding sites.
Fox, K R; Waring, M J
1986-01-01
The hypothesis that sequence-selective DNA-binding antibiotics locate their preferred binding sites by a process involving migration from nonspecific sites has been tested by footprinting with DNAase I. Footprinting patterns on the tyrT DNA fragment produced by nogalamycin and actinomycin change with time after mixing the antibiotic with the DNA. Sites of protection as well as enhanced cleavage are seen to develop in a fashion which is both temperature and concentration-dependent. At certain sites cutting is transiently enhanced, then blocked. Limited evidence for slow reaction with echinomycin and mithramycin is presented, but the kinetics of footprinting with daunomycin and distamycin appear instantaneous. The feasibility of adducing direct evidence for shuffling by footprinting seems to be governed by slow dissociation of the antibiotic-DNA complex. It may also be dependent upon the mode of binding, be it intercalative or non-intercalative in character. Images PMID:2421246
-
Papavasileiou, Konstantinos D; Avramopoulos, Aggelos; Leonis, Georgios; Papadopoulos, Manthos G
2017-06-01
DNA is the building block of life, as it carries the biological information controlling development, function and reproduction of all organisms. However, its central role in storing and transferring genetic information can be severely hindered by molecules with structure altering abilities. Fullerenes are nanoparticles that find a broad spectrum of uses, but their toxicological effects on living organisms upon exposure remain unclear. The present study examines the interactions of a diverse array of fullerenes with DNA, by means of Molecular Dynamics and MM-PBSA methodologies, with special focus on structural deformations that may hint toxicity implications. Our results show that pristine and hydroxylated fullerenes have no unwinding effects upon DNA structure, with the latter displaying binding preference to the DNA major groove, achieved by both direct formation of hydrogen bonds and water molecule mediation. Fluorinated derivatives are capable of penetrating DNA structure, forming intercalative complexes with high binding affinities. Copyright © 2017 Elsevier Inc. All rights reserved.
-
NASA Astrophysics Data System (ADS)
Khan, Asma Yasmeen; Saha, Baishakhi; Kumar, Gopinatha Suresh
2014-10-01
A comprehensive study on the binding of phenazinium dyes viz. janus green B, indoine blue, safranine O and phenosafranine with double stranded poly(A) using various spectroscopic and calorimetric techniques is presented. A higher binding of janus green B and indoine blue over safranine O and phenosafranine to poly(A) was observed from all experiments. Intercalative mode of binding of the dyes was inferred from fluorescence polarization anisotropy, iodide quenching and viscosity experiments. Circular dichroism study revealed significant perturbation of the secondary structure of poly(A) on binding of these dyes. Results from isothermal titration calorimetry experiments suggested that the binding was predominantly entropy driven with a minor contribution of enthalpy to the standard molar Gibbs energy. The results presented here may open new opportunities in the application of these dyes as RNA targeted therapeutic agents.
-
Enantioselective binding of L, D-phenylalanine to ct DNA
NASA Astrophysics Data System (ADS)
Zhang, Lijin; Xu, Jianhua; Huang, Yan; Min, Shungeng
2009-10-01
The enantioselective binding of L, D-phenylalanine to calf thymus DNA was studied by absorption, circular dichroism, fluorescence quenching, viscosity, salt effect and emission experiments. The results obtained from absorption, circular dichroism, fluorescence quenching and viscosity experiments excluded the intercalative binding and salt effect experiments did not support electrostatic binding. So the binding of L, D-phenylalanine to ct DNA should be groove binding. Furthermore, the emission spectra revealed that the binding is enantioselective.
-
Enantioselective binding of L,D-phenylalanine to ct DNA.
Zhang, Lijin; Xu, Jianhua; Huang, Yan; Min, Shungeng
2009-10-15
The enantioselective binding of L,D-phenylalanine to calf thymus DNA was studied by absorption, circular dichroism, fluorescence quenching, viscosity, salt effect and emission experiments. The results obtained from absorption, circular dichroism, fluorescence quenching and viscosity experiments excluded the intercalative binding and salt effect experiments did not support electrostatic binding. So the binding of l,d-phenylalanine to ct DNA should be groove binding. Furthermore, the emission spectra revealed that the binding is enantioselective.
-
Non-intercalative, deoxyribose binding of boric acid to calf thymus DNA.
Ozdemir, Ayse; Gursaclı, Refiye Tekiner; Tekinay, Turgay
2014-05-01
The present study characterizes the effects of the boric acid binding on calf thymus DNA (ct-DNA) by spectroscopic and calorimetric methods. UV-Vis absorbance spectroscopy, circular dichroism (CD) spectroscopy, transmission electron microscopy (TEM), isothermal titration calorimetry (ITC), and Fourier transform infrared (FT-IR) spectroscopy were employed to characterize binding properties. Changes in the secondary structure of ct-DNA were determined by CD spectroscopy. Sizes and morphologies of boric acid-DNA complexes were determined by transmission electron microscopy (TEM). The kinetics of boric acid binding to calf thymus DNA (ct-DNA) was investigated by isothermal titration calorimetry (ITC). ITC results revealed that boric acid exhibits a moderate affinity to ct-DNA with a binding constant (K a) of 9.54 × 10(4) M(-1). FT-IR results revealed that boric acid binds to the deoxyribose sugar of DNA without disrupting the B-conformation at tested concentrations.
-
A comprehensive approach to ascertain the binding mode of curcumin with DNA
NASA Astrophysics Data System (ADS)
Haris, P.; Mary, Varughese; Aparna, P.; Dileep, K. V.; Sudarsanakumar, C.
2017-03-01
Curcumin is a natural phytochemical from the rhizoma of Curcuma longa, the popular Indian spice that exhibits a wide range of pharmacological properties like antioxidant, anticancer, anti-inflammatory, antitumor, and antiviral activities. In the published literatures we can see different studies and arguments on the interaction of curcumin with DNA. The intercalative binding, groove binding and no binding of curcumin with DNA were reported. In this context, we conducted a detailed study to understand the mechanism of recognition of dimethylsulfoxide-solubilized curcumin by DNA. The interaction of curcumin with calf thymus DNA (ctDNA) was confirmed by agarose gel electrophoresis. The nature of binding and energetics of interaction were studied by Isothermal Titration Calorimetry (ITC), Differential Scanning Calorimetry (DSC), UV-visible, fluorescence and melting temperature (Tm) analysis. The experimental data were compared with molecular modeling studies. Our investigation confirmed that dimethylsulfoxide-solubilized curcumin binds in the minor groove of the ctDNA without causing significant structural alteration to the DNA.
-
NASA Astrophysics Data System (ADS)
Alfi, Nafiseh; Khorasani-Motlagh, Mozhgan; Rezvani, Ali Reza; Noroozifar, Meissam; Molčanov, Krešimir
2017-06-01
A heteroleptic europium coordination compound formulated as [Eu(phen)2(OH2)2(Cl)2](Cl)(H2O) (phen = 1,10-phenanthroline), has been synthesized and characterized by elemental analysis, FT-IR spectroscopy, and single-crystal X-ray diffractometer. Crystal structure analysis reveals the complex is crystallized in orthorhombic system with Pca21 space group. Electronic absorption and various emission methods for investigation of the binding system of europium(III) complex to Fish Salmon deoxyribonucleic acid (FS-DNA) and Bovamin Serum Albumin (BSA) have been explored. Furthermore, the binding constants, binding sites and the corresponding thermodynamic parameters of the interaction system based on the van't Hoff equation for FS-DNA and BSA were calculated. The thermodynamic parameters reflect the exothermic nature of emission process (ΔH°<0 and ΔS°<0). The experimental results seem to indicate that the [Eu(phen)2(OH2)2(Cl)2](Cl)(H2O) bound to FS-DNA by non-intercalative mode which the groove binding is preferable mode. Also, the complex exhibits a brilliant antimicrobial activity in vitro against standard bacterial strains.
-
Gao, En-Jun; Wang, Ke-Hua; Zhu, Ming-Chang; Liu, Lei
2010-07-01
A novel tetranuclear palladium(II) complex [Pd(4)(phen)(4) (micro-pydc)(4)].10H(2)O (phen = 1,10-phenanthroline, pydc = pyridine-3,4-dicarboxylate) has been synthesized and characterized. In the tetranuclear complex, two pairs of dipalladated [Pd(phen)] moieties are bridged together by four pydc, presenting a hairpin molecular shape. The binding of the title complex with fish sperm DNA (FS-DNA) has been investigated by UV spectrum and fluorescence spectrum. All the results indicate that the complex bind to DNA in an intercalative mode and considerating the molecular shape and size, the dipalladated phenanthroline moieties bisintercalate to the base pairs of DNA. Agarose gel electrophoresis assay demonstrates the ability of the complex to cleave the pBR322 plasmid DNA. Cytotoxic activity studies show the complex exhibited good cytotoxic activity against four different cancer cell lines. Crown Copyright (c) 2010. Published by Elsevier Masson SAS. All rights reserved.
-
Solution structure and thermodynamics of 2',5' RNA intercalation.
Horowitz, Eric D; Lilavivat, Seth; Holladay, Benjamin W; Germann, Markus W; Hud, Nicholas V
2009-04-29
As a means to explore the influence of the nucleic acid backbone on the intercalative binding of ligands to DNA and RNA, we have determined the solution structure of a proflavine-bound 2',5'-linked octamer duplex with the sequence GCCGCGGC. This structure represents the first NMR structure of an intercalated RNA duplex, of either backbone structural isomer. By comparison with X-ray crystal structures, we have identified similarities and differences between intercalated 3',5' and 2',5'-linked RNA duplexes. First, the two forms of RNA have different sugar pucker geometries at the intercalated nucleotide steps, yet have the same interphosphate distances. Second, as in intercalated 3',5' RNA, the phosphate backbone angle zeta at the 2',5' RNA intercalation site prefers to be in the trans conformation, whereas unintercalated 2',5' and 3',5' RNA prefer the -gauche conformation. These observations provide new insights regarding the transitions required for intercalation of a phosphodiester-ribose backbone and suggest a possible contribution of the backbone to the origin of the nearest-neighbor exclusion principle. Thermodynamic studies presented for intercalation of both structural RNA isomers also reveal a surprising sensitivity of intercalator binding enthalpy and entropy to the details of RNA backbone structure.
-
Shahraki, Somaye; Mansouri-Torshizi, Hassan; Sori Nezami, Ziba; Ghahghaei, Arezou; Yaghoubi, Fatemeh; Divsalar, Adeleh; Saboury, Ali-Akbar; H. Shirazi, Farshad
2014-01-01
In depth interaction studies between calf thymus deoxyribonucleic acid (CT-DNA) and a series of four structurally relative palladium(II) complexes [Pd(en)(HB)](NO3)2 (a-d), where en is ethylenediamine and heterocyclic base (HB) is 2,2'-bipyridine (bpy, a); 1,10-phenanthroline (phen, b); dipyridoquinoxaline (dpq, c) and dipyridophenazine (dppz, d) (Figure 1), were performed. These studies have been investigated by utilizing the electronic absorption spectroscopy, fluorescence spectra and ethidium bromide (EBr) displacement and gel filtration techniques. a-d complexes cooperatively bind and denature the DNA at low concentrations. Their concentration at midpoint of transition, L1/2, follows the order a >> b > c > d. Also the g, the number of binding sites per 1000 nucleotides, follows the order a >> b ~ c > d. EBr and Scatchard experiments for a-d complexes suggest efficient intercalative binding affinity to CT-DNA giving the order: d > c > b > a. Several binding and thermodynamic parameters are also described. The biological activity of these cationic and water soluble palladium complexes were tested against chronic myelogenous leukemia cell line, K562. b, c and d complexes show cytotoxic concentration (Cc50) values much lower than cisplatin. PMID:25587317
-
Guo, Qiong; Li, Lianzhi; Dong, Jianfang; Liu, Hongyan; Xu, Tao; Li, Jinghong
2013-04-01
A divanadium(V) complex, [V2O3(o-van-val)2] (o-van-val=Schiff base derived from o-vanillin and L-valine), has been synthesized and structurally characterized. The crystal structure shows that both of the vanadium centers in the complex have a distorted octahedral coordination environment composed of tridentate Schiff base ligand. A V2O3 core in molecular structure adopts intermediate between cis and trans configuration with the O1V1⋯V1AO1A torsion angle 115.22 (28)° and the V1⋯V1A distance 3.455Å. The binding properties of the complex with calf thymus DNA (CT-DNA) have been investigated by UV-vis absorption, fluorescence, CD spectra and viscosity measurement. The results indicate that the complex binds to CT-DNA in non-classical intercalative mode. Meanwhile, the interaction of the complex with bovine serum albumin (BSA) has been studied by UV-vis absorption, fluorescence and CD spectra. Results indicated that the complex can markedly quench the intrinsic fluorescence of BSA via a static quenching process, and cause its conformational change. The calculated apparent binding constant Kb was 1.05×10(6)M(-1) and the binding site number n was 1.18. Copyright © 2013 Elsevier B.V. All rights reserved.
-
Skyrianou, Kalliopi C; Psycharis, Vassilis; Raptopoulou, Catherine P; Kessissoglou, Dimitris P; Psomas, George
2011-01-01
The nickel(II) complexes with the second-generation quinolone antibacterial agent enrofloxacin in the presence or absence of the nitrogen-donor heterocyclic ligands 1,10-phenanthroline, 2,2'-bipyridine or pyridine have been synthesized and characterized. Enrofloxacin acts as bidentate ligand coordinated to Ni(II) ion through the ketone oxygen and a carboxylato oxygen. The crystal structure of (1,10-phenanthroline)bis(enrofloxacinato)nickel(II) has been determined by X-ray crystallography. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that they bind to CT DNA and bis(pyridine)bis(enrofloxacinato)nickel(II) exhibits the highest binding constant to CT DNA. The cyclic voltammograms of the complexes have shown that in the presence of CT DNA the complexes can bind to CT DNA by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. The complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values. The biological properties of the complexes have been evaluated in comparison to the corresponding Zn(II) enrofloxacinato complexes as well as Ni(II) complexes with the first-generation quinolone oxolinic acid. Copyright © 2010 Elsevier Inc. All rights reserved.
-
A Water‐Soluble Tetraazaperopyrene Dye as Strong G‐Quadruplex DNA Binder
Hahn, Lena
2016-01-01
Abstract The interactions of the water‐soluble tetraazaperopyrene dye 1 with ct‐DNA, duplex‐[(dAdT)12 ⋅(dAdT)12], duplex‐[(dGdC)12 ⋅(dGdC)12] as well as with two G‐quadruplex‐forming sequences, namely the human telomeric 22AG and the promotor sequence c‐myc, were investigated by means of UV/visible and fluorescence spectroscopy, isothermal titration calorimetry (ITC) and molecular docking studies. Dye 1 exhibits a high affinity for G‐quadruplex structures over duplex DNA structures. Furthermore, the ligand shows promising G‐quadruplex discrimination, with an affinity towards c‐myc of 2×107 m −1 (i.e., K d=50 nm), which is higher than for 22AG (4×106 m −1). The ITC data reveal that compound 1 interacts with c‐myc in a stoichiometric ratio of 1:1 but also indicate the presence of two identical lower affinity secondary binding sites per quadruplex. In 22AG, there are two high affinity binding sites per quadruplex, that is, one on each side, with a further four weaker binding sites. For both quadruplex structures, the high affinity interactions between compound 1 and the quadruplex‐forming nucleic acid structures are weakly endothermic. Molecular docking studies suggest an end‐stacking binding mode for compound 1 interacting with quadruplex structures, and a higher affinity for the parallel conformation of c‐myc than for the mixed‐hybrid conformation of 22AG. In addition, docking studies also suggest that the reduced affinity for duplex DNA structures is due to the non‐viability of an intercalative binding mode. PMID:26997208
-
NASA Astrophysics Data System (ADS)
Mohamadi, Maryam; Afzali, Daryoush; Esmaeili-Mahani, Saeed; Mostafavi, Ali; Torkzadeh-Mahani, Masoud
2015-09-01
Interaction of oleuropein, the major bio-phenol in olive leaf and fruit, with salmon sperm double-stranded DNA was investigated by employing electronic absorption titrations, fluorescence quenching spectroscopy, competitive fluorescence spectroscopy, thermal denaturation and voltammetric studies. Titration of oleuropein with the DNA caused a hypochromism accompanied with a red shift indicating an intercalative mode of interaction. Binding constant of 1.4 × 104 M-1 was obtained for this interaction. From the curves of fluorescence titration of oleuropein with the DNA, binding constant and binding sites were calculated to be 8.61 × 103 M-1 and 1.05, respectively. Competitive studies with ethidium bromide (a well-known DNA intercalator) showed that the bio-phenol could take the place of ethidium bromide in the DNA intercalation sites. The interaction of oleuropein with DNA was also studied electrochemically. In the presence of the DNA, the anodic and cathodic peak currents of oleuropein decreased accompanied with increases in peak-to-peak potential separation and formal potential, indicating the intercalation of oleuropein into the DNA double helix. Moreover, melting temperature of the DNA was found to increase in the presence of oleuropein, indicating the stabilization of the DNA double helix due to an intercalative interaction.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Reddy, B.S.; Seshadri, T.P.; Sakore, T.D.
1979-01-01
Acridine orange and proflavine form complexes with the dinucleoside monophosphate, 5-iodocytidylyl(3'-5') guanosine (iodoCpG). The acridine orange-iodoCpG crystals are monoclinic, space group P2/sub 1/, with unit cell dimensions a = 14.36 A, b = 19.64 A, c = 20.67 A, ..beta.. = 102.5. The proflavine-iodoCpG crystals are monoclinic, space group C2, with unit cell dimensions a = 32.14 A, b = 22.23 A, c = 18.42 A, ..beta.. = 123.3. Both structures have been solved to atomic resolution by Patterson and Fourier methods, and refined by full matrix least squares. Acridine orange forms an intercalative structure with iodoCpG but the acridinemore » nucleus lies asymmetrically in the intercalation site. This asymmetric intercalation is accompanied by a sliding of base-pairs upon the acridine nucleus. Base-pairs above and below the drug are separated by about 6.8 A and are twisted about 10/sup 0/. Proflavine demonstrates symmetric intercalation with iodoCpG. Hydrogen bonds connect amino- groups on proflavine with phosphate oxygen atoms on the dinucleotide. Base-pairs above and below the intercalative proflavine molecule are twisted about 36/sup 0/. The altered magnitude of this angular twist reflects the sugar puckering pattern that is observed. We propose a proflavine-DNA and an acridine orange-DNA binding model. We will describe these models in detail in this paper.« less
-
Hossain, Maidul; Haq, Lucy; Suresh Kumar, Gopinatha
2012-01-01
Background Binding of two 9-O-(ω-amino) alkyl ether berberine analogs BC1 and BC2 to the RNA triplex poly(U)•poly(A)*poly(U) was studied by various biophysical techniques. Methodology/Principal Findings Berberine analogs bind to the RNA triplex non-cooperatively. The affinity of binding was remarkably high by about 5 and 15 times, respectively, for BC1 and BC2 compared to berberine. The site size for the binding was around 4.3 for all. Based on ferrocyanide quenching, fluorescence polarization, quantum yield values and viscosity results a strong intercalative binding of BC1 and BC2 to the RNA triplex has been demonstrated. BC1 and BC2 stabilized the Hoogsteen base paired third strand by about 18.1 and 20.5°C compared to a 17.5°C stabilization by berberine. The binding was entropy driven compared to the enthalpy driven binding of berbeine, most likely due to additional contacts within the grooves of the triplex and disruption of the water structure by the alkyl side chain. Conclusions/Significance Remarkably higher binding affinity and stabilization effect of the RNA triplex by the amino alkyl berberine analogs was achieved compared to berberine. The length of the alkyl side chain influence in the triplex stabilization phenomena. PMID:22666416
-
NASA Technical Reports Server (NTRS)
1976-01-01
Papers on major issues and trends that affect the future of intercity transportation are presented. Specific areas covered include: political, social, technological, institutional, and economic mechanisms, the workings of which determine how future intercity transporation technologies will evolve and be put into service; the major issues of intercity transportation from the point of view of reform, including candidate transporation technologies; and technical analysis of trends affecting the evolution of intercity transportation technologies.
-
2009-12-01
6 Intercity Passenger Rail Program (Amtrak) .....................................................................7 Intercity Bus Security Grant...20 Additionally Amtrak is eligible to receive funding to continue security enhancements for its intercity rail services between high-risk urban...Research Service 7 Intercity Passenger Rail Program (Amtrak) The Intercity Passenger Rail Program (IPR) is designed to enhance security of the
-
Amsacrine as a Topoisomerase II Poison: Importance of Drug-DNA Interactions†
Ketron, Adam C.; Denny, William A.; Graves, David E.; Osheroff, Neil
2012-01-01
Amsacrine (m-AMSA) is an anticancer agent that displays activity against refractory acute leukemias as well as Hodgkin’s and non-Hodgkin’s lymphomas. The drug is comprised of an intercalative acridine moiety coupled to a 4’-amino-methanesulfon-m-anisidide head group. m-AMSA is historically significant in that it was the first drug demonstrated to function as a topoisomerase II poison. Although m-AMSA was designed as a DNA binding agent, the ability to intercalate does not appear to be the sole determinant of drug activity. Therefore, to more fully analyze structure-function relationships and the role of DNA binding in the action of m-AMSA, we analyzed a series of derivatives for the ability to enhance DNA cleavage mediated by human topoisomerase IIα and topoisomerase IIβ and to intercalate DNA. Results indicate that the 3’-methoxy (m-AMSA) positively affects drug function, potentially by restricting the rotation of the head group in a favorable orientation. Shifting the methoxy to the 2’-position (o-AMSA), which abrogates drug function, appears to increase rotational freedom of the head group and may impair interactions of the 1’-substituent or other portions of the head group within the ternary complex. Finally, the non-intercalative m-AMSA head group enhanced enzyme-mediated DNA cleavage when it was detached from the acridine moiety, albeit with 100-fold lower affinity. Taken together, our results suggest that much of the activity and specificity of m-AMSA as a topoisomerase II poison is embodied in the head group, while DNA intercalation is used primarily to increase the affinity of m-AMSA for the topoisomerase II-DNA cleavage complex. PMID:22304499
-
Polymorphic Nucleic Acid Binding of Bioactive Isoquinoline Alkaloids and Their Role in Cancer
Maiti, Motilal; Kumar, Gopinatha Suresh
2010-01-01
Bioactive alkaloids occupy an important position in applied chemistry and play an indispensable role in medicinal chemistry. Amongst them, isoquinoline alkaloids like berberine, palmatine and coralyne of protoberberine group, sanguinarine of the benzophenanthridine group, and their derivatives represent an important class of molecules for their broad range of clinical and pharmacological utility. In view of their extensive occurrence in various plant species and significantly low toxicities, prospective development and use of these alkaloids as effective anticancer agents are matters of great current interest. This review has focused on the interaction of these alkaloids with polymorphic nucleic acid structures (B-form, A-form, Z-form, HL-form, triple helical form, quadruplex form) and their topoisomerase inhibitory activity reported by several research groups using various biophysical techniques like spectrophotometry, spectrofluorimetry, thermal melting, circular dichroism, NMR spectroscopy, electrospray ionization mass spectroscopy, viscosity, isothermal titration calorimetry, differential scanning calorimetry, molecular modeling studies, and so forth, to elucidate their mode and mechanism of action for structure-activity relationships. The DNA binding of the planar sanguinarine and coralyne are found to be stronger and thermodynamically more favoured compared to the buckled structure of berberine and palmatine and correlate well with the intercalative mechanism of sanguinarine and coralyne and the partial intercalation by berberine and palmatine. Nucleic acid binding properties are also interpreted in relation to their anticancer activity. PMID:20814427
-
NASA Astrophysics Data System (ADS)
Bathaie, S. Z.; Nikfarjam, L.; Rahmanpour, R.; Moosavi-Movahedi, A. A.
2010-12-01
Among different biological effects of acetylsalicylic acid (ASA), its anticancer property is controversial. Since ASA hydrolyzes rapidly to salicylic acid (SA), especially in the blood, interaction of both ASA and SA (as the small molecules) with ctDNA, oligo(dA·dT) 15 and oligo(dG·dC) 15, as a possible mechanism of their action, is investigated here. The results show that the rate of ASA hydrolysis in the absence and presence of ctDNA is similar. The spectrophotometric results indicate that both ASA and SA cooperatively bind to ctDNA. The binding constants ( K) are (1.7 ± 0.7) × 10 3 M -1 and (6.7 ± 0.2) × 10 3 M -1 for ASA and SA, respectively. Both ligands quench the fluorescence emission of ethidium bromide (Et)-ctDNA complex. The Scatchard plots indicate the non-displacement based quenching (non-intercalative binding). The circular dichroism (CD) spectra of ASA- or SA-ctDsNA complexes show the minor distortion of ctDNA structure, with no characteristic peaks for intercalation of ligands. Tm of ctDNA is decreased up to 3 °C upon ASA binding. The CD results also indicate more distortions on oligo(dG·dC) 15 structure due to the binding of both ASA and SA in comparison with oligo(dA·dT) 15. All data indicate the more affinity for SA binding with DNA minor groove in comparison with ASA which has more hydrophobic character.
-
DNA binding studies of a new dicationic porphyrin. Insights into interligand interactions.
Shelton, Alexander H; Rodger, Alison; McMillin, David R
2007-08-07
Cationic porphyrins have an affinity for DNA and potential for applications in the fields of photodynamic therapy and cellular imaging. This report describes a new dicationic porphyrin, 5,15-dimethyl-10,20-di(N-methylpyridinium-4-yl)porphyrin, abbreviated H2tMe2D4. Although tetrasubstituted, H2tMe2D4 presents modest steric requirements and forms in reasonable yield by a "2+2" synthetic method. Accordingly, studies of the zinc(II)- and copper(II)-containing derivatives, Zn(tMe2D4) and Cu(tMe2D4), have also been possible. Methods used to characterize DNA-binding motifs include absorption, emission, linear, and circular dichroism spectroscopies, as well as viscometry. An unusually detailed picture of porphyrin uptake emerges. As the ratio of DNA to porphyrin increases during a typical titration, H2tMe2D4 or Cu(tMe2D4) initially aggregates on the host and then shifts to intercalative binding at close quarters before finally dispersing into non-interacting intercalation sites of the host. Emission studies of the copper(II) porphyrin have been very valuable. The existence of a measurable signal is diagnostic of intercalative binding, and the saturation behavior establishes that internalization typically monopolizes approximately three base pairs. In the moderate loading regime, emission data are most telling because dipole-dipole interactions between near-neighbor porphyrins tend to confuse other spectroscopic assays. The third ligand, Zn(tMe2D4), behaves differently in that the uptake is a strictly cooperative process. The mode of binding also varies with the base content of the DNA host. When the DNA is rich in A=T base pairs, the porphyrin remains five-coordinate and binds externally; however, Zn(tMe2D4) loses its axial ligand and binds by intercalation if the host contains only G[triple bond]C base pairs.
-
Ali, Amna Qasem; Teoh, Siang Guan; Salhin, Abdussalam; Eltayeb, Naser Eltaher; Khadeer Ahamed, Mohamed B; Abdul Majid, A M S
2014-05-05
New derivatives of thiosemicarbazone Schiff base with isatin moiety were synthesized L1-L6. The structures of these compounds were characterized based on the spectroscopic techniques. Compound L6 was further characterized by XRD single crystal. The interaction of these compounds with calf thymus (CT-DNA) exhibited high intrinsic binding constant (k(b)=5.03-33.00×10(5) M(-1)) for L1-L3 and L5 and (6.14-9.47×10(4) M(-1)) for L4 and L6 which reflect intercalative activity of these compounds toward CT-DNA. This result was also confirmed by the viscosity data. The electrophoresis studies reveal the higher cleavage activity of L1-L3 than L4-L6. The in vitro anti-proliferative activity of these compounds against human colon cancer cell line (HCT 116) revealed that the synthesized compounds (L3, L6 and L2) exhibited good anticancer potency. Copyright © 2014 Elsevier B.V. All rights reserved.
-
2013-01-01
Background To explore novel platinum-based anticancer agents that are distinct from the structure and interaction mode of the traditional cisplatin by forming the bifunctional intrastrand 1,2 GpG adduct, the monofunctional platinum + DNA adducts with extensive non-covalent interactions had been studied. It was reported that the monofunctional testosterone-based platinum(II) agents present the high anticancer activity. Moreover, it was also found that the testosterone-based platinum agents could cause the DNA helix to undergo significant unwinding and bending over the non-testosterone-based platinum agents. However, the interaction mechanisms of these platinum agents with DNA at the atomic level are not yet clear so far. Results In the present work, we used molecular dynamics (MD) simulations and DNA conformational dynamics calculations to study the DNA distortion properties of the testosterone-based platinum + DNA, the improved testosterone-based platinum + DNA and the non-testosterone-based platinum + DNA adducts. The results show that the intercalative interaction of the improved flexible testosterone-based platinum agent with DNA molecule could cause larger DNA conformational distortion than the groove-face interaction of the rigid testosterone-based platinum agent with DNA molecule. Further investigations for the non-testosterone-based platinum agent reveal the occurrence of insignificant change of DNA conformation due to the absence of testosterone ligand in such agent. Based on the DNA dynamics analysis, the DNA base motions relating to DNA groove parameter changes and hydrogen bond destruction of DNA base pairs were also discussed in this work. Conclusions The flexible linker in the improved testosterone-based platinum agent causes an intercalative interaction with DNA in the improved testosterone-based platinum + DNA adduct, which is different from the groove-face interaction caused by a rigid linker in the testosterone-based platinum agent. The present investigations provide useful information of DNA conformation affected by a testosterone-based platinum complex at the atomic level. PMID:23517640
-
Federal Register 2010, 2011, 2012, 2013, 2014
2010-05-12
... performance and service quality of intercity passenger train operations. In compliance with the statute, the FRA and Amtrak jointly drafted performance metrics and standards for intercity passenger rail service... and Standards for Intercity Passenger Rail Service under Section 207 of the Passenger Rail Investment...
-
49 CFR 37.91 - Wheelchair locations and food service on intercity rail trains.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 1 2010-10-01 2010-10-01 false Wheelchair locations and food service on intercity... Entities § 37.91 Wheelchair locations and food service on intercity rail trains. (a) As soon as practicable, but in no event later than July 26, 1995, each person providing intercity rail service shall provide...
-
Code of Federal Regulations, 2012 CFR
2012-10-01
... 49 Transportation 1 2012-10-01 2012-10-01 false Remanufacture of intercity and commuter rail cars and purchase or lease of remanufactured intercity and commuter rail cars. 37.89 Section 37.89... commuter rail cars and purchase or lease of remanufactured intercity and commuter rail cars. (a) This...
-
Code of Federal Regulations, 2013 CFR
2013-10-01
... 49 Transportation 1 2013-10-01 2013-10-01 false Remanufacture of intercity and commuter rail cars and purchase or lease of remanufactured intercity and commuter rail cars. 37.89 Section 37.89... commuter rail cars and purchase or lease of remanufactured intercity and commuter rail cars. (a) This...
-
Code of Federal Regulations, 2011 CFR
2011-04-01
... gasoline used in intercity, local, or school buses. 48.6421-2 Section 48.6421-2 Internal Revenue INTERNAL... Manufacturers Taxes § 48.6421-2 Credits or payments to ultimate purchasers of gasoline used in intercity, local, or school buses. (a) In general. If gasoline is used in an intercity or local bus while engaged in...
-
Code of Federal Regulations, 2010 CFR
2010-04-01
... gasoline used in intercity, local, or school buses. 48.6421-2 Section 48.6421-2 Internal Revenue INTERNAL... Manufacturers Taxes § 48.6421-2 Credits or payments to ultimate purchasers of gasoline used in intercity, local, or school buses. (a) In general. If gasoline is used in an intercity or local bus while engaged in...
-
Code of Federal Regulations, 2012 CFR
2012-04-01
... gasoline used in intercity, local, or school buses. 48.6421-2 Section 48.6421-2 Internal Revenue INTERNAL... Manufacturers Taxes § 48.6421-2 Credits or payments to ultimate purchasers of gasoline used in intercity, local, or school buses. (a) In general. If gasoline is used in an intercity or local bus while engaged in...
-
Code of Federal Regulations, 2013 CFR
2013-04-01
... gasoline used in intercity, local, or school buses. 48.6421-2 Section 48.6421-2 Internal Revenue INTERNAL... Manufacturers Taxes § 48.6421-2 Credits or payments to ultimate purchasers of gasoline used in intercity, local, or school buses. (a) In general. If gasoline is used in an intercity or local bus while engaged in...
-
Intercity bus service in Virginia.
DOT National Transportation Integrated Search
1981-01-01
The intercity bus industry in Virginia was examined to gain information on the status of the industry and to determine the likely impacts of state policy options relating to assistance and deregulation on the industry. The national intercity bus indu...
-
Intercity passenger rail : implications for urban, regional, and national mobility.
DOT National Transportation Integrated Search
2012-01-01
Recent policy and regulatory actions by the U.S. government have revived interest in intercity passenger : rail among transportation planners, policymakers, and the general public. As part of a fully integrated : multimodal intercity corridor, passen...
-
Pennsylvania intercity bus study : final report
DOT National Transportation Integrated Search
1984-09-01
Report presents the findings of a study to inventory the intercity bus industry in Pennsylvania. Objectives were to assemble information about the intercity bus industry in Pennsylvania in a form that can be used for policy formulation and for manage...
-
Benefit-cost analysis framework for evaluating inter-city transit investment.
DOT National Transportation Integrated Search
2008-10-01
This report describes the development and application of a benefit/cost analysis (BCA) model to support the evaluation of investment decisions for intercity bus services. The model recognizes two principle types of intercity bus benefits: benefits th...
-
Evaluating neighborhood structures for modeling intercity diffusion of large-scale dengue epidemics.
Wen, Tzai-Hung; Hsu, Ching-Shun; Hu, Ming-Che
2018-05-03
Dengue fever is a vector-borne infectious disease that is transmitted by contact between vector mosquitoes and susceptible hosts. The literature has addressed the issue on quantifying the effect of individual mobility on dengue transmission. However, there are methodological concerns in the spatial regression model configuration for examining the effect of intercity-scale human mobility on dengue diffusion. The purposes of the study are to investigate the influence of neighborhood structures on intercity epidemic progression from pre-epidemic to epidemic periods and to compare definitions of different neighborhood structures for interpreting the spread of dengue epidemics. We proposed a framework for assessing the effect of model configurations on dengue incidence in 2014 and 2015, which were the most severe outbreaks in 70 years in Taiwan. Compared with the conventional model configuration in spatial regression analysis, our proposed model used a radiation model, which reflects population flow between townships, as a spatial weight to capture the structure of human mobility. The results of our model demonstrate better model fitting performance, indicating that the structure of human mobility has better explanatory power in dengue diffusion than the geometric structure of administration boundaries and geographic distance between centroids of cities. We also identified spatial-temporal hierarchy of dengue diffusion: dengue incidence would be influenced by its immediate neighboring townships during pre-epidemic and epidemic periods, and also with more distant neighbors (based on mobility) in pre-epidemic periods. Our findings suggest that the structure of population mobility could more reasonably capture urban-to-urban interactions, which implies that the hub cities could be a "bridge" for large-scale transmission and make townships that immediately connect to hub cities more vulnerable to dengue epidemics.
-
Measuring the benefits of intercity passenger rail : a study of the Heartland Flyer corridor.
DOT National Transportation Integrated Search
2010-04-01
In recent years, the policy and regulatory environment for intercity passenger rail in the United States has : shifted dramatically, sparking a renewed interest in intercity passenger rail among policymakers, : planners, and the general public. As th...
-
49 CFR 37.55 - Intercity rail station accessibility.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 1 2010-10-01 2010-10-01 false Intercity rail station accessibility. 37.55 Section 37.55 Transportation Office of the Secretary of Transportation TRANSPORTATION SERVICES FOR INDIVIDUALS WITH DISABILITIES (ADA) Transportation Facilities § 37.55 Intercity rail station accessibility...
-
System and prospects of China's intercity rail transit technology
NASA Astrophysics Data System (ADS)
Gong, Ming
2018-06-01
City clusters and metropolitan areas in China are flourishing in the midst of the deepening urbanization in the country, thereby resulting in the emergence of intercity rail transit. Intercity railways connect mainline and urban railways for an integrated regional transportation system that underpins and leads the development of city clusters and metropolitan areas. This study explores the development mode and service characteristics of intercity rail transit, as well as proposes overviews on this system and prospects of its future technology in China.
-
77 FR 69918 - Notice and Request for Comments
Federal Register 2010, 2011, 2012, 2013, 2014
2012-11-21
... Northeast intercity or regional travel experience during the 12 months prior to interview. Estimated Number... information from the public to determine current intercity and regional travel behavior of Northeast residents... experienced a qualifying intercity or regional travel trip to provide more detailed travel information and...
-
2009-02-26
6 Intercity Passenger Rail Program (Amtrak...6 Intercity Bus Security Grant Program................................................................................. 7...for its intercity rail services between high-risk urban areas. 20 U.S. Department of Homeland Security, Federal Emergency Management Agency
-
DOT National Transportation Integrated Search
1999-10-28
The Rail Passenger Service Act of 1970 created Amtrak as the nation's intercity passenger railroad. The act, as amended, gave Amtrak a number of goals, including providing modern, efficient intercity passenger rail service; giving Americans an altern...
-
DOT National Transportation Integrated Search
2000-09-26
Key decisions will soon have to be made regarding the future of Amtrak, the nation's intercity passenger rail operator. If Amtrak does not reach operational self-sufficiency within the next 2 years, federal law requires that the Amtrak Reform Council...
-
DOT National Transportation Integrated Search
2001-03-21
The Rail Passenger Service Act of 1970 created Amtrak to provide intercity passenger rail service. Like other major national intercity passenger rail systems in the world, Amtrak has received substantial government support-nearly $24 billion for capi...
-
NASA Astrophysics Data System (ADS)
Tabrizi, Leila; Chiniforoshan, Hossein; Tavakol, Hossein
2015-04-01
The complexes [Pd(valp)2(imidazole)2] (1), [Pd(valp)2(pyrazine)2] (2) (valp is sodium valproate) have been synthesized and characterized using IR, 1H NMR, 13C{1H} NMR and UV-Vis spectrometry. The interaction of complexes with CT-DNA has been investigated using spectroscopic tools and viscosity measurement. In each case, the association constant (Kb) was deduced from the absorption spectral study and the number of binding sites (n) and the binding constant (K) were calculated from relevant fluorescence quenching data. As a result, a non-covalent interaction between the metal complex and DNA was suggested, which could be assigned to an intercalative binding. In addition, the interaction of 1 and 2 was ventured with bovine serum albumin (BSA) with the help of absorption and fluorescence spectroscopy measurements. Through these techniques, the apparent association constant (Kapp) and the binding constant (K) could be calculated for each complex. Evaluation of cytotoxic activity of the complexes against four different cancer cell lines proved that the complexes exhibited cytotoxic specificity and significant cancer cell inhibitory rate. Moreover, density functional theory (DFT) calculations were employed to provide more evidence about the observed data. The majority of trans isomers were supported not only by energies, but also by the similarity of its calculated IR frequencies, UV adsorptions and NMR chemical shifts to the experimental values.
-
Empirical study of the role of the topology in spreading on communication networks
NASA Astrophysics Data System (ADS)
Medvedev, Alexey; Kertesz, Janos
2017-03-01
Topological aspects, like community structure, and temporal activity patterns, like burstiness, have been shown to severely influence the speed of spreading in temporal networks. We study the influence of the topology on the susceptible-infected (SI) spreading on time stamped communication networks, as obtained from a dataset of mobile phone records. We consider city level networks with intra- and inter-city connections. The networks using only intra-city links are usually sparse, where the spreading depends mainly on the average degree. The inter-city links serve as bridges in spreading, speeding up considerably the process. We demonstrate the effect also on model simulations.
-
Zhang, Hong; Liu, Xuewen; He, Xiaojun; Liu, Ying; Tan, Lifeng
2014-11-01
There is renewed interest in investigating triple helices because these novel structures have been implicated as a possible means of controlling cellular processes by endogenous or exogenous mechanisms. Due to the Hoogsteen base pairing, triple helices are, however, thermodynamically less stable than the corresponding duplexes. The poor stability of triple helices limits their practical applications under physiological conditions. In contrast to DNA triple helices, small molecules stabilizing RNA triple helices at present are less well established. Furthermore, most of these studies are limited to organic compounds and, to a far lesser extent, to metal complexes. In this work, two Ru(II) complexes, [Ru(bpy)2(btip)](2+) (Ru1) and [Ru(phen)2(btip)](2+) (Ru2), have been synthesized and characterized. The binding properties of the two metal complexes with the triple RNA poly(U)˙poly(A)*poly(U) were studied by various biophysical and density functional theory methods. The main results obtained here suggest that the slight binding difference in Ru1 and Ru2 may be attributed to the planarity of the intercalative ligand and the LUMO level of Ru(II) complexes. This study further advances our knowledge on the triplex RNA-binding by metal complexes, particularly Ru(II) complexes.
-
2009-06-08
Security Grant Program ...............................................................................6 Intercity Passenger Rail Program (Amtrak...6 Intercity Bus Security Grant Program...fy2009.pdf. 19 Additionally Amtrak is eligible to receive funding to continue security enhancements for its intercity rail services between high-risk
-
2009-04-21
6 Intercity Passenger Rail Program (Amtrak) .....................................................................6... Intercity Bus Security Grant Program..............................................................................7 Trucking Security Program...continue security enhancements for its intercity rail services between high-risk urban areas. 20 U.S. Department of Homeland Security, Federal Emergency
-
2009-08-05
Freight Rail Security Grant Program ...............................................................................6 Intercity Passenger Rail Program...Amtrak) .....................................................................6 Intercity Bus Security Grant Program...overview- fy2009.pdf. 19 Additionally Amtrak is eligible to receive funding to continue security enhancements for its intercity rail services
-
75 FR 16564 - High-Speed Intercity Passenger Rail (HSIPR) Program
Federal Register 2010, 2011, 2012, 2013, 2014
2010-04-01
... services to avoid shipping delays. Application forms are available at http://www.fra.dot.gov/Pages/2243..., and 501--Intercity Passenger Rail Service Corridor Capital Assistance (codified at 49 U.S.C. chapter... High Speed Rail Corridors and Intercity Passenger Rail Service.'' This document incorporates interim...
-
DOT National Transportation Integrated Search
2011-02-01
Between 2005 and 2010, 3.5 million rural residents lost access to scheduled intercity transportation, increasing the percent of rural residents without access to intercity transportation from 7 to 11 percent. In 2005, 5.4 million rural residents lack...
-
DOT National Transportation Integrated Search
2001-07-25
With the growth in the nation's highway and aviation systems in the : previous decades, intercity passenger rail service lost its competitive edge. Highways have enabled cars to be competitive with conventional passenger trains (those operating up to...
-
Federal Register 2010, 2011, 2012, 2013, 2014
2012-09-20
... Regional and Intercity Household Travel Attitudes and Behavior. Type of Request: New information collection... ages of 18 and 74 who have Northeast intercity or regional travel experience during the 12 months prior... just those who experienced a qualifying intercity or regional travel trip to provide more detailed...
-
DOT National Transportation Integrated Search
1982-03-01
The legislative directive for the State Intercity Bus Plan asked that the Department offer alternatives for future State involvement in the intercity bus area, estimates for the projected State capital and operating costs and revenues for each of the...
-
Zhang, Chao; Guo, Xiaofei; Cai, Wenqian; Ma, Yue; Zhao, Xiaoyan
2015-04-01
The binding characteristics and protective capacity of cyanidin (Cy) and cyanidin-3-glucoside (C3G) to calf thymus DNA were explored for the first time. The Cy and C3G gave a bathochromic shift to the ultraviolet-visible spectra of the DNA, indicating the formation of the DNA-Cy and DNA-C3G complexes. The complexes were formed by an intercalative binding mode based on the results of the fluorescence spectra and competitive binding analysis. Meanwhile, the Cy and C3G protected the DNA from the damage induced by the hydroxyl radical. The binding capacity and protective capacity of the C3G were stronger than that of the Cy. Furthermore, the formation of the DNA-anthocyanin complexes was spontaneous when the hydrogen bond and hydrophobic force played a key role. Hence, the Cy and C3G could protect the DNA automatically from the damage induced by the hydroxyl radical. © 2015 Institute of Food Technologists®
-
NASA Astrophysics Data System (ADS)
Chinnathambi, Shanmugavel; Karthikeyan, Subramani; Velmurugan, Devadasan; Hanagata, Nobutaka; Aruna, Prakasarao; Ganesan, Singaravelu
2015-04-01
In the present study, the interaction of 5-Fluorouracil with herring sperm DNA is reported using spectroscopic and molecular modeling techniques. This binding study of 5-FU with hs-DNA is of paramount importance in understanding chemico-biological interactions for drug design, pharmacy and biochemistry without altering the original structure. The challenge of the study was to find the exact binding mode of the drug 5-Fluorouracil with hs-DNA. From the absorption studies, a hyperchromic effect was observed for the herring sperm DNA in the presence of 5-Fluorouracil and a binding constant of 6.153 × 103 M-1 for 5-Fluorouracil reveals the existence of weak interaction between the 5-Fluorouracil and herring sperm DNA. Ethidium bromide loaded herring sperm DNA showed a quenching in the fluorescence intensity after the addition of 5-Fluorouracil. The binding constants for 5-Fluorouracil stranded DNA and competitive bindings of 5-FU interacting with DNA-EB systems were examined by fluorescence spectra. The Stern-Volmer plots and fluorescence lifetime results confirm the static quenching nature of the drug-DNA complex. The binding constant Kb was 2.5 × 104 L mol-1 and the number of binding sites are 1.17. The 5-FU on DNA system was calculated using double logarithmic plot. From the Forster nonradiative energy transfer study it has been found that the distance of 5-FU from DNA was 4.24 nm. In addition to the spectroscopic results, the molecular modeling studies also revealed the major groove binding as well as the partial intercalation mode of binding between the 5-Fluorouracil and herring sperm DNA. The binding energy and major groove binding as -6.04 kcal mol-1 and -6.31 kcal mol-1 were calculated from the modeling studies. All the testimonies manifested that binding modes between 5-Fluorouracil and DNA were evidenced to be groove binding and in partial intercalative mode.
-
Federal Register 2010, 2011, 2012, 2013, 2014
2010-07-08
... Washington State is to improve intercity passenger rail service by reducing travel times, achieving greater... intercity travel demand. To achieve these goals WSDOT applied for federal funding through the High Speed Intercity Passenger Rail Program (HSIPR Program) administered by the FRA and funded by the American Recovery...
-
Federal Register 2010, 2011, 2012, 2013, 2014
2012-08-17
... represents other transportation modes such as auto, air travel, intercity bus, and existing rail and the... well as making decisions regarding the level of intercity passenger rail service provided in the... growth of 139% between 2000 and 2008. Current intercity passenger rail service in Oregon includes two...
-
49 CFR 37.85 - Purchase or lease of new intercity and commuter rail cars.
Code of Federal Regulations, 2011 CFR
2011-10-01
... rail cars. 37.85 Section 37.85 Transportation Office of the Secretary of Transportation TRANSPORTATION....85 Purchase or lease of new intercity and commuter rail cars. Amtrak or a commuter authority making a solicitation after August 25, 1990, to purchase or lease a new intercity or commuter rail car for use on the...
-
49 CFR 37.85 - Purchase or lease of new intercity and commuter rail cars.
Code of Federal Regulations, 2013 CFR
2013-10-01
... rail cars. 37.85 Section 37.85 Transportation Office of the Secretary of Transportation TRANSPORTATION....85 Purchase or lease of new intercity and commuter rail cars. Amtrak or a commuter authority making a solicitation after August 25, 1990, to purchase or lease a new intercity or commuter rail car for use on the...
-
49 CFR 37.85 - Purchase or lease of new intercity and commuter rail cars.
Code of Federal Regulations, 2014 CFR
2014-10-01
... rail cars. 37.85 Section 37.85 Transportation Office of the Secretary of Transportation TRANSPORTATION....85 Purchase or lease of new intercity and commuter rail cars. Amtrak or a commuter authority making a solicitation after August 25, 1990, to purchase or lease a new intercity or commuter rail car for use on the...
-
49 CFR 37.85 - Purchase or lease of new intercity and commuter rail cars.
Code of Federal Regulations, 2012 CFR
2012-10-01
... rail cars. 37.85 Section 37.85 Transportation Office of the Secretary of Transportation TRANSPORTATION....85 Purchase or lease of new intercity and commuter rail cars. Amtrak or a commuter authority making a solicitation after August 25, 1990, to purchase or lease a new intercity or commuter rail car for use on the...
-
49 CFR 37.91 - Wheelchair locations and food service on intercity rail trains.
Code of Federal Regulations, 2011 CFR
2011-10-01
... on each train a number of spaces— (1) To park wheelchairs (to accommodate individuals who wish to... providing intercity rail service shall provide on each train a number of spaces— (1) To park wheelchairs (to... providing intercity rail service may not provide more than two spaces to park wheelchairs nor more than two...
-
Nový, Jakub; Urbanová, Marie
2007-03-01
The interactions of two different porphyrins, without axial ligands-5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin-Cu(II) tetrachloride (Cu(II)TMPyP) and with bulky meso substituents-5,10,15,20-tetrakis(N,N,N-trimethylanilinium-4-yl)porphyrin tetrachloride (TMAP), with (dG-dC)10 and (dA-dT)10 were studied by combination of vibrational circular dichroism (VCD) and electronic circular dichroism (ECD) spectroscopy at different [oligonucleotide]/[porphyrin] ratios, where [oligonucleotide] and [porphyrin] are the concentrations of oligonucleotide per base-pair and porphyrin, respectively. The combination of VCD and ECD spectroscopy enables us to identify the types of interactions, and to specify the sites of interactions: The intercalative binding mode of Cu(II)TMPyP with (dG-dC)(10), which has been well described, was characterized by a new VCD "marker" and it was shown that the interaction of Cu(II)TMPyP with (dA-dT)10 via external binding to the phosphate backbone and major groove binding caused transition from the B to the non-B conformer. TMAP interacted with the major groove of (dG-dC)10, was semi-intercalated into (dA-dT)10, and caused significant variation in the structure of both oligonucleotides at the higher concentration of porphyrin. The spectroscopic techniques used in this study revealed that porphyrin binding with AT sequences caused substantial variation of the DNA structure. It was shown that VCD spectroscopy is an effective tool for the conformational studies of nucleic acid-porphyrin complexes in solution. (c) 2007 Wiley Periodicals, Inc.
-
2010-04-30
5 Intercity Bus Security Grant Program...eligibility.22 This grant program includes funding for the Freight Rail Security Grant Program (FRSGP), and the Intercity Passenger Rail Program (IPR...eligible to receive funding to continue security enhancements for its intercity rail services between high-risk urban areas. 21 U.S. Department of
-
Shahabadi, Nahid; Mohammadi, Somaye
2012-01-01
A mononuclear complex of Zn(II), [Zn(DIP)2 (DMP)] (NO3)2 ·2H2O in which DIP is 4,7-diphenyl-1,10-phenanthroline and DMP is 4,4′-dimethyl-2,2′-bipyridine has been prepared and characterized by 1HNMR spectroscopy, FT-IR, UV-Vis and elemental analysis techniques. DNA-binding properties of the complex were studied using UV-vis spectra, circular dichroism (CD) spectra, fluorescence, cyclic voltammetry (CV), and viscosity measurements. The results indicate that this zinc(II) complex can intercalate into the stacked base pairs of DNA and compete with the strong intercalator ethidium bromide for the intercalative binding sites. PMID:22956919
-
NASA Astrophysics Data System (ADS)
Kalaiarasi, G.; Rex Jeya Rajkumar, S.; Aswini, G.; Dharani, S.; Fronczek, Frank R.; Prabhakaran, R.
2018-07-01
A series of 3-acetyl-8-methoxycoumarin appended thiosemicarbazones (1-4) was prepared from the reaction of 3-acetyl-8-methoxycoumarin with 4(N)-substituted thiosemicarbazides in a view of ascertaining their biological properties with the change of N-terminal substitution in the thiosemicarbazide moiety. Comprehensive characterization was brought about by various spectral and analytical methods. The molecular structures of all the compounds were determined by single crystal X-ray diffraction analysis. Binding studies with Calf thymus DNA (CT-DNA) and proteins such as Bovine Serum Albumin (BSA) and Human Serum Albumin (HSA) indicated an intercalative mode of binding with DNA and static quenching mechanism with proteins. The compounds cleaved plasmid DNA (pBR322) and acted well as free radical scavengers. A good spectrum of antimicrobial activity was observed against four bacterial and five fungal pathogens. The compounds exhibited profound antiproliferative activity on MCF-7 (human breast cancer) and A549 (human lung carcinoma) cell lines. Assay on human normal keratinocyte cell line HaCaT showed that the compounds were non-toxic to normal cells.
-
NASA Astrophysics Data System (ADS)
Mehta, Jugal V.; Gajera, Sanjay B.; Patel, Mohan N.
2015-02-01
The mononuclear copper(II) complexes with P, O-donor ligand and different fluoroquinolones have been synthesized and characterized by elemental analysis, electronic spectra, TGA, EPR, FT-IR and LC-MS spectroscopy. An antimicrobial efficiency of the complexes has been tested against five different microorganisms in terms of minimum inhibitory concentration (MIC) and displays very good antimicrobial activity. The binding strength and binding mode of the complexes with Herring Sperm DNA (HS DNA) have been investigated by absorption titration and viscosity measurement studies. The studies suggest the classical intercalative mode of DNA binding. Gel electrophoresis assay determines the ability of the complexes to cleave the supercoiled form of pUC19 DNA. Synthesized complexes have been tested for their SOD mimic activity using nonenzymatic NBT/NADH/PMS system and found to have good antioxidant activity. All the complexes show good cytotoxic and in vitro antimalarial activities.
-
Sun, Hui-Juan; Wang, Ai-Ling; Chu, Hai-Bin; Zhao, Yong-Liang
2015-03-01
Twelve lanthanide complexes with cinnamate (cin(-) ) and 1,10-phenanthroline (phen) were synthesized and characterized. Their compositions were assumed to be RE(cin)3 phen (RE(3+) = La(3+) , Pr(3+) , Nd(3+) , Sm(3+) , Eu(3+) , Gd(3+) , Tb(3+) , Dy(3+) , Ho(3+) , Tm(3+) , Yb(3+) , Lu(3+) ). The interaction mode between the complexes and DNA was investigated by fluorescence quenching experiment. The results indicated the complexes could bind to DNA and the main binding mode is intercalative binding. The fluorescence quenching constants of the complexes increased from La(cin)3 phen to Lu(cin)3 phen. Additionally, the antibacterial activity testing showed that the complexes exhibited excellent antibacterial ability against Escherichia coli, and the changes of antibacterial ability are in agreement with that of the fluorescence quenching constants. Copyright © 2014 John Wiley & Sons, Ltd.
-
NASA Astrophysics Data System (ADS)
Fu, Zheng; Cui, Yanrui; Cui, Fengling; Zhang, Guisheng
2016-01-01
A new anthraquinone derivative (AORha) was synthesized. Its interactions with human serum albumin (HSA) and calf thymus DNA (ctDNA) were investigated by fluorescence spectroscopy, UV-visible absorption spectroscopy and molecular modeling. Cell viability assay and cell imaging experiment were performed using cervical cancer cells (HepG2 cells). The fluorescence results revealed that the quenching mechanism was static quenching. At different temperatures (290, 300, 310 K), the binding constants (K) and the number of binding sites (n) were determined, respectively. The positive ΔH and ΔS values showed that the binding of AORha with HSA was hydrophobic force, which was identical with the molecular docking result. Studying the fluorescence spectra, UV spectra and molecular modeling also verified that the binding mode of AORha and ctDNA might be intercalative. When HepG2 cells were treated with AORha, the fluorescence became brighter and turned green, which could be used for bioimaging.
-
Fu, Zheng; Cui, Yanrui; Cui, Fengling; Zhang, Guisheng
2016-01-15
A new anthraquinone derivative (AORha) was synthesized. Its interactions with human serum albumin (HSA) and calf thymus DNA (ctDNA) were investigated by fluorescence spectroscopy, UV-visible absorption spectroscopy and molecular modeling. Cell viability assay and cell imaging experiment were performed using cervical cancer cells (HepG2 cells). The fluorescence results revealed that the quenching mechanism was static quenching. At different temperatures (290, 300, 310 K), the binding constants (K) and the number of binding sites (n) were determined, respectively. The positive ΔH and ΔS values showed that the binding of AORha with HSA was hydrophobic force, which was identical with the molecular docking result. Studying the fluorescence spectra, UV spectra and molecular modeling also verified that the binding mode of AORha and ctDNA might be intercalative. When HepG2 cells were treated with AORha, the fluorescence became brighter and turned green, which could be used for bioimaging. Copyright © 2015 Elsevier B.V. All rights reserved.
-
Technology assessment of future intercity passenger transportation systems. Volume 4: Scenarios
NASA Technical Reports Server (NTRS)
1976-01-01
Four background scenarios that relate to alternative states of society in the next 25 to 50 years are described. The scenarios were developed for use in analyzing and evaluating alternative future intercity transportation technologies. The scenarios are based, in part, on discussions contained in the issue papers and, in part, on separate analysis of social and economic trends considered relevant for the evolution of intercity transportation.
-
Banerjee, T; Banerjee, S; Sett, S; Ghosh, S; Rakshit, T; Mukhopadhyay, R
2016-01-01
DNA threading intercalators are a unique class of intercalating agents, albeit little biophysical information is available on their intercalative actions. Herein, the intercalative effects of nogalamycin, which is a naturally-occurring DNA threading intercalator, have been investigated by high-resolution atomic force microscopy (AFM) and spectroscopy (AFS). The results have been compared with those of the well-known chemotherapeutic drug daunomycin, which is a non-threading classical intercalator bearing structural similarity to nogalamycin. A comparative AFM assessment revealed a greater increase in DNA contour length over the entire incubation period of 48 h for nogalamycin treatment, whereas the contour length increase manifested faster in case of daunomycin. The elastic response of single DNA molecules to an externally applied force was investigated by the single molecule AFS approach. Characteristic mechanical fingerprints in the overstretching behaviour clearly distinguished the nogalamycin/daunomycin-treated dsDNA from untreated dsDNA-the former appearing less elastic than the latter, and the nogalamycin-treated DNA distinguished from the daunomycin-treated DNA-the classically intercalated dsDNA appearing the least elastic. A single molecule AFS-based discrimination of threading intercalation from the classical type is being reported for the first time.
-
Sett, S.; Ghosh, S.; Rakshit, T.; Mukhopadhyay, R.
2016-01-01
DNA threading intercalators are a unique class of intercalating agents, albeit little biophysical information is available on their intercalative actions. Herein, the intercalative effects of nogalamycin, which is a naturally-occurring DNA threading intercalator, have been investigated by high-resolution atomic force microscopy (AFM) and spectroscopy (AFS). The results have been compared with those of the well-known chemotherapeutic drug daunomycin, which is a non-threading classical intercalator bearing structural similarity to nogalamycin. A comparative AFM assessment revealed a greater increase in DNA contour length over the entire incubation period of 48 h for nogalamycin treatment, whereas the contour length increase manifested faster in case of daunomycin. The elastic response of single DNA molecules to an externally applied force was investigated by the single molecule AFS approach. Characteristic mechanical fingerprints in the overstretching behaviour clearly distinguished the nogalamycin/daunomycin-treated dsDNA from untreated dsDNA—the former appearing less elastic than the latter, and the nogalamycin-treated DNA distinguished from the daunomycin-treated DNA—the classically intercalated dsDNA appearing the least elastic. A single molecule AFS-based discrimination of threading intercalation from the classical type is being reported for the first time. PMID:27183010
-
49 CFR Appendix A to Part 37 - Modifications to Standards for Accessible Transportation Facilities
Code of Federal Regulations, 2010 CFR
2010-10-01
... steps may have to travel compared to the general public. 406.8—Modification to 406 of Appendix D to 36... rail, commuter rail, and intercity rail systems where it is not operationally or structurally feasible...
-
A structural survey of classes of vehicles for crashworthiness : final report.
DOT National Transportation Integrated Search
1978-02-01
This document reviews three phases of a study conducted to evaluate and improve the crashworthiness of passenger carrying vehicles in intercity service. Phase I surveyed the accident data over a period 1966 to 1973 and identified those areas responsi...
-
Umadevi, C; Kalaivani, P; Puschmann, H; Murugan, S; Mohan, P S; Prabhakaran, R
2017-02-01
A series of new water soluble nickel(II) complexes containing triphenylphosphine and 4-methoxysalicylaldehyde-4(N)-substituted thiosemicarbazones were synthesized and characterized. Crystallographic investigations confirmed the structure of the complexes (1-4) having the general structure [Ni(4-Msal-Rtsc)(PPh 3 )] (Where R=H (1); CH 3 (2); C 2 H 5 (3); C 6 H 5 (4)) which showed that thiosemicarbazone ligands coordinated to nickel(II) ion as ONS tridentate bibasic donor. DNA/BSA protein binding ability of the ligands and their new complexes were studied by taking calf-thymus DNA (CT-DNA) and Bovine serum albumin (BSA) through absorption and emission titrations. Ethidium bromide (EB) displacement study showed the intercalative binding trend of the complexes to DNA. From the albumin binding studies, the mechanism of quenching was found as static and the alterations in the secondary structure of BSA by the compounds were confirmed with synchronous spectral studies. The binding affinity of the complexes to CT-DNA and BSA has the order of [Ni(4-Msal-etsc)(PPh 3 )] (3) >[Ni(4-Msal-mtsc)(PPh 3 )] (2) >[Ni(4-Msal-tsc)(PPh 3 )] (1) >[Ni(4-Msal-ptsc)(PPh 3 )] (4). In vitro cytotoxicity of the complexes was tested on human lung cancer cells (A549), human cervical cancer cells (HeLa), human liver carcinoma cells (Hep G2). All the complexes exhibited significant activity against three cancer cells. Among them, complex 4 exhibited almost 2.5 fold activity than cisplatin in A549 and HepG2 cell lines. In HeLa cell line, the complexes exhibited significant activity which is less than cisplatin. While comparing the activity of the complexes in A549 and HepG2 cell lines it falls in the order 4>1>2>3>cisplatin. The results obtained from DNA, protein binding and cytotoxicity studies, it is concluded that the cytotoxicity of the complexes as determined by MTT assay were not unduly influenced by the complexes having different binding efficiency with DNA and protein. The complexes exhibited good spectrum of antibacterial activity against four pathogenic bacteria such as E. faecalis (gram +ve), S. aureus (gram +ve), E. coli (gram -ve) and P. aeruginosa (gram -ve). Copyright © 2016 Elsevier B.V. All rights reserved.
-
Zhao, Ping; Xu, Lian-Cai; Huang, Jin-Wang; Liu, Jie; Yu, Han-Cheng; Zheng, Kang-Cheng; Ji, Liang-Nian
2008-12-15
The DNA-binding affinities and DNA photocleavage abilities of cationic porphyrin, 5-(4-carboxyphenyl)-10,15,20-tris(4-methylpyridiniumyl)porphyrin (CTMPyP), and its reference compound meso-tetrakis(N-methyl-4-pyridiniumyl)porphyrin (H2TMPyP) have been investigated. The DNA-binding behaviors of the two compounds in NaH2PO4 buffer were compared systematically by using absorption, fluorescence and circular dichroism (CD) spectra, thermal denaturation as well as viscosity measurements. The experimental results show that CTMPyP binds to DNA in an outside binding mode, while H2TMPyP in an intercalative mode. Photocleavage experiments reveal that both two compounds employ 1O2-mediated mechanism in cleaving DNA and H2TMPyP can cleave DNA more efficiently than CTMPyP. Theoretical calculations were carried out with the density functional theory (DFT), and the calculated results indicate that the character and energies of some frontier orbitals of CTMPyP are quite different from those of H2TMPyP. These theoretical results can be used to explain their different DNA-binding modes and affinities to a certain extent.
-
Wang, Gongke; Li, Xiangrong; Gou, Yaping; Chen, Yuhan; Yan, Changling; Lu, Yan
2013-10-01
The binding properties of two medicinally important dihydropyrimidinones derivatives 5-(Ethoxycarbonyl)-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one (EMPD) and 5-(Ethoxycarbonyl)-6-methyl-4-(4-chlorophenyl)-3,4-dihydropyrimidin-2(1H)-one (EMCD) with calf-thymus DNA (ctDNA) were investigated by spectroscopy, viscosity, isothermal titration calorimetry (ITC) and molecular modeling techniques. Simultaneously, their biological activities were evaluated with MTT assay method. The binding constants determined with spectroscopic titration and ITC were found to be in the same order of 10(4)M(-1). According to the results of viscosity studies, fluorescence competitive binding experiment and ITC investigations, intercalative binding was evaluated as the dominant binding modes between the two compounds and ctDNA. Furthermore, the results of molecular modeling corroborated those obtained from spectroscopic, viscosimetric and ITC investigations. Evaluation of the antitumor activities of the two derivatives against different tumor cell lines proved that they exhibited significant tumor cell inhibition rate, accordingly blocking DNA transcription and replication. The present results favor the development of potential drugs related with dihydropyrimidinones derivatives in the treatment of some diseases. Copyright © 2013 Elsevier B.V. All rights reserved.
-
In vitro DNA binding studies of Aspartame, an artificial sweetener.
Kashanian, Soheila; Khodaei, Mohammad Mehdi; Kheirdoosh, Fahimeh
2013-03-05
A number of small molecules bind directly and selectively to DNA, by inhibiting replication, transcription or topoisomerase activity. In this work the interaction of native calf thymus DNA (CT-DNA) with Aspartame (APM), an artificial sweeteners was studied at physiological pH. DNA binding study of APM is useful to understand APM-DNA interaction mechanism and to provide guidance for the application and design of new and safer artificial sweeteners. The interaction was investigated using spectrophotometric, spectrofluorometric competition experiment and circular dichroism (CD). Hypochromism and red shift are shown in UV absorption band of APM. A strong fluorescence quenching reaction of DNA to APM was observed and the binding constants (Kf) of DNA with APM and corresponding number of binding sites (n) were calculated at different temperatures. Thermodynamic parameters, enthalpy changes (ΔH) and entropy changes (ΔS) were calculated to be +181kJmol(-1) and +681Jmol(-1)K(-1) according to Van't Hoff equation, which indicated that reaction is predominantly entropically driven. Moreover, spectrofluorometric competition experiment and circular dichroism (CD) results are indicative of non-intercalative DNA binding nature of APM. We suggest that APM interacts with calf thymus DNA via groove binding mode with an intrinsic binding constant of 5×10(+4)M(-1). Copyright © 2013 Elsevier B.V. All rights reserved.
-
75 FR 16552 - High-Speed Intercity Passenger Rail (HSIPR) Program
Federal Register 2010, 2011, 2012, 2013, 2014
2010-04-01
..., energy savings from traffic diversions from other modes, employment of green building and manufacturing... selections for the High-Speed Intercity Passenger Rail (HSIPR) Program. This notice builds on the program...
-
NASA Technical Reports Server (NTRS)
1976-01-01
Proceedings of a workshop conducted to identify and debate issues and impacts related to future transporation alternatives are presented. Results of the technology assessment of intercity transportation are reviewed.
-
Intercity Passenger Parametric Analysis: Overview: Maglev Analysis
DOT National Transportation Integrated Search
1990-04-02
This document provides information intended to clarify consideration of some of the technically-based questions which arise in connection with intercity passenger transportation, and to provide insight into the characteristics and potential roles o...
-
Occupational exposure to whole body vibration-train drivers.
Birlik, Gülin
2009-01-01
Whole body vibration exposure of the train drivers working for State Railway Lines is assessed by referring to ISO standard 2631 -1 and EU directive 2002/44/EC. The vibration measurements were done in the cabins of suburban and intercity train drivers. Suburban train driver performs his job usually in standing posture. Whereas intercity train driver works generally in seated (bending forward) posture and exposed to longer periods of continuous vibration, compared to suburban train drivers. The mean accelerations, a, along lateral, y, and vertical, z, directions measured on the driver seat (on the cabin floor) of the intercity (suburban) train were 1.4a (y) = 0.55 (0.28) m/s(2) and a (z) = 0.65 (0.23) m/s(2). Daily exposure action values suggested in EU directive are exceeded in case of intercity train drivers and their exposure falls within the health caution zone of ISO 2631-1. Intercity train drivers are therefore under the risk of having spinal disorders. A health surveillance plan requiring every five years the reassessment of the state of the spinal system of train drivers is suggested. As an early preventive measure, extended work day or more than one shift in a day is advised to be discouraged.
-
Intercity Bus Feeder Project Program Analysis
DOT National Transportation Integrated Search
1990-09-01
Following the passage of the Bus Regualtory Reform Act of 1982 (BRRA), intercity : carriers used their increased regulatory flexibility to discontinue many : underutilized rural and small city services. This was understandable, in light : of the comp...
-
Michigan transportation facts & figures : public transportation
DOT National Transportation Integrated Search
2002-08-16
This on-line document is part of a series, Transportation Facts & Figures, by the Michigan Department of Transportation (MDOT). The Public Transit section of Transportation Facts & Figures cover such topics as intercity bus service, intercity rail se...
-
Energy intensity of intercity passenger rail.
DOT National Transportation Integrated Search
1977-12-01
This research report deals with the Energy Intensity of Intercity Rail Passenger : Systems. Included in the energy evaluation are the impacts of operating conditions : (speed, load factor) and train consists. The report also documents an : extensive ...
-
García, Begoña; Leal, José M; Paiotta, Vittorio; Ruiz, Rebeca; Secco, Fernando; Venturini, Marcella
2008-06-12
The interactions of triple strands of poly(rA).2poly(rU) with proflavine (PR) and the proflavine cis-platinum derivative [{PtCl (tmen)} 2{NC 13H 7(NCH 2CH 2) 2}] (+) (PRPt) are examined at pH 7.0, T = 25 degrees C, and 0.2 M ionic strength by spectrophotometry, spectrofluorometry, circular dichroism, viscosimetry, stopped-flow, and T-jump relaxation techniques. The melting experiments demonstrate that both drugs tend to destabilize the triplex structure, although the PRPt effect is more relevant. By contrast, both drugs tend to slightly stabilize the duplex structure. The viscosity and circular dichroism measurements show that, at a low dye-to-polymer ratio ( C D/ C P), the binding is intercalative, whereas at high C D/ C P values, the external binding dominates. The binding kinetics and equilibria have been investigated over the C D/ C P region, where intercalation is operative. Both drugs bind to the RNA triplex according to the excluded site model. With PR, two kinetic effects have been observed, whereas with PRPt, only one has been observed. The results are interpreted according to the reaction schemes D + S right arrow over left arrow DS I, with PRPt, and D + S right arrow over left arrow DS I right arrow over left arrow DS II, with PR. The electrostatic contribution to the formation activation energy for DS I is similar (40%) for both systems. The results suggest that DS I is a partially intercalated species. Absence of the second step with PRPt is put down to groove interaction of the Pt-containing moiety, which prevents the PR residue from further penetration through the base pairs to form the fully intercalated complex, DS II. Comparison with the binding of the same drugs to the duplex reveals that the occupation of the major groove in poly(rA).2poly(rU) by the third strand plays a critical role in the kinetic behavior.
-
NASA Technical Reports Server (NTRS)
1976-01-01
Research and analysis tasks to alleviate negative impacts, to augment positive impacts, or to better understand the impacts produced by the potential introduction of the alternate transportation technologies are identified. The project team's recommendations on research and analysis efforts which have resulted from the technology assessment are provided. Many of the recommendations apply to the future supply of intercity passenger transportation services, categorized by mode. Other recommendations pertain to broad issues in intercity transportation--e.g., finance, regulation, traveler values--that will affect all modes.
-
Performance Analyses of Intercity Ground Passenger Transportation Systems
DOT National Transportation Integrated Search
1976-04-01
This report documents the development of analytical techniques and their use for investigating the performance of intercity ground passenger transportation systems. The purpose of the study is twofold: (1) to provide a capability of evaluating new pa...
-
90-94 ITS Intercity Corridor Study - Strategic Deployment Plan
DOT National Transportation Integrated Search
1996-12-01
PUBLIC-PRIVATE PARTNERSHIP, COMMERCIAL VEHICLES OPERATIONS OR CVO : THE IH 90/94 ITS INTERCITY CORRIDOR STRATEGIC DEPLOYMENT PLAN IS AN APPROACH FOR IMPLEMENTING INTELLIGENT TRANSPORTATION SYSTEMS (ITS) IN THE IH 90/94 CORRIDORS THAT TRAVERSE THE ...
-
Many intercity travelers face longer travel schedules
DOT National Transportation Integrated Search
2003-10-01
Since 1995, scheduled travel times for direct : intercity air, bus, and rail service without an en : route transfer have measurably lengthened in : most major-market city-pairs. : Long-haul rail city-pairs affected by service : changes and short-...
-
Intercity passenger rail : prospects for Amtrak's financial viability
DOT National Transportation Integrated Search
1998-06-01
Since it began operations in 1971, the National Railroad Passenger Corporation (AmtraK0 has never been profitable and has received about $21 billion in federal subsidies for operating and capital expenses. Amtrak currently provides intercity passenge...
-
Ghimire, Srijana; Fanwick, Phillip E; McMillin, David R
2014-10-20
This investigation explores DNA-binding interactions of various forms of an alkyl-substituted cationic porphyrin, H2TC3 (5,10,15,20-tetra[3-(3'-methylimidazolium-1'-yl)]porphyrin). The motivating idea is that incorporating alkyl rather than aryl substituents in the meso positions will enhance the prospects for intercalative as well as external binding to DNA hosts. The ligands may also be applicable for photodynamic and/or anticancer therapy. Methods employed include absorbance, circular dichroism, and emission spectroscopies, as well as viscometry and X-ray crystallography. By comparison with the classical H2T4 system, H2TC3 exhibits a higher molar extinction coefficient but is more prone to self-association. Findings of note include that the copper(II)-containing form Cu(TC3) is adept at internalizing into single-stranded as well as B-form DNA, regardless of the base composition. Surprisingly, however, external binding of H2TC3 occurs within domains that are rich in adenine-thymine base pairs. The difference in the deformability of H2TC3 versus Cu(TC3) probably accounts for the reactivity difference. Finally, Zn(TC3) binds externally, as the metal center remains five-coordinate.
-
Comprehensive Study of Intercity Bus Service in Nebraska
DOT National Transportation Integrated Search
1988-03-01
This study is prompted by the proposed abandonment of regular-route intercity : bus service across northern Nebraska. The current route, which is operated by : Black Hills Stage Lines, provides service from Omaha through Norfolk and Chadron : to Rapi...
-
Intercity passenger rail : Congress faces critical decisions in developing a national policy
DOT National Transportation Integrated Search
2002-04-11
This document is the statement of JayEtta Z. Hecker, Director, Physical Infrastructure. Testimony before the Subcommittee on Railroads, Committee on Transportation and Infrastructure, House of Representatives on the future of intercity passenger rail...
-
Montana intercity bus service study.
DOT National Transportation Integrated Search
2011-12-01
Intercity bus service funding from the Federal Transit Administration (FTAs) Section 5311(f) program is a part : of the larger 5311 program known as Formula Grants for Other than Urbanized Areas. The S.5311(f), requires : that 15% of the total 531...
-
High-speed and intercity passenger rail testing strategy.
DOT National Transportation Integrated Search
2013-05-01
This high-speed and intercity passenger rail (HSIPR) testing strategy addresses the requirements for testing of high-speed train sets and technology before introduction to the North American railroad system. The report documents the results of a surv...
-
29 CFR 1982.101 - Definitions.
Code of Federal Regulations, 2011 CFR
2011-07-01
... include school buses, charter, or intercity bus transportation or intercity passenger rail transportation... transportation systems that connect metropolitan areas, without regard to whether those systems use new technologies not associated with traditional railroads, but does not include rapid transit operations in an...
-
Scheduled intercity transportation : rural service areas in the United States
DOT National Transportation Integrated Search
2005-06-01
To identify how many of the countrys 82.4 million rural residents are within the reasonable coverage radius of at least one intercity transportation facility, in 2003 the Bureau of Transportation Statistics (BTS) undertook a geospatial analysis us...
-
Commuter-Intercity Rail Improvement Study (Boston-New York)
DOT National Transportation Integrated Search
1993-05-01
This study was carried out under the direction of a departmental task force. The 226 page report identifies and characterizes the costs and benefits of improvements that could be achieved in commuter and intercity rail passenger service on the Boston...
-
Intercity travel in northeastern rural regions of the U.S.
DOT National Transportation Integrated Search
2015-06-01
Much research exists on intercity travel behavior between large metropolitan centers. : There is an opportunity for more research on travel from less populated areas to large : metropolitan ones. When planning a trip from Northern New England to majo...
-
Effects of the Ride Environment on Passenger Activities : A Field Study on Intercity Trains
DOT National Transportation Integrated Search
1979-01-01
A three-part field study of passenger activities (e.g. reading, writing, talking, sleeping) was conducted on intercity Amtrak trains in the northeastern United States to determine the relationships between the ride environment, subjective passenger c...
-
Intercity bus service study 2014.
DOT National Transportation Integrated Search
2015-02-01
Rural transit programs are funded with 5311 funds, named for their description in Section 5311 of United States : Code (49 USC S5311). In Alabama, 15% of 5311 funds are set aside to be spent on improving intercity bus : service through the 5311(f) pr...
-
The effects of the ride environment on passenger activities : a field study on intercity trains
DOT National Transportation Integrated Search
1979-01-01
A three-part field study of passenger activities (e.g. reading, writing, talking, sleeping) was conducted on intercity Amtrak trains in the northeastern United States to determine the relationships between the ride environment, subjective passenger c...
-
Productivity Trends in Intercity Trucking
ERIC Educational Resources Information Center
Carnes, Richard B.
1974-01-01
Productivity trends indicate intercity trucking productivity increased an average 2.7 percent a year, a fairly uniform increased productivity rate but substantially lower as compared to air carrier, railroad, and pipeline transportation. Factors affecting productivity are gradual introduction of technological innovation, larger capacity trucks,…
-
Public transportation and intercity rail passenger plan for Washington state 1997-2016
DOT National Transportation Integrated Search
1996-12-01
The Public Transportation and Intercity Rail Passenger Plan for Washington : State is a 20-year plan for preserving our current public transportation systems : while improving mobility for a growing population. The plan builds toward a : future in wh...
-
Reconnecting Rural America. Report on Rural Intercity Passenger Transportation.
ERIC Educational Resources Information Center
Stommes, Eileen S.
This report summarizes the results of three regional symposia held during 1987-88 to gather grassroots information about rural passenger transportation needs across the country. The first section describes the structural transformation of rural America in the 1980s: (1) the rural economy; (2) rural population trends; (3) impact of information…
-
Mansouri-Torshizi, Hassan; Saeidifar, Maryam; Khosravi, Fatemeh; Divsalar, Adeleh; Saboury, Ali Akbar; Hassani, Fatemeh
2011-01-01
The two water-soluble designed platinum(II) complex, [Pt(Oct-dtc)(bpy)]NO3 (Oct-dtc = Octyldithiocarbamate and bpy = 2,2′ -bipyridine) and palladium(II) complex, [Pd(Oct-dtc)(bpy)]NO3, have been synthesized and characterized by elemental analyses, molar conductivity measurements, IR, 1H NMR, and electronic spectra studies. Studies of antitumor activity of these complexes against human cell tumor lines (K562) have been carried out. They show Ic50 values lower than that of cisplatin. The complexes have been investigated for their interaction with calf thymus DNA (CT-DNA) by utilizing the electronic absorption spectroscopy, fluorescence spectra, and ethidium bromide displacement and gel filtration techniques. Both of these water-soluble complexes bound cooperatively and intercalatively to the CT-DNA at very low concentrations. Several binding and thermodynamic parameters are also described. PMID:22110410
-
Ajloo, Davood; Shabanpanah, Sajede; Shafaatian, Bita; Ghadamgahi, Maryam; Alipour, Yasin; Lashgarbolouki, Taghi; Saboury, Ali Akbar
2015-01-01
Interaction of 1,3-bis(2-hydroxy-benzylidene)-urea (H2L1), 1,3-bis(2-hydroxy-3-methoxy-benzylidene)-urea (H2L2) and 1,3-bis(2-hydroxy-3-methoxy-benzylidene)-urea nickel(II) (NiL2) with calf-thymus DNA were investigated by UV-vis absorption, fluorescence emission and circular dichroism (CD) spectroscopy as well as cyclic voltammetry, viscosity measurements, molecular docking and molecular dynamics simulation. Binding constants were determined using UV-vis absorption and fluorescence spectra. The results indicated that studied Schiff-bases bind to DNA in the intercalative mode in which the metal derivative is more effective than non metals. Their interaction trend is further determined by molecular dynamics (MD) simulation. MD results showed that Ni derivative reduces oligonucleotide intermolecular hydrogen bond and increases solvent accessible surface area more than other compounds. Copyright © 2015 Elsevier B.V. All rights reserved.
-
DOT National Transportation Integrated Search
2009-03-01
This product summarizes the preliminary concept and priority corridors for development of a potential : statewide intercity bus and rail network. The concept is based upon the results of Tasks 1 through 5 of Texas : Department of Transportation Proje...
-
DOT National Transportation Integrated Search
2002-04-01
The National Railroad Passenger Corporation (Amtrak) is the nation's intercity passenger rail operator. In recent years, facing the continuing deterioration of its financial condition and its attempt to eliminate its need for federal operating assist...
-
Potential development of an intercity passenger transit system in Texas : final project report.
DOT National Transportation Integrated Search
2010-05-01
This report describes the findings of a research study of the potential for development of an intercity rail and : express bus system in the state of Texas. Rather than focus on regional commuter or light rail systems : radiating from urban areas, th...
-
47 CFR 74.537 - Temporary authorizations.
Code of Federal Regulations, 2011 CFR
2011-10-01
..., AUXILIARY, SPECIAL BROADCAST AND OTHER PROGRAM DISTRIBUTIONAL SERVICES Aural Broadcast Auxiliary Stations... STL or intercity relay station operation which cannot be conducted in accordance with § 74.24. Such... intercity relay station must be made in accordance with the procedures of § 1.931(b) of this chapter. (c...
-
47 CFR 74.537 - Temporary authorizations.
Code of Federal Regulations, 2013 CFR
2013-10-01
..., AUXILIARY, SPECIAL BROADCAST AND OTHER PROGRAM DISTRIBUTIONAL SERVICES Aural Broadcast Auxiliary Stations... STL or intercity relay station operation which cannot be conducted in accordance with § 74.24. Such... intercity relay station must be made in accordance with the procedures of § 1.931(b) of this chapter. (c...
-
47 CFR 74.537 - Temporary authorizations.
Code of Federal Regulations, 2014 CFR
2014-10-01
..., AUXILIARY, SPECIAL BROADCAST AND OTHER PROGRAM DISTRIBUTIONAL SERVICES Aural Broadcast Auxiliary Stations... STL or intercity relay station operation which cannot be conducted in accordance with § 74.24. Such... intercity relay station must be made in accordance with the procedures of § 1.931(b) of this chapter. (c...
-
DOT National Transportation Integrated Search
1975-11-01
The effect of speed limit and passenger load on fuel consumption was determined using actual intercity buses with simulated passenger loads over different types of terrain. In addition to road tests, laboratory type measurements were made on four int...
-
Potential development of an intercity passenger transit system in Texas : report on tasks 1-5.
DOT National Transportation Integrated Search
2009-11-01
This report summarizes the results of Tasks 1 through 5 of TxDOT Research Project 0-5930: Potential : Development of an Intercity Passenger Transit System in Texas. Rather than focus on any regional : commuter or light rail systems within or radiatin...
-
49 CFR 38.125 - Mobility aid accessibility.
Code of Federal Regulations, 2012 CFR
2012-10-01
... mechanical, electrical or other system operates to ensure that cars do not move when the lift is in use. (3... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Intercity Rail Cars and Systems § 38.125 Mobility aid accessibility. (a)(1) General. All intercity rail cars, other than level entry cars, required to be accessible by...
-
49 CFR 38.125 - Mobility aid accessibility.
Code of Federal Regulations, 2013 CFR
2013-10-01
... mechanical, electrical or other system operates to ensure that cars do not move when the lift is in use. (3... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Intercity Rail Cars and Systems § 38.125 Mobility aid accessibility. (a)(1) General. All intercity rail cars, other than level entry cars, required to be accessible by...
-
49 CFR 38.125 - Mobility aid accessibility.
Code of Federal Regulations, 2014 CFR
2014-10-01
... mechanical, electrical or other system operates to ensure that cars do not move when the lift is in use. (3... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Intercity Rail Cars and Systems § 38.125 Mobility aid accessibility. (a)(1) General. All intercity rail cars, other than level entry cars, required to be accessible by...
-
47 CFR 74.532 - Licensing requirements.
Code of Federal Regulations, 2010 CFR
2010-10-01
... § 74.532 Licensing requirements. (a) An aural broadcast STL or an aural broadcast intercity relay... booster stations. Aural auxiliary stations licensed to low power FM stations will be assigned on a.... (b) More than one aural broadcast STL or intercity relay station may be licensed to a single licensee...
-
47 CFR 74.532 - Licensing requirements.
Code of Federal Regulations, 2013 CFR
2013-10-01
... § 74.532 Licensing requirements. (a) An aural broadcast STL or an aural broadcast intercity relay... booster stations. Aural auxiliary stations licensed to low power FM stations will be assigned on a.... (b) More than one aural broadcast STL or intercity relay station may be licensed to a single licensee...
-
47 CFR 74.532 - Licensing requirements.
Code of Federal Regulations, 2012 CFR
2012-10-01
... § 74.532 Licensing requirements. (a) An aural broadcast STL or an aural broadcast intercity relay... booster stations. Aural auxiliary stations licensed to low power FM stations will be assigned on a.... (b) More than one aural broadcast STL or intercity relay station may be licensed to a single licensee...
-
47 CFR 74.532 - Licensing requirements.
Code of Federal Regulations, 2011 CFR
2011-10-01
... § 74.532 Licensing requirements. (a) An aural broadcast STL or an aural broadcast intercity relay... booster stations. Aural auxiliary stations licensed to low power FM stations will be assigned on a.... (b) More than one aural broadcast STL or intercity relay station may be licensed to a single licensee...
-
47 CFR 74.532 - Licensing requirements.
Code of Federal Regulations, 2014 CFR
2014-10-01
... § 74.532 Licensing requirements. (a) An aural broadcast STL or an aural broadcast intercity relay... booster stations. Aural auxiliary stations licensed to low power FM stations will be assigned on a.... (b) More than one aural broadcast STL or intercity relay station may be licensed to a single licensee...
-
DOT National Transportation Integrated Search
1996-06-01
This study evaluated the full cost of three modes of intercity transportation: air, highway, and high speed rail. The evaluation is done within the context of the California Corridor, connecting the Los Angeles Basin and the San Francisco Bay Area. T...
-
49 CFR 38.125 - Mobility aid accessibility.
Code of Federal Regulations, 2010 CFR
2010-10-01
... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Intercity Rail Cars and Systems § 38.125 Mobility aid accessibility. (a)(1) General. All intercity rail cars, other than level entry cars, required to be accessible by... to be accessible, or mini-high platforms complying with § 38.113(d) are provided, the car is not...
-
DNA interaction, antioxidant activity, and bioactivity studies of two ruthenium(II) complexes
NASA Astrophysics Data System (ADS)
Han, Bing-Jie; Jiang, Guang-Bin; Yao, Jun-Hua; Li, Wei; Wang, Ji; Huang, Hong-Liang; Liu, Yun-Jun
2015-01-01
Two new ruthenium(II) polypyridyl complexes [Ru(dmb)2(dcdppz)](ClO4)2 (1) and [Ru(bpy)2(dcdppz)](ClO4)2 (2) were prepared and characterized. The crystal structure of the complex 2 was solved by single crystal X-ray diffraction. The complex crystallizes in the monoclinic system, space group P21/n with a = 12.9622(14) Å, b = 17.1619(19) Å, c = 22.7210(3) Å, β = 100.930(2)°, R = 0.0536, Rω = 0.1111. The DNA-binding constants for complexes 1 and 2 were determined to be 1.92 × 105 (s = 1.72) and 2.24 × 105 (s = 1.86) M-1, respectively. The DNA-binding behaviors showed that complexes 1 and 2 interact with DNA by intercalative mode. The antioxidant activities of the ligand and the complexes were performed. Ligand, dcdppz, has no cytotoxicity against the selected cell lines. Complex 1 shows higher cytotoxicity than complex 2, but lower than cisplatin toward selected cell lines. The apoptosis and cell cycle arrest were investigated, and the apoptotic mechanism of BEL-7402 cells was studied by reactive oxygen species (ROS), mitochondrial membrane potential and western blot analysis. Complex 1 induces apoptosis in BEL-7402 cells through ROS-mediated mitochondrial dysfunction pathway and by regulating the expression of Bcl-2 family proteins.
-
Barut, Burak; Sofuoğlu, Ayşenur; Biyiklioglu, Zekeriya; Özel, Arzu
2016-09-28
In this study, [2-(2-morpholin-4-ylethoxy)ethoxy] group substituted zinc(ii), manganese(iii) and copper(ii) phthalocyanines 2-4 and their water soluble derivatives 2a, 3a and 4a were synthesized and the interactions of compounds 2a, 3a and 4a with CT-DNA and supercoiled pBR322 plasmid DNA were investigated. The results of binding experiments showed that these compounds were able to interact with CT-DNA via intercalative mode with a strong binding affinity in the order 3a > 2a > 4a. DNA-photocleavage activities of compounds 2a, 3a and 4a were determined. These compounds cleaved supercoiled pBR322 plasmid DNA efficiently under irradiation at 650 nm for 2a and 4a, and at 750 nm for 3a. These compounds displayed remarkable inhibitory activities against topoisomerase I enzyme in a dose-dependent manner. All of these results suggest that these phthalocyanines might be suitable anticancer agents due to their strong binding affinities, significant cleavage activities and effective topoisomerase I inhibition.
-
NASA Astrophysics Data System (ADS)
Hosny, Nasser Mohammed; Hussien, Mostafa A.; Radwan, Fatima M.; Nawar, Nagwa
2014-11-01
Four new metal complexes derived from the reaction of Cu(II), Co(II), Ni(II) and Zn(II) acetates with the Schiff-base ligand (H3L) resulted from the condensation of the amino acid 2-amino-3-hydroxyprobanoic acid (serine) and acetylacetone have been synthesized and characterized by, elemental analyses, ES-MS, IR, UV-Vis., 1H NMR, 13C NMR, ESR, thermal analyses (TGA and DTG) and magnetic measurements. The results showed that the Schiff-base ligand acts as bi-negative tridentate through the azomethine nitrogen, the deprotonated carboxylate oxygen and the enolic carbonyl oxygen. The optical band gaps measurements indicated the semi-conducting nature of these complexes. Molecular docking was used to predict the binding between the Schiff base ligand with the receptor of prostate cancer mutant H874Y. The interactions between the Cu(II) complex and calf thymus DNA (CT-DNA) have been studied by UV spectra. The results confirm that the Cu(II) complex binds to CT-DNA in an intercalative mode.
-
Effects of urban growth controls on intercity commuting.
Ogura, Laudo M
2010-01-01
This paper presents an empirical study of the effects of urban growth controls on the intercity commuting of workers. Growth controls (land use regulations that attempt to restrict population growth and urban sprawl) have increased housing prices and diverted population growth to uncontrolled cities. It has been suggested that resulting changes in local labour supply might stimulate intercity commuting from uncontrolled to controlled cities. To test this hypothesis, a gravity model of commuting flows between places in California is estimated using alternative econometric methods (OLS, Heckman selection and count-data). The possibility of spatial dependence in commuting flows is also taken into consideration. Results suggest larger commuting flows to destination places that restrict residential growth.
-
DOT National Transportation Integrated Search
2017-12-01
Passenger rail is an integral part of intercity transportation networks, especially in areas where residents do not have access to a car or there are not any other options for intercity travel. The Hoosier State Train (HST) line connects five station...
-
DOT National Transportation Integrated Search
1980-01-01
This report describes an evaluation of the effect on intercity bus ridership of changes in frequency of service and cost. The study was based on a comparison of travel between 19 selected cities in Virginia served by air, bus, or rail. These modes we...
-
49 CFR 238.15 - Movement of passenger equipment with power brake defects.
Code of Federal Regulations, 2010 CFR
2010-10-01
... brakes; (C) Piston travel that is in excess of the Class I brake test limits required in § 238.313 but... where the necessary repairs can be made. (3) Commuter, short-distance intercity, and short-distance Tier... brakes. Commuter, short-distance intercity, and short-distance Tier II passenger trains which develop...
-
49 CFR 37.87 - Purchase or lease of used intercity and commuter rail cars.
Code of Federal Regulations, 2010 CFR
2010-10-01
... rail cars. 37.87 Section 37.87 Transportation Office of the Secretary of Transportation TRANSPORTATION....87 Purchase or lease of used intercity and commuter rail cars. (a) Except as provided elsewhere in... car after August 25, 1990, shall ensure that the car is readily accessible to and usable by...
-
49 CFR 37.87 - Purchase or lease of used intercity and commuter rail cars.
Code of Federal Regulations, 2014 CFR
2014-10-01
... rail cars. 37.87 Section 37.87 Transportation Office of the Secretary of Transportation TRANSPORTATION....87 Purchase or lease of used intercity and commuter rail cars. (a) Except as provided elsewhere in... car after August 25, 1990, shall ensure that the car is readily accessible to and usable by...
-
49 CFR 37.87 - Purchase or lease of used intercity and commuter rail cars.
Code of Federal Regulations, 2012 CFR
2012-10-01
... rail cars. 37.87 Section 37.87 Transportation Office of the Secretary of Transportation TRANSPORTATION....87 Purchase or lease of used intercity and commuter rail cars. (a) Except as provided elsewhere in... car after August 25, 1990, shall ensure that the car is readily accessible to and usable by...
-
49 CFR 37.87 - Purchase or lease of used intercity and commuter rail cars.
Code of Federal Regulations, 2013 CFR
2013-10-01
... rail cars. 37.87 Section 37.87 Transportation Office of the Secretary of Transportation TRANSPORTATION....87 Purchase or lease of used intercity and commuter rail cars. (a) Except as provided elsewhere in... car after August 25, 1990, shall ensure that the car is readily accessible to and usable by...
-
49 CFR 37.87 - Purchase or lease of used intercity and commuter rail cars.
Code of Federal Regulations, 2011 CFR
2011-10-01
... rail cars. 37.87 Section 37.87 Transportation Office of the Secretary of Transportation TRANSPORTATION....87 Purchase or lease of used intercity and commuter rail cars. (a) Except as provided elsewhere in... car after August 25, 1990, shall ensure that the car is readily accessible to and usable by...
-
49 CFR 37.49 - Designation of responsible person(s) for intercity and commuter rail stations.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 1 2010-10-01 2010-10-01 false Designation of responsible person(s) for intercity and commuter rail stations. 37.49 Section 37.49 Transportation Office of the Secretary of Transportation TRANSPORTATION SERVICES FOR INDIVIDUALS WITH DISABILITIES (ADA) Transportation Facilities § 37.49...
-
49 CFR 37.85 - Purchase or lease of new intercity and commuter rail cars.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 1 2010-10-01 2010-10-01 false Purchase or lease of new intercity and commuter rail cars. 37.85 Section 37.85 Transportation Office of the Secretary of Transportation TRANSPORTATION SERVICES FOR INDIVIDUALS WITH DISABILITIES (ADA) Acquisition of Accessible Vehicles By Public Entities § 37...
-
DOT National Transportation Integrated Search
2015-12-01
This research examines the impact of intercity passenger rails on change in population and employment at the county level in the continental United States from 2000 to 2010. This research adopts an integrated spatial regression approach that incorpor...
-
Yuan, Cui-Li; Zhang, An-Guo; Zheng, Ze-Bo; Wang, Ke-Zhi
2013-03-01
A phenylthiophenyl-bearing Ru(II) complex of [Ru(bpy)₂(Hbptip)](PF₆)₂ {bpy = 2,2'-bipyridine, Hbptip = 2-(4-phenylthiophen-2-yl)-1H-imidazo[4,5-f][1,10]phenanthroline} was synthesized and characterized by elemental analysis, ¹H NMR spectroscopy, and electrospray ionization mass spectrometry. The ground- and excited-state acid-base properties of the complex were studied by UV-visible absorption and photoluminescence spectrophotometric pH titrations and the negative logarithm values of the ground-state acid ionization constants were derived to be pK(a1) = 1.31 ± 0.09 and pK(a2) = 5.71 ± 0.11 with the pK(a2) associated deprotonation/protonation process occurring over 3 pK(a) units more acidic than thiophenyl-free parent complex of [Ru(bpy)₂(Hpip)]²⁺ {Hpip = 2-phenyl-1H-imidazo[4,5-f][1,10]phenanthroline}. The calf thymus DNA-binding properties of [Ru(bpy)₂(Hbptip)]²⁺ in Tris-HCl buffer (pH 7.1 and 50 mM NaCl) were investigated by DNA viscosities and density functional theoretical calculations as well as UV-visible and emission spectroscopy techniques of UV-visible and luminescence titrations, steady-state emission quenching by [Fe(CN)₆]⁴⁻, DNA competitive binding with ethidium bromide, DNA melting experiments, and reverse salt effects. The complex was evidenced to bind to the DNA intercalatively with binding affinity being greater than those for previously reported analogs of [Ru(bpy)₂(Hip)]²⁺, [Ru(bpy)₂(Htip)]²⁺, and [Ru(bpy)₂(Haptip)]²⁺ {Hip = 1H-imidazo[4,5-f][1,10]phenanthroline, Htip = 2-thiophenimidazo[4,5-f][1,10]phenanthroline, Haptip = 2-(5-phenylthiophen-2-yl)-1H-imidazo[4,5-f][1,10]phenanthroline}.
-
Arshad, Nasima; Ahmad, Mukhtar; Ashraf, Muhammad Zaman; Nadeem, Humaira
2014-09-05
4-Aminophenazone (Ap-1) Schiff bases i.e., 4-{(3,4,5-trimethoxybenzylidine) amino}phenazone (Ap-2), 4-{(2-chlorobenzylidine) amino}phenazone (Ap-3) and 4-{(4-chlorobenzylidine)amino} phenazone (Ap-4) were synthesized and characterized by different spectroscopic techniques. Interaction of these compounds with ds.DNA was investigated through UV-Visible spectroscopy, fluorescence spectroscopy and cyclic voltammetry at stomach (4.7) and blood (7.4) pH under 37 °C (human body temperature). Instrumental findings were further quantified both kinetically and thermodynamically. Results obtained through these techniques inferred intercalative mode of binding of all the compounds with DNA. The binding constant data, "Kb", and free energy change, ΔG, indicated comparatively greater binding affinity and more spontaneity of binding of compounds with DNA at stomach pH (4.7), respectively. However, among these compounds, Ap-4 showed comparatively greater binding at both the pH. Formation of compound-DNA complex was further confirmed through the decrease in diffusion rates after the addition of DNA. The in vivo anti-inflammatory activity of the compounds was evaluated using the carrageenan-induced hind paw edema method. The results revealed that among all the compounds, Ap-4 showed greater percentage of edema inhibition compared to standard drug. Copyright © 2014 Elsevier B.V. All rights reserved.
-
ERIC Educational Resources Information Center
Chow, Alice S. Y.; Loo, Becky P. Y.
2015-01-01
Both the commercial and education sectors experience an increase in inter-city exchanges in the forms of goods, capital, commands, people and information/knowledge under globalization. The quantification of flows and structural relations among cities in globalizing education are under-researched compared to the well-established world/global cities…
-
Federal Register 2010, 2011, 2012, 2013, 2014
2013-09-18
... allowed trains to run from one rail line to the other in order to accommodate intercity travel between... Pass and the Tri Valley area capable of supporting intercity and commuter rail passenger services. The... day, reducing travel times, and eliminating freight railroad delays by providing separate passenger...
-
Federal Register 2010, 2011, 2012, 2013, 2014
2011-01-04
... expected growth in population and resulting increases in intercity travel demand between Los Angeles and San Luis Obispo. As a result of this growth in travel demand, their travel delays from the growing... environmental analysis to help make corridor level decisions regarding the level of intercity passenger rail...
-
36 CFR § 1192.125 - Mobility aid accessibility.
Code of Federal Regulations, 2013 CFR
2013-07-01
..., electrical or other system operates to ensure that cars do not move when the lift is in use. (3) Emergency... VEHICLES Intercity Rail Cars and Systems § 1192.125 Mobility aid accessibility. (a)(1) General. All intercity rail cars, other than level entry cars, required to be accessible by § 1192.111 (a) and (e) of...
-
36 CFR 1192.125 - Mobility aid accessibility.
Code of Federal Regulations, 2012 CFR
2012-07-01
... Intercity Rail Cars and Systems § 1192.125 Mobility aid accessibility. (a)(1) General. All intercity rail cars, other than level entry cars, required to be accessible by § 1192.111 (a) and (e) of this subpart...(d) are provided, at stations or stops required to be accessible by 49 CFR part 37, the car is not...
-
36 CFR 1192.125 - Mobility aid accessibility.
Code of Federal Regulations, 2014 CFR
2014-07-01
... Intercity Rail Cars and Systems § 1192.125 Mobility aid accessibility. (a)(1) General. All intercity rail cars, other than level entry cars, required to be accessible by § 1192.111 (a) and (e) of this subpart...(d) are provided, at stations or stops required to be accessible by 49 CFR part 37, the car is not...
-
36 CFR 1192.125 - Mobility aid accessibility.
Code of Federal Regulations, 2010 CFR
2010-07-01
... Intercity Rail Cars and Systems § 1192.125 Mobility aid accessibility. (a)(1) General. All intercity rail cars, other than level entry cars, required to be accessible by § 1192.111 (a) and (e) of this subpart...(d) are provided, at stations or stops required to be accessible by 49 CFR part 37, the car is not...
-
36 CFR 1192.125 - Mobility aid accessibility.
Code of Federal Regulations, 2011 CFR
2011-07-01
... Intercity Rail Cars and Systems § 1192.125 Mobility aid accessibility. (a)(1) General. All intercity rail cars, other than level entry cars, required to be accessible by § 1192.111 (a) and (e) of this subpart...(d) are provided, at stations or stops required to be accessible by 49 CFR part 37, the car is not...
-
Technology assessment of future intercity passenger transporation systems. Volume 1: Summary report
NASA Technical Reports Server (NTRS)
1976-01-01
Technical, economic, environmental, and sociopolitical issues associated with future intercity transportation system options were assured. Technology assessment was used as a tool to assist in the identification of basic research and technology development tasks that should be undertaken. The emphasis was on domestic passenger transportation, but interfaces with freight and international transportation were considered.
-
Mode shift strategies in intercity transportation and their effect on energy consumption
NASA Technical Reports Server (NTRS)
Sokolsky, S.
1975-01-01
Policies are examined which, if implemented, could lead to significant energy savings in intercity travel in the northeast corridor arena, without restricting the traveler's freedom of mode choice. The effects on arena energy consumption of introducing new, more energy-efficient aircraft are investigated; and several strategies unrelated to the implementation of new aircraft are introduced to yield reductions in overall intercity energy use. In both parts of this analysis, resulting changes in patronage (modal share) and energy use are demonstrated, leading to new insights into the effectiveness of different potential policies for achieving energy conservation. Some observations on induced demand trends that could be associated with certain strategies and the resultant potential effect on energy conservation are provided.
-
Yilmaz, Veysel T; Icsel, Ceyda; Suyunova, Feruza; Aygun, Muhittin; Aztopal, Nazlihan; Ulukaya, Engin
2016-06-21
New 5,5-diethylbarbiturate (barb) complexes of Ni(ii), Cu(ii) and Zn(ii) with 1,10-phenanthroline (phen) and 2,2'-dipyridylamine (dpya), namely [Ni(phen-κN,N')3]Cl(barb)·7H2O (), [Cu(barb-κN)(barb-κ(2)N,O)(phen-κN,N')]·H2O (), [Cu(barb-κN)2(phen-κN,N')] (), [Zn(barb-κN)2(phen-κN,N')]·H2O (), [Ni(barb-κ(2)N,O)(dpya-κN,N')2]Cl·2H2O (), [Cu(barb-κ(2)N,O)2(dpya-κN,N')]·2H2O () and [Zn(barb-κN)2(dpya-κN,N')] (), were synthesized and characterized by elemental analysis, UV-vis, FT-IR and ESI-MS. The structures of the complexes were determined by X-ray crystallography. Notably, and were fluorescent in MeOH : H2O at rt. The interaction of the complexes with fish sperm (FS) DNA and bovine serum albumin (BSA) was investigated in detail by various techniques. The complexes exhibited groove binding along with a partial intercalative interaction with DNA, while the hydrogen bonding and hydrophobic interactions played a major role in binding to BSA. It is noteworthy that exhibited the highest affinity towards DNA and BSA. Enzyme inhibition assay showed that show a preference for both A/T and G/C rich sequences in pUC19 DNA, while and display a binding specificity to the G/C and A/T rich regions, respectively. These findings were further supported by molecular docking. The cellular uptake studies suggested that was deposited mostly in the membrane fraction of the cells. Among the present complexes, exhibited a very strong cytotoxic effect on A549, MCF-7, HT-29 and DU-145 cancer cells, being more potent than cisplatin. Moreover, induces cell death through the apoptotic mode obtained by flow cytometry.
-
Federal Register 2010, 2011, 2012, 2013, 2014
2010-11-04
... purpose of the 3C ``Quick Start'' Passenger Rail Project is to reestablish intercity conventional speed... predictable and consistent travel times. It is intended to provide travel options and develop the passenger... through the High Speed Intercity Passenger Rail Program (HSIPR Program) administered by the FRA and funded...
-
Driver Performance Problems of Intercity Bus Public Transportation Safety in Indonesia
NASA Astrophysics Data System (ADS)
Suraji, A.; Harnen, S.; Wicaksono, A.; Djakfar, L.
2017-11-01
The risk of an inter-city bus public accident can be influenced by various factors such as the driver’s performance. Therefore, knowing the various influential factors related to driver’s performance is very necessary as an effort to realize road traffic safety. This study aims to determine the factors that fall on the accident associated with the driver’s performance and make mathematical modeling factors that affect the accident. Methods of data retrieval were obtained from NTSC secondary data. The data was processed by identifying factors that cause the accident. Furthermore data processing and analysis used the PCA method to obtain mathematical modeling of factors influencing the inter-city bus accidents. The results showed that the main factors that cause accidents are health, discipline, and driver competence.
-
Zhang, Guowen; Ma, Yadi
2013-11-01
The interaction between sodium benzoate (SB) and calf thymus DNA in simulated physiological buffer (pH 7.4) using acridine orange (AO) dye as a fluorescence probe, was investigated by UV-Vis absorption, fluorescence and circular dichroism (CD) spectroscopy along with DNA melting studies and viscosity measurements. An expanded UV-Vis spectral data matrix was resolved by multivariate curve resolution-alternating least squares (MCR-ALS) approach. The equilibrium concentration profiles and the pure spectra for SB, DNA and DNA-SB complex from the high overlapping composite response were simultaneously obtained. The results indicated that SB could bind to DNA, and hydrophobic interactions and hydrogen bonds played a vital role in the binding process. Moreover, SB was able to quench the fluorescence of DNA-AO complex through a static procedure. The quenching observed was indicative of an intercalative mode of interaction between SB and DNA, which was supported by melting studies, viscosity measurements and CD analysis. Copyright © 2013 Elsevier Ltd. All rights reserved.
-
Raman, Natarajan; Mahalakshmi, Rajkumar; Arun, T; Packianathan, S; Rajkumar, R
2014-09-05
The present contribution reports a thorough characterization of newly obtained metallointercalators incorporating Schiff bases, formed by the condensation of N-acetoacetyl-o-toluidine with 1-amino-4-nitrobenzene (L(1))/1-amino-4-chlorobenzene (L(2)) as main ligand and 1,10-phenanthroline as co-ligand respectively. The characterization of newly formed metallointercalators has been done by (1)H NMR, UV-Vis, IR, EPR spectroscopy and molar conductivity studies. X-ray powder diffraction illustrates that they are crystalline nature. Binding interaction of these complexes with calf thymus (CT-DNA) has been investigated by emission, absorption, viscosity, cyclic voltammetry and differential pulse voltammetry. DNA binding experiments results reveal that the synthesized complexes interact with DNA through intercalative mode. The in vitro antibacterial and antifungal assay indicate that these complexes are good antimicrobial agents against various pathogens. The DNA cleavage exhibits that they act as efficient cleaving agents. Copyright © 2014 Elsevier B.V. All rights reserved.
-
Intercalation of a Zn(II) complex containing ciprofloxacin drug between DNA base pairs.
Shahabadi, Nahid; Asadian, Ali Ashraf; Mahdavi, Mryam
2017-11-02
In this study, an attempt has been made to study the interaction of a Zn(II) complex containing an antibiotic drug, ciprofloxacin, with calf thymus DNA using spectroscopic methods. It was found that Zn(II) complex could bind with DNA via intercalation mode as evidenced by: hyperchromism in UV-Vis spectrum; these spectral characteristics suggest that the Zn(II) complex interacts with DNA most likely through a mode that involves a stacking interaction between the aromatic chromophore and the base pairs of DNA. DNA binding constant (K b = 1.4 × 10 4 M -1 ) from spectrophotometric studies of the interaction of Zn(II) complex with DNA is comparable to those of some DNA intercalative polypyridyl Ru(II) complexes 1.0 -4.8 × 10 4 M -1 . CD study showed stabilization of the right-handed B form of DNA in the presence of Zn(II) complex as observed for the classical intercalator methylene blue. Thermodynamic parameters (ΔH < 0 and ΔS < 0) indicated that hydrogen bond and Van der Waals play main roles in this binding prose. Competitive fluorimetric studies with methylene blue (MB) dye have shown that Zn(II) complex exhibits the ability of this complex to displace with DNA-MB, indicating that it binds to DNA in strong competition with MB for the intercalation.
-
NASA Astrophysics Data System (ADS)
Abdel-Rahman, Laila H.; El-Khatib, Rafat M.; Nassr, Lobna A. E.; Abu-Dief, Ahmed M.; Ismael, Mohamed; Seleem, Amin Abdou
2014-01-01
In recent years, great interest has been focused on Fe(II) Schiff base amino acid complexes as cytotoxic and antitumor drugs. Thus a series of new iron(II) complexes based on Schiff bases amino acids ligands have been designed and synthesized from condensation of 5-bromosalicylaldehyde (bs) and α-amino acids (L-alanine (ala), L-phenylalanine (phala), L-aspartic acid (aspa), L-histidine (his) and L-arginine (arg)). The structure of the investigated iron(II) complexes was elucidated using elemental analyses, infrared, ultraviolet-visible, thermogravimetric analysis, as well as conductivity and magnetic susceptibility measurements. Moreover, the stoichiometry and the stability constants of the prepared complexes have been determined spectrophotometrically. The results suggest that 5-bromosalicylaldehyde amino acid Schiff bases (bs:aa) behave as dibasic tridentate ONO ligands and coordinate to Fe(II) in octahedral geometry according to the general formula [Fe(bs:aa)2]ṡnH2O. The conductivity values between 37 and 64 ohm-1 mol-1 cm2 in ethanol imply the presence of nonelectrolyte species. The structure of the complexes was validated using quantum mechanics calculations based on accurate DFT methods. Geometry optimization of the Fe-Schiff base amino acid complexes showed that all complexes had octahedral coordination. In addition, the interaction of these complexes with (CT-DNA) was investigated at pH = 7.2, by using UV-vis absorption, viscosity and agarose gel electrophoresis measurements. Results indicated that the investigated complexes strongly bind to calf thymus DNA via intercalative mode and showed a different DNA binding according to the sequence: bsari > bshi > bsali > bsasi > bsphali. Moreover, the prepared compounds are screened for their in vitro antibacterial and antifungal activity against three types of bacteria, Escherichia coli, Pseudomonas aeruginosa and Bacillus cereus and three types of anti fungal cultures, Penicillium purpurogenium, Aspergillus flavus and Trichotheium rosium. The results of these studies indicated that the metal complexes exhibit a stronger antibacterial and antifungal efficiency than their corresponding Schiff base amino acid ligands.
-
Almaqwashi, Ali A.; Paramanathan, Thayaparan; Lincoln, Per; Rouzina, Ioulia; Westerlund, Fredrik; Williams, Mark C.
2014-01-01
DNA intercalation by threading is expected to yield high affinity and slow dissociation, properties desirable for DNA-targeted therapeutics. To measure these properties, we utilize single molecule DNA stretching to quantify both the binding affinity and the force-dependent threading intercalation kinetics of the binuclear ruthenium complex Δ,Δ-[μ‐bidppz‐(phen)4Ru2]4+ (Δ,Δ-P). We measure the DNA elongation at a range of constant stretching forces using optical tweezers, allowing direct characterization of the intercalation kinetics as well as the amount intercalated at equilibrium. Higher forces exponentially facilitate the intercalative binding, leading to a profound decrease in the binding site size that results in one ligand intercalated at almost every DNA base stack. The zero force Δ,Δ-P intercalation Kd is 44 nM, 25-fold stronger than the analogous mono-nuclear ligand (Δ-P). The force-dependent kinetics analysis reveals a mechanism that requires DNA elongation of 0.33 nm for association, relaxation to an equilibrium elongation of 0.19 nm, and an additional elongation of 0.14 nm from the equilibrium state for dissociation. In cells, a molecule with binding properties similar to Δ,Δ-P may rapidly bind DNA destabilized by enzymes during replication or transcription, but upon enzyme dissociation it is predicted to remain intercalated for several hours, thereby interfering with essential biological processes. PMID:25245944
-
Ganguly, Aniruddha; Ghosh, Soumen; Guchhait, Nikhil
2015-01-07
The present study demonstrates a detailed characterization of the binding interaction of a potential chloride channel blocker 9-methyl anthroate (9-MA) with calf-thymus DNA. The modulated photophysical properties of the emissive molecule within the microheterogeneous bio-assembly have been spectroscopically exploited to monitor the drug-DNA binding interaction. Experimental results based on fluorescence and absorption spectroscopy aided with DNA-melting, viscometric and circular dichroism studies unambiguously establish the binding mode between the drug and DNA to be principally intercalative. Concomitantly, a discernible dependence of the mode of binding between the concerned moieties on the ionic strength of the medium is noteworthy. A dip-and-rise characteristic of the rotational relaxation profile of the drug within the DNA environment has been argued to be originating from a substantial difference in the lifetime as well as amplitude of the free and DNA bound drug molecule. In view of the prospective biological applications of the drug, the issue of facile dissociation of the intercalated drug from the DNA helix via a simple detergent-sequestration technique has also been unveiled. The utility of the present work resides in exploring the potential applicability of the fluorescence properties of 9-MA for studying its interactions with other relevant biological or biomimicking targets.
-
Xu, R; Birke, S; Carberry, S E; Geacintov, N E; Swenberg, C E; Harvey, R G
1992-01-01
The unwinding of supercoiled phi X174 RFI DNA induced by the tumorigenic (+) and non-tumorigenic (-) enantiomers of trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) has been investigated by agarose slab-gel and ethidium titration tube gel electrophoresis. The differences in adduct conformations were verified by flow linear dichroism techniques. Both enantiomers cause a reversible unwinding by the formation of noncovalent intercalative complexes. The effects of covalently bound BPDE residues on the electrophoretic mobilities of the RF I DNA form in agarose gels were investigated in detail in the range of binding ratios rb approximately 0.0-0.06 (covalently bound BPDE residues/nucleotide). In this range of rb values, there is a striking difference in the mobilities of (+)-BPDE- and (-)-BPDE-adducted phi X174 DNA in agarose slab-gels, the covalently bound (+)-BPDE residues causing a significantly greater retardation than (-)-BPDE residues. Increasing the level of covalent adducts beyond rb approximately 0.06 in the case of the (+)-BPDE enantiomer, leads to further unwinding and a minimum in the mobilities (corresponding to comigration of the nicked form and the covalently closed relaxed modified form) at rb 0.10 +/- 0.01; at still higher rb values, rewinding of the modified DNA in the opposite sense is observed. From the minimum in the mobility, a mean unwinding angle (per BPDE residue) of theta = 12 +/- 1.5 degrees is determined, which is in good agreement the value of theta = 11 +/- 1.8 degrees obtained by the tube gel titration method. Using this latter method, values of theta = 6.8 +/- 1.7 degrees for (-)-BPDE-phi X174 adducts are observed. It is concluded that agarose slab gel techniques are not suitable for determining unwinding angles for (-)-BPDE-modified phi X174 DNA because the alterations in the tertiary structures for rb < 0.06 are too small to cause sufficiently large changes in the electrophoretic mobilities. The major trans (+)-BPDE-N2-guanosine covalent adduct is situated at external binding sites and the mechanisms of unwinding are therefore different from those relevant to noncovalent intercalative BPDE-DNA complexes or to classical intercalating drug molecules; a flexible hinge joint and a widening of the minor groove at the site of the lesion may account for the observed unwinding effects. The more heterogeneous (-)-BPDE-nucleoside adducts (involving cis and trans N2-guanosine, and adenosine adducts) are less effective in causing unwinding of supercoiled DNA for reasons which remain to be elucidated. Images PMID:1475180
-
Responses to Fiscal Stress: A Comparative Analysis
2013-12-01
of “a significant decline in market share by the middle of the 20th century as travelers and shippers turned increasingly to airlines, trucks, and...1995). Intercity passenger rail: Financial and operating conditions threaten Amtrak’s long-term viability (GAO-95-71). Washington, DC: U.S...I. (1980). Retrenchment and flexibility in public organizations. Fiscal Stress and Public Policy, 159–178. Scheinberg, P. F. (1998). Intercity
-
Effect of aircraft technology improvements on intercity energy use
NASA Technical Reports Server (NTRS)
1976-01-01
An examination of the growth or decline in energy consumption in short haul, high density intercity transportation is made in relation to changes in aeronautical technology. Improvements or changes in the technology of competitive modes are also included. Certain improvements in air traffic control procedures were included to determine their effectiveness in saving energy along with a fuel efficient turboprop short haul aircraft concept.
-
NASA Astrophysics Data System (ADS)
Abdel-Rahman, Laila H.; El-Khatib, Rafat M.; Nassr, Lobna A. E.; Abu-Dief, Ahmed M.
2013-05-01
New Fe(II) Schiff base amino acid complexes derived from the condensation of o-hydroxynaphthaldehyde with L-alanine, L-phenylalanine, L-aspartic acid, L-histidine and L-arginine were synthesized and characterized by elemental analysis, IR, electronic spectra, and conductance measurements. The stoichiometry and the stability constants of the complexes were determined spectrophotometrically. The investigated Schiff bases exhibited tridentate coordination mode with the general formulae [Fe(HL)2]·nH2O for all amino acids except L-histidine. But in case of L-histidine, the ligand acts as tetradentate ([FeL(H2O)2]·2H2O), where HL = mono anion and L = dianion of the ligand. The structure of the prepared complexes is suggested to be octahedral. The prepared complexes were tested for their toxicity on chick embryos and found to be safe until a concentration of 100 μg/egg with full embryos formation. The interaction between CT-DNA and the investigated complexes were followed by spectrophotometry and viscosity measurements. It was found that, the prepared complexes bind to DNA via classical intercalative mode and showed a different DNA cleavage activity with the sequence: nhi > nari > nali > nasi > nphali. The thermodynamic Profile of the binding of nphali complex and CT-DNA was constructed by analyzing the experimental data of absorption titration and UV melting studies with the McGhee equation, van't Hoff's equation, and the Gibbs-Helmholtz equation.
-
Bazzicalupi, Carla; Bencini, Andrea; Bianchi, Antonio; Biver, Tarita; Boggioni, Alessia; Bonacchi, Sara; Danesi, Andrea; Giorgi, Claudia; Gratteri, Paola; Ingraín, Antonio Marchal; Secco, Fernando; Sissi, Claudia; Valtancoli, Barbara; Venturini, Marcella
2008-01-01
The new bifunctional molecule 3,6-diamine-9-[6,6-bis(2-aminoethyl)-1,6-diaminohexyl]acridine (D), which is characterised by both an aromatic moiety and a separate metal-complexing polyamine centre, has been synthesised. The characteristics of D and its ZnII complex ([ZnD]) (protonation and metal-complexing constants, optical properties and self-aggregation phenomena) have been analysed by means of NMR spectroscopy, potentiometric, spectrophotometric and spectrofluorimetric techniques. The equilibria and kinetics of the binding process of D and [ZnD] to calf thymus DNA have been investigated at I=0.11 M (NaCl) and 298.1 K by using spectroscopic methods and the stopped-flow technique. Static measurements show biphasic behaviour for both D-DNA and [ZnD]-DNA systems; this reveals the occurrence of two different binding processes depending on the polymer-to-dye molar ratio (P/D). The binding mode that occurs at low P/D values is interpreted in terms of external binding with a notable contribution from the polyamine residue. The binding mode at high P/D values corresponds to intercalation of the proflavine residue. Stopped-flow, circular dichroism and supercoiled-DNA unwinding experiments corroborate the proposed mechanism. Molecular-modelling studies support the intercalative process and evidence the influence of NH+...O interactions between the protonated acridine nitrogen atom and the oxygen atoms of the polyanion; these interactions play a key role in determining the conformation of DNA adducts.
-
An Intercity Outbreak of Meningococcal Meningitis in Adults
Oill, Phyllis A.; Chow, Anthony W.; Roberto, Ronald R.; Guze, Lucien B.
1978-01-01
An intercity outbreak of meningococcal meningitis occurred in five adults, with the acute onset of symptoms developing in two of the patients after they returned to Los Angeles from the San Francisco Bay area. The secondary attack rate was 36.4 percent in this entirely adult household. The authors review reports of secondary cases in civilian epidemics, as well as recommendations for chemoprophylaxis in household contacts. PMID:636407
-
The Blueprint for a Secure Energy Future: Progress Report
2012-03-01
Over the past three years, the Administration has continued to develop and expand America’s high-speed and intercity passenger rail system. In May...2011, DOT announced $2 billion in high-speed rail, bringing our unprecedented investment to $10.1 billion to date. In FY 2011, intercity rail...thousands of jobs, improve and expand travel options, cut energy use and help make our communities more livable. Improving Transportation Choices
-
Code of Federal Regulations, 2011 CFR
2011-04-01
... 26 Internal Revenue 16 2011-04-01 2011-04-01 false Credits or payments to purchaser of diesel or special motor fuels used in intercity, local, or school buses. 48.6427-2 Section 48.6427-2 Internal... Retailers and Manufacturers Taxes § 48.6427-2 Credits or payments to purchaser of diesel or special motor...
-
Code of Federal Regulations, 2010 CFR
2010-04-01
... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Credits or payments to purchaser of diesel or special motor fuels used in intercity, local, or school buses. 48.6427-2 Section 48.6427-2 Internal... Retailers and Manufacturers Taxes § 48.6427-2 Credits or payments to purchaser of diesel or special motor...
-
Code of Federal Regulations, 2012 CFR
2012-04-01
... 26 Internal Revenue 16 2012-04-01 2012-04-01 false Credits or payments to purchaser of diesel or special motor fuels used in intercity, local, or school buses. 48.6427-2 Section 48.6427-2 Internal... Retailers and Manufacturers Taxes § 48.6427-2 Credits or payments to purchaser of diesel or special motor...
-
Code of Federal Regulations, 2013 CFR
2013-04-01
... 26 Internal Revenue 16 2013-04-01 2013-04-01 false Credits or payments to purchaser of diesel or special motor fuels used in intercity, local, or school buses. 48.6427-2 Section 48.6427-2 Internal... Retailers and Manufacturers Taxes § 48.6427-2 Credits or payments to purchaser of diesel or special motor...
-
GIS based analysis of Intercity Fatal Road Traffic Accidents in Iran
Alizadeh, A; Zare, M; Darparesh, M; Mohseni, S; Soleimani-Ahmadi, M
2015-01-01
Road traffic accidents including intercity car traffic accidents (ICTAs) are among the most important causes of morbidity and mortality due to the growing number of vehicles, risky behaviors, and changes in lifestyle of the general population. A sound knowledge of the geographical distribution of car traffic accidents can be considered as an approach towards the accident causation and it can be used as an administrative tool in allocating the sources for traffic accidents prevention. This study was conducted to investigate the geographical distribution and the time trend of fatal intercity car traffic accidents in Iran. To conduct this descriptive study, all Iranian intercity road traffic mortality data were obtained from the Police reports in the Statistical Yearbook of the Governor’s Budget and Planning. The obtained data were for 17 complete Iranian calendar years from March 1997 to March 2012. The incidence rate (IR) of fatal ICTAs for each year was calculated as the total number of fatal ICTAs in every 100000 population in specified time intervals. Figures and maps indicating the trends and geographical distribution of fatal ICTAs were prepared while using Microsoft Excel and ArcGis9.2 software. The number of fatal car accidents showed a general increasing trend from 3000 in 1996 to 13500 in 2012. The incidence of fatal intercity car accidents has changed from six in 100000 population in 1996 to 18 in 100000 population in 2012. GIS based data showed that the incidence rate of ICTAs in different provinces of Iran was very divergent. The highest incidence of fatal ICTAs was in Semnan province (IR= 35.2), followed by North Khorasan (IR=22.7), and South Khorasan (IR=22). The least incidence of fatal ICTAs was in Tehran province (IR=2.4) followed by Khozestan (IR=6.5), and Eastern Azarbayejan (IR=6.6). The compensation cost of fatal ICTAs also showed an increasing trend during the studied period. Since an increasing amount of money was being paid yearly for the car accidents, which were in their nature preventable, the key players in road safety including governments, car manufacturers, and road developers were recommended to use GIS based accident data for a more efficient planning and budgeting towards the intercity car accidents reduction. PMID:28255402
-
GIS based analysis of Intercity Fatal Road Traffic Accidents in Iran.
Alizadeh, A; Zare, M; Darparesh, M; Mohseni, S; Soleimani-Ahmadi, M
2015-01-01
Road traffic accidents including intercity car traffic accidents (ICTAs) are among the most important causes of morbidity and mortality due to the growing number of vehicles, risky behaviors, and changes in lifestyle of the general population. A sound knowledge of the geographical distribution of car traffic accidents can be considered as an approach towards the accident causation and it can be used as an administrative tool in allocating the sources for traffic accidents prevention. This study was conducted to investigate the geographical distribution and the time trend of fatal intercity car traffic accidents in Iran. To conduct this descriptive study, all Iranian intercity road traffic mortality data were obtained from the Police reports in the Statistical Yearbook of the Governor's Budget and Planning. The obtained data were for 17 complete Iranian calendar years from March 1997 to March 2012. The incidence rate (IR) of fatal ICTAs for each year was calculated as the total number of fatal ICTAs in every 100000 population in specified time intervals. Figures and maps indicating the trends and geographical distribution of fatal ICTAs were prepared while using Microsoft Excel and ArcGis9.2 software. The number of fatal car accidents showed a general increasing trend from 3000 in 1996 to 13500 in 2012. The incidence of fatal intercity car accidents has changed from six in 100000 population in 1996 to 18 in 100000 population in 2012. GIS based data showed that the incidence rate of ICTAs in different provinces of Iran was very divergent. The highest incidence of fatal ICTAs was in Semnan province (IR= 35.2), followed by North Khorasan (IR=22.7), and South Khorasan (IR=22). The least incidence of fatal ICTAs was in Tehran province (IR=2.4) followed by Khozestan (IR=6.5), and Eastern Azarbayejan (IR=6.6). The compensation cost of fatal ICTAs also showed an increasing trend during the studied period. Since an increasing amount of money was being paid yearly for the car accidents, which were in their nature preventable, the key players in road safety including governments, car manufacturers, and road developers were recommended to use GIS based accident data for a more efficient planning and budgeting towards the intercity car accidents reduction.
-
NASA Technical Reports Server (NTRS)
1976-01-01
Consequences that might occur if certain technological developments take place in intercity transportation are described. These consequences are broad ranging, and include economic, environmental, social, institutional, energy-related, and transportation service implications. The possible consequences are traced through direct (primary) impacts to indirect (secondary, tertiary, etc.) impacts. Chains of consequences are traced, reaching as far beyond the original transportation cause as is necessary to identify all impacts felt to be influenced significantly by the technological development considered.
-
NASA Astrophysics Data System (ADS)
Sirajuddin, Muhammad; Nooruddin; Ali, Saqib; McKee, Vickie; Khan, Shahan Zeb; Malook, Khan
2015-01-01
The titled compound, 4-(5-chloro-2-hydroxyphenylamino)-4-oxobut-2-enoic acid was synthesized and characterized by various techniques like elemental analyses, FT-IR, NMR (1H, and 13C) and single crystal X-ray structural analysis. The appearance of the OH peak of the carboxylic acid in the FT-IR and NMR spectra conform the formation of the compound. A good agreement was found between the calculated values of C, H, N and found values in elemental analysis that show the purity of the compound. Protons H2 and H3 are in cis conformation with each other as conformed both from 1H NMR as well as from single crystal X-ray analysis. The molecular structure of the title compound, C10H10NO3Cl, is stabilized by short intramolecular Osbnd H- - -O hydrogen bonds within the molecule. In the crystal structure, intermolecular Nsbnd H- - -O hydrogen bonds link molecules into zigzag chains resulting in a dendrimer like structure. The title compound was screened for biological activities like interaction with DNA, cytotoxicity, antitumor and antioxidant activities. DNA interaction study reveals that the binding mode of interaction of the compound with SS-DNA is intercalative as it results in hypochromism along with significant red shift of 5 nm. It was also found to be effective antioxidant of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and show almost comparable antioxidant activity to that of the standard and known antioxidant, ascorbic acid, at higher concentration. The antitumor activity data of the compound shows that it can be used as potent antitumor agent.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Salih, A. M.; Ahmad, Mansor Bin; Ibrahim, Nor Azowa
2014-02-12
Palm oil based-polyurethane acrylate (POBUA)/clay nanocomposites were prepared via in-situ intercalative polymerization using epoxidized palm oil acrylate (EPOLA) and 4,4' methylene diphenyl diisocyante (MDI). Organically modified Montmorillonite (ODA-MMT) was incorporated in EPOLA (1, 3 and 5%wt), and then subjected to polycondensation reaction with MDI. Nanocomposites solid films were obtained successfully by electron beam radiation induced free radical polymerization (curing). FTIR results reveal that the prepolymer was obtained successfully, with nanoclay dispersed in the matrix. The intercalation of the clay in the polymer matrix was investigated by XRD and the interlayer spacing of clay was found to be increased up tomore » 37 Å, while the structure morphology of the nanocomposites was investigated by TEM and SEM. The nanocomposites were found to be a mixture of exfoliated and intercalated morphologies. The thermal stability of the nanocomposites was significantly increased by incorporation of nanoclay into the polymer matrix. DSC results reveal that the Tg was shifted to higher values, gradually with increasing the amount of filler in the nanocomposites. Tensile strength and Young's modulus of the nanocomposites showed remarkable improvement compared to the neat POBUA.« less
-
Ganji, Nirmala; Chityala, Vijay Kumar; Marri, Pradeep Kumar; Aveli, Rambabu; Narendrula, Vamsikrishna; Daravath, Sreenu; Shivaraj
2017-10-01
Two new series of binary metal complexes [M(L 1 ) 2 ] and [M(L 2 ) 2 ] where, M=Cu(II), Ni(II) & Co(II) and L 1 =4-((3,4-dimethylisoxazol-5-ylimino)methyl)benzene-1,3-diol; L 2 =2-((3,4-dimethylisoxazol-5-ylimino)methyl)-5-methoxyphenol were synthesized and characterized by elemental analysis, 1 H NMR, 13 C NMR, FT-IR, ESI mass, UV-Visible, magnetic moment, ESR, SEM and powder XRD studies. Based on these results, a square planar geometry is assigned for all the metal complexes where the Schiff base acts as uninegatively charged bidentate chelating agent via the hydroxyl oxygen and azomethine nitrogen atoms. DNA binding studies of all the complexes with calf thymus DNA have been comprehensively investigated using electronic absorption spectroscopy, fluorescence quenching and viscosity studies. The oxidative and photo cleavage affinity of metal complexes towards supercoiled pBR322 DNA has been ascertained by agarose gel electrophoresis assay. From the results, it is observed that all the metal complexes bind effectively to CT-DNA via an intercalative mode of binding and also cleave pBR322 DNA in a promising manner. Further the Cu(II) complexes have shown better binding and cleavage properties towards DNA. The antimicrobial activities of the Schiff bases and their metal complexes were studied on bacterial and fungal strains and the results denoted that the complexes are more potent than their Schiff base ligands. Copyright © 2017 Elsevier B.V. All rights reserved.
-
NASA Technical Reports Server (NTRS)
English, J. M.; Smith, J. L.; Lifson, M. W.
1978-01-01
The objectives of this study are: (1) to determine a unified methodological framework for the comparison of intercity passenger and freight transportation systems; (2) to review the attributes of existing and future transportation systems for the purpose of establishing measures of comparison. These objectives were made more specific to include: (1) development of a methodology for comparing long term transportation trends arising from implementation of various R&D programs; (2) definition of value functions and attribute weightings needed for further transportation goals.
-
Demirezen, Nihat; Tarınç, Derya; Polat, Duygu; Ceşme, Mustafa; Gölcü, Ayşegül; Tümer, Mehmet
2012-08-01
Complexes of trimethoprim (TMP), with Cu(II), Zn(II), Pt(II), Ru(III) and Fe(III) have been synthesized. Then, these complexes have been characterized by spectroscopic techniques involving UV-vis, IR, mass and (1)H NMR. CHN elemental analysis, electrochemical and thermal behavior of complexes have also been investigated. The electrochemical properties of all complexes have been investigated by cyclic voltammetry (CV) using glassy carbon electrode. The biological activity of the complexes has been evaluated by examining their ability to bind to calf-thymus DNA (CT DNA) with UV spectroscopy and cyclic voltammetry. UV studies of the interaction of the complexes with DNA have shown that these compounds can bind to CT DNA. The binding constants of the complexes with CT DNA have also been calculated. The cyclic voltammograms of the complexes in the presence of CT DNA have shown that the complexes can bind to CT DNA by both the intercalative and the electrostatic binding mode. The antimicrobial activity of these complexes has been evaluated against three Gram-positive and four Gram-negative bacteria. Antifungal activity against two different fungi has been evaluated and compared with the reference drug TMP. Almost all types of complexes show excellent activity against all type of bacteria and fungi. The morphology of the CT DNA, TMP, metal ions and metal complexes has been investigated by scanning electron microscopy (SEM). To get the SEM images, the interaction of compounds with CT DNA has been studied by means of differential pulse voltammetry (DPV) at CT DNA modified pencil graphite electrode (PGE). The decrease in intensity of the guanine oxidation signals has been used as an indicator for the interaction mechanism. Copyright © 2012 Elsevier B.V. All rights reserved.
-
NASA Astrophysics Data System (ADS)
Gubendran, Ammavasi; Kesavan, Mookkandi Palsamy; Ayyanaar, Srinivasan; Mitu, Liviu; Athappan, Periyakaruppan; Rajesh, Jegathalaprathaban
2017-06-01
New Schiff base complexes [Cu(L1)Cl] (1), [Ni(L1)Cl] (2), [Zn(L1)Cl] (3), and [Fe(L2)H2OCl] (4) {L1 = (4E)-3-(2-hydroxybenzylidene)-4-(2-hydroxyphenylimino)pentan-2-one, L2 = 2,2‧-(1E,1‧E)-(3-(2-hydroxybenzylidene)-pentane-2,4-diylidene)bis(azan-1-yl-1 idene)diphenol} have been synthesized and characterized by elemental analysis, UV-Vis, IR, FAB-mass, EPR, spectral studies and electrochemical studies, the ligands L1 &L2 were characterized by 1H and 13C NMR spectra. Complex 1 show a visible spectral d-d band near 600 nm and display cyclic voltammetric quasireversible response for the Cu(II)/Cu(I) couple vs Ag/AgCl in DMSO. The EPR spectrum of 1 show g‖ > g⊥ suggesting a square planar geometry around copper with dx2 - y2 as the ground state. The mass spectral results have confirmed the proposed structure for complexes 1-4. DNA binding properties of these complexes 1-4 have been investigated by absorption titrations, cyclic voltammetric studies and circular dichroism studies. On titration with DNA, the complexes 1-4 show hypochromism at the MLCT band (13-31%) with a red shift of 1-8 nm in the electronic spectrum and positive shift of voltammetric E1/2 in the CV studies are in favour of intercalative binding. CD spectra of 1 showed an increase in molar ellipticity (θ278) of the positive band with a minor red shift indicating the transition of B-form of DNA to A like form. DNA cleavage studies of complexes 1 and 4 with pUC18 DNA were studied by gel electrophoresis and complex 4 cleaves supercoiled pUC18 DNA in an oxidative manner in the presence of H2O2 and on photo irradiation at 312 nm.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Ze-xin; Li, Jian; Li, Yan
The inhibitory effect of DNA topoisomerase (Top I) by isoliquiritigenin(ISO) were investigated and their interaction mechanism was evaluated using methods including UV–vis absorption, fluorescence, coupled with molecular simulation, and using the MTT method of inhibition rate of HCC tumor cell SNU475 proliferation assay, finally, the interaction of ISO with calf thymus DNA was investigated by melting measurements and molecular docking studies. It was found that isoliquiritigenin reversibly inhibited DNA Top I in a competitive manner with the concentrations of ISO resulting in 50% activity lost (IC{sub 50}) were estimated to be 0.178 ± 0.12 mM. Isoliquiritigenin exhibited a strong ability to quench themore » intrinsic fluorescence of Top I through a static quenching procedure. The positive values of enthalpy change and entropy change suggested that the binding of isoliquiritigenin to Top I was driven mainly by hydrophobic interactions. The molecular docking results revealed isoliquiritigenin actually interacted with the primary amino acid residues on the active site of Top I, and the detection results of fluorescence staining and the inhibitory effect on the growth of HCC SUN475 showed that isoliquiritigenin induced the apoptosis cells increased gradually. The interaction of ISO with DNA can cause the denaturation temperature to be increased, which indicated that the stabilization of the DNA helix was increased in the presence of ISO, which indicated that the results provide strong evidence for intercalative binding of ISO with DNA. - Highlights: • ISO reversibly inhibits TOP I activity in an A dose dependent manner. • Hydrophobic interactions play a major role in ISO–TOP I interaction. • ISO has a high affinity close to the active site pocket of TOP I. • The binding of ISO to DNA induces the stability of the structure of DNA.« less
-
Raju, Gajjela; Srinivas, Ragampeta; Santhosh Reddy, Vangala; Idris, Mohammed M.; Kamal, Ahmed; Nagesh, Narayana
2012-01-01
Studies on ligand interaction with quadruplex DNA, and their role in stabilizing the complex at concentration prevailing under physiological condition, has attained high interest. Electrospray ionization mass spectrometry (ESI-MS) and spectroscopic studies in solution were used to evaluate the interaction of PBD and TMPyP4 ligands, stoichiometry and selectivity to G-quadruplex DNA. Two synthetic ligands from PBD family, namely pyrene-linked pyrrolo[2,1-c][1,4]benzodiazepine hybrid (PBD1), mixed imine-amide pyrrolobenzodiazepine dimer (PBD2) and 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin (TMPyP4) were studied. G-rich single-stranded oligonucleotide d(5′GGGGTTGGGG3′) designated as d(T2G8), from the telomeric region of Tetrahymena Glaucoma, was considered for the interaction with ligands. ESI-MS and spectroscopic methods viz., circular dichroism (CD), UV-Visible, and fluorescence were employed to investigate the G-quadruplex structures formed by d(T2G8) sequence and its interaction with PBD and TMPyP4 ligands. From ESI-MS spectra, it is evident that the majority of quadruplexes exist as d(T2G8)2 and d(T2G8)4 forms possessing two to ten cations in the centre, thereby stabilizing the complex. CD band of PBD1 and PBD2 showed hypo and hyperchromicity, on interaction with quadruplex DNA, indicating unfolding and stabilization of quadruplex DNA complex, respectively. UV-Visible and fluorescence experiments suggest that PBD1 bind externally where as PBD2 intercalate moderately and bind externally to G-quadruplex DNA. Further, melting experiments using SYBR Green indicate that PBD1 unfolds and PBD2 stabilizes the G-quadruplex complex. ITC experiments using d(T2G8) quadruplex with PBD ligands reveal that PBD1 and PBD2 prefer external/loop binding and external/intercalative binding to quadruplex DNA, respectively. From experimental results it is clear that the interaction of PBD2 and TMPyP4 impart higher stability to the quadruplex complex. PMID:22558271
-
Emission inventory estimation of an intercity bus terminal.
Qiu, Zhaowen; Li, Xiaoxia; Hao, Yanzhao; Deng, Shunxi; Gao, H Oliver
2016-06-01
Intercity bus terminals are hotspots of air pollution due to concentrated activities of diesel buses. In order to evaluate the bus terminals' impact on air quality, it is necessary to estimate the associated mobile emission inventories. Since the vehicles' operating condition at the bus terminal varies significantly, conventional calculation of the emissions based on average emission factors suffers the loss of accuracy. In this study, we examined a typical intercity bus terminal-the Southern City Bus Station of Xi'an, China-using a multi-scale emission model-(US EPA's MOVES model)-to quantity the vehicle emission inventory. A representative operating cycle for buses within the station is constructed. The emission inventory was then estimated using detailed inputs including vehicle ages, operating speeds, operating schedules, and operating mode distribution, as well as meteorological data (temperature and humidity). Five functional areas (bus yard, platforms, disembarking area, bus travel routes within the station, and bus entrance/exit routes) at the terminal were identified, and the bus operation cycle was established using the micro-trip cycle construction method. Results of our case study showed that switching to compressed natural gas (CNG) from diesel fuel could reduce PM2.5 and CO emissions by 85.64 and 6.21 %, respectively, in the microenvironment of the bus terminal. When CNG is used, tail pipe exhaust PM2.5 emission is significantly reduced, even less than brake wear PM2.5. The estimated bus operating cycles can also offer researchers and policy makers important information for emission evaluation in the planning and design of any typical intercity bus terminals of a similar scale.
-
Relationship between occupational stress and cardiovascular diseases risk factors in drivers.
Biglari, Hamed; Ebrahimi, Mohammad Hossein; Salehi, Maryam; Poursadeghiyan, Mohsen; Ahmadnezhad, Iman; Abbasi, Milad
2016-11-18
Of all work stressors, occupational stress is the leading cause of many disorders among workers. Drivers are classified as a high risk group for work related stress. This study set out to determine the relationship between risk factors of cardiovascular diseases and occupational stress among drivers. Two hundred and twenty two Ilam's intercity drivers were selected for the study. For measuring work stress, the Osipow work stress questionnaire was used. After a 10-h fasting period, systolic and diastolic blood pressure was recorded. Intravenous blood samples were taken to determine cholesterol, triglyceride and blood glucose levels. The independent samples t-test and Pearson's correlation test were used to assess the relationship between variables and occupational stress. Seventy-one percent of the intercity drivers suffered from average to acute stress, and 3.1% of them suffered from acute stress. There was no significant relationship between occupational stress and diastolic blood pressure (p = 0.254) among the drivers. Nevertheless, the Pearson's correlation test demonstrated a strong relationship between work stress and blood glucose (p < 0.01), while no strong correlation was found for blood triglycerides and cholesterol levels. Based on the results, high rates of occupational stress were observed in the Ilam's intercity drivers. Occupational stress may have effect on blood glucose levels but the results did not suggest a considerable relationship between risk factors of cardiovascular diseases and occupational stress among intercity drivers. Int J Occup Med Environ Health 2016;29(6):895-901. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.
-
Niu, Yanyan; Li, Sensen; Lin, Zongtao; Liu, Meixian; Wang, Daidong; Wang, Hong; Chen, Shizhong
2016-09-09
Fufang Banbianlian Injection (FBI) has been widely used as an anti-inflammatory and anti-tumor prescription. To understand the relationships between its bioactive ingredients and pharmacological efficacies, our previous study has been successfully identified some DNA-binding compounds in FBI using an established on-line screening system, in which 4',6-diamidino-2-phenylindole (DAPI) was developed as a probe. However, DAPI can be only used to screen ATT-specific DNA minor groove binders, leaving the potential active intercalators unknown in FBI. As a continuation of our studies on FBI, here we present a sensitive analytical method for rapid identification and evaluation of DNA-intercalators using propidium iodide (PI) as a fluorescent probe. We have firstly established the technique of high-performance liquid chromatography-diode-array detector-multistage mass spectrometry-deoxyribonucleic acid-propidium iodide-fluorescence detector (HPLC-DAD-MS(n)-DNA-PI-FLD) system. As a result, 38 of 58 previously identified compounds in FBI were DNA-intercalation active. Interestingly, all previously reported DNA-binders also showed intercalative activities, suggesting they are dual-mode DNA-binders. Quantitative study showed that flavonoid glycosides and chlorogenic acids were the main active compounds in FBI, and displayed similar DNA-binding ability using either DAPI or PI. In addition, 13 active compounds were used to establish the structure-activity relationships. In this study, PI was developed into an on-line method for identifying DNA-intercalators for the first time, and thus it will be a useful high-throughput screening technique for other related samples. Copyright © 2016 Elsevier B.V. All rights reserved.
-
CNG as a Feasible Replacement for the U.S. Transportation Sector
2012-03-01
not convenient for drivers either to have gigantic fuel tanks on vehicles or to stop several times for refueling even in a short distance travel . In... Intercity 31.4 31.4 School 7.0 69.9 76.9 Medium/heavy trucks 611.5 5,452.7 20.3 6,084.5 237.1 NONHIGHWAY 721.4 0.0...18.4 31.6 Intercity 8.6 5.8 14.4 TOTAL HWY & NONHWY 16,898.5 6,735.0 65.3 2,099.3 839.4 638.7 312.9 27,589.0 Figure 24
-
NASA Technical Reports Server (NTRS)
1978-01-01
A unified framework for comparing intercity passenger and freight transportation systems is presented. Composite measures for cost, service/demand, energy, and environmental impact were determined. A set of 14 basic measures were articulated to form the foundation for computing the composite measures. A parameter dependency diagram, constructed to explicitly interrelate the composite and basic measures is discussed. Ground rules and methodology for developing the values of the basic measures are provided and the use of the framework with existing cost and service data is illustrated for various freight systems.
-
Dyes as bifunctional markers of DNA hybridization on surfaces and mutation detection.
García-Mendiola, Tania; Cerro, María Ramos; López-Moreno, José María; Pariente, Félix; Lorenzo, Encarnación
2016-10-01
The interaction of small molecules with DNA has found diagnostic and therapeutic applications. In this work, we propose the use of two different dyes, in particular Azure A and Safranine, as bifunctional markers of on-surface DNA hybridization and potent tools for screening of specific gene mutations directly in real DNA PCR amplicons extracted from blood cells. By combining spectroscopic and electrochemical methods we demonstrate that both dyes can interact with single and double stranded DNA to a different extent, allowing reliable hybridization detection. From these data, we have also elucidated the nature of the interaction. We conclude that the binding mode is fundamentally intercalative with an electrostatic component. The dye fluorescence allows their use as nucleic acid stains for the detection of on-surfaces DNA hybridization. Its redox activity is exploited in the development of selective electrochemical DNA biosensors. Copyright © 2016 Elsevier B.V. All rights reserved.
-
Synthesis, characterization, DNA-binding and cleavage studies of polypyridyl copper(II) complexes
NASA Astrophysics Data System (ADS)
Gubendran, Ammavasi; Rajesh, Jegathalaprathaban; Anitha, Kandasamy; Athappan, Periyakaruppan
2014-10-01
Six new mixed-ligand copper(II) complexes were synthesized namely [Cu(phen)2OAc]ClO4ṡH2O(1), [Cu(bpy)2OAc]ClO4ṡH2O(2), [Cu(o-ampacac)(phen)]ClO4(3), [Cu(o-ampbzac)(phen)]ClO4(4), [Cu(o-ampacac)(bpy)]ClO4(5), and [Cu(o-ampbzac)(bpy)]ClO4(6) (phen = 1,10-phenanthroline, bpy = 2, 2‧-bipyridine, o-ampacac = (Z)-4-(2-hydroxylamino)pent-3-ene-2-one,o-ampbzac = (Z)-4-(2-hydroxylamino)-4-phenylbut-3-ene-2-one)and characterized by UV-Vis, IR, EPR and cyclic voltammetry. Ligands were characterized by NMR spectra. Single crystal X-ray studies of the complex 1 shows Cu(II) ions are located in a highly distorted octahedral environment. Absorption spectral studies reveal that the complexes 1-6 exhibit hypochromicity during the interaction with DNA and binding constant values derived from spectral and electrochemical studies indicate that complexes 1, 2 and 3 bind strongly with DNA possibly by an intercalative mode. Electrochemical studies reveal that the complexes 1-4 prefer to bind with DNA in Cu(I) rather than Cu(II) form. The shift in the formal potentials E1/2 and CD spectral studies suggest groove or electrostatic binding mode for the complexes 4-6. Complex 1 can cleave supercoiled (SC) pUC18 DNA efficiently into nicked form II under photolytic conditions and into an open circular form (form II) and linear form (form III) in the presence of H2O2 at pH 8.0 and 37 °C, while the complex 2 does not cleave DNA under similar conditions.
-
Tan, Yongtao; Liu, Ying; Tang, Zhenghua; Wang, Zhe; Kong, Lingbin; Kang, Long; Liu, Zhen; Ran, Fen
2018-02-13
N-doped carbon nanosheets/vanadium nitride nanoparticles (N-CNS/VNNPs) are synthesized via a novel method combining surface-initiated in-situ intercalative polymerization and thermal-treatment process in NH 3 /N 2 atmosphere. The pH value of the synthesis system plays a critical role in constructing the structure and enhancing electrochemical performance for N-CNS/VNNPs, which are characterized by SEM, TEM, XRD, and XPS, and measured by electrochemical station, respectively. The results show that N-CNS/VNNPs materials consist of 2D N-doped carbon nanosheets and 0D VN nanoparticles. With the pH value decreasing from 2 to 0, the sizes of both carbon nanosheets and VN nanoparticles decreased to smaller in nanoscale. The maximum specific capacitance of 280 F g -1 at the current density of 1 A g -1 for N-CNS/VNNPs is achieved in three-electrode configuration. The asymmetric energy device of Ni(OH) 2 ||N-CNS/VNNPs offers a specific capacitance of 89.6 F g -1 and retention of 60% at 2.7 A g -1 after 5000 cycles. The maximum energy density of Ni(OH) 2 ||N-CNS/VNNPs asymmetric energy device is as high as 29.5 Wh kg -1 .
-
Measuring Polycentricity of Mega-City Regions in China Based on the Intercity Migration Flows
NASA Astrophysics Data System (ADS)
Mu, Xiaoyan; Yeh, Anthony G. O.
2016-06-01
This paper uses the intercity migration flows to examine relations between Chinese cities, identify the important mega-city regions and measure each region's polycentricity from an interaction perspective. Data set contains the long-term residential migration trajectories of three million Sina weibo users across 345 cities. Cities with close connectivity deployed around one or several mega cities are identified as mega-city regions. Features of the mega-city regions are characterized by the strength of migration flows, density of connections, and regional migration patterns. The results show that the disparities exist in different mega-city regions; most mega-city regions are lack of polycentricity.
-
NASA Astrophysics Data System (ADS)
Sirajuddin, Muhammad; Ali, Saqib; McKee, Vickie; Ullah, Hameed
2015-03-01
This paper stresses on the synthesis, characterization of novel carboxylic acid derivative and its application in pharmaceutics. Carboxylic acid derivatives have a growing importance in medicine, particularly in oncology. A novel carboxylic acid, 4-(4-methoxy-2-nitrophenylamino)-4-oxobutanoic acid, was synthesized and characterized by elemental analysis, FT-IR, NMR (1H, and 13C), mass spectrometry and single crystal X-ray structural analysis. The structure of the title compound, C11H12N2O6, shows the molecules dimerised by short intramolecular Osbnd H⋯O hydrogen bonds. The compound was screened for in vitro antimicrobial, anticancer, and antileishmanial activities as well as interaction with SS-DNA. The compound was also checked for in vitro anticancer activity against BHK-21, H-157 and HCEC cell lines, and showed significant anticancer activity. The compound was almost non-toxic towards human corneal epithelial cells (HCEC) and did not show more than 7.4% antiproliferative activity when used at the 2.0 μg/mL end concentration. It was also tested for antileishmanial activity against the promastigote form of leishmania major and obtained attractive result. DNA interaction study exposes that the binding mode of the compound with SS-DNA is an intercalative as it results in hypochromism along with minor red shift. A new and efficient strategy to identify pharmacophores sites in carboxylic acid derivative for antibacterial/antifungal activity using Petra, Osiris and Molinspiration (POM) analyses was also carried out.
-
NASA Astrophysics Data System (ADS)
Piantanida, Ivo; Mašić, Lozika; Rusak, Gordana
2009-04-01
Interactions of five flavonoids with dsRNA and single stranded ssRNA were studied by UV/vis titrations. The results obtained supported the intercalative binding mode as a dominant interaction of studied flavonoids with dsRNA as well as major interaction with ssRNA. Furthermore, changes of the UV/vis spectra of flavonoids induced by addition of poly G or poly C, respectively, are significantly stronger than changes induced by double stranded poly G-poly C, pointing to essential role of the free poly G or poly C sequence (not hydrogen bonded in double helix). Exclusively poly G caused significant batochromic shift of the UV/vis maxima of all studied flavonoids, whereby the intensity of batochromic shift is nicely correlated to the number of OH groups of flavonoid. Unlikely to poly G, addition of poly A and poly U induced measurable changes only in the UV/vis spectra of flavonoids characterised by no OH (galangin) or three OH groups (myricetin) on the phenyl part of the molecule. Consequently, flavonoids with one- or two-OH groups on the phenyl part of the molecule (luteolin, fisetin, kaempferol) specifically differentiate between poly A, poly U (negligible changes in the UV/Vis spectra) and poly G (strong changes in the UV/Vis spectra) as well as poly C (moderate changes in the UV/Vis spectra).
-
Kékedy-Nagy, László; Shipovskov, Stepan; Ferapontova, Elena E
2016-08-16
Charges of redox species can critically affect both the interfacial state of DNA and electrochemistry of DNA-conjugated redox labels and, as a result, the electroanalytical performance of those systems. Here, we show that the kinetics of electron transfer (ET) between the gold electrode and methylene blue (MB) label conjugated to a double-stranded (ds) DNA tethered to gold strongly depend on the charge of the MB molecule, and that affects the performance of genosensors exploiting MB-labeled hairpin DNA beacons. Positively charged MB binds to dsDNA via electrostatic and intercalative/groove binding, and this binding allows the DNA-mediated electrochemistry of MB intercalated into the duplex and, as a result, a complex mode of the electrochemical signal change upon hairpin hybridization to the target DNA, dominated by the "on-off" signal change mode at nanomolar levels of the analyzed DNA. When MB bears an additional carboxylic group, the negative charge provided by this group prevents intimate interactions between MB and DNA, and then the ET in duplexes is limited by the diffusion of the MB-conjugated dsDNA (the phenomenon first shown in Farjami , E. ; Clima , L. ; Gothelf , K. ; Ferapontova , E. E. Anal. Chem. 2011 , 83 , 1594 ) providing the robust "off-on" nanomolar DNA sensing. Those results can be extended to other intercalating redox probes and are of strategic importance for design and development of electrochemical hybridization sensors exploiting DNA nanoswitchable architectures.
-
Structure and information in spatial segregation
2017-01-01
Ethnoracial residential segregation is a complex, multiscalar phenomenon with immense moral and economic costs. Modeling the structure and dynamics of segregation is a pressing problem for sociology and urban planning, but existing methods have limitations. In this paper, we develop a suite of methods, grounded in information theory, for studying the spatial structure of segregation. We first advance existing profile and decomposition methods by posing two related regionalization methods, which allow for profile curves with nonconstant spatial scale and decomposition analysis with nonarbitrary areal units. We then formulate a measure of local spatial scale, which may be used for both detailed, within-city analysis and intercity comparisons. These methods highlight detailed insights in the structure and dynamics of urban segregation that would be otherwise easy to miss or difficult to quantify. They are computationally efficient, applicable to a broad range of study questions, and freely available in open source software. PMID:29078323
-
Structure and information in spatial segregation.
Chodrow, Philip S
2017-10-31
Ethnoracial residential segregation is a complex, multiscalar phenomenon with immense moral and economic costs. Modeling the structure and dynamics of segregation is a pressing problem for sociology and urban planning, but existing methods have limitations. In this paper, we develop a suite of methods, grounded in information theory, for studying the spatial structure of segregation. We first advance existing profile and decomposition methods by posing two related regionalization methods, which allow for profile curves with nonconstant spatial scale and decomposition analysis with nonarbitrary areal units. We then formulate a measure of local spatial scale, which may be used for both detailed, within-city analysis and intercity comparisons. These methods highlight detailed insights in the structure and dynamics of urban segregation that would be otherwise easy to miss or difficult to quantify. They are computationally efficient, applicable to a broad range of study questions, and freely available in open source software. Published under the PNAS license.
-
Living in a network of scaling cities and finite resources.
Qubbaj, Murad R; Shutters, Shade T; Muneepeerakul, Rachata
2015-02-01
Many urban phenomena exhibit remarkable regularity in the form of nonlinear scaling behaviors, but their implications on a system of networked cities has never been investigated. Such knowledge is crucial for our ability to harness the complexity of urban processes to further sustainability science. In this paper, we develop a dynamical modeling framework that embeds population-resource dynamics-a generalized Lotka-Volterra system with modifications to incorporate the urban scaling behaviors-in complex networks in which cities may be linked to the resources of other cities and people may migrate in pursuit of higher welfare. We find that isolated cities (i.e., no migration) are susceptible to collapse if they do not have access to adequate resources. Links to other cities may help cities that would otherwise collapse due to insufficient resources. The effects of inter-city links, however, can vary due to the interplay between the nonlinear scaling behaviors and network structure. The long-term population level of a city is, in many settings, largely a function of the city's access to resources over which the city has little or no competition. Nonetheless, careful investigation of dynamics is required to gain mechanistic understanding of a particular city-resource network because cities and resources may collapse and the scaling behaviors may influence the effects of inter-city links, thereby distorting what topological metrics really measure.
-
NASA Astrophysics Data System (ADS)
Ünver, Hüseyin; Boyacıoğlu, Bahadır; Zeyrek, Celal Tuğrul; Yıldız, Mustafa; Demir, Neslihan; Yıldırım, Nuray; Karaosmanoğlu, Oğuzhan; Sivas, Hülya; Elmalı, Ayhan
2016-12-01
We report the synthesis of a novel Schiff base (E)-3-[(3,5-bis(trifluoromethyl) phenylimino)methyl] benzene-1,2-diol from the reaction of 2,3-dihydroxybenzaldehyde with 3,5-bis(trifluoromethyl)aniline, and its Ni(II) and Cu(II) complexes. The molecular structure of the Schiff base was experimentally determined using X-ray single-crystal data and was compared to the structure predicted by theoretical calculations using density functional theory (DFT), Hartree-Fock (HF) and Möller-Plesset second-order perturbation (MP2). In addition, nonlinear optical (NLO) effects of the compound was predicted using DFT. The antimicrobial activities of the compounds were investigated for their minimum inhibitory concentration. UV-Vis spectroscopy studies of the interactions between the compounds and calf thymus DNA (CT-DNA) showed that the compounds interacts with CT-DNA via intercalative binding. A DNA cleavage study showed that the Cu(II) complex cleaved DNA without any external agents. The compounds inhibited the base pair mutation in the absence of S9 with high inhibition rate. In addition, in vitro cytotoxicity of the Ni(II) complex towards HepG2 cell line was assayed by the MTT method. Also, the colorimetric response of the Schiff base in DMSO to the addition of equivalent amount of anions (F-, Br-, I-, CN-, SCN-, ClO4-, HSO4-, AcO-, H2PO4-, N3- and OH-) was investigated. In this regard, while the addition of F-, CN-, AcO- and OH- anions into the solution containing Schiff base resulted in a significant color change, the addition of Br-, I-, SCN-, ClO4-, HSO4-, H2PO4- and N3- anions resulted in no color change. The most discernable color change in the Schiff base was caused by CN-, which demonstrated that the ligand can be used to selectively detect CN-.
-
49 CFR 38.127 - Sleeping compartments.
Code of Federal Regulations, 2012 CFR
2012-10-01
... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Intercity Rail Cars and Systems § 38.127 Sleeping compartments. (a...., heating and air conditioning controls, lighting controls, call buttons, electrical outlets, etc.) shall be...
-
49 CFR 38.127 - Sleeping compartments.
Code of Federal Regulations, 2013 CFR
2013-10-01
... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Intercity Rail Cars and Systems § 38.127 Sleeping compartments. (a...., heating and air conditioning controls, lighting controls, call buttons, electrical outlets, etc.) shall be...
-
49 CFR 38.127 - Sleeping compartments.
Code of Federal Regulations, 2014 CFR
2014-10-01
... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Intercity Rail Cars and Systems § 38.127 Sleeping compartments. (a...., heating and air conditioning controls, lighting controls, call buttons, electrical outlets, etc.) shall be...
-
49 CFR 38.127 - Sleeping compartments.
Code of Federal Regulations, 2011 CFR
2011-10-01
... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Intercity Rail Cars and Systems § 38.127 Sleeping compartments. (a...., heating and air conditioning controls, lighting controls, call buttons, electrical outlets, etc.) shall be...
-
49 CFR 38.127 - Sleeping compartments.
Code of Federal Regulations, 2010 CFR
2010-10-01
... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Intercity Rail Cars and Systems § 38.127 Sleeping compartments. (a...., heating and air conditioning controls, lighting controls, call buttons, electrical outlets, etc.) shall be...
-
Venkat Reddy, Putta; Reddy, Mallepally Rajender; Avudoddi, Srishailam; Praveen Kumar, Yata; Nagamani, Chintakuntla; Deepika, Nancherla; Nagasuryaprasad, K; Singh, Surya Satyanarayana; Satyanarayana, Sirasani
2015-09-15
A novel polypyridyl ligand CNPFIP (CNPFIP=2-(5(4-chloro-2-nitrophenyl)furan-2-yl)-1H-imidazo[4,5f][1,10]phenanthroline) and its mononuclear Ru(II) polypyridyl complexes of [Ru(phen)2CNPFIP](2+)(1) (phen=1,10-phenanthroline), [Ru(bpy)2CNPFIP](2+)(2) (bpy=2,2'-bipyridine), and [Ru(dmb)2CNPFIP](2+)(3) (dmb=4,4'-dimethyl-2,2'-bipyridine) have been synthesized successfully and characterized thoroughly by elemental analysis, UV/Vis, IR, NMR, and ESI-MS. The interaction of the Ru(II) complexes with calf thymus DNA (CT-DNA) was investigated by absorption titration, fluorescence, viscosity measurements. The experimental results suggest that three complexes bind to CT-DNA through an intercalative mode and the DNA-binding affinity of complex 1 is greater than that of complexes 2 and 3. The photocleavage of plasmid pBR322 DNA by ruthenium complexes 1, 2, and 3 was investigated. We have also tested three complexes for their antimicrobial activity against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) bacteria. The in vitro cytotoxicity of these complexes was evaluated by MTT assay, and complex 1 shows higher cytotoxicity than 2 and 3 on HeLa cells. The induced apoptosis and cell cycle arrest of HeLa cells were investigated by flow cytometry for 24h. The molecular docking of ruthenium complexes 1, 2, and 3 with the active site pocket residues of human DNA TOP1 was performed using LibDock. Copyright © 2015 Elsevier Inc. All rights reserved.
-
NASA Astrophysics Data System (ADS)
Zhang, Fan; Lin, Qiu-Yue; Li, Shi-Kun; Zhao, Yu-Ling; Wang, Peng-Peng; Chen, Miao-Miao
2012-12-01
Four new transition metal complexes (Habtz)2[M(DCA)2]·6H2O (M = Co(II) (1), Ni(II) (2), Cu(II) (3), Zn(II) (4); DCA = demethylcantharate, 7-oxabicyclo [2.2.1]heptane-2,3-dicarboxylate, C8H8O5; Habtz = 2-aminobenzothiazole acid, C7H7N2S) were synthesized and characterized by elemental analysis, molar conductance, infrared spectra and thermogravimetric analysis. The coordination number of complex was six. The X-ray diffraction analysis indicated that complex 3 crystallized in the triclinic crystal system with P1¯ space group. The DNA-binding properties of the complexes were investigated by electronic absorption spectra, fluorescence spectra, viscosity measurements. Title complexes could bind to DNA via partial intercalative mode. The Kb of the complexes were 5.33 × 104 (1), 7.04 × 104 (2), 9.91 × 104 (3) and 5.03 × 104 L mol-1 (4). The results of agarose gel electrophoresis showed that Cu(II) complex could cleave pBR322 plasmid DNA via radical-based mechanism. The complexes could quench the intrinsic fluorescence of bovine serum albumin (BSA) through a static quenching with the binding constants Ka of 1.11 × 104 (1), 1.24 × 106 (2), 8.42 × 105 (3) and 1.75 × 104 L mol-1 (4). The complexes had intense antiproliferative activities against human hepatoma cell lines (SMMC7721) and human gastric cancer cells (MGC80-3) lines in vitro. Cu(II) complex had the strongest activity against human gastric cancer cells.
-
47 CFR 74.655 - Authorization of equipment.
Code of Federal Regulations, 2012 CFR
2012-10-01
... EXPERIMENTAL RADIO, AUXILIARY, SPECIAL BROADCAST AND OTHER PROGRAM DISTRIBUTIONAL SERVICES Television Broadcast... and regulations. (f) Transmitters designed to be used exclusively for a TV STL station, a TV intercity...
-
75 FR 38343 - High-Speed Intercity Passenger Rail (HSIPR) Program
Federal Register 2010, 2011, 2012, 2013, 2014
2010-07-01
...This notice details the application requirements and procedures for obtaining funding for high-speed and intercity passenger rail Service Development Programs available under the Transportation, Housing and Urban Development, and Related Agencies Appropriations Act for 2010 (Div. A of the Consolidated Appropriations Act, 2010 (Pub. L. 111-117, Dec. 16, 2009)). The Federal Railroad Administration has issued a separate notice in today's edition of the Federal Register for Fiscal Year 2010 funding made available for Individual Projects. This document incorporates interim guidance required for the HSIPR program pursuant to the Transportation, Housing and Urban Development, and Related Agencies Appropriations Act for 2010 and 49 U.S.C. 24402(a)(2). The funding opportunities described in this notice are available under Catalog of Federal Domestic Assistance (CFDA) number 20.319.
-
78 FR 57447 - Environmental Impact Statement for the ACEforward
Federal Register 2010, 2011, 2012, 2013, 2014
2013-09-18
... intercity passenger rail capital investments and may provide financial assistance for the program, including...) has responsibility for providing Federal funding for intra-city commuter rail capital investments and...
-
DOT National Transportation Integrated Search
2000-03-01
Intercity passenger transportation in Kansas, as in other Midwest states, is facing enormous : challenges resulting from rapidly changing market forces. These challenges include the : increasing environmental and capital costs of investment in highwa...
-
77 FR 36586 - Proposed Collection; Comment Request
Federal Register 2010, 2011, 2012, 2013, 2014
2012-06-19
... (Oct. 17, 2008) (``Rule 204T Adopting Release''). \\2\\ Because failure to comply with the close-out..., trading in municipal securities, and using NSCC's Envelope Settlement Service or Inter-city Envelope...
-
2006 public transportation fact book
DOT National Transportation Integrated Search
2006-04-01
This book includes only public transportation data and excludes taxicab, unregulated jitney, school, sightseeing, intercity, charter, : military, and non-public service (e.g., governmental and corporate shuttles), and special application systems (e.g...
-
2004 public transportation fact book
DOT National Transportation Integrated Search
2004-03-01
This book includes only public transportation data and excludes taxicab, unregulated jitney, school, sightseeing, intercity, charter, : military, and non-public service (e.g., governmental and corporate shuttles), and special application systems (e.g...
-
2005 public transportation fact book
DOT National Transportation Integrated Search
2005-04-01
This book includes only public transportation data and excludes taxicab, unregulated jitney, school, sightseeing, intercity, charter, military, and non-public service (e.g., governmental and corporate shuttles), and special application systems (e.g.,...
-
Code of Federal Regulations, 2014 CFR
2014-10-01
... system railroad for purposes of moving only cars shipped to or from the plant. A plant or installation... no freight, intercity passenger, or commuter passenger railroad operation on the track); or (3) Used...
-
NASA Astrophysics Data System (ADS)
DELİCE, Yavuz
2015-04-01
Highways, Located in the city and intercity locations are generally prone to many kind of natural disaster risks. Natural hazards and disasters that may occur firstly from highway project making to construction and operation stages and later during the implementation of highway maintenance and repair stages have to be taken into consideration. And assessment of risks that may occur against adverse situations is very important in terms of project design, construction, operation maintenance and repair costs. Making hazard and natural disaster risk analysis is largely depending on the definition of the likelihood of the probable hazards on the highways. However, assets at risk , and the impacts of the events must be examined and to be rated in their own. With the realization of these activities, intended improvements against natural hazards and disasters will be made with the utilization of Failure Mode Effects Analysis (FMEA) method and their effects will be analyzed with further works. FMEA, is a useful method to identify the failure mode and effects depending on the type of failure rate effects priorities and finding the most optimum economic and effective solution. Although relevant measures being taken for the identified risks by this analysis method , it may also provide some information for some public institutions about the nature of these risks when required. Thus, the necessary measures will have been taken in advance in the city and intercity highways. Many hazards and natural disasters are taken into account in risk assessments. The most important of these dangers can be listed as follows; • Natural disasters 1. Meteorological based natural disasters (floods, severe storms, tropical storms, winter storms, avalanches, etc.). 2. Geological based natural disasters (earthquakes, tsunamis, landslides, subsidence, sinkholes, etc) • Human originated disasters 1. Transport accidents (traffic accidents), originating from the road surface defects (icing, signaling caused malfunctions and risks), fire or explosion etc.- In this study, with FMEA method, risk analysis of the urban and intercity motorways against natural disasters and hazards have been performed and found solutions were brought against these risks. Keywords: Failure Modes Effects Analysis (FMEA), Pareto Analyses (PA), Highways, Risk Management.
-
Raza, Aun; Xu, Xiuquan; Xia, Li; Xia, Changkun; Tang, Jian; Ouyang, Zhen
2016-11-01
Quercetin-iron (II) complex was synthesized and characterized by elemental analysis, ultraviolet-visible spectrophotometry, fourier transform infrared spectroscopy, mass spectrometry, proton nuclear magnetic resonance spectroscopy, thermogravimetry and differential scanning calorimetry, scanning electron micrography and molar conductivity. The low molar conductivity value investigates the non-electrolyte nature of the complex. The elemental analysis and other physical and spectroscopic methods reveal the 1:2 stoichiometric ratio (metal:ligand) of the complex. Antioxidant study of the quercetin and its metal complex against 2, 2-di-phenyl-1-picryl hydrazyl radical showed that the complex has much more radical scavenging activity than free quercetin. The interaction of quercetin-iron (II) complex with DNA was determined using ultraviolet visible spectra, fluorescence spectra and agarose gel electrophoresis. The results showed that quercetin-iron (II) complex can intercalate moderately with DNA, quench a strong intercalator ethidium bromide and compete for the intercalative binding sites. The complex showed significant cleavage of pBR 322 DNA from supercoiled form to nicked circular form and these cleavage effects were dose-dependent. Moreover, the mechanism of DNA cleavage indicated that it was an oxidative cleavage pathway. These results revealed the potential nuclease activity of complex to cleave DNA. In addition, antibacterial activity of complex on E.coli and S. aureus was also investigated. The results showed that complex has higher antibacterial activity than ligand.
-
Aviation Careers Series: Pilots and Flight Engineers
DOT National Transportation Integrated Search
1996-01-31
Increasing travel in the United States is threatening the mobility the nations surface transportation system provides. Congestion, particularly in urbanized areas and along heavily traveled intercity corridors, is increasing dramatically. The cost...
-
49 CFR 374.307 - Baggage service.
Code of Federal Regulations, 2010 CFR
2010-10-01
... REGULATIONS Adequacy of Intercity Motor Common Carrier Passenger Service § 374.307 Baggage service. (a... travel on the same schedule. Such baggage must then be placed on the next available bus to its...
-
2007 public transportation fact book
DOT National Transportation Integrated Search
2007-05-01
This book includes only public transportation data and excludes taxicab, unregulated jitney, school, sightseeing, intercity, charter, : military, and services not available to the general public, or segments of the general public (e.g., governmental ...
-
Hyperloop Commercial Feasibility Analysis : High Level Overview
DOT National Transportation Integrated Search
2016-07-01
Hyperloop is a concept for very highspeed, fixedguideway, intercity surface transportation, using capsulelike vehicles that operate in sealed partialvacuum tubes. This report provide a highlevel evaluation of hyperloop in terms of its ...
-
77 FR 51586 - Submission for OMB Review; Comment Request
Federal Register 2010, 2011, 2012, 2013, 2014
2012-08-24
... Release''). \\2\\ Because failure to comply with the close-out requirements of Rule 204(a) is a violation of... NSCC's Envelope Settlement Service or Inter-city Envelope Settlement Service. These activities rarely...
-
Freight Transportation : A Digest of Technical Papers. Volume 1.
DOT National Transportation Integrated Search
1976-10-28
This volume contains a number of technical papers dealing with intercity freight transportation. Collectively, these systems-oriented papers consider a wide range of subject matter including transportation facilitation, commodity flow, regulation, au...
-
36 CFR 1192.127 - Sleeping compartments.
Code of Federal Regulations, 2012 CFR
2012-07-01
... Intercity Rail Cars and Systems § 1192.127 Sleeping compartments. (a) Sleeping compartments required to be... controls, call buttons, electrical outlets, etc.) shall be mounted no more than 48 inches, and no less than...
-
36 CFR 1192.127 - Sleeping compartments.
Code of Federal Regulations, 2014 CFR
2014-07-01
... Intercity Rail Cars and Systems § 1192.127 Sleeping compartments. (a) Sleeping compartments required to be... controls, call buttons, electrical outlets, etc.) shall be mounted no more than 48 inches, and no less than...
-
36 CFR 1192.127 - Sleeping compartments.
Code of Federal Regulations, 2010 CFR
2010-07-01
... Intercity Rail Cars and Systems § 1192.127 Sleeping compartments. (a) Sleeping compartments required to be... controls, call buttons, electrical outlets, etc.) shall be mounted no more than 48 inches, and no less than...
-
36 CFR 1192.127 - Sleeping compartments.
Code of Federal Regulations, 2011 CFR
2011-07-01
... Intercity Rail Cars and Systems § 1192.127 Sleeping compartments. (a) Sleeping compartments required to be... controls, call buttons, electrical outlets, etc.) shall be mounted no more than 48 inches, and no less than...
-
Ma, Haitao; Fang, Chuanglin; Pang, Bo; Li, Guangdong
2014-01-01
Background The relations between geographical proximity and spatial distance constitute a popular topic of concern. Thus, how geographical proximity affects scientific cooperation, and whether geographically proximate scientific cooperation activities in fact exhibit geographic scale features should be investigated. Methodology Selected statistics from the ISI database on cooperatively authored papers, the authors of which resided in 60 typical cites in China, and which were published in the years 1990, 1995, 2000, 2005, and 2010, were used to establish matrices of geographic distance and cooperation levels between cities. By constructing a distance-cooperation model, the degree of scientific cooperation based on spatial distance was calculated. The relationship between geographical proximity and scientific cooperation, as well as changes in that relationship, was explored using the fitting function. Result (1) Instead of declining, the role of geographical proximity in inter-city scientific cooperation has increased gradually but significantly with the popularization of telecommunication technologies; (2) the relationship between geographical proximity and scientific cooperation has not followed a perfect declining curve, and at certain spatial scales, the distance-decay regularity does not work; (3) the Chinese scientific cooperation network gathers around different regional center cities, showing a trend towards a regional network; within this cooperation network the amount of inter-city cooperation occurring at close range increased greatly. Conclusion The relationship between inter-city geographical distance and scientific cooperation has been enhanced and strengthened over time. PMID:25365449
-
36 CFR § 1192.127 - Sleeping compartments.
Code of Federal Regulations, 2013 CFR
2013-07-01
... Intercity Rail Cars and Systems § 1192.127 Sleeping compartments. (a) Sleeping compartments required to be... controls, call buttons, electrical outlets, etc.) shall be mounted no more than 48 inches, and no less than...
-
ADA final rule : rail system accessibility
DOT National Transportation Integrated Search
2011-07-31
This document evaluates the benefits, costs, and other impacts of a DOT rulemaking related to : the accessibility of commuter rail transportation and intercity passenger rail service. In keeping with Executive Order 12866, Executive Order 13563, and ...
-
Air quality impacts of intercity freight. Volume 2 : appendices
DOT National Transportation Integrated Search
1998-07-01
This document presents best practices and practical advice on how to acquire the software components of Intelligent Transportation Systems (ITS). The executive summary briefly describes the themes and activities developed during the project developme...
-
Developing a methodology for projecting intercity commuting.
DOT National Transportation Integrated Search
2015-12-01
Texas agencies are investigating passenger rail options in several corridors connecting people : between the states major cities. Popular thinking is that there is commuter travel between a : number of these markets. In specific, Austin to Houston...
-
Performance Model of Intercity Ground Passenger Transportation Systems
DOT National Transportation Integrated Search
1975-08-01
A preliminary examination of the problems associated with mixed-traffic operations - conventional freight and high speed passenger trains - is presented. Approaches based upon a modest upgrading of existing signal systems are described. Potential cos...
-
KiranKumar, Hulihalli N; RohitKumar, Heggodu G; Advirao, Gopal M
2018-01-01
Two new derivatives of pyrimido[4',5';4,5]thieno(2,3-b)quinoline (PTQ), 9-hydroxy-4-(3-diethylaminopropylamino)pyrimido[4',5';4,5]thieno(2,3-b)quinoline (Hydroxy-DPTQ) and 8-methoxy-4-(3-diethylaminopropylamino)pyrimido[4',5';4,5]thieno(2,3-b)quinoline (Methoxy-DPTQ) were synthesized and their DNA binding ability was analyzed using spectroscopy (UV-visible, fluorescence and circular dichroism), ethidium bromide dye displacement assay, melting temperature (T m ) analysis and computational docking studies. The hypochromism in UV-visible spectrum and increased fluorescence emission of Hydroxy-DPTQ and Methoxy-DPTQ in the presence of DNA suggested the molecule-DNA interaction. The association constants calculated from UV-visible and spectral titrations were of the order 10 4 to 10 6 M -1 . Circular dichroism studies corroborated the induced conformational changes in DNA upon addition of molecules. The change in the ellipticity was observed both in negative and positive peak of DNA, thus, suggesting the intercalation of molecules. The observed displacement of ethidium bromide from the DNA and increased T m , upon addition of DNA confirmed the intercalative mode of binding. This was further validated by computational docking, which showed clear intercalation of molecules into the d(GpC)-d(CpG) site of the receptor DNA. Anticancer activities of these molecules are evaluated by using MTT assay. Both molecules showed antiproliferative activity against all the three cancer cells studied, with Hydroxy-DPTQ being more potential molecule among the two. IC 50 value of Hydroxy-DPTQ and Methoxy-DPTQ were in the range of 3-5μM and 130-250μM, respectively. Copyright © 2017 Elsevier B.V. All rights reserved.
-
Mardanya, Sourav; Karmakar, Srikanta; Mondal, Debiprasad; Baitalik, Sujoy
2016-04-04
We report in this work a new family of homo- and heterobimetallic complexes of the type [(bpy)2M(Py-Biimz)M'(II)(bpy)2](2+) (M = M' = Ru(II) or Os(II); M = Ru(II) and M' = Os(II)) derived from a pyrenyl-biimidazole-based bridge, 2-imidazolylpyreno[4,5-d]imidazole (Py-BiimzH2). The homobimetallic Ru(II) and Os(II) complexes were found to crystallize in monoclinic form with space group P21/n. All the complexes exhibit strong absorptions throughout the entire UV-vis region and also exhibit luminescence at room temperature. For osmium-containing complexes (2 and 3) both the absorption and emission band stretched up to the NIR region and thus afford more biofriendly conditions for probable applications in infrared imaging and phototherapeutic studies. Detailed luminescence studies indicate that the emission originates from the respective (3)MLCT excited state mainly centered in the [M(bpy)2](2+) moiety of the complexes and is only slightly affected by the pyrene moiety. The bimetallic complexes show two successive one-electron reversible metal-centered oxidations in the positive potential window and several reduction processes in the negative potential window. An efficient intramolecular electronic energy transfer is found to occur from the Ru center to the Os-based component in the heterometallic dyad. The binding studies of the complexes with DNA were thoroughly studied through different spectroscopic techniques such as UV-vis absorption, steady-state and time-resolved emission, circular dichroism, and relative DNA binding study using ethidium bromide. The intercalative mode of binding was suggested to be operative in all cases. Finally, computational studies employing DFT and TD-DFT were also carried out to interpret the experimentally observed absorption and emission bands of the complexes.
-
The Chicago to Iowa City intercity passenger rail route : business plan.
DOT National Transportation Integrated Search
2011-03-21
Business Plan Highlights : -No Iowa General Fund or RIIF appropriations : -State/local partnership : -Funds operation for the first 10 years : -Local cash commitment to passenger rail : -Conservative and practical financial forecasts : -Three compone...
-
Intercity passenger rail : financial performance of Amtrak's routes
DOT National Transportation Integrated Search
1998-05-14
Since it began operations in 1971, the National Railroad Passenger Corporation : (Amtrak) has never been profitable and has received about $21 billion in federal : subsidies for operating and capital expenses. In December 1994, at the : direction of ...
-
Intercity passenger rail : Amtrak's financial viability continues to be threatened
DOT National Transportation Integrated Search
1997-03-12
Amtrak's financial condition is still very precarious and heavily dependent on federal operating and capital funds. We previously reported that Amtrak's financial condition had deteriorated steadily since 1990 and that Amtrak was unlikely to overcome...
-
18 CFR 281.202 - Applicability.
Code of Federal Regulations, 2010 CFR
2010-04-01
.... Algonquin Gas Transmission Company. Arkansas Louisiana Natural Gas Company. Cities Service Gas Company.... Florida Gas Transmission Company. Great Lakes Gas Transmission Company. Inter-City Minnesota Pipelines... River Transmission Company. Montana Dakota Utilities Company. National Fuel Gas Supply Company. North...
-
Air quality impacts of intercity freight. Volume 1 : guidebook
DOT National Transportation Integrated Search
2000-01-01
Driver error remains the leading cause of highway crashes. Through the Intelligent Vehicle Initiative (IVI), the Department of Transportation hopes to reduce crashes by helping drivers avoid hazardous mistakes. IVI aims to accelerate the development ...
-
Demand projections for the northeast corridor : financial analysis
DOT National Transportation Integrated Search
1976-06-30
This report describes the development and results of intercity travel demand projections by city-pair prepared for the Northeast Corridor financial analysis. In addition associated analyses of projected passenger volumes by station and of selected al...
-
NASA Technical Reports Server (NTRS)
English, J. M.; Smith, J. L.; Lifson, M. W.
1978-01-01
Decision making in early transportation planning must be responsive to complex value systems representing various policies and objectives. The assessment of alternative transportation concepts during the early initial phases of the system life cycle, when supportive research and technology development activities are defined, requires estimates of transportation, environmental, and socio-economic impacts throughout the system life cycle, which is a period of some 40 or 50 years. A unified methodological framework for comparing intercity passenger and freight transportation systems is described and is extended to include the comparison of long term transportation trends arising from implementation of the various R & D programs. The attributes of existing and future transportation systems are reviewed in order to establish measures for comparison, define value functions, and attribute weightings needed for comparing alternative policy actions for furthering transportation goals. Comparison criteria definitions and an illustrative example are included.
-
Liu, Jianzheng; Li, Weifeng; Wu, Jiansheng; Liu, Yonghong
2018-01-01
The Beijing-Tianjin-Hebei area faces a severe fine particulate matter (PM2.5) problem. To date, considerable progress has been made toward understanding the PM2.5 problem, including spatial-temporal characterization, driving factors, and health effects. However, little research has been done on the dynamic interactions and relationships between PM2.5 concentrations in different cities in this area. To address the research gap, this study discovered a phenomenon of time-lagged intercity correlations of PM2.5 time series and proposed a visualization framework based on this phenomenon to visualize the interaction in PM2.5 concentrations between cities. The visualizations produced using the framework show that there are significant time-lagged correlations between the PM2.5 time series in different cities in this area. The visualizations also show that the correlations are more significant in colder months and between cities that are closer, and that there are seasonal changes in the temporal order of the correlated PM2.5 time series. Further analysis suggests that the time-lagged intercity correlations of PM2.5 time series are most likely due to synoptic meteorological variations. We argue that the visualizations demonstrate the interactions of air pollution between cities in the Beijing-Tianjin-Hebei area and the significant effect of synoptic meteorological conditions on PM2.5 pollution. The visualization framework could help determine the pathway of regional transportation of air pollution and may also be useful in delineating the area of interaction of PM2.5 pollution for impact analysis.
-
Li, Weifeng; Wu, Jiansheng; Liu, Yonghong
2018-01-01
The Beijing-Tianjin-Hebei area faces a severe fine particulate matter (PM2.5) problem. To date, considerable progress has been made toward understanding the PM2.5 problem, including spatial-temporal characterization, driving factors, and health effects. However, little research has been done on the dynamic interactions and relationships between PM2.5 concentrations in different cities in this area. To address the research gap, this study discovered a phenomenon of time-lagged intercity correlations of PM2.5 time series and proposed a visualization framework based on this phenomenon to visualize the interaction in PM2.5 concentrations between cities. The visualizations produced using the framework show that there are significant time-lagged correlations between the PM2.5 time series in different cities in this area. The visualizations also show that the correlations are more significant in colder months and between cities that are closer, and that there are seasonal changes in the temporal order of the correlated PM2.5 time series. Further analysis suggests that the time-lagged intercity correlations of PM2.5 time series are most likely due to synoptic meteorological variations. We argue that the visualizations demonstrate the interactions of air pollution between cities in the Beijing-Tianjin-Hebei area and the significant effect of synoptic meteorological conditions on PM2.5 pollution. The visualization framework could help determine the pathway of regional transportation of air pollution and may also be useful in delineating the area of interaction of PM2.5 pollution for impact analysis. PMID:29438417
-
Bipyrimidine ruthenium(II) arene complexes: structure, reactivity and cytotoxicity.
Betanzos-Lara, Soledad; Novakova, Olga; Deeth, Robert J; Pizarro, Ana M; Clarkson, Guy J; Liskova, Barbora; Brabec, Viktor; Sadler, Peter J; Habtemariam, Abraha
2012-10-01
The synthesis and characterization of complexes [(η(6)-arene)Ru(N,N')X][PF(6)], where arene is para-cymene (p-cym), biphenyl (bip), ethyl benzoate (etb), hexamethylbenzene (hmb), indane (ind) or 1,2,3,4-tetrahydronaphthalene (thn), N,N' is 2,2'-bipyrimidine (bpm) and X is Cl, Br or I, are reported, including the X-ray crystal structures of [(η(6)-p-cym)Ru(bpm)I][PF(6)], [(η(6)-bip)Ru(bpm)Cl][PF(6)], [(η(6)-bip)Ru(bpm)I][PF(6)] and [(η(6)-etb)Ru(bpm)Cl][PF(6)]. Complexes in which N,N' is 1,10-phenanthroline (phen), 1,10-phenanthroline-5,6-dione or 4,7-diphenyl-1,10-phenanthroline (bathophen) were studied for comparison. The Ru(II) arene complexes undergo ligand-exchange reactions in aqueous solution at 310 K; their half-lives for hydrolysis range from 14 to 715 min. Density functional theory calculations on [(η(6)-p-cym)Ru(bpm)Cl][PF(6)], [(η(6)-p-cym)Ru(bpm)Br][PF(6)], [(η(6)-p-cym)Ru(bpm)I][PF(6)], [(η(6)-bip)Ru(bpm)Cl][PF(6)], [(η(6)-bip)Ru(bpm)Br][PF(6)] and [(η(6)-bip)Ru(bpm)I][PF(6)] suggest that aquation occurs via an associative pathway and that the reaction is thermodynamically favourable when the leaving ligand is I > Br ≈ Cl. pK (a)* values for the aqua adducts of the complexes range from 6.9 to 7.32. A binding preference for 9-ethylguanine (9-EtG) compared with 9-ethyladenine (9-EtA) was observed for [(η(6)-p-cym)Ru(bpm)Cl][PF(6)], [(η(6)-hmb)Ru(bpm)Cl](+), [(η(6)-ind)Ru(bpm)Cl](+), [(η(6)-thn)Ru(bpm)Cl](+), [(η(6)-p-cym)Ru(phen)Cl](+) and [(η(6)-p-cym)Ru(bathophen)Cl](+) in aqueous solution at 310 K. The X-ray crystal structure of the guanine complex [(η(6)-p-cym)Ru(bpm)(9-EtG-N7)][PF(6)](2) shows multiple hydrogen bonding. Density functional theory calculations show that the 9-EtG adducts of all complexes are thermodynamically preferred compared with those of 9-EtA. However, the bmp complexes are inactive towards A2780 human ovarian cancer cells. Calf thymus DNA interactions for [(η(6)-p-cym)Ru(bpm)Cl][PF(6)] and [(η(6)-p-cym)Ru(phen)Cl][PF(6)] consist of weak coordinative, intercalative and monofunctional coordination. Binding to biomolecules such as glutathione may play a role in deactivating the bpm complexes.
-
Freight Transportation Information Systems and Their Implications for R&D Policy
DOT National Transportation Integrated Search
1974-03-01
The current use of computerized management information and control systems in intercity freight transportation are examined. Each of the four modes (railroad, motor carrier, maritime and air cargo industries) is investigated. In each case, computer i...
-
The effects of the ride environment on intercity train passenger activities
DOT National Transportation Integrated Search
1979-01-01
The ability to perform activities such as reading, writing, : talking, and sleeping has frequently been cited in the : ride quality literature as an important factor in passengers' : comfort and satisfaction with transportation systems. A field : stu...
-
Occupant Volume Integrity Evaluation in Passenger Rail Cars
DOT National Transportation Integrated Search
2012-02-01
This research, which is intended to enable the growth of high-speed and intercity passenger rail transportation, was sponsored by the Federal Railroad Administration (FRA) Office of Research and Development, as part of the train Occupant Protection r...
-
Occupant volume integrity evaluation in passenger rail cars.
DOT National Transportation Integrated Search
2012-02-01
This research, which is intended to enable the growth of high-speed and intercity passenger rail transportation, was sponsored by the Federal Railroad Administration (FRA) Office of Research and Development, as part of the train Occupant Protection r...
-
Mechanistic design of concrete crossties and fastening systems - Phase 1.
DOT National Transportation Integrated Search
2017-04-28
The objective of this project is the development and deployment of resilient concrete crossties and fastening systems for heavy haul freight, intercity passenger, and rail transit applications. : For a variety of reasons, concrete crossties are a dom...
-
The Chicago-Iowa City passenger rail program : fact sheet.
DOT National Transportation Integrated Search
2011-02-23
Project costs : Overall cost: $310 million : Costs allocated between Iowa and Illinois : Iowa and Illinois submitted a joint application for $248 : million (up to 80 percent of the project cost) from the : High-Speed Intercity Passenger R...
-
Chicago to Iowa City passenger rail : project financial plan.
DOT National Transportation Integrated Search
2009-09-01
The Chicago to Iowa City Intercity Passenger Rail Program (Program) is a joint : undertaking of the Iowa Department of Transportation (Iowa DOT) and the Illinois : Department of Transportation (Illinois DOT). The purpose of the Program is to reestabl...
-
Locomotive crashworthiness research : volume 5 : cab car crashworthiness report
DOT National Transportation Integrated Search
1996-03-01
Models used to analyze locomotive crashworthiness are modified for application to control cab cars of the types used for intercity and commuter rail passenger service. An existing control cab car is analyzed for crashworthiness based on scenarios dev...
-
Promoting intermodal connectivity at California's high-speed rail stations.
DOT National Transportation Integrated Search
2015-07-01
High-speed rail (HSR) has emerged as one of the most revolutionary and transformative transportation technologies, having a : profound impact on urban-regional accessibility and inter-city travel across Europe, Japan, and more recently China and othe...
-
American Airlines Propeller STOL Transport Economic Risk Analysis
NASA Technical Reports Server (NTRS)
Ransone, B.
1972-01-01
A Monte Carlo risk analysis on the economics of STOL transports in air passenger traffic established the probability of making the expected internal rate of financial return, or better, in a hypothetical regular Washington/New York intercity operation.
-
Recommended Emergency Preparedness Guidelines for Passenger Trains
DOT National Transportation Integrated Search
1993-12-01
The Federal Railroad Administration (FRA) has recognized the need for intercity and commuter passenger train systems, : regardless of the size of the system and type of service provided, to engage in careful, advance planning in order to : respond ef...
-
Intercity passenger rail : potential financial issues in the event that Amtrak undergoes liquidation
DOT National Transportation Integrated Search
2002-09-01
If Amtrak had been liquidated on December 31, 2001, secured creditors : and unsecured creditorsincluding the federal government and Amtrak : employeesand stockholders would have had about $44 billion in : potential claims against and ownership ...
-
Intercity passenger rail : issues associated with a possible Amtrak liquidation
DOT National Transportation Integrated Search
1998-03-01
The National Railroad Passenger Corporation (Amtrak) carries over 20 million : passengers a year through the trains that it operates. It also provides services, : such as dispatching, to state and local commuter rail operators. Since 1971, : Amtrak h...
-
75 FR 16562 - High-Speed Intercity Passenger Rail (HSIPR) Program
Federal Register 2010, 2011, 2012, 2013, 2014
2010-04-01
...), passenger traffic and services (marketing, ticketing, station, and on- board services), and general... retention, ``green'' environmental outcomes, potential energy savings, and effects on community livability. Program Management Approach--A phased program implementation strategy including a preliminary description...
-
Passenger train emergency systems : review of egress variables and egress simulation models
DOT National Transportation Integrated Search
2013-05-20
Federal Railroad Administration (FRA) regulations are intended to ensure the safe, timely, and effective evacuation of intercity and commuter rail passengers when necessary during passenger train emergencies. Although it is recognized that during the...
-
Passenger train emergency systems : review of egress variables and egress simulation models.
DOT National Transportation Integrated Search
2013-04-01
Federal Railroad Administration (FRA) regulations are intended to ensure the safe, timely, and effective evacuation of intercity and commuter rail passengers when necessary during passenger train emergencies. Although it is recognized that during the...
-
Seattle To Portland Inter-City ITS Corridor Study And Communications Plan, Final Report
DOT National Transportation Integrated Search
1996-03-01
THIS DOCUMENT IS THE FINAL REPORT PRESENTING THE SEATTLE TO PORTLAND INTELLIGENT TRANSPORTATION SYSTEM (ITS) EARLY DEPLOYMENT PLAN. THE FINAL REPORT SYNTHESIZES INFORMATION FROM TECHNICAL MEMORANDUMS 1 THROUGH 5; INCLUDING EXISTING AND FUTURE CONDITI...
-
NASA Astrophysics Data System (ADS)
Castanheira, Elisabete Ms; Carvalho, Maria Solange D.; Rodrigues, Ana Rita O.; Calhelha, Ricardo C.; Queiroz, Maria-João Rp
2011-05-01
Fluorescence properties of two new potential antitumoral tetracyclic thieno[3,2- b]pyridine derivatives were studied in solution and in liposomes of DPPC (dipalmitoyl phosphatidylcholine), egg lecithin (phosphatidylcholine from egg yolk; Egg-PC) and DODAB (dioctadecyldimethylammonium bromide). Compound 1, pyrido[2',3':3,2]thieno[4,5- d]pyrido[1,2- a]pyrimidin-6-one, exhibits reasonably high fluorescence quantum yields in all solvents studied (0.20 ≤ ΦF ≤ 0.30), while for compound 2, 3-[( p-methoxyphenyl)ethynyl]pyrido[2',3':3,2]thieno[4,5- d]pyrido[1,2- a]pyrimidin-6-one, the values are much lower (0.01 ≤ ΦF ≤ 0.05). The interaction of these compounds with salmon sperm DNA was studied using spectroscopic methods, allowing the determination of intrinsic binding constants, K i = (8.7 ± 0.9) × 103 M-1 for compound 1 and K i = (5.9 ± 0.6) × 103 M-1 for 2, and binding site sizes of n = 11 ± 3 and n = 7 ± 2 base pairs, respectively. Compound 2 is the most intercalative compound in salmon sperm DNA (35%), while for compound 1 only 11% of the molecules are intercalated. Studies of incorporation of both compounds in liposomes of DPPC, Egg-PC and DODAB revealed that compound 2 is mainly located in the hydrophobic region of the lipid bilayer, while compound 1 prefers a hydrated and fluid environment.
-
Comparison of high-speed rail and maglev systems
DOE Office of Scientific and Technical Information (OSTI.GOV)
Najafi, F.T.; Nassar, F.E.
1996-07-01
European and Japanese high-speed rail (HSR) and magnetically levitated (maglev) systems were each developed to respond to specific transportation needs within local economic, social, and political constraints. Not only is maglev technology substantially different from that of HSR, but also HSR and maglev systems differ in trainset design, track characteristics, cost structure, and cost sensitivity to design changes. This paper attempts to go beyond the traditional technology comparison table and focuses on the characteristics and conditions for which existing European and Japanese systems were developed. The technologies considered are the French train a grand vitesse (TGV), the Swedish X2000, themore » German Intercity Express (ICE) and Transrapid, and the Japanese Shinkansen, MLU, and high-speed surface train (HSST).« less
-
Reducing the harm in rail crashes : analysis of injury mechanisms and mitigation strategies
DOT National Transportation Integrated Search
2016-04-12
Twenty-three commuter and inter-city passenger train : accidents, which occurred over the past twenty years, have been : analyzed. The analysis has assessed the potential effectiveness : of various injury mitigation strategies. The strategies with th...
-
Energy and Economic Impacts of Projected Freight Transportation Improvements
DOT National Transportation Integrated Search
1977-05-01
This study examines current and future energy impacts for each major freight mode, by commodity, and, in many cases, by vehicle types. It also discusses potential economic impacts of these anticipated changes. The study is limited to intercity freigh...
-
Fire Safety of Passenger Trains: A Review of U.S. and Foreign Approaches
DOT National Transportation Integrated Search
1993-12-01
could develop into potentially life-threatening events. Fire safety is an area of particular interest for both : conventional intercity and commuter trains, as well as new alternative high-speed train technologies. These : technologies include steel-...
-
Iowa rail route alternatives analysis.
DOT National Transportation Integrated Search
1998-06-01
The development of new rail systems in the first part of the 21st century is the result of a wide range : of trends that are making it increasingly difficult to maintain regional mobility using the two : dominant intercity travel modes, auto and air....
-
47 CFR 74.582 - Station identification.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 47 Telecommunication 4 2010-10-01 2010-10-01 false Station identification. 74.582 Section 74.582..., AUXILIARY, SPECIAL BROADCAST AND OTHER PROGRAM DISTRIBUTIONAL SERVICES Aural Broadcast Auxiliary Stations § 74.582 Station identification. (a) Each aural broadcast STL or intercity relay station, when...
-
DOT National Transportation Integrated Search
2014-11-01
To meet the increasingly stringent design and performance requirements due to increasing cumulative : gross tonnages from heavy-haul freight operations, along with increased high-speed inter-city passenger : rail development, improvements in concrete...
-
36 CFR Appendix F to Part 1191 - Modifications Adopted by the Department of Transportation
Code of Federal Regulations, 2010 CFR
2010-07-01
... negotiate steps may have to travel compared to the general public. Modification to 406 of Appendix D 406... shall be 8 inches (205 mm) minimum above top of rail. In light rail, commuter rail, and intercity rail...
-
Intercity passenger rail : Amtrak's progress in improving its financial condition has been mixed
DOT National Transportation Integrated Search
1999-07-01
Since its creation in 1971, Amtrak has accumulated massive financial losses, with recent losses averaging more than $800 million per year. To help Amtrak sustain operations and make needed capital investments, the federal government has provided Amtr...
-
76 FR 14443 - High-Speed Intercity Passenger Rail (HSIPR) Program
Federal Register 2010, 2011, 2012, 2013, 2014
2011-03-16
... Environmental Policy Act (NEPA) documentation, final design (FD), and construction. For the purpose of this... designing, engineering, location surveying, mapping, environmental studies, and acquiring rights-of-way..., final design, and construction activities are eligible to receive funding. For applications for Service...
-
Chicago to Iowa City intercity passenger rail route : business plan.
DOT National Transportation Integrated Search
2011-03-21
This business plan describes the methods by which the Iowa Department of Transportation (DOT will partner with Iowa counties and cities to fund Iowas share of the operating and maintenance cost for the Chicago-Iowa City passenger-rail service, an ...
-
ERIC Educational Resources Information Center
Journalism Quarterly, 1985
1985-01-01
Presents summaries of research dealing with (1) news coverage of Africa, (2) diffusion of information about cyanide-laced Tylenol, (3) gender representation in elite newspapers, (4) agreement between reporters and editors in Mississippi, (5) monopoly metropolitan dailies and intercity competition, and (6) the effect of endorsements on the…
-
Prediction and Control of Noise and Vibration in Rail Transit Systems
DOT National Transportation Integrated Search
1978-09-01
The purpose of this report is to present a balanced introductory view of noise from rail transportation systems and its control, and to provide references to more specialized material. The emphasis is on urban transit systems. However, data on interc...
-
Biodiesel intercity passenger rail revenue service test.
DOT National Transportation Integrated Search
2013-10-01
Amtrak, with the support of the Federal Railroad Administration, operated a P-32 passenger locomotive in revenue service for a : period of 12 months, on a blend of 20 percent pure biodiesel and 80 percent #2 ultra-low sulfur diesel (ULSD) fuel. The G...
-
The role of stable isotopes in understanding rainfall interception processes: a review
The isotopic composition of water transmitted by the canopy as throughfall or stemflow reflects important hydrologic processes occurring in the canopy. A synthesis of the literature shows that complex spatiotemporal variations of isotopic composition are created by canopy interce...
-
Joint Cost, Production Technology and Output Disaggregation in Regulated Motor Carriers
DOT National Transportation Integrated Search
1978-11-01
The study uses a sample of 252 Class I Instruction 27 Motor Carriers (Instruction 27 carriers earned at least 75 percent of their revenues from intercity transportation of general commodities over a three year period) of general freight that existed ...
-
Impact of Personal Attitudes on Propensity to Use Autonomous Vehicles for Intercity Travel.
DOT National Transportation Integrated Search
2016-01-01
The autonomous vehicles are about to become a reality. The researchers estimate the benefits from each autonomous vehicle to be between $2000 and $4500 per vehicles. The : societal benefits include higher travel time savings, reduced congestion, fuel...
-
DOT National Transportation Integrated Search
2009-02-01
Just over 40 percent of U.S. passenger ferry terminals : offer connections to other scheduled public transportation : modes. That makes ferries less connected than intercity : rail, where 53 percent of stations have links with other : modes, but more...
-
Annoyance caused by the sounds of a magnetic levitation train
NASA Astrophysics Data System (ADS)
Vos, Joos
2004-04-01
In a laboratory study, the annoyance caused by the passby sounds from a magnetic levitation (maglev) train was investigated. The listeners were presented with various sound fragments. The task of the listeners was to respond after each presentation to the question: ``How annoying would you find the sound in the preceding period if you were exposed to it at home on a regular basis?'' The independent variables were (a) the driving speed of the maglev train (varying from 100 to 400 km/h), (b) the outdoor A-weighted sound exposure level (ASEL) of the passbys (varying from 65 to 90 dB), and (c) the simulated outdoor-to-indoor reduction in sound level (windows open or windows closed). As references to the passby sounds from the maglev train (type Transrapid 08), sounds from road traffic (passenger cars and trucks) and more conventional railway (intercity trains) were included for rating also. Four important results were obtained. Provided that the outdoor ASELs were the same, (1) the annoyance was independent of the driving speed of the maglev train, (2) the annoyance caused by the maglev train was considerably higher than that caused by the intercity train, (3) the annoyance caused by the maglev train was hardly different from that caused by road traffic, and (4) the results (1)-(3) held true both for open or closed windows. On the basis of the present results, it might be expected that the sounds are equally annoying if the ASELs of the maglev-train passbys are at least 5 dB lower than those of the intercity train passbys. Consequently, the results of the present experiment do not support application of a railway bonus to the maglev-train sounds.
-
Annoyance caused by the sounds of a magnetic levitation train.
Vos, Joos
2004-04-01
In a laboratory study, the annoyance caused by the passby sounds from a magnetic levitation (maglev) train was investigated. The listeners were presented with various sound fragments. The task of the listeners was to respond after each presentation to the question: "How annoying would you find the sound in the preceding period if you were exposed to it at home on a regular basis?" The independent variables were (a) the driving speed of the maglev train (varying from 100 to 400 km/h), (b) the outdoor A-weighted sound exposure level (ASEL) of the passbys (varying from 65 to 90 dB), and (c) the simulated outdoor-to-indoor reduction in sound level (windows open or windows closed). As references to the passby sounds from the maglev train (type Transrapid 08), sounds from road traffic (passenger cars and trucks) and more conventional railway (intercity trains) were included for rating also. Four important results were obtained. Provided that the outdoor ASELs were the same, (1) the annoyance was independent of the driving speed of the maglev train, (2) the annoyance caused by the maglev train was considerably higher than that caused by the intercity train, (3) the annoyance caused by the maglev train was hardly different from that caused by road traffic, and (4) the results (1)-(3) held true both for open or closed windows. On the basis of the present results, it might be expected that the sounds are equally annoying if the ASELs of the maglev-train passbys are at least 5 dB lower than those of the intercity train passbys. Consequently, the results of the present experiment do not support application of a railway bonus to the maglev-train sounds.
-
Intercity passenger rail : increasing Amtrak's accountability for its Taxpayer Relief Act funds
DOT National Transportation Integrated Search
2000-03-15
Since 1971, the federal government has provided the National Railroad Passenger Corporation (Amtrak) with $23 billion in financial support. This support includes a total of about $2.2 billion in 1998 and 1999 through the Taxpayer Relief Act of 1997 (...
-
DOT National Transportation Integrated Search
2000-05-01
This report responds to the request to review Amtrak's costs and capital investment needs. In particular, this report discusses changes since 1995 in Amtrak's operating costs, including labor costs, payments to freight railroads to access their track...
-
49 CFR 37.21 - Applicability: General.
Code of Federal Regulations, 2010 CFR
2010-10-01
...: (1) Any public entity that provides designated public transportation or intercity or commuter rail transportation; (2) Any private entity that provides specified public transportation; and (3) Any private entity... 49 Transportation 1 2010-10-01 2010-10-01 false Applicability: General. 37.21 Section 37.21...
-
49 CFR 256.13 - Review and approval of applications.
Code of Federal Regulations, 2010 CFR
2010-10-01
... local public and private investment, by transportation carriers and others, in improved intercity and local public transportation facilities and services; (7) Encourage the preservation of railroad... 49 Transportation 4 2010-10-01 2010-10-01 false Review and approval of applications. 256.13...
-
Ports of Delaware Bay: Industry And Public Sector Cooperation For Information Sharing
2010-12-01
Introduction MIST Fall 2010 high-density tunnels, stations, and bridges. Another $20 million was provided for intercity ...passenger rail to protect infrastructure and the traveling public.12 This commitment of funds at a time of shrinking budgets demonstrates the essential
-
Development of techniques and data for evaluating ride quality. Volume 2 : ride-quality research
DOT National Transportation Integrated Search
1978-03-01
Ride-quality models for city buses and intercity trains are presented : and discussed in terms of their ability to predict passenger : comfort and ride acceptability. : This, the second of three volumes, contains a technical discussion, : of the ride...
-
78 FR 65244 - Rail Vehicles Access Advisory Committee
Federal Register 2010, 2011, 2012, 2013, 2014
2013-10-31
...-0001] RIN 3014-AA42 Rail Vehicles Access Advisory Committee AGENCY: Architectural and Transportation Barriers Compliance Board. ACTION: Notice of advisory committee meeting. SUMMARY: The Rail Vehicles Access... vehicles that operate on fixed guideway systems (e.g., rapid rail, light rail, commuter rail, intercity...
-
A School-Community Inter-City Project
ERIC Educational Resources Information Center
Demaray, Elois
1976-01-01
This article briefly outlines the objectives and approaches to be instituted in establishing an environmental studies program for the San Francisco Bay area. The project incorporates community and school resources. The approach will be interdisciplinary combining ecologic concepts with socioeconomic concepts in analyzing the past and present…
-
DOT National Transportation Integrated Search
2014-05-01
With increasing demand and rising fuel costs, both travel time and cost of intercity passenger : transportation are becoming increasingly significant. Around the world, high-speed rail (HSR) is seen as a : way to mitigate the risk of volatile petrole...
-
49 CFR 1139.22 - Revenue data for study carriers.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 8 2010-10-01 2010-10-01 false Revenue data for study carriers. 1139.22 Section 1139.22 Transportation Other Regulations Relating to Transportation (Continued) SURFACE TRANSPORTATION... Intercity Bus Industry § 1139.22 Revenue data for study carriers. The study carriers, as identified above...
-
Work Exploration At The Junior-High Level
ERIC Educational Resources Information Center
Devin, Paul
1969-01-01
The New Horizons Project provides 300 Des Moines inter-city junior high school students, who possess skills but are not making satisfactory academic progress, with work-study, extra guidance, and individual attention in an effort to increase their chance of vocational, social, civic and academic success. (Author/JG)
-
DOT National Transportation Integrated Search
2016-08-01
This project developed a solid-state welding process based on linear friction welding (LFW) technology. While resistance flash welding or : thermite techniques are tried and true methods for joining rails and performing partial rail replacement repai...
-
Code of Federal Regulations, 2010 CFR
2010-10-01
... and others, and other public activities supported in whole or in part under Federal law. (g) Council...: Intercity bus, commuter rail, intra-city rail transit and bus transportation, airport limousine service and... Railroad Revitalization and Regulatory Reform Act of 1976, as amended, Public Law 94-210, 90 Stat. 125, 49...
-
49 CFR 374.309 - Terminal facilities.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 5 2010-10-01 2010-10-01 false Terminal facilities. 374.309 Section 374.309... REGULATIONS Adequacy of Intercity Motor Common Carrier Passenger Service § 374.309 Terminal facilities. (a... attendants and be regularly patrolled. (b) Outside facilities. At terminals and stations that are closed when...
-
Examining long-distance express buses as an extension of and feeder to passenger rail systems.
DOT National Transportation Integrated Search
2011-03-01
One of the mobility challenges facing Texas and other high-population states in the coming years is the : rising travel demand along major intercity travel corridors. Increased passenger rail service may help to : absorb some of the travel demand fro...
-
47 CFR 74.502 - Frequency assignment.
Code of Federal Regulations, 2011 CFR
2011-10-01
... meet the capability or quality requirements. (c) Aural broadcast STL and intercity relay stations that... are not entitled to protection from fixed-satellite service operations and must not cause unacceptable... protection criteria in § 101.105(a), (b), and (c) of this chapter and the frequency usage coordination...
-
47 CFR 74.502 - Frequency assignment.
Code of Federal Regulations, 2010 CFR
2010-10-01
... meet the capability or quality requirements. (c) Aural broadcast STL and intercity relay stations that... are not entitled to protection from fixed-satellite service operations and must not cause unacceptable... protection criteria in § 101.105(a), (b), and (c) of this chapter and the frequency usage coordination...
-
Railway vehicle body structures
DOE Office of Scientific and Technical Information (OSTI.GOV)
Not Available
1985-01-01
The strength and durability of railway vehicle structures is a major topic of engineering research and design. To reflect this importance the Railway Division of the Institution of Mechanical Engineers organised a conference to discuss all matters relating to railway vehicle design. This book presents the papers discussed in that conference. The contents include: Vehicle body design and the UIC's international contribution; LUL prototype 1986 stock - body structure; vehicle structure for the intermediate capacity transmit system vehicles; car body technology of advanced light rapid transit vehicles; concepts, techniques and experience in the idealization of car body structures for finitemore » element analysis; Calcutta metropolitan railway; design for a lightweight diesel multiple unit body; the design of lightweight inter-city coal structures; the BREL international coach body shell structure; new concepts and design techniques versus material standards; structures of BR diesel electric freight locomotives; structural design philosophy for electric locomotives; suspension design for a locomotive with low structural frequencies; freight wagon structures; a finite element study of coal bodyside panels including the effects of joint flexibility; a fresh approach to the problem of car body design strength; energy absorption in automatic couplings and draw gear; passenger vehicle design loads and structural crashworthiness; design of the front part of railway vehicles (in case of frontal impact); the development of a theoretical technique for rail vehicle structural crashworthiness.« less
-
Guo, Xin; Wu, Lili; Navrotsky, Alexandra
2018-02-07
Gas absorption calorimetry has been employed to probe the intercation of water and carbon dioxide with transition metal ion (TM = Mn 2+ , Fe 2+ , Co 2+ , Cu 2+ , and Zn 2+ ) exchanged zeolite A samples. There appears to be a two-phase region, indicative of a guest-induced flexibility transition, separating hydrated zeolite A and its dehydrated form, both of which have variable water content in the single phase region. The differential enthalpy of absorption as a function of water loading directly identifies different strengths of multiple interactions along with possible binding mechanisms of Zn-A and Mn-A exhibiting the highest water absorption with most exothermic initial enthalpies of -125.28 ± 4.82 and -115.30 ± 2.56 kJ mol -1 . Zn-A and Mn-A also show moderately good capture ability for CO 2 with zero-coverage negative enthalpies of -55.59 ± 2.48 and -44.07 ± 1.53 kJ mol -1 . The thermodynamic information derived from differential enthalpy, chemical potential and differential entropy elucidated the multistage interactive behavior of small guest molecules (H 2 O/CO 2 ) and ion-exchanged frameworks.
-
Uddin, Noor; Sirajuddin, Muhammad; Uddin, Nizam; Tariq, Muhammad; Ullah, Hameed; Ali, Saqib; Tirmizi, Syed Ahmed; Khan, Abdur Rehman
2015-04-05
This article contains the synthesis of a novel carboxylic acid derivative, its transition metal complexes and evaluation of biological applications. Six carboxylate complexes of transition metals, Zn(II) and Hg(II), have been successfully synthesized and characterized by FT-IR and NMR (1H, 13C). The ligand, HL, (4-[(2,6-Diethylphenyl)amino]-4-oxobutanoic acid) was also characterized by single crystal X-ray analysis. The complexation occurs via oxygen atoms of the carboxylate moiety. FT-IR date show the bidentate nature of the carboxylate moiety of the ligand as the Δν value in all complexes is less than that of the free ligand. The ligand and its complexes were screened for antifungal and antileishmanial activities. The results showed that the ligand and its complexes are active with few exceptions. UV-visible spectroscopy and viscometry results reveal that the ligand and its complexes interact with the DNA via intercalative mode of interaction. A new and efficient strategy to identify the pharmacophores and anti-pharmacophores sites in carboxylate derivatives for the antibacterial/antifungal activity using Petra, Osiris and Molinspiration (POM) analyses was also carried out. Copyright © 2014 Elsevier B.V. All rights reserved.
-
NASA Astrophysics Data System (ADS)
Uddin, Noor; Sirajuddin, Muhammad; Uddin, Nizam; Tariq, Muhammad; Ullah, Hameed; Ali, Saqib; Tirmizi, Syed Ahmed; Khan, Abdur Rehman
2015-04-01
This article contains the synthesis of a novel carboxylic acid derivative, its transition metal complexes and evaluation of biological applications. Six carboxylate complexes of transition metals, Zn(II) and Hg(II), have been successfully synthesized and characterized by FT-IR and NMR (1H, 13C). The ligand, HL, (4-[(2,6-Diethylphenyl)amino]-4-oxobutanoic acid) was also characterized by single crystal X-ray analysis. The complexation occurs via oxygen atoms of the carboxylate moiety. FT-IR date show the bidentate nature of the carboxylate moiety of the ligand as the Δν value in all complexes is less than that of the free ligand. The ligand and its complexes were screened for antifungal and antileishmanial activities. The results showed that the ligand and its complexes are active with few exceptions. UV-visible spectroscopy and viscometry results reveal that the ligand and its complexes interact with the DNA via intercalative mode of interaction. A new and efficient strategy to identify the pharmacophores and anti-pharmacophores sites in carboxylate derivatives for the antibacterial/antifungal activity using Petra, Osiris and Molinspiration (POM) analyses was also carried out.
-
Rab11a and its binding partners regulate the recycling of the β1-adrenergic receptor
Gardner, Lidia A.; Hajjhussein, Hassan; Frederick, Katherine C.; Bahouth, Suleiman W.
2010-01-01
β1-adrenergic receptors (β1-AR) are internalized in response to agonists and then recycle back for another round of signaling. The serine 312 to alanine mutant of the β1-AR (S312A) is internalized but does not recycle. We determined that WT β1-AR and S312A were internalized initially to an early sorting compartment because they colocalized by >70% with the early endosomal markers rab5a and early endosomal antigen-1 (EEA1). Subsequently, the WT β1-AR trafficked via rab4a-expressing sorting endosomes to recycling endosomes. In recycling endosomes WT β1-AR were colocalized by >70% with the rab11 GTPase. S312A did not colocalize with either rab4a or rab11, instead they exited from early endosomes to late endosomes/lysosomes in which they were degraded. Rab11a played a prominent role in recycling of the WT β1-AR because dominant negative rab11a inhibited, while constitutively active rab11a accelerated the recycling of the β1-AR. Next, we determined the effect of each of the rab11-intercating proteins on trafficking of the WT β1-AR. The recycling of the β1-AR was markedly inhibited when myosin Vb, FIP2, FIP3 and rabphillin were knocked down. These data indicate that rab11a and a select group of its binding partners play a prominent role recycling of the human β1-AR. PMID:20727405
-
Tak, Aijaz Ahmad; Arjmand, Farukh
2002-01-01
Five coordinated novel complexes of Cu II and Ni II have been synthesized from benzil and 1,3- diaminopropane- Cu II / Ni II complex and characterized by elemental analysis, i.r., n.m.r., e.p.r, molar conductance and u.v-vis, spectroscopy. The complexes are ionic in nature and exhibit pentaeoordinated geometry around the metal ion. The reaction kinetics of C 25 H 36 N 5 O 2 CuCl with calf thymus DNA was studied by u.v-vis, spectroscopy in aqueous medium. The complex after interaction with calf thymus DNA shows shift in the absorption spectrum and hypochromicity indicating an intercalative binding mode. The K obs values have been calculated under pseudo-first order conditions. The redox behaviour of complex C 25 H 36 N 5 O 2 CuCl in the presence and in the absence of calf thymus DNA in the aqueous solution has been investigated by cyclic voltammetry. The cyclic voitammogram exhibits one quasi-reversible redox wave corresponding to Cu II / Cu I redox couple with E 1 / 2 values of -0.377 and -0.237 V respectively at a scan rate of 0.1V s - 1 .On interaction with calf thymus DNA, the complex C 25 H 36 N 5 O 2 CuCl exhibits shifts in both E p as well as in E 1 / 2 values, indicating strong binding of the complex to the calf thymus DNA. PMID:18475428
-
Impact of high-speed passenger trains on freight train efficiency in shared railway corridors.
DOT National Transportation Integrated Search
2015-01-01
In the United States, freight rail demand had doubled from 0.9 trillion ton-miles in 1980 to 1.8 trillion tonmiles : in 2007, and railroad carriers reached a 39.5% market penetration in 20071 : . As intercity passenger : rail is widely recognized as ...
-
Airport landside operations and air service
NASA Astrophysics Data System (ADS)
Mandle, P. B.; Whitlock, E. M.; Lamagna, F.; Mundy, R. A.; Oberhausen, P. J.
The following areas are discussed: airport curbside planning and design; analysis of New Orleans airport ground transportation system; time series analysis of intercity air travel volume; economic justification of air service to small communities; and general aviation and the airport and airway system (an analysis of cost allocation and recovery).
-
Pathfinder, Volume 7, Number 3, May/June 2009. A Historic Role
2009-06-01
Intelligence System (DMIGS) into service. These self- contained vehicles represent “NGA on wheels” and can travel to any and all National Special Security...never had any formal military training, but with Hogarth’s interces - sion, he received a commission as a second lieutenant interpreter in the British
-
Transportation Energy Use and Conservation Potential
ERIC Educational Resources Information Center
Hirst, Eric
1973-01-01
Analyzes transportation energy consumption and energy intensiveness for inter-city freight and passenger traffic and urban passenger traffic with the definition of energy intensiveness as Btu per ton-mile or per passenger-mile. Indicates that public education is one of three ways to achieve the goals of energy conservation. (CC)
-
45 CFR 1801.40 - Travel expenses of finalists.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 45 Public Welfare 4 2010-10-01 2010-10-01 false Travel expenses of finalists. 1801.40 Section 1801... FOUNDATION HARRY S. TRUMAN SCHOLARSHIP PROGRAM Payments to Finalists and Scholars § 1801.40 Travel expenses of finalists. The Foundation will provide partial funding for intercity round-trip transportation...
-
47 CFR 74.582 - Station identification.
Code of Federal Regulations, 2013 CFR
2013-10-01
... § 74.582 Station identification. (a) Each aural broadcast STL or intercity relay station, when... each period of operation, and hourly, as close to the hour as feasible, at a natural break in program... identification transmissions during operation need not be made when to make such transmission would interrupt a...
-
47 CFR 74.582 - Station identification.
Code of Federal Regulations, 2012 CFR
2012-10-01
... § 74.582 Station identification. (a) Each aural broadcast STL or intercity relay station, when... each period of operation, and hourly, as close to the hour as feasible, at a natural break in program... identification transmissions during operation need not be made when to make such transmission would interrupt a...
-
47 CFR 74.582 - Station identification.
Code of Federal Regulations, 2014 CFR
2014-10-01
... § 74.582 Station identification. (a) Each aural broadcast STL or intercity relay station, when... each period of operation, and hourly, as close to the hour as feasible, at a natural break in program... identification transmissions during operation need not be made when to make such transmission would interrupt a...
-
47 CFR 74.582 - Station identification.
Code of Federal Regulations, 2011 CFR
2011-10-01
... § 74.582 Station identification. (a) Each aural broadcast STL or intercity relay station, when... each period of operation, and hourly, as close to the hour as feasible, at a natural break in program... identification transmissions during operation need not be made when to make such transmission would interrupt a...
-
DOT National Transportation Integrated Search
1997-04-01
Amtrak is still in a financial crisis despite the fact that its financial : performance (as measured by net losses)2 has improved over the last 2 : years. At the end of fiscal year 1994, Amtraks net loss was about $1.1 : billion (in 1996 dollars)....
-
49 CFR 38.117 - Floors, steps and thresholds.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 1 2010-10-01 2010-10-01 false Floors, steps and thresholds. 38.117 Section 38...) ACCESSIBILITY SPECIFICATIONS FOR TRANSPORTATION VEHICLES Intercity Rail Cars and Systems § 38.117 Floors, steps and thresholds. (a) Floor surfaces on aisles, step treads and areas where wheelchair and mobility aid...
-
47 CFR 74.432 - Licensing requirements and procedures.
Code of Federal Regulations, 2013 CFR
2013-10-01
... EXPERIMENTAL RADIO, AUXILIARY, SPECIAL BROADCAST AND OTHER PROGRAM DISTRIBUTIONAL SERVICES Remote Pickup... transmitter or points of any intercity relay system on frequencies in Groups I and J. (d) Base stations may be... at the control point of the station. (k) In case of permanent discontinuance of operations of a...
-
49 CFR 38.121 - Public information system.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 1 2010-10-01 2010-10-01 false Public information system. 38.121 Section 38.121... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Intercity Rail Cars and Systems § 38.121 Public information system. (a) Each car shall be equipped with a public address system permitting transportation system personnel, or...
-
36 CFR 1192.121 - Public information system.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Public information system... Intercity Rail Cars and Systems § 1192.121 Public information system. (a) Each car shall be equipped with a... messages, to announce stations and provide other passenger information. Alternative systems or devices...
-
DOT National Transportation Integrated Search
1999-11-01
When Argentina initiated the reforms of its transport sector in 1989, it was constructing its own path-breaking way. It was the first in Latin America to privatize its inter-city railroad, the first to organize intra-port competition explicitly, the ...
-
49 CFR 1139.26 - Availability of underlying data.
Code of Federal Regulations, 2010 CFR
2010-10-01
... Intercity Bus Industry § 1139.26 Availability of underlying data. All underlying data used in preparation of... 49 Transportation 8 2010-10-01 2010-10-01 false Availability of underlying data. 1139.26 Section... made available to the Board upon request therefor. The underlying data shall be made available also at...
-
49 CFR 1139.26 - Availability of underlying data.
Code of Federal Regulations, 2011 CFR
2011-10-01
... Intercity Bus Industry § 1139.26 Availability of underlying data. All underlying data used in preparation of... 49 Transportation 8 2011-10-01 2011-10-01 false Availability of underlying data. 1139.26 Section... made available to the Board upon request therefor. The underlying data shall be made available also at...
-
Assessment of air quality impact of a proposed section of Interstate 66.
DOT National Transportation Integrated Search
1972-01-01
This report presents an assessment of the impact of a proposed section of Interstate 66 on the quality of the air in the immediate area of the project and in adjacent areas. The proposed project begins with an extension of existing I-66 at the interc...
-
Driving Occupations. Reprinted from the Occupational Outlook Handbook, 1978-79 Edition.
ERIC Educational Resources Information Center
Bureau of Labor Statistics (DOL), Washington, DC.
Focusing on driving occupations, this document is one in a series of forty-one reprints from the Occupational Outlook Handbook providing current information and employment projections for individual occupations and industries through 1985. The specific occupations covered in this document include intercity busdrivers, local transit busdrivers,…
-
49 CFR Schedule G to Subpart B of... - Selected Statistical Data
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 8 2010-10-01 2010-10-01 false Selected Statistical Data G Schedule G to Subpart... Statistical Data [Dollars in thousands] () Greyhound Lines, Inc. () Trailways combined () All study carriers.... 9002, L. 9, col. (b) Other Statistics: 25Number of regulator route intercity passenger miles Sch. 9002...
-
DOT National Transportation Integrated Search
2016-01-01
The majority of intercity passenger and commuter rail services in the United States (U.S.) operate on the shared-use corridors with : freight rail services. These types of operations tend to be challenging for efficient capacity utilization and relia...
-
Khan, Saman; Malla, Ali Mohammed; Zafar, Atif
2017-01-01
Despite substantial research on cancer therapeutics, systemic toxicity and drug-resistance limits the clinical application of many drugs like cisplatin. Therefore, new chemotherapeutic strategies against different malignancies are needed. Targeted cancer therapy is a new paradigm for cancer therapeutics which targets pathways or chemical entities specific to cancer cells than normal ones. Unlike normal cells, cancer cells contain elevated copper which plays an integral role in angiogenesis. Copper is an important metal ion associated with chromatin DNA, particularly with guanine. Thus, targeting copper via copper-specific chelators in cancer cells can serve as an effective anticancer strategy. New pharmacophore di(2-picolyl)amine (DPA)-3(bromoacetyl) coumarin (ligand-L) was synthesized and characterized by IR, ESI-MS, 1H- and 13C-NMR. Binding ability of ligand-L to DNA/Cu(II) was evaluated using a plethora of biophysical techniques which revealed ligand-L-DNA and ligand-L-Cu(II) interaction. Competitive displacement assay and docking confirmed non-intercalative binding mode of ligand-L with ctDNA. Cyclic voltammetry confirmed ligand-L causes quasi reversible Cu(II)/Cu(I) conversion. Further, acute toxicity studies revealed no toxic effects of ligand-L on mice. To evaluate the chemotherapeutic potential and anticancer mechanism of ligand-L, DNA damage via pBR322 cleavage assay and reactive oxygen species (ROS) generation were studied. Results demonstrate that ligand-L causes DNA cleavage involving ROS generation in the presence of Cu(II). In conclusion, ligand-L causes redox cycling of Cu(II) to generate ROS which leads to oxidative DNA damage and pro-oxidant cancer cell death. These findings will establish ligand-L as a lead molecule to synthesize new molecules with better copper chelating and pro-oxidant properties against different malignancies. PMID:28763458
-
2009-11-08
travel routes, holidays, festivals, sports, and other events; climate and weather; and water. Planning Planning must give appropriate weight...they can be manipulated rather easily, they are militarily significant. (1) Physical patterns such as market locations and travel routes may provide...cycle, cutting or controlling intercity and intracity mobility and communications, triggering an adversary response, or positioning forces to conduct
-
49 CFR Schedule B to Subpart B of... - Study Carriers' Revenue Data
Code of Federal Regulations, 2012 CFR
2012-10-01
... 49 Transportation 8 2012-10-01 2012-10-01 false Study Carriers' Revenue Data B Schedule B to Subpart B of Part 1139 Transportation Other Regulations Relating to Transportation (Continued) SURFACE... PROCEEDINGS Intercity Bus Industry Pt. 1139, Subpt. B, Sch. B Schedule B to Subpart B of Part 1139—Study...
-
49 CFR Schedule B to Subpart B of... - Study Carriers' Revenue Data
Code of Federal Regulations, 2013 CFR
2013-10-01
... 49 Transportation 8 2013-10-01 2013-10-01 false Study Carriers' Revenue Data B Schedule B to Subpart B of Part 1139 Transportation Other Regulations Relating to Transportation (Continued) SURFACE... PROCEEDINGS Intercity Bus Industry Pt. 1139, Subpt. B, Sch. B Schedule B to Subpart B of Part 1139—Study...
-
49 CFR Schedule B to Subpart B of... - Study Carriers' Revenue Data
Code of Federal Regulations, 2014 CFR
2014-10-01
... 49 Transportation 8 2014-10-01 2014-10-01 false Study Carriers' Revenue Data B Schedule B to Subpart B of Part 1139 Transportation Other Regulations Relating to Transportation (Continued) SURFACE... PROCEEDINGS Intercity Bus Industry Pt. 1139, Subpt. B, Sch. B Schedule B to Subpart B of Part 1139—Study...
-
DOT National Transportation Integrated Search
1978-02-01
Ride-quality models for city buses and intercity trains are presented and discussed in terms of their ability to predict passenger comfort and ride acceptability. The report, the last of three volumes, contains procedural guidelines to be employed by...
-
Intercity passenger rail : Amtrak needs to improve its accountability for taxpayer relief act funds
DOT National Transportation Integrated Search
2000-02-01
This report discusses 1) how much Amtrak has spent in TRA (Taxpayer Relief Act) funds and what types of activities it has funded; 2) whether Amtrak has used TRA funds in accordance with the act; 3) what the roles of the Amtrak Reform Council and the ...
-
76 FR 10634 - Agency Information Collection Activity Under OMB Review
Federal Register 2010, 2011, 2012, 2013, 2014
2011-02-25
... assistance from FTA to enter into a charter bus agreement with the Secretary of Transportation (delegated to... intercity charter bus operators from unfair competition by FTA recipients. 49 U.S.C. 5302(a)(10) as..., to provide charter bus service with FTA-funded facilities and equipment only if it is incidental to...
-
49 CFR Appendix D to Part 228 - Guidance on Fatigue Management Plans
Code of Federal Regulations, 2011 CFR
2011-10-01
... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION HOURS OF SERVICE OF RAILROAD EMPLOYEES Pt. 228, App. D Appendix D to..., Substantive Hours of Service Requirements for Train Employees Engaged in Commuter or Intercity Rail Passenger... fatigue experienced by their train employees subject to that subpart and to reduce the likelihood of...
-
Code of Federal Regulations, 2011 CFR
2011-10-01
... 49 Transportation 4 2011-10-01 2011-10-01 false Analysis of work schedules; submissions; FRA... Employees Engaged in Commuter or Intercity Rail Passenger Transportation § 228.407 Analysis of work schedules; submissions; FRA review and approval of submissions; fatigue mitigation plans. (a) Analysis of...
-
Federal Register 2010, 2011, 2012, 2013, 2014
2013-05-16
... the Atlanta to Charlotte Portion of the Southeast High Speed Rail Corridor AGENCY: Federal Rail... potential passenger rail improvements between Atlanta, GA and Charlotte, NC, along the Southeast High-Speed... federal High-Speed Intercity Passenger Rail (HSIPR) program and includes the development of a Passenger...
-
75 FR 38365 - High-Speed Intercity Passenger Rail (HSIPR) Program
Federal Register 2010, 2011, 2012, 2013, 2014
2010-07-01
... notice in today's edition of the Federal Register for Fiscal Year 2010 funding made available for Service... and 49 U.S.C. 24402(a)(2). The funding opportunities described in this notice are available under... [email protected] , or by mail: U.S. Department of Transportation, Federal Railroad Administration, MS-20...
-
DOT National Transportation Integrated Search
2013-01-01
Each railroad covered by 49 CFR 228.407 must perform an analysis of the work schedules of its train employees who are engaged in commuter or intercity rail passenger transportation and identify those schedules that, if worked by such a train employee...
-
The impact of precipitation on land interfacility transport times.
Giang, Wayne C W; Donmez, Birsen; Ahghari, Mahvareh; MacDonald, Russell D
2014-12-01
Timely transfer of patients among facilities within a regionalized critical-care system remains a large obstacle to effective patient care. For medical transport systems where dispatchers are responsible for planning these interfacility transfers, accurate estimates of interfacility transfer times play a large role in planning and resource-allocation decisions. However, the impact of adverse weather conditions on transfer times is not well understood. Precipitation negatively impacts driving conditions and can decrease free-flow speeds and increase travel times. The objective of this research was to quantify and model the effects of different precipitation types on land travel times for interfacility patient transfers. It was hypothesized that the effects of precipitation would accumulate as the distance of the transfer increased, and they would differ based on the type of precipitation. Urgent and emergent interfacility transfers carried out by the medical transport system in Ontario from 2005 through 2011 were linked to Environment Canada's (Gatineau, Quebec, Canada) climate data. Two linear models were built to estimate travel times based on precipitation type and driving distance: one for transfers between cities (intercity) and another for transfers within a city (intracity). Precipitation affected both transfer types. For intercity transfers, the magnitude of the delays increased as driving distance increased. For median-distance intercity transfers (48 km), snow produced delays of approximately 9.1% (3.1 minutes), while rain produced delays of 8.4% (2.9 minutes). For intracity transfers, the magnitude of delays attributed to precipitation did not depend on distance driven. Transfers in rain were 8.6% longer (1.7 minutes) compared to no precipitation, whereas only statistically marginal effects were observed for snow. Precipitation increases the duration of interfacility land ambulance travel times by eight percent to ten percent. For transfers between cities, snow is associated with the longest delays (versus rain), but for transfers within a single city, rain is associated with the longest delays.
-
Surface Transportation Security Priority Assessment
2010-03-01
intercity buses), and pipelines, and related infrastructure (including roads and highways), that are within the territory of the United States...Modernizing the information technology infrastructure used to vet the identity of travelers and transportation workers Using terrorist databases to...examination of persons travelling , surface transportation modes tend to operate in a much more open environment, making it difficult to screen workers
-
49 CFR Schedule B to Subpart B of... - Study Carriers' Revenue Data
Code of Federal Regulations, 2011 CFR
2011-10-01
... 49 Transportation 8 2011-10-01 2011-10-01 false Study Carriers' Revenue Data B Schedule B to... PROCEEDINGS Intercity Bus Industry Pt. 1139, Subpt. B, Sch. B Schedule B to Subpart B of Part 1139—Study Carriers' Revenue Data [Dollars in thousands] Line No. and study carrier (a) Total operating revenue (b...
-
49 CFR Schedule B to Subpart B of... - Study Carriers' Revenue Data
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 8 2010-10-01 2010-10-01 false Study Carriers' Revenue Data B Schedule B to... PROCEEDINGS Intercity Bus Industry Pt. 1139, Subpt. B, Sch. B Schedule B to Subpart B of Part 1139—Study Carriers' Revenue Data [Dollars in thousands] Line No. and study carrier (a) Total operating revenue (b...
-
Transportation. Teacher's Guide and Student Guide. Net Energy Unit. Draft.
ERIC Educational Resources Information Center
Treagust, David F.
This module is intended to increase the students' comprehension of costs, in terms of money and in energy, involved in various modes of transportation. Four main inquiries are covered in the module: (1) money saved by car pooling to school; (2) reductions in fuel consumption possible without car pooling; (3) comparisons of inter-city and urban…
-
DOT National Transportation Integrated Search
2011-12-01
"High-speed passenger rail is seen by many in the U.S. transportation policy and planning communities as : an ideal solution for fast, safe, and resource-efficient mobility in high-demand intercity corridors between : 100 and 500 miles in total endpo...
-
36 CFR 1192.117 - Floors, steps and thresholds.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Floors, steps and thresholds... Intercity Rail Cars and Systems § 1192.117 Floors, steps and thresholds. (a) Floor surfaces on aisles, step.... (b) All step edges and thresholds shall have a band of color(s) running the full width of the step or...
-
49 CFR 38.125 - Mobility aid accessibility.
Code of Federal Regulations, 2011 CFR
2011-10-01
... SPECIFICATIONS FOR TRANSPORTATION VEHICLES Intercity Rail Cars and Systems § 38.125 Mobility aid accessibility... cars, other than level entry cars, required to be accessible by §§ 38.111 (a) and (e) of this subpart... complying with § 38.113(d) are provided, the car is not required to be equipped with a car-borne device. (b...
-
Jalali, Fahimeh; Rasaee, Gelareh
2015-11-01
Possible interaction between immunosuppressive drug, azathioprine, and calf thymus DNA was explored by cyclic voltammetry, spectrophotometry, competitive spectrofluorimetry, circular dichroism spectroscopy (CD), and viscosity measurements. Cyclic voltammetry showed negative shift in the reduction peak of azathioprine in the presence of DNA, and large decrease in peak current, referring to the predominance of electrostatic forces. The binding constant was calculated to be 1.22×10(3)M(-1). Absorption hyperchromism without shift in wavelength was observed when DNA was added to azathioprine solution. Competitive fluorescence experiments were conducted by using Hoechst 33258 and methylene blue as probes for minor groove and intercalation binding modes, respectively. The studies showed that azathioprine could release Hoechst 33258, while negligible effect was detected in the case of methylene blue. Stern-Volmer quenching constant (KSV) and complex formation constant (Kf) were obtained from the fluorescence measurements to be 7.6×10(3)M(-1) and 7.76×10(4)M(-1), respectively, at 298K. Enthalpy and entropy changes during the interaction between azathioprine and DNA were calculated from Van't Hoff plot (ΔH=-20.2kJmol(-1); ΔS=26.11Jmol(-1)K(-1) at 298K) which showed an exothermic spontaneous reaction, and involvement of electrostatic forces in the complex formation with DNA. Moreover, circular dichroism studies revealed that azathioprine induced detectable changes in the negative band of DNA spectrum. Viscosity of DNA solution decreased in the presence of azathioprine, showed a non-intercalative mode of interaction. Finally, molecular docking calculations showed that in the lowest energy level of drug-DNA complex, azathioprine approaches the minor grooves of DNA. Copyright © 2015 Elsevier B.V. All rights reserved.
-
Zafar, Atif; Ahmad, Irshad; Ahmad, Ajaz; Ahmad, Masood
2016-03-30
Mass treatment of lymphatic filariasis with Albendazole (ABZ), a therapeutic benzimidazole, is fraught with serious limitations such as possible drug resistance and poor macrofilaricidal activity. Therefore, we need to develop new ABZ-based formulations to improve its antifilarial effectiveness. CuO nanoparticles were used as an adjuvant with ABZ to form ABZ-CuO nanocomposite, which was characterized by UV-vis spectroscopy, FT-IR, AFM and SEM. Antifilarial activity of nanocomposite was evaluated using relative motility assay and dye exclusion test in dark and under UV light. ROS generation, antioxidant levels, lipid peroxidation and DNA fragmentation in nanocomposite treated parasites were estimated. Biophysical techniques were employed to ascertain the mode of binding of nanocomposite to parasitic DNA. Nanocomposite increases parasite mortality as compared to ABZ in dark, and its antifilarial effect was increased further under UV light. Elevated ROS production and decline of parasitic-GST and GSH levels were observed in nanocomposite treated worms in dark, and these effects were pronounced further under UV light. Nanocomposite leads to higher DNA fragmentation as compared to ABZ alone. Further, we found that nanocomposite binds parasitic DNA in an intercalative manner where it generates ROS to induce DNA damage. Thus, oxidative stress production due to ROS generation and consequent DNA fragmentation leads to apoptosis in worms. This is the first report supporting CuO nanoparticles as a potential adjuvant with ABZ against filariasis along with enhanced antifilarial activity of nanocomposite under UV light. These findings, thus, indicate that development of ABZ-loaded nanoparticle compounds may serve as promising leads for filariasis treatment. Copyright © 2016 Elsevier B.V. All rights reserved.
-
Tamayo, Lenka V; Gouvea, Ligiane R; Sousa, Anna C; Albuquerque, Ronniel M; Teixeira, Sarah Fernandes; de Azevedo, Ricardo Alexandre; Louro, Sonia R W; Ferreira, Adilson Kleber; Beraldo, Heloisa
2016-02-01
Copper(II) complexes [Cu(H2O)2 (L1)(phen)](ClO4) (1) and [Cu(H2O)(L2)(phen)](ClO4) (2) (HL1 = naringenin; HL2 = hesperetin) were obtained, in which an anionic flavonoid ligand is attached to the metal center along with 1,10-phenanthroline (phen) as co-ligand. Complexes (1) and (2) were assayed for their cytotoxic activity against A549 lung carcinoma and against normal lung fibroblasts (LL-24) and human umbilical vein endothelial cells (HUVEC). We found IC50 = 16.42 µM (1) and IC50 = 5.82 µM (2) against A549 tumor cells. Complexes (1) and (2) exhibited slight specificity, being more cytotoxic against malignant than against non-malignant cells. 1 and 2 induced apoptosis on A549 cells in a mitochondria-independent pathway, and showed antioxidant activity. The antioxidant effect of the complexes could possibly improve their apoptotic action, most likely by a PI3K-independent reduction of autophagy. Complexes (1) and (2) interact in vitro with calf thymus DNA by an intercalative binding mode. EPR data indicated that 1 and 2 interact with human serum albumin (HSA) forming mixed ligand species.
-
Kowal, Ewa A.; Lad, Rahul R.; Pallan, Pradeep S.; Dhummakupt, Elizabeth; Wawrzak, Zdzislaw; Egli, Martin; Sturla, Shana J.; Stone, Michael P.
2013-01-01
The 2′-deoxynucleoside containing the synthetic base 1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)-1H-perimidin-2(3H)-one] (dPer) recognizes in DNA the O6-benzyl-2′-deoxyguanosine nucleoside (O6-Bn-dG), formed by exposure to N-benzylmethylnitrosamine. Herein, we show how dPer distinguishes between O6-Bn-dG and dG in DNA. The structure of the modified Dickerson–Drew dodecamer (DDD) in which guanine at position G4 has been replaced by O6-Bn-dG and cytosine C9 has been replaced with dPer to form the modified O6-Bn-dG:dPer (DDD-XY) duplex [5′-d(C1G2C3X4A5A6T7T8Y9G10C11G12)-3′]2 (X = O6-Bn-dG, Y = dPer) reveals that dPer intercalates into the duplex and adopts the syn conformation about the glycosyl bond. This provides a binding pocket that allows the benzyl group of O6-Bn-dG to intercalate between Per and thymine of the 3′-neighbor A:T base pair. Nuclear magnetic resonance data suggest that a similar intercalative recognition mechanism applies in this sequence in solution. However, in solution, the benzyl ring of O6-Bn-dG undergoes rotation on the nuclear magnetic resonance time scale. In contrast, the structure of the modified DDD in which cytosine at position C9 is replaced with dPer to form the dG:dPer (DDD-GY) [5′-d(C1G2C3G4A5A6T7T8Y9G10C11G12)-3′]2 duplex (Y = dPer) reveals that dPer adopts the anti conformation about the glycosyl bond and forms a less stable wobble pairing interaction with guanine. PMID:23748954
-
Bag, Subhendu Sekhar; Talukdar, Sangita; Kundu, Rajen; Saito, Isao; Jana, Subhashis
2014-01-25
Dual door entry to exciplex formation was established in a chimeric DNA duplex wherein a fluorescent non-nucleosidic base surrogate () is paired against a fluorescent nucleosidic base surrogate (). Packing of the nucleobases via intercalative stacking interactions led to an exciplex emission either via FRET from the donor or direct excitation of the FRET acceptor .
-
Code of Federal Regulations, 2010 CFR
2010-04-01
... travelled with passengers as well as mileage travelled incidental to such passenger transportation, such as... which “substantially all” (85 percent or more) of the use involves transporting students and employees... which students or employees of school are transported is considered to be a use which involves...
-
Carbon storage by urban soils in the United States
Richard V. Pouyat; Ian D. Yesilonis; David J. Nowak
2006-01-01
We used data available from the literature and measurements from Baltimore, Maryland to (i) assess inter-city variability of soil oganic carbon (SOC) pools (1-m depth) of six cities (Atlanta, Baltimore, Boston, Chicago, Oakland, and Syracuse); (ii) calculate the net effect of urban land-use conversion on SOC pools for the same cities; (iii) use the National Land Cover...
-
49 CFR 37.49 - Designation of responsible person(s) for intercity and commuter rail stations.
Code of Federal Regulations, 2013 CFR
2013-10-01
...) designated in accordance with this section shall bear the legal and financial responsibility for making a key... party. (c) In the case of a station more than fifty percent of which is owned by a private entity the... of which no entity owns more than fifty percent, the owners of the station (other than private entity...
-
49 CFR 37.49 - Designation of responsible person(s) for intercity and commuter rail stations.
Code of Federal Regulations, 2012 CFR
2012-10-01
...) designated in accordance with this section shall bear the legal and financial responsibility for making a key... party. (c) In the case of a station more than fifty percent of which is owned by a private entity the... of which no entity owns more than fifty percent, the owners of the station (other than private entity...
-
49 CFR 37.49 - Designation of responsible person(s) for intercity and commuter rail stations.
Code of Federal Regulations, 2014 CFR
2014-10-01
...) designated in accordance with this section shall bear the legal and financial responsibility for making a key... party. (c) In the case of a station more than fifty percent of which is owned by a private entity the... of which no entity owns more than fifty percent, the owners of the station (other than private entity...
-
49 CFR 37.49 - Designation of responsible person(s) for intercity and commuter rail stations.
Code of Federal Regulations, 2011 CFR
2011-10-01
...) designated in accordance with this section shall bear the legal and financial responsibility for making a key... party. (c) In the case of a station more than fifty percent of which is owned by a private entity the... of which no entity owns more than fifty percent, the owners of the station (other than private entity...
-
Federal Register 2010, 2011, 2012, 2013, 2014
2011-09-19
... station platforms, that passengers with disabilities can get on and off any accessible car of the train... train car that other passengers can board at the station. These means include providing car-borne lifts... disabilities can get on and off any accessible car that is available to passengers at a station platform. At...
-
49 CFR Schedule G to Subpart B of... - Selected Statistical Data
Code of Federal Regulations, 2012 CFR
2012-10-01
... 49 Transportation 8 2012-10-01 2012-10-01 false Selected Statistical Data G Schedule G to Subpart... PROCEEDINGS Intercity Bus Industry Pt. 1139, Subpt. B, Sch. G Schedule G to Subpart B of Part 1139—Selected... Line No. and Item (a) Source (b) 1972 (c) 1973 (d) 1974 (e) 1975 (f) 1976 (g) Cols. (h)-(l) (1977...
-
49 CFR Schedule G to Subpart B of... - Selected Statistical Data
Code of Federal Regulations, 2014 CFR
2014-10-01
... 49 Transportation 8 2014-10-01 2014-10-01 false Selected Statistical Data G Schedule G to Subpart... PROCEEDINGS Intercity Bus Industry Pt. 1139, Subpt. B, Sch. G Schedule G to Subpart B of Part 1139—Selected... Line No. and Item (a) Source (b) 1972 (c) 1973 (d) 1974 (e) 1975 (f) 1976 (g) Cols. (h)-(l) (1977...
-
49 CFR Schedule G to Subpart B of... - Selected Statistical Data
Code of Federal Regulations, 2013 CFR
2013-10-01
... 49 Transportation 8 2013-10-01 2013-10-01 false Selected Statistical Data G Schedule G to Subpart... PROCEEDINGS Intercity Bus Industry Pt. 1139, Subpt. B, Sch. G Schedule G to Subpart B of Part 1139—Selected... Line No. and Item (a) Source (b) 1972 (c) 1973 (d) 1974 (e) 1975 (f) 1976 (g) Cols. (h)-(l) (1977...
-
Suburb-to-suburb intercity travel: Energy, time and dollar expenditures
NASA Technical Reports Server (NTRS)
Fels, M. F.
1976-01-01
The effect of adding suburb to terminal and terminal to suburb travel is examined. The energy consumed in entire trips was estimated. The total energy costs are compared with total travel times, and dollar costs to the traveler. Trips between origins in seven suburbs of Newark, New Jersey and destinations in two Washington, D. C. suburbs are analyzed.
-
26 CFR 48.6421-3 - Time for filing claim for credit or payment.
Code of Federal Regulations, 2011 CFR
2011-04-01
... respect to gasoline used in a qualified business use or as a fuel in an aircraft (other than aircraft in noncommercial aviation) or in § 48.6421-2 with respect to gasoline used either in an intercity or local bus... public or in school bus transportation operations, shall cover only gasoline used during the taxable year...
-
26 CFR 48.6421-3 - Time for filing claim for credit or payment.
Code of Federal Regulations, 2010 CFR
2010-04-01
... respect to gasoline used in a qualified business use or as a fuel in an aircraft (other than aircraft in noncommercial aviation) or in § 48.6421-2 with respect to gasoline used either in an intercity or local bus... public or in school bus transportation operations, shall cover only gasoline used during the taxable year...
-
Code of Federal Regulations, 2012 CFR
2012-10-01
... plates, ramps or other appropriate devices; (4) Mini-high platforms, with multiple mini-high platforms or... chooses a means of meeting the performance standard other than using car-borne lifts, it must perform a comparison of the costs (capital, operating, and life-cycle costs) of car-borne lifts and the means chosen by...
-
Code of Federal Regulations, 2014 CFR
2014-10-01
... plates, ramps or other appropriate devices; (4) Mini-high platforms, with multiple mini-high platforms or... chooses a means of meeting the performance standard other than using car-borne lifts, it must perform a comparison of the costs (capital, operating, and life-cycle costs) of car-borne lifts and the means chosen by...
-
Code of Federal Regulations, 2011 CFR
2011-10-01
... plates, ramps or other appropriate devices; (4) Mini-high platforms, with multiple mini-high platforms or... chooses a means of meeting the performance standard other than using car-borne lifts, it must perform a comparison of the costs (capital, operating, and life-cycle costs) of car-borne lifts and the means chosen by...
-
Code of Federal Regulations, 2013 CFR
2013-10-01
... plates, ramps or other appropriate devices; (4) Mini-high platforms, with multiple mini-high platforms or... chooses a means of meeting the performance standard other than using car-borne lifts, it must perform a comparison of the costs (capital, operating, and life-cycle costs) of car-borne lifts and the means chosen by...
-
49 CFR Schedule C to Subpart B of... - Schedule C to Subpart B of Part 1139
Code of Federal Regulations, 2014 CFR
2014-10-01
... 49 Transportation 8 2014-10-01 2014-10-01 false Schedule C to Subpart B of Part 1139 C Schedule C... REVENUE PROCEEDINGS Intercity Bus Industry Pt. 1139, Subpt. B, Sch. C Schedule C to Subpart B of Part 1139 Attachment 1 Schedule C Part I—Condensed Income Statement [Dollars in thousands] () Greyhound Lines, Inc...
-
49 CFR Schedule C to Subpart B of... - Schedule C to Subpart B of Part 1139
Code of Federal Regulations, 2011 CFR
2011-10-01
... 49 Transportation 8 2011-10-01 2011-10-01 false Schedule C to Subpart B of Part 1139 C Schedule C... REVENUE PROCEEDINGS Intercity Bus Industry Pt. 1139, Subpt. B, Sch. C Schedule C to Subpart B of Part 1139 Attachment 1 Schedule C Part I—Condensed Income Statement [Dollars in thousands] () Greyhound Lines, Inc...
-
49 CFR Schedule C to Subpart B of... - Schedule C to Subpart B of Part 1139
Code of Federal Regulations, 2010 CFR
2010-10-01
... 49 Transportation 8 2010-10-01 2010-10-01 false Schedule C to Subpart B of Part 1139 C Schedule C... REVENUE PROCEEDINGS Intercity Bus Industry Pt. 1139, Subpt. B, Sch. C Schedule C to Subpart B of Part 1139 Attachment 1 Schedule C Part I—Condensed Income Statement [Dollars in thousands] () Greyhound Lines, Inc...
-
Noise annoyance caused by magnetic levitation train passbys
NASA Astrophysics Data System (ADS)
Vos, Joos
2004-05-01
In a laboratory study, the annoyance caused by the passby sounds from a magnetic levitation (maglev) train was investigated. The outdoor A-weighted sound exposure level (ASEL) of the maglev sounds varied from 65 to 90 dB. The driving speed of the maglev train varied from 100 to 400 km/h. Four important results were obtained. Provided that the outdoor ASELs were the same, (1) the annoyance was independent of the driving speed of the maglev train, (2) the annoyance caused by the maglev train was considerably higher than that caused by intercity trains, (3) the annoyance caused by the maglev train was hardly different from that caused by road traffic (passenger cars and trucks), and (4) the results (1)-(3) held true both for open or closed windows. On the basis of the present results, it might be expected that the sounds are equally annoying if the ASELs of the maglev-train passbys are at least 5 dB lower than those of the intercity train passbys. Consequently, the results of the present experiment do not support application of a railway bonus to the maglev-train sounds. Issues for future research, such as exploring further contributions of nonacoustic factors, will be discussed.
-
Acute subdural hemorrhage while traveling by bus: a risk factor in the elderly?
Soysal, Suna; Topacoglu, Hakan; Acarbay, Sabiha; Ozbas, Kerem
2005-01-01
A 71-year-old man was delivered to our emergency department by an intercity bus. About 4 hours into a journey, he had complained of a headache to his wife. After one more hour, she noted a change in his level of alertness and notified the bus driver. A computed tomography scan of the head showed a subdural hemorrhage.
-
NASA Astrophysics Data System (ADS)
Abdel-Rahman, Laila H.; El-Khatib, Rafat M.; Nassr, Lobna A. E.; Abu-Dief, Ahmed M.; Lashin, Fakhr El-Din
2013-07-01
In this study, new Fe(II) Schiff base amino acid chelates derived from the condensation of o-hydroxynaphthaldehyde with L-alanine, L-phenylalanine, L-aspartic acid, L-histidine and L-arginine were synthesized and characterized via elemental, thermogravimetric analysis, molar conductance, IR, electronic, mass spectra and magnetic moment measurements. The stoichiometry and the stability constants of the complexes were determined spectrophotometrically. Correlation of all spectroscopic data suggested that Schiff bases ligands exhibited tridentate with ONO sites coordinating to the metal ions via protonated phenolic-OH, azomethine-N and carboxylate-O with the general formulae [Fe(HL)2]·nH2O. But in case of L-histidine, the ligand acts as tetradentate via deprotonated phenolic-OH, azomethine-N, carboxylate-O and N-imidazole ring ([FeL(H2O)2]·2H2O), where HL = mono anion and L = dianion of the ligand. The structure of the prepared complexes is suggested to be octahedral. The prepared complexes were tested for their teratogenicity on chick embryos and found to be safe until a concentration of 100 μg/egg with full embryos formation. Moreover, the interaction between CT-DNA and the investigated complexes were followed by spectrophotometric and viscosity measurements. It was found that, the prepared complexes bind to DNA via classical intercalative mode and showed a different DNA activity with the sequence: nhi > nari > nali > nasi > nphali. Furthermore, the free ligands and their complexes are screened for their in vitro antibacterial and antifungal activity against three types of bacteria, Escherichia coli, Pseudomonas aeruginosa and Bacillus cereus and three types of anti fungal cultures, Penicillium purpurogenium, Aspergillus flavus and Trichotheium rosium in order to assess their antimicrobial potential. The results show that the metal complexes are more reactive with respect to their corresponding Schiff base amino acid ligands.
-
Models of metal binding structures in fulvic acid from the Suwannee River, Georgia
Leenheer, J.A.; Brown, G.K.; MacCarthy, P.; Cabaniss, S.E.
1998-01-01
Fulvic acid, isolated from the Suwannee River, Georgia, was assessed for its ability to bind Ca2+, Cd2+, Cu2+, Ni2+, and Zn2+ ions at pH 6 before and after extensive fractionation that was designed to reveal the nature of metal binding functional groups. The binding constant for Ca2+ ion had the greatest increase of all the ions in a metal binding fraction that was selected for intensive characterization for the purpose of building quantitative average model structures. The 'metal binding' fraction was characterized by quantitative 13C NMR, 1H NMR, and FT-1R spectrometry and elemental, titrimetric, and molecular weight determinations. The characterization data revealed that carboxyl groups were clustered in short- chain aliphatic dibasic acid structures. The Ca2+ binding data suggested that ether-substituted oxysuccinic acid structures are good models for the metal binding sites at pH 6. Structural models were derived based upon oxidation and photolytic rearrangements of cutin, lignin, and tannin precursors. These structural models rich in substituted dibasic acid structures revealed polydentate binding sites with the potential for both inner-sphere and outer-sphere type binding. The majority of the fulvic acid molecule was involved with metal binding rather than a small substructural unit.Fulvic acid, isolated from the Suwannee River, Georgia, was assessed for its ability to bind Ca2+, Cd2+, Cu2+, Ni2+, and Zn2+ ions at pH 6 before and after extensive fractionation that was designed to reveal the nature of metal binding functional groups. The binding constant for Ca2+ ion had the greatest increase of all the ions in a metal binding fraction that was selected for intensive characterization for the purpose of building quantitative average model structures. The `metal binding' fraction was characterized by quantitative 13C NMR, 1H NMR, and FT-IR spectrometry and elemental, titrimetric, and molecular weight determinations. The characterization data revealed that carboxyl groups were clustered in short-chain aliphatic dibasic acid structures. The Ca2+ binding data suggested that ether-substituted oxysuccinic acid structures are good models for the metal binding sites at pH 6. Structural models were derived based upon oxidation and photolytic rearrangements of cutin, lignin, and tannin precursors. These structural models rich in substituted dibasic acid structures revealed polydentate binding sites with the potential for both inner-sphere and outer-sphere type binding. The majority of the fulvic acid molecule was involved with metal binding rather than a small substructural unit.
-
A deep learning framework for modeling structural features of RNA-binding protein targets
Zhang, Sai; Zhou, Jingtian; Hu, Hailin; Gong, Haipeng; Chen, Ligong; Cheng, Chao; Zeng, Jianyang
2016-01-01
RNA-binding proteins (RBPs) play important roles in the post-transcriptional control of RNAs. Identifying RBP binding sites and characterizing RBP binding preferences are key steps toward understanding the basic mechanisms of the post-transcriptional gene regulation. Though numerous computational methods have been developed for modeling RBP binding preferences, discovering a complete structural representation of the RBP targets by integrating their available structural features in all three dimensions is still a challenging task. In this paper, we develop a general and flexible deep learning framework for modeling structural binding preferences and predicting binding sites of RBPs, which takes (predicted) RNA tertiary structural information into account for the first time. Our framework constructs a unified representation that characterizes the structural specificities of RBP targets in all three dimensions, which can be further used to predict novel candidate binding sites and discover potential binding motifs. Through testing on the real CLIP-seq datasets, we have demonstrated that our deep learning framework can automatically extract effective hidden structural features from the encoded raw sequence and structural profiles, and predict accurate RBP binding sites. In addition, we have conducted the first study to show that integrating the additional RNA tertiary structural features can improve the model performance in predicting RBP binding sites, especially for the polypyrimidine tract-binding protein (PTB), which also provides a new evidence to support the view that RBPs may own specific tertiary structural binding preferences. In particular, the tests on the internal ribosome entry site (IRES) segments yield satisfiable results with experimental support from the literature and further demonstrate the necessity of incorporating RNA tertiary structural information into the prediction model. The source code of our approach can be found in https://github.com/thucombio/deepnet-rbp. PMID:26467480
-
Code of Federal Regulations, 2013 CFR
2013-10-01
... consecutive hours, until that employee has had at least 10 consecutive hours off duty; or (3) In a series of... first series of at most 14 consecutive calendar days begins on the first calendar day that the employee....413. A series of at most 14 consecutive calendar days either ends on the 14th consecutive day or may...
-
Code of Federal Regulations, 2014 CFR
2014-10-01
... consecutive hours, until that employee has had at least 10 consecutive hours off duty; or (3) In a series of... first series of at most 14 consecutive calendar days begins on the first calendar day that the employee....413. A series of at most 14 consecutive calendar days either ends on the 14th consecutive day or may...
-
Code of Federal Regulations, 2012 CFR
2012-10-01
... consecutive hours, until that employee has had at least 10 consecutive hours off duty; or (3) In a series of... first series of at most 14 consecutive calendar days begins on the first calendar day that the employee....413. A series of at most 14 consecutive calendar days either ends on the 14th consecutive day or may...
-
NASA Technical Reports Server (NTRS)
Schoendorfer, David L.; Morlok, Edward K.
1985-01-01
The cost analysis done to support an assessment of the potential for a small tilt-rotor aircraft to operate in short-haul intercity passenger service is described in detail. Anticipated costs of tilt-rotor air service were compared to the costs of two alternatives: conventional air and high speed rail (HSR). Costs were developed for corridor service, varying key market characteristics including distance, passenger volumes, and minimum frequency standards. The resulting cost vs output information can then be used to compare modal costs for essentially identical service quality and passenger volume or for different service levels and volumes for each mode, as appropriate. Extensive sensitivity analyses are performed. The cost-output features of these technologies are compared. Tilt-rotor is very attractive compared to HSR in terms of costs over the entire range of volume. It also has costs not dramatically different from conventional air, but tilt-rotor costs are generally higher. Thus some of its other advantages, such as the VTOL capability, must offset the cost disadvantage for it to be a preferred or competitive mode in any given market. These issues are addressed in the companion report which considers strategies for tilt-rotor development in commercial air service.
-
McCarthy, Michael J
2011-01-01
As a component of a training development project for intercity air travel providers, we investigated the capacity of the airline industry to meet the needs of travelers with disabilities by exploring: (1) the level of sensitivity among personnel to travelers' needs, (2) training currently provided, (3) areas in which additional training might be beneficial, and (4) organisational/systems-level commitment to dignified assistance to all travelers. Forty-four airline/vendor employees participated in nine focus groups in four US cities. Groups were audio recorded and transcribed. A grounded-theory approach was used to develop a coding system which was then applied to transcripts to identify themes. Factors influencing capacity grouped broadly into four areas: characteristics of the job/system, characteristics of current training, characteristics of providers themselves, and characteristics of travelers. At an interpersonal level, providers were empathetic and desired to provide dignified services. They lacked training and adequate equipment in some cases, however, and organisational commitment varied between companies. Traveler characteristics were also shown to impact service delivery. Results are promising but additional regulatory and organisational policies are needed to ensure quality services. Providers and consumers of intercity air travel services may benefit from the findings and recommendations of this study.
-
Maglev guideway route alignment and right-of-way requirements
NASA Astrophysics Data System (ADS)
Carlton, S.; Andriola, T.
1992-12-01
The use of existing rights-of-way (ROW) is assessed for maglev systems by estimating trip times and land acquisition requirements for potential maglev corridors while meeting passenger comfort limits. Right-of-way excursions improve trip time but incur a cost for purchasing land. The final report documents findings of the eight tasks in establishing right-of-way feasibility by examining three city-pair corridors in detail and developing an approximation method for estimating route length and travel times in 20 additional city-pair corridor portions and 21 new corridors. The use of routes independent of existing railroad or highway right-of-way have trip time advantages and significantly reduce the need for aggressive guideway geometries on intercity corridors. Selection of the appropriate alignment is determined by many corridor specific issues. Use of existing intercity rights-of-way may be appropriate for parts of routes on a corridor-specific basis and for urban penetration where vehicle speeds are likely to be reduced by policy due to noise and safety considerations, and where land acquisition costs are high. Detailed aspects of available rights-of-way, land acquisition costs, geotechnical issues, land use, and population centers must be examined in more detail on a specific corridor basis before the proper or best maglev alignment can be chosen.
-
NASA Astrophysics Data System (ADS)
Ginanjar, Irlandia; Pasaribu, Udjianna S.; Indratno, Sapto W.
2017-03-01
This article presents the application of the principal component analysis (PCA) biplot for the needs of data mining. This article aims to simplify and objectify the methods for objects clustering in PCA biplot. The novelty of this paper is to get a measure that can be used to objectify the objects clustering in PCA biplot. Orthonormal eigenvectors, which are the coefficients of a principal component model representing an association between principal components and initial variables. The existence of the association is a valid ground to objects clustering based on principal axes value, thus if m principal axes used in the PCA, then the objects can be classified into 2m clusters. The inter-city buses are clustered based on maintenance costs data by using two principal axes PCA biplot. The buses are clustered into four groups. The first group is the buses with high maintenance costs, especially for lube, and brake canvass. The second group is the buses with high maintenance costs, especially for tire, and filter. The third group is the buses with low maintenance costs, especially for lube, and brake canvass. The fourth group is buses with low maintenance costs, especially for tire, and filter.
-
Improve the prediction of RNA-binding residues using structural neighbours.
Li, Quan; Cao, Zanxia; Liu, Haiyan
2010-03-01
The interactions between RNA-binding proteins (RBPs) with RNA play key roles in managing some of the cell's basic functions. The identification and prediction of RNA binding sites is important for understanding the RNA-binding mechanism. Computational approaches are being developed to predict RNA-binding residues based on the sequence- or structure-derived features. To achieve higher prediction accuracy, improvements on current prediction methods are necessary. We identified that the structural neighbors of RNA-binding and non-RNA-binding residues have different amino acid compositions. Combining this structure-derived feature with evolutionary (PSSM) and other structural information (secondary structure and solvent accessibility) significantly improves the predictions over existing methods. Using a multiple linear regression approach and 6-fold cross validation, our best model can achieve an overall correct rate of 87.8% and MCC of 0.47, with a specificity of 93.4%, correctly predict 52.4% of the RNA-binding residues for a dataset containing 107 non-homologous RNA-binding proteins. Compared with existing methods, including the amino acid compositions of structure neighbors lead to clearly improvement. A web server was developed for predicting RNA binding residues in a protein sequence (or structure),which is available at http://mcgill.3322.org/RNA/.
-
Functional assignment to JEV proteins using SVM.
Sahoo, Ganesh Chandra; Dikhit, Manas Ranjan; Das, Pradeep
2008-01-01
Identification of different protein functions facilitates a mechanistic understanding of Japanese encephalitis virus (JEV) infection and opens novel means for drug development. Support vector machines (SVM), useful for predicting the functional class of distantly related proteins, is employed to ascribe a possible functional class to Japanese encephalitis virus protein. Our study from SVMProt and available JE virus sequences suggests that structural and nonstructural proteins of JEV genome possibly belong to diverse protein functions, are expected to occur in the life cycle of JE virus. Protein functions common to both structural and non-structural proteins are iron-binding, metal-binding, lipid-binding, copper-binding, transmembrane, outer membrane, channels/Pores - Pore-forming toxins (proteins and peptides) group of proteins. Non-structural proteins perform functions like actin binding, zinc-binding, calcium-binding, hydrolases, Carbon-Oxygen Lyases, P-type ATPase, proteins belonging to major facilitator family (MFS), secreting main terminal branch (MTB) family, phosphotransfer-driven group translocators and ATP-binding cassette (ABC) family group of proteins. Whereas structural proteins besides belonging to same structural group of proteins (capsid, structural, envelope), they also perform functions like nuclear receptor, antibiotic resistance, RNA-binding, DNA-binding, magnesium-binding, isomerase (intra-molecular), oxidoreductase and participate in type II (general) secretory pathway (IISP).
-
Functional assignment to JEV proteins using SVM
Sahoo, Ganesh Chandra; Dikhit, Manas Ranjan; Das, Pradeep
2008-01-01
Identification of different protein functions facilitates a mechanistic understanding of Japanese encephalitis virus (JEV) infection and opens novel means for drug development. Support vector machines (SVM), useful for predicting the functional class of distantly related proteins, is employed to ascribe a possible functional class to Japanese encephalitis virus protein. Our study from SVMProt and available JE virus sequences suggests that structural and nonstructural proteins of JEV genome possibly belong to diverse protein functions, are expected to occur in the life cycle of JE virus. Protein functions common to both structural and non-structural proteins are iron-binding, metal-binding, lipid-binding, copper-binding, transmembrane, outer membrane, channels/Pores - Pore-forming toxins (proteins and peptides) group of proteins. Non-structural proteins perform functions like actin binding, zinc-binding, calcium-binding, hydrolases, Carbon-Oxygen Lyases, P-type ATPase, proteins belonging to major facilitator family (MFS), secreting main terminal branch (MTB) family, phosphotransfer-driven group translocators and ATP-binding cassette (ABC) family group of proteins. Whereas structural proteins besides belonging to same structural group of proteins (capsid, structural, envelope), they also perform functions like nuclear receptor, antibiotic resistance, RNA-binding, DNA-binding, magnesium-binding, isomerase (intra-molecular), oxidoreductase and participate in type II (general) secretory pathway (IISP). PMID:19052658
-
Drakou, Christina E; Tsitsanou, Katerina E; Potamitis, Constantinos; Fessas, Dimitrios; Zervou, Maria; Zographos, Spyros E
2017-01-01
Anopheles gambiae Odorant Binding Protein 1 in complex with the most widely used insect repellent DEET, was the first reported crystal structure of an olfactory macromolecule with a repellent, and paved the way for OBP1-structure-based approaches for discovery of new host-seeking disruptors. In this work, we performed STD-NMR experiments to directly monitor and verify the formation of a complex between AgamOBP1 and Icaridin, an efficient DEET alternative. Furthermore, Isothermal Titration Calorimetry experiments provided evidence for two Icaridin-binding sites with different affinities (Kd = 0.034 and 0.714 mM) and thermodynamic profiles of ligand binding. To elucidate the binding mode of Icaridin, the crystal structure of AgamOBP1•Icaridin complex was determined at 1.75 Å resolution. We found that Icaridin binds to the DEET-binding site in two distinct orientations and also to a novel binding site located at the C-terminal region. Importantly, only the most active 1R,2S-isomer of Icaridin's equimolar diastereoisomeric mixture binds to the AgamOBP1 crystal, providing structural evidence for the possible contribution of OBP1 to the stereoselectivity of Icaridin perception in mosquitoes. Structural analysis revealed two ensembles of conformations differing mainly in spatial arrangement of their sec-butyl moieties. Moreover, structural comparison with DEET indicates a common recognition mechanism for these structurally related repellents. Ligand interactions with both sites and binding modes were further confirmed by 2D 1 H- 15 N HSQC NMR spectroscopy. The identification of a novel repellent-binding site in AgamOBP1 and the observed structural conservation and stereoselectivity of its DEET/Icaridin-binding sites open new perspectives for the OBP1-structure-based discovery of next-generation insect repellents.
-
An Integrative Risk Management/Governance Framework for Homeland Security Decision Making
2008-03-01
key modes of transportation include highways, motor carrier (trucking), motor coach ( intercity bus), maritime, pipeline, rail (passenger and freight...2004 Overview: A blast tore apart a metro train car in Moscow during the morning rush hour on February 6, 2004. The train was traveling between the...Circle Line train, No. 204, traveling from Liverpool Street to Aldgate Station. Within one minute, a second explosion took place on Circle Line train
-
Leveraging the Strategic Value of the U.S. Inland Waterway System
2007-03-14
on the highway system. Although commercial vehicles currently account for less than 10 percent of all vehicle-miles of travel , truck traffic is...growing faster than passenger vehicle traffic and is having major effects on intercity highways. Trucks already account for more than 30 percent of...seen by the traveling public as an unwanted competitor for space on congested highways, but that same public depends on trucking to meet the
-
Ohio River Denial as a Transportation Corridor and Its Economic Impacts on the Energy Industry
2009-03-01
of freight transport market demand elasiticities, and mode choice probability elasticities of rail and full truck load carriers in the intercity ...obvious that under real conditions, travel demand would alter if time and duration of delay could be anticipated. First, cost of delay was defined...replication was expressed in terms of duration of the simulation interval, simulated travel time for this interval time, and expected travel time. Then
-
Electrochemistry of Some New Alkaline Battery Electrodes
1976-02-01
1NýT;7 ~~ AFAPI 4TR- 75)aI Electrochemistry of Somwý New Alkaline V CI RG, 0OTNME Dr/ David F., ’Pickett, IM Wayue ’,Hisb’q Mr. R ic ha rd A I Mid...adding ZnO to the electi-olyte (saturated) and usi .j the interc:ell conrec;tor d isr:ussed earlier ,itLh el4cc.roploated zinc ag inst. the silver fo
-
Shin, Jae-Min; Cho, Doo-Ho
2005-01-01
PDB-Ligand (http://www.idrtech.com/PDB-Ligand/) is a three-dimensional structure database of small molecular ligands that are bound to larger biomolecules deposited in the Protein Data Bank (PDB). It is also a database tool that allows one to browse, classify, superimpose and visualize these structures. As of May 2004, there are about 4870 types of small molecular ligands, experimentally determined as a complex with protein or DNA in the PDB. The proteins that a given ligand binds are often homologous and present the same binding structure to the ligand. However, there are also many instances wherein a given ligand binds to two or more unrelated proteins, or to the same or homologous protein in different binding environments. PDB-Ligand serves as an interactive structural analysis and clustering tool for all the ligand-binding structures in the PDB. PDB-Ligand also provides an easier way to obtain a number of different structure alignments of many related ligand-binding structures based on a simple and flexible ligand clustering method. PDB-Ligand will be a good resource for both a better interpretation of ligand-binding structures and the development of better scoring functions to be used in many drug discovery applications.
-
2007-12-01
Staff) and Mr. Doug Learned ( Intercity Manufacturing), whose efficiency and expertise was vital in manufacturing the parts required for our tests...detonation products caused by the hollow cavity. Upon initiation of a hollow lined charge, the resulting high pressure shock wave travels outward...5.6 km/s for the brass encased charge at 2 and 3 CD. This indicates that the jet must be traveling at velocities greater than the estimates, which
-
Deregulation and Intercity Bus Operations in Florida: A Preliminary Study.
1981-03-02
revenues have been consistent recently, but expenses have risen. The three areas most frequently served by Rabbit Bus Lines are Disney World, Sea World...Manager, Shoreline Stages had annual revenues of roughly $890,000 in 1980. In terms of trips, about ninety percent of this carrier’s traffic is interstate...this traffic constitutes the bulk of Shoreline Stage’s business by revenue , volume of traffic, and number of passengers. Charter trips to Disney
-
STOL Traffic environment and operational procedures
NASA Technical Reports Server (NTRS)
Schlundt, R. W.; Dewolf, R. W.; Ausrotas, R. A.; Curry, R. E.; Demaio, D.; Keene, D. W.; Speyer, J. L.; Weinreich, M.; Zeldin, S.
1972-01-01
The expected traffic environment for an intercity STOL transportation system is examined, and operational procedures are discussed in order to identify problem areas which impact STOL avionics requirements. Factors considered include: traffic densities, STOL/CTOL/VTOL traffic mix, the expect ATC environment, aircraft noise models and community noise models and community noise impact, flight paths for noise abatement, wind considerations affecting landing, approach and landing considerations, STOLport site selection, runway capacity, and STOL operations at jetports, suburban airports, and separate STOLports.
-
Impacts of Water Scarcity on Coast Guard Mission Requirements and Performance.
1981-04-01
Unclassified Unclassified Form DOT F 1700.7 (8-72) Reproduction of completed Page GuthOtod *1" resalesG TABLE OF CONTENTS Page LIST OF TABLES...on the continental United States as rain, snow, and other forms of precipitation; of this, 1450 BGD are stored (as ground- water, in natural and...continental United States. This sytem of navigable waterways is very important to the Nation’s economy, carrying about one-fourth of the total intercity
-
Crystal structure of mouse coronavirus receptor-binding domain complexed with its murine receptor
DOE Office of Scientific and Technical Information (OSTI.GOV)
Peng, Guiqing; Sun, Dawei; Rajashankar, Kanagalaghatta R.
2011-09-28
Coronaviruses have evolved diverse mechanisms to recognize different receptors for their cross-species transmission and host-range expansion. Mouse hepatitis coronavirus (MHV) uses the N-terminal domain (NTD) of its spike protein as its receptor-binding domain. Here we present the crystal structure of MHV NTD complexed with its receptor murine carcinoembryonic antigen-related cell adhesion molecule 1a (mCEACAM1a). Unexpectedly, MHV NTD contains a core structure that has the same {beta}-sandwich fold as human galectins (S-lectins) and additional structural motifs that bind to the N-terminal Ig-like domain of mCEACAM1a. Despite its galectin fold, MHV NTD does not bind sugars, but instead binds mCEACAM1a through exclusivemore » protein-protein interactions. Critical contacts at the interface have been confirmed by mutagenesis, providing a structural basis for viral and host specificities of coronavirus/CEACAM1 interactions. Sugar-binding assays reveal that galectin-like NTDs of some coronaviruses such as human coronavirus OC43 and bovine coronavirus bind sugars. Structural analysis and mutagenesis localize the sugar-binding site in coronavirus NTDs to be above the {beta}-sandwich core. We propose that coronavirus NTDs originated from a host galectin and retained sugar-binding functions in some contemporary coronaviruses, but evolved new structural features in MHV for mCEACAM1a binding.« less
-
Yang, Rui-Nan; Li, Dong-Zhen; Yu, Guangqiang; Yi, Shan-Cheng; Zhang, Yinan; Kong, De-Xin; Wang, Man-Qun
2017-12-01
In light of reverse chemical ecology, the fluorescence competitive binding assays of functional odorant binding proteins (OBPs) is a recent advanced approach for screening behaviorally active compounds of insects. Previous research on Dastareus helophoroides identified a minus-C OBP, DhelOBP21, which preferably binds to several ligands. In this study, only (+)-β-pinene proved attractive to unmated adult beetles. To obtain a more in-depth explanation of the lack of behavioral activity of other ligands we selected compounds with high (camphor) and low (β-caryophyllene) binding affinities. The structural transformation of OBPs was investigated using well-established approaches for studying binding processes, such as fluorescent quenching assays, circular dichroism, and molecular dynamics. The dynamic binding process revealed that the flexibility of DhelOBP21 seems conducive to binding specific ligands, as opposed to broad substrate binding. The compound (+)-β-pinene and DhelOBP21 formed a stable complex through a secondary structural transformation of DhelOBP21, in which its amino-terminus transformed from random coil to an α-helix to cover the binding pocket. On the other hand, camphor could not efficiently induce a stable structural transformation, and its high binding affinities were due to strong hydrogen-bonding, compromising the structure of the protein. The other compound, β-caryophyllene, only collided with DhelOBP21 and could not be positioned in the binding pocket. Studying structural transformation of these proteins through examining the dynamic binding process rather than using approaches that just measure binding affinities such as fluorescence competitive binding assays can provide a more efficient and reliable approach for screening behaviorally active compounds.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Leenheer, J.A.; Brown, G.K.; Cabaniss, S.E.
Fulvic acid, isolated from the Suwannee River, Georgia, was assessed for its ability to bind Ca{sup 2+}, Cd{sup 2+}, Cu{sup 2+}, Ni{sup 2+}, and Zn{sup 2+} ions at pH 6 before and after extensive fractionation that was designed to reveal the nature of metal binding functional groups. The binding constant for Ca{sup 2+} ion had the greatest increase of all the ions in a metal binding fraction that was selected for intensive characterization for the purpose of building quantitative average model structures. The metal binding fraction was characterized by quantitative {sup 13}C NMR, {sup 1}H NMR, and FT-IR spectrometry andmore » elemental, titrimetric, and molecular weight determinations. The characterization data revealed that carboxyl groups were clustered in short-chain aliphatic dibasic acid structures. The Ca{sup 2+} binding data suggested that ether-substituted oxysuccinic acid structures are good models for the metal binding sites at pH 6. Structural models were derived based upon oxidation and photolytic rearrangements of cutin, lignin, and tannin precursors. These structural models rich in substituted dibasic acid structures revealed polydentate binding sites with the potential for both inner-sphere and outer-sphere type binding. The majority of the fulvic acid molecule was involved with metal binding rather than a small substructural unit.« less
-
Hardware device to physical structure binding and authentication
Hamlet, Jason R.; Stein, David J.; Bauer, Todd M.
2013-08-20
Detection and deterrence of device tampering and subversion may be achieved by including a cryptographic fingerprint unit within a hardware device for authenticating a binding of the hardware device and a physical structure. The cryptographic fingerprint unit includes an internal physically unclonable function ("PUF") circuit disposed in or on the hardware device, which generate an internal PUF value. Binding logic is coupled to receive the internal PUF value, as well as an external PUF value associated with the physical structure, and generates a binding PUF value, which represents the binding of the hardware device and the physical structure. The cryptographic fingerprint unit also includes a cryptographic unit that uses the binding PUF value to allow a challenger to authenticate the binding.
-
Lee, Yong-Jik; Lee, Sang-Jae; Kim, Seong-Bo; Lee, Sang Jun; Lee, Sung Haeng; Lee, Dong-Woo
2014-03-18
Structural genomics demonstrates that despite low levels of structural similarity of proteins comprising a metabolic pathway, their substrate binding regions are likely to be conserved. Herein based on the 3D-structures of the α/β-fold proteins involved in the ara operon, we attempted to predict the substrate binding residues of thermophilic Geobacillus stearothermophilus L-arabinose isomerase (GSAI) with no 3D-structure available. Comparison of the structures of L-arabinose catabolic enzymes revealed a conserved feature to form the substrate-binding modules, which can be extended to predict the substrate binding site of GSAI (i.e., D195, E261 and E333). Moreover, these data implicated that proteins in the l-arabinose metabolic pathway might retain their substrate binding niches as the modular structure through conserved molecular evolution even with totally different structural scaffolds. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
-
The helical structure of DNA facilitates binding
NASA Astrophysics Data System (ADS)
Berg, Otto G.; Mahmutovic, Anel; Marklund, Emil; Elf, Johan
2016-09-01
The helical structure of DNA imposes constraints on the rate of diffusion-limited protein binding. Here we solve the reaction-diffusion equations for DNA-like geometries and extend with simulations when necessary. We find that the helical structure can make binding to the DNA more than twice as fast compared to a case where DNA would be reactive only along one side. We also find that this rate advantage remains when the contributions from steric constraints and rotational diffusion of the DNA-binding protein are included. Furthermore, we find that the association rate is insensitive to changes in the steric constraints on the DNA in the helix geometry, while it is much more dependent on the steric constraints on the DNA-binding protein. We conclude that the helical structure of DNA facilitates the nonspecific binding of transcription factors and structural DNA-binding proteins in general.
-
XV-15 Structural-Acoustic Data
NASA Technical Reports Server (NTRS)
Lyle, Karen H.
1997-01-01
Tiltrotor aircraft are a potentially viable means of intercity travel. The tiltrotor is able to transport passengers relatively quickly from the center of a city to destinations within a 300-mile radius. For such vehicles to be commercially viable, the interior noise and vibration levels must be acceptable to the passengers. A review of the literature revealed very little structural-acoustic data related to the tiltrotor. For this reason, structural-acoustic measurements were taken aboard an XV-15 tiltrotor. The six flight conditions included five in level flight, nominally 140-220 knots, for airplane mode (nacelle at 0 degrees) and one out-of-ground-effect (OGE) hover (nacelle at 90 degrees). The flight test measurements included nine exterior surface pressures, five structural accelerations, and two interior pressures. These sensors were located near the tip path plane on the port side of the aircraft. One minute of data was acquired at each condition. The data is presented as time histories, autospectra, coherence functions, and cross-spectra. In general, for level flight, the measured data showed very little effect of forward flight speed except to change the amplitude of the response; however, the character of the response was found to be dependent on spatial location. In contrast, in the hover mode the spatial location had very little effect on the character of the response. Additionally, the report highlights: the coherence between the transducer data and the rotor tach signal; and transfer function calculations between the exterior pressures.
-
Neupane, Durga P; Avalos, Dante; Fullam, Stephanie; Roychowdhury, Hridindu; Yukl, Erik T
2017-10-20
Bacteria can acquire the essential metal zinc from extremely zinc-limited environments by using ATP-binding cassette (ABC) transporters. These transporters are critical virulence factors, relying on specific and high-affinity binding of zinc by a periplasmic solute-binding protein (SBP). As such, the mechanisms of zinc binding and release among bacterial SBPs are of considerable interest as antibacterial drug targets. Zinc SBPs are characterized by a flexible loop near the high-affinity zinc-binding site. The function of this structure is not always clear, and its flexibility has thus far prevented structural characterization by X-ray crystallography. Here, we present intact structures for the zinc-specific SBP AztC from the bacterium Paracoccus denitrificans in the zinc-bound and apo-states. A comparison of these structures revealed that zinc loss prompts significant structural rearrangements, mediated by the formation of a sodium-binding site in the apo-structure. We further show that the AztC flexible loop has no impact on zinc-binding affinity, stoichiometry, or protein structure, yet is essential for zinc transfer from the metallochaperone AztD. We also found that 3 His residues in the loop appear to temporarily coordinate zinc and then convey it to the high-affinity binding site. Thus, mutation of any of these residues to Ala abrogated zinc transfer from AztD. Our structural and mechanistic findings conclusively identify a role for the AztC flexible loop in zinc acquisition from the metallochaperone AztD, yielding critical insights into metal binding by AztC from both solution and AztD. These proteins are highly conserved in human pathogens, making this work potentially useful for the development of novel antibiotics. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
-
Identifying DNA-binding proteins using structural motifs and the electrostatic potential
Shanahan, Hugh P.; Garcia, Mario A.; Jones, Susan; Thornton, Janet M.
2004-01-01
Robust methods to detect DNA-binding proteins from structures of unknown function are important for structural biology. This paper describes a method for identifying such proteins that (i) have a solvent accessible structural motif necessary for DNA-binding and (ii) a positive electrostatic potential in the region of the binding region. We focus on three structural motifs: helix–turn-helix (HTH), helix–hairpin–helix (HhH) and helix–loop–helix (HLH). We find that the combination of these variables detect 78% of proteins with an HTH motif, which is a substantial improvement over previous work based purely on structural templates and is comparable to more complex methods of identifying DNA-binding proteins. Similar true positive fractions are achieved for the HhH and HLH motifs. We see evidence of wide evolutionary diversity for DNA-binding proteins with an HTH motif, and much smaller diversity for those with an HhH or HLH motif. PMID:15356290
-
How Structure Defines Affinity in Protein-Protein Interactions
Erijman, Ariel; Rosenthal, Eran; Shifman, Julia M.
2014-01-01
Protein-protein interactions (PPI) in nature are conveyed by a multitude of binding modes involving various surfaces, secondary structure elements and intermolecular interactions. This diversity results in PPI binding affinities that span more than nine orders of magnitude. Several early studies attempted to correlate PPI binding affinities to various structure-derived features with limited success. The growing number of high-resolution structures, the appearance of more precise methods for measuring binding affinities and the development of new computational algorithms enable more thorough investigations in this direction. Here, we use a large dataset of PPI structures with the documented binding affinities to calculate a number of structure-based features that could potentially define binding energetics. We explore how well each calculated biophysical feature alone correlates with binding affinity and determine the features that could be used to distinguish between high-, medium- and low- affinity PPIs. Furthermore, we test how various combinations of features could be applied to predict binding affinity and observe a slow improvement in correlation as more features are incorporated into the equation. In addition, we observe a considerable improvement in predictions if we exclude from our analysis low-resolution and NMR structures, revealing the importance of capturing exact intermolecular interactions in our calculations. Our analysis should facilitate prediction of new interactions on the genome scale, better characterization of signaling networks and design of novel binding partners for various target proteins. PMID:25329579
-
2011-12-01
The DHC-7 originally flew as a commercial regional airliner, operating on intercity routes between major metropolitan areas from small local...eight hours and travel approximately 1,100 nautical miles. In an effort to maximize their TOS, or loiter time, INSCOM ARL operators currently must...real-world units (3rd MI BN and 204th MI BN) travel their transit legs at approximately 140 knots and conduct their missions at this same speed
-
2002-01-01
8217\\10 tor- pedo boats. There is no evidence that the T-142 relayed it to any other boat or command. (8//81) One more position report on the Desoto...portrays the information in them. For example, the first report mentions the salvage operations of the two damaged DRV tor- pedo boats which had been...intercePte. IS sys- tem transmitted the videopicture of the video radar displays to another station,usually some operating station such as a GCI
-
Measuring the frequency of a Sr optical lattice clock using a 120 km coherent optical transfer.
Hong, F-L; Musha, M; Takamoto, M; Inaba, H; Yanagimachi, S; Takamizawa, A; Watabe, K; Ikegami, T; Imae, M; Fujii, Y; Amemiya, M; Nakagawa, K; Ueda, K; Katori, H
2009-03-01
We demonstrate a precision frequency measurement using a phase-stabilized 120 km optical fiber link over a physical distance of 50 km. The transition frequency of the (87)Sr optical lattice clock at the University of Tokyo is measured to be 429228004229874.1(2.4) Hz referenced to international atomic time. The results demonstrate the excellent functions of the intercity optical fiber link and the great potential of optical lattice clocks for use in the redefinition of the second.
-
NITINOL Interconnect Device for Optical Fiber Waveguides
1981-07-01
LE EL,~NAVSEA REPORT NO. S27L~kV-NL 4P fNSWNC TR 81-129 1 JULY 1981 0 NITINOL INTERC&INECT DEVICE FOR OPTICAL FIBER WAVEGUIDES FINAL REPORT A...ACCESSION NO. 3. RECIPIENT’S CATALOG NUMBER NSWC TR 81-129I 1-19 -A )ci , ’ 4 TI TL E (and Sbtitle) S. TYPE OF REPORT & PERIOD COVERED NITINOL ... NITINOL Optical Fibers 20. ABSTRACT (Continue on reverse side if neceeewy and identify by block number) Two different interconnect devices for optical
-
The role of technology as air transportation faces the fuel situation
NASA Technical Reports Server (NTRS)
Driver, C.
1980-01-01
Perspectives on the air transportation fuel stituation are discussed including intercity air traffic, airline fuel consumption, fuel price effects on ticket price, and projected traffic and fuel useage between now and the year 2000. Actions taken by the airlines to reduce consumption are reviewed, as well as efforts currently underway to improve fuel consumption. Longer range technology payoffs resulting from NASA research programs are reviewed and results from studies on the use of alternate fuels are discussed.
-
1993-01-01
upon designation of DoD Activity Address Code (DoDAAC) or other code coordinated with the value-added network (VAN). Mandatory ISA06 106 Interc.ange...coordinated with the value-added network (VAN). Non-DoD activities use identification code qualified by ISA05 and coordinated with the VAN. Mandatory...designation of DoD Activity Address Code (DoDAAC) or other code coordinated with the value-added network (VAN). Mandatory ISA08 107 Interchange Receiver
-
Timsit, Youri; Bombard, Sophie
2007-12-01
Metal ions play a key role in RNA folding and activity. Elucidating the rules that govern the binding of metal ions is therefore an essential step for better understanding the RNA functions. High-resolution data are a prerequisite for a detailed structural analysis of ion binding on RNA and, in particular, the observation of monovalent cations. Here, the high-resolution crystal structures of the tridecamer duplex r(GCGUUUGAAACGC) crystallized under different conditions provides new structural insights on ion binding on GAAA/UUU sequences that exhibit both unusual structural and functional properties in RNA. The present study extends the repertory of RNA ion binding sites in showing that the two first bases of UUU triplets constitute a specific site for sodium ions. A striking asymmetric pattern of metal ion binding in the two equivalent halves of the palindromic sequence demonstrates that sequence and its environment act together to bind metal ions. A highly ionophilic half that binds six metal ions allows, for the first time, the observation of a disodium cluster in RNA. The comparison of the equivalent halves of the duplex provides experimental evidences that ion binding correlates with structural alterations and groove contraction.
-
A tool for calculating binding-site residues on proteins from PDB structures.
Hu, Jing; Yan, Changhui
2009-08-03
In the research on protein functional sites, researchers often need to identify binding-site residues on a protein. A commonly used strategy is to find a complex structure from the Protein Data Bank (PDB) that consists of the protein of interest and its interacting partner(s) and calculate binding-site residues based on the complex structure. However, since a protein may participate in multiple interactions, the binding-site residues calculated based on one complex structure usually do not reveal all binding sites on a protein. Thus, this requires researchers to find all PDB complexes that contain the protein of interest and combine the binding-site information gleaned from them. This process is very time-consuming. Especially, combing binding-site information obtained from different PDB structures requires tedious work to align protein sequences. The process becomes overwhelmingly difficult when researchers have a large set of proteins to analyze, which is usually the case in practice. In this study, we have developed a tool for calculating binding-site residues on proteins, TCBRP http://yanbioinformatics.cs.usu.edu:8080/ppbindingsubmit. For an input protein, TCBRP can quickly find all binding-site residues on the protein by automatically combining the information obtained from all PDB structures that consist of the protein of interest. Additionally, TCBRP presents the binding-site residues in different categories according to the interaction type. TCBRP also allows researchers to set the definition of binding-site residues. The developed tool is very useful for the research on protein binding site analysis and prediction.
-
Ogawa, Haruo; Qiu, Yue; Philo, John S; Arakawa, Tsutomu; Ogata, Craig M; Misono, Kunio S
2010-03-01
The binding of atrial natriuretic peptide (ANP) to its receptor requires chloride, and it is chloride concentration dependent. The extracellular domain (ECD) of the ANP receptor (ANPR) contains a chloride near the ANP-binding site, suggesting a possible regulatory role. The bound chloride, however, is completely buried in the polypeptide fold, and its functional role has remained unclear. Here, we have confirmed that chloride is necessary for ANP binding to the recombinant ECD or the full-length ANPR expressed in CHO cells. ECD without chloride (ECD(-)) did not bind ANP. Its binding activity was fully restored by bromide or chloride addition. A new X-ray structure of the bromide-bound ECD is essentially identical to that of the chloride-bound ECD. Furthermore, bromide atoms are localized at the same positions as chloride atoms both in the apo and in the ANP-bound structures, indicating exchangeable and reversible halide binding. Far-UV CD and thermal unfolding data show that ECD(-) largely retains the native structure. Sedimentation equilibrium in the absence of chloride shows that ECD(-) forms a strongly associated dimer, possibly preventing the structural rearrangement of the two monomers that is necessary for ANP binding. The primary and tertiary structures of the chloride-binding site in ANPR are highly conserved among receptor-guanylate cyclases and metabotropic glutamate receptors. The chloride-dependent ANP binding, reversible chloride binding, and the highly conserved chloride-binding site motif suggest a regulatory role for the receptor bound chloride. Chloride-dependent regulation of ANPR may operate in the kidney, modulating ANP-induced natriuresis.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ogawa, H.; Qiu, Y; Philo, J
2010-01-01
The binding of atrial natriuretic peptide (ANP) to its receptor requires chloride, and it is chloride concentration dependent. The extracellular domain (ECD) of the ANP receptor (ANPR) contains a chloride near the ANP-binding site, suggesting a possible regulatory role. The bound chloride, however, is completely buried in the polypeptide fold, and its functional role has remained unclear. Here, we have confirmed that chloride is necessary for ANP binding to the recombinant ECD or the full-length ANPR expressed in CHO cells. ECD without chloride (ECD(-)) did not bind ANP. Its binding activity was fully restored by bromide or chloride addition. Amore » new X-ray structure of the bromide-bound ECD is essentially identical to that of the chloride-bound ECD. Furthermore, bromide atoms are localized at the same positions as chloride atoms both in the apo and in the ANP-bound structures, indicating exchangeable and reversible halide binding. Far-UV CD and thermal unfolding data show that ECD(-) largely retains the native structure. Sedimentation equilibrium in the absence of chloride shows that ECD(-) forms a strongly associated dimer, possibly preventing the structural rearrangement of the two monomers that is necessary for ANP binding. The primary and tertiary structures of the chloride-binding site in ANPR are highly conserved among receptor-guanylate cyclases and metabotropic glutamate receptors. The chloride-dependent ANP binding, reversible chloride binding, and the highly conserved chloride-binding site motif suggest a regulatory role for the receptor bound chloride. Chloride-dependent regulation of ANPR may operate in the kidney, modulating ANP-induced natriuresis.« less
-
Ogawa, Haruo; Qiu, Yue; Philo, John S; Arakawa, Tsutomu; Ogata, Craig M; Misono, Kunio S
2010-01-01
The binding of atrial natriuretic peptide (ANP) to its receptor requires chloride, and it is chloride concentration dependent. The extracellular domain (ECD) of the ANP receptor (ANPR) contains a chloride near the ANP-binding site, suggesting a possible regulatory role. The bound chloride, however, is completely buried in the polypeptide fold, and its functional role has remained unclear. Here, we have confirmed that chloride is necessary for ANP binding to the recombinant ECD or the full-length ANPR expressed in CHO cells. ECD without chloride (ECD(−)) did not bind ANP. Its binding activity was fully restored by bromide or chloride addition. A new X-ray structure of the bromide-bound ECD is essentially identical to that of the chloride-bound ECD. Furthermore, bromide atoms are localized at the same positions as chloride atoms both in the apo and in the ANP-bound structures, indicating exchangeable and reversible halide binding. Far-UV CD and thermal unfolding data show that ECD(−) largely retains the native structure. Sedimentation equilibrium in the absence of chloride shows that ECD(−) forms a strongly associated dimer, possibly preventing the structural rearrangement of the two monomers that is necessary for ANP binding. The primary and tertiary structures of the chloride-binding site in ANPR are highly conserved among receptor-guanylate cyclases and metabotropic glutamate receptors. The chloride-dependent ANP binding, reversible chloride binding, and the highly conserved chloride-binding site motif suggest a regulatory role for the receptor bound chloride. Chloride-dependent regulation of ANPR may operate in the kidney, modulating ANP-induced natriuresis. PMID:20066666
-
NASA Astrophysics Data System (ADS)
Knott, Michael; Best, Robert B.
2014-05-01
Many proteins undergo a conformational transition upon binding to their cognate binding partner, with intrinsically disordered proteins (IDPs) providing an extreme example in which a folding transition occurs. However, it is often not clear whether this occurs via an "induced fit" or "conformational selection" mechanism, or via some intermediate scenario. In the first case, transient encounters with the binding partner favour transitions to the bound structure before the two proteins dissociate, while in the second the bound structure must be selected from a subset of unbound structures which are in the correct state for binding, because transient encounters of the incorrect conformation with the binding partner are most likely to result in dissociation. A particularly interesting situation involves those intrinsically disordered proteins which can bind to different binding partners in different conformations. We have devised a multi-state coarse-grained simulation model which is able to capture the binding of IDPs in alternate conformations, and by applying it to the binding of nuclear coactivator binding domain (NCBD) to either ACTR or IRF-3 we are able to determine the binding mechanism. By all measures, the binding of NCBD to either binding partner appears to occur via an induced fit mechanism. Nonetheless, we also show how a scenario closer to conformational selection could arise by choosing an alternative non-binding structure for NCBD.
-
Ensafi, Ali A; Amini, Maryam; Rezaei, Behzad
2013-09-01
The interaction of amitrole and salmon sperm ds-DNA was studied using UV-vis and differential pulse voltammetry (DPV) at both bare and DNA-modified electrodes. Amitrole showed an oxidation peak at 0.445 V at a bare pencil graphite electrode (PGE). When ds-DNA was added into the amitrole solution, the peak current of amitrole decreased and the peak potential underwent a shift. UV-vis spectra showed that the absorption intensity of the ds-DNA at 260 nm decreased with increasing amitrole concentration, proving the interaction between amitrole and the ds-DNA. The results also showed that amitrole could interact with the ds-DNA molecules via the intercalative binding mode. Finally, a pretreated pencil graphite electrode (PGE) modified with multiwall carbon nanotubes (MWCNTs) and chitosan (CHIT) decorated with the ds-DNA were tested in order to determine amitrole content in solution. Electrochemical oxidation of amitrole bonded on DNA/MWCNTs-CHIT/PGE was used to obtain an analytical signal. A linear dependence was observed to exist between the peak current and 0.025-2.4 ng mL(-1) amitrole with a detection limit of 0.017 ng mL(-1). The sensor showed a good selectivity and precision for the determination of amitrole. Finally, applicability of the biosensor was evaluated by measuring the analyte in soil and water samples with good selectivity. Copyright © 2013 Elsevier B.V. All rights reserved.
-
Warfield, Becka M.
2017-01-01
RNA aptamers are oligonucleotides that bind with high specificity and affinity to target ligands. In the absence of bound ligand, secondary structures of RNA aptamers are generally stable, but single-stranded and loop regions, including ligand binding sites, lack defined structures and exist as ensembles of conformations. For example, the well-characterized theophylline-binding aptamer forms a highly stable binding site when bound to theophylline, but the binding site is unstable and disordered when theophylline is absent. Experimental methods have not revealed at atomic resolution the conformations that the theophylline aptamer explores in its unbound state. Consequently, in the present study we applied 21 microseconds of molecular dynamics simulations to structurally characterize the ensemble of conformations that the aptamer adopts in the absence of theophylline. Moreover, we apply Markov state modeling to predict the kinetics of transitions between unbound conformational states. Our simulation results agree with experimental observations that the theophylline binding site is found in many distinct binding-incompetent states and show that these states lack a binding pocket that can accommodate theophylline. The binding-incompetent states interconvert with binding-competent states through structural rearrangement of the binding site on the nanosecond to microsecond timescale. Moreover, we have simulated the complete theophylline binding pathway. Our binding simulations supplement prior experimental observations of slow theophylline binding kinetics by showing that the binding site must undergo a large conformational rearrangement after the aptamer and theophylline form an initial complex, most notably, a major rearrangement of the C27 base from a buried to solvent-exposed orientation. Theophylline appears to bind by a combination of conformational selection and induced fit mechanisms. Finally, our modeling indicates that when Mg2+ ions are present the population of binding-competent aptamer states increases more than twofold. This population change, rather than direct interactions between Mg2+ and theophylline, accounts for altered theophylline binding kinetics. PMID:28437473
-
Nossoni, Zahra; Assar, Zahra; Yapici, Ipek; Nosrati, Meisam; Wang, Wenjing; Berbasova, Tetyana; Vasileiou, Chrysoula; Borhan, Babak; Geiger, James
2014-01-01
Cellular retinol-binding proteins (CRBPs) I and II, which are members of the intracellular lipid-binding protein (iLBP) family, are retinoid chaperones that are responsible for the intracellular transport and delivery of both retinol and retinal. Although structures of retinol-bound CRBPI and CRBPII are known, no structure of a retinal-bound CRBP has been reported. In addition, the retinol-bound human CRBPII (hCRBPII) structure shows partial occupancy of a noncanonical conformation of retinol in the binding pocket. Here, the structure of retinal-bound hCRBPII and the structure of retinol-bound hCRBPII with retinol fully occupying the binding pocket are reported. It is further shown that the retinoid derivative seen in both the zebrafish CRBP and the hCRBPII structures is likely to be the product of flux-dependent and wavelength-dependent X-ray damage during data collection. The structures of retinoid-bound CRBPs are compared and contrasted, and rationales for the differences in binding affinities for retinal and retinol are provided. PMID:25478840
-
Nossoni, Zahra; Assar, Zahra; Yapici, Ipek; Nosrati, Meisam; Wang, Wenjing; Berbasova, Tetyana; Vasileiou, Chrysoula; Borhan, Babak; Geiger, James
2014-12-01
Cellular retinol-binding proteins (CRBPs) I and II, which are members of the intracellular lipid-binding protein (iLBP) family, are retinoid chaperones that are responsible for the intracellular transport and delivery of both retinol and retinal. Although structures of retinol-bound CRBPI and CRBPII are known, no structure of a retinal-bound CRBP has been reported. In addition, the retinol-bound human CRBPII (hCRBPII) structure shows partial occupancy of a noncanonical conformation of retinol in the binding pocket. Here, the structure of retinal-bound hCRBPII and the structure of retinol-bound hCRBPII with retinol fully occupying the binding pocket are reported. It is further shown that the retinoid derivative seen in both the zebrafish CRBP and the hCRBPII structures is likely to be the product of flux-dependent and wavelength-dependent X-ray damage during data collection. The structures of retinoid-bound CRBPs are compared and contrasted, and rationales for the differences in binding affinities for retinal and retinol are provided.
-
Predicting nucleic acid binding interfaces from structural models of proteins
Dror, Iris; Shazman, Shula; Mukherjee, Srayanta; Zhang, Yang; Glaser, Fabian; Mandel-Gutfreund, Yael
2011-01-01
The function of DNA- and RNA-binding proteins can be inferred from the characterization and accurate prediction of their binding interfaces. However the main pitfall of various structure-based methods for predicting nucleic acid binding function is that they are all limited to a relatively small number of proteins for which high-resolution three dimensional structures are available. In this study, we developed a pipeline for extracting functional electrostatic patches from surfaces of protein structural models, obtained using the I-TASSER protein structure predictor. The largest positive patches are extracted from the protein surface using the patchfinder algorithm. We show that functional electrostatic patches extracted from an ensemble of structural models highly overlap the patches extracted from high-resolution structures. Furthermore, by testing our pipeline on a set of 55 known nucleic acid binding proteins for which I-TASSER produces high-quality models, we show that the method accurately identifies the nucleic acids binding interface on structural models of proteins. Employing a combined patch approach we show that patches extracted from an ensemble of models better predicts the real nucleic acid binding interfaces compared to patches extracted from independent models. Overall, these results suggest that combining information from a collection of low-resolution structural models could be a valuable approach for functional annotation. We suggest that our method will be further applicable for predicting other functional surfaces of proteins with unknown structure. PMID:22086767
-
NASA Astrophysics Data System (ADS)
Ezerski, Jacob; Cheung, Margaret
CaM forms distinct conformation states through modifications in its charge distribution upon binding to Ca2+ ions. The occurrence of protein structural change resulting from an altered charge distribution is paramount in the scheme of cellular signaling. Not only is charge induced structural change observed in CaM, it is also seen in an essential binding target: calmodulin-depended protein kinase II (CaMKII). In order to investigate the mechanism of selectivity in relation to changes in secondary structure, the CaM binding domain of CaMKII is isolated. Experimentally, charged residues of the CaMKII peptide are systematically mutated to alanine, resulting in altered binding kinetics between the peptide and the Ca2+ saturated state of CaM. We perform an all atom simulation of the wildtype (RRK) and mutated (AAA) CaMKII peptides and generate structures from the trajectory. We analyze RRK and AAA using DSSP and find significant structural differences due to the mutation. Structures from the RRK and AAA ensembles are then selected and docked onto the crystal structure of Ca2+ saturated CaM. We observe that RRK binds to CaM at the C-terminus, whereas the 3-residue mutation, AAA, shows increased patterns of binding to the N-terminus and linker regions of CaM. Due to the conformational change of the peptide ensemble from charged residue mutation, a distinct change in the binding site can be seen, which offers an explanation to experimentally observed changes in kinetic binding rates
-
Litfin, Thomas; Zhou, Yaoqi; Yang, Yuedong
2017-04-15
The high cost of drug discovery motivates the development of accurate virtual screening tools. Binding-homology, which takes advantage of known protein-ligand binding pairs, has emerged as a powerful discrimination technique. In order to exploit all available binding data, modelled structures of ligand-binding sequences may be used to create an expanded structural binding template library. SPOT-Ligand 2 has demonstrated significantly improved screening performance over its previous version by expanding the template library 15 times over the previous one. It also performed better than or similar to other binding-homology approaches on the DUD and DUD-E benchmarks. The server is available online at http://sparks-lab.org . yaoqi.zhou@griffith.edu.au or yuedong.yang@griffith.edu.au. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com
-
Wei, Qing; La, David; Kihara, Daisuke
2017-01-01
Prediction of protein-protein interaction sites in a protein structure provides important information for elucidating the mechanism of protein function and can also be useful in guiding a modeling or design procedures of protein complex structures. Since prediction methods essentially assess the propensity of amino acids that are likely to be part of a protein docking interface, they can help in designing protein-protein interactions. Here, we introduce BindML and BindML+ protein-protein interaction sites prediction methods. BindML predicts protein-protein interaction sites by identifying mutation patterns found in known protein-protein complexes using phylogenetic substitution models. BindML+ is an extension of BindML for distinguishing permanent and transient types of protein-protein interaction sites. We developed an interactive web-server that provides a convenient interface to assist in structural visualization of protein-protein interactions site predictions. The input data for the web-server are a tertiary structure of interest. BindML and BindML+ are available at http://kiharalab.org/bindml/ and http://kiharalab.org/bindml/plus/ .
-
Gold, Nicola D; Jackson, Richard M
2006-02-03
The rapid growth in protein structural data and the emergence of structural genomics projects have increased the need for automatic structure analysis and tools for function prediction. Small molecule recognition is critical to the function of many proteins; therefore, determination of ligand binding site similarity is important for understanding ligand interactions and may allow their functional classification. Here, we present a binding sites database (SitesBase) that given a known protein-ligand binding site allows rapid retrieval of other binding sites with similar structure independent of overall sequence or fold similarity. However, each match is also annotated with sequence similarity and fold information to aid interpretation of structure and functional similarity. Similarity in ligand binding sites can indicate common binding modes and recognition of similar molecules, allowing potential inference of function for an uncharacterised protein or providing additional evidence of common function where sequence or fold similarity is already known. Alternatively, the resource can provide valuable information for detailed studies of molecular recognition including structure-based ligand design and in understanding ligand cross-reactivity. Here, we show examples of atomic similarity between superfamily or more distant fold relatives as well as between seemingly unrelated proteins. Assignment of unclassified proteins to structural superfamiles is also undertaken and in most cases substantiates assignments made using sequence similarity. Correct assignment is also possible where sequence similarity fails to find significant matches, illustrating the potential use of binding site comparisons for newly determined proteins.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nigro, D.N.; Stewart, R.G.; Apple, S.A.
1982-03-01
The operational experience obtained for the GT404-4 gas turbine engines in the Intercity and Intracity Bus Demonstration Programs is described for the period January 1980 through September 1981. Support for the engines and automatic transmissions involved in this program provided engineering and field service, spare parts and tools, training, and factory overhauls. The Greyhound (intercity) coaches accumulated 183,054 mi (294,595 km) and 5154 hr of total operation. The Baltimore Transit (intracity) coaches accumulated 40,567 mi (65,285 km) and 1840 hr of total operation. In service, the turbine-powered Greyhound and Transit coaches achieved approximately 25% and 40% lower fuel mileage, respectively,more » than did the production diesel-powered coaches. The gas turbine engine will require the advanced ceramic development currently being sponsored by the DOE and NASA to achieve fuel economy equivalent not only to that of today's diesel engines but also to the projected fuel economy of the advanced diesel engines of the 1990s. Sufficient experience was not achieved with the coaches prior to the start of service to identify and eliminate many of the problems associated with the startup of new equipment. Because of these problems, the mean miles between incident were unacceptably low. The future gas turbine system should be developed sufficiently to establish satisfactory durability prior to evaluation in revenue service. Commercialization of the gas turbine bus engine remains a viable goal for the future.« less
-
Support and power plant documentation for the gas turbine powered bus demonstration program
NASA Technical Reports Server (NTRS)
Nigro, D. N.; Stewart, R. G.; Apple, S. A.
1982-01-01
The operational experience obtained for the GT404-4 gas turbine engines in the intercity and intracity Bus Demonstration Programs is described for the period January 1980 through September 1981. Support for the engines and automatic transmissions involved in this program provided engineering and field service, spare parts and tools, training, and factory overhauls. the Greyhound (intercity) coaches accumulated 183,054 mi (294,595 km) and 5154 hr of total operation. The Baltimore Transit (intracity) coaches accumulated 40,567 mi (65,285 km) and 1840 hr of total operation. In service, the turbine powered Greyhound and Transit coaches achieved approximately 25% and 40% lower fuel mileage, respectively, than did the production diesel powered coaches. The gas turbine engine will require the advanced ceramic development currently being sponsored by the DOE and NASA to achieve fuel economy equivalent not only to that of today's diesel engines but also to the projected fuel economy of the advanced diesel engines of the 1990s. Sufficient experience was not achieved with the coaches prior to the start of service to identify and eliminate many of the problems associated with the startup of new equipment. Because of these problems, the mean miles between incident were unacceptably low. The future gas turbine system should be developed sufficiently to establish satisfactory durability prior to evaluation in revenue service. Commercialization of the gas turbine bus engine remains a viable goal for the future.
-
Structural analysis of the receptor binding domain of botulinum neurotoxin serotype D
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhang, Yanfeng; Buchko, Garry W.; Qin, Lin
2010-10-28
Botulinum neurotoxins (BoNTs) are the most toxic proteins known. The mechanism for entry into neuronal cells for serotypes A, B, E, F, and G involves a well understood dual receptor (protein and ganglioside) process, however, the mechanism of entry for serotypes C and D remains unclear. To provide structural insights into how BoNT/D enters neuronal cells, the crystal structure of the receptor binding domain (S863-E1276) for this serotype (BoNT/D-HCR) was determined at 1.65 Å resolution. While BoNT/D-HCR adopts an overall fold similar to that observed in other known BoNT HCRs, several major structural differences are present. These structural differences aremore » located at, or near, putative receptor binding sites and may be responsible for BoNT/D host preferences. Two loops, S1195-I1204 and K1236-N1244, located on both sides of the putative protein receptor binding pocket, are displaced >10 Å relative to the corresponding residues in the crystal structures of BoNT/B and G. Obvious clashes were observed in the putative protein receptor binding site when the BoNT/B protein receptor synaptotagmin II was modeled into the BoNT/D-HCR structure. Although a ganglioside binding site has never been unambiguously identified in BoNT/D-HCR, a shallow cavity in an analogous location to the other BoNT serotypes HCR domains is observed in BoNT/D-HCR that has features compatible with membrane binding. A portion of a loop near the putative receptor binding site, K1236-N1244, is hydrophobic and solvent-exposed and may directly bind membrane lipids. Liposome-binding experiments with BoNT/D-HCR demonstrate that this membrane lipid may be phosphatidylethanolamine.« less
-
Structural Analysis of the Receptor Binding Domain of Botulinum Neurotoxin Serotype D
DOE Office of Scientific and Technical Information (OSTI.GOV)
Y Zhang; G Buchko; L Qin
2011-12-31
Botulinum neurotoxins (BoNTs) are the most toxic proteins known. The mechanism for entry into neuronal cells for serotypes A, B, E, F, and G involves a well understood dual receptor (protein and ganglioside) process, however, the mechanism of entry for serotypes C and D remains unclear. To provide structural insights into how BoNT/D enters neuronal cells, the crystal structure of the receptor binding domain (S863-E1276) for this serotype (BoNT/D-HCR) was determined at 1.65{angstrom} resolution. While BoNT/D-HCR adopts an overall fold similar to that observed in other known BoNT HCRs, several major structural differences are present. These structural differences are locatedmore » at, or near, putative receptor binding sites and may be responsible for BoNT/D host preferences. Two loops, S1195-I1204 and K1236-N1244, located on both sides of the putative protein receptor binding pocket, are displaced >10{angstrom} relative to the corresponding residues in the crystal structures of BoNT/B and G. Obvious clashes were observed in the putative protein receptor binding site when the BoNT/B protein receptor synaptotagmin II was modeled into the BoNT/D-HCR structure. Although a ganglioside binding site has never been unambiguously identified in BoNT/D-HCR, a shallow cavity in an analogous location to the other BoNT serotypes HCR domains is observed in BoNT/D-HCR that has features compatible with membrane binding. A portion of a loop near the putative receptor binding site, K1236-N1244, is hydrophobic and solvent-exposed and may directly bind membrane lipids. Liposome-binding experiments with BoNT/D-HCR demonstrate that this membrane lipid may be phosphatidylethanolamine.« less
-
Structural Basis for Antifreeze Activity of Ice-binding Protein from Arctic Yeast*
Lee, Jun Hyuck; Park, Ae Kyung; Do, Hackwon; Park, Kyoung Sun; Moh, Sang Hyun; Chi, Young Min; Kim, Hak Jun
2012-01-01
Arctic yeast Leucosporidium sp. produces a glycosylated ice-binding protein (LeIBP) with a molecular mass of ∼25 kDa, which can lower the freezing point below the melting point once it binds to ice. LeIBP is a member of a large class of ice-binding proteins, the structures of which are unknown. Here, we report the crystal structures of non-glycosylated LeIBP and glycosylated LeIBP at 1.57- and 2.43-Å resolution, respectively. Structural analysis of the LeIBPs revealed a dimeric right-handed β-helix fold, which is composed of three parts: a large coiled structural domain, a long helix region (residues 96–115 form a long α-helix that packs along one face of the β-helix), and a C-terminal hydrophobic loop region (243PFVPAPEVV251). Unexpectedly, the C-terminal hydrophobic loop region has an extended conformation pointing away from the body of the coiled structural domain and forms intertwined dimer interactions. In addition, structural analysis of glycosylated LeIBP with sugar moieties attached to Asn185 provides a basis for interpreting previous biochemical analyses as well as the increased stability and secretion of glycosylated LeIBP. We also determined that the aligned Thr/Ser/Ala residues are critical for ice binding within the B face of LeIBP using site-directed mutagenesis. Although LeIBP has a common β-helical fold similar to that of canonical hyperactive antifreeze proteins, the ice-binding site is more complex and does not have a simple ice-binding motif. In conclusion, we could identify the ice-binding site of LeIBP and discuss differences in the ice-binding modes compared with other known antifreeze proteins and ice-binding proteins. PMID:22303017
-
Drug Promiscuity in PDB: Protein Binding Site Similarity Is Key.
Haupt, V Joachim; Daminelli, Simone; Schroeder, Michael
2013-01-01
Drug repositioning applies established drugs to new disease indications with increasing success. A pre-requisite for drug repurposing is drug promiscuity (polypharmacology) - a drug's ability to bind to several targets. There is a long standing debate on the reasons for drug promiscuity. Based on large compound screens, hydrophobicity and molecular weight have been suggested as key reasons. However, the results are sometimes contradictory and leave space for further analysis. Protein structures offer a structural dimension to explain promiscuity: Can a drug bind multiple targets because the drug is flexible or because the targets are structurally similar or even share similar binding sites? We present a systematic study of drug promiscuity based on structural data of PDB target proteins with a set of 164 promiscuous drugs. We show that there is no correlation between the degree of promiscuity and ligand properties such as hydrophobicity or molecular weight but a weak correlation to conformational flexibility. However, we do find a correlation between promiscuity and structural similarity as well as binding site similarity of protein targets. In particular, 71% of the drugs have at least two targets with similar binding sites. In order to overcome issues in detection of remotely similar binding sites, we employed a score for binding site similarity: LigandRMSD measures the similarity of the aligned ligands and uncovers remote local similarities in proteins. It can be applied to arbitrary structural binding site alignments. Three representative examples, namely the anti-cancer drug methotrexate, the natural product quercetin and the anti-diabetic drug acarbose are discussed in detail. Our findings suggest that global structural and binding site similarity play a more important role to explain the observed drug promiscuity in the PDB than physicochemical drug properties like hydrophobicity or molecular weight. Additionally, we find ligand flexibility to have a minor influence.
-
Predicting nucleic acid binding interfaces from structural models of proteins.
Dror, Iris; Shazman, Shula; Mukherjee, Srayanta; Zhang, Yang; Glaser, Fabian; Mandel-Gutfreund, Yael
2012-02-01
The function of DNA- and RNA-binding proteins can be inferred from the characterization and accurate prediction of their binding interfaces. However, the main pitfall of various structure-based methods for predicting nucleic acid binding function is that they are all limited to a relatively small number of proteins for which high-resolution three-dimensional structures are available. In this study, we developed a pipeline for extracting functional electrostatic patches from surfaces of protein structural models, obtained using the I-TASSER protein structure predictor. The largest positive patches are extracted from the protein surface using the patchfinder algorithm. We show that functional electrostatic patches extracted from an ensemble of structural models highly overlap the patches extracted from high-resolution structures. Furthermore, by testing our pipeline on a set of 55 known nucleic acid binding proteins for which I-TASSER produces high-quality models, we show that the method accurately identifies the nucleic acids binding interface on structural models of proteins. Employing a combined patch approach we show that patches extracted from an ensemble of models better predicts the real nucleic acid binding interfaces compared with patches extracted from independent models. Overall, these results suggest that combining information from a collection of low-resolution structural models could be a valuable approach for functional annotation. We suggest that our method will be further applicable for predicting other functional surfaces of proteins with unknown structure. Copyright © 2011 Wiley Periodicals, Inc.
-
Chin, Wei-Chien-Benny; Wen, Tzai-Hung
2015-01-01
A network approach, which simplifies geographic settings as a form of nodes and links, emphasizes the connectivity and relationships of spatial features. Topological networks of spatial features are used to explore geographical connectivity and structures. The PageRank algorithm, a network metric, is often used to help identify important locations where people or automobiles concentrate in the geographical literature. However, geographic considerations, including proximity and location attractiveness, are ignored in most network metrics. The objective of the present study is to propose two geographically modified PageRank algorithms-Distance-Decay PageRank (DDPR) and Geographical PageRank (GPR)-that incorporate geographic considerations into PageRank algorithms to identify the spatial concentration of human movement in a geospatial network. Our findings indicate that in both intercity and within-city settings the proposed algorithms more effectively capture the spatial locations where people reside than traditional commonly-used network metrics. In comparing location attractiveness and distance decay, we conclude that the concentration of human movement is largely determined by the distance decay. This implies that geographic proximity remains a key factor in human mobility.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cuneo, Matthew J.; Beese, Lorena S.; Hellinga, Homme W.
Periplasmic binding proteins (PBPs) constitute a protein superfamily that binds a wide variety of ligands. In prokaryotes, PBPs function as receptors for ATP-binding cassette or tripartite ATP-independent transporters and chemotaxis systems. In many instances, PBPs bind their cognate ligands with exquisite specificity, distinguishing, for example, between sugar epimers or structurally similar anions. By contrast, oligopeptide-binding proteins bind their ligands through interactions with the peptide backbone but do not distinguish between different side chains. The extremophile Thermotoga maritima possesses a remarkable array of carbohydrate-processing metabolic systems, including the hydrolysis of cellulosic polymers. Here, we present the crystal structure of a T.more » maritima cellobiose-binding protein (tm0031) that is homologous to oligopeptide-binding proteins. T. maritima cellobiose-binding protein binds a variety of lengths of {beta}(1 {yields} 4)-linked glucose oligomers, ranging from two rings (cellobiose) to five (cellopentaose). The structure reveals that binding is semi-specific. The disaccharide at the nonreducing end binds specifically; the other rings are located in a large solvent-filled groove, where the reducing end makes several contacts with the protein, thereby imposing an upper limit of the oligosaccharides that are recognized. Semi-specific recognition, in which a molecular class rather than individual species is selected, provides an efficient solution for the uptake of complex mixtures.« less
-
Patikoglou, Georgia A; Westblade, Lars F; Campbell, Elizabeth A; Lamour, Valérie; Lane, William J; Darst, Seth A
2007-09-21
The Escherichia coli Rsd protein binds tightly and specifically to the RNA polymerase (RNAP) sigma(70) factor. Rsd plays a role in alternative sigma factor-dependent transcription by biasing the competition between sigma(70) and alternative sigma factors for the available core RNAP. Here, we determined the 2.6 A-resolution X-ray crystal structure of Rsd bound to sigma(70) domain 4 (sigma(70)(4)), the primary determinant for Rsd binding within sigma(70). The structure reveals that Rsd binding interferes with the two primary functions of sigma(70)(4), core RNAP binding and promoter -35 element binding. Interestingly, the most highly conserved Rsd residues form a network of interactions through the middle of the Rsd structure that connect the sigma(70)(4)-binding surface with three cavities exposed on distant surfaces of Rsd, suggesting functional coupling between sigma(70)(4) binding and other binding surfaces of Rsd, either for other proteins or for as yet unknown small molecule effectors. These results provide a structural basis for understanding the role of Rsd, as well as its ortholog, AlgQ, a positive regulator of Pseudomonas aeruginosa virulence, in transcription regulation.
-
Crystal structure of the Escherichia coli regulator of σ70, Rsd, in complex with σ70 domain 4
Patikoglou, Georgia A.; Westblade, Lars F.; Campbell, Elizabeth A.; Lamour, Valérie; Lane, William J.; Darst, Seth A.
2007-01-01
Summary The Escherichia coli Rsd protein binds tightly and specifically to the RNA polymerase (RNAP) σ70 factor. Rsd plays a role in alternative σ factor-dependent transcription by biasing the competition between σ70 and alternative σ factors for the available core RNAP. Here, we determined the 2.6 Å-resolution X-ray crystal structure of Rsd bound to σ70 domain 4 (σ704), the primary determinant for Rsd binding within σ70. The structure reveals that Rsd binding interferes with the two primary functions of σ704, core RNAP binding and promoter –35 element binding. Interestingly, the most highly conserved Rsd residues form a network of interactions through the middle of the Rsd structure that connect the σ704-binding surface with three cavities exposed on distant surfaces of Rsd, suggesting functional coupling between σ704 binding and other binding surfaces of Rsd, either for other proteins or for as yet unknown small molecule effectors. These results provide a structural basis for understanding the role of Rsd, as well as its ortholog, AlgQ, a positive regulator of Pseudomonas aeruginosa virulence, in transcription regulation. PMID:17681541
-
Wong, Edmond; Vaaje-Kolstad, Gustav; Ghosh, Avishek; Hurtado-Guerrero, Ramon; Konarev, Peter V.; Ibrahim, Adel F. M.; Svergun, Dmitri I.; Eijsink, Vincent G. H.; Chatterjee, Nabendu S.; van Aalten, Daan M. F.
2012-01-01
Vibrio cholerae is a bacterial pathogen that colonizes the chitinous exoskeleton of zooplankton as well as the human gastrointestinal tract. Colonization of these different niches involves an N-acetylglucosamine binding protein (GbpA) that has been reported to mediate bacterial attachment to both marine chitin and mammalian intestinal mucin through an unknown molecular mechanism. We report structural studies that reveal that GbpA possesses an unusual, elongated, four-domain structure, with domains 1 and 4 showing structural homology to chitin binding domains. A glycan screen revealed that GbpA binds to GlcNAc oligosaccharides. Structure-guided GbpA truncation mutants show that domains 1 and 4 of GbpA interact with chitin in vitro, whereas in vivo complementation studies reveal that domain 1 is also crucial for mucin binding and intestinal colonization. Bacterial binding studies show that domains 2 and 3 bind to the V. cholerae surface. Finally, mouse virulence assays show that only the first three domains of GbpA are required for colonization. These results explain how GbpA provides structural/functional modular interactions between V. cholerae, intestinal epithelium and chitinous exoskeletons. PMID:22253590
-
Yang, Ran; Yu, Lanlan; Zeng, Huajin; Liang, Ruiling; Chen, Xiaolan; Qu, Lingbo
2012-11-01
In this work, the interactions of twelve structurally different flavonoids with Lysozyme (Lys) were studied by fluorescence quenching method. The interaction mechanism and binding properties were investigated. It was found that the binding capacities of flavonoids to Lys were highly depend on the number and position of hydrogen, the kind and position of glycosyl. To explore the selectivity of the bindings of flavonoids with Lys, the structure descriptors of the flavonoids were calculated under QSAR software package of Cerius2, the quantitative relationship between the structures of flavonoids and their binding activities to Lys (QSAR) was performed through genetic function approximation (GFA) regression analysis. The QSAR regression equation was K(A) = 37850.460 + 1630.01Dipole +3038.330HD-171.795MR. (r = 0.858, r(CV)(2) = 0.444, F((11,3)) = 7.48), where K(A) is binding constants, Dipole, HD and MR was dipole moment, number of hydrogen-bond donor and molecular refractivity, respectively. The obtained results make us understand better how the molecular structures influencing their binding to protein which may open up new avenues for the design of the most suitable flavonoids derivatives with structure variants.
-
SMARTIV: combined sequence and structure de-novo motif discovery for in-vivo RNA binding data.
Polishchuk, Maya; Paz, Inbal; Yakhini, Zohar; Mandel-Gutfreund, Yael
2018-05-25
Gene expression regulation is highly dependent on binding of RNA-binding proteins (RBPs) to their RNA targets. Growing evidence supports the notion that both RNA primary sequence and its local secondary structure play a role in specific Protein-RNA recognition and binding. Despite the great advance in high-throughput experimental methods for identifying sequence targets of RBPs, predicting the specific sequence and structure binding preferences of RBPs remains a major challenge. We present a novel webserver, SMARTIV, designed for discovering and visualizing combined RNA sequence and structure motifs from high-throughput RNA-binding data, generated from in-vivo experiments. The uniqueness of SMARTIV is that it predicts motifs from enriched k-mers that combine information from ranked RNA sequences and their predicted secondary structure, obtained using various folding methods. Consequently, SMARTIV generates Position Weight Matrices (PWMs) in a combined sequence and structure alphabet with assigned P-values. SMARTIV concisely represents the sequence and structure motif content as a single graphical logo, which is informative and easy for visual perception. SMARTIV was examined extensively on a variety of high-throughput binding experiments for RBPs from different families, generated from different technologies, showing consistent and accurate results. Finally, SMARTIV is a user-friendly webserver, highly efficient in run-time and freely accessible via http://smartiv.technion.ac.il/.
-
Das, Kalyan; Acton, Thomas; Chiang, Yiwen; Shih, Lydia; Arnold, Eddy; Montelione, Gaetano T.
2004-01-01
The RlmA class of enzymes (RlmAI and RlmAII) catalyzes N1-methylation of a guanine base (G745 in Gram-negative and G748 in Gram-positive bacteria) of hairpin 35 of 23S rRNA. We have determined the crystal structure of Escherichia coli RlmAI at 2.8-Å resolution, providing 3D structure information for the RlmA class of RNA methyltransferases. The dimeric protein structure exhibits features that provide new insights into its molecular function. Each RlmAI molecule has a Zn-binding domain, responsible for specific recognition and binding of its rRNA substrate, and a methyltransferase domain. The asymmetric RlmAI dimer observed in the crystal structure has a well defined W-shaped RNA-binding cleft. Two S-adenosyl-l-methionine substrate molecules are located at the two valleys of the W-shaped RNA-binding cleft. The unique shape of the RNA-binding cleft, different from that of known RNA-binding proteins, is highly specific and structurally complements the 3D structure of hairpin 35 of bacterial 23S rRNA. Apart from the hairpin 35, parts of hairpins 33 and 34 also interact with the RlmAI dimer. PMID:14999102
-
Joseph, Prem Raj B.; Mosier, Philip D.; Desai, Umesh R.; Rajarathnam, Krishna
2015-01-01
Chemokine CXCL8/interleukin-8 (IL-8) plays a crucial role in directing neutrophils and oligodendrocytes to combat infection/injury and tumour cells in metastasis development. CXCL8 exists as monomers and dimers and interaction of both forms with glycosaminoglycans (GAGs) mediate these diverse cellular processes. However, very little is known regarding the structural basis underlying CXCL8–GAG interactions. There are conflicting reports on the affinities, geometry and whether the monomer or dimer is the high-affinity GAG ligand. To resolve these issues, we characterized the binding of a series of heparin-derived oligosaccharides [heparin disaccharide (dp2), heparin tetrasaccharide (dp4), heparin octasaccharide (dp8) and heparin 14-mer (dp14)] to the wild-type (WT) dimer and a designed monomer using solution NMR spectroscopy. The pattern and extent of binding-induced chemical shift perturbation (CSP) varied between dimer and monomer and between longer and shorter oligosaccharides. NMR-based structural models show that different interaction modes coexist and that the nature of interactions varied between monomer and dimer and oligosaccharide length. MD simulations indicate that the binding interface is structurally plastic and provided residue-specific details of the dynamic nature of the binding interface. Binding studies carried out under conditions at which WT CXCL8 exists as monomers and dimers provide unambiguous evidence that the dimer is the high-affinity GAG ligand. Together, our data indicate that a set of core residues function as the major recognition/binding site, a set of peripheral residues define the various binding geometries and that the structural plasticity of the binding interface allows multiplicity of binding interactions. We conclude that structural plasticity most probably regulates in vivo CXCL8 monomer/dimer–GAG interactions and function. PMID:26371375
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Newberry, K.J.; Huffman, J.L.; Miller, M.C.
2009-05-22
BmrR is a member of the MerR family and a multidrug binding transcription factor that up-regulates the expression of the bmr multidrug efflux transporter gene in response to myriad lipophilic cationic compounds. The structural mechanism by which BmrR binds these chemically and structurally different drugs and subsequently activates transcription is poorly understood. Here, we describe the crystal structures of BmrR bound to rhodamine 6G (R6G) or berberine (Ber) and cognate DNA. These structures reveal each drug stacks against multiple aromatic residues with their positive charges most proximal to the carboxylate group of Glu-253 and that, unlike other multidrug binding pockets,more » that of BmrR is rigid. Substitution of Glu-253 with either alanine (E253A) or glutamine (E253Q) results in unpredictable binding affinities for R6G, Ber, and tetraphenylphosphonium. Moreover, these drug binding studies reveal that the negative charge of Glu-253 is not important for high affinity binding to Ber and tetraphenylphosphonium but plays a more significant, but unpredictable, role in R6G binding. In vitro transcription data show that E253A and E253Q are constitutively active, and structures of the drug-free E253A-DNA and E253Q-DNA complexes support a transcription activation mechanism requiring the expulsion of Tyr-152 from the multidrug binding pocket. In sum, these data delineate the mechanism by which BmrR binds lipophilic, monovalent cationic compounds and suggest the importance of the redundant negative electrostatic nature of this rigid drug binding pocket that can be used to discriminate against molecules that are not substrates of the Bmr multidrug efflux pump.« less
-
Ithuralde, Raúl Esteban; Roitberg, Adrián Enrique; Turjanski, Adrián Gustavo
2016-07-20
Intrinsically disordered proteins (IDPs) are a set of proteins that lack a definite secondary structure in solution. IDPs can acquire tertiary structure when bound to their partners; therefore, the recognition process must also involve protein folding. The nature of the transition state (TS), structured or unstructured, determines the binding mechanism. The characterization of the TS has become a major challenge for experimental techniques and molecular simulations approaches since diffusion, recognition, and binding is coupled to folding. In this work we present atomistic molecular dynamics (MD) simulations that sample the free energy surface of the coupled folding and binding of the transcription factor c-myb to the cotranscription factor CREB binding protein (CBP). This process has been recently studied and became a model to study IDPs. Despite the plethora of available information, we still do not know how c-myb binds to CBP. We performed a set of atomistic biased MD simulations running a total of 15.6 μs. Our results show that c-myb folds very fast upon binding to CBP with no unique pathway for binding. The process can proceed through both structured or unstructured TS's with similar probabilities. This finding reconciles previous seemingly different experimental results. We also performed Go-type coarse-grained MD of several structured and unstructured models that indicate that coupled folding and binding follows a native contact mechanism. To the best of our knowledge, this is the first atomistic MD simulation that samples the free energy surface of the coupled folding and binding processes of IDPs.
-
Binding free energy analysis of protein-protein docking model structures by evERdock.
Takemura, Kazuhiro; Matubayasi, Nobuyuki; Kitao, Akio
2018-03-14
To aid the evaluation of protein-protein complex model structures generated by protein docking prediction (decoys), we previously developed a method to calculate the binding free energies for complexes. The method combines a short (2 ns) all-atom molecular dynamics simulation with explicit solvent and solution theory in the energy representation (ER). We showed that this method successfully selected structures similar to the native complex structure (near-native decoys) as the lowest binding free energy structures. In our current work, we applied this method (evERdock) to 100 or 300 model structures of four protein-protein complexes. The crystal structures and the near-native decoys showed the lowest binding free energy of all the examined structures, indicating that evERdock can successfully evaluate decoys. Several decoys that show low interface root-mean-square distance but relatively high binding free energy were also identified. Analysis of the fraction of native contacts, hydrogen bonds, and salt bridges at the protein-protein interface indicated that these decoys were insufficiently optimized at the interface. After optimizing the interactions around the interface by including interfacial water molecules, the binding free energies of these decoys were improved. We also investigated the effect of solute entropy on binding free energy and found that consideration of the entropy term does not necessarily improve the evaluations of decoys using the normal model analysis for entropy calculation.
-
Binding free energy analysis of protein-protein docking model structures by evERdock
NASA Astrophysics Data System (ADS)
Takemura, Kazuhiro; Matubayasi, Nobuyuki; Kitao, Akio
2018-03-01
To aid the evaluation of protein-protein complex model structures generated by protein docking prediction (decoys), we previously developed a method to calculate the binding free energies for complexes. The method combines a short (2 ns) all-atom molecular dynamics simulation with explicit solvent and solution theory in the energy representation (ER). We showed that this method successfully selected structures similar to the native complex structure (near-native decoys) as the lowest binding free energy structures. In our current work, we applied this method (evERdock) to 100 or 300 model structures of four protein-protein complexes. The crystal structures and the near-native decoys showed the lowest binding free energy of all the examined structures, indicating that evERdock can successfully evaluate decoys. Several decoys that show low interface root-mean-square distance but relatively high binding free energy were also identified. Analysis of the fraction of native contacts, hydrogen bonds, and salt bridges at the protein-protein interface indicated that these decoys were insufficiently optimized at the interface. After optimizing the interactions around the interface by including interfacial water molecules, the binding free energies of these decoys were improved. We also investigated the effect of solute entropy on binding free energy and found that consideration of the entropy term does not necessarily improve the evaluations of decoys using the normal model analysis for entropy calculation.
-
Manjasetty, Babu A; Halavaty, Andrei S; Luan, Chi-Hao; Osipiuk, Jerzy; Mulligan, Rory; Kwon, Keehwan; Anderson, Wayne F; Joachimiak, Andrzej
2016-04-01
Multidrug transcription regulator AcrR from Salmonella enterica subsp. enterica serovar Typhimurium str. LT2 belongs to the tetracycline repressor family, one of the largest groups of bacterial transcription factors. The crystal structure of dimeric AcrR was determined and refined to 1.56Å resolution. The tertiary and quaternary structures of AcrR are similar to those of its homologs. The multidrug binding site was identified based on structural alignment with homologous proteins and has a di(hydroxyethyl)ether molecule bound. Residues from helices α4 and α7 shape the entry into this binding site. The structure of AcrR reveals that the extended helical conformation of helix α4 is stabilized by the hydrogen bond between Glu67 (helix α4) and Gln130 (helix α7). Based on the structural comparison with the closest homolog structure, the Escherichia coli AcrR, we propose that this hydrogen bond is responsible for control of the loop-to-helix transition within helix α4. This local conformational switch of helix α4 may be a key step in accessing the multidrug binding site and securing ligands at the binding site. Solution small-molecule binding studies suggest that AcrR binds ligands with their core chemical structure resembling the tetracyclic ring of cholesterol. Copyright © 2016. Published by Elsevier Inc.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kirschner, Austin N.; Sorem, Jessica; Longnecker, Richard
Epstein-Barr virus requires glycoproteins gH/gL, gB, and gp42 to fuse its lipid envelope with B cells. Gp42 is a type II membrane protein consisting of a flexible N-terminal region, which binds gH/gL, and a C-terminal lectin-like domain that binds to the B-cell entry receptor human leukocyte antigen (HLA) class II. Gp42 triggers membrane fusion after HLA binding, a process that requires simultaneous binding to gH/gL and a functional hydrophobic pocket in the lectin domain adjacent to the HLA binding site. Here we present the structure of gp42 in its unbound form. Comparisons to the previously determined structure of a gp42:HLAmore » complex reveals additional N-terminal residues forming part of the gH/gL binding site and structural changes in the receptor binding domain. Although the core of the lectin domain remains similar, significant shifts in two loops and an {alpha} helix bordering the essential hydrophobic pocket suggest a structural mechanism for triggering fusion.« less
-
Berntsson, Ronnie Per-Arne; Peng, Lisheng; Svensson, Linda Marie; Dong, Min; Stenmark, Pål
2013-09-03
Botulinum neurotoxins (BoNTs) can cause paralysis at exceptionally low concentrations and include seven serotypes (BoNT/A-G). The chimeric BoNT/DC toxin has a receptor binding domain similar to the same region in BoNT/C. However, BoNT/DC does not share protein receptor with BoNT/C. Instead, it shares synaptotagmin (Syt) I and II as receptors with BoNT/B, despite their low sequence similarity. Here, we present the crystal structures of the binding domain of BoNT/DC in complex with the recognition domains of its protein receptors, Syt-I and Syt-II. The structures reveal that BoNT/DC possesses a Syt binding site, distinct from the established Syt-II binding site in BoNT/B. Structure-based mutagenesis further shows that hydrophobic interactions play a key role in Syt binding. The structures suggest that the BoNT/DC ganglioside binding sites are independent of the protein receptor binding site. Our results reveal the remarkable versatility in the receptor recognition of the BoNTs. Copyright © 2013 Elsevier Ltd. All rights reserved.
-
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.
-
Key structural features of nonsteroidal ligands for binding and activation of the androgen receptor.
Yin, Donghua; He, Yali; Perera, Minoli A; Hong, Seoung Soo; Marhefka, Craig; Stourman, Nina; Kirkovsky, Leonid; Miller, Duane D; Dalton, James T
2003-01-01
The purposes of the present studies were to examine the androgen receptor (AR) binding ability and in vitro functional activity of multiple series of nonsteroidal compounds derived from known antiandrogen pharmacophores and to investigate the structure-activity relationships (SARs) of these nonsteroidal compounds. The AR binding properties of sixty-five nonsteroidal compounds were assessed by a radioligand competitive binding assay with the use of cytosolic AR prepared from rat prostates. The AR agonist and antagonist activities of high-affinity ligands were determined by the ability of the ligand to regulate AR-mediated transcriptional activation in cultured CV-1 cells, using a cotransfection assay. Nonsteroidal compounds with diverse structural features demonstrated a wide range of binding affinity for the AR. Ten compounds, mainly from the bicalutamide-related series, showed a binding affinity superior to the structural pharmacophore from which they were derived. Several SARs regarding nonsteroidal AR binding were revealed from the binding data, including stereoisomeric conformation, steric effect, and electronic effect. The functional activity of high-affinity ligands ranged from antagonist to full agonist for the AR. Several structural features were found to be determinative of agonist and antagonist activities. The nonsteroidal AR agonists identified from the present studies provided a pool of candidates for further development of selective androgen receptor modulators (SARMs) for androgen therapy. Also, these studies uncovered or confirmed numerous important SARs governing AR binding and functional properties by nonsteroidal molecules, which would be valuable in the future structural optimization of SARMs.
-
Crochet, Robert B.; Kim, Jeong-Do; Lee, Herie; Yim, Young-Sun; Kim, Song-Gun; Neau, David; Lee, Yong-Hwan
2016-01-01
The heart-specific isoform of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB2) is an important regulator of glycolytic flux in cardiac cells. Here, we present the crystal structures of two PFKFB2 orthologues, human and bovine, at resolutions of 2.0 and 1.8Å, respectively. Citrate, a TCA cycle intermediate and well-known inhibitor of PFKFB2, co-crystallized in the 2-kinase domains of both orthologues, occupying the fructose-6-phosphate binding-site and extending into the γ-phosphate binding pocket of ATP. This steric and electrostatic occlusion of the γ-phosphate site by citrate proved highly consequential to the binding of co-complexed ATP analogues. The bovine structure, which co-crystallized with ADP, closely resembled the overall structure of other PFKFB isoforms, with ADP mimicking the catalytic binding mode of ATP. The human structure, on the other hand, co-complexed with AMPPNP, which, unlike ADP, contains a γ-phosphate. The presence of this γ-phosphate made adoption of the catalytic ATP binding mode impossible for AMPPNP, forcing the analogue to bind atypically with concomitant conformational changes to the ATP binding-pocket. Inhibition kinetics were used to validate the structural observations, confirming citrate’s inhibition mechanism as competitive for F6P and noncompetitive for ATP. Together, these structural and kinetic data establish a molecular basis for citrate’s negative feed-back loop of the glycolytic pathway via PFKFB2. PMID:27802586
-
Patil, Dipak N.; Datta, Manali; Dev, Aditya; Dhindwal, Sonali; Singh, Nirpendra; Dasauni, Pushpanjali; Kundu, Suman; Sharma, Ashwani K.; Tomar, Shailly; Kumar, Pravindra
2013-01-01
The glycosyl hydrolase 18 (GH18) family consists of active chitinases as well as chitinase like lectins/proteins (CLPs). The CLPs share significant sequence and structural similarities with active chitinases, however, do not display chitinase activity. Some of these proteins are reported to have specific functions and carbohydrate binding property. In the present study, we report a novel chitinase like lectin (TCLL) from Tamarindus indica. The crystal structures of native TCLL and its complex with N-acetyl glucosamine were determined. Similar to the other CLPs of the GH18 members, TCLL lacks chitinase activity due to mutations of key active site residues. Comparison of TCLL with chitinases and other chitin binding CLPs shows that TCLL has substitution of some chitin binding site residues and more open binding cleft due to major differences in the loop region. Interestingly, the biochemical studies suggest that TCLL is an N-acetyl glucosamine specific chi-lectin, which is further confirmed by the complex structure of TCLL with N-acetyl glucosamine complex. TCLL has two distinct N-acetyl glucosamine binding sites S1 and S2 that contain similar polar residues, although interaction pattern with N-acetyl glucosamine varies extensively among them. Moreover, TCLL structure depicts that how plants utilize existing structural scaffolds ingenuously to attain new functions. To date, this is the first structural investigation of a chi-lectin from plants that explore novel carbohydrate binding sites other than chitin binding groove observed in GH18 family members. Consequently, TCLL structure confers evidence for evolutionary link of lectins with chitinases. PMID:23717482
-
Shah, Manish B.; Ingram-Smith, Cheryl; Cooper, Leroy L.; Qu, Jun; Meng, Yu; Smith, Kerry S.; Gulick, Andrew M.
2009-01-01
The acyl-AMP forming family of adenylating enzymes catalyze two-step reactions to activate a carboxylate with the chemical energy derived from ATP hydrolysis. X-ray crystal structures have been determined for multiple members of this family and, together with biochemical studies, provide insights into the active site and catalytic mechanisms used by these enzymes. These studies have shown that the enzymes use a domain rotation of 140° to reconfigure a single active site to catalyze the two partial reactions. We present here the crystal structure of a new medium chain acyl-CoA synthetase from Methanosarcina acetivorans. The binding pocket for the three substrates is analyzed, with many conserved residues present in the AMP binding pocket. The CoA binding pocket is compared to the pockets of both acetyl-CoA synthetase and 4-chlorobenzoate:CoA ligase. Most interestingly, the acyl binding pocket of the new structure is compared with other acyl- and aryl-CoA synthetases. A comparison of the acyl-binding pocket of the acyl-CoA synthetase from M. acetivorans with other structures identifies a shallow pocket that is used to bind the medium chain carboxylates. These insights emphasize the high sequence and structural diversity among this family in the area of the acyl binding pocket. PMID:19544569
-
Miyakawa, Takuya; Sawano, Yoriko; Miyazono, Ken-ichi; Miyauchi, Yumiko; Hatano, Ken-ichi
2013-01-01
STK_08120 is a member of the thermoacidophile-specific DUF3211 protein family from Sulfolobus tokodaii strain 7. Its molecular function remains obscure, and sequence similarities for obtaining functional remarks are not available. In this study, the crystal structure of STK_08120 was determined at 1.79-Å resolution to predict its probable function using structure similarity searches. The structure adopts an α/β structure of a helix-grip fold, which is found in the START domain proteins with cavities for hydrophobic substrates or ligands. The detailed structural features implied that fatty acids are the primary ligand candidates for STK_08120, and binding assays revealed that the protein bound long-chain saturated fatty acids (>C14) and their trans-unsaturated types with an affinity equal to that for major fatty acid binding proteins in mammals and plants. Moreover, the structure of an STK_08120-myristic acid complex revealed a unique binding mode among fatty acid binding proteins. These results suggest that the thermoacidophile-specific protein family DUF3211 functions as a fatty acid carrier with a novel binding mode. PMID:23836863
-
Unique structural modulation of a non-native substrate by cochaperone DnaJ.
Tiwari, Satyam; Kumar, Vignesh; Jayaraj, Gopal Gunanathan; Maiti, Souvik; Mapa, Koyeli
2013-02-12
The role of bacterial DnaJ protein as a cochaperone of DnaK is strongly appreciated. Although DnaJ unaccompanied by DnaK can bind unfolded as well as native substrate proteins, its role as an individual chaperone remains elusive. In this study, we demonstrate that DnaJ binds a model non-native substrate with a low nanomolar dissociation constant and, more importantly, modulates the structure of its non-native state. The structural modulation achieved by DnaJ is different compared to that achieved by the DnaK-DnaJ complex. The nature of structural modulation exerted by DnaJ is suggestive of a unique unfolding activity on the non-native substrate by the chaperone. Furthermore, we demonstrate that the zinc binding motif along with the C-terminal substrate binding domain of DnaJ is necessary and sufficient for binding and the subsequent binding-induced structural alterations of the non-native substrate. We hypothesize that this hitherto unknown structural alteration of non-native states by DnaJ might be important for its chaperoning activity by removing kinetic traps of the folding intermediates.
-
Six independent fucose-binding sites in the crystal structure of Aspergillus oryzae lectin
DOE Office of Scientific and Technical Information (OSTI.GOV)
Makyio, Hisayoshi; Shimabukuro, Junpei; Suzuki, Tatsuya
The crystal structure of AOL (a fucose-specific lectin of Aspergillus oryzae) has been solved by SAD (single-wavelength anomalous diffraction) and MAD (multi-wavelength anomalous diffraction) phasing of seleno-fucosides. The overall structure is a six-bladed β-propeller similar to that of other fucose-specific lectins. The fucose moieties of the seleno-fucosides are located in six fucose-binding sites. Although the Arg and Glu/Gln residues bound to the fucose moiety are common to all fucose-binding sites, the amino-acid residues involved in fucose binding at each site are not identical. The varying peak heights of the seleniums in the electron density map suggest that each fucose-binding sitemore » has a different carbohydrate binding affinity. - Highlights: • The six-bladed β-propeller structure of AOL was solved by seleno-sugar phasing. • The mode of fucose binding is essentially conserved at all six binding sites. • The seleno-fucosides exhibit slightly different interactions and electron densities. • These findings suggest that the affinity for fucose is not identical at each site.« less
-
Chu, Byron C. H.; Otten, Renee; Krewulak, Karla D.; Mulder, Frans A. A.; Vogel, Hans J.
2014-01-01
The periplasmic binding protein (PBP) FepB plays a key role in transporting the catecholate siderophore ferric enterobactin from the outer to the inner membrane in Gram-negative bacteria. The solution structures of the 34-kDa apo- and holo-FepB from Escherichia coli, solved by NMR, represent the first solution structures determined for the type III class of PBPs. Unlike type I and II PBPs, which undergo large “Venus flytrap” conformational changes upon ligand binding, both forms of FepB maintain similar overall folds; however, binding of the ligand is accompanied by significant loop movements. Reverse methyl cross-saturation experiments corroborated chemical shift perturbation results and uniquely defined the binding pocket for gallium enterobactin (GaEnt). NMR relaxation experiments indicated that a flexible loop (residues 225–250) adopted a more rigid and extended conformation upon ligand binding, which positioned residues for optimal interactions with the ligand and the cytoplasmic membrane ABC transporter (FepCD), respectively. In conclusion, this work highlights the pivotal role that structural dynamics plays in ligand binding and transporter interactions in type III PBPs. PMID:25173704
-
Structural and Physical Basis for Anti-IgE Therapy
NASA Astrophysics Data System (ADS)
Wright, Jon D.; Chu, Hsing-Mao; Huang, Chun-Hsiang; Ma, Che; Wen Chang, Tse; Lim, Carmay
2015-06-01
Omalizumab, an anti-IgE antibody, used to treat severe allergic asthma and chronic idiopathic urticaria, binds to IgE in blood or membrane-bound on B lymphocytes but not to IgE bound to its high (FcɛRI) or low (CD23) affinity receptor. Mutagenesis studies indicate overlapping FcɛRI and omalizumab-binding sites in the Cɛ3 domain, but crystallographic studies show FcɛRI and CD23-binding sites that are far apart, so how can omalizumab block IgE from binding both receptors? We report a 2.42-Å omalizumab-Fab structure, a docked IgE-Fc/omalizumab-Fab structure consistent with available experimental data, and the free energy contributions of IgE residues to binding omalizumab, CD23, and FcɛRI. These results provide a structural and physical basis as to why omalizumab cannot bind receptor-bound IgE and why omalizumab-bound IgE cannot bind to CD23/FcɛRI. They reveal the key IgE residues and their roles in binding omalizumab, CD23, and FcɛRI.
-
Vu, Michael M. K.; Jameson, Nora E.; Masuda, Stuart J.; Lin, Dana; Larralde-Ridaura, Rosa; Lupták, Andrej
2012-01-01
SUMMARY Aptamers are structured macromolecules in vitro evolved to bind molecular targets, whereas in nature they form the ligand-binding domains of riboswitches. Adenosine aptamers of a single structural family were isolated several times from random pools but they have not been identified in genomic sequences. We used two unbiased methods, structure-based bioinformatics and human genome-based in vitro selection, to identify aptamers that form the same adenosine-binding structure in a bacterium, and several vertebrates, including humans. Two of the human aptamers map to introns of RAB3C and FGD3 genes. The RAB3C aptamer binds ATP with dissociation constants about ten times lower than physiological ATP concentration, while the minimal FGD3 aptamer binds ATP only co-transcriptionally. PMID:23102219
-
Stereochemical model for proflavin intercalation in A-DNA.
Alden, C J; Arnott, S
1977-01-01
Linked-atom molecular modelling was employed to determine the steric and torsional requirements for intercalation of proflavine into a double-stranded region of DNA compatible with adjacent regions of cohelical A-DNA. The optimum intercalation conformation is characterized by the dihedral angles xi and psi becoming trans, with all sugars retaining the characteristics C3'-endo pucker. This extended conformation results in virtually no helical unwinding, suggesting it may be an appropriate model for an intercalative intermediary in mutagenesis by virtue of its similarity to standard helical DNA. PMID:593890
-
Hansen, M R; Simorre, J P; Hanson, P; Mokler, V; Bellon, L; Beigelman, L; Pardi, A
1999-01-01
A novel metal-binding site has been identified in the hammerhead ribozyme by 31P NMR. The metal-binding site is associated with the A13 phosphate in the catalytic core of the hammerhead ribozyme and is distinct from any previously identified metal-binding sites. 31P NMR spectroscopy was used to measure the metal-binding affinity for this site and leads to an apparent dissociation constant of 250-570 microM at 25 degrees C for binding of a single Mg2+ ion. The NMR data also show evidence of a structural change at this site upon metal binding and these results are compared with previous data on metal-induced structural changes in the core of the hammerhead ribozyme. These NMR data were combined with the X-ray structure of the hammerhead ribozyme (Pley HW, Flaherty KM, McKay DB. 1994. Nature 372:68-74) to model RNA ligands involved in binding the metal at this A13 site. In this model, the A13 metal-binding site is structurally similar to the previously identified A(g) metal-binding site and illustrates the symmetrical nature of the tandem G x A base pairs in domain 2 of the hammerhead ribozyme. These results demonstrate that 31P NMR represents an important method for both identification and characterization of metal-binding sites in nucleic acids. PMID:10445883
-
Sakkiah, Sugunadevi; Kusko, Rebecca; Pan, Bohu; Guo, Wenjing; Ge, Weigong; Tong, Weida; Hong, Huixiao
2018-01-01
When a small molecule binds to the androgen receptor (AR), a conformational change can occur which impacts subsequent binding of co-regulator proteins and DNA. In order to accurately study this mechanism, the scientific community needs a crystal structure of the Wild type AR (WT-AR) ligand binding domain, bound with antagonist. To address this open need, we leveraged molecular docking and molecular dynamics (MD) simulations to construct a structure of the WT-AR ligand binding domain bound with antagonist bicalutamide. The structure of mutant AR (Mut-AR) bound with this same antagonist informed this study. After molecular docking analysis pinpointed the suitable binding orientation of a ligand in AR, the model was further optimized through 1 μs of MD simulations. Using this approach, three molecular systems were studied: (1) WT-AR bound with agonist R1881, (2) WT-AR bound with antagonist bicalutamide, and (3) Mut-AR bound with bicalutamide. Our structures were very similar to the experimentally determined structures of both WT-AR with R1881 and Mut-AR with bicalutamide, demonstrating the trustworthiness of this approach. In our model, when WT-AR is bound with bicalutamide, Val716/Lys720/Gln733, or Met734/Gln738/Glu897 move and thus disturb the positive and negative charge clumps of the AF2 site. This disruption of the AF2 site is key for understanding the impact of antagonist binding on subsequent co-regulator binding. In conclusion, the antagonist induced structural changes in WT-AR detailed in this study will enable further AR research and will facilitate AR targeting drug discovery.
-
Carbohydrate recognition: A minimalistic approach to binding
NASA Astrophysics Data System (ADS)
Kubik, Stefan
2012-09-01
Synthetic receptors with properties resembling those of carbohydrate-binding proteins are known, but they are structurally rather complex. Elaborate structures are, however, not always required to bind carbohydrates in water -- much simpler compounds can be just as effective.
-
Lee, Chang Woo; Kim, Jung Eun; Do, Hackwon; Kim, Ryeo-Ok; Lee, Sung Gu; Park, Hyun Ho; Chang, Jeong Ho; Yim, Joung Han; Park, Hyun; Kim, Il-Chan; Lee, Jun Hyuck
2015-09-11
Fatty acid-binding proteins (FABPs) are involved in transporting hydrophobic fatty acids between various aqueous compartments of the cell by directly binding ligands inside their β-barrel cavities. Here, we report the crystal structures of ligand-unbound pFABP4, linoleate-bound pFABP4, and palmitate-bound pFABP5, obtained from gentoo penguin (Pygoscelis papua), at a resolution of 2.1 Å, 2.2 Å, and 2.3 Å, respectively. The pFABP4 and pFABP5 proteins have a canonical β-barrel structure with two short α-helices that form a cap region and fatty acid ligand binding sites in the hydrophobic cavity within the β-barrel structure. Linoleate-bound pFABP4 and palmitate-bound pFABP5 possess different ligand-binding modes and a unique ligand-binding pocket due to several sequence dissimilarities (A76/L78, T30/M32, underlining indicates pFABP4 residues) between the two proteins. Structural comparison revealed significantly different conformational changes in the β3-β4 loop region (residues 57-62) as well as the flipped Phe60 residue of pFABP5 than that in pFABP4 (the corresponding residue is Phe58). A ligand-binding study using fluorophore displacement assays shows that pFABP4 has a relatively strong affinity for linoleate as compared to pFABP5. In contrast, pFABP5 exhibits higher affinity for palmitate than that for pFABP4. In conclusion, our high-resolution structures and ligand-binding studies provide useful insights into the ligand-binding preferences of pFABPs based on key protein-ligand interactions. Copyright © 2015 Elsevier Inc. All rights reserved.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tewary, Sunil K.; Liang, Lingfei; Lin, Zihan
Members of the Parvoviridae family all encode a non-structural protein 1 (NS1) that directs replication of single-stranded viral DNA, packages viral DNA into capsid, and serves as a potent transcriptional activator. Here we report the X-ray structure of the minute virus of mice (MVM) NS1 N-terminal domain at 1.45 Å resolution, showing that sites for dsDNA binding, ssDNA binding and cleavage, nuclear localization, and other functions are integrated on a canonical fold of the histidine-hydrophobic-histidine superfamily of nucleases, including elements specific for this Protoparvovirus but distinct from its Bocaparvovirus or Dependoparvovirus orthologs. High resolution structural analysis reveals a nickase activemore » site with an architecture that allows highly versatile metal ligand binding. The structures support a unified mechanism of replication origin recognition for homotelomeric and heterotelomeric parvoviruses, mediated by a basic-residue-rich hairpin and an adjacent helix in the initiator proteins and by tandem tetranucleotide motifs in the replication origins. - Highlights: • The structure of a parvovirus replication initiator protein has been determined; • The structure sheds light on mechanisms of ssDNA binding and cleavage; • The nickase active site is preconfigured for versatile metal ligand binding; • The binding site for the double-stranded replication origin DNA is identified; • A single domain integrates multiple functions in virus replication.« less
-
Structural basis of redox-dependent substrate binding of protein disulfide isomerase
Yagi-Utsumi, Maho; Satoh, Tadashi; Kato, Koichi
2015-01-01
Protein disulfide isomerase (PDI) is a multidomain enzyme, operating as an essential folding catalyst, in which the b′ and a′ domains provide substrate binding sites and undergo an open–closed domain rearrangement depending on the redox states of the a′ domain. Despite the long research history of this enzyme, three-dimensional structural data remain unavailable for its ligand-binding mode. Here we characterize PDI substrate recognition using α-synuclein (αSN) as the model ligand. Our nuclear magnetic resonance (NMR) data revealed that the substrate-binding domains of PDI captured the αSN segment Val37–Val40 only in the oxidized form. Furthermore, we determined the crystal structure of an oxidized form of the b′–a′ domains in complex with an undecapeptide corresponding to this segment. The peptide-binding mode observed in the crystal structure with NMR validation, was characterized by hydrophobic interactions on the b′ domain in an open conformation. Comparison with the previously reported crystal structure indicates that the a′ domain partially masks the binding surface of the b′ domain, causing steric hindrance against the peptide in the reduced form of the b′–a′ domains that exhibits a closed conformation. These findings provide a structural basis for the mechanism underlying the redox-dependent substrate binding of PDI. PMID:26350503
-
Structural characterization of metal binding to a cold-adapted frataxin.
Noguera, Martín E; Roman, Ernesto A; Rigal, Juan B; Cousido-Siah, Alexandra; Mitschler, André; Podjarny, Alberto; Santos, Javier
2015-06-01
Frataxin is an evolutionary conserved protein that participates in iron metabolism. Deficiency of this small protein in humans causes a severe neurodegenerative disease known as Friedreich's ataxia. A number of studies indicate that frataxin binds iron and regulates Fe-S cluster biosynthesis. Previous structural studies showed that metal binding occurs mainly in a region of high density of negative charge. However, a comprehensive characterization of the binding sites is required to gain further insights into the mechanistic details of frataxin function. In this work, we have solved the X-ray crystal structures of a cold-adapted frataxin from a psychrophilic bacterium in the presence of cobalt or europium ions. We have identified a number of metal-binding sites, mainly solvent exposed, several of which had not been observed in previous studies on mesophilic homologues. No major structural changes were detected upon metal binding, although the structures exhibit significant changes in crystallographic B-factors. The analysis of these B-factors, in combination with crystal packing and RMSD among structures, suggests the existence of localized changes in the internal motions. Based on these results, we propose that bacterial frataxins possess binding sites of moderate affinity for a quick capture and transfer of iron to other proteins and for the regulation of Fe-S cluster biosynthesis, modulating interactions with partner proteins.
-
A Better Fit. An improved anticoagulant drug called RUC-2 (ball and stick structure) fits snugly into its binding pocket on integrin (blue), a protein found on the surface of platelets. RUC-2 binds both subunits of integrin, inhibiting the excessive blood coagulation that can lead to strokes and heart attacks. Unlike similar drugs that alter integrin's structure when they bind
-
Structure of the choline-binding domain of Spr1274 in Streptococcus pneumoniae.
Zhang, Zhenyi; Li, Wenzhe; Frolet, Cecile; Bao, Rui; di Guilmi, Anne Marie; Vernet, Thierry; Chen, Yuxing
2009-08-01
Spr1274 is a putative choline-binding protein that is bound to the cell wall of Streptococcus pneumoniae through noncovalent interactions with the choline moieties of teichoic and lipoteichoic acids. Its function is still unknown. The crystal structure of the choline-binding domain of Spr1274 (residues 44-129) was solved at 2.38 A resolution with three molecules in the asymmetric unit. It may provide a structural basis for functional analysis of choline-binding proteins.
-
Finding the target sites of RNA-binding proteins
Li, Xiao; Kazan, Hilal; Lipshitz, Howard D; Morris, Quaid D
2014-01-01
RNA–protein interactions differ from DNA–protein interactions because of the central role of RNA secondary structure. Some RNA-binding domains (RBDs) recognize their target sites mainly by their shape and geometry and others are sequence-specific but are sensitive to secondary structure context. A number of small- and large-scale experimental approaches have been developed to measure RNAs associated in vitro and in vivo with RNA-binding proteins (RBPs). Generalizing outside of the experimental conditions tested by these assays requires computational motif finding. Often RBP motif finding is done by adapting DNA motif finding methods; but modeling secondary structure context leads to better recovery of RBP-binding preferences. Genome-wide assessment of mRNA secondary structure has recently become possible, but these data must be combined with computational predictions of secondary structure before they add value in predicting in vivo binding. There are two main approaches to incorporating structural information into motif models: supplementing primary sequence motif models with preferred secondary structure contexts (e.g., MEMERIS and RNAcontext) and directly modeling secondary structure recognized by the RBP using stochastic context-free grammars (e.g., CMfinder and RNApromo). The former better reconstruct known binding preferences for sequence-specific RBPs but are not suitable for modeling RBPs that recognize shape and geometry of RNAs. Future work in RBP motif finding should incorporate interactions between multiple RBDs and multiple RBPs in binding to RNA. WIREs RNA 2014, 5:111–130. doi: 10.1002/wrna.1201 PMID:24217996
-
Structural Basis for Sialoglycan Binding by the Streptococcus sanguinis SrpA Adhesin*♦
Bensing, Barbara A.; Loukachevitch, Lioudmila V.; McCulloch, Kathryn M.; Yu, Hai; Vann, Kendra R.; Wawrzak, Zdzislaw; Anderson, Spencer; Chen, Xi; Sullam, Paul M.; Iverson, T. M.
2016-01-01
Streptococcus sanguinis is a leading cause of infective endocarditis, a life-threatening infection of the cardiovascular system. An important interaction in the pathogenesis of infective endocarditis is attachment of the organisms to host platelets. S. sanguinis expresses a serine-rich repeat adhesin, SrpA, similar in sequence to platelet-binding adhesins associated with increased virulence in this disease. In this study, we determined the first crystal structure of the putative binding region of SrpA (SrpABR) both unliganded and in complex with a synthetic disaccharide ligand at 1.8 and 2.0 Å resolution, respectively. We identified a conserved Thr-Arg motif that orients the sialic acid moiety and is required for binding to platelet monolayers. Furthermore, we propose that sequence insertions in closely related family members contribute to the modulation of structural and functional properties, including the quaternary structure, the tertiary structure, and the ligand-binding site. PMID:26833566
-
Is the isolated ligand binding domain a good model of the domain in the native receptor?
Deming, Dustin; Cheng, Qing; Jayaraman, Vasanthi
2003-05-16
Numerous studies have used the atomic level structure of the isolated ligand binding domain of the glutamate receptor to elucidate the agonist-induced activation and desensitization processes in this group of proteins. However, no study has demonstrated the structural equivalence of the isolated ligand binding fragments and the protein in the native receptor. In this report, using visible absorption spectroscopy we show that the electronic environment of the antagonist 6-cyano-7-nitro-2,3-dihydroxyquinoxaline is identical for the isolated protein and the native glutamate receptors expressed in cells. Our results hence establish that the local structure of the ligand binding site is the same in the two proteins and validate the detailed structure-function relationships that have been developed based on a comparison of the structure of the isolated ligand binding domain and electrophysiological consequences in the native receptor.
-
Allosteric Ligand Binding and Anisotropic Energy Flow in Albumin
NASA Astrophysics Data System (ADS)
Dyer, Brian
2014-03-01
Protein allostery usually involves propagation of local structural changes through the protein to a remote site. Coupling of structural changes at remote sites is thought to occur through anisotropic energy transport, but the nature of this process is poorly understood. We have studied the relationship between allosteric interactions of remote ligand binding sites of the protein and energy flow through the structure of bovine serum albumin (BSA). We applied ultrafast infrared spectroscopy to probe the flow of energy through the protein backbone following excitation of a heater dye, a metalloporphyrin or malachite green, bound to different binding sites in the protein. We observe ballistic flow through the protein structure following input of thermal energy into the flexible ligand binding sites. We also observe anisotropic heat flow through the structure, without local heating of the rigid helix bundles that connect these sites. We will discuss the implications of this efficient energy transport mechanism with regard to the allosteric propagation of binding energy through the connecting helix structures.
-
Structure of AadA from Salmonella enterica: a monomeric aminoglycoside (3′′)(9) adenyltransferase
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chen, Yang; Näsvall, Joakim; Wu, Shiying
The crystal structure of the aminoglycoside-adenylating enzyme AadA is reported together with functional experiments providing insights into its oligomeric state, ligand binding and catalysis. Aminoglycoside resistance is commonly conferred by enzymatic modification of drugs by aminoglycoside-modifying enzymes such as aminoglycoside nucleotidyltransferases (ANTs). Here, the first crystal structure of an ANT(3′′)(9) adenyltransferase, AadA from Salmonella enterica, is presented. AadA catalyses the magnesium-dependent transfer of adenosine monophosphate from ATP to the two chemically dissimilar drugs streptomycin and spectinomycin. The structure was solved using selenium SAD phasing and refined to 2.5 Å resolution. AadA consists of a nucleotidyltransferase domain and an α-helical bundlemore » domain. AadA crystallizes as a monomer and is a monomer in solution as confirmed by small-angle X-ray scattering, in contrast to structurally similar homodimeric adenylating enzymes such as kanamycin nucleotidyltransferase. Isothermal titration calorimetry experiments show that ATP binding has to occur before binding of the aminoglycoside substrate, and structure analysis suggests that ATP binding repositions the two domains for aminoglycoside binding in the interdomain cleft. Candidate residues for ligand binding and catalysis were subjected to site-directed mutagenesis. In vivo resistance and in vitro binding assays support the role of Glu87 as the catalytic base in adenylation, while Arg192 and Lys205 are shown to be critical for ATP binding.« less
-
Doxey, Andrew C; Cheng, Zhenyu; Moffatt, Barbara A; McConkey, Brendan J
2010-08-03
Aromatic amino acids play a critical role in protein-glycan interactions. Clusters of surface aromatic residues and their features may therefore be useful in distinguishing glycan-binding sites as well as predicting novel glycan-binding proteins. In this work, a structural bioinformatics approach was used to screen the Protein Data Bank (PDB) for coplanar aromatic motifs similar to those found in known glycan-binding proteins. The proteins identified in the screen were significantly associated with carbohydrate-related functions according to gene ontology (GO) enrichment analysis, and predicted motifs were found frequently within novel folds and glycan-binding sites not included in the training set. In addition to numerous binding sites predicted in structural genomics proteins of unknown function, one novel prediction was a surface motif (W34/W36/W192) in the tobacco pathogenesis-related protein, PR-5d. Phylogenetic analysis revealed that the surface motif is exclusive to a subfamily of PR-5 proteins from the Solanaceae family of plants, and is absent completely in more distant homologs. To confirm PR-5d's insoluble-polysaccharide binding activity, a cellulose-pulldown assay of tobacco proteins was performed and PR-5d was identified in the cellulose-binding fraction by mass spectrometry. Based on the combined results, we propose that the putative binding site in PR-5d may be an evolutionary adaptation of Solanaceae plants including potato, tomato, and tobacco, towards defense against cellulose-containing pathogens such as species of the deadly oomycete genus, Phytophthora. More generally, the results demonstrate that coplanar aromatic clusters on protein surfaces are a structural signature of glycan-binding proteins, and can be used to computationally predict novel glycan-binding proteins from 3 D structure.
-
Altman, Michael D.; Nalivaika, Ellen A.; Prabu-Jeyabalan, Moses; Schiffer, Celia A.; Tidor, Bruce
2009-01-01
Drug resistance in HIV-1 protease, a barrier to effective treatment, is generally caused by mutations in the enzyme that disrupt inhibitor binding but still allow for substrate processing. Structural studies with mutant, inactive enzyme, have provided detailed information regarding how the substrates bind to the protease yet avoid resistance mutations; insights obtained inform the development of next generation therapeutics. Although structures have been obtained of complexes between substrate peptide and inactivated (D25N) protease, thermodynamic studies of peptide binding have been challenging due to low affinity. Peptides that bind tighter to the inactivated protease than the natural substrates would be valuable for thermodynamic studies as well as to explore whether the structural envelope observed for substrate peptides is a function of weak binding. Here, two computational methods — namely, charge optimization and protein design — were applied to identify peptide sequences predicted to have higher binding affinity to the inactivated protease, starting from an RT–RH derived substrate peptide. Of the candidate designed peptides, three were tested for binding with isothermal titration calorimetry, with one, containing a single threonine to valine substitution, measured to have more than a ten-fold improvement over the tightest binding natural substrate. Crystal structures were also obtained for the same three designed peptide complexes; they show good agreement with computational prediction. Thermodynamic studies show that binding is entropically driven, more so for designed affinity enhanced variants than for the starting substrate. Structural studies show strong similarities between natural and tighter-binding designed peptide complexes, which may have implications in understanding the molecular mechanisms of drug resistance in HIV-1 protease. PMID:17729291
-
Real-Time Ligand Binding Pocket Database Search Using Local Surface Descriptors
Chikhi, Rayan; Sael, Lee; Kihara, Daisuke
2010-01-01
Due to the increasing number of structures of unknown function accumulated by ongoing structural genomics projects, there is an urgent need for computational methods for characterizing protein tertiary structures. As functions of many of these proteins are not easily predicted by conventional sequence database searches, a legitimate strategy is to utilize structure information in function characterization. Of a particular interest is prediction of ligand binding to a protein, as ligand molecule recognition is a major part of molecular function of proteins. Predicting whether a ligand molecule binds a protein is a complex problem due to the physical nature of protein-ligand interactions and the flexibility of both binding sites and ligand molecules. However, geometric and physicochemical complementarity is observed between the ligand and its binding site in many cases. Therefore, ligand molecules which bind to a local surface site in a protein can be predicted by finding similar local pockets of known binding ligands in the structure database. Here, we present two representations of ligand binding pockets and utilize them for ligand binding prediction by pocket shape comparison. These representations are based on mapping of surface properties of binding pockets, which are compactly described either by the two dimensional pseudo-Zernike moments or the 3D Zernike descriptors. These compact representations allow a fast real-time pocket searching against a database. Thorough benchmark study employing two different datasets show that our representations are competitive with the other existing methods. Limitations and potentials of the shape-based methods as well as possible improvements are discussed. PMID:20455259
-
Real-time ligand binding pocket database search using local surface descriptors.
Chikhi, Rayan; Sael, Lee; Kihara, Daisuke
2010-07-01
Because of the increasing number of structures of unknown function accumulated by ongoing structural genomics projects, there is an urgent need for computational methods for characterizing protein tertiary structures. As functions of many of these proteins are not easily predicted by conventional sequence database searches, a legitimate strategy is to utilize structure information in function characterization. Of particular interest is prediction of ligand binding to a protein, as ligand molecule recognition is a major part of molecular function of proteins. Predicting whether a ligand molecule binds a protein is a complex problem due to the physical nature of protein-ligand interactions and the flexibility of both binding sites and ligand molecules. However, geometric and physicochemical complementarity is observed between the ligand and its binding site in many cases. Therefore, ligand molecules which bind to a local surface site in a protein can be predicted by finding similar local pockets of known binding ligands in the structure database. Here, we present two representations of ligand binding pockets and utilize them for ligand binding prediction by pocket shape comparison. These representations are based on mapping of surface properties of binding pockets, which are compactly described either by the two-dimensional pseudo-Zernike moments or the three-dimensional Zernike descriptors. These compact representations allow a fast real-time pocket searching against a database. Thorough benchmark studies employing two different datasets show that our representations are competitive with the other existing methods. Limitations and potentials of the shape-based methods as well as possible improvements are discussed.
-
Nesmelova, Irina V; Ermakova, Elena; Daragan, Vladimir A; Pang, Mabel; Menéndez, Margarita; Lagartera, Laura; Solís, Dolores; Baum, Linda G; Mayo, Kevin H
2010-04-16
Galectins are a family of lectins with a conserved carbohydrate recognition domain that interacts with beta-galactosides. By binding cell surface glycoconjugates, galectin-1 (gal-1) is involved in cell adhesion and migration processes and is an important regulator of tumor angiogenesis. Here, we used heteronuclear NMR spectroscopy and molecular modeling to investigate lactose binding to gal-1 and to derive solution NMR structures of gal-1 in the lactose-bound and unbound states. Structure analysis shows that the beta-strands and loops around the lactose binding site, which are more open and dynamic in the unbound state, fold in around the bound lactose molecule, dampening internal motions at that site and increasing motions elsewhere throughout the protein to contribute entropically to the binding free energy. CD data support the view of an overall more open structure in the lactose-bound state. Analysis of heteronuclear single quantum coherence titration binding data indicates that lactose binds the two carbohydrate recognition domains of the gal-1 dimer with negative cooperativity, in that the first lactose molecule binds more strongly (K(1)=21+/-6 x 10(3) M(-1)) than the second (K(2)=4+/-2 x 10(3) M(-1)). Isothermal calorimetry data fit using a sequential binding model present a similar picture, yielding K(1)=20+/-10 x 10(3) M(-1) and K(2)=1.67+/-0.07 x 10(3) M(-1). Molecular dynamics simulations provide insight into structural dynamics of the half-loaded lactose state and, together with NMR data, suggest that lactose binding at one site transmits a signal through the beta-sandwich and loops to the second binding site. Overall, our results provide new insight into gal-1 structure-function relationships and to protein-carbohydrate interactions in general. Copyright (c) 2010. Published by Elsevier Ltd.
-
A genome-wide structure-based survey of nucleotide binding proteins in M. tuberculosis
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bhagavat, Raghu; Kim, Heung -Bok; Kim, Chang -Yub
Nucleoside tri-phosphates (NTP) form an important class of small molecule ligands that participate in, and are essential to a large number of biological processes. Here, we seek to identify the NTP binding proteome (NTPome) in M. tuberculosis (M.tb), a deadly pathogen. Identifying the NTPome is useful not only for gaining functional insights of the individual proteins but also for identifying useful drug targets. From an earlier study, we had structural models of M.tb at a proteome scale from which a set of 13,858 small molecule binding pockets were identified. We use a set of NTP binding sub-structural motifs derived frommore » a previous study and scan the M.tb pocketome, and find that 1,768 proteins or 43% of the proteome can theoretically bind NTP ligands. Using an experimental proteomics approach involving dye-ligand affinity chromatography, we confirm NTP binding to 47 different proteins, of which 4 are hypothetical proteins. Our analysis also provides the precise list of binding site residues in each case, and the probable ligand binding pose. In conclusion, as the list includes a number of known and potential drug targets, the identification of NTP binding can directly facilitate structure-based drug design of these targets.« less
-
A genome-wide structure-based survey of nucleotide binding proteins in M. tuberculosis
Bhagavat, Raghu; Kim, Heung -Bok; Kim, Chang -Yub; ...
2017-10-02
Nucleoside tri-phosphates (NTP) form an important class of small molecule ligands that participate in, and are essential to a large number of biological processes. Here, we seek to identify the NTP binding proteome (NTPome) in M. tuberculosis (M.tb), a deadly pathogen. Identifying the NTPome is useful not only for gaining functional insights of the individual proteins but also for identifying useful drug targets. From an earlier study, we had structural models of M.tb at a proteome scale from which a set of 13,858 small molecule binding pockets were identified. We use a set of NTP binding sub-structural motifs derived frommore » a previous study and scan the M.tb pocketome, and find that 1,768 proteins or 43% of the proteome can theoretically bind NTP ligands. Using an experimental proteomics approach involving dye-ligand affinity chromatography, we confirm NTP binding to 47 different proteins, of which 4 are hypothetical proteins. Our analysis also provides the precise list of binding site residues in each case, and the probable ligand binding pose. In conclusion, as the list includes a number of known and potential drug targets, the identification of NTP binding can directly facilitate structure-based drug design of these targets.« less
-
Wu, Wei; Park, Kyung-Tae; Holyoak, Todd; Lutkenhaus, Joe
2011-01-01
Summary The three Min proteins spatially regulate Z ring positioning in E. coli and are dynamically associated with the membrane. MinD binds to vesicles in the presence of ATP and can recruit MinC or MinE. Biochemical and genetic evidence indicate the binding sites for these two proteins on MinD overlap. Here we solved the structure of a hydrolytic-deficient mutant of MinD truncated for the C-terminal amphipathic helix involved in binding to the membrane. The structure solved in the presence of ATP is a dimer and reveals the face of MinD abutting the membrane. Using a combination of random and extensive site-directed mutagenesis additional residues important for MinE and MinC binding were identified. The location of these residues on the MinD structure confirms that the binding sites overlap and reveals that the binding sites are at the dimer interface and exposed to the cytosol. The location of the binding sites at the dimer interface offers a simple explanation for the ATP-dependency of MinC and MinE binding to MinD. PMID:21231967
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Meyers, Marvin J.; Pelc, Matthew; Kamtekar, Satwik
2010-08-11
The work described herein demonstrates the utility of structure-based drug design (SBDD) in shifting the binding mode of an HTS hit from a DFG-in to a DFG-out binding mode resulting in a class of novel potent CSF-1R kinase inhibitors suitable for lead development.
-
Cai, Jun; Lücke, Christian; Chen, Zhongjing; Qiao, Ye; Klimtchuk, Elena; Hamilton, James A.
2012-01-01
Liver fatty acid binding protein (L-FABP), a cytosolic protein most abundant in liver, is associated with intracellular transport of fatty acids, nuclear signaling, and regulation of intracellular lipolysis. Among the members of the intracellular lipid binding protein family, L-FABP is of particular interest as it can i), bind two fatty acid molecules simultaneously and ii), accommodate a variety of bulkier physiological ligands such as bilirubin and fatty acyl CoA. To better understand the promiscuous binding and transport properties of L-FABP, we investigated structure and dynamics of human L-FABP with and without bound ligands by means of heteronuclear NMR. The overall conformation of human L-FABP shows the typical β-clam motif. Binding of two oleic acid (OA) molecules does not alter the protein conformation substantially, but perturbs the chemical shift of certain backbone and side-chain protons that are involved in OA binding according to the structure of the human L-FABP/OA complex. Comparison of the human apo and holo L-FABP structures revealed no evidence for an “open-cap” conformation or a “swivel-back” mechanism of the K90 side chain upon ligand binding, as proposed for rat L-FABP. Instead, we postulate that the lipid binding process in L-FABP is associated with backbone dynamics. PMID:22713574